CNS/Brain Cancer

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

The first study to systematically address the problem of persistent hair loss in patients who undergo radiation to the scalp for central nervous system or head and neck tumors has found that treatment with topical minoxidil leads to improvement in hair loss.

The study was published online on Aug. 5 in JAMA Dermatology.

Minoxidil has been used for many years to treat age-associated baldness in men, noted the authors. It was used off label in this study to treat radiation-associated persistent hair loss; 82% of patients showed at least some improvement.

For patients who do not improve with minoxidil, hair transplant and scalp reconstruction with plastic surgery were other options, the authors comment.

“Almost in all instances, there is something that can be done to improve persistent hair loss after radiation and give patients a sense of control,” senior author Mario E. Lacouture, MD, said in an interview. He is director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center in New York City.

About 60% of people with CNS tumors and 30% with head and neck cancer receive radiation to the head, and 75%-100% of these patients experience acute hair loss. For many, hair grows back in 2-3 months. However, for about 60%, hair loss persists for 6 or more months after completion of radiotherapy, the authors note.

In past work, Dr. Lacouture and colleagues found that persistent hair loss in cancer survivors is associated with depression, anxiety, and psychosocial distress.

“There are therapies and procedures that may mitigate persistent radiation therapy hair loss that can bring back psychosocial well-being to many of these patients,” Dr. Lacouture said. “These approaches are likely underutilized because patients are not being referred to specialists in hair or scalp reconstruction.”

Specialists can be found through the International Society for Hair Restoration Surgery and the American Academy of Dermatology, he added.

Study details

The retrospective cohort study included 71 children and adults who developed persistent hair loss after radiotherapy for primary CNS tumors (90%, n = 64) or head and neck sarcoma (10%, n = 7). The median age of the patients was 27 years (range, 4-75 years); 72% (n = 51) were female and 82% (n = 58) were White.

These patients had been treated at Memorial Sloan Kettering Cancer Center in New York City or St. Jude Children’s Hospital in Memphis from January 2011 to January 2019.

The team analyzed standardized clinical photographs of the scalp using the Common Terminology Criteria for Adverse Events version 5.0. Grade 1 alopecia was defined as hair loss of less than 50% of normal that does not require camouflage with hair pieces, scarves, or similar items. Grade 2 alopecia was defined as hair loss greater than 50% of normal that requires camouflage and is associated with negative psychosocial effects.

Over half of patients (56%, 40/70) had grade 1 hair loss. Clinical images were available for 54 patients; for most of these patients, hair loss was attributable to radiation alone (74%, n = 40). Evaluation of clinical imaging showed three variants of hair loss: localized (54%, 29/54), diffuse (24%, 13/54), and mixed pattern (22%, 12/54). Data on dermatologic imaging of the scalp (trichoscopy) were available for 28 patients; the main finding was white patches (57%, 16/28).

The median scalp radiation dose was 39.6 Gy (range, 15.1-50.0 Gy). The researchers estimate that a dose of 36.1 Gy (95% CI, 33.7-39.6 Gy) was sufficient to induce grade 2 hair loss in 50% of patients.

Severity of hair loss appeared to increase with radiation dose. For every 1-unit increase in radiation dose, the odds of grade 2 hair loss increased by 15% (odds ratio, 1.15; 95% CI, 1.04-1.28; P < .001). Proton irradiation was associated with even higher odds of severe hair loss (OR, 5.7; 95% CI, 1.05-30.8; P < .001). Results remained significant when analyses were controlled for sex, age at time of radiotherapy, and concurrent chemotherapy.

The majority of evaluable patients who were treated with topical minoxidil (5%) twice daily showed a response (82%, 28/34) during a median follow-up of 61 weeks (interquartile range, 21-105 weeks).

Among 25 of these patients for whom clinical images were available, 16% (4/25) showed complete response. Two patients improved with hair transplant, and one showed complete response with plastic surgery reconstruction of the hair.

The study had several limitations, including its retrospective design and a lack of complete data for certain variables, such as standardized clinical photographs, trichoscopy images, and radiotherapy treatment plans.

On the basis of these results, the authors are seeking funding for a prospective study of the use of minoxidil for persistent radiation-induced alopecia.

The study was funded in part by the National Institutes of Health/National Cancer Institute Cancer Center. One or more authors has relationships with pharmaceutical companies, as listed in the original article.

This article first appeared on Medscape.com.

The first study to systematically address the problem of persistent hair loss in patients who undergo radiation to the scalp for central nervous system or head and neck tumors has found that treatment with topical minoxidil leads to improvement in hair loss.

The study was published online on Aug. 5 in JAMA Dermatology.

Minoxidil has been used for many years to treat age-associated baldness in men, noted the authors. It was used off label in this study to treat radiation-associated persistent hair loss; 82% of patients showed at least some improvement.

For patients who do not improve with minoxidil, hair transplant and scalp reconstruction with plastic surgery were other options, the authors comment.

“Almost in all instances, there is something that can be done to improve persistent hair loss after radiation and give patients a sense of control,” senior author Mario E. Lacouture, MD, said in an interview. He is director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center in New York City.

About 60% of people with CNS tumors and 30% with head and neck cancer receive radiation to the head, and 75%-100% of these patients experience acute hair loss. For many, hair grows back in 2-3 months. However, for about 60%, hair loss persists for 6 or more months after completion of radiotherapy, the authors note.

In past work, Dr. Lacouture and colleagues found that persistent hair loss in cancer survivors is associated with depression, anxiety, and psychosocial distress.

“There are therapies and procedures that may mitigate persistent radiation therapy hair loss that can bring back psychosocial well-being to many of these patients,” Dr. Lacouture said. “These approaches are likely underutilized because patients are not being referred to specialists in hair or scalp reconstruction.”

Specialists can be found through the International Society for Hair Restoration Surgery and the American Academy of Dermatology, he added.

Study details

The retrospective cohort study included 71 children and adults who developed persistent hair loss after radiotherapy for primary CNS tumors (90%, n = 64) or head and neck sarcoma (10%, n = 7). The median age of the patients was 27 years (range, 4-75 years); 72% (n = 51) were female and 82% (n = 58) were White.

These patients had been treated at Memorial Sloan Kettering Cancer Center in New York City or St. Jude Children’s Hospital in Memphis from January 2011 to January 2019.

The team analyzed standardized clinical photographs of the scalp using the Common Terminology Criteria for Adverse Events version 5.0. Grade 1 alopecia was defined as hair loss of less than 50% of normal that does not require camouflage with hair pieces, scarves, or similar items. Grade 2 alopecia was defined as hair loss greater than 50% of normal that requires camouflage and is associated with negative psychosocial effects.

Over half of patients (56%, 40/70) had grade 1 hair loss. Clinical images were available for 54 patients; for most of these patients, hair loss was attributable to radiation alone (74%, n = 40). Evaluation of clinical imaging showed three variants of hair loss: localized (54%, 29/54), diffuse (24%, 13/54), and mixed pattern (22%, 12/54). Data on dermatologic imaging of the scalp (trichoscopy) were available for 28 patients; the main finding was white patches (57%, 16/28).

The median scalp radiation dose was 39.6 Gy (range, 15.1-50.0 Gy). The researchers estimate that a dose of 36.1 Gy (95% CI, 33.7-39.6 Gy) was sufficient to induce grade 2 hair loss in 50% of patients.

Severity of hair loss appeared to increase with radiation dose. For every 1-unit increase in radiation dose, the odds of grade 2 hair loss increased by 15% (odds ratio, 1.15; 95% CI, 1.04-1.28; P < .001). Proton irradiation was associated with even higher odds of severe hair loss (OR, 5.7; 95% CI, 1.05-30.8; P < .001). Results remained significant when analyses were controlled for sex, age at time of radiotherapy, and concurrent chemotherapy.

The majority of evaluable patients who were treated with topical minoxidil (5%) twice daily showed a response (82%, 28/34) during a median follow-up of 61 weeks (interquartile range, 21-105 weeks).

Among 25 of these patients for whom clinical images were available, 16% (4/25) showed complete response. Two patients improved with hair transplant, and one showed complete response with plastic surgery reconstruction of the hair.

The study had several limitations, including its retrospective design and a lack of complete data for certain variables, such as standardized clinical photographs, trichoscopy images, and radiotherapy treatment plans.

On the basis of these results, the authors are seeking funding for a prospective study of the use of minoxidil for persistent radiation-induced alopecia.

The study was funded in part by the National Institutes of Health/National Cancer Institute Cancer Center. One or more authors has relationships with pharmaceutical companies, as listed in the original article.

This article first appeared on Medscape.com.

The first study to systematically address the problem of persistent hair loss in patients who undergo radiation to the scalp for central nervous system or head and neck tumors has found that treatment with topical minoxidil leads to improvement in hair loss.

The study was published online on Aug. 5 in JAMA Dermatology.

Minoxidil has been used for many years to treat age-associated baldness in men, noted the authors. It was used off label in this study to treat radiation-associated persistent hair loss; 82% of patients showed at least some improvement.

For patients who do not improve with minoxidil, hair transplant and scalp reconstruction with plastic surgery were other options, the authors comment.

“Almost in all instances, there is something that can be done to improve persistent hair loss after radiation and give patients a sense of control,” senior author Mario E. Lacouture, MD, said in an interview. He is director of the Oncodermatology Program at Memorial Sloan Kettering Cancer Center in New York City.

About 60% of people with CNS tumors and 30% with head and neck cancer receive radiation to the head, and 75%-100% of these patients experience acute hair loss. For many, hair grows back in 2-3 months. However, for about 60%, hair loss persists for 6 or more months after completion of radiotherapy, the authors note.

In past work, Dr. Lacouture and colleagues found that persistent hair loss in cancer survivors is associated with depression, anxiety, and psychosocial distress.

“There are therapies and procedures that may mitigate persistent radiation therapy hair loss that can bring back psychosocial well-being to many of these patients,” Dr. Lacouture said. “These approaches are likely underutilized because patients are not being referred to specialists in hair or scalp reconstruction.”

Specialists can be found through the International Society for Hair Restoration Surgery and the American Academy of Dermatology, he added.

Study details

The retrospective cohort study included 71 children and adults who developed persistent hair loss after radiotherapy for primary CNS tumors (90%, n = 64) or head and neck sarcoma (10%, n = 7). The median age of the patients was 27 years (range, 4-75 years); 72% (n = 51) were female and 82% (n = 58) were White.

These patients had been treated at Memorial Sloan Kettering Cancer Center in New York City or St. Jude Children’s Hospital in Memphis from January 2011 to January 2019.

The team analyzed standardized clinical photographs of the scalp using the Common Terminology Criteria for Adverse Events version 5.0. Grade 1 alopecia was defined as hair loss of less than 50% of normal that does not require camouflage with hair pieces, scarves, or similar items. Grade 2 alopecia was defined as hair loss greater than 50% of normal that requires camouflage and is associated with negative psychosocial effects.

Over half of patients (56%, 40/70) had grade 1 hair loss. Clinical images were available for 54 patients; for most of these patients, hair loss was attributable to radiation alone (74%, n = 40). Evaluation of clinical imaging showed three variants of hair loss: localized (54%, 29/54), diffuse (24%, 13/54), and mixed pattern (22%, 12/54). Data on dermatologic imaging of the scalp (trichoscopy) were available for 28 patients; the main finding was white patches (57%, 16/28).

The median scalp radiation dose was 39.6 Gy (range, 15.1-50.0 Gy). The researchers estimate that a dose of 36.1 Gy (95% CI, 33.7-39.6 Gy) was sufficient to induce grade 2 hair loss in 50% of patients.

Severity of hair loss appeared to increase with radiation dose. For every 1-unit increase in radiation dose, the odds of grade 2 hair loss increased by 15% (odds ratio, 1.15; 95% CI, 1.04-1.28; P < .001). Proton irradiation was associated with even higher odds of severe hair loss (OR, 5.7; 95% CI, 1.05-30.8; P < .001). Results remained significant when analyses were controlled for sex, age at time of radiotherapy, and concurrent chemotherapy.

The majority of evaluable patients who were treated with topical minoxidil (5%) twice daily showed a response (82%, 28/34) during a median follow-up of 61 weeks (interquartile range, 21-105 weeks).

Among 25 of these patients for whom clinical images were available, 16% (4/25) showed complete response. Two patients improved with hair transplant, and one showed complete response with plastic surgery reconstruction of the hair.

The study had several limitations, including its retrospective design and a lack of complete data for certain variables, such as standardized clinical photographs, trichoscopy images, and radiotherapy treatment plans.

On the basis of these results, the authors are seeking funding for a prospective study of the use of minoxidil for persistent radiation-induced alopecia.

The study was funded in part by the National Institutes of Health/National Cancer Institute Cancer Center. One or more authors has relationships with pharmaceutical companies, as listed in the original article.

This article first appeared on Medscape.com.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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. He is based in St. Louis. He has no conflicts of interest.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

Adding intraventricular methotrexate to systemic chemotherapy produced favorable survival outcomes in patients with desmoplastic medulloblastoma (DMB) and medulloblastoma with extensive nodularity (MBEN), according to research published in the Journal of Clinical Oncology.

Investigators conducted a prospective trial of 87 children diagnosed with nonmetastatic medulloblastoma before the age of 4 years who were treated from 2001-2011.

At 5 years after diagnosis, the 42 DMB/MBEN patients had a 93% progression-free survival (PFS) rate, a 100% overall survival (OS) rate, and a 93% craniospinal irradiation (CSI)–free survival rate.

“Our results suggest that ... poor outcomes of patients treated with systemic chemotherapy alone can be improved by the addition of intraventricular [methotrexate],” wrote Martin Mynarek, MD, of the University Medical Center Hamburg-Eppendorf (Germany), and colleagues.

However, it was a different story for the 45 patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (CLA), in which outcomes are historically worse. At 5 years, the PFS was 37%, the OS was 62%, and the CSI-free survival was 39% in these patients.

In 2006, the CMB and CLA patients started receiving local radiotherapy in addition to chemotherapy and intraventricular methotrexate, but the radiotherapy did not seem to help with their disease.

“Because data suggest no effects, or even adverse effects, of local radiotherapy, additional development of this approach does not seem justified,” the investigators wrote.

“Interestingly, almost all patients with CMB/LCA had distant or combined relapses after local radiotherapy,” they added. “One might speculate that local radiotherapy reduced disease burden of the primary tumor and subclinical metastasis in the posterior fossa, leading to a survival advantage of distant subclinical metastasis over local residues.”
 

Treatment details

The 87 patients were enrolled in the BIS4 arm of the HIT 2000 trial (NCT00303810), which was designed to test six protocols and identify the optimal approach for treating young patients with medulloblastoma, supratentorial primitive neuroectodermal tumor, or ependymoma.

Patients started “HIT-SKK” chemotherapy within 2-4 weeks of surgery. They received three cycles of intravenous cyclophosphamide, vincristine, methotrexate (followed by leucovorin rescue after 42 hours), carboplatin, and etoposide, with concomitant intraventricular methotrexate, for a duration of 6 months (Neuro Oncol. 2011 Jun;13[6]:669-79).

Among patients who achieved a complete remission, treatment was ended after two additional cycles of chemotherapy. For other patients, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended.

Starting in 2006, DMB and MBEN patients without complete remissions, as well as those with CMB or LCA, received 54 Gy of focal radiotherapy to the tumor bed after the first three treatment cycles.
 

SHH-I vs. SHH-II DMB/MBEN

DNA methylation profiling was available for 50 of the 87 patients in this analysis, 28 of whom had infantile sonic hedgehog (SHH)–activated DMB/MBEN. Data from these 28 patients – and 71 patients in a validation cohort – revealed no significant difference in 5-year PFS or OS based on methylation subtype.

The 5-year PFS was 73% in SHH-I patients and 83% in SHH-II patients (P = .25). The 5-year OS was 88% and 97%, respectively (P = .099).

“This suggests that the higher risk of relapse in the less favorable [SHH-I subtype] can be abrogated by the addition of intraventricular [methotrexate] to systemic chemotherapy,” the investigators wrote.

The results suggest SHH-I patients “markedly benefit” from the addition of intraventricular chemotherapy, according to the authors of a related editorial, Giles Robinson, MD, and Amar Gajjar, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn.

“However, cross-trial comparison of PFS among the SHH-II subtype does not suggest that SHH-II patients derive the same benefit,” the editorialists wrote.

These data divide SHH medulloblastoma into SHH-I, which benefits from chemotherapy with intraventricular methotrexate, and SHH-II, which can be cured without intraventricular methotrexate, high-dose chemotherapy, or focal radiotherapy, according to the editorialists.

This new information might prompt investigation of a risk-adapted approach. SHH-II patients would receive a reduced-intensity regimen with systemic chemotherapy only, and SHH-I patients would receive systemic chemotherapy combined with intraventricular methotrexate. This could avoid exposing young children to “more intensive therapy than necessary,” according to the editorialists.
 

Non-WNT/non-SHH disease

Patients with non-WNT/non-SHH medulloblastoma (CMB or LCA) were divided into molecularly defined subtypes group 3 (n = 14) and group 4 (n = 6). The patients in group 3 had lower survival rates than patients in group 4. The 5-year PFS rate was 36% and 83%, respectively (P < .001 ). The 5-year OS rate was 49% and 100%, respectively (P < .001).

“This represents the third recent publication to describe a poor PFS for group 3, and it signals a desperate need for better therapy,” the editorialists wrote. As for the “encouraging” survival rate for group 4 patients, there were only six subjects, which makes this finding “worthy of follow-up but not actionable.”

Even so, the investigators noted that “although poor survival has been reported for non-SHH CMB/LCA in almost every series of patients treated with CSI-sparing approaches, again, use of intraventricular [methotrexate] might be associated with slightly higher PFS, compared with conventional chemotherapy alone.”

As expected, IQ was significantly lower in patients who received CSI salvage. The mean IQ was 74 in patients who received CSI and 90 in patients who did not (P = .012). Neurocognitive outcomes were poor in general among CMB/LCA survivors, “which was closely related to use of radiotherapy,” according to the investigators.

“It is important to recognize that these studies were not designed to define outcome on the basis of molecular subgroup or subtype and that the sample size in all these studies is small,” Dr. Robinson and Dr. Gajjar wrote. “Thus, caution should be used when basing any treatment recommendation on these results, and it is our strong-held opinion that any treatment change be done on a well-planned and well-monitored clinical trial.”

This research was supported by the German Childhood Cancer Foundation, Styrian Childhood Cancer Foundation, and other organizations. Dr. Mynarek and colleagues disclosed relationships with Medac, Novartis, Eli Lilly, Bayer, Roche, and numerous other companies. Dr. Robinson disclosed relationships with Eli Lilly, Genentech, and Novartis. Dr. Gajjar reported relationships with Genentech and Kazia Therapeutics.

[email protected]

SOURCE: Mynarek M et al. J Clin Oncol. 2020 Jun 20;38(18):2028-40.
 

Adding intraventricular methotrexate to systemic chemotherapy produced favorable survival outcomes in patients with desmoplastic medulloblastoma (DMB) and medulloblastoma with extensive nodularity (MBEN), according to research published in the Journal of Clinical Oncology.

Investigators conducted a prospective trial of 87 children diagnosed with nonmetastatic medulloblastoma before the age of 4 years who were treated from 2001-2011.

At 5 years after diagnosis, the 42 DMB/MBEN patients had a 93% progression-free survival (PFS) rate, a 100% overall survival (OS) rate, and a 93% craniospinal irradiation (CSI)–free survival rate.

“Our results suggest that ... poor outcomes of patients treated with systemic chemotherapy alone can be improved by the addition of intraventricular [methotrexate],” wrote Martin Mynarek, MD, of the University Medical Center Hamburg-Eppendorf (Germany), and colleagues.

However, it was a different story for the 45 patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (CLA), in which outcomes are historically worse. At 5 years, the PFS was 37%, the OS was 62%, and the CSI-free survival was 39% in these patients.

In 2006, the CMB and CLA patients started receiving local radiotherapy in addition to chemotherapy and intraventricular methotrexate, but the radiotherapy did not seem to help with their disease.

“Because data suggest no effects, or even adverse effects, of local radiotherapy, additional development of this approach does not seem justified,” the investigators wrote.

“Interestingly, almost all patients with CMB/LCA had distant or combined relapses after local radiotherapy,” they added. “One might speculate that local radiotherapy reduced disease burden of the primary tumor and subclinical metastasis in the posterior fossa, leading to a survival advantage of distant subclinical metastasis over local residues.”
 

Treatment details

The 87 patients were enrolled in the BIS4 arm of the HIT 2000 trial (NCT00303810), which was designed to test six protocols and identify the optimal approach for treating young patients with medulloblastoma, supratentorial primitive neuroectodermal tumor, or ependymoma.

Patients started “HIT-SKK” chemotherapy within 2-4 weeks of surgery. They received three cycles of intravenous cyclophosphamide, vincristine, methotrexate (followed by leucovorin rescue after 42 hours), carboplatin, and etoposide, with concomitant intraventricular methotrexate, for a duration of 6 months (Neuro Oncol. 2011 Jun;13[6]:669-79).

Among patients who achieved a complete remission, treatment was ended after two additional cycles of chemotherapy. For other patients, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended.

Starting in 2006, DMB and MBEN patients without complete remissions, as well as those with CMB or LCA, received 54 Gy of focal radiotherapy to the tumor bed after the first three treatment cycles.
 

SHH-I vs. SHH-II DMB/MBEN

DNA methylation profiling was available for 50 of the 87 patients in this analysis, 28 of whom had infantile sonic hedgehog (SHH)–activated DMB/MBEN. Data from these 28 patients – and 71 patients in a validation cohort – revealed no significant difference in 5-year PFS or OS based on methylation subtype.

The 5-year PFS was 73% in SHH-I patients and 83% in SHH-II patients (P = .25). The 5-year OS was 88% and 97%, respectively (P = .099).

“This suggests that the higher risk of relapse in the less favorable [SHH-I subtype] can be abrogated by the addition of intraventricular [methotrexate] to systemic chemotherapy,” the investigators wrote.

The results suggest SHH-I patients “markedly benefit” from the addition of intraventricular chemotherapy, according to the authors of a related editorial, Giles Robinson, MD, and Amar Gajjar, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn.

“However, cross-trial comparison of PFS among the SHH-II subtype does not suggest that SHH-II patients derive the same benefit,” the editorialists wrote.

These data divide SHH medulloblastoma into SHH-I, which benefits from chemotherapy with intraventricular methotrexate, and SHH-II, which can be cured without intraventricular methotrexate, high-dose chemotherapy, or focal radiotherapy, according to the editorialists.

This new information might prompt investigation of a risk-adapted approach. SHH-II patients would receive a reduced-intensity regimen with systemic chemotherapy only, and SHH-I patients would receive systemic chemotherapy combined with intraventricular methotrexate. This could avoid exposing young children to “more intensive therapy than necessary,” according to the editorialists.
 

Non-WNT/non-SHH disease

Patients with non-WNT/non-SHH medulloblastoma (CMB or LCA) were divided into molecularly defined subtypes group 3 (n = 14) and group 4 (n = 6). The patients in group 3 had lower survival rates than patients in group 4. The 5-year PFS rate was 36% and 83%, respectively (P < .001 ). The 5-year OS rate was 49% and 100%, respectively (P < .001).

“This represents the third recent publication to describe a poor PFS for group 3, and it signals a desperate need for better therapy,” the editorialists wrote. As for the “encouraging” survival rate for group 4 patients, there were only six subjects, which makes this finding “worthy of follow-up but not actionable.”

Even so, the investigators noted that “although poor survival has been reported for non-SHH CMB/LCA in almost every series of patients treated with CSI-sparing approaches, again, use of intraventricular [methotrexate] might be associated with slightly higher PFS, compared with conventional chemotherapy alone.”

As expected, IQ was significantly lower in patients who received CSI salvage. The mean IQ was 74 in patients who received CSI and 90 in patients who did not (P = .012). Neurocognitive outcomes were poor in general among CMB/LCA survivors, “which was closely related to use of radiotherapy,” according to the investigators.

“It is important to recognize that these studies were not designed to define outcome on the basis of molecular subgroup or subtype and that the sample size in all these studies is small,” Dr. Robinson and Dr. Gajjar wrote. “Thus, caution should be used when basing any treatment recommendation on these results, and it is our strong-held opinion that any treatment change be done on a well-planned and well-monitored clinical trial.”

This research was supported by the German Childhood Cancer Foundation, Styrian Childhood Cancer Foundation, and other organizations. Dr. Mynarek and colleagues disclosed relationships with Medac, Novartis, Eli Lilly, Bayer, Roche, and numerous other companies. Dr. Robinson disclosed relationships with Eli Lilly, Genentech, and Novartis. Dr. Gajjar reported relationships with Genentech and Kazia Therapeutics.

[email protected]

SOURCE: Mynarek M et al. J Clin Oncol. 2020 Jun 20;38(18):2028-40.
 

Adding intraventricular methotrexate to systemic chemotherapy produced favorable survival outcomes in patients with desmoplastic medulloblastoma (DMB) and medulloblastoma with extensive nodularity (MBEN), according to research published in the Journal of Clinical Oncology.

Investigators conducted a prospective trial of 87 children diagnosed with nonmetastatic medulloblastoma before the age of 4 years who were treated from 2001-2011.

At 5 years after diagnosis, the 42 DMB/MBEN patients had a 93% progression-free survival (PFS) rate, a 100% overall survival (OS) rate, and a 93% craniospinal irradiation (CSI)–free survival rate.

“Our results suggest that ... poor outcomes of patients treated with systemic chemotherapy alone can be improved by the addition of intraventricular [methotrexate],” wrote Martin Mynarek, MD, of the University Medical Center Hamburg-Eppendorf (Germany), and colleagues.

However, it was a different story for the 45 patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (CLA), in which outcomes are historically worse. At 5 years, the PFS was 37%, the OS was 62%, and the CSI-free survival was 39% in these patients.

In 2006, the CMB and CLA patients started receiving local radiotherapy in addition to chemotherapy and intraventricular methotrexate, but the radiotherapy did not seem to help with their disease.

“Because data suggest no effects, or even adverse effects, of local radiotherapy, additional development of this approach does not seem justified,” the investigators wrote.

“Interestingly, almost all patients with CMB/LCA had distant or combined relapses after local radiotherapy,” they added. “One might speculate that local radiotherapy reduced disease burden of the primary tumor and subclinical metastasis in the posterior fossa, leading to a survival advantage of distant subclinical metastasis over local residues.”
 

Treatment details

The 87 patients were enrolled in the BIS4 arm of the HIT 2000 trial (NCT00303810), which was designed to test six protocols and identify the optimal approach for treating young patients with medulloblastoma, supratentorial primitive neuroectodermal tumor, or ependymoma.

Patients started “HIT-SKK” chemotherapy within 2-4 weeks of surgery. They received three cycles of intravenous cyclophosphamide, vincristine, methotrexate (followed by leucovorin rescue after 42 hours), carboplatin, and etoposide, with concomitant intraventricular methotrexate, for a duration of 6 months (Neuro Oncol. 2011 Jun;13[6]:669-79).

Among patients who achieved a complete remission, treatment was ended after two additional cycles of chemotherapy. For other patients, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended.

Starting in 2006, DMB and MBEN patients without complete remissions, as well as those with CMB or LCA, received 54 Gy of focal radiotherapy to the tumor bed after the first three treatment cycles.
 

SHH-I vs. SHH-II DMB/MBEN

DNA methylation profiling was available for 50 of the 87 patients in this analysis, 28 of whom had infantile sonic hedgehog (SHH)–activated DMB/MBEN. Data from these 28 patients – and 71 patients in a validation cohort – revealed no significant difference in 5-year PFS or OS based on methylation subtype.

The 5-year PFS was 73% in SHH-I patients and 83% in SHH-II patients (P = .25). The 5-year OS was 88% and 97%, respectively (P = .099).

“This suggests that the higher risk of relapse in the less favorable [SHH-I subtype] can be abrogated by the addition of intraventricular [methotrexate] to systemic chemotherapy,” the investigators wrote.

The results suggest SHH-I patients “markedly benefit” from the addition of intraventricular chemotherapy, according to the authors of a related editorial, Giles Robinson, MD, and Amar Gajjar, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn.

“However, cross-trial comparison of PFS among the SHH-II subtype does not suggest that SHH-II patients derive the same benefit,” the editorialists wrote.

These data divide SHH medulloblastoma into SHH-I, which benefits from chemotherapy with intraventricular methotrexate, and SHH-II, which can be cured without intraventricular methotrexate, high-dose chemotherapy, or focal radiotherapy, according to the editorialists.

This new information might prompt investigation of a risk-adapted approach. SHH-II patients would receive a reduced-intensity regimen with systemic chemotherapy only, and SHH-I patients would receive systemic chemotherapy combined with intraventricular methotrexate. This could avoid exposing young children to “more intensive therapy than necessary,” according to the editorialists.
 

Non-WNT/non-SHH disease

Patients with non-WNT/non-SHH medulloblastoma (CMB or LCA) were divided into molecularly defined subtypes group 3 (n = 14) and group 4 (n = 6). The patients in group 3 had lower survival rates than patients in group 4. The 5-year PFS rate was 36% and 83%, respectively (P < .001 ). The 5-year OS rate was 49% and 100%, respectively (P < .001).

“This represents the third recent publication to describe a poor PFS for group 3, and it signals a desperate need for better therapy,” the editorialists wrote. As for the “encouraging” survival rate for group 4 patients, there were only six subjects, which makes this finding “worthy of follow-up but not actionable.”

Even so, the investigators noted that “although poor survival has been reported for non-SHH CMB/LCA in almost every series of patients treated with CSI-sparing approaches, again, use of intraventricular [methotrexate] might be associated with slightly higher PFS, compared with conventional chemotherapy alone.”

As expected, IQ was significantly lower in patients who received CSI salvage. The mean IQ was 74 in patients who received CSI and 90 in patients who did not (P = .012). Neurocognitive outcomes were poor in general among CMB/LCA survivors, “which was closely related to use of radiotherapy,” according to the investigators.

“It is important to recognize that these studies were not designed to define outcome on the basis of molecular subgroup or subtype and that the sample size in all these studies is small,” Dr. Robinson and Dr. Gajjar wrote. “Thus, caution should be used when basing any treatment recommendation on these results, and it is our strong-held opinion that any treatment change be done on a well-planned and well-monitored clinical trial.”

This research was supported by the German Childhood Cancer Foundation, Styrian Childhood Cancer Foundation, and other organizations. Dr. Mynarek and colleagues disclosed relationships with Medac, Novartis, Eli Lilly, Bayer, Roche, and numerous other companies. Dr. Robinson disclosed relationships with Eli Lilly, Genentech, and Novartis. Dr. Gajjar reported relationships with Genentech and Kazia Therapeutics.

[email protected]

SOURCE: Mynarek M et al. J Clin Oncol. 2020 Jun 20;38(18):2028-40.
 

Ivosidenib may be effective against nonenhancing IDH1-mutated (mIDH1) advanced glioma, a phase 1 study suggests.

The median progression-free survival was 13.6 months for patients with nonenhancing tumors and 1.4 months for patients with enhancing tumors in a study of 66 adults with mIDH1 advanced glioma.

“On the basis of these data, additional clinical development of mIDH inhibitors for mIDH low-grade gliomas is warranted,” Ingo Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in the Journal of Clinical Oncology.

“This is not a home run but is of interest to the community,” said Lawrence Recht, MD, of Stanford (Calif.) University, who was not involved in this study. “Other companies are also developing agents like this.”

Considering that the ivosidenib study “is uncontrolled, one cannot say for sure that this wasn’t just the natural history of the disease,” Dr. Recht continued. “This type of tumor can behave very indolently, and patients can survive years without treatment, so this is rather a short interval to make a long-time statement. I think the authors are a bit overenthusiastic.”

The authors tested ivosidenib in 66 adults with mIDH1 glioma – 35 with nonenhancing glioma and 31 with enhancing glioma. Tumors had recurred after, or did not respond to, initial surgery, radiation, or chemotherapy.

The patients’ median age was 41 years (range, 21-71 years), and 25 patients (37.9%) were women. The most common tumor type at screening was oligodendroglioma in 23 patients (34.8%).

Patients received ivosidenib at doses ranging from 100 mg twice a day to 900 mg once a day. A total of 50 patients received the phase 2 recommended dose – 500 mg once a day. There were no dose-limiting toxicities, and there was no maximum-tolerated dose.

Adverse events of grade 3 or higher occurred in 19.7% of patients and included headache, seizure, hyperglycemia, neutropenia, and hypophosphatemia. Grade 3 or higher treatment-related adverse events occurred in two patients.

A total of 30 patients with nonenhancing tumors (85.7%) and 14 with enhancing tumors (45.2%) had a best response of stable disease. There was one partial response in a nonenhancing patient on 500 mg/day. The rest of the subjects had a best response of progressive disease.

The median treatment duration was 18.4 months among patients with nonenhancing tumors and 1.9 months among those with enhancing tumors. Discontinuation was caused byo progression in all but one case.

Among patients with measurable disease, tumor measurements decreased from baseline in 22 nonenhancing tumors (66.7%) and in 9 enhancing tumors (33.3%).

“Despite the heterogeneous patient population in our trial, the nonrandomized design, and the lack of central pathology review, the data from our trial suggest that ivosidenib has greater activity against nonenhancing gliomas than against enhancing gliomas,” the investigators wrote. “This finding may seem surprising because the absence of contrast enhancement is typically associated with impaired drug delivery.

“We hypothesize that ivosidenib may be more effective in nonenhancing gliomas because these tumors represent an earlier disease stage with fewer genetic alterations, reminiscent of the greater antitumor activity of the BCR-ABL inhibitor imatinib in earlier stages of chronic myeloid leukemia,” the investigators wrote.

The team also noted that the median progression-free survival for patients with nonenhancing gliomas in the current study “compares favorably to that reported for temozolomide” in advanced mIDH1 low-grade glioma, which was approximately 7 months.

This research was funded by Agios Pharmaceuticals, the company developing ivosidenib. Dr. Mellinghoff receives travel compensation from and is an adviser to the company. Several other investigators are employees. Dr. Recht disclosed no conflicts of interest.

[email protected]

SOURCE: Mellinghoff I et al. J Clin Oncol. 2020 Jun 12. doi: 10.1200/JCO.19.03327

Ivosidenib may be effective against nonenhancing IDH1-mutated (mIDH1) advanced glioma, a phase 1 study suggests.

The median progression-free survival was 13.6 months for patients with nonenhancing tumors and 1.4 months for patients with enhancing tumors in a study of 66 adults with mIDH1 advanced glioma.

“On the basis of these data, additional clinical development of mIDH inhibitors for mIDH low-grade gliomas is warranted,” Ingo Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in the Journal of Clinical Oncology.

“This is not a home run but is of interest to the community,” said Lawrence Recht, MD, of Stanford (Calif.) University, who was not involved in this study. “Other companies are also developing agents like this.”

Considering that the ivosidenib study “is uncontrolled, one cannot say for sure that this wasn’t just the natural history of the disease,” Dr. Recht continued. “This type of tumor can behave very indolently, and patients can survive years without treatment, so this is rather a short interval to make a long-time statement. I think the authors are a bit overenthusiastic.”

The authors tested ivosidenib in 66 adults with mIDH1 glioma – 35 with nonenhancing glioma and 31 with enhancing glioma. Tumors had recurred after, or did not respond to, initial surgery, radiation, or chemotherapy.

The patients’ median age was 41 years (range, 21-71 years), and 25 patients (37.9%) were women. The most common tumor type at screening was oligodendroglioma in 23 patients (34.8%).

Patients received ivosidenib at doses ranging from 100 mg twice a day to 900 mg once a day. A total of 50 patients received the phase 2 recommended dose – 500 mg once a day. There were no dose-limiting toxicities, and there was no maximum-tolerated dose.

Adverse events of grade 3 or higher occurred in 19.7% of patients and included headache, seizure, hyperglycemia, neutropenia, and hypophosphatemia. Grade 3 or higher treatment-related adverse events occurred in two patients.

A total of 30 patients with nonenhancing tumors (85.7%) and 14 with enhancing tumors (45.2%) had a best response of stable disease. There was one partial response in a nonenhancing patient on 500 mg/day. The rest of the subjects had a best response of progressive disease.

The median treatment duration was 18.4 months among patients with nonenhancing tumors and 1.9 months among those with enhancing tumors. Discontinuation was caused byo progression in all but one case.

Among patients with measurable disease, tumor measurements decreased from baseline in 22 nonenhancing tumors (66.7%) and in 9 enhancing tumors (33.3%).

“Despite the heterogeneous patient population in our trial, the nonrandomized design, and the lack of central pathology review, the data from our trial suggest that ivosidenib has greater activity against nonenhancing gliomas than against enhancing gliomas,” the investigators wrote. “This finding may seem surprising because the absence of contrast enhancement is typically associated with impaired drug delivery.

“We hypothesize that ivosidenib may be more effective in nonenhancing gliomas because these tumors represent an earlier disease stage with fewer genetic alterations, reminiscent of the greater antitumor activity of the BCR-ABL inhibitor imatinib in earlier stages of chronic myeloid leukemia,” the investigators wrote.

The team also noted that the median progression-free survival for patients with nonenhancing gliomas in the current study “compares favorably to that reported for temozolomide” in advanced mIDH1 low-grade glioma, which was approximately 7 months.

This research was funded by Agios Pharmaceuticals, the company developing ivosidenib. Dr. Mellinghoff receives travel compensation from and is an adviser to the company. Several other investigators are employees. Dr. Recht disclosed no conflicts of interest.

[email protected]

SOURCE: Mellinghoff I et al. J Clin Oncol. 2020 Jun 12. doi: 10.1200/JCO.19.03327

Ivosidenib may be effective against nonenhancing IDH1-mutated (mIDH1) advanced glioma, a phase 1 study suggests.

The median progression-free survival was 13.6 months for patients with nonenhancing tumors and 1.4 months for patients with enhancing tumors in a study of 66 adults with mIDH1 advanced glioma.

“On the basis of these data, additional clinical development of mIDH inhibitors for mIDH low-grade gliomas is warranted,” Ingo Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in the Journal of Clinical Oncology.

“This is not a home run but is of interest to the community,” said Lawrence Recht, MD, of Stanford (Calif.) University, who was not involved in this study. “Other companies are also developing agents like this.”

Considering that the ivosidenib study “is uncontrolled, one cannot say for sure that this wasn’t just the natural history of the disease,” Dr. Recht continued. “This type of tumor can behave very indolently, and patients can survive years without treatment, so this is rather a short interval to make a long-time statement. I think the authors are a bit overenthusiastic.”

The authors tested ivosidenib in 66 adults with mIDH1 glioma – 35 with nonenhancing glioma and 31 with enhancing glioma. Tumors had recurred after, or did not respond to, initial surgery, radiation, or chemotherapy.

The patients’ median age was 41 years (range, 21-71 years), and 25 patients (37.9%) were women. The most common tumor type at screening was oligodendroglioma in 23 patients (34.8%).

Patients received ivosidenib at doses ranging from 100 mg twice a day to 900 mg once a day. A total of 50 patients received the phase 2 recommended dose – 500 mg once a day. There were no dose-limiting toxicities, and there was no maximum-tolerated dose.

Adverse events of grade 3 or higher occurred in 19.7% of patients and included headache, seizure, hyperglycemia, neutropenia, and hypophosphatemia. Grade 3 or higher treatment-related adverse events occurred in two patients.

A total of 30 patients with nonenhancing tumors (85.7%) and 14 with enhancing tumors (45.2%) had a best response of stable disease. There was one partial response in a nonenhancing patient on 500 mg/day. The rest of the subjects had a best response of progressive disease.

The median treatment duration was 18.4 months among patients with nonenhancing tumors and 1.9 months among those with enhancing tumors. Discontinuation was caused byo progression in all but one case.

Among patients with measurable disease, tumor measurements decreased from baseline in 22 nonenhancing tumors (66.7%) and in 9 enhancing tumors (33.3%).

“Despite the heterogeneous patient population in our trial, the nonrandomized design, and the lack of central pathology review, the data from our trial suggest that ivosidenib has greater activity against nonenhancing gliomas than against enhancing gliomas,” the investigators wrote. “This finding may seem surprising because the absence of contrast enhancement is typically associated with impaired drug delivery.

“We hypothesize that ivosidenib may be more effective in nonenhancing gliomas because these tumors represent an earlier disease stage with fewer genetic alterations, reminiscent of the greater antitumor activity of the BCR-ABL inhibitor imatinib in earlier stages of chronic myeloid leukemia,” the investigators wrote.

The team also noted that the median progression-free survival for patients with nonenhancing gliomas in the current study “compares favorably to that reported for temozolomide” in advanced mIDH1 low-grade glioma, which was approximately 7 months.

This research was funded by Agios Pharmaceuticals, the company developing ivosidenib. Dr. Mellinghoff receives travel compensation from and is an adviser to the company. Several other investigators are employees. Dr. Recht disclosed no conflicts of interest.

[email protected]

SOURCE: Mellinghoff I et al. J Clin Oncol. 2020 Jun 12. doi: 10.1200/JCO.19.03327

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

[email protected]

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

[email protected]

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

Patients with early onset cancers have an increased prevalence of germline pathogenic variants, suggesting that genetic testing would be worthwhile in this population, according to a presentation at the AACR virtual meeting II.

Investigators analyzed blood samples from 1,201 patients who were aged 18-39 years when diagnosed with a solid tumor malignancy.

In this group, there were 877 patients with early onset cancers, defined as cancers for which 39 years of age is greater than 1 standard deviation below the mean age of diagnosis for the cancer type.

The remaining 324 patients had young adult cancers, defined as cancers for which 39 years of age is less than 1 standard deviation below the mean age of diagnosis.

The most common early onset cancers were breast, colorectal, kidney, pancreas, and ovarian cancer.

The most common young adult cancers were sarcoma, brain cancer, and testicular cancer, as expected, said investigator Zsofia K. Stadler, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Stadler and colleagues performed next-generation sequencing of the patient samples using a panel of up to 88 genes previously implicated in cancer predisposition. This revealed a significantly higher prevalence of germline mutations in patients with early onset cancers than in those with young adult cancers – 21% and 13%, respectively (P = .002).

In patients with only high- and moderate-risk cancer susceptibility genes, the prevalence was 15% in the early onset group and 10% in the young adult group (P = .01). “Among the early onset cancer group, pancreas, breast, and kidney cancer patients harbored the highest rates of germline mutations,” Dr. Stadler said, noting that the spectrum of mutated genes differed in early onset and young adult cancer patients.

“In early onset patients, the most commonly mutated genes were BRCA1 and BRCA2 [4.9%], Lynch syndrome genes [2.2%], ATM [1.6%], and CHECK2 [1.7%],” Dr. Stadler said. “On the other hand, in young adults, TP53 mutations [2.2%], and SDHA and SDHB mutations dominated [1.9%], with the majority of mutations occurring in sarcoma patients.”

These findings suggest the prevalence of inherited cancer susceptibility syndromes in young adults with cancer is not uniform.

“We found a very high prevalence of germline mutations in young patients with cancer types that typically present at later ages,” Dr. Stadler said, referring to the early onset patients.

Conversely, the young adult cancer patients had a prevalence and spectrum of mutations more similar to what is seen in pediatric cancer populations, she noted.

The findings are surprising, according to AACR past president Elaine R. Mardis, PhD, of The Ohio State University in Columbus.

Dr. Mardis said the results show that, in young adults with early onset cancers, “the germline prevalence of these mutations is significantly higher than we had previously thought.”

“Although representing only about 4% of all cancers, young adults with cancer ... face unique challenges,” Dr. Stadler said. “Identifying whether a young patient’s cancer occurred in the setting of an inherited cancer predisposition syndrome is especially important in this patient population.”

Such knowledge “can significantly impact the risk of second primary cancers and the need for increased surveillance measures or even risk-reducing surgeries,” Dr. Stadler explained. She added that it can also have implications for identifying at-risk family members, such as younger siblings or children who should pursue genetic testing and appropriate prevention measures.

“Our results suggest that, among patients with early onset cancer, the increased prevalence of germline mutations supports a role for genetic testing, irrespective of tumor type,” Dr. Stadler said.

This study was partially funded by the Precision, Interception and Prevention Program, the Robert and Katie Niehaus Center for Inherited Cancer Genomics, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, and a National Cancer Institute Cancer Center Core Grant. Dr. Stadler reported that an immediate family member serves as a consultant in ophthalmology for Allergan, Adverum Biotechnologies, Alimera Sciences, BioMarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Mardis disclosed relationships with Qiagen NV, Pact Pharma LLC, Moderna Inc., and Interpreta LLC.

[email protected]

SOURCE: Stadler Z et al. AACR 2020, Abstract 1122.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.