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局部晚期食管癌新辅助放化疗方案的回顾性比较

A retrospective comparison of neoadjuvant chemoradiotherapy regimens for locally advanced esophageal cancer.

作者信息

Sanford N N, Catalano P J, Enzinger P C, King B L, Bueno R, Martin N E, Hong T S, Wo J Y, Mamon H J

机构信息

Departments of Radiation Oncology.

Departments of Biostatistics and Computational Biology.

出版信息

Dis Esophagus. 2017 Jul 1;30(7):1-8. doi: 10.1093/dote/dox025.

Abstract

Preoperative chemoradiotherapy (CRT) with carboplatin/paclitaxel has been shown to increase survival in patients with esophageal cancer, including gastroesophageal junction (GE) junction cancer, over surgery alone; however, there have been no studies comparing the different neoadjuvant CRT regimens. We retrospectively evaluated the long-term results of trimodality therapy for patients with locally advanced esophageal cancer treated on several chemotherapy regimens. Between 1999 and 2014, 215 patients with locally advanced esophageal cancer underwent neoadjuvant CRT followed by surgical resection. The median age was 62 years (range 21-84), 80.5% were men and 86% had adenocarcinoma. The following chemotherapy regimens were administered: cisplatin/5FU (14.9%), cisplatin/irinotecan (35.8%), carboplatin/paclitaxel (35.8%), and other (9.7%). The majority of patients (92.1%) received a radiation dose of 50.4 Gy. Predictors of toxicities and surgical complications were assessed using logistic regression. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and proportional hazards regression was used to model time-to-event outcomes. The median follow-up among surviving patients was 4.1 years (range 0.4,13). The median OS was 3.0 years from time of diagnosis and OS was 36.8% at 5 years. RFS was 34.9% at 5 years. After neoadjuvant CRT, 34.7% of patients achieved a pathologic complete response including 60.7% of squamous cell carcinoma patients and 18.4% of adenocarcinoma patients (P < 0.001) and 66% were downstaged. Of the variables examined, pathologic stage, preoperative baseline cardiac comorbidity, postoperative cardiac or pulmonary complications, and chemotherapy regimen were associated with OS. Using cisplatin and 5FU as the reference regimen, patients treated with carboplatin/paclitaxel had significantly improved OS (HR = 0.47, P = 0.017 after adjusting for surgery type, radiation modality, baseline cardiac comorbidity, and preoperative stage) with 5-year OS rate of 66%. The most common surgical complications were cardiac in 61 patients (28.5%) and pulmonary in 52 patients (24.3%). Cardiac complications were associated with age (OR 1.05, P = 0.007) and cardiac comorbidity (OR 2.6, P = 0.02) and pulmonary complications with female gender (OR 3.98, P < 0.001). Forty-four patients (20.5%) required readmission within 30 days of discharge, and readmission was associated with cardiac comorbidity (OR 2.7, P = 0.017). Three patients died within 30 days of surgery. We observed an association between neoadjuvant carboplatin/paclitaxel and improved overall survival that requires confirmation in a prospective randomized trial.

摘要

术前使用卡铂/紫杉醇进行放化疗(CRT)已被证明可提高食管癌患者(包括胃食管交界部(GE)癌)的生存率,优于单纯手术;然而,尚无研究比较不同的新辅助CRT方案。我们回顾性评估了采用几种化疗方案治疗的局部晚期食管癌患者接受三联疗法的长期结果。1999年至2014年期间,215例局部晚期食管癌患者接受了新辅助CRT,随后进行手术切除。中位年龄为62岁(范围21 - 84岁),80.5%为男性,86%患有腺癌。采用了以下化疗方案:顺铂/5氟尿嘧啶(14.9%)、顺铂/伊立替康(35.8%)、卡铂/紫杉醇(35.8%)和其他方案(9.7%)。大多数患者(92.1%)接受的放射剂量为50.4 Gy。使用逻辑回归评估毒性和手术并发症的预测因素。采用Kaplan-Meier方法估计总生存期(OS)和无复发生存期(RFS),并使用比例风险回归对事件发生时间结局进行建模。存活患者的中位随访时间为4.1年(范围0.4 - 13年)。自诊断起的中位OS为3.0年,5年OS率为36.8%。5年RFS为34.9%。新辅助CRT后,34.7%的患者达到病理完全缓解,包括60.7%的鳞状细胞癌患者和18.4%的腺癌患者(P < 0.001),66%的患者分期降低。在所检查的变量中,病理分期、术前基线心脏合并症、术后心脏或肺部并发症以及化疗方案与OS相关。以顺铂和5氟尿嘧啶作为对照方案,接受卡铂/紫杉醇治疗的患者OS显著改善(调整手术类型、放疗方式、基线心脏合并症和术前分期后,HR = 0.47,P = 0.017),5年OS率为66%。最常见的手术并发症是心脏并发症,61例患者(28.5%)发生,肺部并发症52例患者(24.3%)发生。心脏并发症与年龄相关(OR 1.05,P = 0.007)和心脏合并症相关(OR 2.6,P = 0.02),肺部并发症与女性性别相关(OR 3.98,P < 0.001)。44例患者(20.5%)在出院后30天内需要再次入院,再次入院与心脏合并症相关(OR 2.7,P = 0.017)。3例患者在手术后30天内死亡。我们观察到新辅助卡铂/紫杉醇与总体生存率提高之间存在关联,这需要在前瞻性随机试验中得到证实。

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