Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results

Abstract

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.

Dose-Limiting Organs at Risk in Carbon Ion Re-Irradiation of Head and Neck Malignancies: An Individual Risk-Benefit Tradeoff

“…The cumulative rates of acute and late severe (≥ grade III) side effects after CIR were acceptable at 1.8% and 14.3%, respectively. Prior studies on re-irradiation of HNC with carbon ions reported similar toxicity profiles [6,23,24]. However, the distribution of re-irradiation sites in our assessment was quite different from those of prior studies on CIR in recurrent HNC.…”

“…Hayashi et al [21] reported absolute dose constraints at CIR of 30 Gy (RBE) for the brainstem and spinal cord and 40 Gy (RBE) for the optic system. Hu et al [6] assumed a recovery from the previous photon radiotherapy set at 70%, independent of the RT interval. Consequently, the CTV was reduced if it was close to OAR.…”

“…Furthermore, simultaneous systemic therapies lead to a significant increase in treatment-related toxicities [1,2]. However, in prior evaluations on heavy-ion re-irradiation [3,6,23], concomitant systemic therapies were primarily excluded. The clinical effects of CIR in combination with systemic agents have yet to be evaluated.…”

“…Re-irradiation in cases of head and neck cancer (HNC) is associated with an increased risk of severe side effects [1][2][3]. The total cumulative applied radiation dose, the irradiated volume [4], and the time interval [5][6][7] are crucial when considering a second course of irradiation at the same anatomical site. Nonetheless, toxicity rates are frequently underestimated, even in prospective clinical studies [8].…”

Prognostic potential of liquid biopsy tracking in the posttreatment surveillance of patients with nonmetastatic nasopharyngeal carcinoma

“…However, despite its potential significance, to our knowledge supporting data investigating the value of cfEBV DNA for disease surveillance are limited; relevant studies mainly have focused on cfEBV DNA prognostication before and in the middle of treatment . Generally, the detection of early recurrent and/or metastatic disease is crucial for better salvage results in patients with NPC because those individuals with early‐stage recurrent disease and a low tumor burden usually have higher treatment response and survival rates . Conventional workups, including physical and imaging examinations, have limited sensitivity and accuracy in diagnosing tumor recurrence early.…”