Survival impact of radiotherapy interruption in nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A big-data intelligence platform-based analysis

Abstract

Purpose: To evaluate the effect of radiotherapy interruption (RTI) in patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).

Patients and methods: A total of 7826 patients using the well-established big-data intelligence platform were identified. Computer-generated random numbers were used to assign these patients into a training cohort (n = 3913 patients) and an internal validation cohort (n = 3913 patients). RTI was defined as the difference between radiation treatment time and planned radiation time (assuming a Monday start). Survival analysis was performed using the Kaplan-Meier method for survival, and log-rank test to evaluate difference. Optimal RTI threshold was identified using the recursive partitioning analyses (RPAs). Multivariate analysis was performed using the Weibull model. The primary endpoint was overall survival (OS).

Results: The optimal threshold of RTI with respect to OS in the training cohort was 6.5 d based on RPAs. Therefore, a uniform threshold of 7 d (<7 vs. ≥7 d) was selected to classify both training and validation cohorts into high and low RTI groups for survival analysis. RTI of ≥7 d showed significant detrimental effects on OS in both training (5-y OS, 82.4% vs 86.5%; P = 0.001) and validation cohorts (5-y OS, 85.2% vs 86.7%; P = 0.013) than those patients with RTI of <7 d. Consistent with results of the univariate analysis, RTI of ≥7 d was found to be an independent unfavorable prognostic factor for OS in both training (HR, 1.49; 95% CI, 1.14-1.95; P = 0.003) and validation cohort (HR, 1.37; 95% CI, 1.07-1.65; P = 0.031). Subgroup analysis showed that RTI of ≥7 d had significant adverse effects on prognosis of NPC patients receiving IMRT, regardless of TNM stage and chemotherapy (P < 0.05 for all).

Conclusions: In the IMRT era, RTI independently influences survival. Raising RTI ≥ 7 d was consistently unfavorable for NPC survival. Medical practitioners must remind patients on the importance of minimizing RT interruptions.

Keywords: Intensity-modulated radiotherapy; Nasopharyngeal carcinoma; Optimal threshold; Prognostic impact; Radiotherapy interruption.