Induction and Concurrent Taxanes Enhance Both the Pulmonary Metabolic Radiation Response and the Radiation Pneumonitis Response in Patients With Esophagus Cancer

Abstract

Purpose The primary aim of this study was to quantitatively assess pulmonary radiation toxicity in patients who received thoracic radiotherapy combined with induction and/or concurrent chemotherapy with or without taxanes for esophageal cancer. Materials/Methods Subjects were 139 patients treated at The University of Texas M. D. Anderson Cancer Center for esophageal cancer and who had [18F]-fluorodeoxyglucose positron emission tomography/computed tomography imaging from November 1, 2003 to December 15, 2007, for disease restaging after chemoradiotherapy. Patients were grouped as having had (1) no taxanes, (2) induction or concurrent taxanes, and (3) both induction and concurrent taxanes. Clinical pulmonary toxicity was scored using the NCI Common Terminology Criteria for Adverse Events version 3. Linear regression was applied to the FDG uptake versus radiation dose to determine the pulmonary metabolic radiation response (PMRR) for each case. Clinical toxicity scores and PMRR among groups were evaluated for significance differences. Results The crude rates of pneumonitis symptoms were 46%, 62%, and 74% for groups 1, 2, and 3, respectively. The ANOVA test of log(PMRR) by treatment was significant (p=0.0046). Group 3 had 61% higher PMRR compared with group 1 (p=0.002). Group 2 had 38% higher PMRR compared with group 1 (p=0.015). Group 3 had 17% higher PMRR compared with group 2 (p=0.31). A PMRR enhancement ratio of 1.60 (95% CI: 1.19–2.14) was observed for group 3 versus group 1. Conclusions Patients given taxanes chemotherapy as induction and concurrent chemotherapy had significantly higher PMRR and clinical pneumonitis symptoms than did patients whose chemotherapy did not include taxanes.

Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

“…While some studies have suggested that rates of esophagitis are higher with platinum agents than with taxanes (13, 14), data directly comparing chemotherapeutic agents and the risk of esophagitis in locally advanced NSCLC are sparse. Moreover, our institution recently reported an association between taxanes and an increased risk of pneumonitis (15). Given the prevalence of taxanes in definitive chemoradiation, the toxicity profile should continue to be explored both prospectively and retrospectively, particularly as radiation doses are further escalated.…”

Failure patterns in patients with esophageal cancer treated with definitive chemoradiation

“…35, 36 Finally, even though we found that the GTV was the most common site of initial failure, our patients also experienced high rates of systemic failure; thus efforts to increase local control may not necessarily translate into improved survival unless systemic therapies also improve. Thus far, trials to evaluate intensification of chemotherapy through the addition of induction chemotherapy have shown a mixed response 37, 38 . Perhaps the utility of this approach will not be fully realized until the high local failure rate is addressed.…”

Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

“…It occurs after radiotherapy for esophagus cancer 6, 7 and for breast cancer 8 . Radiation pneumonitis is an inflammatory reaction within irradiated normal lung tissue in response to radiation injury 9, 10 .…”