Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer
Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer
复制标题
DOI：
10.1093/jnci/djx095
复制
发表时间：
2017-12-01
影响因子：
10.3
通讯作者：
Roedel, Claus
中科院分区：
文献类型：
--
作者：
Fokas, Emmanouil;Stroebel, Philipp;Roedel, Claus
背景：我们研究了肿瘤消退分级（TRG）作为治疗直肠癌患者无病生存（DFS）的预后指标和个体水平替代指标，该试验是在Chirurgische Arbeitsgemeinschaft for Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04随机试验中进行的。方法：对1179例术前加或不加奥沙利铂的氟尿嘧啶放化疗（CRT）患者，采用Dworak分级前瞻性记录TRG。采用Cox回归模型进行多变量分析，校正治疗组、切除情况和病理分期。使用四个Prentice标准（PC1-4）检查个体水平的DFS的TRG代孕。所有统计检验均为双侧检验。结果：中位随访50个月，与单独使用氟尿嘧啶的CRT相比，奥沙利铂在氟尿嘧啶为主的CRT中添加可显著改善3年DFS (75.9%, 95% CI = 72.3 ~ 79.5, vs 71.3%, 95% CI = 67.6 ~ 74.9, P = 0.04, pc1)，并转向更晚期的TRG组（P < 0.001, pc2）。TRG 0 + 1（差回归）、TRG 2 + 3（中间回归）和TRG 4（完全回归）的3年DFS分别为64.6% （95% CI = 57.3 ~ 71.9）、77.6% （95% CI = 74.5 ~ 80.7）和92.3% (95% CI = 88.4 ~ 96.2) （P < 0.001, pc3）。TRG是DFS的独立预后因素（TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 ~ 0.90, P = 0.007）。由于多重共线性，不能在同一模型中检测trg4和病理分期。治疗效果以TRG衡量，满足个体水平PC4。结论：术前CRT后较高的TRG预示着良好的长期预后。在个体患者水平上，TRG是DFS的替代标志物。需要进一步的III期试验来验证TRG在试验水平上的替代作用。
Background: We investigated tumor regression grading (TRG) as a prognosticmarker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial.Methods: TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided.Results: With amedian follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups (P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively (P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due tomulticollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4.Conclusions: Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.