Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P. R. China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, P. R. China.
Cancer Commun (Lond). 2024 Oct;44(10):1173-1188. doi: 10.1002/cac2.12601. Epub 2024 Aug 19.
Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields.
This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field.
The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons.
IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.
同期放化疗（CCRT）是局部晚期食管鳞状细胞癌（ESCC）的标准治疗方法。然而，最佳放疗方案，特别是在总剂量和计划照射野范围方面，仍不清楚。这项 III 期临床试验旨在比较不同放射剂量和不同靶区之间的生存获益。
该试验采用两因素析因设计比较了放射治疗的两个方面，即总剂量和靶区。高剂量（HD）组接受 59.4 Gy 放射治疗，标准剂量（SD）组接受 50.4 Gy。累及野照射（IFI）组和选择性淋巴结照射（ENI）组采用不同的照射范围。参与者被分配到四个组之一（HD+ENI、HD+IFI、SD+ENI 和 SD+IFI）。主要终点是总生存期（OS），次要终点包括无进展生存期（PFS）。采用协同指数来衡量剂量与靶区之间的相互作用效应。
交互分析并未显示剂量与照射野之间存在显著的协同作用。与靶区相比，IFI 或 ENI 组患者的 OS（风险比[HR] = 0.99，95%CI：0.80-1.23，p = 0.930）和 PFS（HR = 1.02，95%CI：0.82-1.25）相似。与 SD 相比，HD 治疗并未显著延长 OS（HR = 0.90，95%CI：0.72-1.11，p = 0.318），但提示 PFS 有所改善（25.2 个月至 18.0 个月）。在这四个组中，HD+IFI 组的生存情况最好，而 SD+IFI 组的预后最差。在剂量或靶区比较中，未发现严重不良事件的发生率有显著差异。
IFI 在 ESCC 的 CCRT 中与 ENI 具有相似的治疗效果。HD 改善了 PFS，但并未显著改善 OS。基于 IFI（HD+IFI）的剂量升级显示出比当前推荐（SD+ENI）更好的治疗效果，值得进一步验证。
