For patients with early-stage esophageal cancer, undergoing chemotherapy and radiotherapy before surgical excision failed to improve the rate of curative resection and, most importantly, failed to boost survival in a phase III clinical trial, according to a report published online June 30 in the Journal of Clinical Oncology.

        一项Ⅲ期临床试验显示，对于早期食管癌患者，在手术切除之前接受化疗和放疗并不能提高根治性切除率，而且最重要的是，不能改善生存率。这项研究于6月30日发表在《临床肿瘤学杂志》在线版上(J. Clin. Oncol.2014 June 30 [doi:10.1200/JCO.2013.53.6532])。

        Unfortunately this treatment strategy also tripled postoperative mortality, making the risk-benefit ratio even more lopsided for this patient population, said Dr. Christophe Mariette of the department of digestive and oncologic surgery, University Hospital Claude Huriez-Regional University Hospital Center, Lille (France), and his associates.

        法国里昂Claude Huriez大学医院消化与肿瘤外科的Christophe Mariette医生指出，不幸的是，这种治疗策略还使术后死亡率增加了2倍，从而使这一患者群的风险-获益比率变得更加不平衡。

        Clinical trials examining neoadjuvantchemoradiotherapy for esophageal cancer have produced conflicting results, with some showing that the approach is effective, in some cases doubling median survival, while others showed no benefit. Most such studies have been limited by small sample sizes, heterogeneity of tumor types, variations in radiation doses and chemotherapy regiments, and differences in preoperative staging techniques and the adequacy of surgical resections.Moreover, the number of study participants with early-stage esophageal cancer has been very small because most patients already have more advanced disease at presentation, the investigators noted.

        既往评价食管癌新辅助化放疗的临床试验得出了相互矛盾的结果，其中一些试验显示该治疗有效，部分试验甚至显示患者的中位生存率倍增，而其他试验则未观察到获益。这些研究多数存在样本量小、肿瘤类型多样、辐射剂量和化疗方案不同，以及术前分期技术和手术切除充分程度不同等局限性。此外，研究受试者中的早期食管癌患者一直较少，因为多数患者在入组时已处于疾病更晚期。

        For their study, Dr. Mariette and his associates confined the cohort to patients younger than 75 years with treatment-naive esophageal adenocarcinoma or squamous-cell carcinoma judged to be stage I or II using thoracoabdominal CT and endoscopic ultrasound; additional preoperative assessments using PET scanning, cervical ultrasound, or radionuclide bone scanning were optional.

        在本项研究中，Mariette医生及其同事招募的受试者仅限于：年龄<75岁、初治、根据胸腹CT和内镜超声判断为Ⅰ期或Ⅱ期食管腺癌或鳞状细胞癌;可以选择采用PET扫描、颈部超声或放射性核素骨扫描进行术前评估。

        It required 9 years to enroll 195 patients at 30 French medical centers. These study participants were randomly assigned to receive either neoadjuvant chemotherapy plus radiotherapy before potentially curative surgery (98 subjects) or potentially curative surgery alone (97 subjects).

        该研究花费了9年时间从30家法国医疗中心招募了195例患者。这些受试者被随机分组，在潜在根治性手术前接受新辅助化疗+放疗(干预组，98例)，或单纯接受潜在根治性手术(单纯手术组，97例)。

        In the intervention group, radiotherapy involved a total dose of 45 Gy delivered in 25 fractions over the course of 5 weeks. Chemotherapy was administered during the same time period and involved two cycles of fluorouracil and cisplatin infusions. All patients in this group were clinically reevaluated 2-4 weeks after completing this regimen, and surgery was performed soon afterward.

        在干预组中，放疗总剂量为45 Gy，分25次在5周内完成。在同一时间内给予化疗，包括2个周期的氟尿嘧啶和顺铂输注。干预组所有患者均在完成治疗后2~4周时再次接受评估，继而实施手术。

        Surgery comprised a transthoracic esophagectomy with extended two-field lymphadenectomy and either high intrathoracic anastomosis (for tumors with an infra carinal proximal margin) or cervical anastomosis (for tumors with a proximal margin above the carina).

        手术包括经胸食管切除术与扩展双野淋巴结清扫和高位胸内吻合(针对近端边缘位于隆突下方的肿瘤)/颈部吻合(针对近端边缘位于隆突上方的肿瘤)。

        Median follow-up was 7.8 years. There were 125 deaths: 62.4% of the intervention group died, as did 66% of the surgery-only group, a nonsignificant difference, the investigators said (J. Clin. Oncol.2014 June 30 [doi:10.1200/JCO.2013.53.6532]). Median overall survival was 31.8 months in the intervention group and 41.2 months in the surgery-only group, a nonsignificant difference. Similarly, 3-year overall survival was 47.5% and 5-year overall survival was 41.1% in the intervention group, compared with 53% and 33.8%, respectively, in the surgery-only group, which were also nonsignificant differences.

        经过中位时间7.8年的随访，有125人死亡：干预组有62.4%的患者死亡，单纯手术组死亡率为66%，差异无显著性。干预组患者的中位总生存期为31.8个月，单纯手术组为41.2个月，无统计学差异。同样，干预组患者的3年总生存率为47.5%，5年总生存率为41.1%，而单纯手术组分别为53%和33.8%，也无显著差异。

        The rate of curative resection also was not significantly different between the intervention group (93.8%) and the surgery-only group (92.1%), indicating that reducing the tumor with chemotherapy and radiotherapy had no beneficial effect in these early-stage cancers. Previous studies have demonstrated that such downsizing is effective in more advanced esophageal cancers, Dr. Mariette and his associates noted.

        干预组和单纯手术组的根治性切除率也无显著差异(93.8% vs. 92.1%)，表明化疗和放疗对这些早期肿瘤没有益处。既往研究已经表明，此类减瘤治疗在更晚期的食管癌中更有效。

        Postoperative mortality was more than threefold higher among patients who underwent preoperative chemoradiotherapy (11.1%) than in the surgery-only group (3.4%). The causes of postoperative death included aortic rupture, uncontrollable chylothorax, anastomotic leak, gastric conduit necrosis, mesenteric and lower limb ischemia, and acute RDS in the intervention group, compared with pneumonia and acute RDS in the surgery-only group.

        接受术前化放疗的患者的术后死亡率，是单纯接受手术的患者的3倍以上(11.1% vs. 3.4%)。干预组患者的术后死亡原因包括主动脉破裂、无法控制的乳糜胸、吻合口漏、胃导管坏死、肠系膜和下肢缺血，以及急性RDS，而单纯手术组患者的术后死亡原因为肺炎和急性RDS。

        These findings suggest that preoperative chemoradiotherapy "is not the appropriate neoadjuvant therapeutic strategy for stage I or II esophageal cancer," the investigators said.

        上述结果提示，术前化放疗“并不是Ⅰ期或Ⅱ期食管癌的合理新辅助治疗策略”。

Commentary – Try definitive, not adjuvant, chemoradiotherapy

随刊述评：尝试决定性而非辅助性的化放疗

        Dr. Brian G. Czito, Dr. ManishaPalta, and Dr. Christopher G. Willett comment: This study was supported by the French National Cancer Institute’s ProgrammeHospitalier pour la RechercheClinque and Lille University Hospital; it received no commercial support. Dr. Mariette reported no financial conflicts of interest; one of his associates reported ties to Roche and Merck.

        这项研究是在法国国立癌症研究所和里尔大学医院的支持下开展的，没有接受商业支持。Mariette医生报告称无相关利益冲突，一名作者报告称与罗氏和默克存在利益关系。

        Since patients with early-stage esophageal cancer don’t appear to benefit from preoperative neoadjuvantchemoradiotherapy, perhaps it is time to consider a different approach: definitive rather than neoadjuvantchemoradiotherapy as the first-line treatment, said Dr. Czito, Dr. Palta, and Dr. Willett.

        杜克癌症研究所肿瘤放疗科的Brian G. czito医生、ManishaPalta医生和Christopher G. Willett医生评论指出，鉴于早期食管癌患者似乎不能从术前新辅助化放疗中获益，也许是时候考虑其他方法了：将决定性而非新辅助化放疗作为一线治疗。

        Some medical centers have already adopted this approach for patients with potentially curable esophageal cancer, reserving surgery as salvage treatment. Compared with surgery as first-line treatment, definitive chemoradiotherapy is associated with a lower rate of treatment-related mortality and similar survival outcomes, they noted.

        一些医疗中心已经开始对潜在可治愈性食管癌患者采用这种方法了，从而手术留作抢救治疗手段。与将手术作为一线治疗相比，决定性化放疗与较低的治疗相关死亡率和相似的生存结局相关。

        Dr. Czito, Dr. Palta, and Dr. Willett are in the department of radiation oncology at Duke Cancer Institute, Durham, N.C. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Mariette’s report(J. Clin. Oncol.2014 June 30 [doi:10.1200/JCO.2013.53.6532]).

        Czito医生、Palta医生和Willett医生报告称无相关利益冲突(J. Clin. Oncol.2014 June 30 [doi:10.1200/JCO.2013.53.6532])。