The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study.
The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study.
复制标题
使用下一代测序衍生的机器学习风险预测模型（OncoCast-MPM）治疗恶性胸膜间皮瘤：一项回顾性研究
DOI：
10.1016/s2589-7500(21)00104-7
复制
发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Shen R
中科院分区：
文献类型：
--
作者：
Zauderer MG;Martin A;Egger J;Rizvi H;Offin M;Rimner A;Adusumilli PS;Rusch VW;Kris MG;Sauter JL;Ladanyi M;Shen R
目前恶性胸膜间皮瘤患者基于疾病分期和组织学的风险分层是不充分的。对于一些患有早期上皮样肿瘤的患者，按照目前的指导方针，预后良好的患者可以迅速进展；对于其他晚期肉瘤样癌患者，预后不良的患者可以进展缓慢。因此，我们的目标是开发和验证一种机器学习工具-OncoCast-MPM-可以为患者的预后创建一个模型。我们对恶性胸膜间皮瘤进行了一项回顾性研究，使用纪念斯隆-凯特琳癌症中心的下一代测序-可操作癌症目标的综合突变分析(MSK-IMPACT)。我们收集了在纪念斯隆-凯特琳癌症中心(纽约，纽约，美国)连续治疗的恶性胸膜间皮瘤患者的临床、病理和常规下一代测序数据，以及MSK-Impact数据。这些数据加在一起，构成了MSK-IMPACT队列。使用OncoCast-MPM，一个开源的、网络可访问的、机器学习的风险预测模型，我们整合了可用的数据来创建风险评分，将患者分为低风险组和高风险组。然后使用癌症基因组图谱(即TCGA队列)中公开可用的恶性胸膜间皮瘤数据来验证MSK-IMPACT队列的风险分层。在2014年2月15日至2019年1月28日期间，我们从MSK-Impact队列中194名患者的肿瘤组织中收集了MSK-Impact数据。低风险组的中位总生存期高于高危组(30·8个月[95%可信区间22·7~36·2]比13·9个月[10·7~18·0]；危险比[HR]3·0[95%可信区间2·0~4·5]；P<；0·0001)。没有单一因素或基因改变驱动风险分化。OncoCast-MPM针对TCGA队列进行了验证，该队列包括74名患者。低危组的中位总生存期高于高危组(23.6月[95%CI 15·1~28.4]vs 13.6个月[9.8~17.9]；HR 2.3[95%CI 1·3~3·8]；p=0.0019)。虽然在MSK-IMPACT队列中，基于分期的风险分层不能区分3年内不同风险组的存活率(早期疾病为31%，晚期疾病为30%；p=0.90)，但低风险组的OncoCast-MPM衍生的3年生存率显著高于高风险组(40%对7%；p=0.0052)。OncoCast-MPM生成了准确的、个别患者级别的风险评估分数。经过TCGA队列的前瞻性验证后，OncoCast-MPM可能会在临床试验和药物开发中为提高恶性胸膜间皮瘤患者的风险分层提供新的机会。美国国立卫生研究院/国家癌症研究所。
Current risk stratification for patients with malignant pleural mesothelioma based on disease stage and histology is inadequate. For some individuals with early-stage epithelioid tumours, a good prognosis by current guidelines can progress rapidly; for others with advanced sarcomatoid cancers, a poor prognosis can progress slowly. Therefore, we aimed to develop and validate a machine-learning tool—known as OncoCast-MPM—that could create a model for patient prognosis. We did a retrospective study looking at malignant pleural mesothelioma tumours using next-generation sequencing from the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). We collected clinical, pathological, and routine next-generation sequencing data from consecutive patients with malignant pleural mesothelioma treated at the Memorial Sloan Kettering Cancer Center (New York, NY, USA), as well as the MSK-IMPACT data. Together, these data comprised the MSK-IMPACT cohort. Using OncoCast-MPM, an open-source, web-accessible, machine-learning risk-prediction model, we integrated available data to create risk scores that stratified patients into low-risk and high-risk groups. Risk stratification of the MSK-IMPACT cohort was then validated using publicly available malignant pleural mesothelioma data from The Cancer Genome Atlas (ie, the TCGA cohort). Between Feb 15, 2014, and Jan 28, 2019, we collected MSK-IMPACT data from the tumour tissue of 194 patients in the MSK-IMPACT cohort. The median overall survival was higher in the low-risk group than in the high-risk group as determined by OncoCast-MPM (30·8 months [95% CI 22·7–36·2] vs 13·9 months [10·7–18·0]; hazard ratio [HR] 3·0 [95% CI 2·0–4·5]; p<0·0001). No single factor or gene alteration drove risk differentiation. OncoCast-MPM was validated against the TCGA cohort, which consisted of 74 patients. The median overall survival was higher in the low-risk group than in the high-risk group (23·6 months [95% CI 15·1–28·4] vs 13·6 months [9·8–17·9]; HR 2·3 [95% CI 1·3–3·8]; p=0·0019). Although stage-based risk stratification was unable to differentiate survival among risk groups at 3 years in the MSK-IMPACT cohort (31% for early-stage disease vs 30% for advanced-stage disease; p=0·90), the OncoCast-MPM-derived 3-year survival was significantly higher in the low-risk group than in the high-risk group (40% vs 7%; p=0·0052). OncoCast-MPM generated accurate, individual patient-level risk assessment scores. After prospective validation with the TCGA cohort, OncoCast-MPM might offer new opportunities for enhanced risk stratification of patients with malignant pleural mesothelioma in clinical trials and drug development. US National Institutes of Health/National Cancer Institute.