Renal Cell Carcinoma

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

An individual patient data meta-analysis of patients undergoing stereotactic ablative body radiotherapy for primary renal cell carcinoma gives support for SABR as a treatment option for patients unwilling or unfit to undergo surgery, shows a study published in The Lancet Oncology.

The analysis, led by Shankar Siva, PhD, of the Peter MacCallum Cancer Centre, Melbourne, also showed that single-fraction SABR might yield less local failure than multifraction SABR.

The incidence of renal cell carcinoma is rising especially in patients older than 70 years, particularly among those with a greater burden of medical comorbidities who face additional risks from anesthesia and major surgery. As alternatives to radical or partial nephrectomy, guidelines recommend nephron-sparing approaches such as thermal ablation and SABR, a noninvasive procedure that avoids anesthesia. While a 2019 meta-analysis revealed promising safety and efficacy for SABR in patients with comorbidities, tumors of stage T1b or higher (that is, ≥ 4 cm) and in solitary kidneys, follow-up was only 28 months and long term outcome data have been awaited.

The current study assessed 5-year outcomes after SABR in primary renal cell carcinoma from the International Radiosurgery Consortium of the Kidney database plus patient data from 12 new contributing institutions in Australia, Canada, Germany, Japan and the United States. The primary endpoint was investigator-assessed local failure. Among 190 patients (median age, 73.6 years), 81 patients (43%) received single-fraction SABR and 109 (57%) received multifraction SABR, with all fractions greater than 5 Gy. Median tumor diameter was 4.0 cm (interquartile range, 2.8-4.9). Among patients with operability details available, referring urologists deemed 75% inoperable; 29% had a solitary kidney.

The cumulative incidence of local failure at 5 years was 5.5% (95% confidence interval, 2.8%–9.5%) overall. Patients receiving single-fraction SABR were observed to have improved local failure and progression-free survival, but not cancer-specific survival, compared with those receiving multifraction SABR.

“We found that multifraction SABR was associated with a 6-times higher risk of local failure after adjustment for baseline characteristics. This data is provocative and needs to be tested in a randomized trial,” Dr. Siva said in a Lancet Oncology podcast interview. There were no grade 3 toxic effects or treatment-related deaths. One patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis.

Reductions in estimated glomerular filtration rate (eGFR), from a median of 60.0 mL/min per 1.73 m2 at baseline were 10.0 mL/min per 1.73 m² at 3 years and by 14.2 mL/min per 1.73 m² at 5 years post SABR. “Most of these patients had severe chronic kidney disease, the median eGFR being only 33 mL/min,” Dr. Siva stated. “So overall the kidney function declines were quite acceptable.”

The results show, Dr. Siva and colleagues stated, that SABR is effective and safe in the long term for patients with primary renal cell carcinoma, and lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. In the audio interview, Dr. Siva said, “I would suggest that we consider SABR for those patients who have larger, inoperable kidney cancers. SABR, in this context, is particularly attractive because these patients don’t have any alternative cure or treatment options. In my opinion, this group should be given compassionate access to SABR. It would be a great place to start.”

The authors acknowledged that because toxicity data were collected retrospectively, low rates of treatment-related toxic effects might be caused by underreporting.

Dr. Siva and colleagues reported no outside funding. Dr. Siva was supported by the Cancer Council Victoria Colebatch Fellowship.

An individual patient data meta-analysis of patients undergoing stereotactic ablative body radiotherapy for primary renal cell carcinoma gives support for SABR as a treatment option for patients unwilling or unfit to undergo surgery, shows a study published in The Lancet Oncology.

The analysis, led by Shankar Siva, PhD, of the Peter MacCallum Cancer Centre, Melbourne, also showed that single-fraction SABR might yield less local failure than multifraction SABR.

The incidence of renal cell carcinoma is rising especially in patients older than 70 years, particularly among those with a greater burden of medical comorbidities who face additional risks from anesthesia and major surgery. As alternatives to radical or partial nephrectomy, guidelines recommend nephron-sparing approaches such as thermal ablation and SABR, a noninvasive procedure that avoids anesthesia. While a 2019 meta-analysis revealed promising safety and efficacy for SABR in patients with comorbidities, tumors of stage T1b or higher (that is, ≥ 4 cm) and in solitary kidneys, follow-up was only 28 months and long term outcome data have been awaited.

The current study assessed 5-year outcomes after SABR in primary renal cell carcinoma from the International Radiosurgery Consortium of the Kidney database plus patient data from 12 new contributing institutions in Australia, Canada, Germany, Japan and the United States. The primary endpoint was investigator-assessed local failure. Among 190 patients (median age, 73.6 years), 81 patients (43%) received single-fraction SABR and 109 (57%) received multifraction SABR, with all fractions greater than 5 Gy. Median tumor diameter was 4.0 cm (interquartile range, 2.8-4.9). Among patients with operability details available, referring urologists deemed 75% inoperable; 29% had a solitary kidney.

The cumulative incidence of local failure at 5 years was 5.5% (95% confidence interval, 2.8%–9.5%) overall. Patients receiving single-fraction SABR were observed to have improved local failure and progression-free survival, but not cancer-specific survival, compared with those receiving multifraction SABR.

“We found that multifraction SABR was associated with a 6-times higher risk of local failure after adjustment for baseline characteristics. This data is provocative and needs to be tested in a randomized trial,” Dr. Siva said in a Lancet Oncology podcast interview. There were no grade 3 toxic effects or treatment-related deaths. One patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis.

Reductions in estimated glomerular filtration rate (eGFR), from a median of 60.0 mL/min per 1.73 m2 at baseline were 10.0 mL/min per 1.73 m² at 3 years and by 14.2 mL/min per 1.73 m² at 5 years post SABR. “Most of these patients had severe chronic kidney disease, the median eGFR being only 33 mL/min,” Dr. Siva stated. “So overall the kidney function declines were quite acceptable.”

The results show, Dr. Siva and colleagues stated, that SABR is effective and safe in the long term for patients with primary renal cell carcinoma, and lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. In the audio interview, Dr. Siva said, “I would suggest that we consider SABR for those patients who have larger, inoperable kidney cancers. SABR, in this context, is particularly attractive because these patients don’t have any alternative cure or treatment options. In my opinion, this group should be given compassionate access to SABR. It would be a great place to start.”

The authors acknowledged that because toxicity data were collected retrospectively, low rates of treatment-related toxic effects might be caused by underreporting.

Dr. Siva and colleagues reported no outside funding. Dr. Siva was supported by the Cancer Council Victoria Colebatch Fellowship.

An individual patient data meta-analysis of patients undergoing stereotactic ablative body radiotherapy for primary renal cell carcinoma gives support for SABR as a treatment option for patients unwilling or unfit to undergo surgery, shows a study published in The Lancet Oncology.

The analysis, led by Shankar Siva, PhD, of the Peter MacCallum Cancer Centre, Melbourne, also showed that single-fraction SABR might yield less local failure than multifraction SABR.

The incidence of renal cell carcinoma is rising especially in patients older than 70 years, particularly among those with a greater burden of medical comorbidities who face additional risks from anesthesia and major surgery. As alternatives to radical or partial nephrectomy, guidelines recommend nephron-sparing approaches such as thermal ablation and SABR, a noninvasive procedure that avoids anesthesia. While a 2019 meta-analysis revealed promising safety and efficacy for SABR in patients with comorbidities, tumors of stage T1b or higher (that is, ≥ 4 cm) and in solitary kidneys, follow-up was only 28 months and long term outcome data have been awaited.

The current study assessed 5-year outcomes after SABR in primary renal cell carcinoma from the International Radiosurgery Consortium of the Kidney database plus patient data from 12 new contributing institutions in Australia, Canada, Germany, Japan and the United States. The primary endpoint was investigator-assessed local failure. Among 190 patients (median age, 73.6 years), 81 patients (43%) received single-fraction SABR and 109 (57%) received multifraction SABR, with all fractions greater than 5 Gy. Median tumor diameter was 4.0 cm (interquartile range, 2.8-4.9). Among patients with operability details available, referring urologists deemed 75% inoperable; 29% had a solitary kidney.

The cumulative incidence of local failure at 5 years was 5.5% (95% confidence interval, 2.8%–9.5%) overall. Patients receiving single-fraction SABR were observed to have improved local failure and progression-free survival, but not cancer-specific survival, compared with those receiving multifraction SABR.

“We found that multifraction SABR was associated with a 6-times higher risk of local failure after adjustment for baseline characteristics. This data is provocative and needs to be tested in a randomized trial,” Dr. Siva said in a Lancet Oncology podcast interview. There were no grade 3 toxic effects or treatment-related deaths. One patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis.

Reductions in estimated glomerular filtration rate (eGFR), from a median of 60.0 mL/min per 1.73 m2 at baseline were 10.0 mL/min per 1.73 m² at 3 years and by 14.2 mL/min per 1.73 m² at 5 years post SABR. “Most of these patients had severe chronic kidney disease, the median eGFR being only 33 mL/min,” Dr. Siva stated. “So overall the kidney function declines were quite acceptable.”

The results show, Dr. Siva and colleagues stated, that SABR is effective and safe in the long term for patients with primary renal cell carcinoma, and lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. In the audio interview, Dr. Siva said, “I would suggest that we consider SABR for those patients who have larger, inoperable kidney cancers. SABR, in this context, is particularly attractive because these patients don’t have any alternative cure or treatment options. In my opinion, this group should be given compassionate access to SABR. It would be a great place to start.”

The authors acknowledged that because toxicity data were collected retrospectively, low rates of treatment-related toxic effects might be caused by underreporting.

Dr. Siva and colleagues reported no outside funding. Dr. Siva was supported by the Cancer Council Victoria Colebatch Fellowship.

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

A systematic review of immune checkpoint inhibitor (ICI) combinations for advanced renal cancer finds that treatment with ICIs has a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib. The combination treatment should be made readily available worldwide to patients with advanced renal cell carcinoma (RCC), the authors said.

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials have examined ICIs in combination with VEGF-directed therapies.

In a review published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and 1 each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared to sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate poor-risk patients compared to sunitinib, but the combination led to more frequent discontinuation due to toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation due to toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation due to toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggest that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual ICI combination therapy were similar to those seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors noted that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, International Metastatic RCC Database Consortium (IMDC) risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.