Journal of Clinical Oncology最新文献

{"title":"Cyclin-Dependent Kinase 4/6 Inhibition as a Novel Therapy for Peritoneal Mucinous Carcinomatosis With GNAS Mutations.","authors":"Jonathan Weitz, Daisuke Nishizaki, Joy Liau, Jay Patel, Isabella Ng, Siming Sun, Dana Ramms, Jingjing Zou, Brian Wishart, Jordan Rull, Joel Baumgartner, Kaitlyn Kelly, Rebekah White, Jula Veerapong, Mojgan Hosseini, Hitendra Patel, Gregory Botta, J Sylvio Gutkind, Herve Tiriac, Shumei Kato, Andrew M Lowy","doi":"10.1200/JCO.24.00511","DOIUrl":"10.1200/JCO.24.00511","url":null,"abstract":"<p><strong>Purpose: </strong>Mucinous neoplasms of the gastrointestinal tract are characterized by a propensity for metastasis to the peritoneum, resulting in peritoneal mucinous carcinomatosis (PMC). A subset of these tumors, most often originating in the appendix, harbor mutations in the <i>GNAS</i> oncogene. While the natural history of <i>GNAS</i>-mutant PMC varies, patient outcomes are generally poor, as is response to cytotoxic chemotherapy. The purpose of this study was to evaluate the clinical efficacy of single-agent palbociclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, in patients with <i>GNAS</i>-mutant PMC.</p><p><strong>Patients and methods: </strong>We enrolled 16 patients with PMC in a single-arm personalized cancer therapy trial. For all patients, tumor tissue and/or circulating tumor DNA genomic profiling using next-generation sequencing and, when possible, PD-L1 expression, tumor mutational burden, and microsatellite instability status was assessed. Twelve of 16 patients had previous disease progression on at least one previous line of chemotherapy. The primary tumor was appendix in 13 patients, unknown in two patients, and pancreas in one patient. Eleven cases were classified as low grade, and five as high grade.</p><p><strong>Results: </strong>In 13 of 16 patients, we observed a decrease in carcinoembryonic antigen (CEA), and in six patients, the CEA declined by >50%. As measured by clinical and modified peritoneal RECIST criteria, 50% of evaluable patients had stable disease after 12 months of palbociclib. At a median follow-up of 17.6 months, median survival has not been reached. Clinical response to CDK4/6 inhibition was mirrored in tumors with <i>GNAS</i> mutation and mucinous histology using an ex vivo preclinical platform.</p><p><strong>Conclusion: </strong>CDK4/6 inhibition with palbociclib had clinical activity in PMC characterized by mutations in <i>GNAS</i> that was superior to that previously reported with cytotoxic chemotherapy. CDK4/6 inhibition is a novel therapeutic strategy worthy of further evaluation in this subgroup of gastrointestinal neoplasms.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"705-715"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining Available Therapy in Oncology Accelerated Approval Decisions.","authors":"Shruti Rajesh Patel, Maya Ramachandran, Angela Ai, Christopher T Chen","doi":"10.1200/JCO.24.00892","DOIUrl":"10.1200/JCO.24.00892","url":null,"abstract":"<p><p>When weighing rapid approval for follow-on drugs, should @FDAOncology recognize the drugs that came before?</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"629-632"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501184","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":"Human Leukocyte Antigen Mismatching and the Role of Killer Cell Immunoglobulin-Like Receptor Mismatch in Hematopoietic Cell Transplantation for Hematologic Malignancies.","authors":"Yutaka Shimazu","doi":"10.1200/JCO-24-01869","DOIUrl":"10.1200/JCO-24-01869","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"759"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864350","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":"Significance of Up-Front Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Patients With Brain Metastases in the Era of New Generation Tyrosine Kinase Inhibitors.","authors":"Masamune Noguchi, Yurika Shindo, Kohei Wakabayashi, Yutaro Koide","doi":"10.1200/JCO-24-01876","DOIUrl":"10.1200/JCO-24-01876","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"760-762"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638830","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":"Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.","authors":"Ivone U S Leong, Claudia P Cabrera, Valentina Cipriani, Paul J Ross, Richard M Turner, Alex Stuckey, Sonali Sanghvi, Dorota Pasko, Loukas Moutsianas, Christopher A Odhams, Greg S Elgar, Georgia Chan, Adam Giess, Susan Walker, Rebecca E Foulger, Eleanor M Williams, Louise C Daugherty, Antonio Rueda-Martin, Daniel J Rhodes, Olivia Niblock, Alexandra Pickard, Lauren Marks, Sarah E A Leigh, Matthew J Welland, Marta Bleda, Catherine Snow, Zandra Deans, Nirupa Murugaesu, Richard H Scott, Michael R Barnes, Matthew A Brown, Augusto Rendon, Sue Hill, Alona Sosinsky, Mark J Caulfield, Ellen M McDonagh","doi":"10.1200/JCO.23.02761","DOIUrl":"10.1200/JCO.23.02761","url":null,"abstract":"<p><strong>Purpose: </strong>As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.</p><p><strong>Methods: </strong>Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (<i>DPYD</i>, <i>NUDT15</i>, <i>TPMT</i>, <i>UGT1A1</i>) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants. In a subset of 7,081 patients with cancer, <i>DPYD</i> variants were reported back to clinicians and outcomes were collected.</p><p><strong>Results: </strong>We identified clinically relevant PGx variants across the four genes in 62.7% of participants in our cohort. Extending this to annual prescription numbers in England for the drugs affected by these PGx variants, approximately 14,540 patients per year could potentially benefit from a reduced dose or alternative drug to reduce the risk of ADRs. Validating PGx associations in a real-world data set, we found a significant association between PGx variants in <i>DPYD</i> and toxicity-related phenotypes in patients treated with capecitabine or fluorouracil. Reported <i>DPYD</i> variants were deemed informative for clinical decision making in a majority of cases.</p><p><strong>Conclusion: </strong>Reporting PGx variants from germline WGS relevant to patients with cancer alongside primary findings related to their cancer can be clinically informative, informing prescribing to reduce the risk of ADRs. Extending the range of actionable variants to those found in patients of non-European ancestry is important and will extend the potential clinical impact.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"682-693"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Total Neoadjuvant Therapy With Selective Nonoperative Management for Locally Advanced Rectal Cancer: Analysis of Data From the Organ Preservation for Rectal Adenocarcinoma Trial.","authors":"Maria Widmar, Mason McCain, Akriti Mishra Meza, Charles Ternent, Andrew Briggs, Julio Garcia-Aguilar","doi":"10.1200/JCO.24.00681","DOIUrl":"10.1200/JCO.24.00681","url":null,"abstract":"<p><strong>Purpose: </strong>The clinical efficacy of total neoadjuvant therapy (TNT) followed by selective nonoperative management (NOM) for locally advanced rectal cancer (LARC) was examined in the Organ Preservation for Rectal Adenocarcinoma (OPRA) trial. We investigated the cost and quality-of-life implications of adopting this treatment approach.</p><p><strong>Methods: </strong>We analyzed clinical, cost, and quality-of-life outcomes for TNT with selective NOM in comparison with chemoradiotherapy (CRT)-surgery-adjuvant chemotherapy (standard of care [SOC]) using data from OPRA, prospective cohorts, and published studies. Cost-effectiveness was evaluated over varying willingness-to-pay thresholds, and sensitivity analyses evaluated cost-effectiveness for different surgical contexts and SOC variants as well as a 10-year time horizon.</p><p><strong>Results: </strong>SOC was dominated by TNT with selective NOM in the base case analysis. TNT in which CRT was followed by consolidation chemotherapy (CNCT) was the least costly at $89,712 in Medicare proportionate US dollars (MP$), followed by TNT in which induction chemotherapy was followed by CRT (INCT) at MP$90,259 and SOC at MP$98,755. INCT was the preferred strategy, with 4.56 quality-adjusted life years, followed by CNCT at 4.42 and SOC at 4.29. TNT with selective NOM dominated SOC in all sensitivity analyses except when SOC omitted adjuvant chemotherapy without an impact on disease-free survival. CNCT was more cost effective than SOC when the proportion of patients entering NOM after TNT was ≥22% or ≥43%, for SOC with and without adjuvant therapy, both well below the rates seen in OPRA.</p><p><strong>Conclusion: </strong>TNT with selective NOM is cost effective. The cost-effectiveness of CNCT with NOM relative to SOC is dependent on CNCT being made available to a sufficiently large proportion of patients with LARC. Additional analyses are needed to validate these findings from a societal perspective and in the context of other emerging treatment paradigms for LARC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"672-681"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557959","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":"Comment on the Definition and Interpretation of Complete Mesocolic Excision in the RELARC Trial.","authors":"Willemijn A Jongsma, Alexander A J Grüter, Boudewijn R Toorenvliet, Jurriaan B Tuynman, Pieter J Tanis","doi":"10.1200/JCO-24-02228","DOIUrl":"10.1200/JCO-24-02228","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"763-764"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813366","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":"ALK Tyrosine Kinase Inhibitors Induced Weight Gain: More Refined Definition of Weight Gain, Glucagon-Like Peptide-1 Agonist Treatment, and Therapeutic Drug Monitoring of <i>ALK+</i> Non-Small Cell Lung Cancer?","authors":"Cathleen June Park, Alexandria T M Lee, Sai-Hong Ignatius Ou","doi":"10.1200/JCO-24-02514","DOIUrl":"10.1200/JCO-24-02514","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"625-628"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949438","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 Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years.","authors":"Jianwei Zhang, Pan Chi, Lishuo Shi, Long Cui, Jinbo Gao, Wanglin Li, Hongbo Wei, Longqing Cheng, Zonghai Huang, Guangfu Cai, Ren Zhao, Zhongcheng Huang, Hongfeng Zhou, Yisheng Wei, Hao Zhang, Jian Zheng, Yan Huang, Yue Cai, Zhiyang Zhou, Liang Kang, Meijin Huang, Xiaojian Wu, Junsheng Peng, Donglin Ren, Ping Lan, Jianping Wang, Yanhong Deng","doi":"10.1200/JCO-24-01676","DOIUrl":"10.1200/JCO-24-01676","url":null,"abstract":"<p><p>We present 10-year results of the phase Ⅲ FOWARC trial, which evaluated the efficacy of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with or without radiation compared with fluorouracil with radiation in patients with locally advanced rectal cancer. A total of 495 patients age 18-75 years with stage Ⅱ-Ⅲ rectal cancer were randomly assigned to three treatment arms: fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, or mFOLFOX6 alone, followed by surgery and adjuvant chemotherapy. With a median follow-up of 10 years, the 10-year disease-free survival (DFS) rates were 52.5%, 62.6%, and 60.5%, respectively (<i>P</i> = .56). The 10-year locoregional recurrence (LR) rates were 10.8%, 8.0%, and 9.6% (<i>P</i> = .57), and the 10-year overall survival (OS) rates were 65.9%, 72.3%, and 73.4% (<i>P</i> = .90). Subgroup analysis identified ypTNM stage as a significant prognostic factor for DFS, LR, and OS (<i>P</i> < .0001, <i>P</i> < .006, <i>P</i> < .0001, respectively). Patients achieving pathologic complete response had 10-year DFS, LR, and OS rates of 84.3%, 3.0%, and 92.4%, respectively. No significant difference was observed in long-term survival outcome between mFOLFOX6 with and without radiation and fluorouracil plus radiation. These results demonstrate that neoadjuvant mFOLFOX6 chemotherapy can be considered as a therapeutic option in LARC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"633-640"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822265","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":"Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.","authors":"Evan Y Yu, R Bryan Rumble, Neeraj Agarwal, Heather H Cheng, Scott E Eggener, Rhonda L Bitting, Himisha Beltran, Veda N Giri, Daniel Spratt, Brandon Mahal, Kevin Lu, Tony Crispino, Edouard J Trabulsi","doi":"10.1200/JCO-24-02608","DOIUrl":"10.1200/JCO-24-02608","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.</p><p><strong>Methods: </strong>A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications.</p><p><strong>Results: </strong>A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials.</p><p><strong>Recommendations: </strong>Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor <i>v</i> metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"748-758"},"PeriodicalIF":42.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949490","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}