Carbon Ion Radiation Therapy for Salvage Treatment of Locoregionally Recurrent Nasopharyngeal Carcinoma

Abstract

Reirradiation for locally recurrent nasopharyngeal carcinoma (LR-NPC) after a definitive radiotherapy is challenging and usually associated with severe adverse-effects. The 2-year overall survival (OS) rates of LR-NPC patients treated with X-ray based intensity-modulated radiation (IMRT) ranged between 45%∼60%, depends on the stage at local recurrence. Carbon-ion radiotherapy (CIRT) offers both physical and biological advantages over IMRT. To report the outcomes of 205 LR-NPC patients treated with intensity-modulated CIRT. Patients with locoregionally recurrent, poorly or un-differentiated NPC (WHO type II or III) who underwent salvage therapy with CIRT at the Shanghai Proton and Heavy Ion Center (SPHIC) between May 2015 and June 2019 were included in this analysis. The CIRT doses were 50 to 69 Gray equivalent (GyE) (2.0-3.0 GyE/daily fraction), delivered via raster scanning technology. The 2-year OS, progression-free survival (PFS), local recurrence free survival (LPFS), regional progression-free survival (RPFS), distant metastasis-free survival (DMFS) as well as acute and late toxicities were analyzed. Prognostic indicators of the outcomes were analyzed for overall survival. Among the 205 patients included, 17 patients, 50 patients, 60 patients, and 78 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 18.4 (range, 2.0-74.6) months, the 2-year OS, PFS, LPFS, RPFS, and DMFS rates were 83.1%, 41.8%, 54.0%, 85.4%, and 94.8%, respectively. Favorable prognostic indicators that reached statistical significance included a longer disease-free interval (p=0.001), small volume of gross tumor (p=0.025), stage I-II (vs. stage III-IVB) disease (p < 0.001), lack of necrosis (p=0.023) and carotid artery encasement (p=0.017) before CIRT. No patient developed acute toxicity of grade ≥3 during CIRT. Late treatment-induced severe (grade 3-4) toxicities included mucosal necrosis (20.5%, including patients presented with mucosal necrosis prior to re-irradiation), xerostomia (0.5%), cranial neuropathy (0.5%), and temporal lobe necrosis (0.98%). Among patients experienced mucosal necrosis, grade 4 and 5 hemorrhage were seen in 3.4% (7 patients) and 5.8% (12 patients) with or without local disease progression. The treatment results of the 205 patients received salvage CIRT suggested that the new radiation technology substantially improved the survival outcomes and toxicities profile for LR-NPC, as compared to re-irradiation with photon-based IMRT. Further investigation that compares the efficacy and safety between CIRT vs. IMRT, preferably in prospective manner and with longer follow-up, are needed to confirm these findings.