Unraveling the Patterns and Pathways of Local Recurrence of Nasopharyngeal Carcinoma: Evidence for Individualized Clinical Target Volume Delineation

Abstract

Backgrounds: Despite publication of international guidelines, there are notable controversial points of clinical target volume (CTV) delineation in nasopharyngeal carcinoma (NPC). Recently, scholars proposed a novel way of delineation of CTV in NPC -- individualization of CTV delineation based on T classification and spread patterns, which yielded excellent long-term local control with limited late toxicities. The aim of this study was to clarify the anatomic patterns and pathways of local recurrence of NPC and provide a clinical reference for the delineation of CTV. Methods: A total of 869 patients with non-metastatic NPC were treated with intensity-modulated radiation therapy (IMRT) at our institution between 2009 and 2010. Among the 57 cases of local/locoregional recurrence, 52 cases with traceable radiotherapy plans and magnetic resonance imaging at the time of the first diagnosis of recurrence were included. Anatomical structures and gross tumor volume of local recurrence were contoured. The incidence of relapse of each anatomic structure, route of local recurrence, and their correlation were analyzed. Results: Locally advanced disease had a significantly increased risk of recurrence in the posterior nasal cavityand a trend towards higher risk of recurrence in the clivus, lateral pterygoid muscle, and hypoglossal canal. Based on the incidence of local recurrence, we constructed a high-risk map for the early and locally advanced stages. Given the higher incidence of relapses in locally advanced disease, these structures were strongly recommended to be encompassed by the CTV of T3-4 diseases, including posterior ethmoid sinus, lateral pterygoid muscle, hypoglossal canal, inferior orbital fissure, and cavernous sinus. Local recurrences were classified into five routes, where anterior extension accounted for the majority (30.8%), and caudal tumor extension pathway had the lowest incidence (5.8%). There was a significant correlation between the local recurrences of neural foramina and neighboring anatomical structures along each pathway. All cases relapsed at unilateral cavernous sinus, most at the same side of primary tumor. Conclusions: Local recurrence of NPC varied according to T classification, followed a stepwise pattern, spread via neural foramina, and recurred at ipsilateral cavernous sinus. This provides meaningful clinical evidence for delineation of CTV, especially individualized delineation.

Patterns and Prognosis of Local Recurrence of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy

“…In the present study, the most common sites of local recurrence were the nasopharynx (93%) and skull base (53.7%), followed by the parapharyngeal space, prevertebral space, cavernous sinus, masticator space, and the pterygopalatine fossa. This is consistent with previous reports [6,18,19]. In 32 patients with rNPC after IMRT, Li et al reported recurrence rates of 78.1% and 59.4% in the nasopharynx and skull base, respectively; the authors also found significantly higher invasion rate of the ethmoid sinus in patients with rNPC than in patients with primary NPC [6].…”