JCO precision oncology最新文献

{"title":"Enhanced Detection of Druggable Mutations in Non-Small Cell Lung Cancer Using Targeted Collection of Bronchial Washing Fluid Compared With Plasma and Tumor Tissue.","authors":"Mi-Hyun Kim, Soo Han Kim, Hayoung Seong, Jung Seop Eom","doi":"10.1200/PO-25-00299","DOIUrl":"10.1200/PO-25-00299","url":null,"abstract":"<p><strong>Purpose: </strong>Next-generation sequencing (NGS) has become the gold standard for the molecular testing of patients with non-small cell lung cancer (NSCLC). This prospective study evaluated the performance of NGS using cell-free tumor DNA (ctDNA) extracted from bronchial washing fluid (BWF) collected via a targeted washing technique to detect druggable mutations.</p><p><strong>Materials and methods: </strong>All study participants simultaneously underwent NGS using three sample types: (1) BWF, (2) plasma, and (3) tumor tissue collected during bronchoscopy. The full patient set (FPS) included all enrolled patients, whereas the analysis intent group (AIG) included patients who underwent successful NGS across all specimen types (BWF, plasma, and tissue).</p><p><strong>Results: </strong>Sixty and 50 patients were included in the FPS and AIG groups, respectively. In FPS, the detection rate of druggable mutations in BWF using NGS was 65%, which was significantly higher than that of plasma (47%) and tissue samples (48%; <i>P</i> = .003 and <i>P</i> = .002, respectively). In the AIG, the concordance rate for detecting druggable mutations between BWF and tissue samples was 94%. In addition, the detection rate of co-occurring genetic alterations in BWF using NGS was significantly higher than that in plasma samples (92% <i>v</i> 64%, <i>P</i> = .001), whereas it was comparable with that in tissue samples (92% <i>v</i> 94%, <i>P</i> = 1.000). No significant adverse events occurred during the BWF collection.</p><p><strong>Conclusion: </strong>NGS using ctDNA from BWF obtained through a targeted washing technique is a feasible and reliable method for genomic profiling of NSCLC, providing a promising approach for identifying druggable mutations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500299"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764914","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":"Using Dose-Escalation and -Expansion Cohort Study as Pivotal Trial for Targeted Anticancer Drug Approval.","authors":"Yafang Huang, Ting Zhu, Jinjia Zhong, Jinqiu Yuan","doi":"10.1200/PO-25-00253","DOIUrl":"10.1200/PO-25-00253","url":null,"abstract":"<p><p>Early-phase clinical trials (EPCTs) have been increasingly adopted as the pivotal trial to support US Food and Drug Administration (FDA) approval of novel anticancer drugs. Among EPCT designs, dose-escalation and -expansion cohort (DEEC) substantially reduces the time and resources that are required in the traditional three-phase paradigm. DEEC facilitates expedited approvals of investigational drugs, particularly those targeting novel mechanisms, helping to address the pressing needs of patients with cancer. From 2012 to 2023, DEECs provided pivotal trial evidence that supported the FDA approval for 46 indications across 36 targeted anticancer drugs. Dose escalation uses 3 + 3, Bayesian optimal interval design, or continual reassessment method to explore the optimal dose level, whereas expansion cohorts directly incorporate dose-escalation cohort at the recommended phase II dose level. Expansion cohorts adopt flexible designs such as basket, umbrella, and platform trials. In addition, each expansion cohort in DEEC often uses adaptive approaches, such as Simon's two-stage design. To avoid the bias of end point assessment, conducting DEEC trials requires end point adjudication, often by an independent review committee. The design, conduct, and analysis of DEEC trials each have distinct characteristics. However, these characteristics were often overlooked in DEEC reporting. We reviewed the structural domains and items in trial design and conduct and discussed the strengths and limitations of DEEC studies, aiming to enhance the utilization of this trial design to generate higher-quality clinical evidence and ultimately contribute to better outcomes for patients with cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500253"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764917","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":"Prognostic Indicators of Preoperative Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Efficacy in Locally Advanced Gastroesophageal and Gastric Cancer: Integrating Biomarker Analysis and Clinicopathological Factors.","authors":"Amane Jubashi, Izuma Nakayama, Naoya Sakamoto, Shogo Takei, Yuki Matsubara, Yu Miyashita, Seiya Sato, Shinpei Ushiyama, Akinori Kobayashi, Ukyo Okazaki, Dai Okemoto, Kazumasa Yamamoto, Saori Mishima, Daisuke Kotani, Akihito Kawazoe, Tadayoshi Hashimoto, Yoshiaki Nakamura, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Takeshi Kuwata, Kazuma Sato, Takeo Fujita, Mitsumasa Yoshida, Masahiro Yura, Takahiro Kinoshita, Kohei Shitara","doi":"10.1200/PO-24-00925","DOIUrl":"10.1200/PO-24-00925","url":null,"abstract":"<p><strong>Purpose: </strong>Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is a standard treatment for locally advanced gastric/gastroesophageal junction cancer (GC/GEJC). The impact of biomarker status on the efficacy of perioperative FLOT remains unclear. This study evaluated the association between clinicopathological features, including biomarker status, and the efficacy of perioperative FLOT in patients with resectable GC/GEJC.</p><p><strong>Patients and methods: </strong>A retrospective observational study was conducted by reviewing medical records of patients treated with perioperative FLOT between February 2020 and March 2024. Eligible patients had histologically confirmed adenocarcinoma, resectable disease at stages cT2-4a and/or N0-3, M0, and underwent biomarker testing.</p><p><strong>Results: </strong>Among 116 eligible patients, human epidermal growth factor receptor 2 (HER2) positivity was observed in 7.8%, whereas PD-L1 combined positive score (CPS) of ≥1, ≥5, and ≥10 was detected in 90.5%, 44.0%, and 15.5% of patients, respectively. Claudin-18 isoform 2 (CLDN18.2) positivity (2+/3+ in ≥75% of tumor cells) was observed in 30.2% of patients. Major pathological response (MPR) and pathological complete response (pCR) rates were 22.4% (95% CI, 15.3 to 31.0) and 8.6% (95% CI, 4.2 to 15.3), respectively. Diffuse-type histology was a negative indicator for pathological response. CLDN18.2 expression decreased significantly after preoperative FLOT, with the median H-score declining from 285.0 to 187.5 (<i>P</i> < .001) in patients with CLDN18.2 positivity at initiation. Maintained CLDN18.2 positivity was more frequently observed in patients without MPR compared with those with MPR (53.8% <i>v</i> 12.5%, <i>P</i> = .05).</p><p><strong>Conclusion: </strong>HER2, PD-L1, and CLDN18.2 statuses were not linked to pathological response to FLOT in resectable GC/GEJC. CLDN18.2 expression significantly decreased after preoperative FLOT but remained higher in patients without MPR, suggesting that CLDN18.2-targeted therapy may warrant investigation in the perioperative setting.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400925"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764916","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":"Mucin 16-Directed Therapy in Pediatric Sarcomas: Case Evidence of Ubamatamab Efficacy in Epithelioid Sarcoma and Its Implications for Other Sarcoma Subtypes.","authors":"Denise M Connolly, Gabriel Revon-Rivière, Rose Chami, Denise Mills, Ailish C Coblentz, Thomas S Uldrick, David A Knorr, Priscila Goncalves, Michael Dobosz, Sumreen Jalal, Sarah Cohen-Gogo, Daniel A Morgenstern","doi":"10.1200/PO-25-00404","DOIUrl":"10.1200/PO-25-00404","url":null,"abstract":"<p><strong>Purpose: </strong>Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) are rare soft tissue sarcomas with poor prognoses. Although mucin 16 (MUC16) and its soluble form, cancer antigen 125 (CA125), are established as biomarkers and therapeutic targets in ovarian cancer, emerging data suggest MUC16 may also be expressed in ES and MRT. In this study, we present a patient with ES, who demonstrated a response to ubamatamab, a novel bispecific T-cell engager (MUC16xCD3), and analyze treatment resistance after disease progression. Additionally, we examine MUC16 expression across pediatric and adolescent and young adult (AYA) sarcomas, to evaluate the frequency of this target and explore the broader application of ubamatamab in this population.</p><p><strong>Materials and methods: </strong>We performed a retrospective clinical case review and immunohistochemical analysis of pediatric and AYA (0-25 years) sarcoma samples from 2015 to 2021, evaluating MUC16 expression using anti-CA125 immunohistochemistry (IHC) on the DAKO Omnis platform.</p><p><strong>Results: </strong>A 23-year-old female patient with multiply relapsed metastatic ES, harboring MUC16 expression by IHC and elevated serum CA125, received intravenous ubamatamab (250 mg) once per week as part of a single patient study. After 11 weeks of ubamatamab, a RECIST v1.1 partial response was demonstrated, along with serum CA125 normalization, lasting 43 weeks. During the initial step-up dosing, the patient experienced grade 2 cytokine release syndrome. Treatment-emergent adverse events included grade 2 pleural effusion, pericardial effusion, and palmar-plantar erythrodysesthesia, all resolving without intervention. IHC analysis of retrospective samples showed positive MUC16 staining in six of eight (75%) ES and two of four (50%) MRT samples, with no immunoreactivity observed in other pediatric/AYA sarcoma subtypes.</p><p><strong>Conclusion: </strong>MUC16 is frequently detected in ES and MRTs. Ubamatamab is an encouraging anti-MUC16 therapy, demonstrating clinical efficacy. Ongoing trials (ClinicalTrials.gov identifier: NCT06444880) are evaluating ubamatamab in other rare MUC16-positive tumors.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500404"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764915","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":"Fidelity of Next-Generation Sequencing to Predict Human Epidermal Growth Factor 2 Overexpression Across Solid Tumors.","authors":"Mya Tran, Christopher A Fausel, Steven Bray, Guanglong Jiang, Erica Cantor, Santosh Philips, Fei Shen, Bryan P Schneider","doi":"10.1200/PO-24-00935","DOIUrl":"https://doi.org/10.1200/PO-24-00935","url":null,"abstract":"<p><strong>Purpose: </strong>Human epidermal growth factor 2 (HER2/ERBB2) has recently become a pan-tumor-agnostic target after the approval of trastuzumab deruxtecan for solid tumors with HER2 overexpression (3+). HER2 positivity is currently assessed by immunohistochemistry (IHC) and/or <i>HER2</i> amplification through in situ hybridization (ISH), owing to the fact that HER2 overexpression is secondary to HER2 gene amplification in many cases. Outside of breast/gastroesophageal cancer, the optimal IHC scoring method to assess overexpression across solid tumors remains undefined. Next-generation sequencing (NGS) is frequently used in practice and could be leveraged to predict HER2 positivity. However, less is known regarding the correlation between these methodologies. We sought to evaluate the ability of NGS to predict HER2 overexpression.</p><p><strong>Methods: </strong>We compared the concordance of HER2 IHC and/or ISH results with <i>HER2</i> amplification status detected by NGS in 1,009 patients with solid tumors who were referred to the Indiana University Precision Genomics program between September 2021 and October 2024.</p><p><strong>Results: </strong>HER2 3+ by IHC was identified in 4.3% (43 of 1,009) of cases. When including HER2 2+/ISH-positive (ISH+), the overall incidence of HER2 positivity was 5.1% (51 of 1,009). <i>HER2</i> amplification was not detected by NGS in 20.9% (9 of 43) of HER2 3+ and 75.0% (6 of 8) of HER2 2+/ISH+ cases. The rate of discordance varies across the type of NGS testing platform and sample status, with the highest incidence seen in liquid NGS (80.3%) and the lowest incidence observed when the same sample was used for testing (26.7%).</p><p><strong>Conclusion: </strong>Relying solely on NGS-based <i>HER2</i> amplification could result in missing cases of HER2 positivity and thus deprive patients of anti-HER2 therapy options. NGS, IHC, and/or ISH should be used as complementary tools for optimal detection of HER2 positivity.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400935"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540259","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":"Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors.","authors":"Geraldine O'Sullivan Coyne, Khanh T Do, Shivaani Kummar, Sarina Piha-Paul, Lawrence Rubinstein, Robert Kinders, Ralph E Parchment, Deborah Wilsker, Katherine Ferry-Galow, Brandon Miller, Naoko Takebe, Lamin Juwara, Mary Jane Ong, Ashley Bruns, Murielle Hogu, Abdul Rafeh Naqash, Arjun Mittra, Andrea Regier Voth, James H Doroshow, Alice P Chen","doi":"10.1200/PO-25-00055","DOIUrl":"10.1200/PO-25-00055","url":null,"abstract":"<p><strong>Purpose: </strong>We conducted a phase I trial of the combination of cisplatin with the ataxia-telangiectasia-related protein kinase inhibitor berzosertib and the poly (ADP-ribose) polymerase inhibitor (PARPi) veliparib, with the objective of creating a DNA damage response (DDR)-impaired, BRCA null-like phenotype to potentiate the antitumor activity of cisplatin.</p><p><strong>Patients and methods: </strong>In this open label, 3 + 3 trial design, cisplatin and berzosertib were administered intravenously on day 1 (D1) and D8, and D2 and D9, respectively, together with twice-daily oral veliparib on D1-D3 and D8-D10 in 21-day cycles. Previous platinum and PARPi therapy were permitted. A pharmacodynamic study compared tumor nuclear DDR biomarker response on C1D1 and C1D9 at the combination maximum tolerated dose (MTD).</p><p><strong>Results: </strong>Fifty-three patients enrolled with 46 evaluable for response (41 with measurable disease). The MTD and recommended phase II dose (RP2D) were determined to be cisplatin 40 mg/m² once daily on D1/D8, berzosertib 210 mg/m² once daily on D2/D9, and veliparib 200 mg twice a day on D1-D3 and D8-D10. Three patients achieved confirmed partial responses (PRs; 3/41, 7.3%); two patients experienced unconfirmed PRs. Median time on study was four cycles (range, 1-25), and 35 patients (66.0%) required at least one dose reduction. The most common grade 3/4 adverse events were myelosuppressive (anemia [37.7%], thrombocytopenia [32.1%], leukopenia [24.5%], neutropenia [22.6%], lymphopenia [20.8%]); no new safety signals were observed. Adding berzosertib to veliparib/cisplatin increased the frequency of RAD51-positive tumor cells in <i>BRCA</i>-wildtype biopsy specimens.</p><p><strong>Conclusion: </strong>This combination shows antitumor activity, including in patients with and without homologous recombination-compromised tumors and those previously treated with platinum. Adding berzosertib further increases the DDR response elicited by combination cisplatin/veliparib treatment in <i>BRCA</i>-wildtype patients, indicating increased replication stress at the RP2D/MTD.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500055"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649497","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":"Reducing Fluorouracil Doses in Patients With Partial Dihydropyrimidine Dehydrogenase Deficiency Is a Treatment Safety Strategy, Not a Panacea of Precision Dosing.","authors":"Daniel L Hertz, Alan P Venook","doi":"10.1200/PO-25-00440","DOIUrl":"https://doi.org/10.1200/PO-25-00440","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500440"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608400","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":"Quantitative Multiplex Immunofluorescence Assay for Trophoblast Cell-Surface Antigen 2 and Human Epidermal Growth Factor Receptor 2 Expression in Breast Cancer: Toward Guiding Patient Selection for Antibody-Drug Conjugate Therapies.","authors":"Charles J Robbins, Mengni He, Nay Chan, Revekka Khaimova, Katherine Bates, Ioannis P Trontzas, Liam Scott, Myrto Moutafi, Chandra B Coleman, Salisha Hill, Daniel C Liebler, Regan Fulton, David L Rimm","doi":"10.1200/PO-25-00128","DOIUrl":"https://doi.org/10.1200/PO-25-00128","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate quantification of human epidermal growth factor receptor 2 (HER2) and trophoblast cell-surface antigen 2 (TROP2) expression could aid in identifying patients with cancer likely to benefit from emerging HER2 and TROP2 antibody-drug conjugate (ADC) therapies or potentially help oncologists choose which drug to use first, on the basis of the level of the ADC target in the tumor. We developed a standardized multiplex quantitative immunofluorescence (QIF) assay to simultaneously measure HER2 and TROP2 protein levels in cancer tissue.</p><p><strong>Materials and methods: </strong>A multiplex QIF assay was optimized on tissue microarrays (TMAs) by selecting optimal antibody clones and concentrations to achieve maximal signal-to-noise ratios. We create and release Qymia, a QuPath extension to enable simultaneous molecular compartmentalization and fluorescence quantification in TMAs and whole-slide images. Calibration curves, generated from cell line microarrays with HER2/TROP2 measured by mass spectrometry, were used to convert QIF signal into protein concentrations (attomoles/mm²). The validated assay was applied to a serial collection of 323 breast cancer specimens in TMA format to characterize HER2 and TROP2 expression distributions.</p><p><strong>Results: </strong>The assay demonstrated linearity across a wide dynamic range of biomarker expression with strong interassay and interoperator reproducibility. Application to 323 breast cancer TMA specimens revealed a weak inverse correlation between HER2 and TROP2 (<i>r</i> = -0.17; <i>P</i> = .001). HER2 was detectable in approximately 85% of TMA cores, including 51% of triple-negative breast cancer TMA cores. TROP2 was detectable in over 96% of specimens across all subtypes.</p><p><strong>Conclusion: </strong>This multiplex immunofluorescence assay provides an approach to accurately and precisely measure HER2/TROP2 levels within breast cancer tissue and compare relative levels of target expression in a breast cancer tissue population. This assay is now ready for studies to assess clinical validity and utility.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500128"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649495","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":"Deep-Learning Model for Real-Time Prediction of Recurrence in Early-Stage Non-Small Cell Lung Cancer: A Multimodal Approach (RADAR CARE Study).","authors":"Hyun Ae Jung, Daehwan Lee, Boram Park, Kiwon Lee, Ho Yun Lee, Tae Jung Kim, Yeong Jeong Jeon, Junghee Lee, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Hong Kwan Kim","doi":"10.1200/PO-25-00172","DOIUrl":"10.1200/PO-25-00172","url":null,"abstract":"<p><strong>Purpose: </strong>The surveillance protocol for early-stage non-small cell lung cancer (NSCLC) is not contingent upon individualized risk factors for recurrence. This study aimed to use comprehensive data from clinical practice to develop a deep-learning model for practical longitudinal monitoring.</p><p><strong>Methods: </strong>A multimodal deep-learning model with transformers was developed for real-time recurrence prediction using baseline clinical, pathological, and molecular data with longitudinal laboratory and radiologic data collected during surveillance. Patients with NSCLC (stage I to III) who underwent surgery with curative intent between January 2008 and September 2022 were included. The primary outcome was predicting recurrence within 1 year after the monitoring point. This study demonstrates the timely provision of risk scores (RADAR score) and determined thresholds and the corresponding AUC.</p><p><strong>Results: </strong>A total of 14,177 patients were enrolled (10,262 with stage I, 2,380 with stage II, and 1,703 with stage III). The model incorporated 64 clinical-pathological-molecular factors at baseline, along with longitudinal laboratory and computed tomography imaging interpretation data. The mean baseline RADAR score was 0.324 (standard deviation [SD], 0.256) in stage I, 0.660 (SD, 0.210) in stage II, and 0.824 (SD, 0.140) in stage III. The AUC for predicting relapse within 1 year of the monitoring point was 0.854 across all stages, with a sensitivity of 86.0% and a specificity of 71.3% (AUC = 0.872 in stage I, AUC = 0.737 in stage II, and AUC = 0.724 in stage III).</p><p><strong>Conclusion: </strong>This pilot study introduces a deep-learning model that uses multimodal data from routine clinical practice to predict relapses in early-stage NSCLC. It demonstrates the timely provision of RADAR risk scores to clinicians for recurrence prediction, potentially guiding risk-adapted surveillance strategies and aggressive adjuvant systemic treatment.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500172"},"PeriodicalIF":5.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698603","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":"CNS Involvement by North American-Adult T-cell Leukemia/Lymphoma Is Associated With Discrete Dissemination Patterns and Molecular Profiles, Involving XPO1 E571 and KLF2/PI3KCD in Selected Cases.","authors":"Nishi Shah, Melissa Suchanek, Astha Thakkar, Riya Jayesh Patel, Shafia Rahman, Ana Acuna-Villaorduna, Urvi Shah, Diego Adrianzen Herrera, Shira Slasky, Kira Gritsman, Mendel Goldfinger, Aditi Shastri, Ioannis Mantzaris, Noah Kornblum, Lizamarie Bachier-Rodriguez, Eric Feldman, Dennis Cooper, Katharine Anne McNeill, Yanhua Wang, Yang Shi, Amit Verma, B Hilda Ye, Murali Janakiram, R Alejandro Sica","doi":"10.1200/PO.23.00526","DOIUrl":"10.1200/PO.23.00526","url":null,"abstract":"<p><strong>Purpose: </strong>CNS involvement in North American adult T-cell leukemia/lymphoma (NA-ATLL) remains poorly understood. This study examined the CNS involvement in patients with ATLL treated at a tertiary hospital in New York City.</p><p><strong>Methods: </strong>CNS involvement was defined by positive cerebrospinal fluid (CSF) cytology, flow cytometry, positive CNS imaging, or neurological examination findings.</p><p><strong>Results: </strong>Among 94 patients with NA-ATLL, 21 (22.3%) had CNS involvement. CSF was involved in 13 patients at diagnosis and five at relapse. Magnetic resonance imaging detected brain and spinal involvement in 24% and 14% of the patients, respectively. Results of neurological examinations were abnormal in 33% and 14% of the patients at diagnosis and relapse, respectively. The <i>XPO1</i> <i>E571K</i> mutation was found in two patients with extensive, treatment-refractory CNS disease, with a median overall survival (OS) of 2 months. Other mutations, including <i>KLF2</i> and <i>PI3KCD</i>, were noted in two patients. The median OS was 8.5 months, and the median relapse-free survival (RFS) was 6.5 months in our series. In most cases (5/21), the lymphomatous phenotype appeared to have a direct mass-like extension, whereas in patients with predominant blood involvement tended to spread to the CSF by traversing the blood-brain barrier.</p><p><strong>Conclusion: </strong>In this report, we describe the patterns of CNS involvement in ATLL and their association with mutations. We also describe two rapidly fatal cases with the <i>XPO1 E571K</i> mutation, which may represent a novel therapeutic target for T-cell lymphomas.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2300526"},"PeriodicalIF":5.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715076","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}