Patterns of Local-Regional Relapse Following Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Despite definite radiotherapy, post-treatment recurrence remains a major challenge for patients with nasopharyngeal carcinoma (NPC). This study aimed to evaluate risk factors for local-regional relapse in patients with non-metastatic NPC treated with intensity-modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> We retrospectively analyzed data from 1040 patients with newly diagnosed, non-metastatic, biopsy-proven NPC from 2013 to 2019 (including 7, 133, 475, and 425 cases of stage I, II, III, and IVA disease, respectively, according to the 8th edition of the American Joint Committee on Cancer staging system). All patients received IMRT at a single institution in China (with or without concurrent chemotherapy). Recurrent sites were delineated on imaging and coregistered with the initial treatment planning computed tomography. The recurrences were classified as "in-field failure" if 95% of GTVr (gross tumor volume of recurrence) was within the 95% isodose; "marginal failure" if 20%–95% of GTVr was within the 95% isodose, or "out-field failure" if less than 20% of GTVr was inside the 95% isodose. Univariate and multivariate analyses with the Cox proportional hazards model were performed to identify the independent risk factors. <h3>Results</h3> With a median follow-up of 44 months, 76 patients (7.3%) developed a recurrence. The median interval of relapse was 20.5 months (range: 7–109 months). The 2-year overall survival, local relapse-free survival and regional relapse-free survival were 95.8%, 96.4% and 98.4%, respectively. Local-alone, regional-alone and synchronous local-regional failures accounted for 57.9% (44/76), 32.9% (25/76), and 9.2% (7/76) of recurrent NPC cases, respectively. In these patients, the male:female ratio was 2.4:1 and the median age was 50 years (range: 21–74 years). Among the 62 local-regional failures with available diagnostic images, 53 cases (85.4%) were "in-field", 5 cases (8.1%) had "marginal", 4 cases (6.5%) were as "out-field". Multivariate analysis showed that the non-keratinizing differentiated subtype and the absence of concurrent chemotherapy (CCT) were independent factors for local recurrence after IMRT (differentiated NPC versus undifferentiated NPC HR = 1.987, 95% CI 1.056–3.738, <i>P</i> = 0.033; non-CCT versus CCT HR = 2.098, 95% CI 1.134–3.884, <i>P</i> = 0.018). The rate of lymph nodes associated with liquefaction was 12.4% by the primary tumors but 46.7% at regional recurrence (liquefaction versus non-liquefaction HR = 11.031, 95% CI 4.992–24.372, <i>P</i><0.001). <h3>Conclusion</h3> The major recurrence patterns were in-field failures. The poor local control rates may be associated with the absence of CCT and differentiated carcinoma of NPC. Lymph node with liquefaction was an independent prognostic factor for regional recurrence.