Lung Cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

For patients with early stage non–small cell lung cancer (NSCLC), the survival outcomes can be just as good with sublobar resection as with the more invasive lobar resection, suggest results from the CALGB 140503 trial, although strict patient selection remains key.

These new results contrast with those from a previous study from 1995, which found that local recurrence was three times higher and cancer mortality was twice as high with the less invasive procedure.

Those results from nearly 30 years ago established lobectomy as the standard of surgical care in this patient population, but since then advances in imaging and staging have allowed the detection of smaller and earlier tumors, which has “rekindled interest in sublobar resection,” the authors comment.

Hence, they conducted the new trial, which involved almost 700 U.S. patients with clinical T1aN0 NSCLC and a tumor size up to 2 cm, who were randomly assigned to lobar or sublobar tumor resection, and followed for 7 years.

The rates of both disease-free and overall survival were similar between the two groups, with no significant differences observed. There were also no substantial differences in rates of distant and locoregional recurrence.

In addition, there was a suggestion of less reduction in pulmonary function following the less invasive procedure.

“These findings affirm that sublobar resection ... is an effective management approach for this subgroup of patients with NSCLC,” says lead author Nasser Altorki, MD, Weill Cornell Medicine, NewYork–Presbyterian Hospital, New York.

“It is important that these results are interpreted strictly within the constraints of the eligibility criteria mandated by the trial, he emphasizes. “Specifically, the results are applicable only to a highly selected group of patients ... in whom the absence of metastases to hilar and mediastinal lymph nodes is pathologically confirmed.”

Nevertheless, Dr. Altorki said that “these results will become increasingly relevant as the proportion of patients with early-stage lung cancer increases with expanded implementation of lung cancer screening, and as the number of older persons with early-stage disease in whom sublobar resection may be the preferred surgical option increases.”

The study was published online in the New England Journal of Medicine.

In an accompanying editorial, Valerie W. Rusch, MD, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York, agrees. “As CT screening becomes more widespread, this patient population will increase in clinical practice,” she explains.

However, Dr. Rusch also urges caution around patient selection, underlining that the results do not “provide a license for suboptimal surgical care.”

She says that “safeguards” such as the meticulous and strict patient criteria used in the trial “must be preserved in routine practice.”

“Thoracic surgeons will need to expand their expertise in sublobar resections, especially complex segmentectomies, and will need to collaborate closely with pathologists in assessing margins of resection, adequacy of lymph-node staging, and tumor characteristics that may predict recurrence.”

While emphasizing that lobectomy should still be performed when appropriate, Dr. Rusch nevertheless says: “The era of ‘precision’ surgery for NSCLC has arrived.”


 

Consistent with Japanese results

The investigators also point out that their findings are “consistent” with those of a recent Japanese study that compared lobectomy with anatomical segmentectomy, which found that the 5-year overall survival was 91.1% for lobectomy and 94.3% for segmentectomy.

The authors suggest that the difference in overall survival rates between the two trials might be due to anatomical segmentectomy being “considered by most surgeons to be more oncologically sound than wedge resection.”

In the current trial, wedge resection was allowed, however, “because it is the most frequently practiced method of sublobar resection in North America and Europe; thus, its inclusion would make the trial more representative of a ‘real world’ setting.”

Another important difference could be that more than 90% of the patients in the Japanese trial had adenocarcinoma, 45% with an associated ground-glass component, which is associated with better survival than a completely solid adenocarcinoma.

Dr. Rusch agrees that there are likely to be various factors related to the survival differences between the two trials, including patient selection, intraoperative management, and tumor characteristics.

“However, these two landmark trials are practice-changing because they establish sublobar resection as the standard of care for a select group of patients with NSCLC,” Dr. Rusch concluded.
 

Study details

Dr. Altorki and colleagues conducted the multicenter, international, randomized, noninferiority, phase 3 trial in patients with clinically staged T1aN0 NSCLC from 83 academic and community-based institutions in the United States, Canada, and Australia.

Patients were required to have a peripheral lung nodule with a solid component of up to 2 cm on preoperative CT, a tumor center in the outer third of the lung, and a tumor location amenable to sublobar resection, whether wedge or segment, or lobar resection, among other criteria.

In all, 697 patients were randomly assigned to undergo either lobar resection or sublobar resection, of whom 59.1% had wedge resection and 37.9% anatomical segmental resection. The median age was 67.9 years, and 57.4% were female. The vast majority (90%) were White.

After a median follow-up of 7 years, the 5-year disease-free survival was 63.6% with sublobar resection and 64.1% following lobar resection.

The team found that sublobar resection was not inferior to lobectomy for disease-free survival, at a hazard ratio for disease recurrence or death of 1.01 (90% confidence interval, 0.83-1.24), which adjusted to 0.99 after taking into account the site where the patient was treated.

The 5-year overall survival rate was 80.3% after sublobar resection, and 78.9% following lobar resection, at a hazard ratio for death of 0.95 (95% CI, 0.72-1.26).

The results were “generally consistent” when accounting for factors such as age group, sex, tumor location, histologic type, smoking history, tumor size, and ECOG performance status, the team says.

Turning to recurrence, they showed that, among 687 patients eligible for assessment, 30.4% of those in the sublobar resection group and 29.3% of those assigned to lobar resection experienced disease recurrence, with 13.4% and 10%, respectively, having locoregional recurrence.

An exploratory analysis indicated that 5-year recurrence-free survival was similar in the two groups, at 70.2% vs. 71.2% or a hazard ratio for recurrence of 1.05 (95% CI, 0.80-1.39). The cumulative incidence of death was also similar.

It was also notable that reduction in predictive forced expiratory volume in 1 second from baseline was lower with sublobar than lobar resection, at –4.0 vs. –6.0, as was the reduction in predicted forced vital capacity, at –3.0 vs. –5.0.

“Although this difference is arguably not clinically meaningful in this patient population with normal baseline pulmonary functions,” the team writes, “it may be more clinically relevant in patients with compromised pulmonary functions, or in those with lower-lobe disease in whom lobar resection may be associated with greater impairment of pulmonary function.”

Dr. Rusch suggests that “more sensitive or functional assessments” of pulmonary function might include “diffusion capacity and 6-minute walk tests,” although she noted that even short-term differences in pulmonary function “may affect perioperative and functional outcomes, especially for tumors in the lower lobe.”

The study was supported by the National Cancer Institute of the National Institutes of Health, including via grants to the Alliance for Clinical Trials in Oncology and the Canadian Cancer Trials Group, and supported in part by Covidien and Ethicon.

Dr. Altorki reports relationships with AstraZeneca, Genentech, Johnson & Johnson, and Regeneron. Dr. Rusch reports relationships with Cancer Research UK, Genentech, and the National Cancer Institute.

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

For patients with early stage non–small cell lung cancer (NSCLC), the survival outcomes can be just as good with sublobar resection as with the more invasive lobar resection, suggest results from the CALGB 140503 trial, although strict patient selection remains key.

These new results contrast with those from a previous study from 1995, which found that local recurrence was three times higher and cancer mortality was twice as high with the less invasive procedure.

Those results from nearly 30 years ago established lobectomy as the standard of surgical care in this patient population, but since then advances in imaging and staging have allowed the detection of smaller and earlier tumors, which has “rekindled interest in sublobar resection,” the authors comment.

Hence, they conducted the new trial, which involved almost 700 U.S. patients with clinical T1aN0 NSCLC and a tumor size up to 2 cm, who were randomly assigned to lobar or sublobar tumor resection, and followed for 7 years.

The rates of both disease-free and overall survival were similar between the two groups, with no significant differences observed. There were also no substantial differences in rates of distant and locoregional recurrence.

In addition, there was a suggestion of less reduction in pulmonary function following the less invasive procedure.

“These findings affirm that sublobar resection ... is an effective management approach for this subgroup of patients with NSCLC,” says lead author Nasser Altorki, MD, Weill Cornell Medicine, NewYork–Presbyterian Hospital, New York.

“It is important that these results are interpreted strictly within the constraints of the eligibility criteria mandated by the trial, he emphasizes. “Specifically, the results are applicable only to a highly selected group of patients ... in whom the absence of metastases to hilar and mediastinal lymph nodes is pathologically confirmed.”

Nevertheless, Dr. Altorki said that “these results will become increasingly relevant as the proportion of patients with early-stage lung cancer increases with expanded implementation of lung cancer screening, and as the number of older persons with early-stage disease in whom sublobar resection may be the preferred surgical option increases.”

The study was published online in the New England Journal of Medicine.

In an accompanying editorial, Valerie W. Rusch, MD, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York, agrees. “As CT screening becomes more widespread, this patient population will increase in clinical practice,” she explains.

However, Dr. Rusch also urges caution around patient selection, underlining that the results do not “provide a license for suboptimal surgical care.”

She says that “safeguards” such as the meticulous and strict patient criteria used in the trial “must be preserved in routine practice.”

“Thoracic surgeons will need to expand their expertise in sublobar resections, especially complex segmentectomies, and will need to collaborate closely with pathologists in assessing margins of resection, adequacy of lymph-node staging, and tumor characteristics that may predict recurrence.”

While emphasizing that lobectomy should still be performed when appropriate, Dr. Rusch nevertheless says: “The era of ‘precision’ surgery for NSCLC has arrived.”


 

Consistent with Japanese results

The investigators also point out that their findings are “consistent” with those of a recent Japanese study that compared lobectomy with anatomical segmentectomy, which found that the 5-year overall survival was 91.1% for lobectomy and 94.3% for segmentectomy.

The authors suggest that the difference in overall survival rates between the two trials might be due to anatomical segmentectomy being “considered by most surgeons to be more oncologically sound than wedge resection.”

In the current trial, wedge resection was allowed, however, “because it is the most frequently practiced method of sublobar resection in North America and Europe; thus, its inclusion would make the trial more representative of a ‘real world’ setting.”

Another important difference could be that more than 90% of the patients in the Japanese trial had adenocarcinoma, 45% with an associated ground-glass component, which is associated with better survival than a completely solid adenocarcinoma.

Dr. Rusch agrees that there are likely to be various factors related to the survival differences between the two trials, including patient selection, intraoperative management, and tumor characteristics.

“However, these two landmark trials are practice-changing because they establish sublobar resection as the standard of care for a select group of patients with NSCLC,” Dr. Rusch concluded.
 

Study details

Dr. Altorki and colleagues conducted the multicenter, international, randomized, noninferiority, phase 3 trial in patients with clinically staged T1aN0 NSCLC from 83 academic and community-based institutions in the United States, Canada, and Australia.

Patients were required to have a peripheral lung nodule with a solid component of up to 2 cm on preoperative CT, a tumor center in the outer third of the lung, and a tumor location amenable to sublobar resection, whether wedge or segment, or lobar resection, among other criteria.

In all, 697 patients were randomly assigned to undergo either lobar resection or sublobar resection, of whom 59.1% had wedge resection and 37.9% anatomical segmental resection. The median age was 67.9 years, and 57.4% were female. The vast majority (90%) were White.

After a median follow-up of 7 years, the 5-year disease-free survival was 63.6% with sublobar resection and 64.1% following lobar resection.

The team found that sublobar resection was not inferior to lobectomy for disease-free survival, at a hazard ratio for disease recurrence or death of 1.01 (90% confidence interval, 0.83-1.24), which adjusted to 0.99 after taking into account the site where the patient was treated.

The 5-year overall survival rate was 80.3% after sublobar resection, and 78.9% following lobar resection, at a hazard ratio for death of 0.95 (95% CI, 0.72-1.26).

The results were “generally consistent” when accounting for factors such as age group, sex, tumor location, histologic type, smoking history, tumor size, and ECOG performance status, the team says.

Turning to recurrence, they showed that, among 687 patients eligible for assessment, 30.4% of those in the sublobar resection group and 29.3% of those assigned to lobar resection experienced disease recurrence, with 13.4% and 10%, respectively, having locoregional recurrence.

An exploratory analysis indicated that 5-year recurrence-free survival was similar in the two groups, at 70.2% vs. 71.2% or a hazard ratio for recurrence of 1.05 (95% CI, 0.80-1.39). The cumulative incidence of death was also similar.

It was also notable that reduction in predictive forced expiratory volume in 1 second from baseline was lower with sublobar than lobar resection, at –4.0 vs. –6.0, as was the reduction in predicted forced vital capacity, at –3.0 vs. –5.0.

“Although this difference is arguably not clinically meaningful in this patient population with normal baseline pulmonary functions,” the team writes, “it may be more clinically relevant in patients with compromised pulmonary functions, or in those with lower-lobe disease in whom lobar resection may be associated with greater impairment of pulmonary function.”

Dr. Rusch suggests that “more sensitive or functional assessments” of pulmonary function might include “diffusion capacity and 6-minute walk tests,” although she noted that even short-term differences in pulmonary function “may affect perioperative and functional outcomes, especially for tumors in the lower lobe.”

The study was supported by the National Cancer Institute of the National Institutes of Health, including via grants to the Alliance for Clinical Trials in Oncology and the Canadian Cancer Trials Group, and supported in part by Covidien and Ethicon.

Dr. Altorki reports relationships with AstraZeneca, Genentech, Johnson & Johnson, and Regeneron. Dr. Rusch reports relationships with Cancer Research UK, Genentech, and the National Cancer Institute.

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

For patients with early stage non–small cell lung cancer (NSCLC), the survival outcomes can be just as good with sublobar resection as with the more invasive lobar resection, suggest results from the CALGB 140503 trial, although strict patient selection remains key.

These new results contrast with those from a previous study from 1995, which found that local recurrence was three times higher and cancer mortality was twice as high with the less invasive procedure.

Those results from nearly 30 years ago established lobectomy as the standard of surgical care in this patient population, but since then advances in imaging and staging have allowed the detection of smaller and earlier tumors, which has “rekindled interest in sublobar resection,” the authors comment.

Hence, they conducted the new trial, which involved almost 700 U.S. patients with clinical T1aN0 NSCLC and a tumor size up to 2 cm, who were randomly assigned to lobar or sublobar tumor resection, and followed for 7 years.

The rates of both disease-free and overall survival were similar between the two groups, with no significant differences observed. There were also no substantial differences in rates of distant and locoregional recurrence.

In addition, there was a suggestion of less reduction in pulmonary function following the less invasive procedure.

“These findings affirm that sublobar resection ... is an effective management approach for this subgroup of patients with NSCLC,” says lead author Nasser Altorki, MD, Weill Cornell Medicine, NewYork–Presbyterian Hospital, New York.

“It is important that these results are interpreted strictly within the constraints of the eligibility criteria mandated by the trial, he emphasizes. “Specifically, the results are applicable only to a highly selected group of patients ... in whom the absence of metastases to hilar and mediastinal lymph nodes is pathologically confirmed.”

Nevertheless, Dr. Altorki said that “these results will become increasingly relevant as the proportion of patients with early-stage lung cancer increases with expanded implementation of lung cancer screening, and as the number of older persons with early-stage disease in whom sublobar resection may be the preferred surgical option increases.”

The study was published online in the New England Journal of Medicine.

In an accompanying editorial, Valerie W. Rusch, MD, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York, agrees. “As CT screening becomes more widespread, this patient population will increase in clinical practice,” she explains.

However, Dr. Rusch also urges caution around patient selection, underlining that the results do not “provide a license for suboptimal surgical care.”

She says that “safeguards” such as the meticulous and strict patient criteria used in the trial “must be preserved in routine practice.”

“Thoracic surgeons will need to expand their expertise in sublobar resections, especially complex segmentectomies, and will need to collaborate closely with pathologists in assessing margins of resection, adequacy of lymph-node staging, and tumor characteristics that may predict recurrence.”

While emphasizing that lobectomy should still be performed when appropriate, Dr. Rusch nevertheless says: “The era of ‘precision’ surgery for NSCLC has arrived.”


 

Consistent with Japanese results

The investigators also point out that their findings are “consistent” with those of a recent Japanese study that compared lobectomy with anatomical segmentectomy, which found that the 5-year overall survival was 91.1% for lobectomy and 94.3% for segmentectomy.

The authors suggest that the difference in overall survival rates between the two trials might be due to anatomical segmentectomy being “considered by most surgeons to be more oncologically sound than wedge resection.”

In the current trial, wedge resection was allowed, however, “because it is the most frequently practiced method of sublobar resection in North America and Europe; thus, its inclusion would make the trial more representative of a ‘real world’ setting.”

Another important difference could be that more than 90% of the patients in the Japanese trial had adenocarcinoma, 45% with an associated ground-glass component, which is associated with better survival than a completely solid adenocarcinoma.

Dr. Rusch agrees that there are likely to be various factors related to the survival differences between the two trials, including patient selection, intraoperative management, and tumor characteristics.

“However, these two landmark trials are practice-changing because they establish sublobar resection as the standard of care for a select group of patients with NSCLC,” Dr. Rusch concluded.
 

Study details

Dr. Altorki and colleagues conducted the multicenter, international, randomized, noninferiority, phase 3 trial in patients with clinically staged T1aN0 NSCLC from 83 academic and community-based institutions in the United States, Canada, and Australia.

Patients were required to have a peripheral lung nodule with a solid component of up to 2 cm on preoperative CT, a tumor center in the outer third of the lung, and a tumor location amenable to sublobar resection, whether wedge or segment, or lobar resection, among other criteria.

In all, 697 patients were randomly assigned to undergo either lobar resection or sublobar resection, of whom 59.1% had wedge resection and 37.9% anatomical segmental resection. The median age was 67.9 years, and 57.4% were female. The vast majority (90%) were White.

After a median follow-up of 7 years, the 5-year disease-free survival was 63.6% with sublobar resection and 64.1% following lobar resection.

The team found that sublobar resection was not inferior to lobectomy for disease-free survival, at a hazard ratio for disease recurrence or death of 1.01 (90% confidence interval, 0.83-1.24), which adjusted to 0.99 after taking into account the site where the patient was treated.

The 5-year overall survival rate was 80.3% after sublobar resection, and 78.9% following lobar resection, at a hazard ratio for death of 0.95 (95% CI, 0.72-1.26).

The results were “generally consistent” when accounting for factors such as age group, sex, tumor location, histologic type, smoking history, tumor size, and ECOG performance status, the team says.

Turning to recurrence, they showed that, among 687 patients eligible for assessment, 30.4% of those in the sublobar resection group and 29.3% of those assigned to lobar resection experienced disease recurrence, with 13.4% and 10%, respectively, having locoregional recurrence.

An exploratory analysis indicated that 5-year recurrence-free survival was similar in the two groups, at 70.2% vs. 71.2% or a hazard ratio for recurrence of 1.05 (95% CI, 0.80-1.39). The cumulative incidence of death was also similar.

It was also notable that reduction in predictive forced expiratory volume in 1 second from baseline was lower with sublobar than lobar resection, at –4.0 vs. –6.0, as was the reduction in predicted forced vital capacity, at –3.0 vs. –5.0.

“Although this difference is arguably not clinically meaningful in this patient population with normal baseline pulmonary functions,” the team writes, “it may be more clinically relevant in patients with compromised pulmonary functions, or in those with lower-lobe disease in whom lobar resection may be associated with greater impairment of pulmonary function.”

Dr. Rusch suggests that “more sensitive or functional assessments” of pulmonary function might include “diffusion capacity and 6-minute walk tests,” although she noted that even short-term differences in pulmonary function “may affect perioperative and functional outcomes, especially for tumors in the lower lobe.”

The study was supported by the National Cancer Institute of the National Institutes of Health, including via grants to the Alliance for Clinical Trials in Oncology and the Canadian Cancer Trials Group, and supported in part by Covidien and Ethicon.

Dr. Altorki reports relationships with AstraZeneca, Genentech, Johnson & Johnson, and Regeneron. Dr. Rusch reports relationships with Cancer Research UK, Genentech, and the National Cancer Institute.

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

When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.

A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.

Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.

Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.

Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality. 
 

Human hibernation

Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.

Rare cases of accidental hypothermia prove that full recovery is possible even after the heart stops beating. The drop in body temperature slows metabolism and reduces the need for oxygen, stalling brain damage for an hour or more. (In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)

Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.

That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.

Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).

But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”

The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.

Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
 

Artificial womb

Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”

In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.

Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.

The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.

The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.

Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.

No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
 

Messenger RNA therapeutics

Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.

But vaccines are just the beginning of what this technology can do.

A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.

The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.

Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.

As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.

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

When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.

A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.

Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.

Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.

Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality. 
 

Human hibernation

Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.

Rare cases of accidental hypothermia prove that full recovery is possible even after the heart stops beating. The drop in body temperature slows metabolism and reduces the need for oxygen, stalling brain damage for an hour or more. (In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)

Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.

That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.

Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).

But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”

The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.

Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
 

Artificial womb

Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”

In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.

Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.

The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.

The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.

Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.

No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
 

Messenger RNA therapeutics

Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.

But vaccines are just the beginning of what this technology can do.

A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.

The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.

Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.

As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.

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

When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.

A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.

Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.

Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.

Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality. 
 

Human hibernation

Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.

Rare cases of accidental hypothermia prove that full recovery is possible even after the heart stops beating. The drop in body temperature slows metabolism and reduces the need for oxygen, stalling brain damage for an hour or more. (In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)

Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.

That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.

Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).

But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”

The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.

Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
 

Artificial womb

Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”

In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.

Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.

The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.

The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.

Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.

No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
 

Messenger RNA therapeutics

Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.

But vaccines are just the beginning of what this technology can do.

A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.

The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.

Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.

As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.

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

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

A case series of epidermal growth factor receptor (EGFR) exon 20 insertion–mutated advanced non–small cell lung cancer patients with dermatologic adverse events (dAEs) subsequent to treatment with amivantamab showed classic toxic effects associated with EGFR inhibitors and atypical presentations. Toxic effects, however, were mitigated by dose interruptions, dAE management, and amivantamab dose reductions, allowing for cancer therapy continuation in all cases. Amivantamab doses were reduced in 5 out of 6 cases, according to a research letter published in JAMA Dermatology.

The EGFR exon 20 insertion–mutation portends insensitivity to EGFR tyrosine kinase inhibitors and poor prognosis. Amivantamab, a bispecific monoclonal antibody targeting EGFR and mesenchymal epithelial transition factor (MET) is Food and Drug Administration approved for this population. Acneiform eruptions and pruritus are the most common dAEs associated with EGFR inhibitors, with xerosis, fissures, and nail and hair changes occurring additionally. While no FDA-approved monoclonal antibody targets MET exclusively, capmatinib and tepotinib (both tyrosine kinase inhibitors) inhibit MET. They have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.

The Belzer et al. letter reviewed six consecutive cases (mean age, 58) of dAEs associated with amivantamab at two academic health centers (treated June 2021 to August 2022) in order to describe dAEs associated with amivantamab use. “I suspect the rate of dAEs with amivantamab is similar to the rate of dAEs associated with first- and second-generation EGFR inhibitors, where the majority of patients, actually 75%-90%, develop cutaneous toxicity,” said Jonathan Leventhal, MD, Yale University, New Haven, Conn., corresponding author for the Belzer et al. letter.

Time from treatment initiation with amivantamab to dAE ranged from less than 1 month to 4 months. All dAEs were grade 2 or 3 and all included acneiform eruptions. These were widespread in four cases and in another case complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus), and a further case was limited to the scalp, face, upper back, and upper chest. Others with widespread acneiform eruption included the face with hyperkeratotic crust of the scalp and dermatitis of the posterior neck. Fissuring of the palms and soles was noted in two cases with widespread acneiform eruptions. Paronychia with pyogenic granulomas was reported in four cases. Another case included onycholysis with suppurative paronychia.

In five cases amivantamab was stopped but successfully reinitiated at 67%-75% of the original dose. In one case amivantamab was continued at the original dose.

Doxycycline at 100 mg twice daily was included among all of the treatments for cutaneous dAEs. Silver nitrate cautery was applied for pyogenic granulomas in clinic. The case of grade 3 acneiform eruption of the scalp and face was treated with hydrogen peroxide soaks with debridement in clinic, doxycycline, aluminum acetate soaks, and triamcinolone ointment. All dermatologic cases resolved fully without scarring.

“It is very likely that this series highlights the more severe and unusual presentations of dAEs which were referred to oncodermatology. I suspect milder presentations were likely managed by oncologists,” Dr. Leventhal said in the interview.

“It is important for dermatologists and oncologists to be aware of the more severe and atypical dAEs associated with this novel FDA-approved targeted therapy.” Dr. Belzer said. “As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.”

One trial, the authors stated, revealed more than half of patients receiving EGFR inhibitors taking preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline to have more than a 50% reduction in grade 2 or higher dAEs. Belzer et al. concluded that prophylactic treatment, including sun protection, should be considered before initiating treatment with amivantamab.

A limitation of the study, Belzer et al. acknowledged, was the small sample size.

Dr. Leventhal reported receiving personal fees from the advisory boards of Sanofi, Regeneron, and La Roche-Posay as well as clinical trial funding from Azitra and OnQuality Pharmaceuticals outside the submitted work.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

Several decades ago, a new patient came to my office with her family. She was elderly, in good health, spoke no English, and her extended family translated for her. Their request: “Don’t tell her that she has cancer.” Sharing her diagnosis with her would cause too much stress, they said. Their mother would not be able to tolerate the bad news, they said. She would “give up.”

I asked her (through her family and an interpreter) how much she wanted to know about what was going on, or would she prefer I confine my remarks to her family? It turns out that she did want to know her diagnosis and prognosis, and after a thorough discussion in front of her family about her treatment options, she decided she did not want to proceed with additional therapy. She wanted to focus on quality of life. I did not get the impression that this is what her family would have opted for.

The patient’s voice can take multiple directions, such as making informed decisions about their own care. When empowered, patients can and will express their wants, needs, feelings, and priorities to their providers, and they’ll participate in directing their own care. There is a growing body of evidence that shows patients who are more engaged and share decision-making with their health care professionals have better health outcomes and care experiences. Engaged patients feel more empowered and are more motivated to take action. They’re also more likely to follow treatment plans, take their medications, and heed their provider’s recommendations. By virtue of better treatments for lung cancer, many patients are living longer and better lives. Some of these patients even become “experts” on their own care, often bringing questions about research and clinical trials to the attention of their providers.
 

The patient’s voice in research and advocacy

The patient’s perspective is also key to a meaningful, successful clinical research project. Rather than being carried out to, about, or for the patient, patient involvement means research being carried out with or by patients. A patient and researcher may have different research goals. For example, patients may value being able to work, be with family, and live without pain, whereas a clinical researcher’s goal may be inducing responses. Patient involvement is important in both laboratory research and clinical research. The best-designed projects involve patient advocates from the beginning of the project to help make research relevant and meaningful to patients and include these perspectives through project completion.

More and more pharmaceutical companies are actively involving patients at all levels of protocol development, including protocol design and selection of relevant outcomes to patients. Benefits of engaging patients as partners in research include inclusion of real-world data, increased study enrollment, and translation of results to the cancer community in an understandable and accessible manner.
 

Accelerated research

Advocating for accelerated research is another area where the patient’s voice is important. Patients can and do identify research priorities for researchers, funding agencies, and pharma. Patients who support research advocacy are frequently part of meetings and panel discussions with researchers, the Food and Drug Administration, and the National Cancer Institute. And, they serve on advisory boards for pharmaceutical companies. They participate in grant reviews and institutional review boards, review manuscripts, and are active members of the cooperative groups and other professional societies. In fact, patient-led advocacy groups are raising money to help fund research they feel is most important to them. In lung cancer, for example, there are many groups organized around biomarkers, including the EGFR Resisters, ALK Positive, ROS1ders, MET Crusaders, and KRAS Kickers, who have raised hundreds of thousands of dollars to fund investigator-led translational research that would not have occurred without their involvement.

It is important to recognize that all patients are different and have different values and motivations that are important to them and influence their life decisions. Some patients want to know more about their condition and their preferences should be respected. Similarly, it’s critical to understand that not every patient is an advocate and not every advocate is a research advocate. Research advocates have more in-depth knowledge about the science of lung cancer and focus on representing the patient perspective for all lung cancer patients.

So, getting back to my original story: Did my patient “give up” by choosing palliative care without chemotherapy? Perhaps, but I don’t think she considered her decision “giving up.” Instead, she made the best decision possible for herself. What would have happened had she not been told of her diagnosis? She probably would not have spent extra quality time with her family, as they tried to ignore the obvious. And, after all, quality time with her family was all she wanted.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

Several decades ago, a new patient came to my office with her family. She was elderly, in good health, spoke no English, and her extended family translated for her. Their request: “Don’t tell her that she has cancer.” Sharing her diagnosis with her would cause too much stress, they said. Their mother would not be able to tolerate the bad news, they said. She would “give up.”

I asked her (through her family and an interpreter) how much she wanted to know about what was going on, or would she prefer I confine my remarks to her family? It turns out that she did want to know her diagnosis and prognosis, and after a thorough discussion in front of her family about her treatment options, she decided she did not want to proceed with additional therapy. She wanted to focus on quality of life. I did not get the impression that this is what her family would have opted for.

The patient’s voice can take multiple directions, such as making informed decisions about their own care. When empowered, patients can and will express their wants, needs, feelings, and priorities to their providers, and they’ll participate in directing their own care. There is a growing body of evidence that shows patients who are more engaged and share decision-making with their health care professionals have better health outcomes and care experiences. Engaged patients feel more empowered and are more motivated to take action. They’re also more likely to follow treatment plans, take their medications, and heed their provider’s recommendations. By virtue of better treatments for lung cancer, many patients are living longer and better lives. Some of these patients even become “experts” on their own care, often bringing questions about research and clinical trials to the attention of their providers.
 

The patient’s voice in research and advocacy

The patient’s perspective is also key to a meaningful, successful clinical research project. Rather than being carried out to, about, or for the patient, patient involvement means research being carried out with or by patients. A patient and researcher may have different research goals. For example, patients may value being able to work, be with family, and live without pain, whereas a clinical researcher’s goal may be inducing responses. Patient involvement is important in both laboratory research and clinical research. The best-designed projects involve patient advocates from the beginning of the project to help make research relevant and meaningful to patients and include these perspectives through project completion.

More and more pharmaceutical companies are actively involving patients at all levels of protocol development, including protocol design and selection of relevant outcomes to patients. Benefits of engaging patients as partners in research include inclusion of real-world data, increased study enrollment, and translation of results to the cancer community in an understandable and accessible manner.
 

Accelerated research

Advocating for accelerated research is another area where the patient’s voice is important. Patients can and do identify research priorities for researchers, funding agencies, and pharma. Patients who support research advocacy are frequently part of meetings and panel discussions with researchers, the Food and Drug Administration, and the National Cancer Institute. And, they serve on advisory boards for pharmaceutical companies. They participate in grant reviews and institutional review boards, review manuscripts, and are active members of the cooperative groups and other professional societies. In fact, patient-led advocacy groups are raising money to help fund research they feel is most important to them. In lung cancer, for example, there are many groups organized around biomarkers, including the EGFR Resisters, ALK Positive, ROS1ders, MET Crusaders, and KRAS Kickers, who have raised hundreds of thousands of dollars to fund investigator-led translational research that would not have occurred without their involvement.

It is important to recognize that all patients are different and have different values and motivations that are important to them and influence their life decisions. Some patients want to know more about their condition and their preferences should be respected. Similarly, it’s critical to understand that not every patient is an advocate and not every advocate is a research advocate. Research advocates have more in-depth knowledge about the science of lung cancer and focus on representing the patient perspective for all lung cancer patients.

So, getting back to my original story: Did my patient “give up” by choosing palliative care without chemotherapy? Perhaps, but I don’t think she considered her decision “giving up.” Instead, she made the best decision possible for herself. What would have happened had she not been told of her diagnosis? She probably would not have spent extra quality time with her family, as they tried to ignore the obvious. And, after all, quality time with her family was all she wanted.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

Several decades ago, a new patient came to my office with her family. She was elderly, in good health, spoke no English, and her extended family translated for her. Their request: “Don’t tell her that she has cancer.” Sharing her diagnosis with her would cause too much stress, they said. Their mother would not be able to tolerate the bad news, they said. She would “give up.”

I asked her (through her family and an interpreter) how much she wanted to know about what was going on, or would she prefer I confine my remarks to her family? It turns out that she did want to know her diagnosis and prognosis, and after a thorough discussion in front of her family about her treatment options, she decided she did not want to proceed with additional therapy. She wanted to focus on quality of life. I did not get the impression that this is what her family would have opted for.

The patient’s voice can take multiple directions, such as making informed decisions about their own care. When empowered, patients can and will express their wants, needs, feelings, and priorities to their providers, and they’ll participate in directing their own care. There is a growing body of evidence that shows patients who are more engaged and share decision-making with their health care professionals have better health outcomes and care experiences. Engaged patients feel more empowered and are more motivated to take action. They’re also more likely to follow treatment plans, take their medications, and heed their provider’s recommendations. By virtue of better treatments for lung cancer, many patients are living longer and better lives. Some of these patients even become “experts” on their own care, often bringing questions about research and clinical trials to the attention of their providers.
 

The patient’s voice in research and advocacy

The patient’s perspective is also key to a meaningful, successful clinical research project. Rather than being carried out to, about, or for the patient, patient involvement means research being carried out with or by patients. A patient and researcher may have different research goals. For example, patients may value being able to work, be with family, and live without pain, whereas a clinical researcher’s goal may be inducing responses. Patient involvement is important in both laboratory research and clinical research. The best-designed projects involve patient advocates from the beginning of the project to help make research relevant and meaningful to patients and include these perspectives through project completion.

More and more pharmaceutical companies are actively involving patients at all levels of protocol development, including protocol design and selection of relevant outcomes to patients. Benefits of engaging patients as partners in research include inclusion of real-world data, increased study enrollment, and translation of results to the cancer community in an understandable and accessible manner.
 

Accelerated research

Advocating for accelerated research is another area where the patient’s voice is important. Patients can and do identify research priorities for researchers, funding agencies, and pharma. Patients who support research advocacy are frequently part of meetings and panel discussions with researchers, the Food and Drug Administration, and the National Cancer Institute. And, they serve on advisory boards for pharmaceutical companies. They participate in grant reviews and institutional review boards, review manuscripts, and are active members of the cooperative groups and other professional societies. In fact, patient-led advocacy groups are raising money to help fund research they feel is most important to them. In lung cancer, for example, there are many groups organized around biomarkers, including the EGFR Resisters, ALK Positive, ROS1ders, MET Crusaders, and KRAS Kickers, who have raised hundreds of thousands of dollars to fund investigator-led translational research that would not have occurred without their involvement.

It is important to recognize that all patients are different and have different values and motivations that are important to them and influence their life decisions. Some patients want to know more about their condition and their preferences should be respected. Similarly, it’s critical to understand that not every patient is an advocate and not every advocate is a research advocate. Research advocates have more in-depth knowledge about the science of lung cancer and focus on representing the patient perspective for all lung cancer patients.

So, getting back to my original story: Did my patient “give up” by choosing palliative care without chemotherapy? Perhaps, but I don’t think she considered her decision “giving up.” Instead, she made the best decision possible for herself. What would have happened had she not been told of her diagnosis? She probably would not have spent extra quality time with her family, as they tried to ignore the obvious. And, after all, quality time with her family was all she wanted.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.

Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.

Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Because we care about our patients, we need to get involved in the climate change movement. If we want to help prevent cancer and deliver the best possible care to our patients, we need to stop burning fossil fuels. As addressed in an earlier version of this column, burning fossil fuels results in the release of particulate matter and particles measuring 2.5 micrometers in diameter (PM2.5), are classified as group 1 carcinogens by the International Association of Research and Cancer.

Fossil fuels also release greenhouse gases (carbon dioxide, methane, nitrous oxide, and fluorinated gases) which trap solar radiation that would otherwise have been reflected back into space after hitting the earth’s surface. Instead, it is redirected back to earth as infrared radiation warming the planet by 1.1° C since preindustrial times.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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.

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.