Radiotherapy Dose Escalation in the Primary Treatment of Nasopharyngeal Carcinoma A Systematic Review and Meta-analysis

Abstract

Purpose/Objective(s)

Dose escalation in nasopharyngeal carcinoma remains underutilized despite significant advances in methods of radiation delivery. Brachytherapy, EBRT or SRT boost during primary treatment has been shown to improve local control rates, which could have an impact on survival. Our objective is to summarize the currently available evidence for dose escalation in nasopharyngeal carcinoma.

Materials/Methods

Databases were systematically searched for eligible studies with dose escalation (BED >70 Gy) in the form of brachytherapy, EBRT or SRT boost during the primary treatment of nasopharyngeal cancer with EBRT. Single-arm, non-English, study population <10 and studies published before 2000 were excluded. LRFS, OS, PFS, DFS and toxicity outcomes for the chosen studies were then pooled and analyzed.

Results

2 RCTs and 7 retrospective cohort studies with a total of 2145 patients were included in the final analysis. 988 patients received dose escalation, mainly in the form of brachytherapy (90%). Patients were mostly male, from Southeast Asia, had T1-T2 disease (80%), underwent radiotherapy via 2D techniques (87%), but less than half received concurrent chemotherapy. From the 2 RCTs, 3-year LRFS (RR 1.04; 95% CI: 0.85 – 1.28, p=0.71), OS, PFS and DFS 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 3-year LRFS (RR 1.04; 95% CI: 1.01 – 1.07, p=0.003 benefit with dose escalation. Patients with T1/T2 disease also had significantly improved LRFS benefit with dose escalation. Toxicities were not significantly increased with dose escalation.

Conclusion

Dose escalation in the primary treatment of NPC does not lead to an increase in LRFS, OS, PFS or DFS. 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. More prospective studies are needed to define other subsets of patients will truly benefit from dose escalation.