Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan.
Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):454-462. doi: 10.1016/j.ijrobp.2022.07.007. Epub 2022 Aug 4.
Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival.
Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/m on days 1 and 29) and 5-fluorouracil (1000 mg/m/d on days 1-4 and 29-32). Radiation therapy was administered at a total dose of 50.4 Gy. Good responders received 1 to 2 additional cycles of chemotherapy. For residual or recurrent disease, salvage endoscopic resection or salvage surgery was performed based on specific criteria. The primary endpoint was 3-year overall survival (OS). The calculated sample size was 95 patients, with a 1-sided alpha of 5% and a power of 80%. The expected and threshold 3-year OS were 55% and 42%, respectively.
Overall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%).
The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC.
对于拒绝初始手术治疗的局部晚期食管癌（EC）患者，确定性放化疗（CRT）是标准治疗方法。然而，较差的生存预后、晚期毒性发生率高以及挽救性手术后严重并发症仍然是亟待解决的问题。这项由日本癌症研究集团（JCOG）开展的单臂多中心研究（JCOG0909）旨在确认 CRT 改良方案（包括挽救性治疗以降低 CRT 相关毒性和促进挽救性治疗以提高生存预后）的疗效。
符合条件的患者为临床分期 II/III 期 EC（国际抗癌联盟第六版，非 T4 期）。化疗方案为顺铂（75 mg/m 2 ，第 1 天和 29 天）和 5-氟尿嘧啶（1000 mg/m 2 /d，第 1-4 天和 29-32 天）。放疗总剂量为 50.4 Gy。完全缓解的患者接受 1-2 个周期的辅助化疗。对于残留或复发疾病，根据具体标准进行挽救性内镜切除或挽救性手术。主要终点为 3 年总生存（OS）。计算得出的样本量为 95 例患者，单侧α值为 5%，效能为 80%。预期和阈值 3 年 OS 分别为 55%和 42%。
共有 96 例患者入组，94 例患者纳入疗效分析。55 例（59%）患者达到完全缓解。5 例（5%）和 25 例（27%）患者分别进行了挽救性内镜切除和挽救性手术。25 例接受挽救性手术的患者中，19 例（76%）达到了 R0 切除。5 例（20%）患者发生 3 级或 4 级早期手术并发症，9 例（9.6%）患者在长期随访中出现 3 级晚期毒性。3 年 OS 为 74.2%（90%置信区间，65.9%-80.8%）。
确定性 CRT 联合挽救性治疗可降低 CRT 相关毒性，并获得良好的 OS，因此为局部晚期 EC 患者提供了一种有前景的新治疗选择。
