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Updates on pregnancy outcomes in transgender men
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
NORD: Making Progress Through Collaboration
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
While people living with rare cancers continue to face daunting obstacles, progress is being made, and there are reasons to hope for a better future. Advances in genomic testing and precision medicine provide increasing evidence that rare cancers can be more efficiently and effectively diagnosed and treated. Genomic tests examine tumor DNA to identify mutations that are unique to an individual’s cancer. This genetic information enables a more precise diagnosis and targeted treatment approach. Jim Palma, Co-Lead of the NORD Rare Cancer Coalition, said “There is promise for rare cancer patients due to increased legislative efforts to cover the costs of genomic testing coupled by an increase in FDA approvals for targeted and tissue agnostic therapies.”
In 2019, the National Cancer Institute established MyPART, a vast pediatric and adult rare tumor network that aims to bolster patient involvement in research and develop effective therapies through tumor sample collection, shared data, shared samples, new methods to test treatments, and new trial designs. In 2022, MyPART welcomed NORD’s Rare Cancer Coalition as an advocacy partner.
Meanwhile, advocacy organizations are giving rare cancer a rising voice. NORD’s Rare Cancer Coalition unites rare cancer patient advocacy organizations and helps them drive progress together. The coalition promotes research and awareness through its annual Rare Cancer Day (September 30) campaign. Additionally, NORD has produced over 22 continuing medical education modules on rare cancers in collaboration with PlatformQ Health, providing updates on new therapies and treatment approaches. NORD also offers rare disease reports and educational videos on rare cancers, sessions inclusive of rare cancer topics at the annual NORD Summit, and a quarterly e-newsletter, “Caring for Rare” for healthcare professionals. Please visit us at rarediseases.org to access these resources.
Much work on rare cancers remains to be done, but the progress over recent years points to better outcomes moving forward. We are grateful for the work you do and your dedication to your patients, including those with rare cancers and other rare conditions. We hope you will find the information in this special issue useful for your clinical practice.
– Katie Kowalski, MPH
Associate Director of Education
National Organization for Rare Disorders
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
- About Rare Cancers. National Cancer Institute. Posted February 27, 2019. Accessed April 28, 2023. http://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/about-rare-cancers
- Gatta G, Capocaccia R, Botta L, et al. Burden and centralized treatment in Europe of rare tumours: Results of RARECAREnet-a population-based study. Lancet Oncol. 2017,18(8):1022–1039. doi:10.1016/S1470-2045(17)30445-X
2023 Rare Diseases Report: Cancers
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
This edition of Rare Diseases Report: Cancers highlights the latest breakthroughs and remaining unmet needs in the management of rare cancers. In addition to celebrating the great progress that has been made in recent years, we also discuss new challenges, such as how the healthcare system can prepare to manage the growing number of rare cancer survivors who are living longer due to improvements in disease management.
INTRODUCTION
NORD: Making Progress Through Collaboration
By Katie Kowalski, MPH
IN THIS ISSUE
The Complex Challenge of Survival After HPV-Associated Oropharyngeal Cancer
By Vlad C. Sandulache, MD, PhD
Progress in Ovarian Cancer: Discovery of Fallopian Tube Involvement
By Ronny Drapkin, MD, PhD
An Evolving Understanding of Adenosquamous Carcinoma of the Lung
By Rajwanth Veluswamy, MD, MSCR
Gastrointestinal Stromal Tumor: Reflecting on 2 Decades of Clinical Advancements
By Jason K. Sicklick, MD, FACS
Progress in Treating Testicular Cancer
By Liang Cheng, MD
Strategies to Improve Long-Term Outcomes in Younger Patients with Hodgkin Lymphoma
By Ann LaCasce, MD, MMSc
Targeted Therapies in Younger and Older Patients with Mantle Cell Lymphoma
By Reem Karmali, MD, MS
Advances in Management of Relapsed/Refractory Hairy Cell Leukemia
By Robert J. Kreitman, MD
Treatment Needs of Older Adults With Newly Diagnosed Acute Myeloid Leukemia
By Harry Erba, MD, PhD
Progress in Management of Advanced Acute Lymphocytic Leukemia in Children
By Susan Colace, MD, MSCI
The metaverse is the dermatologist’s ally
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
MADRID – There are endless possibilities within the dermoverse (a term coined by joining “dermatology” and “metaverse”), from a robot office assistant to the brand new world it offers for virtual training and simulation.
A group of dermatologists expert in new technologies came together at the 50th National Congress of the Spanish Academy for Dermatology and Venereology to discuss the metaverse: that sum of all virtual spaces that bridges physical and digital reality, where users interact through their avatars and where these experts are discovering new opportunities for treating their patients. The metaverse and AI offer a massive opportunity for improving telehealth visits, immersive surgical planning, or virtual training using 3-D skin models. These are just a few examples of what this technology may eventually provide.
“The possibilities offered by the metaverse in the field of dermatology could be endless,” explained Miriam Fernández-Parrado, MD, dermatologist at Navarre Hospital, Pamplona, Spain. To her, “the metaverse could mean a step forward in teledermatology, which has come of age as a result of the pandemic.” These past few years have shown that it’s possible to perform some screenings online. This, in turn, has produced significant time and cost savings, along with greater efficacy in initial screening and early detection of serious diseases.
The overall percentage of cases that are potentially treatable in absentia is estimated to exceed 70%. “This isn’t a matter of replacing in-person visits but of finding a quality alternative that, far from dehumanizing the doctor-patient relationship, helps to satisfy the growing need for this relationship,” said Dr. Fernández-Parrado.
Always on duty
Julián Conejo-Mir, MD, PhD, professor and head of dermatology at the Virgen del Rocío Hospital in Seville, Spain, told this news organization that AI will help with day-to-day interactions with patients. It’s already a reality. “But to say that with a simple photo, we can address 70% of dermatology cases without being physically present with our patients – I don’t think that will become a reality in the next 20 years.”
Currently, algorithms can identify tumors with high success rates (80%-90%) using photographs and dermoscopic images; rates increase significantly when both kinds of images are available. These high success rates are possible because tumor morphology is stationary. “However, for inflammatory conditions, accurate diagnosis generally doesn’t exceed 60%, since these are conditions in which morphology can change a lot from one day to the next and can vary significantly, depending on their anatomic location or the patient’s age.”
Maybe once metaclinics, with 3-D virtual reality, have been established and clinicians can see the patient in real time from their offices, the rate of accurate diagnosis will reach 70%, especially with patients who have limited mobility or who live at a distance from the hospital. “But that’s still 10-15 years away, since more powerful computers are needed, most likely quantum computers,” cautioned Dr. Conejo-Mir.
The patient’s ally
In clinical practice, facilitating access to the dermoverse may help reduce pain and divert the patient’s attention, especially during in-person visits that require bothersome or uncomfortable interventions. “This is especially effective in pediatric dermatology, since settings of immersive virtual reality may contribute to relaxation among children,” explained Dr. Fernández-Parrado. She also sees potential applications among patients who need surgery. The metaverse would allow them to preview a simulation of their operation before undergoing it, thus reducing their anxiety and allaying their fears about these procedures.
Two lines are being pursued: automated diagnosis for telehealth consultations, which are primarily for tumors, and robotic office assistants.
“We have been using the first one in clinical practice, and we can achieve a success rate of 85%-90%.” The second one is much more complex, “and we’re having a hard time moving it forward within our research team, since it doesn’t involve only one algorithm. Instead, it requires five algorithms working together simultaneously (chatbot, automatic writing, image analysis, selecting the most appropriate treatment, ability to make recommendations, and even an additional one involving feelings),” explained Dr. Conejo-Mir.
A wise consultant
Dr. Conejo-Mir offered examples of how this might work in the near future. “In under 5 years, you’ll be able to sit in front of a computer or your smartphone, talk to an avatar that we’re able to select (sex, appearance, age, kind/serious), show the avatar your lesions, and it will tell us a basic diagnostic impression and even the treatment.”
With virtual learning, physicians can also gather knowledge or take refresher courses, using skin models in augmented reality with tumors and other skin lesions, or using immersive simulation courses that aid learning. Digital models that replicate the anatomy and elasticity of the skin or other characteristics unique to the patient can be used to reach decisions regarding surgeries and to practice interventions before entering the operating room, explained Dr. Fernández-Parrado.
Optimal virtual training
Virtual reality and simulation will doubtless play a major role in this promising field of using these devices for training purposes. “There will be virtual dermatology clinics or metaclinics, where you can do everything with virtual simulated patients, from gaining experience in interviews or health histories (even with patients who are difficult to deal with), to taking biopsies and performing interventions,” said Dr. Conejo-Mir.
A recent study titled “How the World Sees the Metaverse and Extended Reality” gathered data from 29 countries regarding the next 10 years. One of the greatest benefits of this technology is expected in health resources (59%), even more than in the trading of digital assets. While it is difficult to predict when the dermoverse will be in operation, Dr. Fernández-Parrado says she’s a techno-optimist. Together with Dr. Héctor Perandones, MD, a dermatologist at the University Healthcare Complex in León, Spain, and coauthor with Dr. Fernández-Parrado of the article, “A New Universe in Dermatology: From Metaverse to Dermoverse,” she’s convinced that “if we can imagine it, we can create it.”
A differential diagnostician
Over the past 10 years, AI has become a major ally of dermatology, providing new techniques that simplify the diagnosis and treatment of patients. There are many applications for which it adds tremendous value in dermatology: establishing precise differential diagnoses for common diseases, such as psoriasis, atopic dermatitis, or acne; eveloping personalized therapeutic protocols; and predicting medium- and long-term outcomes.
Furthermore, in onco-dermatology, AI has helped to automate the diagnosis of skin tumors by making it possible to differentiate between melanocytic and nonmelanocytic lesions. This distinction promotes early diagnosis and helps produce screening systems that are capable of prioritizing cases on the basis of their seriousness.
When asked whether any group has published any promising tools with good preliminary results, Dr. Conejo-Mir stated that his group has produced three articles that have been published in top-ranking journals. In these articles, “we explain our experience with artificial intelligence in Mohs surgery, in automated diagnosis, and for calculating the thickness of melanomas.” The eight-person research team, which comprises dermatologists and software engineers, has been working together in this area for the past 4 years.
Aesthetic dermatology
Unlike other specialists, dermatologists have 4-D vision when it comes to aesthetics, since they are also skin experts. AI plays a major role in aesthetic dermatology. It supports this specialty by providing a greater analytic capacity and by evaluating the procedure and technique to be used. “It’s going to help us think and make decisions. It has taken great strides in aesthetic dermatology, especially when it comes to techniques and products. There have been products like collagen, hyaluronic acid, then thread lifts ... Also, different techniques have been developed, like Botox, for example. Before, Botox was given following one method. Now, there are other methods,” explained Dr. Conejo-Mir.
He explained, “We have analyzed the facial image to detect wrinkles, spots, enlarged pores, et cetera, to see whether there are any lesions, and, depending on what the machine says you have, it provides you with a personalized treatment. It tells you the pattern of care that the patient should follow. It also tells you what you’re going to do, whether or not there is any problem, depending on the location and on what the person is like, et cetera. Then, for follow-up, you’re given an AI program that tells you if you’re doing well or not. Lastly, it gives you product recommendations.
“We are among the specialties that are going through the most change,” said Dr. Conejo-Mir.
An intrusive technology?
AI will be a tremendous help in decision-making, to the point where “in 4 or 5 years, it will become indispensable, just like the loupe in years past, and then the dermatoscope.” However, the machine will have to depend on human beings. “They won’t replace us, but they will become unavoidable assistants in our day-to-day medical practice.”
Questions have arisen regarding the potential dangers of these new technologies, like that of reducing the number of dermatologists within the population, and whether they might encourage intrusiveness. Dr. Conejo-Mir made no bones about it. “AI will never cut back the number of specialists. That is false. When AI supports us in teledermatology, even currently on our team, it spits out information, but the one making the decision is the practitioner, not the machine.”
AI is a tool but is not in itself something that treats patients. It is akin to the dermatoscope. Dermatologists use these tools every day, and they help arrive at diagnoses in difficult cases, but they are not a replacement for humans. “At least for the next 50 years, then we’ll see. In 2050 is when they say AI will surpass humans in its intelligence and reasoning capacity,” said Dr. Conejo-Mir.
Dr. Conejo-Mir has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.
FDA approves ritlecitinib for ages 12 and up for alopecia areata
Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.
It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.
The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
Approval based on ALLEGRO trials
Approval was based on previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).
Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.
Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.
According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%).
Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
Ritlecitinib evaluated for other diseases
In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.
In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.
Alopecia areata affects about 6.8 million people in the United States and 147 million globally.
In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”
A version of this article first appeared on Medscape.com.
Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.
It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.
The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
Approval based on ALLEGRO trials
Approval was based on previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).
Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.
Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.
According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%).
Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
Ritlecitinib evaluated for other diseases
In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.
In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.
Alopecia areata affects about 6.8 million people in the United States and 147 million globally.
In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”
A version of this article first appeared on Medscape.com.
Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3). The recommended dose of ritlecitinib, which will be marketed as Litfulo, is 50 mg once a day, according to the statement announcing the approval from Pfizer.
It is the second JAK inhibitor approved for treating alopecia areata, following approval of baricitinib (Olumiant) in June 2022 for AA in adults. Ritlecitinib is the first JAK inhibitor approved for children ages 12 and older with AA.
The European Medicines Agency has also accepted the Marketing Authorization Application for ritlecitinib in the same population and a decision is expected in the fourth quarter of this year.
Approval based on ALLEGRO trials
Approval was based on previously announced results from trials, including the phase 2b/3 ALLEGRO study of ritlecitinib in 718 patients aged 12 years and older with alopecia areata, with 50% of more scalp hair loss, as measured by the Severity of Alopecia Tool (SALT), including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face, and body hair loss).
Patients in the trial were experiencing a current episode of alopecia areata that had lasted between 6 months and 10 years. They were randomized to receive once-daily ritlecitinib at doses of 30 mg or 50 mg (with or without 1 month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg, or placebo.
Statistically significantly higher proportions of patients treated with ritlecitinib 30 mg and 50 mg (with or without the loading dose) had 80% or more scalp hair coverage, as measured by a SALT score of 20 or less after 6 months of treatment versus placebo. After 6 months of treatment, among those on the 50-mg dose, 23% had achieved a SALT score of 20 or less, compared with 2% of those on placebo. The results were published in The Lancet.
According to the company release, efficacy and safety of ritlecitinib was consistent between those ages 12-17 and adults, and the most common adverse events reported in the study, in at least 4% of patients treated with ritlecitinib, were headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and urticaria (4.6%).
Ritlecitinib labeling includes the boxed warning about the risk for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, which is included in the labels for other JAK inhibitors.
Ritlecitinib evaluated for other diseases
In addition to alopecia areata, ritlecitinib has shown efficacy and acceptable safety in treating ulcerative colitis and is being evaluated for treating vitiligo, Crohn’s disease, and rheumatoid arthritis.
In the statement, the company says that ritlecitinib will be available “in the coming weeks.” The manufacturer says it also has completed regulatory submissions for ritlecitinib in the United Kingdom, China, and Japan, and expects decisions this year.
Alopecia areata affects about 6.8 million people in the United States and 147 million globally.
In a statement, Nicole Friedland, president and CEO of the National Alopecia Areata Foundation, said that NAAF “is thrilled to have a second FDA-approved treatment for alopecia areata, which is the first approved for adolescents.”
A version of this article first appeared on Medscape.com.
Strategies to Improve Long-Term Outcomes in Younger Patients With Hodgkin Lymphoma
Background
Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,1 but it is one of the most common types of cancer in AYAs.2 For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.5 Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.6
In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.7 Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.9
Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.12 Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.13 The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.16
First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.17 This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.
Risk-Adapted Therapies
While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,18 can be omitted in patients with a complete response after chemotherapy.11 This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.9
However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.
Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.19 This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.
Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.
Novel Targeted Therapies
The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.20 The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.
Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.21 BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.22 In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.
A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.23 In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.
In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.
If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.24 If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.
Summary
In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.
- Hodgkin Lymphoma. American Cancer Society. Accessed March 20, 2023. https://www.cancer.org/cancer/hodgkin-lymphoma.html
- Aben KK, van Gaal C, van Gils NA, van der Graaf WT, Zielhuis GA. Cancer in adolescents and young adults (15-29 years): a population-based study in the Netherlands 1989-2009. Acta Oncol. 2012;51(7):922-933. doi:10.3109/0284186X.2012.705891
- Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and
management. Am J Hematol. 2016;91(4):434-442. doi:10.1002/ajh.24272 - Cartwright RA, Watkins G. Epidemiology of Hodgkin’s disease: a review. Hematol Oncol. 2004;22(1):11-26. doi:10.1002/hon.723
- Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506-1514. doi:10.1056/NEJM199811193392104
- Bleyer A, Barr R, Hayes-Lattin B, et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8(4):288-298. doi:10.1038/nrc2349
- Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132. doi:10.3322/caac.21438
- Bigenwald C, Galimard JE, Quero L, et al. Hodgkin lymphoma in adolescent and young adults: insights from an adult tertiary single-center cohort of 349 patients. Oncotarget. 2017;8(45):80073-80082. doi:10.18632/oncotarget.20684
- Kahn JM, Kelly KM. Adolescent and young adult Hodgkin lymphoma: raising the bar through collaborative science and multidisciplinary care. Pediatr Blood Cancer. 2018;65(7):e27033. doi:10.1002/pbc.27033
- Yung L, Smith P, Hancock BW, et al. Long term outcome in adolescents with Hodgkin’s lymphoma: poor results using regimens designed for adults. Leuk Lymphoma. 2004;45(8):1579-1585. doi:10.1080/1042819042000209404
- Dorffel W, Ruhl U, Luders H, et al. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. J Clin Oncol. 2013;31(12):1562-1568. doi:10.1200/JCO.2012.45.3266
- National Cancer Institute. Childhood Hodgkin lymphoma treatment (PDQ®)–Health Professional Version. National Institutes of Health. Updated February 14, 2023. Accessed March 20, 2023. https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq
- Daw S, Hasenclever D, Mascarin M, et al. Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. Hemasphere. 2020;4(1):e329. doi:10.1097/HS9.0000000000000329
- Flerlage JE, Hiniker SM, Armenian S, et al. Pediatric Hodgkin lymphoma, version 3.2021. J Natl Compr Canc Netw. 2021;19(6):733-754. doi:10.6004/jnccn.2021.0027
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Hodgkin lymphoma. Version 2.2023. November 8, 2022. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Adolescent and young adult (AYA) oncology. Version 3.2023. January 9, 2023. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/aya.pdf
- Mohty R, Dulery R, Bazarbachi AH, et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 2021;11(7):126. doi:10.1038/s41408-021-00518-z
- Witkowska M, Majchrzak A, Smolewski P. The role of radiotherapy in Hodgkin’s lymphoma: what has been achieved during the last 50 years? Biomed Res Int. 2015;2015:485071. doi:10.1155/2015/485071
- Borchmann P, Moccia A, Greil R, et al. Treatment-related morbidity in patients with classical Hodgkin lymphoma: results of the ongoing, randomized phase II HD21 trial by the German Hodgkin Study Group. Hemasphere. 2022;6(suppl ):1-2. doi:10.1097/01.HS9.0000890576.23258.1c
- Immunotherapy (nivolumab or brentuximab vedotin) plus combination chemotherapy in treating patients with newly diagnosed stage III-IV classic Hodgkin lymphoma. ClinicalTrials.gov. Updated March 8, 2023. Accessed March 20, 2023. https://clinicaltrials.gov/ct2/show/NCT03907488
- Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183-2189. doi:10.1200/JCO.2011.38.0410
- Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331-344. doi:10.1056/NEJMoa1708984
- Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin’s lymphoma. N Engl J Med. 2022;387(18):1649-1660. doi:10.1056/NEJMoa2206660
- Sobesky S, Mammadova L, Cirillo M, et al. In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin’s lymphoma and facilitates ultrasensitive residual disease detection. Med (N Y). 2021;2(10):1171-1193.e11. doi:10.1016/j.medj.2021.09.002
Background
Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,1 but it is one of the most common types of cancer in AYAs.2 For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.5 Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.6
In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.7 Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.9
Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.12 Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.13 The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.16
First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.17 This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.
Risk-Adapted Therapies
While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,18 can be omitted in patients with a complete response after chemotherapy.11 This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.9
However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.
Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.19 This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.
Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.
Novel Targeted Therapies
The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.20 The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.
Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.21 BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.22 In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.
A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.23 In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.
In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.
If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.24 If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.
Summary
In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.
Background
Hodgkin lymphoma occurs in fewer than 9,000 individuals in the United States each year,1 but it is one of the most common types of cancer in AYAs.2 For the purposes of cHL, AYA is typically defined as an age range of 18 to 39 years, which covers the first of 2 bimodal peaks in incidence but stops short of the second.3,4 The first of these peaks occurs between the ages of 15 and 34 years, while the second begins at about age 55.5 Children younger than 15 years of age can also develop Hodgkin lymphoma, but it is less common.6
In AYAs and in adults, more than 90% of patients with Hodgkin lymphoma have cHL.7 Most AYAs present with the nodular sclerosis subtype, but cHL is managed differently in pediatric patients versus in adult centers.8,9 Evidence suggests that the specific risks of common treatment protocols, although similar, are not the same in AYAs as in adults.10,11 Even though the literature evaluating the presentation and management of AYA cHL has been growing since 2005, when the AYA Oncology Progress Review Group called for AYAs to be recognized
as a distinct group, clinical trials specific to AYA cHL remain limited.9
Major Hodgkin lymphoma guidelines only partially address AYAs as a distinct group. In guidelines issued by the National Cancer Institute, the differences in clinical presentation of AYAs are described for young children, AYAs, and older adults, but there are no treatment recommendations specific to AYAs.12 Guidelines from the EuroNet Paediatric Hodgkin Lymphoma Group offer recommendations for relapsed and refractory Hodgkin lymphoma, but do not differentiate between children and adolescents.13 The National Comprehensive Cancer Network (NCCN) provides separate treatment recommendations for patients 18 years or younger and those who are older than 18.14,15 For Hodgkin lymphoma, AYA is not addressed as a separate category even though the NCCN has provided general guidelines for treatment of malignancies in AYA.16
First-line therapies are effective in children, AYAs, and adults. Survival rates at 5 years have increased steadily, approaching or exceeding 90% across age groups even for patients with unfavorable risk characteristics.17 This success has permitted greater focus on developing strategies that preserve efficacy with lower acute and long-term risks.
Risk-Adapted Therapies
While the potential for new and novel therapies to reduce the risk of long-term toxicities continues to be explored, adjusting existing regimens to reduce these risks has proven to be a viable strategy. This adjustment is a standard of care in the pediatric setting based on results from such studies as German GPOH-HD 95, which suggested that doses of radiotherapy, a major contributor to late toxicities,18 can be omitted in patients with a complete response after chemotherapy.11 This pediatric trial contained both younger children and adolescents, but subsequent secondary analyses looking specifically at AYAs in this and other trials have suggested that efficacy is similarly preserved with risk-adapted strategies.9
However, due to AYA patients with cHL being treated using both pediatric and adult approaches, the persistent debate about optimal therapies in this age group complicates the effort to define a well-accepted strategy for risk adjustment. While risk-adapted strategies that rely on interim positron emission tomography (PET) to calibrate treatment intensity are now being used routinely across age stratifications, other initiatives are creating additional opportunities to gauge the impact on late effects in AYAs. These include strategies to improve collaboration across groups of trialists and data generated by observational cohorts, which can evaluate late effects not captured in time-limited clinical trials.
Among recent data supporting risk-adjusted therapy, the toxicity outcomes from a multicenter trial of PET-guided intensive treatment in patients with newly diagnosed advanced cHL were presented at the 2022 annual meeting of the American Society of Hematology.19 This phase 3 trial enrolled patients younger than 60 years, 79% of whom were younger than 45 years. Building on previous evidence that PET guidance improves the safety of eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), nearly 1,500 patients were randomized to this strategy or to PET-guided BrECADD, a modified eBEACOPP in which the antibody conjugate brentuximab vedotin (BV) was substituted for bleomycin. For an adjudicated endpoint of treatment-related morbidity, the experimental BrECAAD regimen reduced the risk by nearly 30% (hazard ratio [HR] 0.72). It is unclear whether this strategy will be used in the United States, where trials have been built on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) rather than BEACOPP.
Efficacy data from this trial are not yet available, and these data will be important. There is concern that PET-directed therapy might result in lower toxicity at a cost of reduced rates of disease control. It is possible that the serious consequences of late toxicities—including infertility, compromised cardiovascular function, secondary cancers, and other organ damage—might need to be balanced against some loss of efficacy.
Novel Targeted Therapies
The goal of reducing late toxicities of cHL therapy in AYAs is also likely to be advanced by novel therapies. Research endeavors include a multicenter collaboration between US and Canadian investigators that is exploring the combination of nivolumab (a checkpoint inhibitor) plus BV.20 The trial recently completed accrual and includes both adult and pediatric patients. If novel agents prove effective for improving efficacy while reducing the risk of late complications in AYAs, they are expected to have a profound effect on clinical practice.
Arguably, the era of targeted and novel therapies in cHL was initiated more than 10 years ago with the introduction of BV for the treatment of advanced disease in older adults.21 BV was moved into the front line for patients 18 years of age or older with advanced cHL in a trial that compared the standard of ABVD to the same drugs with BV substituted for bleomycin.22 In this study, the BV-containing regimen was associated with a significantly improved progression-free survival (PFS) (P = .04) and a lower rate of adverse events, including pulmonary toxicity (1% vs 3%) after 2 years of follow-up.
A similar study recently associated a BV-containing regimen with even greater efficacy in pediatric high-risk cHL.23 In this multicenter study with 600 treatment-naïve patients ranging in age from 2 to 21 years, the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide was compared to the same regimen with BV substituted for bleomycin. With event-free survival as the primary endpoint, the experimental regimen was associated with a nearly 60% reduction in the risk of an adverse event or death (HR 0.41). However, no substantial differences were noted in toxicity after a follow-up of 42 months. It not yet clear whether the elimination of bleomycin will translate into less late toxicity, such as pulmonary or cardiovascular morbidity.
In the era of targeted therapies, the experience with BV has been a step toward more effective treatments using novel mechanisms of action to improve outcomes when used in the first-line treatment of patients with high-risk disease. Historically, many regimens and treatments that have demonstrated efficacy in relapsed and refractory cHL have found their way into the first-line setting. This trend might also be true of the checkpoint inhibitors, which have been tested extensively in relapsed/refractory cHL. In AYA patients with cHL, the rationale for these treatments might not only include a poor predicted response to current regimens, but a reduced risk of late toxicities if long-term follow-up demonstrates these treatments reduce late complications, such as secondary malignancies, which are associated with standard strategies, particularly those that include radiotherapy.
If targeted therapies do preserve efficacy and reduce risk of late complications, strategies to individualize therapy will remain relevant. Many of the emerging targeted therapies involve challenging and costly treatment protocols that demand selective application. Efforts to develop simpler and more precise biomarkers might streamline this task. Of promising developments in this area, cell-free DNA (cfDNA) appears to be near routine clinical application. A small study of cfDNA conducted in 121 patients found that minimal residual disease assessment by repeat cfDNA sequencing predicted response and PFS when performed as early as a week after treatment initiation.24 If larger studies confirm accuracy, this biomarker strategy might prove simpler and more convenient than PET imaging.
Summary
In the treatment of hematologic malignancies, cHL is widely regarded as a success story with high rates of extended survival among children, AYAs, and older adults. This level of success does not obviate the need for even more effective treatments, and also permits more attention to be directed to reducing the risk of late toxicities. For the AYA population, which represents a large group with cHL, the current directions of clinical research offer the promise of imminent changes in how the disease is controlled and a reduction in treatment-related late morbidity and mortality.
- Hodgkin Lymphoma. American Cancer Society. Accessed March 20, 2023. https://www.cancer.org/cancer/hodgkin-lymphoma.html
- Aben KK, van Gaal C, van Gils NA, van der Graaf WT, Zielhuis GA. Cancer in adolescents and young adults (15-29 years): a population-based study in the Netherlands 1989-2009. Acta Oncol. 2012;51(7):922-933. doi:10.3109/0284186X.2012.705891
- Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and
management. Am J Hematol. 2016;91(4):434-442. doi:10.1002/ajh.24272 - Cartwright RA, Watkins G. Epidemiology of Hodgkin’s disease: a review. Hematol Oncol. 2004;22(1):11-26. doi:10.1002/hon.723
- Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506-1514. doi:10.1056/NEJM199811193392104
- Bleyer A, Barr R, Hayes-Lattin B, et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8(4):288-298. doi:10.1038/nrc2349
- Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132. doi:10.3322/caac.21438
- Bigenwald C, Galimard JE, Quero L, et al. Hodgkin lymphoma in adolescent and young adults: insights from an adult tertiary single-center cohort of 349 patients. Oncotarget. 2017;8(45):80073-80082. doi:10.18632/oncotarget.20684
- Kahn JM, Kelly KM. Adolescent and young adult Hodgkin lymphoma: raising the bar through collaborative science and multidisciplinary care. Pediatr Blood Cancer. 2018;65(7):e27033. doi:10.1002/pbc.27033
- Yung L, Smith P, Hancock BW, et al. Long term outcome in adolescents with Hodgkin’s lymphoma: poor results using regimens designed for adults. Leuk Lymphoma. 2004;45(8):1579-1585. doi:10.1080/1042819042000209404
- Dorffel W, Ruhl U, Luders H, et al. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. J Clin Oncol. 2013;31(12):1562-1568. doi:10.1200/JCO.2012.45.3266
- National Cancer Institute. Childhood Hodgkin lymphoma treatment (PDQ®)–Health Professional Version. National Institutes of Health. Updated February 14, 2023. Accessed March 20, 2023. https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq
- Daw S, Hasenclever D, Mascarin M, et al. Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. Hemasphere. 2020;4(1):e329. doi:10.1097/HS9.0000000000000329
- Flerlage JE, Hiniker SM, Armenian S, et al. Pediatric Hodgkin lymphoma, version 3.2021. J Natl Compr Canc Netw. 2021;19(6):733-754. doi:10.6004/jnccn.2021.0027
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Hodgkin lymphoma. Version 2.2023. November 8, 2022. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Adolescent and young adult (AYA) oncology. Version 3.2023. January 9, 2023. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/aya.pdf
- Mohty R, Dulery R, Bazarbachi AH, et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 2021;11(7):126. doi:10.1038/s41408-021-00518-z
- Witkowska M, Majchrzak A, Smolewski P. The role of radiotherapy in Hodgkin’s lymphoma: what has been achieved during the last 50 years? Biomed Res Int. 2015;2015:485071. doi:10.1155/2015/485071
- Borchmann P, Moccia A, Greil R, et al. Treatment-related morbidity in patients with classical Hodgkin lymphoma: results of the ongoing, randomized phase II HD21 trial by the German Hodgkin Study Group. Hemasphere. 2022;6(suppl ):1-2. doi:10.1097/01.HS9.0000890576.23258.1c
- Immunotherapy (nivolumab or brentuximab vedotin) plus combination chemotherapy in treating patients with newly diagnosed stage III-IV classic Hodgkin lymphoma. ClinicalTrials.gov. Updated March 8, 2023. Accessed March 20, 2023. https://clinicaltrials.gov/ct2/show/NCT03907488
- Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183-2189. doi:10.1200/JCO.2011.38.0410
- Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331-344. doi:10.1056/NEJMoa1708984
- Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin’s lymphoma. N Engl J Med. 2022;387(18):1649-1660. doi:10.1056/NEJMoa2206660
- Sobesky S, Mammadova L, Cirillo M, et al. In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin’s lymphoma and facilitates ultrasensitive residual disease detection. Med (N Y). 2021;2(10):1171-1193.e11. doi:10.1016/j.medj.2021.09.002
- Hodgkin Lymphoma. American Cancer Society. Accessed March 20, 2023. https://www.cancer.org/cancer/hodgkin-lymphoma.html
- Aben KK, van Gaal C, van Gils NA, van der Graaf WT, Zielhuis GA. Cancer in adolescents and young adults (15-29 years): a population-based study in the Netherlands 1989-2009. Acta Oncol. 2012;51(7):922-933. doi:10.3109/0284186X.2012.705891
- Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and
management. Am J Hematol. 2016;91(4):434-442. doi:10.1002/ajh.24272 - Cartwright RA, Watkins G. Epidemiology of Hodgkin’s disease: a review. Hematol Oncol. 2004;22(1):11-26. doi:10.1002/hon.723
- Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506-1514. doi:10.1056/NEJM199811193392104
- Bleyer A, Barr R, Hayes-Lattin B, et al. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8(4):288-298. doi:10.1038/nrc2349
- Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132. doi:10.3322/caac.21438
- Bigenwald C, Galimard JE, Quero L, et al. Hodgkin lymphoma in adolescent and young adults: insights from an adult tertiary single-center cohort of 349 patients. Oncotarget. 2017;8(45):80073-80082. doi:10.18632/oncotarget.20684
- Kahn JM, Kelly KM. Adolescent and young adult Hodgkin lymphoma: raising the bar through collaborative science and multidisciplinary care. Pediatr Blood Cancer. 2018;65(7):e27033. doi:10.1002/pbc.27033
- Yung L, Smith P, Hancock BW, et al. Long term outcome in adolescents with Hodgkin’s lymphoma: poor results using regimens designed for adults. Leuk Lymphoma. 2004;45(8):1579-1585. doi:10.1080/1042819042000209404
- Dorffel W, Ruhl U, Luders H, et al. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. J Clin Oncol. 2013;31(12):1562-1568. doi:10.1200/JCO.2012.45.3266
- National Cancer Institute. Childhood Hodgkin lymphoma treatment (PDQ®)–Health Professional Version. National Institutes of Health. Updated February 14, 2023. Accessed March 20, 2023. https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq
- Daw S, Hasenclever D, Mascarin M, et al. Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. Hemasphere. 2020;4(1):e329. doi:10.1097/HS9.0000000000000329
- Flerlage JE, Hiniker SM, Armenian S, et al. Pediatric Hodgkin lymphoma, version 3.2021. J Natl Compr Canc Netw. 2021;19(6):733-754. doi:10.6004/jnccn.2021.0027
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Hodgkin lymphoma. Version 2.2023. November 8, 2022. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Adolescent and young adult (AYA) oncology. Version 3.2023. January 9, 2023. Accessed March 20, 2023. https://www.nccn.org/professionals/physician_gls/pdf/aya.pdf
- Mohty R, Dulery R, Bazarbachi AH, et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 2021;11(7):126. doi:10.1038/s41408-021-00518-z
- Witkowska M, Majchrzak A, Smolewski P. The role of radiotherapy in Hodgkin’s lymphoma: what has been achieved during the last 50 years? Biomed Res Int. 2015;2015:485071. doi:10.1155/2015/485071
- Borchmann P, Moccia A, Greil R, et al. Treatment-related morbidity in patients with classical Hodgkin lymphoma: results of the ongoing, randomized phase II HD21 trial by the German Hodgkin Study Group. Hemasphere. 2022;6(suppl ):1-2. doi:10.1097/01.HS9.0000890576.23258.1c
- Immunotherapy (nivolumab or brentuximab vedotin) plus combination chemotherapy in treating patients with newly diagnosed stage III-IV classic Hodgkin lymphoma. ClinicalTrials.gov. Updated March 8, 2023. Accessed March 20, 2023. https://clinicaltrials.gov/ct2/show/NCT03907488
- Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183-2189. doi:10.1200/JCO.2011.38.0410
- Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331-344. doi:10.1056/NEJMoa1708984
- Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin’s lymphoma. N Engl J Med. 2022;387(18):1649-1660. doi:10.1056/NEJMoa2206660
- Sobesky S, Mammadova L, Cirillo M, et al. In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin’s lymphoma and facilitates ultrasensitive residual disease detection. Med (N Y). 2021;2(10):1171-1193.e11. doi:10.1016/j.medj.2021.09.002
AAP issues guidance on inguinal hernias
Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.
An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.
The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.
The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.
Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.
Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.
Repair can wait until babies have left NICU
The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.
But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.
“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
Laparoscopic approach as good, sometimes better
Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.
The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.
Laparoscopy also appears to be a feasible option in managing recurrent hernias.
Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
Who should perform the surgeries?
The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.
They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.
Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.
Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
No evidence that anesthetic exposure affects neurodevelopment
The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.
Contralateral exploration with unilateral hernia
Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.
Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.
The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”
Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”
The authors and Dr. Gosain declare no relevant financial relationships.
Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.
An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.
The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.
The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.
Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.
Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.
Repair can wait until babies have left NICU
The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.
But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.
“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
Laparoscopic approach as good, sometimes better
Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.
The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.
Laparoscopy also appears to be a feasible option in managing recurrent hernias.
Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
Who should perform the surgeries?
The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.
They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.
Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.
Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
No evidence that anesthetic exposure affects neurodevelopment
The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.
Contralateral exploration with unilateral hernia
Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.
Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.
The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”
Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”
The authors and Dr. Gosain declare no relevant financial relationships.
Faraz A. Khan, MD, an adjunct associate professor in the division of pediatric surgery at Loma Linda (Calif.) University Children’s Hospital, led the AAP’s Committee on Fetus and Newborn, sections on surgery and urology, in writing the guidance, published in Pediatrics.
An inguinal hernia, a common pediatric surgical condition (90% are in boys, the authors wrote), appears as a bulge in the groin or scrotum and requires surgical repair to prevent a more severe incarcerated hernia, which occurs when organs from the abdomen become trapped in the hernia.
The risk of that incarceration drives the preference and timing of surgical repair, the authors wrote.
The incidence of inguinal hernias is about 8-50 per 1,000 live births in term infants and is much higher in extremely low-birth-weight infants.
Ankush Gosain, MD, PhD, chief of pediatric surgery at Children’s Hospital Colorado, Aurora, who was not involved in the AAP clinical report, said in an interview that the best timing for the surgery on a premature infant has been an unanswered question and this guidance is helpful.
Inguinal hernias in preterm infants are especially common. The incidence is reported to be as high as 20%.
Repair can wait until babies have left NICU
The authors concluded that there was moderate-quality evidence supporting deferring hernia repair until after discharge from the neonatal intensive care unit because this may reduce the risk of respiratory problems without increasing risk of incarceration or another operation.
But Dr. Gosain noted that the authors left the door open for data from a study that recently finished enrolling patients. That trial (Dr. Gosain is a site investigator) is expected to help determine whether an early- or late-term approach is best in preterm infants.
“There are pluses and minuses that we and the neonatologists and the anesthesiologists recognize,” he said.
Laparoscopic approach as good, sometimes better
Dr. Gosain also said he was glad to see the authors addressed the merits of the laparoscopic approach and when it is preferred.
The authors noted that a laparoscopic approach is increasingly popular – rates have grown fivefold between 2009 and 2018 – and they found it is “at least as effective as, if not better than,” the current preferred method, traditional open high ligation of the hernia sac.
Laparoscopy also appears to be a feasible option in managing recurrent hernias.
Dr. Gosain said that, when the laparoscopic approach was developed, there was concern that it would lead to higher recurrence of the hernias. “That concern has diminished over time,” he added. The paper helps give surgeons and pediatricians peace of mind that this is a safe approach.
Who should perform the surgeries?
The authors concluded that, ideally, pediatric surgical specialists, pediatric urologists, or general surgeons with a significant yearly case volume should perform the surgeries.
They found a significant inverse relationship between recurrence rates and general surgeon case volume: general surgeons who completed fewer than 10 pediatric inguinal hernias per year had the highest recurrence rates and the highest-volume general surgeons had recurrence rates similar to pediatric surgical specialists.
Pediatric surgical specialists trained in fellowships had the lowest rate of hernia recurrences.
Dr. Gosain said he was glad the authors pointed out that both the surgeon and the anesthesiologist ideally should have that specialty training.
No evidence that anesthetic exposure affects neurodevelopment
The researchers found no conclusive evidence that otherwise-healthy children’s exposure to a single relatively short duration of anesthetic adds any significant risk to neurodevelopment or academic performance, or increases risk of ADHD or autism spectrum disorder.
Contralateral exploration with unilateral hernia
Providers continue to debate contralateral exploration among patients with unilateral inguinal hernia. Proponents of exploration cite a 10%-15% rate of developing of a hernia at a later time. Therefore, routine exploration and, if identified, ligation of a patent processus vaginalis (PPV) may avoid a subsequent anesthetic.
Opponents counter that not all PPVs will become clinically significant inguinal hernias, and doing routine exploration exposes the patient to potentially unnecessary complications.
The authors wrote: “In the absence of strong data for or against repair of incidentally discovered contralateral PPV, family values related to the risks and benefits of each approach from a nuanced preoperative discussion should be considered.”
Dr. Gosain said that, with all of the guidance points, “you need to have a true conversation between the surgeon and the parents with pluses and minuses of the different approaches because one is not necessarily absolutely better than the other.”
The authors and Dr. Gosain declare no relevant financial relationships.
FROM PEDIATRICS
Study supports new NCCN classification for cutaneous squamous cell carcinoma
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107; P < .001; very-high-risk SHR, 6.3 × 108; P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107; P < .001; very-high-risk SHR, 6.3 × 108; P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107; P < .001; very-high-risk SHR, 6.3 × 108; P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
FROM JAMA DERMATOLOGY
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
I selected a GI career path aligned with my goals
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.