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BACKGROUNDReirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC) after a definitive dose of radiotherapy (RT) is challenging and usually associated with severe toxicities. Intensity‐modulated carbon ion RT (IMCT) offers physical/biologic advantages over photon‐based intensity‐modulated RT. Herein, the authors report their initial experience of IMCT in previously irradiated patients with locoregionally recurrent NPC.METHODSPatients with locoregionally recurrent, poorly differentiated or undifferentiated NPC who underwent salvage therapy with IMCT at the Shanghai Proton and Heavy Ion Center between May 2015 and August 2017 were included in the current study. The IMCT doses were 50 to 66 Gray equivalent (GyE) (2.0‐3.0 GyE/daily fraction), delivered via raster scanning technology. The 1‐year overall survival, disease‐specific survival, progression‐free survival (PFS), local recurrence‐free survival, regional recurrence‐free survival, and distant metastasis‐free survival were calculated. Univariate and multivariate analyses of PFS were performed to identify possible predictive factors.RESULTSAmong the 75 patients included, 4 patients, 14 patients, 29 patients, and 28 patients, respectively, had recurrent American Joint Committee on Cancer stage I, stage II, stage III, and stage IVA/B disease. With a median follow‐up of 15.4 months (range, 2.6‐29.7 months), the 1‐year overall survival, disease‐specific survival, PFS, local recurrence‐free survival, regional recurrence‐free survival, and distant metastasis‐free survival rates were 98.1%, 98.1%, 82.2%, 86.6%, 97.9%, and 96.2%, respectively. A higher fraction size of 3 GyE (vs <3 GyE) or a higher biological equivalent dose significantly improved the PFS rate on univariate analysis, but not on multivariate analysis. No patient developed acute toxicity of grade ≥2 during IMCT. Late treatment‐induced severe (grade 3 or 4) toxicities were infrequent, but included mucosal necrosis (9.3%), xerostomia (1.3%), and temporal lobe necrosis (1.3%).CONCLUSIONSThis initial experience in the first 75 patients with locoregionally recurrent NPC was encouraging. Carbon ion RT could provide promising survival rates with infrequent severe toxicities for patients with locoregionally recurrent NPC. Cancer 2018;124:2427‐37. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m2 and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.

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Locally recurrent nasopharyngeal carcinoma (rNPC) after definitive IMRT occurs in 10% of all cases and represents a distinct clinical entity that has been selectively enriched by radio-resistant cancer cells. Therefore, we report of the outcomes of 77 patients who had repeat salvage-IMRT for rNPC after only a definitive course of IMRT. Various clinical outcomes were measured. Log-rank tests were used to detect differences in the survival outcomes between factor-defined subgroups. Multivariable analysis was performed using the Cox proportional hazard model. The median follow-up time was 25.7 months (range 3.0–75.7 months), measured from the time of recurrence. The median OS time and PFS time of the entire cohort was 37.0 and 20.5 months, respectively. Thirty-four patients (44.2%) died. Approximately 35% of these patients died from disease progression, but 53% were from treatment-induced severe adverse effects (SAEs) without evidence of disease progression. Higher T-classification of the recurrent tumor and the development of SAEs were found to be the only independent and significant adverse prognostic factors on multivariable analysis. These outcomes underscore the particularly virulent characteristics of rNPC after definitive IMRT. Concerning is the impact of re-irradiation toxicity on patient mortality.

BACKGROUND:The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA=IVB nasopharyngeal cancer (NPC

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