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New Molecular Targets in Prostate Cancer-The Emerging Role of ACP1 and Low Molecular Weight Protein Tyrosine Phosphatase. 前列腺癌的新分子靶点--ACP1 和低分子量蛋白酪氨酸磷酸酶的新作用
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-11-20 DOI: 10.1200/PO-24-00682
Miguel Zugman, Alexander Chehrazi-Raffle, Oren Smaletz
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引用次数: 0
Evidenced-Based Prior for Estimating the Treatment Effect of Phase III Randomized Trials in Oncology. 估算肿瘤学 III 期随机试验治疗效果的循证先例。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1200/PO.24.00363
Alexander D Sherry, Pavlos Msaouel, Gabrielle S Kupferman, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Zachary R McCaw, Ethan B Ludmir, Erik van Zwet

Purpose: The primary results of phase III oncology trials may be challenging to interpret, given that results are generally based on P value thresholds. The probability of whether a treatment is beneficial, although more intuitive, is not usually provided. Here, we developed and released a user-friendly tool that calculates the probability of treatment benefit using trial summary statistics.

Methods: We curated 415 phase III randomized trials enrolling 338,600 patients published between 2004 and 2020. A phase III prior probability distribution for the treatment effect was developed on the basis of a three-component zero-mean mixture distribution of the observed z-scores. Using this prior, we computed the probability of clinically meaningful benefit (hazard ratio [HR] <0.8). The distribution of signal-to-noise ratios and power of phase III oncology trials were compared with that of 23,551 randomized trials from the Cochrane Database.

Results: The signal-to-noise ratios of phase III oncology trials tended to be much larger than randomized trials from the Cochrane Database. Still, the median power of phase III oncology trials was only 49% (IQR, 14%-95%), and the power was <80% in 65% of trials. Using the phase III oncology-specific prior, only 53% of trials claiming superiority (114 of 216) had a ≥90% probability of clinically meaningful benefits. Conversely, the probability that the experimental arm was superior to the control arm (HR <1) exceeded 90% in 17% of trials interpreted as having no benefit (34 of 199).

Conclusion: By enabling computation of contextual probabilities for the treatment effect from summary statistics, our robust, highly practical tool, now posted on a user-friendly webpage, can aid the wider oncology community in the interpretation of phase III trials.

目的:III 期肿瘤试验的主要结果通常以 P 值阈值为基础,因此解释这些结果可能具有挑战性。治疗是否获益的概率虽然更直观,但通常不会提供。在此,我们开发并发布了一款用户友好型工具,可使用试验摘要统计计算治疗获益概率:我们整理了 2004 年至 2020 年间发表的 415 项 III 期随机试验,共招募了 338600 名患者。在观察到的 z 分数的三组零均值混合分布的基础上,我们建立了 III 期治疗效果的先验概率分布。利用该先验值,我们计算了有临床意义的获益概率(危险比 [HR] 结果):肿瘤学 III 期试验的信噪比往往比 Cochrane 数据库中的随机试验大得多。尽管如此,III 期肿瘤学试验的中位研究功率仅为 49%(IQR,14%-95%),研究功率为结论值:我们的工具功能强大、实用性强,目前已发布在用户友好型网页上,可帮助广大肿瘤学界解读III期试验。
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引用次数: 0
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
Erratum: A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease. 勘误:一种基于目标甲基化的多癌早期检测血液检验能优先检测高级别前列腺癌,同时最大限度地减少对隐匿性疾病的过度诊断。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-16 DOI: 10.1200/PO-24-00637
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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
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
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。
{"title":"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.","authors":"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","doi":"10.1200/PO.24.00297","DOIUrl":"https://doi.org/10.1200/PO.24.00297","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400297"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390683","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
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
Uptake of Aspirin Chemoprevention in Patients With Lynch Syndrome. 林奇综合征患者对阿司匹林化学预防的接受程度。
IF 5.3 2区 医学 Q1 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-11-15 DOI: 10.1200/PO-24-00562
Sachi Singhal, Emma D Riggs, Karen J Ruth, Juan Pablo Chavez-Salas, Yana Chertock, Mary B Daly, Michael J Hall

Purpose: Individuals with Lynch syndrome (LS) are at a high lifetime risk of colorectal cancer (CRC) and other cancers. Aspirin (ASA), a nonsteroidal anti-inflammatory drug (NSAID), has proven chemopreventive benefits in LS, with the CAPP2 randomized double-blind placebo-controlled trial demonstrating a 60% relative risk reduction for CRC among participants who adhered to ASA for 2 years or more. This study sought to characterize uptake of ASA/NSAIDs among individuals with LS and to understand factors associated with use.

Methods: Individuals with LS were invited (June 2020-August 2022) to complete a one-time electronic survey about LS screening behaviors, uptake of ASA/NSAIDs, and current/emerging cancer prevention options. Participants were recruited from the Fox Chase Cancer Center (FCCC) Risk Assessment Program Registry and through a research invitation posted to two patient-facing LS advocacy websites.

Results: Two hundred and ninety-six participants completed the survey including 116 (39.2%) from FCCC and 180 (60.8%) recruited via the Internet, including 14.9% non-US based individuals. Uptake of regular ASA or NSAIDs was modest at 34.8% and was even lower (25.7%) when focusing on individuals taking ASA or NSAIDs solely for chemoprevention of LS. More than half (55%) were taking <100 mg ASA daily. In multivariable modeling, lower perceived threat of LS (odds ratio [OR], 0.84 [95% CI, 0.72 to 0.98]), lower concern for side effects (OR, 0.86 [95% CI, 0.76 to 0.99]), and higher likelihood of recommending ASA/NSAIDs to family or a friend were all associated with ASA/NSAIDs use (OR, 1.70 [95% CI, 1.37 to 2.10]).

Conclusion: Uptake of ASA/NSAIDs chemoprevention is modest among individuals with LS. Patient perceptions of the pros and cons of ASA, more so than demographic and disease-related factors, were associated with chemoprevention uptake.

目的:林奇综合征(LS)患者终生罹患结直肠癌(CRC)和其他癌症的风险很高。阿司匹林(ASA)是一种非甾体抗炎药(NSAID),已被证实对林奇综合征患者有化学预防作用,CAPP2 随机双盲安慰剂对照试验表明,坚持服用阿司匹林 2 年或更长时间的参与者患 CRC 的相对风险降低了 60%。本研究旨在了解LS患者服用ASA/NSAIDs的情况,并了解与使用ASA/NSAIDs相关的因素:邀请 LS 患者(2020 年 6 月至 2022 年 8 月)完成一次性电子调查,了解 LS 筛查行为、ASA/NSAIDs 摄入情况以及当前/新出现的癌症预防方案。参与者是从福克斯蔡斯癌症中心(FCCC)风险评估项目登记处以及两个面向患者的LS宣传网站上发布的研究邀请中招募的:296 名参与者完成了调查,其中 116 人(39.2%)来自 FCCC,180 人(60.8%)通过互联网招募,包括 14.9% 的非美国居民。定期服用 ASA 或非甾体抗炎药的人数不多,仅占 34.8%,如果仅为化学预防 LS 而服用 ASA 或非甾体抗炎药的人数更少(25.7%)。半数以上(55%)服用者担心副作用(OR,0.86 [95% CI,0.76 至 0.99]),向家人或朋友推荐ASA/NSAIDs的可能性较高,这些都与服用ASA/NSAIDs有关(OR,1.70 [95% CI,1.37 至 2.10]):LS患者对ASA/NSAIDs化学预防的接受程度不高。患者对ASA利弊的看法比人口统计学和疾病相关因素更能影响化学预防的使用率。
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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
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