Radiotherapy dose escalation in the primary treatment of nasopharyngeal carcinoma: a systematic review and meta-analysis

Lester Bryan A. Co, Ryan Anthony F. Agas, JC Kennetth M. Jacinto, Kelvin Ken L. Yu, Michael A. Mejia, Warren R. Bacorro


Background: Dose escalation with radiotherapy (RT) in nasopharyngeal carcinoma (NPC) remains underutilized despite significant advances in methods of radiation delivery. RT boost during primary treatment has been shown to improve local control rates, which could have an impact on survival. We summarize the currently available evidence for dose escalation in the primary treatment of NPC.
Methods: Databases were systematically searched for eligible studies from the year 2000. Included studies utilized RT dose escalation (BED >70 Gy) in the form of brachytherapy, external beam RT or stereotactic RT boost after external beam RT for primary treatment of NPC. Local recurrence-free survival (LRFS), overall survival (OS), toxicities and other relevant factors for the chosen studies were then pooled and analyzed.
Results: Two randomized trials and 7 retrospective cohort studies with a total of 2,145 patients were included in the final analysis. Nine hundred and eighty-eight patients received dose escalation, mainly in the form of brachytherapy (90%). Patients were mostly male, from China/Southeast Asia, had T1-T2 disease (80%), underwent RT via conventional techniques (87%). Less than half received concurrent chemotherapy. Three-year LRFS (RR 1.04; 95% CI: 0.85–1.28, P=0.71) and OS were not significantly improved with dose escalation. However, the subset of patients pooled from the retrospective studies who did not receive concurrent chemotherapy showed significant a 5-year locoregional failure-free survival (RR 1.05; 95% CI: 1.02–1.09, P=0.005) benefit. Toxicities were not significantly increased with dose escalation.
Conclusions: RT dose escalation in the primary treatment of NPC does not lead to an increase in LRFS, OS, progression free-survival and disease free-survival. However, there seems to be a LRFS benefit with dose escalation using brachytherapy in patients with T1-T2 disease and in patients who did not receive concurrent chemotherapy. Dose escalation with brachytherapy is likewise not significantly associated with any increase in the rate of complications. Data for the efficacy and toxicity of EBRT and SRT boost is currently still lacking.