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.

        一項Ⅲ期臨床試驗顯示，對於早期食管癌患者，在手術切除之前接受化療和放療並不能提高根治性切除率，而且最重要的是，不能改善生存率。這項研究於6月30日發表在《臨床腫瘤學雜誌》在線版上(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.

        法國裏昂Claude Huriez大學醫院消化與腫瘤外科的Christophe Mariette醫生指出，不幸的是，這種治療策略還使術後死亡率增加了2倍，從而使這一患者群的風險-獲益比率變得更加不平衡。

        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.

        既往評價食管癌新輔助化放療的臨床試驗得出了相互矛盾的結果，其中一些試驗顯示該治療有效，部分試驗甚至顯示患者的中位生存率倍增，而其他試驗則未觀察到獲益。這些研究多數存在樣本量小、腫瘤類型多樣、輻射劑量和化療方案不同，以及術前分期技術和手術切除充分程度不同等局限性。此外，研究受試者中的早期食管癌患者一直較少，因為多數患者在入組時已處於疾病更晚期。

        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.

        在本項研究中，Mariette醫生及其同事招募的受試者僅限於：年齡<75歲、初治、根據胸腹CT和內鏡超聲判斷為Ⅰ期或Ⅱ期食管腺癌或鱗狀細胞癌;可以選擇采用PET掃描、頸部超聲或放射性核素骨掃描進行術前評估。

        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).

        該研究花費了9年時間從30家法國醫療中心招募了195例患者。這些受試者被隨機分組，在潛在根治性手術前接受新輔助化療+放療(幹預組，98例)，或單純接受潛在根治性手術(單純手術組，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.

        在幹預組中，放療總劑量為45 Gy，分25次在5周內完成。在同一時間內給予化療，包括2個周期的氟尿嘧啶和順鉑輸注。幹預組所有患者均在完成治療後2~4周時再次接受評估，繼而實施手術。

        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).

        手術包括經胸食管切除術與擴展雙野淋巴結清掃和高位胸內吻合(針對近端邊緣位於隆突下方的腫瘤)/頸部吻合(針對近端邊緣位於隆突上方的腫瘤)。

        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.

        經過中位時間7.8年的隨訪，有125人死亡：幹預組有62.4%的患者死亡，單純手術組死亡率為66%，差異無顯著性。幹預組患者的中位總生存期為31.8個月，單純手術組為41.2個月，無統計學差異。同樣，幹預組患者的3年總生存率為47.5%，5年總生存率為41.1%，而單純手術組分別為53%和33.8%，也無顯著差異。

        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.

        幹預組和單純手術組的根治性切除率也無顯著差異(93.8% vs. 92.1%)，表明化療和放療對這些早期腫瘤沒有益處。既往研究已經表明，此類減瘤治療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.

        接受術前化放療的患者的術後死亡率，是單純接受手術的患者的3倍以上(11.1% vs. 3.4%)。幹預組患者的術後死亡原因包括主動脈破裂、無法控製的乳糜胸、吻合口漏、胃導管壞死、腸係膜和下肢缺血，以及急性RDS，而單純手術組患者的術後死亡原因為肺炎和急性RDS。

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

        上述結果提示，術前化放療“並不是Ⅰ期或Ⅱ期食管癌的合理新輔助治療策略”。

Commentary – Try definitive, not adjuvant, chemoradiotherapy

隨刊述評：嚐試決定性而非輔助性的化放療

        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.

        這項研究是在法國國立癌症研究所和裏爾大學醫院的支持下開展的，沒有接受商業支持。Mariette醫生報告稱無相關利益衝突，一名作者報告稱與羅氏和默克存在利益關係。

        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.

        杜克癌症研究所腫瘤放療科的Brian G. czito醫生、ManishaPalta醫生和Christopher G. Willett醫生評論指出，鑒於早期食管癌患者似乎不能從術前新輔助化放療中獲益，也許是時候考慮其他方法了：將決定性而非新輔助化放療作為一線治療。

        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.

        一些醫療中心已經開始對潛在可治愈性食管癌患者采用這種方法了，從而手術留作搶救治療手段。與將手術作為一線治療相比，決定性化放療與較低的治療相關死亡率和相似的生存結局相關。

        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醫生、Palta醫生和Willett醫生報告稱無相關利益衝突(J. Clin. Oncol.2014 June 30 [doi:10.1200/JCO.2013.53.6532])。