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Cancer Treatment 101: A Primer for Non-Oncologists
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
When Childhood Cancer Survivors Face Sexual Challenges
Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.
This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.
Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.
The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
Characteristics and Mechanisms
Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.
As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.
Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.
Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects.
Sexual Function in CCS
A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.
The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.
Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.
In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.
The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
Factors Influencing Sexual Function
The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.
Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.
Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.
Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.
The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.
Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.
Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.
Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.
This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.
Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.
The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
Characteristics and Mechanisms
Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.
As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.
Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.
Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects.
Sexual Function in CCS
A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.
The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.
Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.
In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.
The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
Factors Influencing Sexual Function
The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.
Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.
Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.
Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.
The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.
Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.
Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.
Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.
This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.
Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.
The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
Characteristics and Mechanisms
Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.
As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.
Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.
Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects.
Sexual Function in CCS
A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.
The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.
Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.
In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.
The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
Factors Influencing Sexual Function
The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.
Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.
Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.
Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.
The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.
Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.
Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.
Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Low HPV Vaccination in the United States Is a Public Health ‘Failure’
This transcript has been edited for clarity.
I would like to briefly discuss what I consider to be a very discouraging report and one that I believe we as an oncology society and, quite frankly, as a medical community need to deal with.
The manuscript I’m referring to is from the United States Department of Health and Human Services, titled, “Human Papillomavirus Vaccination Coverage in Children Ages 9-17 Years: United States, 2022.” This particular analysis looked at the coverage of both men and women — young boys and young girls, I would say — receiving at least one dose of the recommended human papillomavirus (HPV) vaccination.
Since 2006, girls have been recommended to receive HPV vaccination; for boys, it’s been since 2011. Certainly, the time period that we’re considering falls within the recommendations based on overwhelmingly positive data. Now, today, still, the recommendation is for more than one vaccine. Obviously, there may be evidence in the future that a single vaccination may be acceptable or appropriate. But today, it’s more than one.
In this particular analysis, they were looking at just a single vaccination. The vaccines have targeted young individuals, both male and female children aged 11-12 years, but it’s certainly acceptable to look starting at age 9.
What is the bottom line? At least one dose of the HPV vaccination was given to 38.6% of children aged 9-17 years in 2022. We are talking about a cancer-preventive vaccine, which on the basis of population-based data in the United States, but also in other countries, is incredibly effective in preventing HPV-associated cancers. This not only includes cervical cancer, but also a large percentage of head and neck cancers.
For this vaccine, which is incredibly safe and incredibly effective, in this country, only 38.6% have received even a single dose. It is noted that the individuals with private insurance had a higher rate, at 41.5%, than individuals with no insurance, at only 20.7%.
In my opinion, this is clearly a failure of our public health establishment at all levels. My own focus has been in gynecologic cancers. I’ve seen young women with advanced cervical cancer, and this is a disease we can prevent. Yet, this is where we are.
For those of you who are interested in cancer prevention or public health, I think this is a very sobering statistic. It’s my plea and my hope that we can, as a society, somehow do something about it.
I thank you for listening. I would encourage you to think about this question if you’re in this area.
Dr. Markman, professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix, disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I would like to briefly discuss what I consider to be a very discouraging report and one that I believe we as an oncology society and, quite frankly, as a medical community need to deal with.
The manuscript I’m referring to is from the United States Department of Health and Human Services, titled, “Human Papillomavirus Vaccination Coverage in Children Ages 9-17 Years: United States, 2022.” This particular analysis looked at the coverage of both men and women — young boys and young girls, I would say — receiving at least one dose of the recommended human papillomavirus (HPV) vaccination.
Since 2006, girls have been recommended to receive HPV vaccination; for boys, it’s been since 2011. Certainly, the time period that we’re considering falls within the recommendations based on overwhelmingly positive data. Now, today, still, the recommendation is for more than one vaccine. Obviously, there may be evidence in the future that a single vaccination may be acceptable or appropriate. But today, it’s more than one.
In this particular analysis, they were looking at just a single vaccination. The vaccines have targeted young individuals, both male and female children aged 11-12 years, but it’s certainly acceptable to look starting at age 9.
What is the bottom line? At least one dose of the HPV vaccination was given to 38.6% of children aged 9-17 years in 2022. We are talking about a cancer-preventive vaccine, which on the basis of population-based data in the United States, but also in other countries, is incredibly effective in preventing HPV-associated cancers. This not only includes cervical cancer, but also a large percentage of head and neck cancers.
For this vaccine, which is incredibly safe and incredibly effective, in this country, only 38.6% have received even a single dose. It is noted that the individuals with private insurance had a higher rate, at 41.5%, than individuals with no insurance, at only 20.7%.
In my opinion, this is clearly a failure of our public health establishment at all levels. My own focus has been in gynecologic cancers. I’ve seen young women with advanced cervical cancer, and this is a disease we can prevent. Yet, this is where we are.
For those of you who are interested in cancer prevention or public health, I think this is a very sobering statistic. It’s my plea and my hope that we can, as a society, somehow do something about it.
I thank you for listening. I would encourage you to think about this question if you’re in this area.
Dr. Markman, professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix, disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I would like to briefly discuss what I consider to be a very discouraging report and one that I believe we as an oncology society and, quite frankly, as a medical community need to deal with.
The manuscript I’m referring to is from the United States Department of Health and Human Services, titled, “Human Papillomavirus Vaccination Coverage in Children Ages 9-17 Years: United States, 2022.” This particular analysis looked at the coverage of both men and women — young boys and young girls, I would say — receiving at least one dose of the recommended human papillomavirus (HPV) vaccination.
Since 2006, girls have been recommended to receive HPV vaccination; for boys, it’s been since 2011. Certainly, the time period that we’re considering falls within the recommendations based on overwhelmingly positive data. Now, today, still, the recommendation is for more than one vaccine. Obviously, there may be evidence in the future that a single vaccination may be acceptable or appropriate. But today, it’s more than one.
In this particular analysis, they were looking at just a single vaccination. The vaccines have targeted young individuals, both male and female children aged 11-12 years, but it’s certainly acceptable to look starting at age 9.
What is the bottom line? At least one dose of the HPV vaccination was given to 38.6% of children aged 9-17 years in 2022. We are talking about a cancer-preventive vaccine, which on the basis of population-based data in the United States, but also in other countries, is incredibly effective in preventing HPV-associated cancers. This not only includes cervical cancer, but also a large percentage of head and neck cancers.
For this vaccine, which is incredibly safe and incredibly effective, in this country, only 38.6% have received even a single dose. It is noted that the individuals with private insurance had a higher rate, at 41.5%, than individuals with no insurance, at only 20.7%.
In my opinion, this is clearly a failure of our public health establishment at all levels. My own focus has been in gynecologic cancers. I’ve seen young women with advanced cervical cancer, and this is a disease we can prevent. Yet, this is where we are.
For those of you who are interested in cancer prevention or public health, I think this is a very sobering statistic. It’s my plea and my hope that we can, as a society, somehow do something about it.
I thank you for listening. I would encourage you to think about this question if you’re in this area.
Dr. Markman, professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix, disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
Cannabis Overuse Linked to Increased Risk for Head and Neck Cancer
TOPLINE:
The study analyzed data from over four million patients, highlighting the potential carcinogenic effects of the substance.
METHODOLOGY:
- Researchers analyzed data from a globally federated health research network TriNetX, which included over 90 million men and women from 64 health care organizations in the United States.
- More than 4.1 million patients were included in the analysis, including 116,076 individuals diagnosed with cannabis-related disorder and 3.9 million without the disorder. Cannabis-related disorders involve the excessive use of cannabis with associated psychosocial symptoms, such as impaired social and/or occupational functioning.
- Patients with cannabis-related disorder were matched with those without the disorder based on demographic characteristics, alcohol-related disorders, and tobacco use.
- The primary outcome was the diagnosis of head and neck cancer, including subsites such as oral, oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal, and salivary gland malignancies.
- Propensity score matching and Poisson regression analysis were used to compare the incidence of head and neck cancers between the groups.
TAKEAWAY:
- According to the researchers, patients with a cannabis-related disorder had a higher risk for any head and neck cancer (relative risk [RR], 3.49; 95% CI, 2.78-4.39) than those without the disorder.
- The risk for specific cancers was also higher in the group with cannabis-related disorders, including oral (RR, 2.51; 95% CI, 1.81-3.47) and oropharyngeal malignancies (RR, 4.90; 95% CI, 2.99-8.02).
- The RR for laryngeal cancer was significantly higher in the patients with a cannabis-related disorder (RR, 8.39; 95% CI, 4.72-14.90).
- The findings suggest that cannabis use disorder is associated with an increased risk for head and neck cancers, highlighting the need for further research to understand the mechanisms involved.
IN PRACTICE:
“In this cohort study, cannabis disorder diagnosis was independently associated with greater risk of subsequent development of any [head or neck cancer] as well as cancers in various subsites of the head and neck among US adults. When limited to cases of [such cancers] occurring greater than 1 year after cannabis use disorder diagnosis, many of the associations increased, demonstrating additional strength in the association,” the authors of the study wrote.
“The association of cannabis and head and neck cancer in this study spanned 2 decades during a rapid growth in use. If this association is causative, the burden of [head and neck cancers] attributable to cannabis will continue to increase, and perhaps dramatically,” said the authors of an editorial accompanying the journal article. “Given that cannabis is now a $20 billion industry in the US alone with expanding availability, use, and popularity, this may be “déjà vu, all over again” without appropriate research to understand the potential carcinogenic and salutatory effects of cannabis. Or, in the words of Yogi Berra, “If you don’t know where you are going, you might wind up someplace else.”
SOURCE:
The study was led by Tyler J. Gallagher and Niels C. Kokot, MD, at the Keck School of Medicine of the University of Southern California in Los Angeles. It was published online in JAMA Otolaryngology–Head & Neck Surgery.
LIMITATIONS:
The study had limited information about cohort composition and length of follow-up, which may affect the generalizability of the findings. The lack of direct exposure duration, intensity, and dosage information limits the ability to analyze dose-response relationships. Potential inconsistency of diagnosis and reliance on medical record codes may introduce bias. Cannabis use is likely underreported, which could decrease the relative risks discovered. The study was further limited by the lack of information on dosage and frequency of cannabis use, as well as some controls, including alcohol and tobacco use.
DISCLOSURES:
Gallagher disclosed receiving grants from the Keck School of Medicine of the University of Southern California, Los Angeles. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The study analyzed data from over four million patients, highlighting the potential carcinogenic effects of the substance.
METHODOLOGY:
- Researchers analyzed data from a globally federated health research network TriNetX, which included over 90 million men and women from 64 health care organizations in the United States.
- More than 4.1 million patients were included in the analysis, including 116,076 individuals diagnosed with cannabis-related disorder and 3.9 million without the disorder. Cannabis-related disorders involve the excessive use of cannabis with associated psychosocial symptoms, such as impaired social and/or occupational functioning.
- Patients with cannabis-related disorder were matched with those without the disorder based on demographic characteristics, alcohol-related disorders, and tobacco use.
- The primary outcome was the diagnosis of head and neck cancer, including subsites such as oral, oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal, and salivary gland malignancies.
- Propensity score matching and Poisson regression analysis were used to compare the incidence of head and neck cancers between the groups.
TAKEAWAY:
- According to the researchers, patients with a cannabis-related disorder had a higher risk for any head and neck cancer (relative risk [RR], 3.49; 95% CI, 2.78-4.39) than those without the disorder.
- The risk for specific cancers was also higher in the group with cannabis-related disorders, including oral (RR, 2.51; 95% CI, 1.81-3.47) and oropharyngeal malignancies (RR, 4.90; 95% CI, 2.99-8.02).
- The RR for laryngeal cancer was significantly higher in the patients with a cannabis-related disorder (RR, 8.39; 95% CI, 4.72-14.90).
- The findings suggest that cannabis use disorder is associated with an increased risk for head and neck cancers, highlighting the need for further research to understand the mechanisms involved.
IN PRACTICE:
“In this cohort study, cannabis disorder diagnosis was independently associated with greater risk of subsequent development of any [head or neck cancer] as well as cancers in various subsites of the head and neck among US adults. When limited to cases of [such cancers] occurring greater than 1 year after cannabis use disorder diagnosis, many of the associations increased, demonstrating additional strength in the association,” the authors of the study wrote.
“The association of cannabis and head and neck cancer in this study spanned 2 decades during a rapid growth in use. If this association is causative, the burden of [head and neck cancers] attributable to cannabis will continue to increase, and perhaps dramatically,” said the authors of an editorial accompanying the journal article. “Given that cannabis is now a $20 billion industry in the US alone with expanding availability, use, and popularity, this may be “déjà vu, all over again” without appropriate research to understand the potential carcinogenic and salutatory effects of cannabis. Or, in the words of Yogi Berra, “If you don’t know where you are going, you might wind up someplace else.”
SOURCE:
The study was led by Tyler J. Gallagher and Niels C. Kokot, MD, at the Keck School of Medicine of the University of Southern California in Los Angeles. It was published online in JAMA Otolaryngology–Head & Neck Surgery.
LIMITATIONS:
The study had limited information about cohort composition and length of follow-up, which may affect the generalizability of the findings. The lack of direct exposure duration, intensity, and dosage information limits the ability to analyze dose-response relationships. Potential inconsistency of diagnosis and reliance on medical record codes may introduce bias. Cannabis use is likely underreported, which could decrease the relative risks discovered. The study was further limited by the lack of information on dosage and frequency of cannabis use, as well as some controls, including alcohol and tobacco use.
DISCLOSURES:
Gallagher disclosed receiving grants from the Keck School of Medicine of the University of Southern California, Los Angeles. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
The study analyzed data from over four million patients, highlighting the potential carcinogenic effects of the substance.
METHODOLOGY:
- Researchers analyzed data from a globally federated health research network TriNetX, which included over 90 million men and women from 64 health care organizations in the United States.
- More than 4.1 million patients were included in the analysis, including 116,076 individuals diagnosed with cannabis-related disorder and 3.9 million without the disorder. Cannabis-related disorders involve the excessive use of cannabis with associated psychosocial symptoms, such as impaired social and/or occupational functioning.
- Patients with cannabis-related disorder were matched with those without the disorder based on demographic characteristics, alcohol-related disorders, and tobacco use.
- The primary outcome was the diagnosis of head and neck cancer, including subsites such as oral, oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal, and salivary gland malignancies.
- Propensity score matching and Poisson regression analysis were used to compare the incidence of head and neck cancers between the groups.
TAKEAWAY:
- According to the researchers, patients with a cannabis-related disorder had a higher risk for any head and neck cancer (relative risk [RR], 3.49; 95% CI, 2.78-4.39) than those without the disorder.
- The risk for specific cancers was also higher in the group with cannabis-related disorders, including oral (RR, 2.51; 95% CI, 1.81-3.47) and oropharyngeal malignancies (RR, 4.90; 95% CI, 2.99-8.02).
- The RR for laryngeal cancer was significantly higher in the patients with a cannabis-related disorder (RR, 8.39; 95% CI, 4.72-14.90).
- The findings suggest that cannabis use disorder is associated with an increased risk for head and neck cancers, highlighting the need for further research to understand the mechanisms involved.
IN PRACTICE:
“In this cohort study, cannabis disorder diagnosis was independently associated with greater risk of subsequent development of any [head or neck cancer] as well as cancers in various subsites of the head and neck among US adults. When limited to cases of [such cancers] occurring greater than 1 year after cannabis use disorder diagnosis, many of the associations increased, demonstrating additional strength in the association,” the authors of the study wrote.
“The association of cannabis and head and neck cancer in this study spanned 2 decades during a rapid growth in use. If this association is causative, the burden of [head and neck cancers] attributable to cannabis will continue to increase, and perhaps dramatically,” said the authors of an editorial accompanying the journal article. “Given that cannabis is now a $20 billion industry in the US alone with expanding availability, use, and popularity, this may be “déjà vu, all over again” without appropriate research to understand the potential carcinogenic and salutatory effects of cannabis. Or, in the words of Yogi Berra, “If you don’t know where you are going, you might wind up someplace else.”
SOURCE:
The study was led by Tyler J. Gallagher and Niels C. Kokot, MD, at the Keck School of Medicine of the University of Southern California in Los Angeles. It was published online in JAMA Otolaryngology–Head & Neck Surgery.
LIMITATIONS:
The study had limited information about cohort composition and length of follow-up, which may affect the generalizability of the findings. The lack of direct exposure duration, intensity, and dosage information limits the ability to analyze dose-response relationships. Potential inconsistency of diagnosis and reliance on medical record codes may introduce bias. Cannabis use is likely underreported, which could decrease the relative risks discovered. The study was further limited by the lack of information on dosage and frequency of cannabis use, as well as some controls, including alcohol and tobacco use.
DISCLOSURES:
Gallagher disclosed receiving grants from the Keck School of Medicine of the University of Southern California, Los Angeles. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Immunotherapy May Be Overused in Dying Patients With Cancer
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Can Addressing Depression Reduce Chemo Toxicity in Older Adults?
TOPLINE:
METHODOLOGY:
- Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
- A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
- Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
- Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
- The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.
TAKEAWAY:
- According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
- The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
- No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
- The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
- An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.
IN PRACTICE:
“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”
SOURCE:
Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer.
LIMITATIONS:
The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.
DISCLOSURES:
This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
- A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
- Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
- Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
- The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.
TAKEAWAY:
- According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
- The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
- No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
- The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
- An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.
IN PRACTICE:
“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”
SOURCE:
Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer.
LIMITATIONS:
The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.
DISCLOSURES:
This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
- A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
- Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
- Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
- The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.
TAKEAWAY:
- According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
- The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
- No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
- The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
- An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.
IN PRACTICE:
“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”
SOURCE:
Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer.
LIMITATIONS:
The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.
DISCLOSURES:
This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
FDA Approves First Engineered Cell Therapy for a Solid Tumor
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
Ancient Viruses in Our DNA Hold Clues to Cancer Treatment
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
FROM SCIENCE ADVANCES
Greater Transparency of Oncologists’ Pharma Relationships Needed
The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”
Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.
Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.
What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.
Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
Open Payments Houses US Physicians’ Conflicts of Interest
To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.
“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”
Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).
The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.
From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.
Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.
The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.
Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.
“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.
Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
Exposing Industry Payments May Have Perverse Effect
A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.
That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.
“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”
The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.
Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.
The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.
A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
Experts: Professional Societies Should Further Limit Industry Payments
While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.
For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.
The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.
Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.
“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”
For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.
From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.
The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.
Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.
When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.
“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”
Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.
“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.
“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”
Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”
Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.
The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”
Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.
Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.
What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.
Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
Open Payments Houses US Physicians’ Conflicts of Interest
To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.
“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”
Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).
The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.
From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.
Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.
The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.
Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.
“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.
Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
Exposing Industry Payments May Have Perverse Effect
A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.
That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.
“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”
The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.
Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.
The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.
A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
Experts: Professional Societies Should Further Limit Industry Payments
While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.
For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.
The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.
Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.
“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”
For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.
From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.
The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.
Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.
When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.
“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”
Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.
“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.
“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”
Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”
Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.
The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”
Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.
Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.
What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.
Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
Open Payments Houses US Physicians’ Conflicts of Interest
To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.
“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”
Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).
The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.
From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.
Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.
The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.
Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.
“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.
Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
Exposing Industry Payments May Have Perverse Effect
A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.
That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.
“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”
The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.
Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.
The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.
A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
Experts: Professional Societies Should Further Limit Industry Payments
While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.
For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.
The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.
Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.
“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”
For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.
From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.
The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.
Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.
When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.
“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”
Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.
“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.
“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”
Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”
Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.
FROM ASCO 2024
Should Cancer Trial Eligibility Become More Inclusive?
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.
The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.
“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”
Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.
In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.
In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.
Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing.
The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers.
Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.
A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.
The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).
“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.
The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.
So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.
Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.
Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”
However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.
“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”
Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
A version of this article appeared on Medscape.com.