Nasopharyngeal Cancer in Non-Endemic Areas: Impact of Treatment Intensity within a Large Retrospective Multicenter Cohort

Background: Recommendations for managing nasopharyngeal carcinoma (NPC) patients in non-endemic areas are largely derived from studies conducted in endemic areas. We aimed to analyse the impact of treatment approaches on survival in this patients’ setting Methods: In an international, multicenter, retrospective study, we analysed clinical data of consecutive NPC patients diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy (RT), three-dimensional conformal RT or intensity modulated RT, IMRT), alone or concomitant radio-chemotherapy (RT-CT), and intensive (IT) including RT-CT preceded by induction and/or followed by adjuvant chemotherapy (CT). We fitted Cox proportional hazard models for both overall and Epstein Barr-Encoded RNA (EBER) status-specific analyses. The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. Findings: Overall, 1021 and 1113 patients were eligible for OS and DFS analyses, respectively (501 and 554 with EBER status available). In the whole group, 5-year OS and DFS were 84% and 65%, respectively. The use of NIT was associated with a risk of death or recurrence 1·37 times higher than patients receiving IT. Patients submitted to NIT and induction CT + concurrent 3DRT-CT had a risk of death or recurrence 1·5 and 1·7 times higher than patients treated with induction CT + concurrent IMRT-CT, respectively. The IT had no impact on OS in neither EBER+ nor EBER- patients; however, IT showed better DFS in EBER+ but not in EBER- patients. Interpretation: This study represents, the largest data analysis on NPC patients in low-incidence areas. Among IT approaches, induction CT followed by concurrent IMRT-CT achieved the highest DFS rate, confirming the potential role of this approach in advanced EBER+ disease. The benefit of IT on DFS was restricted to EBER+ patients, suggesting that additional therapy offers no advantages in EBER- cases. Funding: None to declare. Declaration of Interest: Dr Bossi reports personal fees from Merck, Sanofi Regeneron, BMS, MSD, GSK, Astrazeneca, Sunpharma, Angelini and grants from GSK and Sunpharma, outside the submitted work. Dr Buglione reports personal fees from Meck Serono, outside the submitted work. Dr Cirauqui Cirauqui reports congress support from MSD, Merck, BMS and Roche, and personal fees from BMS and Roche, outside the submitted work. Dr Ursino reports grants from Merck Serono, Nestle, Kyowakirin and Astrazeneca, outside the submitted work. Dr D’angelo reports personal fees from Astrazeneca, Nestle and Merck Spa, outside the submitted work. Dr. Licitra reports personal fees and grants from Astrazeneca, Bayer, BMS, Boehringer ingelheim, Debiopharm International SA, EISAI, Merck Serono MSD, Novartis, Roche; Personal fee from Bayer, SOBI, IPSEN, GSK, Doxa Pharma srl, Incyte Biosciences Italy srl, Amgen, Nanobiotics Sa; Grants from Celgene International, Exelixis inc, grants Hoffmann-La Roche ltd, IRX Therapeutics inc Medpace inc, grants Pfizer, outside the submitted work. Dr Mesia reports Consulting and advisory role for Merck, MSD, Roche, Astazeneca, BMS and speaker's Bureau for Merck, MSD, BMS, Roche. All the other authors have nothing to disclose. Ethical Approval: Ethics approval was obtained from all concerned Institutional Review Boards and the Ethics Committees.