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Molecular Subtypes Are Associated With Clinical Benefit in Cisplatin-Treated Metastatic Urothelial Cancer Patients. 分子亚型与顺铂治疗转移性尿路上皮癌患者的临床获益有关
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1200/PO.24.00209
Karin Holmsten, Gottfrid Sjödahl, Johan Abrahamsson, Carina Bernardo, Pontus Eriksson, Mattias Höglund, Fredrik Liedberg, Anders Ullén

Purpose: Cisplatin-based combination chemotherapy (CHT) is standard of care in metastatic urothelial cancer (mUC); however, no predictive molecular biomarkers are available for clinical use. The aim of this study was to investigate the impact of molecular subtypes in relation to treatment response and survival in patients with mUC treated with first-line CHT.

Patients and methods: Molecular subtype classification according to the Lund Taxonomy (LundTax) was performed by tumor transcriptomic profiling and immunostaining in a retrospective cohort. Molecular subtypes were investigated in relation to the primary end point overall response rate (ORR) and secondary end points progression-free survival (PFS) and overall survival (OS). Differential gene expression and association to treatment response were explored.

Results: Ninety-five patients with mUC were classified into urothelial-like (Uro, 43%), genomically unstable (GU, 26%), basal squamous-like (Ba/Sq, 20%), mesenchymal-like (Mes-like, 8%), and small cell neuroendocrine-like (Sc/NE, 3%) subtypes. Patients with Mes-like tumors had lower ORR (14%) compared with Uro (70%), GU (77%), Ba/Sq (75%), and Sc/NE (67%; odds ratio, 0.06 [95% CI, 0.01 to 0.54], P = .012). Furthermore, patients with Mes-like tumors had significantly shorter PFS (hazard ratio [HR], 5.18 [95% CI, 2.28 to 11.76], P < .001) and OS (HR, 3.19 [95% CI, 1.45 to 7.03], P = .004). Patients with Uro and GU showed the longest survival. In responders, an enrichment of downregulated stromal- and immune-related genes was seen. Downregulation of interferon-induced transmembrane protein 2 was associated with increased ORR and improved OS.

Conclusion: This study identifies different CHT responses by LundTax molecular subtypes in patients with mUC, where the Mes-like subtype was associated with lower response rate and shorter survival.

目的:以顺铂为基础的联合化疗(CHT)是转移性尿路上皮癌(mUC)的标准治疗方法;然而,目前尚无可用于临床的预测性分子生物标记物。本研究旨在调查分子亚型对接受一线CHT治疗的mUC患者的治疗反应和生存期的影响:在一个回顾性队列中,通过肿瘤转录组学分析和免疫染色,根据隆德分类法(LundTax)进行分子亚型分类。研究了分子亚型与主要终点总反应率(ORR)及次要终点无进展生存期(PFS)和总生存期(OS)的关系。研究还探讨了基因表达的差异及其与治疗反应的关系:95名mUC患者被分为尿路上皮样(Uro,43%)、基因组不稳定(GU,26%)、基底鳞状细胞样(Ba/Sq,20%)、间质样(Mes,8%)和小细胞神经内分泌样(Sc/NE,3%)亚型。Mes样肿瘤患者的ORR(14%)低于Uro(70%)、GU(77%)、Ba/Sq(75%)和Sc/NE(67%;几率比为0.06 [95% CI, 0.01 to 0.54],P = .012)。此外,Mes 样肿瘤患者的 PFS(危险比 [HR],5.18 [95% CI,2.28 至 11.76],P < .001)和 OS(HR,3.19 [95% CI,1.45 至 7.03],P = .004)明显较短。泌尿系统和生殖系统疾病患者的生存期最长。在应答者中,基质和免疫相关基因的下调幅度较大。干扰素诱导跨膜蛋白2的下调与ORR增加和OS改善有关:这项研究发现了mUC患者中LundTax分子亚型的不同CHT反应,其中Mes样亚型与较低的反应率和较短的生存期相关。
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引用次数: 0
Impact of Comprehensive Genome Profiling on the Management of Advanced Non-Small Cell Lung Cancer: Preliminary Results From the Lung Cancer Cohort of the FPG500 Program. 综合基因组图谱分析对晚期非小细胞肺癌治疗的影响:FPG500计划肺癌队列的初步结果。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-07 DOI: 10.1200/PO.24.00297
Antonio Vitale, Luca Mastrantoni, Jacopo Russo, Flavia Giacomini, Diana Giannarelli, Simona Duranti, Emanuele Vita, Camilla Nero, Ettore D'Argento, Tina Pasciuto, Luciano Giacò, Mariantonietta Di Salvatore, Arianna Panfili, Alessio Stefani, Alessandra Cancellieri, Filippo Lococo, Elisa De Paolis, Vanina Livi, Gennaro Daniele, Rocco Trisolini, Angelo Minucci, Stefano Margaritora, Domenica Lorusso, Nicola Normanno, Giovanni Scambia, Giampaolo Tortora, Emilio Bria

Purpose: The clinical and research FPG500 program (ClinicalTrials.gov identifier: NCT06020625) is currently ongoing at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS to tailor matched targeted therapies (MTTs) according to biomarkers predictive of response identified by comprehensive genome profiling (CGP).

Materials and methods: The non-small cell lung cancer (NSCLC) cohort results from the FPG500 program are outlined. CGP was performed by TruSight Oncology 500 High Throughput (TSO500HT) assay or Oncomine Focus Assay plus Archer's FusionPlex Lung Panel according to tumor cell content and DNA/RNA quantity. Relevant issues for Molecular Tumor Board (MTB) evaluation included uncommon genomic findings, evaluation for off-label therapies, uncertain result confirmation, and variants of suspect germline origin requiring genetic counseling. Progression-free survival (PFS) and overall survival (OS) for the enrolled patients were assessed using Kaplan-Meier analysis.

Results: In 2022, 283 patients with NSCLC were considered for sequencing, with 93% meeting eligibility criteria. TSO500HT sequencing was conducted in 76% of patients. Follow-up data were obtained for 187 patients, among whom 81% received treatment. Potential driver alterations were identified in 59% of patients, with 41% receiving MTT: 25% were prescribed approved MTTs, whereas 16% gained access to experimental drugs post-MTB evaluation; of note, 18% did not receive any MTT because the regimen was not yet reimbursed in our country. Median PFS and OS varied among treatment groups, with standard chemotherapy/immunotherapy at 7.7 and 10.7 months, approved tyrosine kinase inhibitors at 18.8 and 23.9 months, and MTT post-MTB discussion at 14 and 23.4 months, respectively.

Conclusion: The early data of the FPG program (NSCLC cohort) support the implementation of CGP and MTB in clinical practice to grant access to patients harboring actionable molecular alterations to the most effective and individualized available treatment options, thus improving their survival outcomes.

目的:Fondazione Policlinico Universitario Agostino Gemelli IRCCS目前正在开展临床和研究FPG500计划(ClinicalTrials.gov标识符:NCT06020625),根据综合基因组图谱(CGP)确定的预测反应的生物标志物定制匹配的靶向疗法(MTT):概述了FPG500计划的非小细胞肺癌(NSCLC)队列结果。根据肿瘤细胞含量和DNA/RNA数量,采用TruSight Oncology 500高通量(TSO500HT)测定或Oncomine Focus测定加Archer's FusionPlex Lung Panel进行CGP分析。肿瘤分子委员会(MTB)评估的相关问题包括:不常见的基因组发现、标签外疗法评估、不确定的结果确认以及需要遗传咨询的可疑种系变异。采用 Kaplan-Meier 分析法评估了入组患者的无进展生存期(PFS)和总生存期(OS):2022年,283名NSCLC患者被考虑进行测序,其中93%符合资格标准。76%的患者进行了TSO500HT测序。获得了187名患者的随访数据,其中81%的患者接受了治疗。59%的患者确定了潜在的驱动基因改变,41%的患者接受了MTT治疗:25%的患者获得了批准的MTT处方,而16%的患者在MTB评估后获得了实验性药物;值得注意的是,18%的患者没有接受任何MTT治疗,因为该方案在我国尚未报销。各治疗组的中位生存期和OS各不相同,标准化疗/免疫疗法分别为7.7个月和10.7个月,获批的酪氨酸激酶抑制剂分别为18.8个月和23.9个月,MTB讨论后的MTT分别为14个月和23.4个月:FPG项目(NSCLC队列)的早期数据支持在临床实践中实施CGP和MTB,使携带可操作分子改变的患者获得最有效的个体化治疗方案,从而改善他们的生存预后。
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引用次数: 0
Salvage Surgery for Unifocal Progressive Metastatic Mismatch Repair-Deficient GI Cancer Responding to Immune Checkpoint Inhibition. 对免疫检查点抑制剂有反应的单灶进展性转移性错配修复缺陷消化道癌症的挽救手术
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-11 DOI: 10.1200/PO.24.00176
Pieterjan Perremans, Filip Van Herpe, Gertjan Rasschaert, Johan Van Ongeval, Jochen Decaestecker, Baki Topal, Gabriele Bislenghi, Albert Wolthuis, Halit Topal, Christophe Deroose, Eric Van Cutsem, Jeroen Dekervel

Case series describing excellent outcomes for patients with dMMR GI cancer after resection of a single progressive lesion under immunotherapy.

系列病例描述了 dMMR 消化道癌症患者在免疫疗法下切除单个进展性病变后的良好疗效。
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引用次数: 0
Poly (ADP-ribose) Polymerase Inhibitor Resistance Driven by Emergence of Polyclonal Mutations With Convergent Evolution: A Molecular Tumor Board Discussion. 多聚(ADP-核糖)聚合酶抑制剂耐药性由趋同进化的多克隆突变驱动:分子肿瘤委员会的讨论。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-11 DOI: 10.1200/PO.24.00254
Maria Fatteh, Jaime Wehr, Katerina Karaindrou, Rena R Xian, Christopher Gocke, Ming-Tseh Lin, Dana Petry, Kala Visvanathan, Rima Couzi, Cesar Santa Maria, Vered Stearns, Jessica J Tao, Valsamo Anagnostou, Jenna V Canzoniero

Polyclonal convergent evolution to PARPi resistance in a patient with metastatic breast cancer with gPALB2.

一名患有 gPALB2 的转移性乳腺癌患者对 PARPi 耐药性的多克隆趋同进化。
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引用次数: 0
Reply to E. Shash. 答复 E. Shash。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-21 DOI: 10.1200/PO-24-00585
Vrutangkumar Shah, Daniel Muzyka, Carolyn Guidarelli, Kristen Sowlasky, Fay Horak, Kerri Winters-Stone
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引用次数: 0
Erratum: Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib. 勘误:接受他唑帕尼治疗的 BRCA1/2 基因突变乳腺癌患者体内 [18F]-Fluorthanatrace 多聚(ADP-核糖)聚合酶正电子发射断层扫描的药效学活性。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-16 DOI: 10.1200/PO-24-00676
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引用次数: 0
Artificial Intelligence Hybrid Survival Assessment System for Robot-Assisted Proctectomy: A Retrospective Cohort Study. 机器人辅助直肠切除术的人工智能混合生存评估系统:回顾性队列研究
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-21 DOI: 10.1200/PO.24.00089
Shiqian Zhang, Ge Zhang, Ming Wang, Song-Bin Guo, Fuqi Wang, Yun Li, Kaisaierjiang Kadier, Zhaokai Zhou, Pengpeng Zhang, Hao Chi, Chuchu Zhang, Quanbo Zhou, Pin Lyu, Shuaiya Zhao, Shuaixi Yang, Weitang Yuan

Purpose: Robotic-assisted proctectomy (RAP) has emerged as the predominant surgical approach for patients with rectal cancer in recent years; although good postoperative patient recovery with accurate prediction is a guarantee of adaptive surveillance management, there is still a lack of easy-to-use prognostic tools and risk scores designed specifically for those patients undergoing RAP.

Methods: This study used the electronic health records of 506 RAP participants, including a National Specialist Center for da Vinci Robotic Colorectal Surgery (NSCVRCS) meta cohort, and an independent external validation Sun Yat-sen Memorial Hospital cohort. In the NSCVRCS meta cohort, patients were divided into a discovery cohort (70%, n = 268), where the best-fit model was applied to model our prediction system, RAP-AIscore. Subsequently, an internal validation process for RAP-AIscore was conducted using a replication cohort (30%, n = 116). The study designed and implemented a large-scale artificial intelligence (AI) hybrid framework to identify the best strategy for building a survival assessment system, the RAP-AIscore, from 132 potential modeling scenarios through a combination of iterative cross-validation, Monte Carlo cross-validation, and bootstrap resampling. The 10 variables most relevant to clinical interpretability were identified on the basis of the AI hybrid optimal model values, which helps provide reliable prognostic survival guidance for new patients.

Results: The consistent evaluation of discrimination, calibration, generalization, and prognostic value across cohorts reaffirmed the accuracy and robust extrapolation capability of this system. The 10 feature variables most associated with clinical interpretability on the basis of Shapley values were identified, facilitating reliable prognostic survival guidance for new patients.

Conclusion: This study introduces a promising and informative tool, the RAP-AIscore, which can be explained through nomograms for interpreting clinical outcomes. It facilitates postoperative risk stratification management and enhances clinical management of prognosis for RAP patients.

目的近年来,机器人辅助直肠切除术(RAP)已成为直肠癌患者的主要手术方式;虽然术后患者恢复良好且预测准确是适应性监测管理的保证,但目前仍缺乏专为RAP患者设计的易于使用的预后工具和风险评分:本研究使用了506名RAP参与者的电子病历,包括国家达芬奇机器人结直肠手术专科中心(NSCVRCS)的元队列和独立外部验证的中山大学孙逸仙纪念医院队列。在NSCVRCS元队列中,患者被分为发现队列(70%,n = 268),其中最佳拟合模型被用于建立我们的预测系统RAP-AIscore。随后,利用复制队列(30%,n = 116)对 RAP-AIscore 进行了内部验证。该研究设计并实施了一个大规模人工智能(AI)混合框架,通过迭代交叉验证、蒙特卡罗交叉验证和引导重采样相结合的方法,从 132 种潜在建模方案中找出建立生存评估系统 RAP-AIscore 的最佳策略。在人工智能混合最佳模型值的基础上,确定了与临床可解释性最相关的 10 个变量,这有助于为新患者提供可靠的预后生存指导:结果:对不同队列的区分度、校准、泛化和预后价值的一致评估再次证明了该系统的准确性和强大的外推能力。根据沙普利值确定了与临床可解释性最相关的 10 个特征变量,从而为新患者提供了可靠的预后生存指导:本研究介绍了一种前景广阔、信息丰富的工具--RAP-AIscore,它可以通过提名图来解释临床结果。它有助于术后风险分层管理,加强对 RAP 患者预后的临床管理。
{"title":"Artificial Intelligence Hybrid Survival Assessment System for Robot-Assisted Proctectomy: A Retrospective Cohort Study.","authors":"Shiqian Zhang, Ge Zhang, Ming Wang, Song-Bin Guo, Fuqi Wang, Yun Li, Kaisaierjiang Kadier, Zhaokai Zhou, Pengpeng Zhang, Hao Chi, Chuchu Zhang, Quanbo Zhou, Pin Lyu, Shuaiya Zhao, Shuaixi Yang, Weitang Yuan","doi":"10.1200/PO.24.00089","DOIUrl":"https://doi.org/10.1200/PO.24.00089","url":null,"abstract":"<p><strong>Purpose: </strong>Robotic-assisted proctectomy (RAP) has emerged as the predominant surgical approach for patients with rectal cancer in recent years; although good postoperative patient recovery with accurate prediction is a guarantee of adaptive surveillance management, there is still a lack of easy-to-use prognostic tools and risk scores designed specifically for those patients undergoing RAP.</p><p><strong>Methods: </strong>This study used the electronic health records of 506 RAP participants, including a National Specialist Center for da Vinci Robotic Colorectal Surgery (NSCVRCS) meta cohort, and an independent external validation Sun Yat-sen Memorial Hospital cohort. In the NSCVRCS meta cohort, patients were divided into a discovery cohort (70%, n = 268), where the best-fit model was applied to model our prediction system, RAP-AIscore. Subsequently, an internal validation process for RAP-AIscore was conducted using a replication cohort (30%, n = 116). The study designed and implemented a large-scale artificial intelligence (AI) hybrid framework to identify the best strategy for building a survival assessment system, the RAP-AIscore, from 132 potential modeling scenarios through a combination of iterative cross-validation, Monte Carlo cross-validation, and bootstrap resampling. The 10 variables most relevant to clinical interpretability were identified on the basis of the AI hybrid optimal model values, which helps provide reliable prognostic survival guidance for new patients.</p><p><strong>Results: </strong>The consistent evaluation of discrimination, calibration, generalization, and prognostic value across cohorts reaffirmed the accuracy and robust extrapolation capability of this system. The 10 feature variables most associated with clinical interpretability on the basis of Shapley values were identified, facilitating reliable prognostic survival guidance for new patients.</p><p><strong>Conclusion: </strong>This study introduces a promising and informative tool, the RAP-AIscore, which can be explained through nomograms for interpreting clinical outcomes. It facilitates postoperative risk stratification management and enhances clinical management of prognosis for RAP patients.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465968","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}
引用次数: 0
Expert-Guided Large Language Models for Clinical Decision Support in Precision Oncology. 专家指导的大型语言模型为精准肿瘤学提供临床决策支持。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1200/PO-24-00478
Jacqueline Lammert, Tobias Dreyer, Sonja Mathes, Leonid Kuligin, Kai J Borm, Ulrich A Schatz, Marion Kiechle, Alisa M Lörsch, Johannes Jung, Sebastian Lange, Nicole Pfarr, Anna Durner, Kristina Schwamborn, Christof Winter, Dyke Ferber, Jakob Nikolas Kather, Carolin Mogler, Anna L Illert, Maximilian Tschochohei

Purpose: Rapidly expanding medical literature challenges oncologists seeking targeted cancer therapies. General-purpose large language models (LLMs) lack domain-specific knowledge, limiting their clinical utility. This study introduces the LLM system Medical Evidence Retrieval and Data Integration for Tailored Healthcare (MEREDITH), designed to support treatment recommendations in precision oncology. Built on Google's Gemini Pro LLM, MEREDITH uses retrieval-augmented generation and chain of thought.

Methods: We evaluated MEREDITH on 10 publicly available fictional oncology cases with iterative feedback from a molecular tumor board (MTB) at a major German cancer center. Initially limited to PubMed-indexed literature (draft system), MEREDITH was enhanced to incorporate clinical studies on drug response within the specific tumor type, trial databases, drug approval status, and oncologic guidelines. The MTB provided a benchmark with manually curated treatment recommendations and assessed the clinical relevance of LLM-generated options (qualitative assessment). We measured semantic cosine similarity between LLM suggestions and clinician responses (quantitative assessment).

Results: MEREDITH identified a broader range of treatment options (median 4) compared with MTB experts (median 2). These options included therapies on the basis of preclinical data and combination treatments, expanding the treatment possibilities for consideration by the MTB. This broader approach was achieved by incorporating a curated medical data set that contextualized molecular targetability. Mirroring the approach MTB experts use to evaluate MTB cases improved the LLM's ability to generate relevant suggestions. This is supported by high concordance between LLM suggestions and expert recommendations (94.7% for the enhanced system) and a significant increase in semantic similarity from the draft to the enhanced system (from 0.71 to 0.76, P = .01).

Conclusion: Expert feedback and domain-specific data augment LLM performance. Future research should investigate responsible LLM integration into real-world clinical workflows.

目的:快速扩充的医学文献给肿瘤学家寻求有针对性的癌症疗法带来了挑战。通用大型语言模型(LLM)缺乏特定领域的知识,限制了其临床实用性。本研究介绍了用于定制医疗保健的医学证据检索和数据整合(MEREDITH)LLM 系统,该系统旨在为精准肿瘤学的治疗建议提供支持。MEREDITH 基于谷歌的 Gemini Pro LLM,使用检索增强生成和思维链:我们利用德国一家大型癌症中心的分子肿瘤委员会(MTB)提供的迭代反馈,在 10 个公开的虚构肿瘤病例上对 MEREDITH 进行了评估。MEREDITH 最初仅限于 PubMed 索引的文献(系统草案),后来进行了改进,纳入了特定肿瘤类型药物反应的临床研究、试验数据库、药物批准状态和肿瘤指南。MTB提供了人工策划的治疗建议基准,并评估了LLM生成的方案的临床相关性(定性评估)。我们测量了LLM建议与临床医生回复之间的语义余弦相似度(定量评估):结果:与 MTB 专家(中位数为 2)相比,MEREDITH 确定了范围更广的治疗方案(中位数为 4)。这些方案包括基于临床前数据的疗法和联合疗法,从而扩大了 MTB 考虑的治疗可能性。这种更广泛的方法是通过纳入一个经过整理的医学数据集来实现的,该数据集将分子靶向性的背景情况具体化。参照 MTB 专家评估 MTB 病例的方法,提高了 LLM 生成相关建议的能力。LLM 建议与专家建议之间的高度一致性(增强型系统为 94.7%)以及从草案到增强型系统之间语义相似性的显著提高(从 0.71 到 0.76,P = .01)都证明了这一点:专家反馈和特定领域的数据增强了 LLM 的性能。未来的研究应将 LLM 负责任地整合到真实世界的临床工作流程中。
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引用次数: 0
Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report. KIT Q556_K558 框内缺失的胃腺癌患者对伊马替尼的反应:病例报告。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 DOI: 10.1200/PO.24.00228
Kiichiro Ninomiya, Daisuke Ennishi, Kunio Okamoto, Midori Ando, Satoko Nakamura, Shuta Tomida, Yoshiyuki Ayada, Go Makimoto, Eiki Ichihara, Natsuko Okita, Shinichi Toyooka, Yoshinobu Maeda, Masahiro Tabata

Imatinib may be a useful targeted agent for patients with advanced gastric adenocarcinoma who have KIT mutations.

伊马替尼可能是一种有效的靶向药物,可用于KIT突变的晚期胃腺癌患者。
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引用次数: 0
Personalized Therapy Selection by Integration of Molecular Cancer Classification by the 92-Gene Assay and Tumor Profiling in Patients With Cancer of Unknown Primary. 通过整合 92 基因检测的癌症分子分类和肿瘤图谱,为不明原发性癌症患者提供个性化治疗选择。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-09-01 DOI: 10.1200/PO.24.00191
Harry E Fuentes Bayne, Pashtoon M Kasi, Li Ma, Lowell L Hart, Jenna Wong, David R Spigel, Catherine A Schnabel, James A Reeves, Thorvardur R Halfdanarson, Kai Treuner, F Anthony Greco

Purpose: Cancer of unknown primary (CUP) is a syndrome comprising metastatic cancers without a clinically identified primary site. Although patients with CUP have an unfavorable prognosis, treatment with site-specific therapies guided by clinical features, standard pathology, and molecular assays can improve overall survival. The 92-gene assay (CancerTYPE ID) is a gene expression-based classifier that helps identify the tissue of origin for metastatic cancers with unknown or uncertain diagnoses. This study reports the frequency of selected molecular aberrations of oncogenes, including KRAS, IDH1/2, BRCA1/2, and BRAF, in patients with CUP in the MOSAIC database to highlight potential treatment options.

Methods: MOSAIC is a database of patients with CUP submitted for CancerTYPE ID testing and NeoTYPE biomarker testing. Tumor biopsy samples were analyzed by CancerTYPE ID for tumor type identification and further tested for molecular aberrations of oncogenes, including KRAS, IDH1/2, BRCA1/2, and BRAF.

Results: CancerTYPE ID identified a specific tumor type in 92.5% (2,929 of 3,168) of CUP cases in the MOSAIC database. The most commonly identified histological type was adenocarcinoma (75.4%), with pancreaticobiliary being the most common molecularly diagnosed cancer (24.9%). Aberrations in KRAS, IDH1/2, BRCA, and BRAF genes were identified in 18.8% (n = 597) of biopsies. A cancer-specific US Food and Drug Administration (FDA)-approved or investigational targeted therapy was potentially available for 24.6% (n = 147) of these patients.

Conclusion: This retrospective analysis supports incorporating CancerTYPE ID into the evaluation for patients with CUP to help determine the tissue of origin and identify actionable genetic alterations. This approach may allow more patients with CUP to benefit from site-specific FDA-approved targeted therapies or enrollment into clinical trials.

目的:原发性不明癌症(CUP)是一种由转移性癌症组成的综合征,临床上无法确定其原发部位。虽然 CUP 患者预后不良,但在临床特征、标准病理学和分子检测的指导下采用特定部位疗法可提高总生存率。92 个基因检测(CancerTYPE ID)是一种基于基因表达的分类器,有助于确定诊断不明或不确定的转移性癌症的原发组织。本研究报告了MOSAIC数据库中CUP患者的部分癌基因分子畸变频率,包括KRAS、IDH1/2、BRCA1/2和BRAF,以突出潜在的治疗方案:MOSAIC是一个CUP患者数据库,这些患者已提交CancerTYPE ID检测和NeoTYPE生物标记物检测。通过CancerTYPE ID分析肿瘤活检样本以确定肿瘤类型,并进一步检测KRAS、IDH1/2、BRCA1/2和BRAF等癌基因的分子畸变:CancerTYPE ID 在 MOSAIC 数据库中 92.5% 的 CUP 病例(3168 例中的 2929 例)中识别出了特定的肿瘤类型。最常见的组织学类型是腺癌(75.4%),胰胆管癌是最常见的分子诊断癌症(24.9%)。在18.8%(n = 597)的活检中发现了KRAS、IDH1/2、BRCA和BRAF基因的畸变。这些患者中有 24.6%(n = 147)可能接受了美国食品药品管理局(FDA)批准的癌症特异性靶向治疗或研究性靶向治疗:这项回顾性分析支持将 CancerTYPE ID 纳入 CUP 患者的评估中,以帮助确定原发组织并识别可操作的基因改变。这种方法可以让更多的 CUP 患者从 FDA 批准的特定部位靶向疗法或临床试验中获益。
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引用次数: 0
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JCO precision oncology
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