Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Department of Informatics, University of Oslo, Oslo, Norway.
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Lancet Oncol. 2022 Sep;23(9):1221-1232. doi: 10.1016/S1470-2045(22)00391-6. Epub 2022 Aug 11.
The DoMore-v1-CRC marker was recently developed using deep learning and conventional haematoxylin and eosin-stained tissue sections, and was observed to outperform established molecular and morphological markers of patient outcome after primary colorectal cancer resection. The aim of the present study was to develop a clinical decision support system based on DoMore-v1-CRC and pathological staging markers to facilitate individualised selection of adjuvant treatment.
We estimated cancer-specific survival in subgroups formed by pathological tumour stage (pT<4 or pT4), pathological nodal stage (pN0, pN1, or pN2), number of lymph nodes sampled (≤12 or >12) if not pN2, and DoMore-v1-CRC classification (good, uncertain, or poor prognosis) in 997 patients with stage II or III colorectal cancer considered to have no residual tumour (R0) from two community-based cohorts in Norway and the UK, and used these data to define three risk groups. An external cohort of 1075 patients with stage II or III R0 colorectal cancer from the QUASAR 2 trial was used for validation; these patients were treated with single-agent capecitabine. The proposed risk stratification system was evaluated using Cox regression analysis. We similarly evaluated a risk stratification system intended to reflect current guidelines and clinical practice. The primary outcome was cancer-specific survival.
The new risk stratification system provided a hazard ratio of 10·71 (95% CI 6·39-17·93; p<0·0001) for high-risk versus low-risk patients and 3·06 (1·73-5·42; p=0·0001) for intermediate versus low risk in the primary analysis of the validation cohort. Estimated 3-year cancer-specific survival was 97·2% (95% CI 95·1-98·4; n=445 [41%]) for the low-risk group, 94·8% (91·7-96·7; n=339 [32%]) for the intermediate-risk group, and 77·6% (72·1-82·1; n=291 [27%]) for the high-risk group. The guideline-based risk grouping was observed to be less prognostic and informative (the low-risk group comprised only 142 [13%] of the 1075 patients).
Integrating DoMore-v1-CRC and pathological staging markers provided a clinical decision support system that risk stratifies more accurately than its constituent elements, and identifies substantially more patients with stage II and III colorectal cancer with similarly good prognosis as the low-risk group in current guidelines. Avoiding adjuvant chemotherapy in these patients might be safe, and could reduce morbidity, mortality, and treatment costs.
The Research Council of Norway.
最近使用深度学习和常规苏木精和伊红染色组织切片开发了 DoMore-v1-CRC 标志物，并观察到其在预测原发性结直肠癌切除术后患者的生存方面优于已建立的分子和形态学标志物。本研究的目的是开发一种基于 DoMore-v1-CRC 和病理分期标志物的临床决策支持系统，以促进辅助治疗的个体化选择。
我们在挪威和英国的两个社区队列中，对 997 名 II 期或 III 期结直肠癌患者进行了基于病理肿瘤分期（pT<4 或 pT4）、病理淋巴结分期（pN0、pN1 或 pN2）、如果不是 pN2 则取样的淋巴结数量（≤12 或>12）和 DoMore-v1-CRC 分类（预后良好、不确定或不良）的亚组中估计癌症特异性生存，使用这些数据定义了三个风险组。使用来自 QUASAR 2 试验的 1075 名 II 期或 III 期 R0 结直肠癌患者的外部队列进行验证；这些患者接受单药卡培他滨治疗。使用 Cox 回归分析评估了所提出的风险分层系统。我们还评估了一种旨在反映当前指南和临床实践的风险分层系统。主要结局是癌症特异性生存。
新的风险分层系统在验证队列的主要分析中，为高危与低危患者提供了 10.71（95%CI 6.39-17.93；p<0.0001）的风险比，为中危与低危患者提供了 3.06（1.73-5.42；p=0.0001）的风险比。低危组的估计 3 年癌症特异性生存率为 97.2%（95%CI 95.1-98.4；n=445 [41%]），中危组为 94.8%（91.7-96.7；n=339 [32%]），高危组为 77.6%（72.1-82.1；n=291 [27%]）。观察到基于指南的风险分组预后和信息性较差（低危组仅包括 1075 名患者中的 142 名[13%]）。
整合 DoMore-v1-CRC 和病理分期标志物提供了一种临床决策支持系统，该系统在预测方面比其组成部分更准确，并且比当前指南中确定具有相似良好预后的 II 期和 III 期结直肠癌患者多得多。避免这些患者的辅助化疗可能是安全的，并且可以降低发病率、死亡率和治疗成本。
挪威研究理事会。
