Journal of Clinical Oncology最新文献

{"title":"Molecular and Clinicopathologic Impact of GNAS Variants Across Solid Tumors.","authors":"Paul Johannet, Somer Abdelfattah, Callahan Wilde, Shrey Patel, Henry Walch, Benoit Rousseau, Guillem Argiles, Oliver Artz, Miteshkumar Patel, Andrea Arfe, Andrea Cercek, Rona Yaeger, Karuna Ganesh, Nikolaus Schultz, Luis A Diaz, Michael B Foote","doi":"10.1200/JCO.24.00186","DOIUrl":"10.1200/JCO.24.00186","url":null,"abstract":"<p><strong>Purpose: </strong>The molecular drivers underlying mucinous tumor pathogenicity are poorly understood. <i>GNAS</i> mutations predict metastatic burden and treatment resistance in mucinous appendiceal adenocarcinoma. We investigated the pan-cancer clinicopathologic relevance of <i>GNAS</i> variants.</p><p><strong>Methods: </strong>We assessed 58,043 patients with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT)-sequenced solid tumors to identify oncogenic variants, including <i>GNAS</i>, associated with mucinous tumor phenotype. We then performed comprehensive molecular analyses to compare <i>GNAS-</i>mutant (mut) and wild-type tumors across cancers. Gene expression patterns associated with <i>GNAS-</i>mut tumors were assessed in a The Cancer Genome Atlas cohort. Associations between <i>GNAS</i> variant status and peritoneal metastasis, first-line systemic therapy response, progression-free survival (PFS), and overall survival (OS) were determined using a propensity-matched subcohort of patients with metastatic disease.</p><p><strong>Results: </strong>Mucinous tumors were enriched for oncogenic <i>GNAS</i> variants. <i>GNAS</i> was mutated in >1% of small bowel, cervical, colorectal, pancreatic, esophagogastric, hepatobiliary, and GI neuroendocrine cancers. Across these cancers, <i>GNAS-</i>mut tumors exhibited a generally conserved C-to-T mutation-high, aneuploidy-low molecular profile with co-occurring prevalent <i>KRAS</i> variants (65% of GNAS-mut tumors) and fewer <i>TP53</i> alterations. <i>GNAS-</i>mut tumors exhibited recurrently comutated alternative tumor suppressors (<i>RBM10</i>, <i>INPPL1</i>) and upregulation of MAPK and cell surface modulators. <i>GNAS-</i>mut tumors demonstrate an increased prevalence of peritoneal metastases (odds ratio [OR], 1.7 [95% CI, 1.1 to 2.5]; <i>P =</i> .006), worse response to first-line systemic therapy (OR, 2.2 [95% CI, 1.3 to 3.8]; <i>P =</i> .003), and shorter PFS (median, 5.6 <i>v</i> 7.0 months; <i>P =</i> .047). In a multivariable analysis, <i>GNAS</i> mutated status was independently prognostic of worse OS (hazard ratio, 1.25 [95% CI, 1.01 to 1.56]; adjusted <i>P =</i> .04).</p><p><strong>Conclusion: </strong>Across the assessed cancers, <i>GNAS-</i>mut tumors exhibit a conserved molecular and clinical phenotype defined by mucinous tumor status, increased peritoneal metastasis, poor response to first-line systemic therapy, and worse survival.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3847-3857"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909805","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":"Stockholm3 in a Multiethnic Cohort: Optimizing Prostate Cancer Screening to Reduce Harm and Improve Equity.","authors":"James D Brooks","doi":"10.1200/JCO.24.00941","DOIUrl":"10.1200/JCO.24.00941","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3768-3772"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371963","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":"Establishing a Role for Local Therapy in Oligometastatic Pancreatic Cancer.","authors":"Hannah J Roberts, Colin D Weekes, Jennifer Y Wo","doi":"10.1200/JCO-24-01264","DOIUrl":"10.1200/JCO-24-01264","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3765-3767"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371960","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 Sonic Hedgehog Inhibitors Combined With Radiotherapy Is a Promising Strategy for Locally Advanced Basal Cell Carcinoma.","authors":"Marie Boileau, Alexandre Taillez, Pauline Lemoine, Manon Dubois, Laurent Mortier, Xavier Mirabel","doi":"10.1200/JCO.24.01042","DOIUrl":"10.1200/JCO.24.01042","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3882-3883"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878773","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":"Breast Cancer Screening Interval: Effect on Rate of Late-Stage Disease at Diagnosis and Overall Survival.","authors":"Margarita L Zuley, Andriy I Bandos, Stephen W Duffy, Durwin Logue, Rohit Bhargava, Priscilla F McAuliffe, Adam M Brufsky, Robert M Nishikawa","doi":"10.1200/JCO.24.00285","DOIUrl":"10.1200/JCO.24.00285","url":null,"abstract":"<p><strong>Purpose: </strong>Controversy continues regarding the effect of screening mammography on breast cancer outcomes. We evaluated late-stage cancer rate and overall survival (OS) for different screening intervals using a real-world institutional research data mart.</p><p><strong>Methods: </strong>Patients having both a cancer registry record of new breast cancer diagnosis and prediagnosis screening history between 2004 and 2019 were identified from our institutional research breast data mart. Time interval between the two screening mammograms immediately preceding diagnosis and the time to cancer diagnosis were determined. Screening interval was deemed annual if ≤15 months, biennial if >15 and ≤27 months, intermittent if >27 months, and baseline if only one prediagnosis screen was known. The primary end point was late-stage cancer (TNM stage IIB or worse), and the secondary end point was OS. The association of screening interval and late-stage cancer was analyzed using multivariable logistic regression adjusting for prediagnosis characteristics. Proportional hazards regression was used for survival analysis. Potential lead time was analyzed using survival from a uniform fixed time point.</p><p><strong>Results: </strong>In total, 8,145 patients with breast cancer had prediagnosis screening mammography in the timeframe. The percentage of late-stage cancers diagnosed increased significantly with screening interval with 9%, 14%, and 19% late stages for annual, biennial, and intermittent groups (<i>P</i> < .001), respectively. The trend persisted regardless of age, race, and menopausal status. Biennial and intermittent groups had substantially worse OS than the annual screened group, with relative hazards of 1.42 (95% CI, 1.11 to 1.82) and 2.69 (95% CI, 2.11 to 3.43), respectively, and 1.39 (95% CI, 1.08 to 1.78) and 2.01 (95% CI, 1.58 to 2.55) after adjustment for potential lead time.</p><p><strong>Conclusion: </strong>Annual mammographic screening was associated with lower risk of late-stage cancer and better OS across clinical and demographic subgroups. Our study suggests benefit of annual screening for women 40 years and older.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3837-3846"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017670","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":"Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.","authors":"Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang","doi":"10.1200/JCO.24.00081","DOIUrl":"10.1200/JCO.24.00081","url":null,"abstract":"<p><strong>Purpose: </strong>The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures.</p><p><strong>Results: </strong>Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (<i>P</i> = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS.</p><p><strong>Conclusion: </strong>This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3795-3805"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893511","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":"Equipoise Lost? Trial Conduct Challenges in an Era of Breakthrough Therapies.","authors":"Jaleh Fallah, Flora Mulkey, Mallorie H Fiero, Haley Gittleman, Chi Song, Jeevan Puthiamadathil, Anup Amatya, Sundeep Agrawal, Paz Vellanki, Daniel L Suzman, Harpreet Singh, Laleh Amiri-Kordestani, Pallavi Mishra-Kalyani, Richard Pazdur, Paul G Kluetz","doi":"10.1200/JCO-24-01200","DOIUrl":"10.1200/JCO-24-01200","url":null,"abstract":"<p><p>FDA Oncology Center's @Falleh_Fallah and colleagues discuss loss of equipoise and other trial conduct challenges in an era of breakthrough therapies - via @JCO_ASCO.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3783-3787"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288213","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":"Structural Racism and Treatment Delay Among Black and White Patients With Breast Cancer.","authors":"Katherine E Reeder-Hayes, Bradford E Jackson, Tzy-Mey Kuo, Chris D Baggett, Juan Yanguela, Matthew R LeBlanc, Mya L Roberson, Stephanie B Wheeler","doi":"10.1200/JCO.23.02483","DOIUrl":"10.1200/JCO.23.02483","url":null,"abstract":"<p><strong>Purpose: </strong>Structural racism (SR) is a potential driver of health disparities, but research quantifying its impacts on cancer outcomes has been limited. We aimed to develop a multidimensional county-level SR measure and to examine the association of SR with breast cancer (BC) treatment delays among Black and White patients.</p><p><strong>Methods: </strong>The cohort included 32,095 individuals from the North Carolina Central Cancer Registry with stage I to III BC diagnosed between 2004 and 2017 and linked to multipayer insurance claims from the Cancer Information and Population Health Resource. County-level data were drawn from multiple public sources aggregated in the Robert Wood Johnson County Health Rankings database. Racial gaps in eight social determinants across five domains were quantified at the county level and ranked on a 0-100 minimum-maximum scale. Domain scores were averaged to create a SR Composite Index (SRCI) score. We used multilevel logistic regression with random intercepts and multiple cross-level interaction terms to evaluate the association between county-level SRCI and patient-level treatment delays, adjusting for patient-level characteristics and stratified by race.</p><p><strong>Results: </strong>The SRCI score ranged from 21 to 75 with a median (IQR) of 39.0 (31.8, 45.7). For Black patients, a 10-unit increase in SRCI score was associated with increased odds of delay (Adjusted odds ratios [aOR], 1.25; 95% confidence limits [CL], 1.08 to 1.45). No such association was found for White patients (OR, 1.05; 95% CL, 0.97 to 1.15).</p><p><strong>Conclusion: </strong>Area-level SR measured by a composite index is associated with higher odds of BC treatment delays among Black, but not White patients. Increasing county-level SR is associated with increasing Black-White disparities in treatment delay. Further research is needed to refine the measurement of SR and to examine its association with other cancer care disparities.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3858-3866"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897547","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":"Erratum: CML and the WHO: Why?","authors":"","doi":"10.1200/JCO-24-02083","DOIUrl":"10.1200/JCO-24-02083","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3885"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375489","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":"Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial.","authors":"Hari T Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A Hubbard, Nathan Perlis, Michael R Abern, Daniel M Moreira, Scott Eggener, Paul Yonover, Alexander K Chow, Kara Watts, Michael A Liss, Gregory R Thoreson, Andre L Abreu, Geoffrey A Sonn, Thorgerdur Palsdottir, Anna Plym, Fredrik Wiklund, Henrik Grönberg, Adam B Murphy","doi":"10.1200/JCO.24.00152","DOIUrl":"10.1200/JCO.24.00152","url":null,"abstract":"<p><strong>Purpose: </strong>Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort.</p><p><strong>Methods: </strong>An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity).</p><p><strong>Results: </strong>A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups.</p><p><strong>Conclusion: </strong>In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"3806-3816"},"PeriodicalIF":42.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748338","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}