User login
Lung Cancer Screening Unveils Hidden Health Risks
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
FROM ELCC 2024
The Simple Change That Can Improve Patient Satisfaction
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.
This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.
We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.
We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.
There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.
I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”
It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.
What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.
In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.
The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.
This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.
It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.
I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.
I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.
For the time being, over and out. Ahoy. Thanks for listening.
Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.
This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.
We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.
We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.
There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.
I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”
It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.
What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.
In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.
The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.
This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.
It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.
I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.
I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.
For the time being, over and out. Ahoy. Thanks for listening.
Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine from University of Oxford. I’d like to talk today about how we communicate with patients.
This is current on my mind because on Friday after clinic, I popped around to see a couple of patients who were in our local hospice. They were there for end-of-life care, being wonderfully well looked after. These were patients I have looked after for 3, 4, or 5 years, patients whom I cared for, and patients of whom I was fond. I think that relationship was reciprocated by them.
We know that any effective communication between patients and doctors is absolutely critical and fundamental to the delivery of patient-centered care. It’s really hard to measure and challenging to attain in the dynamic, often noisy environment of a busy ward or even in the relative peace and quiet of a hospice.
We know that specific behavior by doctors can make a real difference to how they’re perceived by the patient, including their communicative skills and so on. I’ve been a doctor for more than 40 years, but sophisticated communicator though I think I am, there I was, standing by the bedside. It’s really interesting and odd, actually, when you stop and think about it.
There’s an increasing body of evidence that suggests that if the physician sits at the patient’s bedside, establishes better, more direct eye-to-eye contact and so on, then the quality of communication and patient satisfaction is improved.
I picked up on a recent study published just a few days ago in The BMJ; the title of the study is “Effect of Chair Placement on Physicians’ Behavior and Patients’ Satisfaction: Randomized Deception Trial.”
It was done in a single center and there were 125 separate physician interactions. In half of them, the chair in the patient’s room was in its conventional place back against the wall, round a corner, not particularly accessible. The randomization, or the active intervention, if you like, was to have a chair placed less than 3 feet from the patient’s bed and at the patient’s eye level.
What was really interesting was that of these randomized interventions in the setting in which the chair placement was close to the patient’s bed — it was accessible, less than 3 feet — 38 of the 60 physicians sat down in the chair and engaged with the patient from that level.
In the other setting, in which the chair wasn’t immediately adjacent to the bedside (it was back against the wall, out of the way), only in 5 of 60 did the physician retrieve the chair and move it to the right position. Otherwise, they stood and talked to the patient in that way.
The patient satisfaction scores that were measured using a conventional tool were much better for those seated physicians rather than those who stood and towered above.
This is an interesting study with statistically significant findings. It didn’t mean that the physicians who sat spent more time with the patient. It was the same in both settings, at about 10 or 11 minutes. It didn’t alter the physician’s perception of how long they spent with the patient — they guessed it was about 10 minutes, equally on both sides — or indeed the patient’s interpretation of how long the physician stayed.
It wasn’t a temporal thing but just the quality of communication. The patient satisfaction was much better, just simply by sitting at the patient’s bedside and engaging with them. It’s a tiny thing to do that made for a significant qualitative improvement. I’ve learned that lesson. No more towering above. No more standing at the bottom of the patient’s bedside, as I was taught and as I’ve always done.
I’m going to nudge my behavior. I’m going to use the psychology of that small study to nudge myself, the junior doctors that I train, and perhaps even my consultant colleagues, to do the same. It’s a small but effective step forward in improving patient-centered communication.
I’d be delighted to see what you think. How many of you stand? Being old-school, I would have thought that that’s most of us. How many of you make the effort to drag the chair over to sit at the patient’s bedside and to engage more fully? I’d be really interested in any comments that you’ve got.
For the time being, over and out. Ahoy. Thanks for listening.
Dr. Kerr disclosed the following relevant financial relationships Served as a director, officer, partner, employee, advisor, consultant, or trustee for Celleron Therapeutics and Oxford Cancer Biomarkers (board of directors); Afrox (charity; trustee); and GlaxoSmithKline and Bayer HealthCare Pharmaceuticals (consultant). Serve(d) as a speaker or a member of a speakers bureau for Genomic Health and Merck Serono. Received research grant from Roche. Has a 5% or greater equity interest in Celleron Therapeutics and Oxford Cancer Biomarkers.
A version of this article appeared on Medscape.com.
Therapeutic HPV16 vaccine clears virus in most patients with CIN
The vaccine, pNGVL4a-CRTE6E7L2, also showed signs of efficacy in patients living with HIV, reported Kimberly Lynn Levinson, MD, MPH, associate professor of obstetrics and gynecology at Johns Hopkins Medicine in Baltimore.
“We demonstrated a 78% rate of clearance for both histologic regression and HPV16, with some clearance of other HPV types,” she said in an oral abstract presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.
Further evaluation of the vaccine in vulvar, vaginal, and other tissue types is required, and evaluation of immune response at the local and systemic is ongoing, Dr. Levinson said.
In contrast to HPV16 prophylactic vaccines, which form an antibody-specific response to HPV, therapeutic vaccines elicit a cell-mediated immunity, primarily focusing on the virus’ E6 and E7 proteins.
There are currently only three Food and Drug Administration–approved therapeutic vaccines for cancer, but none are as yet approved for treatment of gynecologic malignancies.
According to the US National Institutes of Health, there are multiple therapeutic HPV vaccines in development using either vector-based, peptide and protein-based, or nucleic-acid based approaches, or whole cell (dendritic cell) approaches.
Current Study
Dr. Levinson noted that “DNA vaccines are both well tolerated and simple to produce, and the addition of calreticulin enhances immune response.”
The investigational vaccine is delivered via an electoporation device (TriGrid delivery system) that stimulates muscle at the injection site to produce an enhanced immune response.
In preclinical studies the device was associated with an enhanced immune response compared with standard intramuscular injection. The enhance immune effect persisted despite CD4 T cell depletion.
The investigators conducted a phase 1 dose-escalation study, administering the vaccine to two separate cohorts: women without HIV who had HPV16-positive cervical dysplasia (CIN 2/3) and women living with HIV with HPV16-positive cervical or vulvovaginal dysplasia (CIN 2/3, VIN 2/3 or VAIN 2/3).
The vaccine was delivered at weeks 0, 4, and 8, at doses of 0.3 mg, 1.0 mg, or 3.0 mg. At week 12, all patients underwent site-specific biopsy to verify non-progression.
At 6 months, the patients then underwent definitive treatment with either loop electro excision or vulvar/vaginal excision. At 12 months, all patients had standard evaluations with biopsies.
Dr. Levinson reported results for the first 14 women enrolled, 10 of whom were HIV-negative and 4 of whom were HIV-positive.
Of nine women in the HIV-negative arm who had completed 6-month visits and were evaluable, two had HPV16 clearance by 2-month follow-up, and seven had clearance at 6 months. Other HPV subtypes cleared in two of five patients at 3 months and in three of five at 6 months.
In addition, seven of nine patients in this arm had histologic regression at 6 months.
In the HIV-positive arm, the two patients with CIN had no HPV16 clearance at 3 months, but both had clearance at 16 months. The vaccine did not clear other HPV subtypes in these patients, however.
Of the two women in this arm who had VIN, one had HPV16 clearance and histologic regression at 6 months. The other patient had neither viral clearance nor histologic regression.
All participants tolerated each vaccine well. Adverse events were all grade 1 in severity and resolved within 4 weeks. The most common event was tenderness at the injection site. There were also three cases of mild headache, two cases of drowsiness, and one of nausea.
What’s Next?
In the question-and-answer session following the presentation, Ronald D. Alvarez, MD, MBA, chairman and clinical service chief of obstetrics and gynecology at Vanderbilt University Medical Center in Nashville, Tennessee, asked Dr. Levinson how the vaccine development will proceed.
“Obviously, you have more data to collect and analyze, but how are you going to move forward with what looks like equal efficacy between the 1 milligram and the 3 milligram doses? Are you just going to go with the maximum tolerated dose, or consider a lower dose if it shows equal efficacy in terms of histologic regression as well as HPV clearance?” he asked.
“This is something we’re very interested in, and we do plan for the dose-expansion phase to go with the higher dose,” Dr. Levinson replied. “We need to evaluate it further and we may need to do further randomization between the medium dose and the highest dose to determine if there are differences both with systemic and local responses.”
Robert DeBernardo, MD, section head of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic, asked whether Dr. Levinson and colleagues were considering evaluating the vaccine in transplant recipients, “because we have a lot of persistent HPV in that subgroup.”
Dr. Levinson said that one of the dose-expansion cohorts for further study is a population of patients scheduled for transplantation.
“What we’re interested in is looking at whether we can ‘cure’ HPV prior to transplantation, and we think that’s going to be the best way to show that this vaccine potentially eliminates the virus, because if we can eliminate the virus and then take a population that’s going to be immunodeficient, then that would show that there’s no reactivation of the virus,” she said.
The study is supported by the National Institutes of Health. Dr. Levinson, Dr. Alvarez, and Dr. DeBernardo had no conflicts of interest to report.
The vaccine, pNGVL4a-CRTE6E7L2, also showed signs of efficacy in patients living with HIV, reported Kimberly Lynn Levinson, MD, MPH, associate professor of obstetrics and gynecology at Johns Hopkins Medicine in Baltimore.
“We demonstrated a 78% rate of clearance for both histologic regression and HPV16, with some clearance of other HPV types,” she said in an oral abstract presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.
Further evaluation of the vaccine in vulvar, vaginal, and other tissue types is required, and evaluation of immune response at the local and systemic is ongoing, Dr. Levinson said.
In contrast to HPV16 prophylactic vaccines, which form an antibody-specific response to HPV, therapeutic vaccines elicit a cell-mediated immunity, primarily focusing on the virus’ E6 and E7 proteins.
There are currently only three Food and Drug Administration–approved therapeutic vaccines for cancer, but none are as yet approved for treatment of gynecologic malignancies.
According to the US National Institutes of Health, there are multiple therapeutic HPV vaccines in development using either vector-based, peptide and protein-based, or nucleic-acid based approaches, or whole cell (dendritic cell) approaches.
Current Study
Dr. Levinson noted that “DNA vaccines are both well tolerated and simple to produce, and the addition of calreticulin enhances immune response.”
The investigational vaccine is delivered via an electoporation device (TriGrid delivery system) that stimulates muscle at the injection site to produce an enhanced immune response.
In preclinical studies the device was associated with an enhanced immune response compared with standard intramuscular injection. The enhance immune effect persisted despite CD4 T cell depletion.
The investigators conducted a phase 1 dose-escalation study, administering the vaccine to two separate cohorts: women without HIV who had HPV16-positive cervical dysplasia (CIN 2/3) and women living with HIV with HPV16-positive cervical or vulvovaginal dysplasia (CIN 2/3, VIN 2/3 or VAIN 2/3).
The vaccine was delivered at weeks 0, 4, and 8, at doses of 0.3 mg, 1.0 mg, or 3.0 mg. At week 12, all patients underwent site-specific biopsy to verify non-progression.
At 6 months, the patients then underwent definitive treatment with either loop electro excision or vulvar/vaginal excision. At 12 months, all patients had standard evaluations with biopsies.
Dr. Levinson reported results for the first 14 women enrolled, 10 of whom were HIV-negative and 4 of whom were HIV-positive.
Of nine women in the HIV-negative arm who had completed 6-month visits and were evaluable, two had HPV16 clearance by 2-month follow-up, and seven had clearance at 6 months. Other HPV subtypes cleared in two of five patients at 3 months and in three of five at 6 months.
In addition, seven of nine patients in this arm had histologic regression at 6 months.
In the HIV-positive arm, the two patients with CIN had no HPV16 clearance at 3 months, but both had clearance at 16 months. The vaccine did not clear other HPV subtypes in these patients, however.
Of the two women in this arm who had VIN, one had HPV16 clearance and histologic regression at 6 months. The other patient had neither viral clearance nor histologic regression.
All participants tolerated each vaccine well. Adverse events were all grade 1 in severity and resolved within 4 weeks. The most common event was tenderness at the injection site. There were also three cases of mild headache, two cases of drowsiness, and one of nausea.
What’s Next?
In the question-and-answer session following the presentation, Ronald D. Alvarez, MD, MBA, chairman and clinical service chief of obstetrics and gynecology at Vanderbilt University Medical Center in Nashville, Tennessee, asked Dr. Levinson how the vaccine development will proceed.
“Obviously, you have more data to collect and analyze, but how are you going to move forward with what looks like equal efficacy between the 1 milligram and the 3 milligram doses? Are you just going to go with the maximum tolerated dose, or consider a lower dose if it shows equal efficacy in terms of histologic regression as well as HPV clearance?” he asked.
“This is something we’re very interested in, and we do plan for the dose-expansion phase to go with the higher dose,” Dr. Levinson replied. “We need to evaluate it further and we may need to do further randomization between the medium dose and the highest dose to determine if there are differences both with systemic and local responses.”
Robert DeBernardo, MD, section head of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic, asked whether Dr. Levinson and colleagues were considering evaluating the vaccine in transplant recipients, “because we have a lot of persistent HPV in that subgroup.”
Dr. Levinson said that one of the dose-expansion cohorts for further study is a population of patients scheduled for transplantation.
“What we’re interested in is looking at whether we can ‘cure’ HPV prior to transplantation, and we think that’s going to be the best way to show that this vaccine potentially eliminates the virus, because if we can eliminate the virus and then take a population that’s going to be immunodeficient, then that would show that there’s no reactivation of the virus,” she said.
The study is supported by the National Institutes of Health. Dr. Levinson, Dr. Alvarez, and Dr. DeBernardo had no conflicts of interest to report.
The vaccine, pNGVL4a-CRTE6E7L2, also showed signs of efficacy in patients living with HIV, reported Kimberly Lynn Levinson, MD, MPH, associate professor of obstetrics and gynecology at Johns Hopkins Medicine in Baltimore.
“We demonstrated a 78% rate of clearance for both histologic regression and HPV16, with some clearance of other HPV types,” she said in an oral abstract presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.
Further evaluation of the vaccine in vulvar, vaginal, and other tissue types is required, and evaluation of immune response at the local and systemic is ongoing, Dr. Levinson said.
In contrast to HPV16 prophylactic vaccines, which form an antibody-specific response to HPV, therapeutic vaccines elicit a cell-mediated immunity, primarily focusing on the virus’ E6 and E7 proteins.
There are currently only three Food and Drug Administration–approved therapeutic vaccines for cancer, but none are as yet approved for treatment of gynecologic malignancies.
According to the US National Institutes of Health, there are multiple therapeutic HPV vaccines in development using either vector-based, peptide and protein-based, or nucleic-acid based approaches, or whole cell (dendritic cell) approaches.
Current Study
Dr. Levinson noted that “DNA vaccines are both well tolerated and simple to produce, and the addition of calreticulin enhances immune response.”
The investigational vaccine is delivered via an electoporation device (TriGrid delivery system) that stimulates muscle at the injection site to produce an enhanced immune response.
In preclinical studies the device was associated with an enhanced immune response compared with standard intramuscular injection. The enhance immune effect persisted despite CD4 T cell depletion.
The investigators conducted a phase 1 dose-escalation study, administering the vaccine to two separate cohorts: women without HIV who had HPV16-positive cervical dysplasia (CIN 2/3) and women living with HIV with HPV16-positive cervical or vulvovaginal dysplasia (CIN 2/3, VIN 2/3 or VAIN 2/3).
The vaccine was delivered at weeks 0, 4, and 8, at doses of 0.3 mg, 1.0 mg, or 3.0 mg. At week 12, all patients underwent site-specific biopsy to verify non-progression.
At 6 months, the patients then underwent definitive treatment with either loop electro excision or vulvar/vaginal excision. At 12 months, all patients had standard evaluations with biopsies.
Dr. Levinson reported results for the first 14 women enrolled, 10 of whom were HIV-negative and 4 of whom were HIV-positive.
Of nine women in the HIV-negative arm who had completed 6-month visits and were evaluable, two had HPV16 clearance by 2-month follow-up, and seven had clearance at 6 months. Other HPV subtypes cleared in two of five patients at 3 months and in three of five at 6 months.
In addition, seven of nine patients in this arm had histologic regression at 6 months.
In the HIV-positive arm, the two patients with CIN had no HPV16 clearance at 3 months, but both had clearance at 16 months. The vaccine did not clear other HPV subtypes in these patients, however.
Of the two women in this arm who had VIN, one had HPV16 clearance and histologic regression at 6 months. The other patient had neither viral clearance nor histologic regression.
All participants tolerated each vaccine well. Adverse events were all grade 1 in severity and resolved within 4 weeks. The most common event was tenderness at the injection site. There were also three cases of mild headache, two cases of drowsiness, and one of nausea.
What’s Next?
In the question-and-answer session following the presentation, Ronald D. Alvarez, MD, MBA, chairman and clinical service chief of obstetrics and gynecology at Vanderbilt University Medical Center in Nashville, Tennessee, asked Dr. Levinson how the vaccine development will proceed.
“Obviously, you have more data to collect and analyze, but how are you going to move forward with what looks like equal efficacy between the 1 milligram and the 3 milligram doses? Are you just going to go with the maximum tolerated dose, or consider a lower dose if it shows equal efficacy in terms of histologic regression as well as HPV clearance?” he asked.
“This is something we’re very interested in, and we do plan for the dose-expansion phase to go with the higher dose,” Dr. Levinson replied. “We need to evaluate it further and we may need to do further randomization between the medium dose and the highest dose to determine if there are differences both with systemic and local responses.”
Robert DeBernardo, MD, section head of obstetrics and gynecology and the Women’s Health Institute at the Cleveland Clinic, asked whether Dr. Levinson and colleagues were considering evaluating the vaccine in transplant recipients, “because we have a lot of persistent HPV in that subgroup.”
Dr. Levinson said that one of the dose-expansion cohorts for further study is a population of patients scheduled for transplantation.
“What we’re interested in is looking at whether we can ‘cure’ HPV prior to transplantation, and we think that’s going to be the best way to show that this vaccine potentially eliminates the virus, because if we can eliminate the virus and then take a population that’s going to be immunodeficient, then that would show that there’s no reactivation of the virus,” she said.
The study is supported by the National Institutes of Health. Dr. Levinson, Dr. Alvarez, and Dr. DeBernardo had no conflicts of interest to report.
FROM SGO 2024
Upfront Low-Dose Radiation Improves Advanced SCLC Outcomes
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ELCC 2024
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
Diagnosis Denial: How Doctors Help Patients Accept Their Condition
Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.
“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”
Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.
“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.
And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.
“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.
“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”
More advice on helping patients who are in denial about their medical condition:
Make Sure They Understand What’s Going on
In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.
“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
Share the Data
If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.
“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
Help Them Wrap Their Mind Around a Lifelong Condition
It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”
Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
Be Ready to Respond
Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.
“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”
They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”
Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
Acknowledge Differences
News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.
“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
Find Mutual Ground
If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.
“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
Seven Ways to Cope With Diagnosis Denial
This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:
- Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
- Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
- Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
- Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
- Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
- Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
- Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.
A version of this article first appeared on Medscape.com.
Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.
“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”
Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.
“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.
And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.
“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.
“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”
More advice on helping patients who are in denial about their medical condition:
Make Sure They Understand What’s Going on
In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.
“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
Share the Data
If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.
“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
Help Them Wrap Their Mind Around a Lifelong Condition
It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”
Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
Be Ready to Respond
Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.
“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”
They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”
Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
Acknowledge Differences
News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.
“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
Find Mutual Ground
If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.
“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
Seven Ways to Cope With Diagnosis Denial
This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:
- Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
- Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
- Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
- Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
- Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
- Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
- Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.
A version of this article first appeared on Medscape.com.
Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.
“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”
Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.
“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.
And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.
“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.
“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”
More advice on helping patients who are in denial about their medical condition:
Make Sure They Understand What’s Going on
In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.
“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
Share the Data
If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.
“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
Help Them Wrap Their Mind Around a Lifelong Condition
It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”
Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
Be Ready to Respond
Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.
“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”
They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”
Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
Acknowledge Differences
News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.
“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
Find Mutual Ground
If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.
“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
Seven Ways to Cope With Diagnosis Denial
This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:
- Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
- Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
- Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
- Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
- Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
- Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
- Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.
A version of this article first appeared on Medscape.com.
ctDNA May Predict Early Response to Radiation of Gynecologic Cancers
Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.
“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.
Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
Correlating treatment with responses
Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.
Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.
The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.
The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.
Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.
Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
Results
At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).
There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).
All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.
From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.
Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.
“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.
In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
How to Use It?
Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.
“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.
The answers will be found only with further prospective studies, he emphasized.
“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.
Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”
The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.
Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.
“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.
Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
Correlating treatment with responses
Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.
Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.
The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.
The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.
Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.
Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
Results
At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).
There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).
All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.
From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.
Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.
“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.
In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
How to Use It?
Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.
“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.
The answers will be found only with further prospective studies, he emphasized.
“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.
Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”
The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.
Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.
“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.
Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
Correlating treatment with responses
Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.
Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.
The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.
The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.
Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.
Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
Results
At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).
There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).
All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.
From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.
Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.
“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.
In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
How to Use It?
Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.
“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.
The answers will be found only with further prospective studies, he emphasized.
“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.
Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”
The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.
FROM SGO 2024
New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
Non-Radical Surgery a Win-Win for Early Cervical Cancer
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
according to results of the GOG-278 trial.
In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.
Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.
He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”
GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.
The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.
Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.
Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.
In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.
He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
‘Impressive’ Data
Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”
She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.
Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.
The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.
Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.
A version of this article appeared on Medscape.com.
FROM SGO 2024
Extraordinary Patients Inspired Father of Cancer Immunotherapy
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.