JCO precision oncology最新文献

{"title":"Optimizing Radiotherapy Timing for Nasopharyngeal Carcinoma: The Impact of Radiation Scheduling on Survival.","authors":"Ying Li, Youliang Weng, Zongwei Huang, Lishui Wu, Siqi Xu, Yingjie Xie, Haolan Li, Jinghua Lai, Dan Hu, Sufang Qiu","doi":"10.1200/PO-24-00603","DOIUrl":"10.1200/PO-24-00603","url":null,"abstract":"<p><strong>Purpose: </strong>Chronoradiobiology has emerged as a potential field of study with therapeutic implications for cancer treatment. We aimed to investigate the association between radiation chronotherapy and the efficacy and toxicity of patients with nasopharyngeal carcinoma (NPC).</p><p><strong>Patients and methods: </strong>Patients with nonmetastatic NPC treated with intensity-modulated radiotherapy in Fujian Cancer Hospital between January 2017 and December 2019 were included. Propensity score matching (PSM) with 1:1:1 was used to account for selection bias. Cox regression analysis was performed to explore the impact of radiotherapy timing on patient survival. Sensitivity analysis was implemented to determine the size and directional stability.</p><p><strong>Results: </strong>One thousand forty patients met study inclusion criteria and 332 patients were included in a PSM cohort. In the unmatched cohort analysis, morning radiotherapy exhibited a significantly superior overall survival (OS) outcome (hazard ratio [HR], 0.60 [95% CI, 0.40 to 0.91], adjusted log-rank <i>P</i> = .028) than the afternoon one. After PSM analysis, it was observed that individuals undergoing radiotherapy in the afternoon group (HR, 5.88 [95% CI, 2.55 to 13.58], adjusted log-rank <i>P</i> = .004) and the night group (HR, 4.81 [95% CI, 1.91 to 12.11], adjusted log-rank <i>P</i> = .018) displayed a tendency toward shorter OS compared with the morning group. No significant differences in acute treatment-related adverse effects were observed among the three groups. Morning radiotherapy demonstrated consistent robustness in the multivariable analysis, thereby establishing an association with higher OS. The directionality of the effect size was consistent across sensitivity analysis.</p><p><strong>Conclusion: </strong>These results underscore the potential benefits of scheduling radiotherapy in the morning for NPC management, although prospective studies are needed to confirm these findings.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400603"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948851","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":"Reply to: Addressing Bias in Feature Importance: A Hybrid Approach for Risk Prediction in Prognostic Survival Models.","authors":"Ge Zhang, Shiqian Zhang, Haonan Zhang, Ruhao Wu, Haoze Zheng","doi":"10.1200/PO-24-00875","DOIUrl":"https://doi.org/10.1200/PO-24-00875","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400875"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948919","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":"Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.","authors":"Stephen J Luen, Lauren C Brown, Courtney T van Geelen, Peter Savas, Roswitha Kammler, Patrizia Dell'Orto, Olivia Biasi, Alan S Coates, Richard D Gelber, Beat Thürlimann, Marco Colleoni, Gini F Fleming, Prudence A Francis, Meredith M Regan, Giuseppe Viale, Sherene Loi","doi":"10.1200/PO-24-00599","DOIUrl":"10.1200/PO-24-00599","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.</p><p><strong>Methods: </strong>This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.</p><p><strong>Results: </strong>A total of 1,795 tumors were evaluable for this study (BIG 1-98 n = 520, SOFT n = 1,275). The frequency of HER2-low tumors was 37% and 21% in the postmenopausal BIG 1-98 and premenopausal SOFT cohorts, respectively. There were no significant differences in clinicopathologic variables between HER2-low and HER2-zero groups which was consistent across both trials. There was no significant difference in risk of distant recurrence for patients with HER2-low tumors versus HER2-zero tumors (5-year % distant recurrence-free 94.0% <i>v</i> 92.8%, <i>P</i> = .61, in BIG 1-98; 89.4% <i>v</i> 92.7%, <i>P</i> = .31, in SOFT, respectively). Somatic genomic profiles were similar with the exception of <i>MAP3K1</i> mutations which were more frequent in HER2-zero tumors (BIG 1-98 19% <i>v</i> 5%, SOFT 11% <i>v</i> 6%). Both <i>ERBB2</i> copy number and <i>ERBB2</i> gene expression abundance were significantly higher in HER2-low tumors compared with HER2-zero tumors; however, the absolute difference was small. Correlation between <i>ERBB2</i> copy number values and gene expression was modest (<i>r</i> = 0.17).</p><p><strong>Conclusion: </strong>In two large clinical trials with centrally reviewed HER2 IHC, our findings do not support HER2-low breast cancer as a distinct clinical or biologic entity among HR+HER2- early breast cancers. Absolute differences in median <i>ERBB2</i> copy number levels or gene expression are small and of unclear biologic relevance.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400599"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033114","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":"Coding Variants of the Genitourinary Development Gene <i>WNT9B</i> Carry High Risk for Prostate Cancer.","authors":"William D Dupont, Angela L Jones, Jeffrey R Smith","doi":"10.1200/PO-24-00569","DOIUrl":"10.1200/PO-24-00569","url":null,"abstract":"<p><strong>Purpose: </strong>Considerable genetic heterogeneity is currently thought to underlie hereditary prostate cancer (HPC). Most families meeting criteria for HPC cannot be attributed to currently known pathogenic variants.</p><p><strong>Methods: </strong>To discover pathogenic variants predisposing to prostate cancer, we conducted a familial case-control association study using both genome-wide single-allele and identity-by-descent analytic approaches. Sequence of high-risk haplotype carriers was used for variant detection. Candidate pathogenic variants were tested for association with prostate cancer across independent biobanks for replication of observations.</p><p><strong>Results: </strong>Pathogenic variants within <i>WNT9B</i> were associated with familial prostate cancer and observations replicated within four of four independent biobanks. <i>WNT9B</i> E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing a half million patients. <i>WNT9B</i> Q47R was also associated with prostate cancer with genome-wide significance among Finns, for which identity-by-descent analyses confirmed a founder effect. <i>WNT9B</i> shares an unexpected commonality with the previously established prostate cancer risk genes <i>HOXB13</i> and <i>HNF1B</i>: they are each required for embryonic prostate development. With this recognition, we further evaluated two additional genes known to cause Mendelian genitourinary developmental defects, <i>KMT2D</i> and <i>DHCR7</i>. These too were nominally associated with prostate cancer under meta-analyses.</p><p><strong>Conclusion: </strong><i>WNT9B</i> and additional genes that are required for early genitourinary development are also involved in the later development of prostate cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400569"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059086","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":"Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.","authors":"Matthew Dankner, Emmanuelle Rousselle, Sarah Petrecca, François Fabi, Alexander Nowakowski, Anna-Maria Lazaratos, Charles Vincent Rajadurai, Andrew J B Stein, David Bian, Peter Tai, Alicia Belaiche, Meredith Li, Andrea Quaiattini, Nicola Normanno, Maria Arcila, Arielle Elkrief, Douglas B Johnson, Marc Ladanyi, April A N Rose","doi":"10.1200/PO.24.00199","DOIUrl":"10.1200/PO.24.00199","url":null,"abstract":"<p><strong>Purpose: </strong>MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined. We sought to characterize the genomic and clinical landscape of MAP2K1 mutant tumors to evaluate the relationship between MAP2K1 mutation class and clinical activity of MAPKi.</p><p><strong>Methods: </strong>We interrogated American Association for Cancer Research (AACR) GENIE (v13) to analyze solid tumors with MAP2K1 mutations. We performed a systematic review and meta-analysis of published reports of patients with MAP2K1-mutant cancers treated with MAPKi according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary end point was progression-free survival (PFS), and secondary end points were overall treatment response rate (ORR), duration of response (DOR), and overall survival.</p><p><strong>Results: </strong>In the AACR GENIE data set, class 2 MAP2K1 mutations (63%) were more prevalent than class 1 (24%) and class 3 (13%) mutations (<i>P</i> < .0001). Co-occurring MAPK pathway-activating mutations were more likely to occur in class 1 versus class 2 or 3 MAP2K1-mutant tumors (<i>P</i> < .0001). Our systematic meta-analysis of the literature identified 46 patients with MAP2K1-mutant tumors who received MAPKi. In these patients, ORR was 28% and median PFS was 3.9 months. ORR did not differ according to MAP2K1 mutation class or cancer type. However, patients with class 2 mutations experienced longer PFS (5.0 months) and DOR (23.8 months) compared with patients with class 1, 3, or unclassified MAP2K1 mutations (PFS 3.5 months, <i>P</i> = .04; DOR 4.2 months, <i>P</i> = .02).</p><p><strong>Conclusion: </strong>Patients with class 2 MAP2K1 mutations represent a novel subgroup that may derive benefit from MAPKi. Prospective clinical studies with novel MAPKi regimens are warranted in these patients.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400199"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052677","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":"Addressing Bias in Feature Importance: A Hybrid Approach for Risk Prediction in Prognostic Survival Models.","authors":"Yoshiyasu Takefuji","doi":"10.1200/PO-24-00785","DOIUrl":"https://doi.org/10.1200/PO-24-00785","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400785"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949296","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":"Leveraging Artificial Intelligence to Improve Risk Stratification in Nonmetastatic Castration-Resistant Prostate Cancer.","authors":"Charles B Nguyen, Tanya B Dorff","doi":"10.1200/PO-24-00877","DOIUrl":"https://doi.org/10.1200/PO-24-00877","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400877"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070899","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":"Quantitation of Plasma Proteins to Predict Taxane-Induced Peripheral Neuropathy.","authors":"Nam Nguyen-Hoang, Yaping Liu, N Lynn Henry, Manjunath P Pai, Hao-Jie Zhu, Daniel L Hertz","doi":"10.1200/PO-24-00380","DOIUrl":"10.1200/PO-24-00380","url":null,"abstract":"<p><strong>Purpose: </strong>Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting toxicity of paclitaxel in patients with cancer. TIPN prediction is challenging although patients with higher systemic paclitaxel exposure have higher TIPN risk. This study aimed to identify protein predictors of TIPN and paclitaxel pharmacokinetics (PK).</p><p><strong>Methods: </strong>This is a retrospective analysis of a prospective study of females with early-stage breast cancer receiving weekly paclitaxel. TIPN was assessed using the sensory subscale of the European Organisation for Research and Treatment of Cancer QLQ-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 (CIPN8). A blood sample was collected within 10 minutes before the end of the first paclitaxel infusion to measure plasma proteins using liquid chromatography-mass spectrometry and to estimate maximum systemic paclitaxel concentration (<i>C</i>_max). A second sample was collected approximately 24 hours after the first infusion to estimate paclitaxel time above threshold (<i>T</i>_{<i>c</i>>0.05}). Linear mixed-effect and regression models were used to identify proteins predictive of TIPN and paclitaxel PK parameters, respectively, using a Bonferroni-adjusted α = .0006.</p><p><strong>Results: </strong>Data from 36 participants were included in the analysis testing associations of 83 proteins with TIPN or PK. Higher levels of complement C3 were associated with more severe TIPN trajectories (<i>P</i> = .0002). No proteins were associated with either <i>C</i>_max or <i>T</i>_{<i>c</i>>0.05} (all <i>P</i> > .0006).</p><p><strong>Conclusion: </strong>Complement C3 concentration at the end of initial paclitaxel infusion may be useful for identifying patients with breast cancer and potentially other tumor types who could benefit from TIPN prevention strategies to improve long-term treatment outcomes.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400380"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070901","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":"Genomic and Immune Landscape of Non-Small Cell Lung Cancer Brain Metastases.","authors":"Manlu Liu, Justin C Jagodinsky, S Carson Callahan, Rachel L Minne, D Bryan Johnson, Scott A Tomlins, Gopal Iyer, Andrew M Baschnagel","doi":"10.1200/PO-24-00690","DOIUrl":"https://doi.org/10.1200/PO-24-00690","url":null,"abstract":"<p><strong>Purpose: </strong>Metastatic spread of non-small cell lung cancer (NSCLC) to the brain is a commonly occurring and challenging clinical problem, often resulting in patient mortality. Systemic therapies including immunotherapy have modest efficacy in treating brain metastases. Moreover, the local immune environment of brain metastases remains poorly described. This study aims to understand the genomic and immune landscape of NSCLC brain metastases.</p><p><strong>Methods: </strong>A total of 3,060 patients with NSCLC sequenced with the Strata Select assay on the Strata Oncology Platform were analyzed. Genomic alterations, tumor mutation burden (TMB), <i>PD-L1</i> expression, and immune gene expression were compared across different tissue sites and histologies and within brain metastases.</p><p><strong>Results: </strong>A significant increase in TMB was observed in the brain metastasis samples compared with nonbrain metastasis samples. Mutations in <i>TP53</i>, <i>KRAS</i>, and <i>CDKNA2A</i> were more prevalent within the brain metastasis cohort compared with other tissue locations. In addition, <i>PD-L1</i> expression was significantly decreased within brain metastasis samples compared with other sites. The overall immune landscape within the brain metastasis samples was largely reduced compared with primary lung samples. However, an immune-enriched brain metastasis cohort was identified with higher expressions of <i>PD-L1</i> and other immune-related genes.</p><p><strong>Conclusion: </strong>The overall TMB is increased within brain metastases compared with primary lung and other metastasis sites and is associated with a markedly diminished overall immune landscape. The identification of an immune-enriched brain metastasis subgroup suggests potential heterogeneity within the brain metastasis patient cohort, which might have implications for the development of targeted therapies.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400690"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472509","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":"Molecular Profiling of Biliary Tract Cancers in African American and Caucasian Patients.","authors":"Zishuo Ian Hu, Dean C Pavlick, Jeffrey S Ross, Sunyoung S Lee, Madhulika Eluri, Milind Javle","doi":"10.1200/PO-24-00712","DOIUrl":"10.1200/PO-24-00712","url":null,"abstract":"<p><strong>Purpose: </strong>Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancers. BTCs have a number of genomic alterations, including isocitrate dehydrogenase 1 (<i>IDH1</i>) mutations, fibroblast growth factor receptor 2 (<i>FGFR2</i>) rearrangements, and <i>ERBB2</i> amplifications. Therapies targeting these alterations have shown clinical benefit in patients with BTCs in the United States. However, molecular differences between races in BTCs are largely unknown. In particular, the genomic profiles of African American (AA) patients with BTCs have been infrequently reported. We sought to identify key genomic differences between AA and Caucasian patients with BTCs in the United States in the Foundation Medicine and American Association for Cancer Research (AACR) GENIE databases.</p><p><strong>Methods: </strong>BTC patients from AA and Caucasian patients from the Foundation Medicine and AACR GENIE databases were retrospectively reviewed. BTCs were divided into ICC, ECC, and GBCs in the Foundation Medicine database. BTCs were divided into cholangiocarcinomas and GBCs in the AACR GENIE database.</p><p><strong>Results: </strong>The mean age of AA patients with BTCs was lower compared with Caucasians. <i>TP53</i> and <i>FGFR2</i> alterations were significantly more frequent in AA patients compared with Caucasian patients with BTCs. <i>IDH1</i> mutations in Caucasian patients with BTCs were double that of AA patients.</p><p><strong>Conclusion: </strong>The results of this study suggest that significant genomic differences exist between races and warrant further investigation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400712"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948846","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}