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Congratulations to AGA’s New Leaders
Each January, the AGA Nominating Committee meets to complete a very important task — namely, selection of new members of AGA’s Governing Board, pending approval by the membership.
Having served on this committee in the past, I can attest to how challenging a task it is to select these leaders from such a talented and committed pool of candidates, each of whom have served the organization in numerous impactful roles over the course of many years.
This year’s recently announced additions to the Governing Board, who will assume their roles this summer, include Dr. Byron Cryer (incoming Vice President), Dr. Shahnaz Sultan (Clinical Research Councillor), and Dr. Jonathan Rosenberg (Practice Councillor). I have had the pleasure of working with each of them over the years from my very early days at AGA and am confident that AGA will continue to thrive under their leadership. Please join me in congratulating Byron, Shahnaz, and Jonathan on their new roles!
In this month’s issue of GIHN, we highlight a phase 3 RCT from NEJM demonstrating the efficacy of seladelpar, an alternative to ursodeoxycholic acid in patients with PBC with refractory pruritus. From the CGH Practice Management section, Dr. Michelle Kim (Cleveland Clinic) and colleagues provide helpful tips on how to optimize EHR use in GI practice, including by incorporating novel tools based on AI, natural language processing, and speech recognition. In our April Member Spotlight, we are excited to feature gastroenterologist and stand-up comedienne Dr. Shida Haghighat of UCLA, who shares her passion for addressing health disparities and highlights how humor helped her cope with the demands of medical training. We hope you enjoy these, and all the stories included in our April issue.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
Each January, the AGA Nominating Committee meets to complete a very important task — namely, selection of new members of AGA’s Governing Board, pending approval by the membership.
Having served on this committee in the past, I can attest to how challenging a task it is to select these leaders from such a talented and committed pool of candidates, each of whom have served the organization in numerous impactful roles over the course of many years.
This year’s recently announced additions to the Governing Board, who will assume their roles this summer, include Dr. Byron Cryer (incoming Vice President), Dr. Shahnaz Sultan (Clinical Research Councillor), and Dr. Jonathan Rosenberg (Practice Councillor). I have had the pleasure of working with each of them over the years from my very early days at AGA and am confident that AGA will continue to thrive under their leadership. Please join me in congratulating Byron, Shahnaz, and Jonathan on their new roles!
In this month’s issue of GIHN, we highlight a phase 3 RCT from NEJM demonstrating the efficacy of seladelpar, an alternative to ursodeoxycholic acid in patients with PBC with refractory pruritus. From the CGH Practice Management section, Dr. Michelle Kim (Cleveland Clinic) and colleagues provide helpful tips on how to optimize EHR use in GI practice, including by incorporating novel tools based on AI, natural language processing, and speech recognition. In our April Member Spotlight, we are excited to feature gastroenterologist and stand-up comedienne Dr. Shida Haghighat of UCLA, who shares her passion for addressing health disparities and highlights how humor helped her cope with the demands of medical training. We hope you enjoy these, and all the stories included in our April issue.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
Each January, the AGA Nominating Committee meets to complete a very important task — namely, selection of new members of AGA’s Governing Board, pending approval by the membership.
Having served on this committee in the past, I can attest to how challenging a task it is to select these leaders from such a talented and committed pool of candidates, each of whom have served the organization in numerous impactful roles over the course of many years.
This year’s recently announced additions to the Governing Board, who will assume their roles this summer, include Dr. Byron Cryer (incoming Vice President), Dr. Shahnaz Sultan (Clinical Research Councillor), and Dr. Jonathan Rosenberg (Practice Councillor). I have had the pleasure of working with each of them over the years from my very early days at AGA and am confident that AGA will continue to thrive under their leadership. Please join me in congratulating Byron, Shahnaz, and Jonathan on their new roles!
In this month’s issue of GIHN, we highlight a phase 3 RCT from NEJM demonstrating the efficacy of seladelpar, an alternative to ursodeoxycholic acid in patients with PBC with refractory pruritus. From the CGH Practice Management section, Dr. Michelle Kim (Cleveland Clinic) and colleagues provide helpful tips on how to optimize EHR use in GI practice, including by incorporating novel tools based on AI, natural language processing, and speech recognition. In our April Member Spotlight, we are excited to feature gastroenterologist and stand-up comedienne Dr. Shida Haghighat of UCLA, who shares her passion for addressing health disparities and highlights how humor helped her cope with the demands of medical training. We hope you enjoy these, and all the stories included in our April issue.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
It Takes a Village: Treating Patients for NSCLC Brain Metastases
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
FROM ELCC 2024
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Minimally Invasive Cytoreductive Approach Comparable to Open Surgery for Ovarian Cancer
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.
Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.
“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.
The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
Growing Use of MIS
Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).
Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
Outcomes Compared
Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.
As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.
Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.
Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.
Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.
As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).
There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.
The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
MIS Use Debatable: CON
Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.
In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.
“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.
Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.
Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.
In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.
Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.
She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.
MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
Debate: PRO
Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”
He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.
In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.
Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.
To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.
The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.
FROM SGO 2024
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
Acne Risk With Progestin-Only Long-Acting Reversible Contraceptives Evaluated
TOPLINE:
Despite the .
METHODOLOGY:
- Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
- In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
- Overall, 24% of participants had acne at the time of LARC insertion.
- Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.
TAKEAWAY:
- During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
- Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
- Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.
IN PRACTICE:
The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”
SOURCE:
The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.
LIMITATIONS:
Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.
DISCLOSURES:
The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
Despite the .
METHODOLOGY:
- Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
- In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
- Overall, 24% of participants had acne at the time of LARC insertion.
- Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.
TAKEAWAY:
- During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
- Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
- Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.
IN PRACTICE:
The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”
SOURCE:
The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.
LIMITATIONS:
Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.
DISCLOSURES:
The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
Despite the .
METHODOLOGY:
- Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
- In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
- Overall, 24% of participants had acne at the time of LARC insertion.
- Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.
TAKEAWAY:
- During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
- Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
- Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.
IN PRACTICE:
The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”
SOURCE:
The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.
LIMITATIONS:
Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.
DISCLOSURES:
The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.
A version of this article appeared on Medscape.com.
Secondary Cancers Post CAR T Therapy: A Concern?
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
Non-Radical Surgery a Win-Win for Early Cervical Cancer
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
FROM SGO 2024
Flexibility Recommended for Patients With Personality Disorders
SAN DIEGO — .
“You want to recognize the personality disorder, understand that there are underlying conflicts and needs, and adjust accordingly,” Dr. Nakamura, clinical assistant professor of dermatology at the University of Michigan, Ann Arbor, said at the annual meeting of the American Academy of Dermatology.
Personality disorders, which she defined as enduring patterns of maladaptive thinking and behavior that deviate from the cultural norm, affect up to 15% of the general population and can be difficult “if not impossible to treat, which can be frustrating.” She shared her approach to providing dermatologic care for individuals with these three conditions:
Borderline personality disorder (BPD). This condition is marked by instability in interpersonal relationships, self-image, and emotions. Affected individuals are usually impulsive and often demonstrate self-injurious conduct such as risky sexual behaviors, cutting, or suicide attempts. “They often express feelings of emptiness, a fear of abandonment, and they are labile and sensitive to environmental circumstances,” Dr. Nakamura said. “They can be needy and display inappropriate, intense anger.”
In her clinical experience, a patient’s presenting dermatologic complaint is often a “screen” to hide a real, inner psychological problem, “a need to fill the emptiness,” she explained. “They’re kind of lonely, and there is a fear of abandonment. Rejection is frequently perceived as abandonment, creating intense anger and other negative emotions such as splitting.”
She advises against providing tests, treatments, or procedures for individuals with BPD that are not clinically indicated. “If the test is negative, such patients may ask for further testing,” she said. “Especially for cosmetic procedures, the patient may be more dissatisfied with the outcome of a procedure compared to before. Don’t let the patient’s emotions cloud your judgment. Trying to reason with the patient is often ineffective.”
To avoid saying “no” to such patients, Dr. Nakamura recommended discussing other treatment options so that they don’t feel abandoned. “Show that you care,” she said. “Meet the patient’s emotional needs, which may be the real agenda, and schedule regular follow-ups.”
Obsessive-compulsive personality disorder (OCPD). This condition is characterized by a preoccupation with orderliness, perfectionism, and control. “OCPD individuals are excessively concerned with details, rules, and organization to the extent that the major point of the activity is often lost,” Dr. Nakamura said. “They can be over-conscientious with excessive regard for morality and ethics.”
Such patients often fear losing control, she continued, which can lead to anxiety, depression, and sometimes anger. During office visits with patients with OCPD, she recommends that dermatologists “focus on facts and knowledge to replace or subdue emotions. Knowledge and information give a sense of control over illness.” Her approach involves professional, structured encounters that include detailed explanations and plans. “Provide step-by-step written instructions and give specific reasons for the prescribed treatment,” Dr. Nakamura advised. “Schedule regular follow-up appointments.”
Narcissistic personality disorder (NPD). This condition is characterized by a grandiose sense of self-importance, in which the person believes that they are special, unique, and superior to others. These individuals have a sense of entitlement, fantasize about unlimited success or power, display a lack of empathy toward others, and show a constant need for admiration. “The patient’s personality traits are often a ‘screen’ to hide a real, inner psychological problem such as unrecognized low self-esteem or insecurity,” Dr. Nakamura said. “These patients need praise and a sense of power.”
To provide patients with NPD with “a sense of uniqueness,” she recommended engaging with them at a medical level as one might with a work colleague. “Such patients often respond better to respect and concern rather than warmth and caring,” she said. Asking them to make decisions about their care can also give them a sense of power: asking them, for example, about which type of topical steroid they might prefer from those in the same class, whether they prefer creams or ointments, and that they can choose to follow up in 4 weeks or 6 weeks.
“Do not let the patient dictate the encounter [or] get under your skin,” Dr. Nakamura emphasized. “Be careful about rejecting the patient from your practice. Even though that is perfectly within your rights, it could lead to ‘narcissistic injury’ where the patient becomes very angry and wants to get back at you.”
Dr. Nakamura disclosed that she is an investigator for Amgen, argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Regeneron. She is also a member of the advisory board for argenx, Boehringer Ingelheim, and Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
SAN DIEGO — .
“You want to recognize the personality disorder, understand that there are underlying conflicts and needs, and adjust accordingly,” Dr. Nakamura, clinical assistant professor of dermatology at the University of Michigan, Ann Arbor, said at the annual meeting of the American Academy of Dermatology.
Personality disorders, which she defined as enduring patterns of maladaptive thinking and behavior that deviate from the cultural norm, affect up to 15% of the general population and can be difficult “if not impossible to treat, which can be frustrating.” She shared her approach to providing dermatologic care for individuals with these three conditions:
Borderline personality disorder (BPD). This condition is marked by instability in interpersonal relationships, self-image, and emotions. Affected individuals are usually impulsive and often demonstrate self-injurious conduct such as risky sexual behaviors, cutting, or suicide attempts. “They often express feelings of emptiness, a fear of abandonment, and they are labile and sensitive to environmental circumstances,” Dr. Nakamura said. “They can be needy and display inappropriate, intense anger.”
In her clinical experience, a patient’s presenting dermatologic complaint is often a “screen” to hide a real, inner psychological problem, “a need to fill the emptiness,” she explained. “They’re kind of lonely, and there is a fear of abandonment. Rejection is frequently perceived as abandonment, creating intense anger and other negative emotions such as splitting.”
She advises against providing tests, treatments, or procedures for individuals with BPD that are not clinically indicated. “If the test is negative, such patients may ask for further testing,” she said. “Especially for cosmetic procedures, the patient may be more dissatisfied with the outcome of a procedure compared to before. Don’t let the patient’s emotions cloud your judgment. Trying to reason with the patient is often ineffective.”
To avoid saying “no” to such patients, Dr. Nakamura recommended discussing other treatment options so that they don’t feel abandoned. “Show that you care,” she said. “Meet the patient’s emotional needs, which may be the real agenda, and schedule regular follow-ups.”
Obsessive-compulsive personality disorder (OCPD). This condition is characterized by a preoccupation with orderliness, perfectionism, and control. “OCPD individuals are excessively concerned with details, rules, and organization to the extent that the major point of the activity is often lost,” Dr. Nakamura said. “They can be over-conscientious with excessive regard for morality and ethics.”
Such patients often fear losing control, she continued, which can lead to anxiety, depression, and sometimes anger. During office visits with patients with OCPD, she recommends that dermatologists “focus on facts and knowledge to replace or subdue emotions. Knowledge and information give a sense of control over illness.” Her approach involves professional, structured encounters that include detailed explanations and plans. “Provide step-by-step written instructions and give specific reasons for the prescribed treatment,” Dr. Nakamura advised. “Schedule regular follow-up appointments.”
Narcissistic personality disorder (NPD). This condition is characterized by a grandiose sense of self-importance, in which the person believes that they are special, unique, and superior to others. These individuals have a sense of entitlement, fantasize about unlimited success or power, display a lack of empathy toward others, and show a constant need for admiration. “The patient’s personality traits are often a ‘screen’ to hide a real, inner psychological problem such as unrecognized low self-esteem or insecurity,” Dr. Nakamura said. “These patients need praise and a sense of power.”
To provide patients with NPD with “a sense of uniqueness,” she recommended engaging with them at a medical level as one might with a work colleague. “Such patients often respond better to respect and concern rather than warmth and caring,” she said. Asking them to make decisions about their care can also give them a sense of power: asking them, for example, about which type of topical steroid they might prefer from those in the same class, whether they prefer creams or ointments, and that they can choose to follow up in 4 weeks or 6 weeks.
“Do not let the patient dictate the encounter [or] get under your skin,” Dr. Nakamura emphasized. “Be careful about rejecting the patient from your practice. Even though that is perfectly within your rights, it could lead to ‘narcissistic injury’ where the patient becomes very angry and wants to get back at you.”
Dr. Nakamura disclosed that she is an investigator for Amgen, argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Regeneron. She is also a member of the advisory board for argenx, Boehringer Ingelheim, and Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
SAN DIEGO — .
“You want to recognize the personality disorder, understand that there are underlying conflicts and needs, and adjust accordingly,” Dr. Nakamura, clinical assistant professor of dermatology at the University of Michigan, Ann Arbor, said at the annual meeting of the American Academy of Dermatology.
Personality disorders, which she defined as enduring patterns of maladaptive thinking and behavior that deviate from the cultural norm, affect up to 15% of the general population and can be difficult “if not impossible to treat, which can be frustrating.” She shared her approach to providing dermatologic care for individuals with these three conditions:
Borderline personality disorder (BPD). This condition is marked by instability in interpersonal relationships, self-image, and emotions. Affected individuals are usually impulsive and often demonstrate self-injurious conduct such as risky sexual behaviors, cutting, or suicide attempts. “They often express feelings of emptiness, a fear of abandonment, and they are labile and sensitive to environmental circumstances,” Dr. Nakamura said. “They can be needy and display inappropriate, intense anger.”
In her clinical experience, a patient’s presenting dermatologic complaint is often a “screen” to hide a real, inner psychological problem, “a need to fill the emptiness,” she explained. “They’re kind of lonely, and there is a fear of abandonment. Rejection is frequently perceived as abandonment, creating intense anger and other negative emotions such as splitting.”
She advises against providing tests, treatments, or procedures for individuals with BPD that are not clinically indicated. “If the test is negative, such patients may ask for further testing,” she said. “Especially for cosmetic procedures, the patient may be more dissatisfied with the outcome of a procedure compared to before. Don’t let the patient’s emotions cloud your judgment. Trying to reason with the patient is often ineffective.”
To avoid saying “no” to such patients, Dr. Nakamura recommended discussing other treatment options so that they don’t feel abandoned. “Show that you care,” she said. “Meet the patient’s emotional needs, which may be the real agenda, and schedule regular follow-ups.”
Obsessive-compulsive personality disorder (OCPD). This condition is characterized by a preoccupation with orderliness, perfectionism, and control. “OCPD individuals are excessively concerned with details, rules, and organization to the extent that the major point of the activity is often lost,” Dr. Nakamura said. “They can be over-conscientious with excessive regard for morality and ethics.”
Such patients often fear losing control, she continued, which can lead to anxiety, depression, and sometimes anger. During office visits with patients with OCPD, she recommends that dermatologists “focus on facts and knowledge to replace or subdue emotions. Knowledge and information give a sense of control over illness.” Her approach involves professional, structured encounters that include detailed explanations and plans. “Provide step-by-step written instructions and give specific reasons for the prescribed treatment,” Dr. Nakamura advised. “Schedule regular follow-up appointments.”
Narcissistic personality disorder (NPD). This condition is characterized by a grandiose sense of self-importance, in which the person believes that they are special, unique, and superior to others. These individuals have a sense of entitlement, fantasize about unlimited success or power, display a lack of empathy toward others, and show a constant need for admiration. “The patient’s personality traits are often a ‘screen’ to hide a real, inner psychological problem such as unrecognized low self-esteem or insecurity,” Dr. Nakamura said. “These patients need praise and a sense of power.”
To provide patients with NPD with “a sense of uniqueness,” she recommended engaging with them at a medical level as one might with a work colleague. “Such patients often respond better to respect and concern rather than warmth and caring,” she said. Asking them to make decisions about their care can also give them a sense of power: asking them, for example, about which type of topical steroid they might prefer from those in the same class, whether they prefer creams or ointments, and that they can choose to follow up in 4 weeks or 6 weeks.
“Do not let the patient dictate the encounter [or] get under your skin,” Dr. Nakamura emphasized. “Be careful about rejecting the patient from your practice. Even though that is perfectly within your rights, it could lead to ‘narcissistic injury’ where the patient becomes very angry and wants to get back at you.”
Dr. Nakamura disclosed that she is an investigator for Amgen, argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Regeneron. She is also a member of the advisory board for argenx, Boehringer Ingelheim, and Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
FROM AAD 2024