Fiorino Claudio, Passoni Paolo, Palmisano Anna, Gumina Calogero, Cattaneo Giovanni M, Broggi Sara, Di Chiara Alessandra, Esposito Antonio, Mori Martina, Ronzoni Monica, Rosati Riccardo, Slim Najla, De Cobelli Francesco, Calandrino Riccardo, Di Muzio Nadia G
Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
Radiotherapy, San Raffaele Scientific Institute, Milano, Italy.
Clin Transl Radiat Oncol. 2019 Jul 3;19:12-16. doi: 10.1016/j.ctro.2019.07.001. eCollection 2019 Nov.
An early tumor regression index (ERI) was previously introduced and found to predict pathological response after neo-adjuvant radio-chemotherapy of rectal cancer. ERI was tested as a potential biomarker in predicting long-term disease-free survival.
Data of 65 patients treated with an early regression-guided adaptive boosting technique (ART) were available. Overall, loco-regional relapse-free and distant metastasis-free survival (OS, LRFS, DMFS) were considered. Patients received 41.4 Gy in 18 fractions (2.3 Gy/fr), including ART concomitant boost on the residual GTV during the last 6 fractions (3 Gy/fr, D: 45.6 Gy). Chemotherapy included oxaliplatin and 5-fluorouracil (5-FU). T2-weighted MRI taken before (MRI) and at half therapy (MRI) were available and GTVs were contoured (V, V). The parameter ERI = -ln[(1 - (V/V))] was calculated for all patients. Cox regression models were assessed considering several clinical and histological variables. Cox models not including/including ERI (CONV_model and REGR_model respectively) were assessed and their discriminative power compared.
At a median follow-up of 47 months, OS, LRFS and DMFS were 94%, 95% and 78%. Due to too few events, multivariable analyses focused on DMFS: the resulting CONV_model included pathological complete remission or clinical complete remission followed by surgery refusal (HR: 0.15, p = 0.07) and 5-FU dose >90% (HR: 0.29, p = 0.03) as best predictors, with AUC = 0.75. REGR_model included ERI (HR: 1.019, p < 0.0001) and 5-FU dose >90% (HR: 0.18, p = 0.005); AUC was 0.86, significantly higher than CONV_model (p = 0.05). Stratifying patients according to the best cut-off value for ERI and to 5-FU dose (> vs <90%) resulted in 47-month DMFS equal to 100%/69%/0% for patients with two/one/zero positive factors respectively (p = 0.0002). ERI was also the only variable significantly associated to OS (p = 0.01) and LRFS (p = 0.03).
ERI predicts long-term DMFS after radio-chemotherapy for rectal cancer: an independent impact of the 5-FU dose was also found. This result represents a first step toward application of ERI in treatment personalization: additional confirmation on independent cohorts is warranted.
先前已引入早期肿瘤消退指数（ERI），并发现其可预测直肠癌新辅助放化疗后的病理反应。对ERI作为预测长期无病生存的潜在生物标志物进行了测试。
有65例接受早期消退引导的自适应增强技术（ART）治疗患者的数据。总体上，考虑了总生存（OS）、局部区域无复发生存（LRFS）和远处转移无复发生存（DMFS）。患者接受18次分割的41.4 Gy（2.3 Gy/次）照射，包括在最后6次分割期间对残留大体肿瘤体积（GTV）进行ART同步加量（3 Gy/次，D：45.6 Gy）。化疗包括奥沙利铂和5-氟尿嘧啶（5-FU）。可获得治疗前（MRI）和治疗中期（MRI）的T2加权MRI图像，并勾画GTV（V，V）。为所有患者计算参数ERI = -ln[(1 - (V/V))]。考虑了几个临床和组织学变量，评估Cox回归模型。评估不包括/包括ERI的Cox模型（分别为CONV模型和REGR模型），并比较它们的判别能力。
中位随访47个月时，OS、LRFS和DMFS分别为94%、95%和78%。由于事件数过少，多变量分析聚焦于DMFS：最终的CONV模型包括病理完全缓解或临床完全缓解后拒绝手术（HR：0.15，p = 0.07）和5-FU剂量>90%（HR：0.29，p = 0.03）作为最佳预测因素，AUC = 0.75。REGR模型包括ERI（HR：1.019，p < 0.0001）和5-FU剂量>90%（HR：0.18，p = 0.005）；AUC为0.86，显著高于CONV模型（p = 0.05）。根据ERI的最佳临界值和5-FU剂量（> vs <90%）对患者进行分层，结果显示，分别具有两个/一个/零个阳性因素的患者47个月的DMFS分别为100%/69%/0%（p = 应为0.0002）。ERI也是与OS（p = 0.01）和LRFS（p = 0.03）显著相关的唯一变量。
ERI可预测直肠癌放化疗后的长期DMFS：还发现了5-FU剂量的独立影响。这一结果代表了将ERI应用于治疗个体化的第一步：需要在独立队列中进行进一步验证。
