APOPTOSIS IN ESOPHAGEAL CANCER FOLLOWING INDUCTION CHEMORADIOTHERAPY

Background, The poor survival of patients with esophageal cancer follo wing esophagectomy has led to intense investigation into combined moda lity therapy. Based on results from clinical trials examining chemorad iotherapy alone without surgery, resection has come under increased sc rutiny and its necessity as a component of a multimodal approach has b een questioned. In this study, we examined whether residual tumor cell s in esophagectomy specimens following induction chemoradiotherapy are viable and, therefore, provide putative evidence for the appropriaten ess of esophagectomy. Materials and methods. Between August 1991 and J anuary 1995, 46 patients were entered into an induction chemoradiother apy trial consisting of B-fluorouracil, cisplatin, alpha-interferon, a nd concurrent external beam radiotherapy followed by esophagectomy. Re sponse was determined histologically and apoptosis assessed with a ter minal deoxytransferase assay system. p53 status was determined by immu nohistochemistry and mutational analysis. Results. Thirty-eight patien ts underwent esophagectomy, 33 of whom had either a complete (n = 10) or partial (n = 23) response; None of the 28 patients with residual tu mor in the resected specimen had 100% apoptotic cells and the vast maj ority of specimens had less than a 10% apoptotic rate. The percentage of apoptotic cells did correlate with tumor differentiation but not wi th histologic type nor presence of p53 mutations. Conclusions. These d ata suggest that resection following upfront chemoradiotherapy is a ne cessary component of a multimodality approach to esophageal cancer and will ultimately provide superior local-regional control to a nonsurgi cal approach. (C) 1998 Academic Press.