新辅助放化疗联合手术治疗食管癌的 10 年结果：随机对照 CROSS 试验。

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.

机构信息

Department of Surgery, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

Formerly at Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.

出版信息

J Clin Oncol. 2021 Jun 20;39(18):1995-2004. doi: 10.1200/JCO.20.03614. Epub 2021 Apr 23.

DOI:10.1200/JCO.20.03614

PMID:33891478

Abstract

PURPOSE

Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen.

METHODS

From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses.

RESULTS

The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( value for interaction, = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13).

CONCLUSION

The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

摘要

目的

根据食管癌同期放化疗后手术研究（CROSS）进行的术前放化疗已成为局部晚期可切除食管或交界性癌患者的标准治疗方法。我们旨在评估该方案的长期疗效。

方法

2004 年至 2008 年，我们将 366 例患者随机分为每周 5 个周期的卡铂和紫杉醇联合放疗（23 个分次，5 天/周，41.4 Gy），随后进行手术，或单独手术。通过 2018 年收集随访数据。采用 Cox 回归分析比较总生存、特异性生存以及局部复发和远处复发的风险。通过时间依赖性 Cox 回归和 landmark 分析检验新辅助放化疗超过 5 年的效果。

结果

中位随访时间为 147 个月（四分位距，134-157）。接受新辅助放化疗的患者总生存更好（风险比[HR]，0.70；95%CI，0.55 至 0.89）。新辅助放化疗对总生存的影响不是时间依赖性的（检验交互作用的值为 0.73），landmark 分析表明，新辅助放化疗在 10 年随访期内对总生存的影响稳定。10 年总生存获益绝对增加 13%（38% 25%）。新辅助放化疗降低了死于食管癌的风险（HR，0.60；95%CI，0.46 至 0.80）。两组死于其他原因的风险相似（HR，1.17；95%CI，0.68 至 1.99）。虽然局部复发（HR，0.40；95%CI，0.21 至 0.72）和同期局部复发加远处复发（HR，0.43；95%CI，0.26 至 0.72）的风险明显降低，但孤立性远处复发无差异（HR，0.76；95%CI，0.52 至 1.13）。