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Ob.gyns. on the day that Roe v. Wade was overturned
“I’m happy to contribute, but can you keep it anonymous? It’s a safety concern for me.”
On the day that the Supreme Court of the United States voted to strike down Roe v. Wade, I reached out to ob.gyn.s across the country, wanting to hear their reactions. My own response, like that of many doctors and women, was a visceral mix of anger, fear, and grief. I could only begin to imagine what the real experts on reproductive health care were going through.
When the first ob.gyn. responded to my request by expressing concerns around anonymity and personal safety, I was shocked – but I shouldn’t have been. For starters, there is already a storied history in this country of deadly attacks on abortion providers. David Gunn, MD; Barnett Slepian, MD; and George Tiller, MD, were all tragically murdered by antiabortion extremists. Then, there’s the existence of websites that keep logs of abortion providers and sometimes include photos, office contact information, or even home addresses.
The idea that any reproductive health care provider should have to think twice before offering their uniquely qualified opinion is profoundly disturbing, nearly as disturbing as the Supreme Court’s decision itself. But it’s more critical than ever for ob.gyn. voices to be amplified. This is the time for the healthcare community to rally around women’s health providers, to learn from them, to support them.
I asked ob.gyns. around the country to tell me what they were thinking and feeling on the day that Roe v. Wade was overturned. We agreed to keep the responses anonymous, given that several people expressed very understandable safety concerns.
Here’s what they had to say.
Tennessee ob.gyn.
“Today is an emotionally charged day for many people in this country, yet as I type this, with my ob.gyn. practice continuing around me, with my own almost 10-week pregnancy growing inside me, I feel quite blunted. I feel powerless to answer questions that are variations on ‘what next?’ or ‘how do we fight back?’ All I can think of is, I am so glad I do not have anyone on my schedule right now who does not want to be pregnant. But what will happen when that eventually changes? What about my colleagues who do have these patients on their schedules today? On a personal level, what if my prenatal genetic testing comes back abnormal? How can we so blatantly disregard a separation of church and state in this country? What ways will our government interfere with my practice next? My head is spinning, but I have to go see my next patient. She is a 25-year-old who is here to have an IUD placed, and that seems like the most important thing I can do today.”
South Carolina ob.gyn.
“I’m really scared. For my patients and for myself. I don’t know how to be a good ob.gyn. if my ability to offer safe and accessible abortion care is being threatened.”
Massachusetts ob.gyn.
“Livid and devastated and sad and terrified.”
California family planning specialist
“The fact is that about one in four people with uteruses have had an abortion. I can’t tell you how many abortions I’ve provided for people who say that they don’t ‘believe’ in them or that they thought they’d never be in this situation. ... The fact is that pregnancy is a life-threatening condition in and of itself. I am an ob.gyn., a medical doctor, and an abortion provider. I will not stop providing abortions or helping people access them. I will dedicate my life to ensuring this right to bodily autonomy. Today I am devastated by the Supreme Court’s decision to force parenthood that will result in increased maternal mortality. I am broken, but I have never been more proud to be an abortion provider.”
New York ob.gyn.
“Grateful to live in a state and work for a hospital where I can provide abortions but feel terrible for so many people less fortunate and underserved.”
Illinois maternal-fetal medicine specialist
“As a maternal-fetal medicine specialist, I fear for my patients who are at the highest risk of pregnancy complications having their freedom taken away. For the tragic ultrasound findings that make a pregnant person carry a baby who will never live. For the patients who cannot use most forms of contraception because of their medical comorbidities. For the patients who are victims of intimate partner violence or under the influence of their culture, to continue having children regardless of their desires or their health. ... The freedom to prevent or end a pregnancy has enabled women to become independent and productive members of society on their own terms, with or without children. My heart breaks for the children and adolescents and adults who are being told they are second-class citizens, not worthy of making their own decisions. Politicians and Supreme Court justices are not in the clinic room, ultrasound suite, operating room, or delivery room when we have these intense conversations and pregnancy outcomes. They have no idea that of which they speak, and it’s unconscionable that they can determine what healthcare decisions my patients can make for their own lives. Nobody knows a body better than the patient themselves.”
Texas ob.gyn.
“In the area where I live and practice, it feels like guns and the people who use them have more legal rights than people with uteruses in desperate or life-threatening situations. I’m afraid for my personal safety as a women’s health practitioner in this political climate. I feel helpless, but I’m supposed to be able to help my patients.”
Missouri family planning specialist
“Abortion is an essential part of healthcare, and the only people that should get a say in it are the patient and their doctor. Period. The fact that some far-off court without any medical expertise can insert itself into individual medical decisions is oppressive and unethical.”
Georgia ob.gyn.
“I can’t even think straight right now. I feel sick. Honestly, I’ve been thinking about moving for a long time now. Somewhere where I would actually be able to offer good, comprehensive care.”
New York ob.gyn.
“I graduated from my ob.gyn. residency hours after the Roe v. Wade news broke. It was so emotional for me. I’ve dedicated my life to caring for people with uteruses and I will not let this heartbreaking news change that. I feel more committed than ever to women’s health. I fully plan to continue delivering babies, providing contraception, and performing abortions. I will be there to help women with desired pregnancies who received unspeakably bad news about fetal anomalies. I will be there to help women with life-threatening pregnancy complications before fetal viability. I will be there to help women with ectopic pregnancies. I will be there to help women who were raped or otherwise forced into pregnancy. I will always be there to help women.”
Dr. Croll is a neurovascular fellow at New York University Langone Health. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
“I’m happy to contribute, but can you keep it anonymous? It’s a safety concern for me.”
On the day that the Supreme Court of the United States voted to strike down Roe v. Wade, I reached out to ob.gyn.s across the country, wanting to hear their reactions. My own response, like that of many doctors and women, was a visceral mix of anger, fear, and grief. I could only begin to imagine what the real experts on reproductive health care were going through.
When the first ob.gyn. responded to my request by expressing concerns around anonymity and personal safety, I was shocked – but I shouldn’t have been. For starters, there is already a storied history in this country of deadly attacks on abortion providers. David Gunn, MD; Barnett Slepian, MD; and George Tiller, MD, were all tragically murdered by antiabortion extremists. Then, there’s the existence of websites that keep logs of abortion providers and sometimes include photos, office contact information, or even home addresses.
The idea that any reproductive health care provider should have to think twice before offering their uniquely qualified opinion is profoundly disturbing, nearly as disturbing as the Supreme Court’s decision itself. But it’s more critical than ever for ob.gyn. voices to be amplified. This is the time for the healthcare community to rally around women’s health providers, to learn from them, to support them.
I asked ob.gyns. around the country to tell me what they were thinking and feeling on the day that Roe v. Wade was overturned. We agreed to keep the responses anonymous, given that several people expressed very understandable safety concerns.
Here’s what they had to say.
Tennessee ob.gyn.
“Today is an emotionally charged day for many people in this country, yet as I type this, with my ob.gyn. practice continuing around me, with my own almost 10-week pregnancy growing inside me, I feel quite blunted. I feel powerless to answer questions that are variations on ‘what next?’ or ‘how do we fight back?’ All I can think of is, I am so glad I do not have anyone on my schedule right now who does not want to be pregnant. But what will happen when that eventually changes? What about my colleagues who do have these patients on their schedules today? On a personal level, what if my prenatal genetic testing comes back abnormal? How can we so blatantly disregard a separation of church and state in this country? What ways will our government interfere with my practice next? My head is spinning, but I have to go see my next patient. She is a 25-year-old who is here to have an IUD placed, and that seems like the most important thing I can do today.”
South Carolina ob.gyn.
“I’m really scared. For my patients and for myself. I don’t know how to be a good ob.gyn. if my ability to offer safe and accessible abortion care is being threatened.”
Massachusetts ob.gyn.
“Livid and devastated and sad and terrified.”
California family planning specialist
“The fact is that about one in four people with uteruses have had an abortion. I can’t tell you how many abortions I’ve provided for people who say that they don’t ‘believe’ in them or that they thought they’d never be in this situation. ... The fact is that pregnancy is a life-threatening condition in and of itself. I am an ob.gyn., a medical doctor, and an abortion provider. I will not stop providing abortions or helping people access them. I will dedicate my life to ensuring this right to bodily autonomy. Today I am devastated by the Supreme Court’s decision to force parenthood that will result in increased maternal mortality. I am broken, but I have never been more proud to be an abortion provider.”
New York ob.gyn.
“Grateful to live in a state and work for a hospital where I can provide abortions but feel terrible for so many people less fortunate and underserved.”
Illinois maternal-fetal medicine specialist
“As a maternal-fetal medicine specialist, I fear for my patients who are at the highest risk of pregnancy complications having their freedom taken away. For the tragic ultrasound findings that make a pregnant person carry a baby who will never live. For the patients who cannot use most forms of contraception because of their medical comorbidities. For the patients who are victims of intimate partner violence or under the influence of their culture, to continue having children regardless of their desires or their health. ... The freedom to prevent or end a pregnancy has enabled women to become independent and productive members of society on their own terms, with or without children. My heart breaks for the children and adolescents and adults who are being told they are second-class citizens, not worthy of making their own decisions. Politicians and Supreme Court justices are not in the clinic room, ultrasound suite, operating room, or delivery room when we have these intense conversations and pregnancy outcomes. They have no idea that of which they speak, and it’s unconscionable that they can determine what healthcare decisions my patients can make for their own lives. Nobody knows a body better than the patient themselves.”
Texas ob.gyn.
“In the area where I live and practice, it feels like guns and the people who use them have more legal rights than people with uteruses in desperate or life-threatening situations. I’m afraid for my personal safety as a women’s health practitioner in this political climate. I feel helpless, but I’m supposed to be able to help my patients.”
Missouri family planning specialist
“Abortion is an essential part of healthcare, and the only people that should get a say in it are the patient and their doctor. Period. The fact that some far-off court without any medical expertise can insert itself into individual medical decisions is oppressive and unethical.”
Georgia ob.gyn.
“I can’t even think straight right now. I feel sick. Honestly, I’ve been thinking about moving for a long time now. Somewhere where I would actually be able to offer good, comprehensive care.”
New York ob.gyn.
“I graduated from my ob.gyn. residency hours after the Roe v. Wade news broke. It was so emotional for me. I’ve dedicated my life to caring for people with uteruses and I will not let this heartbreaking news change that. I feel more committed than ever to women’s health. I fully plan to continue delivering babies, providing contraception, and performing abortions. I will be there to help women with desired pregnancies who received unspeakably bad news about fetal anomalies. I will be there to help women with life-threatening pregnancy complications before fetal viability. I will be there to help women with ectopic pregnancies. I will be there to help women who were raped or otherwise forced into pregnancy. I will always be there to help women.”
Dr. Croll is a neurovascular fellow at New York University Langone Health. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
“I’m happy to contribute, but can you keep it anonymous? It’s a safety concern for me.”
On the day that the Supreme Court of the United States voted to strike down Roe v. Wade, I reached out to ob.gyn.s across the country, wanting to hear their reactions. My own response, like that of many doctors and women, was a visceral mix of anger, fear, and grief. I could only begin to imagine what the real experts on reproductive health care were going through.
When the first ob.gyn. responded to my request by expressing concerns around anonymity and personal safety, I was shocked – but I shouldn’t have been. For starters, there is already a storied history in this country of deadly attacks on abortion providers. David Gunn, MD; Barnett Slepian, MD; and George Tiller, MD, were all tragically murdered by antiabortion extremists. Then, there’s the existence of websites that keep logs of abortion providers and sometimes include photos, office contact information, or even home addresses.
The idea that any reproductive health care provider should have to think twice before offering their uniquely qualified opinion is profoundly disturbing, nearly as disturbing as the Supreme Court’s decision itself. But it’s more critical than ever for ob.gyn. voices to be amplified. This is the time for the healthcare community to rally around women’s health providers, to learn from them, to support them.
I asked ob.gyns. around the country to tell me what they were thinking and feeling on the day that Roe v. Wade was overturned. We agreed to keep the responses anonymous, given that several people expressed very understandable safety concerns.
Here’s what they had to say.
Tennessee ob.gyn.
“Today is an emotionally charged day for many people in this country, yet as I type this, with my ob.gyn. practice continuing around me, with my own almost 10-week pregnancy growing inside me, I feel quite blunted. I feel powerless to answer questions that are variations on ‘what next?’ or ‘how do we fight back?’ All I can think of is, I am so glad I do not have anyone on my schedule right now who does not want to be pregnant. But what will happen when that eventually changes? What about my colleagues who do have these patients on their schedules today? On a personal level, what if my prenatal genetic testing comes back abnormal? How can we so blatantly disregard a separation of church and state in this country? What ways will our government interfere with my practice next? My head is spinning, but I have to go see my next patient. She is a 25-year-old who is here to have an IUD placed, and that seems like the most important thing I can do today.”
South Carolina ob.gyn.
“I’m really scared. For my patients and for myself. I don’t know how to be a good ob.gyn. if my ability to offer safe and accessible abortion care is being threatened.”
Massachusetts ob.gyn.
“Livid and devastated and sad and terrified.”
California family planning specialist
“The fact is that about one in four people with uteruses have had an abortion. I can’t tell you how many abortions I’ve provided for people who say that they don’t ‘believe’ in them or that they thought they’d never be in this situation. ... The fact is that pregnancy is a life-threatening condition in and of itself. I am an ob.gyn., a medical doctor, and an abortion provider. I will not stop providing abortions or helping people access them. I will dedicate my life to ensuring this right to bodily autonomy. Today I am devastated by the Supreme Court’s decision to force parenthood that will result in increased maternal mortality. I am broken, but I have never been more proud to be an abortion provider.”
New York ob.gyn.
“Grateful to live in a state and work for a hospital where I can provide abortions but feel terrible for so many people less fortunate and underserved.”
Illinois maternal-fetal medicine specialist
“As a maternal-fetal medicine specialist, I fear for my patients who are at the highest risk of pregnancy complications having their freedom taken away. For the tragic ultrasound findings that make a pregnant person carry a baby who will never live. For the patients who cannot use most forms of contraception because of their medical comorbidities. For the patients who are victims of intimate partner violence or under the influence of their culture, to continue having children regardless of their desires or their health. ... The freedom to prevent or end a pregnancy has enabled women to become independent and productive members of society on their own terms, with or without children. My heart breaks for the children and adolescents and adults who are being told they are second-class citizens, not worthy of making their own decisions. Politicians and Supreme Court justices are not in the clinic room, ultrasound suite, operating room, or delivery room when we have these intense conversations and pregnancy outcomes. They have no idea that of which they speak, and it’s unconscionable that they can determine what healthcare decisions my patients can make for their own lives. Nobody knows a body better than the patient themselves.”
Texas ob.gyn.
“In the area where I live and practice, it feels like guns and the people who use them have more legal rights than people with uteruses in desperate or life-threatening situations. I’m afraid for my personal safety as a women’s health practitioner in this political climate. I feel helpless, but I’m supposed to be able to help my patients.”
Missouri family planning specialist
“Abortion is an essential part of healthcare, and the only people that should get a say in it are the patient and their doctor. Period. The fact that some far-off court without any medical expertise can insert itself into individual medical decisions is oppressive and unethical.”
Georgia ob.gyn.
“I can’t even think straight right now. I feel sick. Honestly, I’ve been thinking about moving for a long time now. Somewhere where I would actually be able to offer good, comprehensive care.”
New York ob.gyn.
“I graduated from my ob.gyn. residency hours after the Roe v. Wade news broke. It was so emotional for me. I’ve dedicated my life to caring for people with uteruses and I will not let this heartbreaking news change that. I feel more committed than ever to women’s health. I fully plan to continue delivering babies, providing contraception, and performing abortions. I will be there to help women with desired pregnancies who received unspeakably bad news about fetal anomalies. I will be there to help women with life-threatening pregnancy complications before fetal viability. I will be there to help women with ectopic pregnancies. I will be there to help women who were raped or otherwise forced into pregnancy. I will always be there to help women.”
Dr. Croll is a neurovascular fellow at New York University Langone Health. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
My picks for best of ASCO 2022
CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
AT ASCO 2022
Adjuvant vs. neoadjuvant? What has ASCO 2022 taught us regarding resectable NSCLC?
for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.
Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.
In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.
In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.
The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
What else did we learn about neoadjuvant treatment at the meeting?
Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).
Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).
We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.
Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.
Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).
KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
What to do when a patient presents with resectable disease?
Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.
Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.
Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.
So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.
Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).
Hopefully, ASCO 2023 will provide more answers.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.
Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.
In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.
In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.
The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
What else did we learn about neoadjuvant treatment at the meeting?
Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).
Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).
We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.
Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.
Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).
KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
What to do when a patient presents with resectable disease?
Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.
Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.
Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.
So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.
Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).
Hopefully, ASCO 2023 will provide more answers.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
for non–small cell lung cancer (NSCLC). While there has been some notable progress in this area, we need phase 3 trials that compare the two therapeutic approaches.
Investigators reporting at the 2022 annual meeting of American Society of Clinical Oncology focused primarily on neoadjuvant treatment, which I’ll address here.
In the randomized, phase 2 NADIM II clinical trial reported at the meeting, researchers expanded on the results of NADIM published in 2020 in the Lancet Oncology and in May 2022 in the Journal of Clinical Oncology along with CheckMate 816 results published in the New England Journal of Medicine.
In each of these three studies, researchers compared nivolumab plus chemotherapy versus chemotherapy alone (abstract 8501) as a neoadjuvant treatment for resectable stage IIIA NSCLC. In the study reported at ASCO 2022, patients with resectable clinical stage IIIA-B (per American Joint Committee on Cancer 8th edition) NSCLC and no known EGFR/ALK alterations, were randomized to receive preoperative nivolumab plus chemotherapy (paclitaxel and carboplatin; n = 57) or chemotherapy (n = 29) alone followed by surgery.
The primary endpoint was pathological complete response (pCR); secondary endpoints included major pathological response, safety and tolerability, impact on surgical issues such as delayed or canceled surgeries or length of hospital stay, overall survival and progression free survival. The pCR rate was 36.8% in the neoadjuvant nivolumab plus chemotherapy arm and 6.9% in the chemotherapy alone arm. (P = .0068). 25% of patients on the nivolumab plus chemo arm had grade 3-4 adverse events, compared with 10.3% in the control arm. 93% of patients on the nivolumab plus chemo arm underwent definitive surgery whereas 69.0% of the patients on the chemo alone arm had definitive surgery. (P = .008)
What else did we learn about neoadjuvant treatment at the meeting?
Investigators looking at the optimal number of neoadjuvant cycles (abstract 8500) found that three cycles of sintilimab (an investigational PD-1 inhibitor) produced a numerically higher major pathological response rate, compared with two cycles (when given in concert with platinum-doublet chemotherapy). And, neoadjuvant chemoradiotherapy does not result in significant survival benefits when compared with neoadjuvant chemotherapy alone (abstract 8503).
Of course, when it comes to resectable NSCLC, the goal of treatment is to increase the cure rate and improve survival. No randomized studies have reported yet on overall survival, probably because they are too immature. Instead, disease-free survival (DFS) or event-free survival (EFS) are often used as surrogate endpoints. Since none of the studies reported at ASCO reported on DFS or EFS, we need to look elsewhere. CheckMate 816 was a phase 3 study which randomized patients with stages IB-IIIA NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy or neoadjuvant platinum-based chemotherapy alone, followed by resection. The median EFS was 31.6 months with nivolumab plus chemotherapy and 20.8 months with chemotherapy alone (P = .005). The percentage of patients with a pCR was 24.0% and 2.2%, respectively (P < .001).
We all know one has to be careful when doing cross-trial comparisons as these studies differ by the percentage of patients with various stages of disease, the type of immunotherapy and chemotherapy used, etc. However, I think we can agree that neoadjuvant chemoimmunotherapy results in better outcomes than chemotherapy alone.
Of course, resectable NSCLC is, by definition, resectable. And traditionally, resection is followed by adjuvant chemotherapy to eradicate micrometastases. Unfortunately, the current standard of care for completely resected early-stage NSCLC (stage I [tumor ≥ 4 cm] to IIIA) involves adjuvant platinum-based combination chemotherapy which results in only a modest 4%-5% improvement in survival versus observation.
Given these modest results, as in the neoadjuvant space, investigators have looked at the benefit of adding immunotherapy to adjuvant chemotherapy. One such study has been reported. IMpower 010 randomly assigned patients with completely resected stage IB (tumors ≥ 4 cm) to IIIA NSCLC, whose tumor cells expressed at least 1% PD-L1, to receive adjuvant atezolizumab or best supportive care after adjuvant platinum-based chemotherapy. In the stage II-IIIA population whose tumors expressed PD-L1 on 1% or more of tumor cells, 3-year DFS rates were 60% and 48% in the atezolizumab and best supportive care arms, respectively (hazard ratio, 0·66 P =·.0039). In all patients in the stage II-IIIA population, the 3-year DFS rates were 56% in the atezolizumab group and 49% in the best supportive care group, (HR, 0.79; P = .020).
KEYNOTE-091, reported at the 2021 annual meeting of the European Society for Medical Oncology, randomized early-stage NSCLC patients following complete resection and adjuvant chemotherapy to pembrolizumab or placebo. Median DFS for the overall population was 53.6 months for patients in the pembro arm versus 42 months in the placebo arm (HR, 0.76; P = .0014). Interestingly, the benefit was not seen in patients with PD-L1 with at least 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm (HR, 0.82; P = .14). Although the contradictory results of PD-L1 as a biomarker is puzzling, I think we can agree that the addition of immunotherapy following adjuvant chemotherapy improves outcomes compared to adjuvant chemotherapy alone.
What to do when a patient presents with resectable disease?
Cross-trial comparisons are fraught with danger. Until we have a phase 3 study comparing concurrent neoadjuvant chemo/immunotherapy with concurrent adjuvant chemo/immunotherapy, I do not think we can answer the question “which is better?” However, there are some caveats to keep in mind when deciding on which approach to recommend to our patients: First, neoadjuvant treatment requires biomarker testing to ensure the patient does not have EGFR or ALK mutations. This will necessitate a delay in the operation. Will patients be willing to wait? Will the surgeon? Or, would patients prefer to proceed with surgery while the results are pending? Yes, neoadjuvant therapy gives you information regarding the pCR rate, but does that help you in subsequent management of the patient? We do not know.
Secondly, the two adjuvant studies used adjuvant chemotherapy followed by adjuvant immunotherapy, as contrasted to the neoadjuvant study which used concurrent chemo/immunotherapy. Given the longer duration of treatment in postoperative sequential adjuvant studies, there tends to be more drop off because of patients being unwilling or unfit postoperatively to receive long courses of therapy. In IMpower 010, 1,269 patients completed adjuvant chemotherapy; 1,005 were randomized, and of the 507 assigned to the atezolizumab/chemo group, only 323 completed treatment.
Finally, we must beware of using neoadjuvant chemo/immunotherapy to “down-stage” a patient. KEYNOTE-091 included patients with IIIA disease and no benefit to adjuvant chemotherapy followed by immunotherapy was found in this subgroup of patients, which leads me to wonder if these patients were appropriately selected as surgical candidates. In the NADIM II trials, 9 of 29 patients on the neoadjuvant chemotherapy were not resected.
So, many questions remain. In addition to the ones we’ve raised, there is a clear and immediate need for predictive and prognostic biomarkers. In the NADIM II trial, PD-L1 expression was a predictive biomarker of response. The pCR rate for patients with a PD-L1 tumor expression of less than 1%, 1%-49%, and 50% or higher was 15%, 41.7%, and 61.1%, respectively. However, in KEYNOTE-091, the benefit was not seen in patients with PD-L1 of at least than 50%, where the 18-month DFS rate was 71.7% in the pembro arm and 70.2% in the placebo arm.
Another possible biomarker: circulating tumor DNA. In the first NADIM study, three low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and overall survival (HR, 0.20 and HR, 0.07, respectively). Although clinical response did not predict survival outcomes, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and overall survival (HR, 0.26 and HR0.04, respectively). Similarly, in CheckMate 816, clearance of ctDNA was associated with longer EFS in patients with ctDNA clearance than in those without ctDNA clearance in both the nivolumab/chemotherapy group (HR, 0.60) and the chemotherapy-alone group (HR, 0.63).
Hopefully, ASCO 2023 will provide more answers.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.
Racial disparities in endometrial cancer
Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.1 Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.
Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.2 In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.2
Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.2
EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.1 As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.2 Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.
The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.3 In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.3
Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.
A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.4 A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.5 Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?
Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.
References
1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.
2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.
3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.
4. Makker V et al. N Engl J Med. 2022;386:437-48.
5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.
Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.1 Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.
Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.2 In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.2
Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.2
EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.1 As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.2 Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.
The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.3 In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.3
Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.
A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.4 A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.5 Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?
Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.
References
1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.
2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.
3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.
4. Makker V et al. N Engl J Med. 2022;386:437-48.
5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.
Endometrial cancer (EC) is the most common gynecologic malignancy and is the fourth most common cancer seen in U.S. women. It is the only major cancer that has continued to see a rise in incidence and mortality for the past 2 decades, and it is anticipated that nearly 66,000 new cases of EC will be diagnosed this year with 12,550 deaths.1 Given that the well-established risk factors for developing EC including obesity, diabetes, and insulin resistance, the obesity epidemic is indisputably playing a significant role in the increasing incidence.
Historically, White women were thought to have the highest incidence of EC; however, this incidence rate did not account for hysterectomy prevalence, which can vary widely by numerous factors including age, race, ethnicity, and geographic region. When correcting EC incidence rates for prevalence of hysterectomy, Black women have had the highest incidence of EC since 2007, and rates continue to climb.2 In fact, the average annual percent change (APC) in EC incidence from 2000 to 2015 was stable for White women at 0.2% while Black women had a near order of magnitude greater APC at 2.1%.2
Differing incidence rates of EC can also be seen by histologic subtype. Endometrioid EC is the more common and less lethal histology of EC that often coincides with the type I classification of EC. These tumors are estrogen driven; therefore, they are associated with conditions resulting in excess estrogen (for example, anovulation, obesity, and hyperlipidemia). Nonendometrioid histologies, primarily composed of serous tumors, are more rare, are typically more aggressive, are not estrogen driven, and are commonly classified as type II tumors. Racial differences between type I and type II tumors are seen with White women more commonly being diagnosed with type I tumors while Black women more typically have type II tumors. White women have the greatest incidence rate of endometrioid EC with an APC that remained relatively unchanged from 2000 to 2015. Black women’s APC in incidence rate of endometrioid EC has increased during this same period at 1.3%. For nonendometrioid tumors, an increasing incidence is seen in all races and ethnicities; however, Black women have a much higher incidence of these tumors, with a rate that continues to increase at an APC of 3.2%.2
EC incidence is increasing with a particularly concerning rise in those who report Black race, but are these same disparities being seen in EC mortality? Unfortunately, drastic disparities are seen in survival data for Black women afflicted with EC. Black patients are more likely to be diagnosed with advanced or metastatic EC and less likely to be diagnosed with localized tumors. While being diagnosed with a more advanced stage of disease does affect survival in EC, Black patients have worse survival regardless of stage of disease at the time of diagnosis.1 As discussed earlier, the more aggressive type II tumors are composed of nonendometrioid histologies and are more common in Black women. This could lead to the false assumption that these higher-risk tumors are why Black women are disproportionately dying from EC; however, when examining survival by histologic subtype, Black women are more frequently dying from the lower-risk endometrioid EC regardless of stage of disease. The same disparate survival outcomes are also seen in nonendometrioid histologies.2 Thus, Black patients have the lowest survival rates irrespective of stage at diagnosis or histologic subtype.
The disparities seen in EC mortality are not new. They can be seen in data for over 30 years and are only widening. While there has been an increase in mortality rates from EC across all races and ethnicities from 2015 to 2019 compared with 1990 to 1994, the mortality rate ratio for Black women compared with White women has increased from 1.83 in 1990-1994 to 1.98 in 2015-2019.3 In the early 1990s, the risk of death from ovarian cancer was twice that of EC. The mortality of EC is now similar to that of ovarian cancer. This threshold in mortality ratio of EC to ovarian cancer has already been seen in Black women, who have experienced greater mortality in EC compared with ovarian cancer since 2005. In fact, the EC mortality of Black women in 2019 was similar to the mortality of White women with ovarian cancer nearly 30 years ago.3
Decades of data have demonstrated the glaring racial disparities seen in EC, and yet, no significant progress has been made in addressing this inequity. Oncology research is now beginning to move beyond describing these differences to a strategy of achieving equitable cancer care. While the study frameworks and novel investigations aimed at addressing the disparities in EC is outside the scope of this article, disparities in clinical trial enrollment continue to exist.
A recent example can be seen in the practice-changing KEYNOTE-775 trial, which led to the Food and Drug Administration approval of lenvatinib plus pembrolizumab in EC treatment.4 A total of 827 patients with EC that progressed or recurred following treatment with platinum-based chemotherapy were enrolled in this multinational, multicenter trial. Thirty-one (3.7%) of the patients enrolled were Black. Of those who were enrolled in the United States, 14% were Black. The authors report that this proportion of Black patients in the United States is consistent with 2020 census data, which reported 13.4% of people identified as Black. However, using census data as a benchmark for equitable enrollment is inappropriate. Certain demographic groups are historically more difficult to count, and the COVID-19 pandemic exacerbated the challenge in obtaining an accurate count through job loss, government distrust, and access restrictions resulting in an estimated net undercount of 2.45% in those who report Black race.5 Composition of trial enrollment should mirror the population that will be affected by the study results. As advanced EC disproportionately affects Black patients, their enrollment must be higher in these pivotal trials. How else are we to know if these novel therapeutics will work in the population that is most afflicted by EC?
Future studies must account for socioeconomic factors while acknowledging the role of social determinants of health. It is imperative that we use the knowledge that race is a social construct created to control access to power and that there are biologic responses to environmental stresses, including that of racism, affecting health and disease. Changes at every level, from individual practitioners up to federal policies, will need to be enacted or else the unacceptable status quo will continue.
Dr. Burkett is a clinical fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina at Chapel Hill.
References
1. Siegel RL et al. CA Cancer J Clin. 2022;72:7-33.
2. Clarke MA et al. J Clin Oncol. 2019;37:1895-908.
3. Giaquinto AN et al. Obstet Gynecol. 2022;139:440-2.
4. Makker V et al. N Engl J Med. 2022;386:437-48.
5. Elliott D et al. Simulating the 2020 Census: Miscounts and the fairness of outcomes. Urban Institute; 2021.
Patients with blood cancers underutilize palliative care
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
FROM ASCO 2022
iLet system simplifies insulin delivery for type 1 diabetes
This transcript has been edited for clarity.
Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.
Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.
One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.
Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.
There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.
It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.
They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.
There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.
There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.
I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.
More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.
I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.
Thank you very much. This has been Dr Anne Peters for Medscape.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.
Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.
One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.
Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.
There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.
It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.
They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.
There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.
There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.
I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.
More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.
I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.
Thank you very much. This has been Dr Anne Peters for Medscape.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.
Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.
One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.
Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.
There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.
It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.
They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.
There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.
There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.
I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.
More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.
I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.
Thank you very much. This has been Dr Anne Peters for Medscape.
Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.
A version of this article first appeared on Medscape.com.
Moderate activity versus sweat equity
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
It’s no secret that the fitness level of all age groups in our country is poor. A recent study in Pediatrics sharpens the focus on the question of how we might address the problem in the teenage population. Based in England, the investigators placed wrist accelerometers on their 13- and 14-year-old subjects who were then assessed using shuttle runs at progressively faster speeds.
The researchers found that the participants’ cardiorespiratory fitness improved as the subjects’ time doing vigorous activity increased up to 20 minutes and then plateaued. The study authors could not prove that the vigorous activity caused the increased in fitness. However, they were impressed by the plateau phenomenon and suggest that this might suggest a change in the recommendations by the World Health Organization and U.S. Department of Health & Human Services which currently call for 60 minutes of moderate to vigorous physical activity per day for adolescents
At first blush a shift down to 20 minutes of vigorous activity would appear to be workable and achievable. This would be particularly true for public school systems that are already struggling to get any kind of activity shoehorned into their schedules that are already crammed in an attempt to address mandated academic achievement goals. Freeing up an additional 40 minutes of the school day and yielding improved cardiorespiratory fitness sounds like a win-win.
But, let’s take a deep breath and for a few moments return to the world of reality. First, how many school systems are providing that 60 minutes of moderate activity (let’s forget the vigorous piece for the moment) included in the current WHO/HHS recommendations? Next, let’s take a look at what “vigorous” activity means. There are variety of definitions but in general they include sweating, flushing, and dyspnea to the point of having difficulty speaking.
Let’s just focus on the “sweating” part. To me that sounds like an activity that would require some wardrobe alteration at a minimum and very likely a locker room and a shower. Those can be fightin’ words for many teenagers. Even if a school can provide adequate locker room and shower infrastructure change-ups and showers are time-gobbling activities. And, more realistically, what are the chances of getting body image–challenged adolescents to willingly take advantage of them? You don’t have to talk to very many adults before you will hear stories of discomfort and embarrassment resulting from forced locker room and shower experiences. When I was a teenager the only way you could flunk physical education was to refuse to go in the locker room and “change up.” I think or at least hope that physical educators are more sensitive to the fragility of their adolescents students. But, the bottom line is that creating a curriculum that will improve cardiorespiratory fitness is fraught with challenges most school systems can’t address. It’s sad but true.
So, where does that leave us? This new study from England may be helpful for families who are caught in a time crunch and looking improve their fitness or for the physical educator who would like to help his/her motivated students get on a healthier track. But, this study should not prompt us to throw up our hands and toss out the current recommendations of an hour of moderate activity. As unrealistic as it may be for most school systems it allows for the injection of physical activity into academic settings where creative educators can offer things like walking lectures and field trips. It all boils down to the fact that some activity is better than none at all with or without the sweat equity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Updates in aspirin use, aducanumab, and CKD diagnostic criteria in geriatric medicine
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.
I selected these topics as they were among the most discussed by my colleagues in geriatric medicine and inquired about by my primary care patients in geriatric medicine clinic. I hope that these updates provide primary care clinicians who care for older adults with more context and background information regarding new Alzheimer’s disease therapy to better answer patient inquiries, and to feel empowered to deprescribe aspirin and reframe the diagnostic criteria of chronic kidney disease (CKD).
Aspirin for primary prevention
It was welcome news in the geriatrics community when the United States Preventive Services Task Force updated their guidelines in April 2022 to recommend against the initiation of aspirin for primary prevention in adults aged 60 or older. This recommendation was based on studies that found that net benefits of CVD prevention in older adults are outweighed by risk of bleeding.1
The risk of bleeding increases with age and can occur in individuals without common risk factors for bleeding, such as prior gastrointestinal bleeding, peptic ulcer disease, concurrent NSAID use, or corticosteroid use.
While it may be easier to not initiate aspirin for primary prevention, deprescribing aspirin for patients who have been on aspirin long term for primary prevention presents more of a challenge. Modeling data from the USPTSF suggest stopping aspirin at age 75 for those taking aspirin for primary prevention.2
Behavioral change, particularly for patients who have been on aspirin for decades, can be difficult. A 2021 study by Green et al. found that language that resonates the most with older adults when deprescribing emphasized the side effects rather than statements such as “this will not help you” or “do not need anymore.”3
Aducanumab for mild cognitive impairment and mild Alzheimer’s dementia
One of the most discussed topics this past year is the Food and Drug Administration approval of aducanumab (brand name Aduhelm) in June 2021. Aducanumab is the first approved disease-modifying therapy for Alzheimer’s disease and the first drug approved for the treatment of Alzheimer’s disease since 2003. Aducanumab is an antiamyloid monoclonal antibody that was developed to reduce amyloid plaque in the brain, one of the features of Alzheimer’s disease pathology.
Uptake of aducanumab by dementia providers has been limited for several reasons. Firstly, the clinical significance of the drug remains in question. ENGAGE and EMERGE were the two main randomized clinical trials that studied the effect of aducanumab on amyloid burden and clinical stages of dementia over 18 months. While both studies demonstrated that aducanumab reduced amyloid burden based on neuroimaging and in cerebrospinal fluid, the ENGAGE trial found no difference in the stage of dementia. The EMERGE trial did note a small, statistically significant difference in stage of dementia, however the participants of the EMERGE trial had a faster rate of progression of dementia than the placebo participants in the ENGAGE trial, which could have contributed to the difference detected.4
Additionally, exclusion criteria for both trials call into question the generalizability of this study. Participants over age 85, with CKD, prior stroke, or transient ischemic attacks, or on anticoagulation were excluded. One of the drivers for the exclusion criteria is the increased risk of macro and microhemorrhages.
Thirty-five percent of research participants were incidentally noted to have brain edema, an abnormality called amyloid-related imaging abnormality or ARIA-E, that necessitated serial monitoring with brain MRIs. It is also important to highlight that inclusion of African American, Hispanic, and Latinx participants in these studies was less than 5%, despite a higher incidence of Alzheimer’s disease in these populations.5
Lastly, economic implications for the U.S. health care system with increased uptake of aducanumab could be enormous. Originally quoted at $56,000 yearly, Biogen, the maker of aducanumab, recently reduced annual costs to $28,200 per patient.
In April 2022, CMS released a statement that antiamyloid monoclonal antibodies and related services, including PET scans, would be covered under Medicare for those with mild cognitive impairment and mild Alzheimer’s dementia with confirmed presence of amyloid. A study by Mafi et al. estimated that aducanumab could cost Medicare between $7 billion and $37.4 billion annually based on lower and upper bound estimates of eligible Medicare beneficiaries.6
Overdiagnosis of CKD in older adults
The current diagnostic criteria of CKD, which is based on an estimated glomerular filtration rate (eGFR) of less than 60, has been up for debate, as glomerular filtration rate (GFR) physiologically decreases with age. Fixed thresholds can lead to underdiagnosis of CKD in younger adults and overdiagnosis of CKD in older adults. Age-adapted thresholds for the diagnosis of CKD have been proposed, with the suggestion of an eGFR threshold of 45mL/min/1.73 m2 for adults aged 65 and older.7
The clinical implication of using an age-adapted eGFR threshold definition was investigated in a 2021 cohort study by Liu et al.8 In this study, outcomes of adults diagnosed with CKD using a fixed threshold versus age-adapted threshold were compared with a healthy cohort.
A fixed threshold led to a 60% higher incidence of CKD diagnosis. However, incidence of renal failure and all-cause mortality in older adults with an eGFR between 45-59 /min/1.73 m2 with normal or mild albuminuria was of similar magnitude to the healthy cohort at 5 years of follow-up.
These findings support the use of age-adapted thresholds for the diagnosis of CKD in older adults, as an earlier diagnosis of mild CKD does not equate to clinical benefits, but could lead to harms of unnecessary interventions and patient anxiety.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. Selak Vet al. Predicting bleeding risk to guide aspirin use for the primary prevention of cardiovascular disease: A cohort study. Ann Intern Med. 2019;170(6):357-68. doi: 10.7326/M18-2808.
2. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-84. doi: 10.1001/jama.2022.4983.
3. Green AR et al. Assessment of patient-preferred language to achieve goal-aligned deprescribing in older adults. JAMA Netw Open. 2021;4(4):e212633. doi: 10.1001/jamanetworkopen.2021.2633.
4. Oh ES. Use of anti-amyloid therapy for Alzheimer’s disease in clinical practice. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at American Geriatrics Society Meeting, 2022. Orlando.
5. Amjad H. Issues of Access and Marginalization. An update on Alzheimer’s disease diagnosis and therapeutics. Presentation at: American Geriatrics Society Meeting, 2022. Orlando.
6. Mafi JN et al. Estimated annual spending on aducanumab in the U.S. Medicare program. JAMA Health Forum. 2022;3(1):e214495. doi: 10.1001/jamahealthforum.2021.4495.
7. Delanaye P et al. CKD: A call for an age-adapted definition. J Am Soc Nephrol. 2019;30(10):1785-1805. doi: 10.1681/ASN.2019030238.
8. Liu Pet al. Accounting for age in the definition of chronic kidney disease. JAMA Intern Med. 2021;181(10):1359-66. doi: 10.1001/jamainternmed.2021.4813.
Understanding filler reversal with hyaluronidase
Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. . However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.
Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.
Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.
In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.
In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.
Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.
For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.
Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.
Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.
It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.
Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.
References
Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.
DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.
Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.
King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.
Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.
Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. . However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.
Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.
Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.
In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.
In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.
Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.
For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.
Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.
Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.
It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.
Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.
References
Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.
DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.
Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.
King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.
Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.
Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. . However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.
Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.
Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.
In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.
In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.
Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.
For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.
Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.
Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.
It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.
Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.
References
Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.
DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.
Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.
King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.
Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.
“How long, how long to sing this song?”
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].