目前的指南建议许多胃肠道间质瘤（GIST）患者使用伊马替尼辅助治疗；然而，其最佳治疗持续时间尚不清楚，并且某些患者群体并未从该治疗中受益。我们的目标是将最先进的、可解释的人工智能（即易于理解的预测或处方逻辑）方法应用于现实世界的数据，以确定哪些 GIST 患者群体应该接受伊马替尼辅助治疗，这是其最佳治疗方法在这项观察性队列研究中，我们考虑纳入在纪念斯隆凯特琳癌症中心（MSKCC；美国纽约州纽约市）接受原发性非转移性 GIST 切除术的所有患者1982年10月1日至2017年12月31日，根据武装部队病理学研究所Miettinen标准划分为中危或高危且随访数据完整、无遗漏的人员。在 MSKCC 中训练了一个反事实随机森林模型，该模型使用复发预测因子（有丝分裂计数、肿瘤大小和肿瘤部位）和伊马替尼持续时间来推断给定患者在每个伊马替尼治疗持续时间下 7 年复发的概率队列。最优策略树（OPT）是一种最先进的可解释的基于人工智能的方法，通过用反事实预测训练决策树来读取反事实随机森林模型。 OPT 建议在来自波兰（波兰临床 GIST 登记处）和来自西班牙（西班牙肉瘤研究小组）的两组患者中进行了外部验证，这些患者在 1981 年 12 月 1 日至 2011 年 12 月 31 日期间接受了 GIST 切除术， 1987年10月1日至2011年1月30日期间接受手术切除的患者。在MSKCC接受GIST手术的1007例患者中，117例被纳入内部队列；对于外部队列，波兰队列包括 363 名患者，西班牙队列包括 239 名患者。 OPT 不建议将伊马替尼用于胃源性 GIST 小于 15·9 cm、有丝分裂计数每 5 mm2 少于 11·5 个有丝分裂的患者或任何部位的小 GIST（<5·4 cm）的患者每 5 mm2 有丝分裂计数少于 11·5 个。在该队列中，OPT 截止值的敏感性为 92·7% (95% CI 82·4-98·0)，特异性为 33·9% (22·3-47·0)。在两个外部队列中应用这些截止值将使西班牙队列中 131 名患者中的 38 名患者 (29%) 和波兰队列中 126 名患者中 44 名患者 (35%) 免受不必要的伊马替尼治疗。同时，这些队列中患者治疗不足的风险很小（西班牙队列的敏感性为 95·4% [95% CI 89·5-98·5]，西班牙队列的敏感性为 92·4% [88·3-95·4]）波兰队列）。 OPT 测试了 33 种不同持续时间的伊马替尼治疗（<5 年），发现 5 年治疗带来的益处最大。如果将确定的患者亚组应用于临床实践，目前候选队列中多达三分之一的患者会接受未从伊马替尼辅助治疗中获益的患者将被鼓励不接受伊马替尼治疗，从而避免对患者造成不必要的毒性以及对医疗保健系统造成财务压力。我们发现 5 年是伊马替尼治疗的最佳持续时间，这可能是 2028 年之前临床实践的最佳证据来源，届时具有相同目标的随机对照试验预计将报告其结果。国家癌症研究所。版权所有 © 2024 Elsevier保留所有权利，包括文本和数据挖掘、人工智能培训和类似技术的权利。

Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy.In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries. A counterfactual random forest model, which used predictors of recurrence (mitotic count, tumour size, and tumour site) and imatinib duration to infer the probability of recurrence at 7 years for a given patient under each duration of imatinib treatment, was trained in the MSKCC cohort. Optimal policy trees (OPTs), a state-of-the-art interpretable AI-based method, were used to read the counterfactual random forest model by training a decision tree with the counterfactual predictions. The OPT recommendations were externally validated in two cohorts of patients from Poland (the Polish Clinical GIST Registry), who underwent GIST resection between Dec 1, 1981, and Dec 31, 2011, and from Spain (the Spanish Group for Research in Sarcomas), who underwent resection between Oct 1, 1987, and Jan 30, 2011.Among 1007 patients who underwent GIST surgery in MSKCC, 117 were included in the internal cohort; for the external cohorts, the Polish cohort comprised 363 patients and the Spanish cohort comprised 239 patients. The OPT did not recommend imatinib for patients with GISTs of gastric origin measuring less than 15·9 cm with a mitotic count of less than 11·5 mitoses per 5 mm2 or for those with small GISTs (<5·4 cm) of any site with a count of less than 11·5 mitoses per 5 mm2. In this cohort, the OPT cutoffs had a sensitivity of 92·7% (95% CI 82·4-98·0) and a specificity of 33·9% (22·3-47·0). The application of these cutoffs in the two external cohorts would have spared 38 (29%) of 131 patients in the Spanish cohort and 44 (35%) of 126 patients in the Polish cohort from unnecessary treatment with imatinib. Meanwhile, the risk of undertreating patients in these cohorts was minimal (sensitivity 95·4% [95% CI 89·5-98·5] in the Spanish cohort and 92·4% [88·3-95·4] in the Polish cohort). The OPT tested 33 different durations of imatinib treatment (<5 years) and found that 5 years of treatment conferred the most benefit.If the identified patient subgroups were applied in clinical practice, as many as a third of the current cohort of candidates who do not benefit from adjuvant imatinib would be encouraged to not receive imatinib, subsequently avoiding unnecessary toxicity on patients and financial strain on health-care systems. Our finding that 5 years is the optimal duration of imatinib treatment could be the best source of evidence to inform clinical practice until 2028, when a randomised controlled trial with the same aims is expected to report its findings.National Cancer Institute.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.