An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

A version of this article first appeared on Medscape.com.

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

A version of this article first appeared on Medscape.com.

For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.

“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they wrote.

“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” compared with the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reported.

The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.

Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they wrote.

Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.

Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators pointed out. There is also a high incidence of skin and other toxicities and, in some studies, nonideal survival outcomes, they noted.

The new study was published online in the Journal of Clinical Oncology.

It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” commented the authors of an accompanying editorial (J Clin Oncol. 2023 Feb 1. doi: 10.1200/JCO.22.02350).

“Docetaxel belongs in the armamentarium of go-to regimens,” wrote radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.

This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard. ... It is high time to shift the conversation from whether radiosensitizers are beneficial to which regimen (if any) provides the most benefit and should define the standard of care,” they added.

The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.

The addition of docetaxel improved 2-year disease-free survival (42% vs. 30.3%; hazard ratio, 0.673; P = .002); 2-year overall survival (50.8% vs. 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs. 54.7%; HR, 0.661; P = .002).

Median overall survival was 25.5 months with docetaxel versus 15.3 months with radiation alone (P = .035).

Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators said.

There was a higher incidence of grade 3 or greater mucositis (49.7% vs. 22.2%), odynophagia (52.5% vs. 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reported. Overall, 86% of patients received five or more cycles docetaxel.

In their editorial, Dr. Mell and Dr. Wong noted that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but added that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”

The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Dr. Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Dr. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Dr. Wong disclosed research funding from Novartis and Merck.

A version of this article first appeared on Medscape.com.

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

Caring for a child with autism is a long haul for families and not often a smooth ride. Medications can help improve child functioning and family quality of life but the evidence may require our careful consideration.

Although I am discussing medication treatment here, the best evidence-based treatments for autism symptoms such as poor social communication and repetitive restricted behavior (RRB) are behavioral (for example, applied behavior analysis), cognitive-behavioral therapy (CBT), and parent training. These modalities also augment the effectiveness of medications in many cases. Educational adjustments and specific therapies, when indicated, such as speech-language, occupational, and physical therapy are also beneficial.

Autism symptoms change with age from early regression, later to RRB, then depression, and they are complicated by coexisting conditions. Not surprisingly then, studying the effectiveness and side effects of medications is complex and guidance is in flux as reliable data emerge.

Because of the shortage of specialists and increasing prevalence of autism, we need to be prepared to manage, monitor, and sometimes start medications for our autistic patients. With great individual differences and the hopes and fears of distressed parents making them desperate for help, we need to be as evidence-based as possible to avoid serious side effects or delay effective behavioral treatments.

Our assistance is mainly to address the many co-occurring symptoms in autism: 37%-85% ADHD, 50% anxiety, 7.3% bipolar disorder, and 54.1% depression (by age 30). Many autistic children have problematic irritability, explosive episodes, repetitive or rigid routines, difficulty with social engagement, or trouble sleeping.

We need to be clear with families about the evidence and, whenever possible, use our own time-limited trials with placebos and objective measures that target symptoms and goals for improvement. This is complicated by that fact that the child may have trouble communicating about how they feel, have hypo- or hypersensitivity to feelings, as well as confounding coexisting conditions.

The Food and Drug Administration has approved the atypical antipsychotics risperidone (ages 5-16) and aripiprazole (ages 6-17) for reducing symptoms of irritability by 25%-50% – such as agitation, stereotypy, anger outbursts, self-injurious behavior, and hyperactivity within 8 weeks. The Aberrant Behavior Checklist can be used for monitoring. These benefits are largest with behavior therapy and at doses of 1.25-1.75  mg/day (risperidone) or 2-15 mg/day (aripiprazole). Unfortunately, side effects of these medications include somnolence, increased appetite and weight gain (average of 5.1 kg), abnormal blood lipids and glucose, dyskinesia, and elevated prolactin (sometimes galactorrhea). Aripiprazole is equivalent to risperidone for irritability, has less prolactin and fewer metabolic effects, but sometimes has extrapyramidal symptoms. Other second-generation atypical antipsychotics have less evidence but may have fewer side effects. With careful monitoring, these medications can make a major difference in child behavior.

ADHD symptoms often respond to methylphenidate within 4 weeks but at a lower dose and with more side effects of irritability, social withdrawal, and emotional outbursts than for children with ADHD without autism. Formulations such as liquid (short or long acting) or dermal patch may facilitate the important small-dose adjustments and slow ramp-up we should use with checklist monitoring (for example, Vanderbilt Assessment). Atomoxetine also reduces hyperactivity, especially when used with parent training, but has associated nausea, anorexia, early awakening, and rare unpredictable liver failure. Mixed amphetamine salts have not been studied. Clonidine (oral or patch) and guanfacine extended release have also shown some effectiveness for hyperarousal, social interaction, and sleep although they can cause drowsiness/hypotension.

Sleep issues such as sleep onset, duration, and disruptions can improve with melatonin, especially combined with CBT, and it can even sometimes help with anxiety, rigidity, and communication. Use a certified brand and prevent accidental ingestion of gummy forms. Note that obstructive sleep apnea is significantly more common in children with autism spectrum disorder (ASD) and should be evaluated if there are signs. The Childhood Sleep Questionnaire can be used to monitor.

There aren’t data available for selective serotonin reuptake inhibitors in treating depression and anxiety in autistic children but CBT may help. Buspirone improved RRB (at 2.5 mg b.i.d.) but did not help mood. Mood-stabilizing antiepileptics have had mixed results (valproate reduced irritability but with serious side effects), no benefits (lamotrigine and levetiracetam), or no trials (lithium, oxcarbazepine, and topiramate). In spite of this, a Cochrane report recommends antidepressants “on a case by case basis” for children with ASD, keeping in mind the higher risks of behavioral activation (consider comorbid bipolar disorder), irritability, akathisia, and sleep disturbance. We can monitor with Short Moods and Feelings Questionnaire and Problem Behavior Checklist.

NMDA and GABA receptors are implicated in the genesis of ASD. Bumetanide, a GABA modulator, at 1 mg b.i.d., improved social communication and restricted interests, but had dose-related hypokalemia, increased urination, dehydration, loss of appetite, and asthenia. Donepezil (cholinesterase inhibitor) in small studies improved autism scores and expressive/receptive language. N-acetylcysteine, D-cycloserine, and arbaclofen did not show efficacy.

Currently, 64% of children with ASD are prescribed one psychotropic medication, 35% more than two classes, and 15% more than three. While we may look askance at polypharmacy, several medications not effective as monotherapy for children with ASD have significant effects in combination with risperidone; notably memantine, riluzole, N-acetylcysteine, amantadine, topiramate, and buspirone, compared with placebo. Memantine alone has shown benefits in 60% of autistic patients on social, language, and self-stimulatory behaviors at 2.5-30 mg; effective enough that 80% chose continuation.

Families often use complementary or alternative medicines (CAM) so we need to ask about them because CAM may interact with prescribed drugs or complicate determining the source of side effects or benefits. Oxytocin has promising but inconclusive data for improving social cognition but only for 3-8 year olds. Omega-3 fatty acid had benefits for young child stereotypy and lethargy but only by parent report. Vitamin B12, folinic acid, vitamin D3, and digestive enzymes may help but lack data. It is important that families not replace evidence-based treatments with CAM when there are significant symptoms needing treatment.

Being a person with autism, beyond the stress of rigid routines and social difficulties, may include being a target of physical or sexual abuse or bullying, which are risks for suicide. Suicide is eightfold greater in people with autism, especially those who are high functioning; thus, we need to include children with ASD in our routine suicide screening.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

References

Goel R et al. Int Rev Psychiatry. 2018;30(1):78-95.

Stepanova E et al. Dialogues Clin Neurosci. 2017;19(4):395-402.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on researchsquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• A few key factors predict when gallbladder cancer will be found on routine cholecystectomy, allowing for better surgical planning and treatment.

Why this matters

• More than 60% of gallbladder cancers are diagnosed incidentally following cholecystectomy for benign reasons.
• Identifying predictors allows surgeons to send high-risk individuals for oncologic evaluation beforehand and to prepare for intraoperative frozen pathology and more appropriate surgery, including extended cholecystectomy and lymph node dissection.

Study design

• The investigators analyzed 403,443 cholecystectomies in the American College of Surgeons’ NSQIP database from 2007 to 2017.
• They used multivariable logistic regression to identify risk factors for gallbladder cancers.
• Patients undergoing cholecystectomy for suspected or confirmed gallbladder cancer were excluded.

Key results

• The incidence of gallbladder cancer was 0.11% (441 of 403,443 patients).
• Preoperative factors significantly associated with gallbladder cancer included age older than 60 years (odds ratio [OR], 6.51), female sex (OR, 1.75), weight loss (OR, 2.58), and elevated alkaline phosphatase level (OR, 1.67).
• Starting with or converting to an open approach – both potential indicators of more complex disease – were associated with seven times’ higher odds of gallbladder cancer (OR, 7.33; P < .001), as were longer operative times (127 minutes vs. 70.7 minutes; P < .001).

Limitations

• There is a risk of selection bias regarding which patients were included in the database.
• Presenting symptoms, preoperative imaging findings, and pathologic staging were not available.
• The database did not record the reasons for choosing open surgery rather than laparoscopic surgery or for converting to an open approach.

Disclosures

• There was no funding for the work, and the investigators did not disclose any relevant financial relationships.

This is a summary of a preprint research study, “Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors,” led by Elizabeth Olecki of Penn State University, State College. The study has not been peer reviewed. The full text can be found at researchsquare.com. A version of this article first appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

The increased risk for diabetes following COVID-19 infection has persisted into the Omicron era, but vaccination against SARS-CoV-2 appears to diminish that likelihood, new data suggest.

The findings, from more than 20,000 patients in the Cedars-Sinai Health System in Los Angeles, suggest that “continued efforts to prevent COVID-19 infection may be beneficial to patient health until we develop better understanding of the effects of potential long-term effects of COVID-19,” lead author Alan C. Kwan, MD, of the department of cardiology at Cedars Sinai’s Smidt Heart Institute, said in an interview.

Several studies conducted early in the pandemic suggested increased risks for both new-onset diabetes and cardiometabolic diseases following COVID-19 infection, possibly because of persistent inflammation contributing to insulin resistance.

However, it hasn’t been clear if those risks have persisted with the more recent predominance of the less-virulent Omicron variant or whether the COVID-19 vaccine influences the risk. This new study suggests that both are the case.

“Our results verify that the risk of developing type 2 diabetes after a COVID-19 infection was not just an early observation but, in fact, a real risk that has, unfortunately, persisted through the Omicron era,” Dr. Kwan noted.

“While the level of evidence by our study and others may not reach the degree needed to affect formal guidelines at this time, we believe it is reasonable to have increased clinical suspicion for diabetes after COVID-19 infection and a lower threshold for testing,” he added.

Moreover, “we believe that our study and others suggest the potential role of COVID-19 to affect cardiovascular risk, and so both prevention of COVID-19 infection, through reasonable personal practices and vaccination, and an increased attention to cardiovascular health after COVID-19 infection is warranted.”

The findings were published online in JAMA Network Open.

Dr. Kwan and colleagues analyzed data for a total of 23,709 patients treated (inpatient and outpatient) for at least one COVID-19 infection between March 2020 and June 2022.

Rates of new-onset diabetes (using ICD-10 codes, primarily type 2 diabetes), hypertension, and hyperlipidemia were all elevated in the 90 days following COVID-19 infection compared with the 90 days prior. The same was true of two diagnoses unrelated to COVID-19, urinary tract infection and gastroesophageal reflux, used as benchmarks of health care engagement.

The highest odds for post versus preinfection were for diabetes (odds ratio, 2.35; P < .001), followed by hypertension (OR, 1.54; P < .001), the benchmark diagnoses (OR, 1.42; P < .001), and hyperlipidemia (OR, 1.22; P = .03).

Following adjustments, the risk versus the benchmark conditions for new-onset diabetes before versus after COVID-19 was significantly elevated (OR, 1.58; P < .001), while the risks for hypertension and hyperlipidemia versus benchmark diagnoses were not (OR, 1.06; P = .52 and 0.91, P = .43, respectively).

The diabetes risk after versus before COVID-19 infection was higher among those who had not been vaccinated (OR, 1.78; P < .001), compared with those who had received the vaccine (OR, 1.07; P = .80).

However, there was no significant interaction between vaccination and diabetes diagnosis (P = .08). “For this reason, we believe our data are suggestive of a protective effect in the population who received vaccination prior to infection, but [this is] not definitive,” Dr. Kwan said.

There were no apparent interactions by age, sex, or pre-existing cardiovascular risk factors, including hypertension or hyperlipidemia. Age, sex, and timing of index infection regarding the Omicron variant were not associated with an increased risk of a new cardiometabolic diagnosis before or after COVID-19 infection in any of the models.

Dr. Kwan said in an interview: “We have continued to be surprised by the evolving understanding of the SARS-CoV-2 virus and the effects on human health. In the beginning of the pandemic it was framed as a purely respiratory virus, which we now know to be a severely limited description of all of its potential effects on the human body. We believe that our research and others raise a concern for increased cardiometabolic risk after COVID infection.”

He added that, “while knowledge is incomplete on this topic, we believe that clinical providers may wish to have a higher degree of suspicion for both diabetes and risk of future cardiac events in patients after COVID infection, and that continued efforts to prevent COVID infection may be beneficial to patient health until we develop better understanding of the potential long-term effects of COVID.”

This study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and grants from the National Institutes of Health. Dr. Kwan reported receiving grants from the Doris Duke Charitable Foundation during the conduct of the study.

A version of this article originally appeared on Medscape.com.

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

A version of this article originally appeared on Medscape.com.

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

A version of this article originally appeared on Medscape.com.

Young premenopausal women with early stage hormone receptor (HR)-positive, HER2-negative breast cancer have notable genomic features that may help explain their historically poor outcomes and offer clues about molecular targets for future trials.

Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.

“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”

Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.

“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.

Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.

Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.

To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).

Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).

Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).

Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.

In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.

Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.

Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.

How might these results inform potential therapeutics?

Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.

In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.

An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.

Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”

Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.

Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”

She added that future research should also include ancestry and racial diversity.

“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.

The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
 

A version of this article originally appeared on Medscape.com.

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

“Don’t close the barn door after the horse is gone,” the old proverb goes. In other words, there’s no sense in trying to prevent something when it’s already too late.

In many ways and for many years, this saying has applied to providing local therapies to treat cancers that have metastasized to distant sites. I learned this lesson early on from my mentors and have relayed it to countless patients with advanced cancer over the past several decades.

But a growing body of evidence, alongside promising new therapies, highlights more and more exceptions to this long-held belief. Over my career, I have increasingly learned about the nuances of metastatic disease, specifically that metastasis represents a broad spectrum of indolent to extremely aggressive cancers.

This concept was outlined decades ago for oligometastatic disease and has since been studied in greater depth, and is even being applied in practice. Local therapy for colorectal cancer with limited liver-only metastases is now established as a path to potentially excellent long-term survival. And prospective randomized trials of local therapies for oligometastatic lung cancer or prostate cancer have also demonstrated improvements in clinical outcomes that should lead us to strongly consider integrating local therapy for appropriately selected patients.

In addition, early retrospective studies have provided a proof of principle that patients with solitary brain or adrenal metastases from non–small cell lung cancer (NSCLC) can do exceptionally well and even remain disease-free for many years after definitive local therapy to the primary tumor and oligometastatic disease. For example, a recent press release on the LUNAR trial reported an improvement in overall survival with tumor-treating fields (TTFs), a local therapy, compared with docetaxel as second-line therapy for patients with advanced NSCLC.

That said, the selection process for who receives local therapy remains subjective. In practice, I see patients who fall well outside of conventional oligometastatic parameters but who are directed to local therapy, commonly when systemic therapy is considered futile or prohibitively toxic.

At the same time, however, I also see many patients who would be appropriate candidates for local therapy for oligometastatic disease for whom this strategy is not pursued, perhaps because some oncologists remain dubious about the value of local therapy in this setting. And although we await the full data from the LUNAR trial, I would expect TTFs to face challenges in broad adoption because it is a novel platform with cumbersome practical application, particularly outside of larger centers.

But beyond the potential for TTFs to change management of previously treated advanced NSCLC, I think the findings are more significant because they represent a step, perhaps even a quantum leap, in the role that local therapy could play in improving survival in a broad, unselected population with advanced disease. That is a far more meaningful prospect than conferring benefits in well-selected patients with a narrow subtype of lung cancer. It will be important to determine whether certain subgroups from the LUNAR trial are driving this overall survival benefit.

Local therapy may even have value in the advanced cancer setting beyond oligometastatic disease. That potential is being explored in the SABR-COMET-10 trial, which randomly assigned 159 patients with 4-10 metastatic lesions from various cancers to stereotactic ablative body radiation with standard systemic therapy or the latter alone. With overall survival as the primary endpoint, this study could further revise our understanding of the use of local therapy for treating patients whose cancer biology does not fit the definition of oligometastatic disease.

Does this evolving landscape mean that we were wrong to minimize the role of local therapy?

I don’t think so. The risk/benefit of local therapy today is predicated on two key factors that were absent a few decades ago. First, local therapies such as stereotactic ablative body radiation, minimally invasive surgery, and TTFs now offer disease control with far less attendant toxicity than conventional external beam radiation therapy or open surgery. Second, newer systemic therapies that include targeted therapies and immunotherapy confer remarkably greater disease control for far more patients than does conventional chemotherapy alone.

It is this combination of local therapy’s excellent therapeutic index applied against a background of far better systemic disease control that makes the interplay of local and systemic treatments a newly relevant, open question.

We have yet to see the details of several pivotal trials, but I feel that we should be prepared to question some of the historic dogma in our field to achieve better outcomes not just for selected, narrow subgroups but for a broader population with different types of metastatic cancer.
 

Dr. West is clinical associate professor, department of medical oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He disclosed ties with Ariad/Takeda, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Merck, Pfizer, and Spectrum. A version of this article originally appeared on Medscape.com.

All adolescents, with or without chronic medical conditions, will eventually need the guidance of their pediatric clinicians to transition into adult medical care. However, many clinicians feel insufficiently prepared to provide comprehensive transition services. This can result in the actual handoff or transfer into adult care being abrupt, incomplete, or outright unsuccessful. By following the recommended best practices of transitions, providers of pediatric care can ensure that this challenging goodbye prepares everyone for the next steps ahead.

Using a structured transition process

In 2011, a health care transition clinical report based on expert opinion and practice consensus and endorsed by the American Academy of Pediatrics, American Academy of Family Physicians, and American College of Physicians – Society of Internal Medicine was released. This report provided a decision-making algorithm for “practice-based implementation of transition for all youth beginning in early adolescence.”

The Got Transition organization, funded by the Maternal Child Health Bureau and Health Resources and Services Administration, provides web-based information and materials for health care providers and families to establish a smooth and successful transition. At the center of these recommendations are the Six Core Elements of Health Care Transition – the essential components of a structured transition process: 1) transition policy/guide; 2) tracking and monitoring; 3) readiness; 4) planning; 5) transfer of care, and 6) transition completion.

This transition process should start early in adolescence, preferably by age 12-14 years, to give adequate time to progress successfully through these elements and improve the likelihood of a smooth, final transfer into the care of an adult clinician.
 

Preparing your patients for transfer

Despite the availability of these recommendations, national surveys show that the overwhelming majority of adolescents with and without special health care needs report not receiving transition services. Lack of time, resources, interest, and patients being lost to care during adolescence all contribute to this deficit in care. Without transition preparation, the actual handoff or transfer to adult care can be difficult for adolescents, caregivers, and clinicians alike. Adolescents and caregivers may feel a sense of abandonment or have inadequate health knowledge/literacy, pediatric clinicians may fear that the patient is not ready for the expected independence, and adult clinicians face numerous challenges integrating these young patients into their practice.

A structured transition process can help the family and clinicians know what to expect during the transfer of care. Pediatric clinicians can gradually move from a pediatric model of care, in which the caregiver is the center of communication, to an adult model, putting the patient at the center. By encouraging the adolescent to be the direct communicator, the pediatric clinician can promote independence and assess health knowledge, allowing for education where gaps exist.

Assisting the patient in identifying and even meeting the adult clinician well ahead of the final transfer date can also make the process less daunting for the adolescent.

Adult clinicians should consider allowing more time for the first visit with a new young adult patient and welcome caregiver input early in the transfer process, particularly for patients with a chronic disease. By engaging patients and families in an intentional, gradual transition process with an expected outcome, all those involved will be more prepared for the final handoff.
 

Utilizing transition tools and engaging the adolescent

Numerous tools can assist in the preparation for transfer to adult care. These include transition summaries and emergency plans, which contain essential information such as current medical problems, allergies, medications, prior procedures and treatments, and sick day plans. Such tools can also be built into electronic medical records for easy modification and updating. They can be used as methods to engage and teach adolescents about their disease history and current regimen and can contain essential components for information handoff at the time of transfer to adult care. If the patient carries a rare diagnosis, or one that has historically been associated with lower survival to adulthood, these transfer documents can also include summary information about disease states and contact information for pediatric specialty clinicians.

Adolescent engagement in their health care during the time of transition can also be prompted through the use of patient portals within an electronic health record. Such portals put health information directly at the adolescent’s fingertips, provide them with an outlet for communication with their clinicians, and give reminders regarding health maintenance.
 

Completing the transfer: The final handoff

The best and most recommended means of relaying information at the time of transfer to adult care is a direct, verbal handoff between clinicians. This direct handoff has several goals:

(1) To ensure the patient has scheduled or attended the first appointment with the adult clinician

(2) To ensure record transfer has occurred successfully

(3) To answer any questions the receiving clinician may have about prior or ongoing care.

(4) To offer the adult clinician ongoing access to the pediatric clinician as an “expert” resource for additional questions.

By remaining available as a resource, the pediatric clinician can alleviate concerns for both the patient and caregiver as well as the receiving adult clinician.

As valuable as verbal handoffs can be, they are not always possible due to patients not having selected an adult clinician prior to leaving the pediatric clinician, an inability to reach the receiving clinician, and/or time limitations. Many of these barriers can be alleviated by early discussions of transitions of care as well as utilization of structured documentation tools as noted above.

It is also recommended that the pediatric clinician follows up with the patient and/or caregiver several months after the transfer is complete. This allows for the adolescent and/or the caregiver to reflect on the transition process and provide feedback to the pediatric clinicians and their practice for ongoing process improvement.
 

Reflection as a pediatrician

Ideally, all transition steps occur for the adolescent; in our opinion, a crucial component is to prepare the adolescent patient for the change from a pediatric to adult model of care, in which they are independent in their health communication and decision-making. By engaging adolescents to understand their health, how to maintain it, and when to seek care, we empower them to advocate for their own health as young adults. With appropriate health knowledge and literacy, adolescents are more likely to actively engage with their health care providers and make healthy lifestyle choices. So though saying goodbye may still be difficult, it can be done with the confidence that the patients will continue to get the care they need as they transition into adulthood.
 

Dr. Kim is assistant clinical professor, department of pediatrics, University of California, San Diego. Dr. Mennito is associate professor of pediatrics and internal medicine, Medical University of South Carolina, Charleston, S.C. Dr. Kim and Dr. Mennito have disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

All adolescents, with or without chronic medical conditions, will eventually need the guidance of their pediatric clinicians to transition into adult medical care. However, many clinicians feel insufficiently prepared to provide comprehensive transition services. This can result in the actual handoff or transfer into adult care being abrupt, incomplete, or outright unsuccessful. By following the recommended best practices of transitions, providers of pediatric care can ensure that this challenging goodbye prepares everyone for the next steps ahead.

Using a structured transition process

In 2011, a health care transition clinical report based on expert opinion and practice consensus and endorsed by the American Academy of Pediatrics, American Academy of Family Physicians, and American College of Physicians – Society of Internal Medicine was released. This report provided a decision-making algorithm for “practice-based implementation of transition for all youth beginning in early adolescence.”

The Got Transition organization, funded by the Maternal Child Health Bureau and Health Resources and Services Administration, provides web-based information and materials for health care providers and families to establish a smooth and successful transition. At the center of these recommendations are the Six Core Elements of Health Care Transition – the essential components of a structured transition process: 1) transition policy/guide; 2) tracking and monitoring; 3) readiness; 4) planning; 5) transfer of care, and 6) transition completion.

This transition process should start early in adolescence, preferably by age 12-14 years, to give adequate time to progress successfully through these elements and improve the likelihood of a smooth, final transfer into the care of an adult clinician.
 

Preparing your patients for transfer

Despite the availability of these recommendations, national surveys show that the overwhelming majority of adolescents with and without special health care needs report not receiving transition services. Lack of time, resources, interest, and patients being lost to care during adolescence all contribute to this deficit in care. Without transition preparation, the actual handoff or transfer to adult care can be difficult for adolescents, caregivers, and clinicians alike. Adolescents and caregivers may feel a sense of abandonment or have inadequate health knowledge/literacy, pediatric clinicians may fear that the patient is not ready for the expected independence, and adult clinicians face numerous challenges integrating these young patients into their practice.

A structured transition process can help the family and clinicians know what to expect during the transfer of care. Pediatric clinicians can gradually move from a pediatric model of care, in which the caregiver is the center of communication, to an adult model, putting the patient at the center. By encouraging the adolescent to be the direct communicator, the pediatric clinician can promote independence and assess health knowledge, allowing for education where gaps exist.

Assisting the patient in identifying and even meeting the adult clinician well ahead of the final transfer date can also make the process less daunting for the adolescent.

Adult clinicians should consider allowing more time for the first visit with a new young adult patient and welcome caregiver input early in the transfer process, particularly for patients with a chronic disease. By engaging patients and families in an intentional, gradual transition process with an expected outcome, all those involved will be more prepared for the final handoff.
 

Utilizing transition tools and engaging the adolescent

Numerous tools can assist in the preparation for transfer to adult care. These include transition summaries and emergency plans, which contain essential information such as current medical problems, allergies, medications, prior procedures and treatments, and sick day plans. Such tools can also be built into electronic medical records for easy modification and updating. They can be used as methods to engage and teach adolescents about their disease history and current regimen and can contain essential components for information handoff at the time of transfer to adult care. If the patient carries a rare diagnosis, or one that has historically been associated with lower survival to adulthood, these transfer documents can also include summary information about disease states and contact information for pediatric specialty clinicians.

Adolescent engagement in their health care during the time of transition can also be prompted through the use of patient portals within an electronic health record. Such portals put health information directly at the adolescent’s fingertips, provide them with an outlet for communication with their clinicians, and give reminders regarding health maintenance.
 

Completing the transfer: The final handoff

The best and most recommended means of relaying information at the time of transfer to adult care is a direct, verbal handoff between clinicians. This direct handoff has several goals:

(1) To ensure the patient has scheduled or attended the first appointment with the adult clinician

(2) To ensure record transfer has occurred successfully

(3) To answer any questions the receiving clinician may have about prior or ongoing care.

(4) To offer the adult clinician ongoing access to the pediatric clinician as an “expert” resource for additional questions.

By remaining available as a resource, the pediatric clinician can alleviate concerns for both the patient and caregiver as well as the receiving adult clinician.

As valuable as verbal handoffs can be, they are not always possible due to patients not having selected an adult clinician prior to leaving the pediatric clinician, an inability to reach the receiving clinician, and/or time limitations. Many of these barriers can be alleviated by early discussions of transitions of care as well as utilization of structured documentation tools as noted above.

It is also recommended that the pediatric clinician follows up with the patient and/or caregiver several months after the transfer is complete. This allows for the adolescent and/or the caregiver to reflect on the transition process and provide feedback to the pediatric clinicians and their practice for ongoing process improvement.
 

Reflection as a pediatrician

Ideally, all transition steps occur for the adolescent; in our opinion, a crucial component is to prepare the adolescent patient for the change from a pediatric to adult model of care, in which they are independent in their health communication and decision-making. By engaging adolescents to understand their health, how to maintain it, and when to seek care, we empower them to advocate for their own health as young adults. With appropriate health knowledge and literacy, adolescents are more likely to actively engage with their health care providers and make healthy lifestyle choices. So though saying goodbye may still be difficult, it can be done with the confidence that the patients will continue to get the care they need as they transition into adulthood.
 

Dr. Kim is assistant clinical professor, department of pediatrics, University of California, San Diego. Dr. Mennito is associate professor of pediatrics and internal medicine, Medical University of South Carolina, Charleston, S.C. Dr. Kim and Dr. Mennito have disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

All adolescents, with or without chronic medical conditions, will eventually need the guidance of their pediatric clinicians to transition into adult medical care. However, many clinicians feel insufficiently prepared to provide comprehensive transition services. This can result in the actual handoff or transfer into adult care being abrupt, incomplete, or outright unsuccessful. By following the recommended best practices of transitions, providers of pediatric care can ensure that this challenging goodbye prepares everyone for the next steps ahead.

Using a structured transition process

In 2011, a health care transition clinical report based on expert opinion and practice consensus and endorsed by the American Academy of Pediatrics, American Academy of Family Physicians, and American College of Physicians – Society of Internal Medicine was released. This report provided a decision-making algorithm for “practice-based implementation of transition for all youth beginning in early adolescence.”

The Got Transition organization, funded by the Maternal Child Health Bureau and Health Resources and Services Administration, provides web-based information and materials for health care providers and families to establish a smooth and successful transition. At the center of these recommendations are the Six Core Elements of Health Care Transition – the essential components of a structured transition process: 1) transition policy/guide; 2) tracking and monitoring; 3) readiness; 4) planning; 5) transfer of care, and 6) transition completion.

This transition process should start early in adolescence, preferably by age 12-14 years, to give adequate time to progress successfully through these elements and improve the likelihood of a smooth, final transfer into the care of an adult clinician.
 

Preparing your patients for transfer

Despite the availability of these recommendations, national surveys show that the overwhelming majority of adolescents with and without special health care needs report not receiving transition services. Lack of time, resources, interest, and patients being lost to care during adolescence all contribute to this deficit in care. Without transition preparation, the actual handoff or transfer to adult care can be difficult for adolescents, caregivers, and clinicians alike. Adolescents and caregivers may feel a sense of abandonment or have inadequate health knowledge/literacy, pediatric clinicians may fear that the patient is not ready for the expected independence, and adult clinicians face numerous challenges integrating these young patients into their practice.

A structured transition process can help the family and clinicians know what to expect during the transfer of care. Pediatric clinicians can gradually move from a pediatric model of care, in which the caregiver is the center of communication, to an adult model, putting the patient at the center. By encouraging the adolescent to be the direct communicator, the pediatric clinician can promote independence and assess health knowledge, allowing for education where gaps exist.

Assisting the patient in identifying and even meeting the adult clinician well ahead of the final transfer date can also make the process less daunting for the adolescent.

Adult clinicians should consider allowing more time for the first visit with a new young adult patient and welcome caregiver input early in the transfer process, particularly for patients with a chronic disease. By engaging patients and families in an intentional, gradual transition process with an expected outcome, all those involved will be more prepared for the final handoff.
 

Utilizing transition tools and engaging the adolescent

Numerous tools can assist in the preparation for transfer to adult care. These include transition summaries and emergency plans, which contain essential information such as current medical problems, allergies, medications, prior procedures and treatments, and sick day plans. Such tools can also be built into electronic medical records for easy modification and updating. They can be used as methods to engage and teach adolescents about their disease history and current regimen and can contain essential components for information handoff at the time of transfer to adult care. If the patient carries a rare diagnosis, or one that has historically been associated with lower survival to adulthood, these transfer documents can also include summary information about disease states and contact information for pediatric specialty clinicians.

Adolescent engagement in their health care during the time of transition can also be prompted through the use of patient portals within an electronic health record. Such portals put health information directly at the adolescent’s fingertips, provide them with an outlet for communication with their clinicians, and give reminders regarding health maintenance.
 

Completing the transfer: The final handoff

The best and most recommended means of relaying information at the time of transfer to adult care is a direct, verbal handoff between clinicians. This direct handoff has several goals:

(1) To ensure the patient has scheduled or attended the first appointment with the adult clinician

(2) To ensure record transfer has occurred successfully

(3) To answer any questions the receiving clinician may have about prior or ongoing care.

(4) To offer the adult clinician ongoing access to the pediatric clinician as an “expert” resource for additional questions.

By remaining available as a resource, the pediatric clinician can alleviate concerns for both the patient and caregiver as well as the receiving adult clinician.

As valuable as verbal handoffs can be, they are not always possible due to patients not having selected an adult clinician prior to leaving the pediatric clinician, an inability to reach the receiving clinician, and/or time limitations. Many of these barriers can be alleviated by early discussions of transitions of care as well as utilization of structured documentation tools as noted above.

It is also recommended that the pediatric clinician follows up with the patient and/or caregiver several months after the transfer is complete. This allows for the adolescent and/or the caregiver to reflect on the transition process and provide feedback to the pediatric clinicians and their practice for ongoing process improvement.
 

Reflection as a pediatrician

Ideally, all transition steps occur for the adolescent; in our opinion, a crucial component is to prepare the adolescent patient for the change from a pediatric to adult model of care, in which they are independent in their health communication and decision-making. By engaging adolescents to understand their health, how to maintain it, and when to seek care, we empower them to advocate for their own health as young adults. With appropriate health knowledge and literacy, adolescents are more likely to actively engage with their health care providers and make healthy lifestyle choices. So though saying goodbye may still be difficult, it can be done with the confidence that the patients will continue to get the care they need as they transition into adulthood.
 

Dr. Kim is assistant clinical professor, department of pediatrics, University of California, San Diego. Dr. Mennito is associate professor of pediatrics and internal medicine, Medical University of South Carolina, Charleston, S.C. Dr. Kim and Dr. Mennito have disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

Regularly using a mobile device as a calming strategy for your child could lead to worse behavioral challenges down the road, according to developmental behavioral pediatricians at University of Michigan Health C. S. Mott Children’s Hospital, Ann Arbor.

What to know

• Using a mobile device to distract children from how they are feeling may displace opportunities for them to develop independent, alternative methods to self-regulate, especially in early childhood.
• Signs of increased dysregulation could include rapid shifts between sadness and excitement, a sudden change in mood or feelings, and heightened impulsivity.
• The association between device-calming and emotional consequences may be particularly high among young boys and children who are already experiencing hyperactivity, impulsiveness, and a strong temperament that makes them more likely to react intensely to feelings such as anger, frustration, and sadness.
• While occasional use of media to occupy children is expected and understandable, it is important that it not become a primary or regular soothing tool, and children should be given clear expectations of when and where devices can be used.
• The preschool-to-kindergarten period is a developmental stage in which children may be more likely to exhibit difficult behaviors, such as tantrums, defiance, and intense emotions, but parents should resist using devices as a parenting strategy.
•  

This is a summary of the article, “Longitudinal Association Between Use of Mobile Devices for Calming and Emotional Reactivity and Executive Functioning in Children Aged 3 to 5 Years,” published in JAMA Pediatrics on Dec. 20, 2022. The full article can be found on jamanetwork.com. A version of this article originally appeared on Medscape.com.

Regularly using a mobile device as a calming strategy for your child could lead to worse behavioral challenges down the road, according to developmental behavioral pediatricians at University of Michigan Health C. S. Mott Children’s Hospital, Ann Arbor.

What to know

• Using a mobile device to distract children from how they are feeling may displace opportunities for them to develop independent, alternative methods to self-regulate, especially in early childhood.
• Signs of increased dysregulation could include rapid shifts between sadness and excitement, a sudden change in mood or feelings, and heightened impulsivity.
• The association between device-calming and emotional consequences may be particularly high among young boys and children who are already experiencing hyperactivity, impulsiveness, and a strong temperament that makes them more likely to react intensely to feelings such as anger, frustration, and sadness.
• While occasional use of media to occupy children is expected and understandable, it is important that it not become a primary or regular soothing tool, and children should be given clear expectations of when and where devices can be used.
• The preschool-to-kindergarten period is a developmental stage in which children may be more likely to exhibit difficult behaviors, such as tantrums, defiance, and intense emotions, but parents should resist using devices as a parenting strategy.
•  

This is a summary of the article, “Longitudinal Association Between Use of Mobile Devices for Calming and Emotional Reactivity and Executive Functioning in Children Aged 3 to 5 Years,” published in JAMA Pediatrics on Dec. 20, 2022. The full article can be found on jamanetwork.com. A version of this article originally appeared on Medscape.com.

Regularly using a mobile device as a calming strategy for your child could lead to worse behavioral challenges down the road, according to developmental behavioral pediatricians at University of Michigan Health C. S. Mott Children’s Hospital, Ann Arbor.

What to know

• Using a mobile device to distract children from how they are feeling may displace opportunities for them to develop independent, alternative methods to self-regulate, especially in early childhood.
• Signs of increased dysregulation could include rapid shifts between sadness and excitement, a sudden change in mood or feelings, and heightened impulsivity.
• The association between device-calming and emotional consequences may be particularly high among young boys and children who are already experiencing hyperactivity, impulsiveness, and a strong temperament that makes them more likely to react intensely to feelings such as anger, frustration, and sadness.
• While occasional use of media to occupy children is expected and understandable, it is important that it not become a primary or regular soothing tool, and children should be given clear expectations of when and where devices can be used.
• The preschool-to-kindergarten period is a developmental stage in which children may be more likely to exhibit difficult behaviors, such as tantrums, defiance, and intense emotions, but parents should resist using devices as a parenting strategy.
•  

This is a summary of the article, “Longitudinal Association Between Use of Mobile Devices for Calming and Emotional Reactivity and Executive Functioning in Children Aged 3 to 5 Years,” published in JAMA Pediatrics on Dec. 20, 2022. The full article can be found on jamanetwork.com. A version of this article originally appeared on Medscape.com.

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

A version of this article originally appeared on Medscape.com.

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

A version of this article originally appeared on Medscape.com.

Family medicine physician Kenneth Cheng, DO, was on-call at a local hospital when a nurse told him that a patient needing evaluation hated Asians.

“I talked to him about whether he was okay seeing me and he said yes,” Dr. Cheng said. “But I remained vigilant and conscious of what the patient was doing the whole time so he couldn’t take advantage of the situation.”

Dr. Cheng never turned his back to the patient and even backed out of the exam room. That encounter passed without incident. However, a urologist Dr. Cheng knew from residency wasn’t so fortunate. Ronald Gilbert, MD, of Newport Beach, Calif., was shot and killed by a patient in his office. The patient blamed him for complications following prostate surgery 25 years earlier.

In 2022, a gunman in Tulsa, Okla., blamed his physician for pain from a recent back surgery and shot and killed him, another physician, and two others in a medical building before taking his own life.

Nearly 9 in 10 physicians reported in a recent Medscape poll that they had experienced one or more violent or potentially violent incidents in the past year. The most common patient behaviors were verbal abuse, getting angry and leaving, and behaving erratically.

About one in three respondents said that the patients threatened to harm them, and about one in five said that the patients became violent.

Experts say that many factors contribute to this potentially lethal situation: Health care services have become more impersonal, patients experience longer wait times, some abuse prescription drugs, mental health services are lacking, and security is poor or nonexistent at some health care facilities.

Violence against hospital workers has become so common that a bill was introduced in 2022 in Congress to better protect them. The Safety From Violence for Healthcare Employees Act includes stiffer penalties for acts involving the use of a dangerous weapon or committed during a public emergency and would also provide $25 million in grants to hospitals for programs aimed at reducing violent incidents in health care settings, including de-escalation training. The American Hospital Association and American College of Emergency Physicians support the bill, which is now before the House Judiciary Subcommittee on Crime, Terrorism, and Homeland Security.
 

The worst day of their lives

“You have people who already are having the worst day of their lives and feeling on edge. If they already have a short fuse or substance abuse issues, that can translate into agitation, violence, or aggression,” said Scott Zeller, MD, vice president of acute psychiatry at Vituity, a physician-owned multispecialty group that operates in several states.

Health care workers in psychiatric and substance abuse hospitals were 10 times more likely to experience nonfatal injuries by others in 2018 than were health care workers in ambulatory settings, according to an April 2020 Bureau of Labor Statistics report. In addition, health care workers were five times more likely to suffer a workplace violence injury than were workers overall in 2018.

Psychiatrists who responded to the poll were the specialists most likely to report that they encountered violent patients and potentially violent patients. “Historically, inpatient psychiatry, which requires more acute care and monitoring, is considered the most dangerous profession outside of the police,” said Dr. Zeller.

Emergency physicians have reported an uptick in violence from patients; 85% said in a survey by ACEP in 2022 that they believed the rate of violence in emergency departments has increased over the past 5 years, whereas 45% indicated that it has greatly increased.

Some doctors have been threatened with violence or actually killed by family members. Alex Skog, MD, president-elect of ACEP’s Oregon chapter, told HealthCare Dive that “a patient’s family member with a gun holster on his hip threatened to kill me and kill my entire family after I told his father that he needed to be admitted because he had coronavirus.”

“I’ve been scared for my safety as well as the safety of my family,” Dr. Skog said. “That was just not something that we were seeing 3, 4, or 5 years ago.”

Many patients are already upset by the time they see doctors, according to the poll.

“The most common reason patients are upset is that they’re already in a lot of pain, which can be expressed as anger, hostility, or aggression. They’re very anxious and afraid of what’s happening and may be thinking about the worst-case scenario – that a bump or lump is cancer,” Dr. Zeller said.

Patients may also get upset if they disagree with their doctors’ diagnosis or treatment plan or the doctor refuses to prescribe them the drugs or tests they want.

“One doctor commented recently: ‘After over 30 years in this business, I can say patients are worse now than at any point in my career. Entitled, demanding, obnoxious. Any denial is met with outrage and indignity, whether it’s an opioid request or a demand for MRI of something because they ‘want to know.’ ”

An orthopedic surgeon in Indiana lost his life after he refused to prescribe opioids to a patient. Her angry husband shot and killed the doctor in the parking lot only 2 hours after confronting him in his office.
 

Decreased physician-patient trust

“When doctors experience something frightening, they become more apprehensive in the future. There’s no doubt that after the first violent experience, they think of things differently,” said Dr. Zeller.

More than half of the doctors who reported experiencing at least one violent or potentially violent incident in the poll said they trusted patients less.

This diminished trust can negatively impact the physician-patient relationship, said the authors of a recent Health Affairs article.

“The more patients harm their health care providers, intentionally or unintentionally, the more difficult it will be for those providers to trust them, leading to yet another unfortunate pattern: physicians pulling back on some of the behaviors thought to be most trust-building, for example, talking about their personal lives, building rapport, displaying compassion, or giving out their personal cell phone numbers,” the article stated.
 

What doctors can do

Most doctors who experienced a violent or potentially violent incident said they had tried to defuse the situation and that they succeeded at least some of the time, the poll results show.

One of the best ways to defuse a situation is to be empathetic and show the person that you’re on their side and not the enemy, said Dr. Cheng,.

“Rather than making general statements like ‘I understand that you’re upset,’ it’s better to be specific about the reason the person is upset. For example: ‘I understand that you’re upset that the pharmacy didn’t fill your prescription’ or ‘I understand how you’re feeling about Doctor So-and-so, who didn’t treat you right,’ ” Dr. Cheng stated.

Dr. Zeller urged physicians to talk to patients about why they’re upset and how they can help them. That approach worked with a patient who was having a psychotic episode.

“I told the staff, who wanted to forcibly restrain him and inject him with medication, that I would talk to him. I asked the patient, who was screaming ‘ya ya ya ya,’ whether he would take his medication if I gave it to him and he said yes. When he was calm, he explained that he was screaming to stop the voices telling him to kill his parents. He then got the help he needed,” said Dr. Zeller.

Dr. Cheng was trained in de-escalation techniques as an Orange County reserve deputy sheriff. He and Dr. Zeller recommended that physicians and staff receive training in how to spot potentially violent behavior and defuse these situations before they escalate.

Dr. Cheng suggests looking at the person’s body language for signs of increasing agitation or tension, such as clenched fists, tense posture, tight jaw, or fidgeting that may be accompanied by shouting and/or verbal abuse.

Physicians also need to consider where they are physically in relation to patients they see. “You don’t want to be too close to the patient or stand in front of them, which can be seen as confrontational. Instead, stand or sit off to the side, and never block the door if the patient’s upset,” said Dr. Cheng.

He recommended that physician practices prepare for violent incidents by developing detailed plans, including how and when to escape, how to protect patients, and how to cooperate with law enforcement.

“If a violent incident is inescapable, physicians and staff must be ready to fight back with whatever tools they have available, which may include fire extinguishers, chairs, or scalpels,” said Dr. Cheng.

A version of this article originally appeared on Medscape.com.