Breast Cancer

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Spironolactone for the treatment of endocrine therapy–induced alopecia in breast cancer survivors was not associated with increased risk of recurrence of the malignancy in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.

Not so, said Mr. Wei, from George Washington University.

He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.

“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.

In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.

In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.

Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.

“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).

Mr. Wei reported having no financial conflicts regarding his unfunded study.
 

[email protected]

Spironolactone for the treatment of endocrine therapy–induced alopecia in breast cancer survivors was not associated with increased risk of recurrence of the malignancy in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.

Not so, said Mr. Wei, from George Washington University.

He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.

“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.

In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.

In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.

Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.

“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).

Mr. Wei reported having no financial conflicts regarding his unfunded study.
 

[email protected]

Spironolactone for the treatment of endocrine therapy–induced alopecia in breast cancer survivors was not associated with increased risk of recurrence of the malignancy in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.

Not so, said Mr. Wei, from George Washington University.

He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.

“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.

In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.

In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.

Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.

“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).

Mr. Wei reported having no financial conflicts regarding his unfunded study.
 

[email protected]

Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.

James Gathany/CDC

The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.

The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).

In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.

Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.

“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.

The authors reported that they had no competing interests.

[email protected]

SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.

Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.

James Gathany/CDC

The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.

The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).

In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.

Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.

“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.

The authors reported that they had no competing interests.

[email protected]

SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.

Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.

James Gathany/CDC

The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.

The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).

In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.

Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.

“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.

The authors reported that they had no competing interests.

[email protected]

SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190