Pub Date : 2024-09-12DOI: 10.1001/jamaoncol.2024.3679
Paolo Tarantino,Gabriel Hortobagyi,Sara M Tolaney,Elizabeth A Mittendorf
ImportanceOver the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary.ObservationsNovel antibody-drug conjugates, anti-ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD.Conclusions and RelevanceEscalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.
{"title":"Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review.","authors":"Paolo Tarantino,Gabriel Hortobagyi,Sara M Tolaney,Elizabeth A Mittendorf","doi":"10.1001/jamaoncol.2024.3679","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3679","url":null,"abstract":"ImportanceOver the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary.ObservationsNovel antibody-drug conjugates, anti-ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD.Conclusions and RelevanceEscalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"2015 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1001/jamaoncol.2024.3466
Sjoerd J. F. Hermans, Niek G. van der Maas, Yvette van Norden, Avinash G. Dinmohamed, Elizabeth Berkx, Peter C. Huijgens, Donna R. Rivera, R. Angelo de Claro, Francesco Pignatti, Jurjen Versluis, Jan J. Cornelissen
ImportanceThe use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.ObjectiveTo address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.Evidence ReviewA systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023.FindingsThirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10 594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm.Conclusions and RelevanceIn this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.
{"title":"Externally Controlled Studies Using Real-World Data in Patients With Hematological Cancers","authors":"Sjoerd J. F. Hermans, Niek G. van der Maas, Yvette van Norden, Avinash G. Dinmohamed, Elizabeth Berkx, Peter C. Huijgens, Donna R. Rivera, R. Angelo de Claro, Francesco Pignatti, Jurjen Versluis, Jan J. Cornelissen","doi":"10.1001/jamaoncol.2024.3466","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3466","url":null,"abstract":"ImportanceThe use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.ObjectiveTo address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.Evidence ReviewA systematic search across 4 electronic databases and Google Scholar was conducted from January 1, 2000, to October 23, 2023. Studies were included in the systematic review if they compared an intervention arm in a clinical trial to an RWD control arm in patients with hematological cancers and if they were published between 2000 and 2023.FindingsThirty-two prospective intervention studies incorporating external control data from RWD sources of patients with hematological cancers were identified. A total of 4306 patients from intervention arms and 10 594 from RWD control arms were included across all studies. Only 2 studies (6%) included prospectively collected RWD. The complete trial inclusion criteria were applied to the RWD cohort in 7 studies (22%). Four studies (13%) published the statistical analysis plan and prespecified use of RWD. A total of 23 studies (72%) applied matching algorithms for trial and RWD cohorts, including matching for demographic, disease, and/or therapy-related characteristics. The end point criteria were the same as the trial in 8 studies (25%). In contrast, 12 studies (38%) used different end points, and 12 (38%) did not provide an end point definition for the RWD. Twelve studies (38%) had a median follow-up difference of less than a year between arms. Eight studies (25%) reported toxic effect data for the trial arm, of which 5 studies reported toxic effect data for the RWD arm.Conclusions and RelevanceIn this systematic review, limitations were observed in the application of clinical trial eligibility criteria to RWD, statistical rigor and application of matching methods, the definition of end points, follow-up, and reporting of adverse events, which may challenge the conclusions reported in studies using RWD.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"6 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1001/jamaoncol.2024.3033
Manu Mysore, Dylan Singhi, Eric K. Singhi
This JAMA Oncology Patient Page describes cardio-oncology, a relatively new area in medicine that focuses on taking care of the heart while going through cancer treatments.
{"title":"Caring for Your Heart During Cancer Treatment","authors":"Manu Mysore, Dylan Singhi, Eric K. Singhi","doi":"10.1001/jamaoncol.2024.3033","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3033","url":null,"abstract":"This <jats:italic>JAMA Oncology</jats:italic> Patient Page describes cardio-oncology, a relatively new area in medicine that focuses on taking care of the heart while going through cancer treatments.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1001/jamaoncol.2024.3104
Karina N. Ruiz-Esteves, Kaitlyn R. Shank, Aaron J. Deutsch, Alekhya Gunturi, Natalia Chamorro-Pareja, Caitlin A. Colling, Leyre Zubiri, Katherine Perlman, Tianqi Ouyang, Alexandra-Chloé Villani, Jose C. Florez, Alexander Gusev, Kerry L. Reynolds, Karen K. Miller, Miriam S. Udler, Meghan E. Sise, Michelle Rengarajan
ImportanceImmune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.ObjectiveTo define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes.Design, Setting, and ParticipantsThis cohort study, conducted at an academic integrated health care system examined 14 328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined.Main Outcomes and MeasuresFor ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated.ResultsOf 14 328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14 328), with an incidence of 124.8 per 100 000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation.Conclusions and RelevanceThe results of this analysis of 14 328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.
{"title":"Identification of Immune Checkpoint Inhibitor–Induced Diabetes","authors":"Karina N. Ruiz-Esteves, Kaitlyn R. Shank, Aaron J. Deutsch, Alekhya Gunturi, Natalia Chamorro-Pareja, Caitlin A. Colling, Leyre Zubiri, Katherine Perlman, Tianqi Ouyang, Alexandra-Chloé Villani, Jose C. Florez, Alexander Gusev, Kerry L. Reynolds, Karen K. Miller, Miriam S. Udler, Meghan E. Sise, Michelle Rengarajan","doi":"10.1001/jamaoncol.2024.3104","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3104","url":null,"abstract":"ImportanceImmune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.ObjectiveTo define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes.Design, Setting, and ParticipantsThis cohort study, conducted at an academic integrated health care system examined 14 328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined.Main Outcomes and MeasuresFor ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated.ResultsOf 14 328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14 328), with an incidence of 124.8 per 100 000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation.Conclusions and RelevanceThe results of this analysis of 14 328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1001/jamaoncol.2024.3456
Guillermo Villacampa, Victor Navarro, Alexios Matikas, Joana Mourato Ribeiro, Francesco Schettini, Pablo Tolosa, Olga Martínez-Sáez, Rodrigo Sánchez-Bayona, Juan M. Ferrero-Cafiero, Fernando Salvador, Andri Papakonstantinou, Aleix Prat, Mafalda Oliveira, Tomas Pascual
ImportanceRecent studies have investigated the combination of immune checkpoint inhibitors (ICIs) with (neo)adjuvant chemotherapy in early-stage breast cancer. However, there is an ongoing debate about the optimal approach for integrating this strategy.ObjectivesTo evaluate the association of neoadjuvant ICIs with pathologic complete response (pCR) across molecular phenotypes, to quantify the survival benefits of ICIs beyond pCR status, and to estimate the incidence of specific adverse events.Data SourcesThe PubMed database was searched on December 10, 2023, to identify all potential eligible studies.Study SelectionRandomized clinical trials (RCTs) that assessed (neo)adjuvant ICI plus chemotherapy in early breast cancer.Data Extraction and SynthesisData from the eligible RCTs were extracted by 2 reviewers. An extracted individual patient data meta-analysis and a trial-level random-effect meta-analysis were performed.Main Outcome(s) and Measure(s)Outcomes were pCR, event-free survival (EFS) in patients with and without pCR, and adverse events. Hazard ratios were estimated using stratified Cox proportional hazards regression models.ResultsNine RCTs involving 5114 patients met the inclusion criteria (2097 triple-negative breast cancer [TNBC], 1924 hormone receptor–positive [HR+]/ERBB2-negative [ERBB2−], and 1115 ERBB2+ tumors). In TNBC, the addition of ICIs was associated with an improved pCR rate regardless of programmed cell death ligand 1 (PD-L1) status (absolute improvement, &gt;10%). In HR+/ ERBB2− tumors, the administration of ICIs was associated with improved pCR only in the PD-L1–positive (PD-L1+) population (absolute improvement, +12.2%), whereas no benefit was observed in ERBB2+ tumors. In patients with TNBC achieving a pCR, the addition of ICIs was associated with improved EFS (hazard ratio, 0.65; 95% CI, 0.42-1.00), resulting in a 5-year EFS of 92.0% with ICIs compared with 88.0% without them. In patients with residual disease, ICIs also showed better EFS (hazard ratio, 0.77; 95% CI, 0.61-0.98), resulting in a 5-year EFS of 63.3% with ICIs and 56.1% without them. Adjuvant ICI did not show numerical improvement in patients with either pCR or residual disease (all hazard ratios &gt;1). During the neoadjuvant treatment, the incidence of grade 3 or greater immune-related adverse events with ICI was 10.3%.Conclusions and RelevanceThese findings suggest that neoadjuvant ICI therapy improves efficacy outcomes in early-stage TNBC and PD-L1+ HR+/ERBB2− tumors with an acceptable safety profile; however, no benefit was observed with adjuvant ICI. Given the financial and toxicity costs associated with ICIs, future research should prioritize identifying patients most likely to benefit from the addition of ICIs to neoadjuvant chemotherapy.
{"title":"Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Early Breast Cancer","authors":"Guillermo Villacampa, Victor Navarro, Alexios Matikas, Joana Mourato Ribeiro, Francesco Schettini, Pablo Tolosa, Olga Martínez-Sáez, Rodrigo Sánchez-Bayona, Juan M. Ferrero-Cafiero, Fernando Salvador, Andri Papakonstantinou, Aleix Prat, Mafalda Oliveira, Tomas Pascual","doi":"10.1001/jamaoncol.2024.3456","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3456","url":null,"abstract":"ImportanceRecent studies have investigated the combination of immune checkpoint inhibitors (ICIs) with (neo)adjuvant chemotherapy in early-stage breast cancer. However, there is an ongoing debate about the optimal approach for integrating this strategy.ObjectivesTo evaluate the association of neoadjuvant ICIs with pathologic complete response (pCR) across molecular phenotypes, to quantify the survival benefits of ICIs beyond pCR status, and to estimate the incidence of specific adverse events.Data SourcesThe PubMed database was searched on December 10, 2023, to identify all potential eligible studies.Study SelectionRandomized clinical trials (RCTs) that assessed (neo)adjuvant ICI plus chemotherapy in early breast cancer.Data Extraction and SynthesisData from the eligible RCTs were extracted by 2 reviewers. An extracted individual patient data meta-analysis and a trial-level random-effect meta-analysis were performed.Main Outcome(s) and Measure(s)Outcomes were pCR, event-free survival (EFS) in patients with and without pCR, and adverse events. Hazard ratios were estimated using stratified Cox proportional hazards regression models.ResultsNine RCTs involving 5114 patients met the inclusion criteria (2097 triple-negative breast cancer [TNBC], 1924 hormone receptor–positive [HR+]/<jats:italic>ERBB2</jats:italic>-negative [<jats:italic>ERBB2</jats:italic>−], and 1115 <jats:italic>ERBB2</jats:italic>+ tumors). In TNBC, the addition of ICIs was associated with an improved pCR rate regardless of programmed cell death ligand 1 (PD-L1) status (absolute improvement, &amp;gt;10%). In HR+/ <jats:italic>ERBB2</jats:italic>− tumors, the administration of ICIs was associated with improved pCR only in the PD-L1–positive (PD-L1+) population (absolute improvement, +12.2%), whereas no benefit was observed in <jats:italic>ERBB2</jats:italic>+ tumors. In patients with TNBC achieving a pCR, the addition of ICIs was associated with improved EFS (hazard ratio, 0.65; 95% CI, 0.42-1.00), resulting in a 5-year EFS of 92.0% with ICIs compared with 88.0% without them. In patients with residual disease, ICIs also showed better EFS (hazard ratio, 0.77; 95% CI, 0.61-0.98), resulting in a 5-year EFS of 63.3% with ICIs and 56.1% without them. Adjuvant ICI did not show numerical improvement in patients with either pCR or residual disease (all hazard ratios &amp;gt;1). During the neoadjuvant treatment, the incidence of grade 3 or greater immune-related adverse events with ICI was 10.3%.Conclusions and RelevanceThese findings suggest that neoadjuvant ICI therapy improves efficacy outcomes in early-stage TNBC and PD-L1+ HR+/<jats:italic>ERBB2</jats:italic>− tumors with an acceptable safety profile; however, no benefit was observed with adjuvant ICI. Given the financial and toxicity costs associated with ICIs, future research should prioritize identifying patients most likely to benefit from the addition of ICIs to neoadjuvant chemotherapy.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1001/jamaoncol.2024.0985
Laura W. Dillon, Gege Gui, Niveditha Ravindra, Georgia Andrew, Devdeep Mukherjee, Zoë C. Wong, Ying Huang, Jason Gerhold, Matt Holman, Julian D’Angelo, Jeffrey Miller, Jake Higgins, Jesse J. Salk, Jeffery J. Auletta, Firas El Chaer, Steven M. Devine, Antonio Martin Jimenez-Jimenez, Marcos J. G. De Lima, Mark R. Litzow, Partow Kebriaei, Wael Saber, Stephen R. Spellman, Scott L. Zeger, Kristin M. Page, Christopher S. Hourigan
ImportancePersistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.ObjectiveTo examine the association between pre–allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR.Design, Setting, and ParticipantsIn this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023.ExposureCentralized DNA sequencing for FLT3-ITD in pre–allogeneic HCT first CR blood using a commercially available kit.Main Outcomes and MeasuresThe primary outcomes were overall survival and cumulative incidence of relapse, with non–relapse-associated mortality as a competing risk post–allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points.ResultsOf 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning.Conclusions and RelevanceThis study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.
{"title":"Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia","authors":"Laura W. Dillon, Gege Gui, Niveditha Ravindra, Georgia Andrew, Devdeep Mukherjee, Zoë C. Wong, Ying Huang, Jason Gerhold, Matt Holman, Julian D’Angelo, Jeffrey Miller, Jake Higgins, Jesse J. Salk, Jeffery J. Auletta, Firas El Chaer, Steven M. Devine, Antonio Martin Jimenez-Jimenez, Marcos J. G. De Lima, Mark R. Litzow, Partow Kebriaei, Wael Saber, Stephen R. Spellman, Scott L. Zeger, Kristin M. Page, Christopher S. Hourigan","doi":"10.1001/jamaoncol.2024.0985","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0985","url":null,"abstract":"ImportancePersistence of <jats:italic>FLT3</jats:italic> internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.ObjectiveTo examine the association between pre–allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR.Design, Setting, and ParticipantsIn this cohort study, DNA sequencing was performed on first CR blood from patients with <jats:italic>FLT3</jats:italic>-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023.ExposureCentralized DNA sequencing for <jats:italic>FLT3</jats:italic>-ITD in pre–allogeneic HCT first CR blood using a commercially available kit.Main Outcomes and MeasuresThe primary outcomes were overall survival and cumulative incidence of relapse, with non–relapse-associated mortality as a competing risk post–allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points.ResultsOf 537 included patients with <jats:italic>FLT3</jats:italic>-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 <jats:italic>FLT3</jats:italic>-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual <jats:italic>FLT3</jats:italic>-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning.Conclusions and RelevanceThis study provides generalizable and clinically applicable evidence that the detection of residual <jats:italic>FLT3</jats:italic>-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"52 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1001/jamaoncol.2024.0851
Pedro C. Barata, Jonathan Assayag, Benjamin Li, Gordon Siu, Alexander Niyazov
This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).
这项横断面研究评估了同源重组修复突变基因检测和转移性抗性前列腺癌（mCRPC）男性患者的相关特征。
{"title":"Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer","authors":"Pedro C. Barata, Jonathan Assayag, Benjamin Li, Gordon Siu, Alexander Niyazov","doi":"10.1001/jamaoncol.2024.0851","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0851","url":null,"abstract":"This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"5 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140820920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1001/jamaoncol.2024.0827
Qunfeng Liang, Trasias Mukama, Kristina Sundquist, Jan Sundquist, Hermann Brenner, Elham Kharazmi, Mahdi Fallah
ImportanceFor individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded.ObjectiveTo assess how many years after a first colonoscopy with findings negative for CRC a second colonoscopy can be performed.Design, Setting, and ParticipantsThis cohort study leveraged Swedish nationwide register-based data to examine CRC diagnoses and CRC-specific mortality among individuals without a family history of CRC. The exposed group included individuals who had a first colonoscopy with findings negative for CRC at age 45 to 69 years between 1990 and 2016. The control group included individuals matched by sex, birth year, and baseline age (ie, the age of their matched exposed individual when the exposed individual’s first colonoscopy with findings negative for CRC was performed). Individuals in the control group either did not have a colonoscopy during the follow-up or underwent colonoscopy that resulted in a CRC diagnosis. Up to 18 controls were matched with each exposed individual. Individuals were followed up from 1990 to 2018, and data were analyzed from November 2022 to November 2023.ExposureA first colonoscopy with findings negative for CRC, defined as a first colonoscopy without a diagnosis of colorectal polyp, adenoma, carcinoma in situ, or CRC before or within 6 months after screening.Main Outcomes and MeasuresThe primary outcomes were CRC diagnosis and CRC-specific death. The 10-year standardized incidence ratio and standardized mortality ratio were calculated to compare risks of CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.ResultsThe sample included 110 074 individuals (65 147 females [59.2%]) in the exposed group and 1 981 332 (1 172 646 females [59.2%]) in the control group. The median (IQR) age for individuals in both groups was 59 (52-64) years. During up to 29 years of follow-up of individuals with a first colonoscopy with findings negative for CRC, 484 incident CRCs and 112 CRC-specific deaths occurred. After a first colonoscopy with findings negative for CRC, the risks of CRC and CRC-specific death in the exposed group were significantly lower than those in their matched controls for 15 years. At 15 years after a first colonoscopy with findings negative for CRC, the 10-year standardized incidence ratio was 0.72 (95% CI, 0.54-0.94) and the 10-year standardized mortality ratio was 0.55 (95% CI, 0.29-0.94). In other words, the 10-year cumulative risk of CRC in year 15 in the exposed group was 72% that of the 10-year cumulative risk of CRC in the control group. Extending the colonoscopy screening interval from 10 to 15 years in individuals with a first colonoscopy with findings negative for CRC could miss the early detection of only 2 CRC cases and the prevention of 1 CRC-specific death pe
{"title":"Longer Interval Between First Colonoscopy With Negative Findings for Colorectal Cancer and Repeat Colonoscopy","authors":"Qunfeng Liang, Trasias Mukama, Kristina Sundquist, Jan Sundquist, Hermann Brenner, Elham Kharazmi, Mahdi Fallah","doi":"10.1001/jamaoncol.2024.0827","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0827","url":null,"abstract":"ImportanceFor individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded.ObjectiveTo assess how many years after a first colonoscopy with findings negative for CRC a second colonoscopy can be performed.Design, Setting, and ParticipantsThis cohort study leveraged Swedish nationwide register-based data to examine CRC diagnoses and CRC-specific mortality among individuals without a family history of CRC. The exposed group included individuals who had a first colonoscopy with findings negative for CRC at age 45 to 69 years between 1990 and 2016. The control group included individuals matched by sex, birth year, and baseline age (ie, the age of their matched exposed individual when the exposed individual’s first colonoscopy with findings negative for CRC was performed). Individuals in the control group either did not have a colonoscopy during the follow-up or underwent colonoscopy that resulted in a CRC diagnosis. Up to 18 controls were matched with each exposed individual. Individuals were followed up from 1990 to 2018, and data were analyzed from November 2022 to November 2023.ExposureA first colonoscopy with findings negative for CRC, defined as a first colonoscopy without a diagnosis of colorectal polyp, adenoma, carcinoma in situ, or CRC before or within 6 months after screening.Main Outcomes and MeasuresThe primary outcomes were CRC diagnosis and CRC-specific death. The 10-year standardized incidence ratio and standardized mortality ratio were calculated to compare risks of CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.ResultsThe sample included 110 074 individuals (65 147 females [59.2%]) in the exposed group and 1 981 332 (1 172 646 females [59.2%]) in the control group. The median (IQR) age for individuals in both groups was 59 (52-64) years. During up to 29 years of follow-up of individuals with a first colonoscopy with findings negative for CRC, 484 incident CRCs and 112 CRC-specific deaths occurred. After a first colonoscopy with findings negative for CRC, the risks of CRC and CRC-specific death in the exposed group were significantly lower than those in their matched controls for 15 years. At 15 years after a first colonoscopy with findings negative for CRC, the 10-year standardized incidence ratio was 0.72 (95% CI, 0.54-0.94) and the 10-year standardized mortality ratio was 0.55 (95% CI, 0.29-0.94). In other words, the 10-year cumulative risk of CRC in year 15 in the exposed group was 72% that of the 10-year cumulative risk of CRC in the control group. Extending the colonoscopy screening interval from 10 to 15 years in individuals with a first colonoscopy with findings negative for CRC could miss the early detection of only 2 CRC cases and the prevention of 1 CRC-specific death pe","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"62 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1001/jamaoncol.2024.0578
Giacomo Montagna, Mary M. Mrdutt, Susie X. Sun, Callie Hlavin, Emilia J. Diego, Stephanie M. Wong, Andrea V. Barrio, Astrid Botty van den Bruele, Neslihan Cabioglu, Varadan Sevilimedu, Laura H. Rosenberger, E. Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Díaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Hasan Karanlık, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Mahmut Muslumanoglu, Maria Del Rosario Cueva Perez, Marcelo Chávez Díaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Mustafa Tukenmez, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis R. Paulinelli, Sebastián Solé Zarhi, Sherko Kuemmel, Simona Bruzas, Simona di Lascio, Tamara K. Parissenti, Tanya L. Hoskin, Uwe Güth, Valentina Ovalle, Christoph Tausch, Henry M. Kuerer, Abigail S. Caudle, Jean-Francois Boileau, Judy C. Boughey, Thorsten Kühn, Monica Morrow, Walter P. Weber
ImportanceData on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown.ObjectiveTo investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node.Design, Setting, and ParticipantsIn this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis.ExposureOmission of ALND after SLNB or TAD.Main Outcomes and MeasuresThe primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed.ResultsA total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)–positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P &lt; .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P &lt; .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55).Conclusions and RelevanceThe results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.
{"title":"Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy","authors":"Giacomo Montagna, Mary M. Mrdutt, Susie X. Sun, Callie Hlavin, Emilia J. Diego, Stephanie M. Wong, Andrea V. Barrio, Astrid Botty van den Bruele, Neslihan Cabioglu, Varadan Sevilimedu, Laura H. Rosenberger, E. Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Díaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Hasan Karanlık, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Mahmut Muslumanoglu, Maria Del Rosario Cueva Perez, Marcelo Chávez Díaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Mustafa Tukenmez, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis R. Paulinelli, Sebastián Solé Zarhi, Sherko Kuemmel, Simona Bruzas, Simona di Lascio, Tamara K. Parissenti, Tanya L. Hoskin, Uwe Güth, Valentina Ovalle, Christoph Tausch, Henry M. Kuerer, Abigail S. Caudle, Jean-Francois Boileau, Judy C. Boughey, Thorsten Kühn, Monica Morrow, Walter P. Weber","doi":"10.1001/jamaoncol.2024.0578","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0578","url":null,"abstract":"ImportanceData on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown.ObjectiveTo investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node.Design, Setting, and ParticipantsIn this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis.ExposureOmission of ALND after SLNB or TAD.Main Outcomes and MeasuresThe primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed.ResultsA total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had <jats:italic>ERBB2</jats:italic> (formerly <jats:italic>HER2</jats:italic>)–positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; <jats:italic>P</jats:italic> = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (<jats:italic>P</jats:italic> &amp;lt; .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (<jats:italic>P</jats:italic> &amp;lt; .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; <jats:italic>P</jats:italic> = .55).Conclusions and RelevanceThe results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"53 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1001/jamaoncol.2024.0565
Won Kyung Cho, Won Park, Sang-Won Kim, Kang Kyu Lee, Ki Jung Ahn, Jin Hwa Choi
ImportanceProspective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking.ObjectiveTo evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy.Design, Setting, and ParticipantsThe POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer.InterventionPostoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy.Main Outcomes and MeasuresThe primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion.ResultsOf 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients’ median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%.ConclusionsFindings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT03239613
{"title":"Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer","authors":"Won Kyung Cho, Won Park, Sang-Won Kim, Kang Kyu Lee, Ki Jung Ahn, Jin Hwa Choi","doi":"10.1001/jamaoncol.2024.0565","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0565","url":null,"abstract":"ImportanceProspective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking.ObjectiveTo evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy.Design, Setting, and ParticipantsThe POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer.InterventionPostoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy.Main Outcomes and MeasuresThe primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion.ResultsOf 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients’ median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%.ConclusionsFindings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://classic.clinicaltrials.gov/ct2/show/NCT03239613\">NCT03239613</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"23 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140649095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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