Introduction: T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well-studied. Methods: 104 T4 or N3 NPC patients were retrospectively reviewed during 2007-2018. They were planned for IC followed by CCRT using intensitymodulated radiotherapy. Results: In the whole group, five-year failure-free survival (FFS), locoregional failure-free survival (LRFS), distant failure-free survival (DFFS) and overall survival (OS) were 40.9%, 45.7%, 46.9% and 53.6% respectively. Isolated marginal failure rate was 5% (4/80) among patients with primary tumours located close to critical OARs. Pre-IC gross tumour volume primary (GTVp) total volume > 110 cm 3 correlated with worse five-year LRFS (OR 6.37, P = 0.008), DFFS (OR 8.89, P = 0.003) and OS (OR 50.12, P < 0.001). In the T4 subgroup, IC improved D100% GTVp from 61.39 Gy to 64.71 Gy (P < 0.001) and V100% GTVp from 98.78% to 99.28% (P < 0.001). Conclusion: Our study demonstrated improved dosimetric parameters and low isolated marginal failure rate. It supported the use of IC and CCRT for tumours located close to critical OARs. Further research is warranted to compare predictive roles of pre-and post-IC tumour volumes. For high-risk patients being defined by pre-IC volume or other prognostic models, treatment escalation should be considered.
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