JAMA Oncology最新文献

{"title":"Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.","authors":"Mahmoud Yousef,Abdelrahman Yousef,Saikat Chowdhury,Mohammad M Fanaeian,Mark Knafl,Jennifer Peterson,Mohammad Zeineddine,Kristin Alfaro,Fadl Zeineddine,Drew Goldstein,Nicholas Hornstein,Arvind Dasari,Ryan Huey,Benny Johnson,Victoria Higbie,Alisha Bent,Bryan Kee,Michael Lee,Maria Pia Morelli,Van Karlyle Morris,Daniel Halperin,Michael J Overman,Christine Parseghian,Eduardo Vilar,Robert Wolff,Kanwal P Raghav,Michael G White,Abhineet Uppal,Ryan Sun,Wenyi Wang,Scott Kopetz,Jason Willis,John Paul Shen","doi":"10.1001/jamaoncol.2024.3666","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3666","url":null,"abstract":"ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.Design, Setting, and ParticipantsThis single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.Main OutcomeOS, from diagnosis date and from start of first-line chemotherapy.ResultsThe study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%).ConclusionsThis single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and ","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174605","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}

{"title":"Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring TP53 Germline Variants.","authors":"Gustav Y Cederquist,Lillian A Boe,Michael Walsh,Gary M Freedman,Kara N Maxwell,Neil Taunk,Lior Z Braunstein","doi":"10.1001/jamaoncol.2024.3683","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3683","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174531","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}

{"title":"Cervical Cancer Incidence in the US-Affiliated Pacific Islands.","authors":"Sameer V Gopalani,Jin Qin,Janos Baksa,Trevor D Thompson,Mona Saraiya,Virginia Senkomago,Paran Pordell,Youngju Jeong,Neal A Palafox,Martina Reichhardt,Lee E Buenconsejo-Lum","doi":"10.1001/jamaoncol.2024.3675","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3675","url":null,"abstract":"ImportanceThe World Health Organization has called for eliminating cervical cancer as a public health problem. Accurate and up-to-date estimates of population-based cervical cancer incidence are essential for monitoring progress toward elimination and informing local cancer control strategies, but these estimates are lacking for the US-Affiliated Pacific Islands (USAPI).ObjectiveTo calculate age-standardized incidence rates for cervical cancer in the 6 USAPI and compare these rates with rates in the US (50 states and the District of Columbia).Design, Setting, and ParticipantsThis cross-sectional study used population-based data from the Pacific Regional Central Cancer Registry for women aged 20 years or older who were diagnosed with invasive cervical cancer from January 1, 2007, to December 31, 2020. The registry comprises data on all cervical cancers from the USAPI, which include 3 US territories (American Samoa, Commonwealth of the Northern Mariana Islands, and Guam) and 3 freely associated states (Federated States of Micronesia [FSM], Republic of the Marshall Islands [RMI], and Republic of Palau). Data were analyzed from July 10, 2023, to November 28, 2023.Main Outcomes and MeasuresThe main outcome was age-standardized cervical cancer incidence rates, stratified by age, stage, and histologic code for the USAPI using population estimates from 3 different sources (US Census Bureau International Database, United Nations Population Division, and Pacific Data Hub). Rate ratios were calculated to compare incidence rates between the USAPI and the US.ResultsFrom 2007 to 2020, 409 cases of cervical cancer were diagnosed in the USAPI (median age at diagnosis, 46.0 years [25th-75th percentile, 39.0-55.0 years]), with an age-standardized incidence rate ranging from 21.7 (95% CI, 19.6-23.9) to 22.1 (95% CI, 20.0-24.4) per 100 000 women, depending on the population estimate. Incidence rates were highest in RMI, ranging from 58.1 (95% CI, 48.0-69.7) to 83.4 (95% CI, 68.3-101.0) per 100 000 women, followed by FSM, ranging from 28.7 (95% CI, 23.4-34.9) to 29.8 (95% CI, 24.3-36.3) per 100 000 women. Compared with the US, incidence rates were highest in RMI (rate ratio, 5.7 [95% CI, 4.7-6.8] to 8.2 [95% CI, 6.7-9.9]) and FSM (rate ratio; 2.8; 95% CI, 2.3-3.4). Of all cases in the USAPI, 213 (68.2%) were diagnosed at a late stage.Conclusions and RelevanceIn this cross-sectional study, cervical cancer remained a major public health issue in some USAPI, with RMI reporting the highest incidence rates. The findings suggest that improvements in human papillomavirus vaccination and cancer screening coverage through efforts tailored to the unique geographic, sociocultural, economic, and health care landscape of the USAPI may reduce the burden of cervical cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174532","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}

{"title":"Accrual to Radiotherapy Trials in the US-Pitfalls and Potential Solutions.","authors":"Nina N Sanford,William A Hall","doi":"10.1001/jamaoncol.2024.3663","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3663","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":null,"pages":null},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174624","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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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;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;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":null,"pages":null},"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}

{"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":null,"pages":null},"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}