免疫评分在接受奥沙利铂治疗的 III 期结肠癌患者中的预后和预测价值：法国 IDEA PRODIGE-GERCOR 前瞻性队列研究。
Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study.
机构信息
Department of Immunology, Européen Georges Pompidou Hospital, AP-HP, Paris, France; French National Institute of Health and Medical Research (INSERM), Centre de Recherche des Cordeliers, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université de Paris, Paris, France; Laboratory of Integrative Cancer Immunology, INSERM, Centre de Recherche des Cordeliers, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne University and AP-HP, Paris, France.
出版信息
Ann Oncol. 2020 Jul;31(7):921-929. doi: 10.1016/j.annonc.2020.03.310. Epub 2020 Apr 12.
BACKGROUND
The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients.
PATIENTS AND METHODS
Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance.
RESULTS
Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6.
CONCLUSIONS
The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS.
GOV REGISTRATION
NCT03422601; EudraCT Number: 2009-010384-16.
背景
免疫评分（IS）用于对 I-III 期结肠癌（CC）患者进行预后分类，该评分在评估 III 期 CC 患者接受奥沙利铂为基础的辅助化疗 3 个月与 6 个月的国际辅助化疗持续时间评估（IDEA）法国队列研究中进行了评估。
患者和方法
通过免疫组织化学法检测肿瘤和侵袭边缘的 CD3+和 CD8+T 细胞密度，通过数字病理学进行定量，并转换为 IS。通过免疫组织化学法或五重 PCR 法确定错配修复状态。在每个研究组中，通过多变量 Cox 回归模型分析 IS 对无病生存（DFS）的预测。哈雷尔 C 统计量用于研究 IS 的性能。
结果
共获得了 1322 例患者的样本。IS 低、中（Int）和高分别见于 43.6%、47.0%和 9.4%的患者。与 Int+高相比，IS 低患者复发或死亡风险更高[风险比（HR）=1.54；95%置信区间（CI）1.24-1.93，P=0.0001]。IS 低的 3 年 DFS 为 66.80%（95%CI 62.23-70.94），IS Int+高为 77.14%（95%CI 73.50-80.35）。多变量分析显示，在调整性别、组织学分级、T/N 分期和微卫星不稳定性后，IS 与 DFS 仍显著相关（P=0.003）。对于接受 mFOLFOX6 治疗的患者（队列的 91.6%），在 DFS 方面，IS 对治疗持续时间（3 个月与 6 个月）的预测价值存在统计学显著的交互作用（P=0.057）。IS Int+高显著预测 6 个月治疗获益（HR=0.53；95%CI 0.37-0.75；P=0.0004），包括临床低危和高危 III 期 CC（均 P<0.001）。相反，IS 低的患者（46.4%）未从 mFOLFOX6 6 个月治疗中显著获益。
结论
IS 对接受奥沙利铂为基础化疗的 III 期 CC 患者的 DFS 预后价值得到了证实。在 IS Int+高的患者中，发现 IS 对 mFOLFOX6 辅助治疗延长时间的 DFS 获益具有预测价值。这些结果将在外部独立队列中得到验证。临床试验。
政府注册
NCT03422601；EudraCT 编号：2009-010384-16。
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