Prolonged Interval between Initiation of Neoadjuvant Chemotherapy and Radiotherapy Impairs Long Term Survivals in Locoregionally Advanced Nasopharyngeal Carcinoma

Abstract

Longer waiting time for radiotherapy (RT) has been associated with inferior survival in nasopharyngeal carcinoma (NPC), but this effect is unclear with the inclusion of neoadjuvant chemotherapy (NACT). Our study aimed to investigate the impact of time factor between NACT and RT in locoregionally advanced NPC. Clinical data on 577 patients with locoregionally advanced NPC treated with intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. The optimal cut-off value of time interval was identified using a “surv_cutpoint” function in R software. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. Univariate and multivariable survival analyses were performed with Cox proportional hazards models. Univariate analysis showed that patients with longer interval between initiation of NACT and RT (≥70 days) had significantly worse OS (81.9% vs. 68.0%, P=0.012), DMFS (83.6% vs. 63.9%, P=0.001) and DFS (69.4% vs. 51.4%, P=0.001), compared those with shorter waiting time. This difference remained significant when stratified by N classification and cycles of NACT (≤2 vs. >2) (P<0.05). No difference was observed in LRFS. After adjusting for clinical variables including age, sex, T and N classification, treatment modality and cumulative cisplatin dose, multivariable models revealed that time interval (≥70 days) was an independent predictor for OS (HR 1.88, 95%CI: 1.16-3.03, p=0.011), DMFS (HR 2.08, 95%CI: 1.27-3.41, p=0.004) and DFS (HR 1.83, 95%CI: 1.24-2.69, p=0.002). Severe delay of radiotherapy by NACT may detriment long-term survivals for locoregionally advanced NPC patients, most likely through enhanced distant metastasis rate. Long-course NACT and extended RT planning process should be avoided.