Wang H H, Nolte I M, Verhoeven R H A, Oppedijk V, van Etten B, Kats-Ugurlu G, Plukker J T M, Hospers G A P
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
ESMO Open. 2025 May;10(5):105098. doi: 10.1016/j.esmoop.2025.105098. Epub 2025 May 15.
The Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) regimen is currently offered to locally advanced esophageal cancer patients beyond the original eligibility criteria. This national population-based study assessed the safety in implementation regarding treatment outcome when extending these criteria.
Locally advanced esophageal cancer (cT1N+/T2-4aN0-3/M0) patients (n = 5061) from the Netherlands Cancer Registry treated according to the neoadjuvant chemoradiotherapy (nCRT) CROSS regimen between 2015 and 2022 were analyzed. A total of 1958 complied with the original criteria (O-CROSS group) and 1348 with one or more extended criteria (tumor length >8 cm, age >75 years, WHO score >2 and/or weight loss >10%) (E-CROSS group), eventually followed by resection in 1342 O-CROSS patients and 852 E-CROSS patients. Primary outcome was overall survival (OS), i.e. time interval from onset of nCRT (OS-nCRT) and from date of surgery (OS-surgery) until death or last follow-up. Secondary outcomes were disease-free survival, pathological complete response (pCR), surgical radicality, post-operative morbidity and mortality. Data were analyzed using the Kaplan-Meier method and Cox proportional hazards models.
OS-nCRT was significantly lower in the E-CROSS compared with the O-CROSS (median of 30.3 months, 95% confidence interval 27.2-33.5 months versus 45.9 months, 95% CI 38.4-53.4 months, P < 0.001). Similarly, differences were observed in OS-surgery. When OS-nCRT and OS-surgery were adjusted for baseline covariates, however, no difference was found between both groups. Moreover, no differences were observed in disease-free survival, surgical radicality, and pCR. While not affecting post-operative mortality, significantly more anastomotic leakages and thromboembolic post-operative complications were seen in the O-CROSS group.
Extending the CROSS criteria was associated with lower OS, which was caused by the higher age, weight loss >10% and WHO score in the E-CROSS group. The CROSS regimen can be used in a 'real-world' setting but individual factors that may contribute to OS should be considered in decision-making.
目前，对于局部晚期食管癌患者，在其超出原入选标准的情况下，可采用食管癌放化疗后手术研究（CROSS）方案。这项基于全国人群的研究评估了扩大这些标准后治疗效果的实施安全性。
分析了2015年至2022年间荷兰癌症登记处中5061例根据新辅助放化疗（nCRT）CROSS方案治疗的局部晚期食管癌（cT1N+/T2 - 4aN0 - 3/M0）患者。共有1958例符合原标准（O - CROSS组），1348例符合一项或多项扩大标准（肿瘤长度>8 cm、年龄>75岁、世界卫生组织评分>2和/或体重减轻>10%）（E - CROSS组），最终1342例O - CROSS患者和852例E - CROSS患者接受了手术切除。主要结局为总生存期（OS），即从nCRT开始（OS - nCRT）和从手术日期（OS - 手术）至死亡或最后一次随访的时间间隔。次要结局为无病生存期、病理完全缓解（pCR）、手术根治性、术后发病率和死亡率。使用Kaplan - Meier方法和Cox比例风险模型进行数据分析。
与O - CROSS组相比，E - CROSS组的OS - nCRT显著更低（中位数分别为30.3个月，95%置信区间27.2 - 33.5个月与45.9个月，95% CI 38.4 - 53.4个月，P < 0.001）。同样，在OS - 手术方面也观察到差异。然而，在对OS - nCRT和OS - 手术进行基线协变量调整后，两组之间未发现差异。此外，在无病生存期、手术根治性和pCR方面未观察到差异。虽然不影响术后死亡率，但O - CROSS组的吻合口漏和血栓栓塞性术后并发症明显更多。
扩大CROSS标准与较低的OS相关，这是由E - CROSS组中较高的年龄、体重减轻>10%和世界卫生组织评分导致的。CROSS方案可在“真实世界”环境中使用，但在决策时应考虑可能影响OS的个体因素。
