这项研究的目的是评估Immunoscore在III期结肠癌(CC)患者中的预后价值,并分析其与化疗对复发时间(TTR)的影响的相关性。
由癌症免疫治疗协会领导的一项国际研究评估了来自队列1(加拿大/美国)和队列2(欧洲/亚洲)的763名美国癌症联合委员会/国际癌症控制联盟TNMIII期CC患者的预定义共识免疫评分。通过数字病理对肿瘤和浸润性切缘中的CD3和细胞毒性CD8T淋巴细胞密度进行定量。主要终点是TTR。次要终点是总生存期(OS),无病生存率(DFS),微卫星稳定(MSS)状态的预后,化疗疗效的预测价值。
高免疫评分患者的复发风险最低,在两个队列中。3年无复发率为56.9%(95%CI,50.3%至64.4%),65.9%(95%CI,60.8%至71.4%),和76.4%(95%CI,69.3%至84.3%)的患者低,中间,和高免疫分数,分别(危险比[HR;高v低],0.48;95%CI,0.32至0.71;P=.0003)。高Immunoscore患者与延长的TTR显著相关,操作系统,和DFS(所有P<.001)。在按参与中心分层的Cox多变量分析中,免疫分数与TTR的关联是独立的(HR[高v低],0.41;95%CI,0.25至0.67;P=.0003)患者性别,T级,N级,片面性,和微卫星不稳定状态。在MSS患者中也发现了高免疫分数与延长TTR的显着关联(HR[高v低],0.36;95%CI,0.21至0.62;P=.0003)。免疫评分对影响生存(TTR和OS)的贡献最大的是χ2比例。在低风险的高免疫评分组中,化疗与生存率显着相关(HR[化疗与无化疗],0.42;95%CI,0.25至0.71;P=.0011)和高风险(HR[化疗与无化疗],0.5;95%CI,0.33至0.77;P=.0015)患者,与低免疫分数组相反(P>.12)。
这项研究表明,在III期CC中,高免疫分数与延长的生存期显着相关。我们的发现表明,就复发风险而言,高免疫分数的患者将从化疗中受益最大。
The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR).
An international study led by the Society for Immunotherapy of Cancer evaluated the predefined
consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy.
Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient\'s sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low], 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group (P > .12).
This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.