JCO precision oncology最新文献

{"title":"Palbociclib in Patients With Soft Tissue Sarcoma With <i>CDK4</i> Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study.","authors":"Scott Schuetze, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Funda Meric-Bernstam, Carmen J Calfa, Laura Catherine Farrington, Michael B Livingston, Kristopher Wentzel, Deepti Behl, Yelena Kier, Alissa S Marr, Margaret von Mehren, Joshua Z Press, Ramya Thota, Gina N Grantham, Abigail Gregory, Dominique C Hinshaw, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO.24.00219","DOIUrl":"10.1200/PO.24.00219","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (<i>CDK4</i>) amplification treated with palbociclib are reported.</p><p><strong>Methods: </strong>Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety.</p><p><strong>Results: </strong>Forty-two patients with <i>CDK4</i> amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported.</p><p><strong>Conclusion: </strong>Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and <i>CDK4</i> amplification.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400219"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and Practical Challenges in Applying National Comprehensive Cancer Network Guidelines for Suspected Pathogenic TP53 Mosaicism.","authors":"Daniel I Nathan, Tehilla Brander, Julie Gold, Deborah Paul, Paula Klein, Kit Cheng, Johnson M Liu, Bridget K Marcellino","doi":"10.1200/PO.24.00006","DOIUrl":"10.1200/PO.24.00006","url":null,"abstract":"<p><p>Benefits and limitations in using NCCN guidelines to distinguish TP53 CH from mosaic LFS.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400006"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization of Metastatic Oncocytoma With Exceptional Response to Treatment: A Case Report.","authors":"Bradley R Webster, Christopher J Ricketts, Cathy D Vocke, Dionna Gamble, Daniel R Crooks, Ye Yang, Lindsay Friedman, Antoun Toubaji, Pavlos Msaouel, Jonathan M Hernandez, W Marston Linehan, Mark W Ball","doi":"10.1200/PO.24.00188","DOIUrl":"10.1200/PO.24.00188","url":null,"abstract":"<p><p>Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400188"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Course and Treatment Outcomes in Patients With De Novo Small-Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 20 Insertion: Two Case Reports.","authors":"Lodovica Zullo, Elora Castanet, Zineb Maaradji, Maria Rosa Ghigna, Benjamin Bonhomme, Melissa Alamé, Benjamin Besse, Sophie Cousin, Mihaela Aldea","doi":"10.1200/PO.24.00257","DOIUrl":"https://doi.org/10.1200/PO.24.00257","url":null,"abstract":"<p><p>We report the first two cases of EGFR exon20ins SCLC, treated with amivantamab and TKIs.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400257"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations.","authors":"N Jewel Samadder, Emily Gay, Vanda Lindpere, Michelle L Bublitz, Lorelei A Bandel, Sebastian M Armasu, Robert A Vierkant, Matthew J Ferber, Eric W Klee, Nicholas B Larson, Teresa M Kruisselbrink, Jan B Egan, Jennifer L Kemppainen, Jessa S Bidwell, Jennifer L Anderson, Tammy M McAllister, T'Nita S Walker, Katie L Kunze, Michael A Golafshar, Margaret A Klint, Richard J Presutti, William V Bobo, Aleksander Sekulic, Jolene M Summer-Bolster, Cheryl L Willman, Konstantinos N Lazaridis","doi":"10.1200/PO.24.00106","DOIUrl":"https://doi.org/10.1200/PO.24.00106","url":null,"abstract":"<p><strong>Purpose: </strong>The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS.</p><p><strong>Methods: </strong>Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC (<i>BRCA1</i> and <i>BRCA1</i>) and LS (<i>MLH1</i>, <i>MSH2</i>, <i>MSH6</i>, <i>PMS2</i>, and <i>EPCAM</i>). Chart review was performed to collect demographics and personal and family cancer history.</p><p><strong>Results: </strong>To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% <i>BRCA1</i>, 42.8% <i>BRCA2</i>) and 163 with LS (12.3% <i>MSH6</i>, 8.8% <i>PMS2</i>, 4.5% <i>MLH1</i>, 3.8% <i>MSH2</i>, and 0.2% <i>EPCAM</i>). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% <i>v</i> 37.5%, <i>P</i> = .028).</p><p><strong>Conclusion: </strong>Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400106"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAPping Into PD-L1 Testing Efficiency for Gastroesophageal Cancer.","authors":"Brian S Henick, Ryan H Moy","doi":"10.1200/PO.24.00344","DOIUrl":"10.1200/PO.24.00344","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400344"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extrahepatic Cholangiocarcinoma: Genomic Variables Associated With Anatomic Location and Outcome.","authors":"William A Preston, Esther Drill, Thomas Boerner, Rebecca Gelfer, James J Harding, Eileen M O'Reilly, Andrea Cercek, Ghassan Abou-Alfa, Wungki Park, Vinod P Balachandran, Jeffrey Drebin, Kevin C Soares, Alice Wei, T Peter Kingham, Michael I D'Angelica, William R Jarnagin","doi":"10.1200/PO.24.00206","DOIUrl":"10.1200/PO.24.00206","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to define genomic differences between perihilar cholangiocarcinoma (PCA) and distal cholangiocarcinoma (DCA) and identify genomic determinants of survival.</p><p><strong>Materials and methods: </strong>Consecutive patients with ECA with tissue for targeted next-generation sequencing were analyzed, stratified by anatomic site (PCA/DCA), disease extent, and treatment. Associations between genomic alterations, clinicopathologic features, and outcomes were analyzed using Cox proportional hazards regression to compare survival.</p><p><strong>Results: </strong>In total, 224 patients diagnosed between 2004 and 2022 (n = 127 PCA; n = 97 DCA) met inclusion criteria. The median survival was 29 months (43 after resection and 17 from diagnosis for unresectable disease). Compared with PCA, DCA was enriched in <i>TP53alt</i> (alterations; 69% <i>v</i> 33%; <i>Q</i> < 0.01), epigenetic pathway alterations (45% <i>v</i> 29%; <i>Q</i> = 0.041), and had more total altered pathways (median 3 <i>v</i> 2; <i>Q</i> < 0.01). <i>KRASalt</i> frequency was similar between PCA (36%) and DCA (37%); however, DCA was enriched in <i>KRAS</i> G12D (19% <i>v</i> 9%; <i>P = .002</i>). No other clinicopathologic or genomic variables distinguished subtypes. In resected patients, no genomic alterations were associated with outcome. However, in unresectable patients, <i>CDKN2Aalt</i> (hazard ratio [HR], 2.59 [1.48 to 4.52]) and <i>APCalt</i> (HR, 5.11 [1.96 to 13.3]) were associated with reduced survival. For the entire cohort, irresectability (HR, 3.13 [2.25 to 4.36]), <i>CDKN2Aalt</i> (HR, 1.80 [1.80 to 2.68]), and <i>APCalt</i> (HR, 2.00 [1.04 to 3.87]) were associated with poor survival.</p><p><strong>Conclusion: </strong><i>CDKN2Aalt</i> and <i>APCalt</i> were associated with poor survival in ECA, primarily in advanced disease. As PCA and DCA were genetically similar, coanalysis of PCA and DCA in future genomic studies is reasonable.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400206"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion Challenges in Solid Tumors: Shaping the Landscape of Cancer Care in Precision Medicine.","authors":"Jibran Ahmed, Carlos Torrado, Anca Chelariu, Sun-Hee Kim, Jordi Rodon Ahnert","doi":"10.1200/PO.24.00038","DOIUrl":"10.1200/PO.24.00038","url":null,"abstract":"<p><p>Targeting actionable fusions has emerged as a promising approach to cancer treatment. Next-generation sequencing (NGS)-based techniques have unveiled the landscape of actionable fusions in cancer. However, these approaches remain insufficient to provide optimal treatment options for patients with cancer. This article provides a comprehensive overview of the actionability and clinical development of targeted agents aimed at driver fusions. It also highlights the challenges associated with fusion testing, including the evaluation of patients with cancer who could potentially benefit from testing and devising an effective strategy. The implementation of DNA NGS for all tumor types, combined with RNA sequencing, has the potential to maximize detection while considering cost effectiveness. Herein, we also present a fusion testing strategy aimed at improving outcomes in patients with cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400038"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Integrative Survival Prediction in Multiple Myeloma Patients Treated With Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation.","authors":"Manuela Hummel, Thomas Hielscher, Martina Emde-Rajaratnam, Hans Salwender, Susanne Beck, Christof Scheid, Uta Bertsch, Hartmut Goldschmidt, Anna Jauch, Jérôme Moreaux, Anja Seckinger, Dirk Hose","doi":"10.1200/PO.23.00613","DOIUrl":"10.1200/PO.23.00613","url":null,"abstract":"<p><strong>Purpose: </strong>Given the high heterogeneity in survival for patients with multiple myeloma, it would be clinically useful to quantitatively predict the individual survival instead of attributing patients to two to four risk groups as in current models, for example, revised International Staging System (R-ISS), R2-ISS, or Mayo-2022-score.</p><p><strong>Patients and methods: </strong>Our aim was to develop a quantitative prediction tool for individual patient's 3-/5-year overall survival (OS) probability. We integrated established clinical and molecular risk factors into a comprehensive prognostic model and evaluated and validated its risk discrimination capabilities versus R-ISS, R2-ISS, and Mayo-2022-score.</p><p><strong>Results: </strong>A nomogram for estimating OS probabilities was built on the basis of a Cox regression model. It allows one to translate the individual risk profile of a patient into 3-/5-year OS probabilities by attributing points to each prognostic factor and summing up all points. The nomogram was externally validated regarding discrimination and calibration. There was no obvious bias or overfitting of the prognostic index on the validation cohort. Resampling-based and external evaluation showed good calibration. The c-index of the model was similar on the training (0.76) and validation cohort (0.75) and significantly higher than for the R-ISS (<i>P</i> < .001) or R2-ISS (<i>P</i> < .01).</p><p><strong>Conclusion: </strong>In summary, we developed and validated individual quantitative nomogram-based OS prediction. Continuous risk assessment integrating molecular prognostic factors is superior to R-ISS, R2-ISS, or Mayo-2022-score alone.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2300613"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers in Oncology: Complexities in Biomarker-Driven Studies and Statistical Analysis.","authors":"Hajime Uno, Miki Horiguchi","doi":"10.1200/PO.24.00358","DOIUrl":"10.1200/PO.24.00358","url":null,"abstract":"<p><p>Biomarker-driven trials are key for precision oncology but challenge design and analysis.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400358"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}