Impact of Chemoradiotherapy Intensity on Pathological Complete Response in Patients with Esophageal Cancer Receiving Trimodality Therapy

Abstract

Despite the current standard of neoadjuvant chemoradiation therapy followed by radical surgery improving outcomes in patients with operable esophageal carcinoma (EC), there are still limited reports of clinical and treatment-related features that might predict pathological complete response (pathCR), which indicated superior survival outcome in many series. The purpose of this study is to evaluate if chemoradiotherapy intensity and other clinical or treatment-related features might predict pathCR and acute toxicity in patients with esophageal cancer who received trimodality therapy. We retrospectively analyzed clinical and treatment-related features of 127 consecutive patients with EC who received trimodality therapy in two tertiary centers between January 2010 and December 2015. Either primary or nodal specimens with no residual carcinoma were defined as pathCR. We applied logistic regressions to identify independent clinical or treatment related features, especially chemoradiotherapy intensity, associated with pathCR and acute toxicity. The receiver-operating characteristic (ROC) curve was also generated to obtain the best cut-off point. With a majority of squamous cell histology (N=124, 97.6%) and male gender (N= 121, 95.3%), all patients received neoadjuvant therapy with cisplatin and fluorouracil chemotherapy and radiotherapy. A pathCR was achieved in 47 (37%) of 127 patients. Low-grade tumors (odds ratio [OR]: 32.279; p < .0001) and cumulative cisplatin dose (mg/m2) during radiotherapy (OR: 1.031; p < .0001, cut-off point: 128.5 mg/m2) significantly predicted higher pathCR rates in multivariate logistic regression models. A lower pathCR rate was observed in patients with greater body weight loss (by percentage) during neoadjuvant therapy (OR: 0.865, p= .010, cut-off point: 8.85%). Meanwhile, the higher radiation dose to gross tumors was not associated with pathCR (OR: 1.000, p= .374), but was the only independent factor that significantly predicted severe (≥ grade 3) acute hematologic toxicity (OR: 1.002, p< .001, cut-off point: 5200 cGy). Low-grade tumors and cumulative cisplatin dose during radiotherapy were predictive of a higher possibility of pathCR. Greater body weight lost during neoadjuvant therapy was a negative predictor for pathCR. Increasing radiation dose did not contribute to pathCR, but did increase the severity of acute hematologic toxicity. Interventions that improve treatment tolerance as per protocol and nutrition status during neoadjuvant therapy are needed to achieve higher pathCR rates and potentially better outcomes.