Nasopharyngeal necrosis following intensity-modulated radiation therapy of primary nasopharyngeal carcinoma-incidence rate and predictors of risk.

OBJECTIVES: This study aimed to investigate the incidence of post radiation nasopharyngeal necrosis (PRNN) in primary NPC after intensity modulated radiation therapy (IMRT) and identify the predictors of risk. METHODS: Data of 5798 NPC patients who received IMRT-based treatment between April 2009 and December 2015 were retrospectively reviewed. PRNN was diagnosed by MRI or nasopharyngoscopy. Dosimetric factors were selected by the least absolute shrinkage and selection operator logistic regression and applied to Cox proportional hazards modeling with clinical predictors. RESULTS: Among the 5798 patients, 53 developed PRNN-an incidence rate of 0.89%. Age > 55 years, diabetes, LDH > 170 U/L, and tumor volume of nasopharynx > 60.5 cm(3),were independently associated with risk of PRNN(all p < 0.05. Dosimetric analysis showed that D(0.5cc)(EQD2) of 80.20 Gy might be the dose constraint for nasopharynx (sensitivity = 62.3%, 33 out of 53; specificity = 84.2%, 4897 out of 5925). Besides, the RTOG dose constraints of V(110%) (V(77.0)) should be less than 0.2% in case of increasing risk of PRNN(HR = 2.28, 95% CI: 1.26-4.41, p = 0. 01). CONCLUSION: Nasopharyngeal necrosis is rare after primary IMRT. The independent risk factors for this rare complication include age > 55 years, diabetes mellitus, LDH > 170 U/L, tumor volume of nasopharynx > 60.5 cm(3), D(0.5cc)(EQD2) > 80.20 Gy, and V(77.0) < 0.2% to the planning treatment volume of nasopharynx. KEYPOINTS: High radiation dose may lead to devastating nasopharyngeal necrosis after primary IMRT. Real world analysis will provide valuable information for prevention. FINDINGS: The aged, diabetes mellitus, large tumor volume, D(0.5cc)(EQD2) > 80.20 Gy and V(77.0) < 0.2% to planning treatment volume increased the risk of nasopharyngeal necrosis. CLINICAL RELEVANCE: This real-world study provided valuable information for prevention of PRNN. Compared with RTOG protocol, D(0.5cc)(EQD2) > 80.20 Gy is a reliable evidence-based new complement to dose constraint, especially for T3-4 disease, who received high prescribe dose in China.