Role of sequential chemoradiotherapy in stage II and low-risk stage III-IV nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: A propensity score-matched analysis

Objectives: To investigate the role of sequential chemoradiotherapy (SCRT; induction chemotherapy [IC] followed by intensity-modulated radiotherapy [IMRT]) in stage II and low-risk stage III-IV nasopharyngeal carcinoma (NPC). Materials and methods: Four well-matched groups were individually generated using propensity score matching in patients (n = 689) with stage II (SCRT vs. concurrent chemoradiotherapy [CCRT], SCRT vs. IMRT alone) and low-risk stage III-IV NPC (SCRT vs. CCRT, SCRT vs. IC + CCRT). Five-year overall/disease-free/locoregional relapse-free/distant metastasis-free survival (OS/DFS/LRRFS/DMFS) and acute hematological toxicities were compared between groups. The value of SCRT was further investigated in multivariate analysis and subgroup analysis by adjusting for covariates and limiting IC-to-IMRT time interval, respectively. Results: SCRT led to equivalent survival outcomes compared to CCRT/IMRT alone and CCRT/IC + CCRT in stage II and low-risk stage III-IV NPC, respectively (all P >. 050). In multivariate analysis, patients with stage II NPC treated by SCRT obtained higher DMFS (AHR = 0.22, 95% CI = 0.05-1.00, P =. 050), but not OS, DFS or LRRFS, compared to patients receiving CCRT; non-significant differences were observed between SCRT and other treatments. SCRT with short IC-to-IMRT time interval (<= 70 days) achieved higher 5-year survival rates than IMRT alone (DMFS: P =. 046), CCRT (stage II NPC; OS: P =. 047; DMFS: P =. 020) and IC + CCRT (DFS: P =. 041). Moreover, SCRT was associated with higher, equivalent and lower frequencies of acute hematological toxicities than IMRT alone, CCRT and IC + CCRT, respectively. Conclusion: SCRT is mainly beneficial in stage II NPC, leading to better DMFS and/or equivalent acute hematological toxicities compared to CCRT/IMRT alone. CCRT is still the best choice for low-risk stage III-IV NPC.