Preoperative chemotherapy is considered a standard option for resectable adenocarcinoma of the GEJ but remains controversial for the preoperative management of intrathoracic esophageal cancer. Preoperative chemoradiotherapy versus surgery alone Surgery is considered important in the management of esophageal cancers. The CALGB 9781 study randomized esophageal cancer patients (77% adenocarcinoma, 24% squamous cell carcinoma) to preoperative chemoradiation (cisplatin, 5-FU, and RT to 50.4 Gy) followed by surgery versus surgery alone (12). Despite poor accrual (56 out of a planned 475 patients), a significant survival advantage was seen in the trimodality group with 5-year survival of 39% versus 16%

Inhibitors,research,lifescience,medical with surgery alone and median survival of 4.5 years compared to 1.8 years with surgery alone (p=0.002). The addition of chemoradiation in this setting afforded a convincing survival benefit and provided justification for the existing de-facto standard of care in patients with clinical stage II-III disease. In an EORTC Inhibitors,research,lifescience,medical study reported by Bosset, 282 patients with squamous cell carcinoma were randomized to preoperative cisplatin with radiation therapy (split course 37 Gy using Inhibitors,research,lifescience,medical 3.7 Gy per fraction) followed by surgery versus surgery alone (13). Results showed significant

improvements in favor of preoperative therapy for disease-free survival, local control, cancer-related deaths, and curative resection Inhibitors,research,lifescience,medical rates; however, there was no difference in overall survival (18.6 months for both groups).

Significantly more postoperative deaths were seen in the group treated with preoperative CRT (12% versus 4% with surgery alone), mainly because of the higher number of patients with respiratory insufficiency, mediastinal infection or sepsis. The authors discussed that the increased number of postoperative deaths in the CRT could have been due to the “deleterious effects of high dose of radiation per fraction or of CRT on lung tissue.” They recommended future studies click here incorporate 2-Gy range fraction sizes, continuous radiation to overcome repopulation seen with Inhibitors,research,lifescience,medical split course therapy, and 5-FU chemotherapy. This trial therefore showed that preoperative CRT could prolong disease-free survival and local control but not overall survival although was likely limited Thiamine-diphosphate kinase by the radiation scheme. An Australian study by Burmeister et al evaluated 257 patients with both adenocarcinoma (63%) and squamous cell carcinoma (27%) of the esophagus (14). Patients were randomized to preoperative cisplatin and 5-FU with concurrent radiation therapy (35 Gy in 15 fractions) or immediate surgical resection. The CRT and surgery groups had significantly more complete resections with clear margins and fewer positive lymph nodes than the surgery alone group did. However, neither progression-free survival (16 months with CRT and surgery versus 12 months with surgery alone, HR=0.82, p=0.