Abstract
Because of tumor heterogeneity, overall survival (OS) differs significantly among individuals with nasopharyngeal carcinoma (NPC), even among those with the same clinical stage. Relying solely on TNM staging to guide treatment remains imperfect. To establish a comprehensive nomogram to estimate individualized OS and to explore stratified treatment regimens for risk subgroups in nonmetastatic NPC. This cohort study included 8093 patients diagnosed with NPC at a single center in China from April 2009 to December 2015. The sample was split into a training cohort (5398 participants [66.7%]) and validation cohort (2695 [33.3%]). Data were analyzed in May 2020. Age, T stage, N stage, Epstein-Barr virus (EBV) DNA level, serum lactate dehydrogenase (LDH) levels, and albumin (ALB) levels. The primary end point was OS. The nomogram for estimating OS was generated based on multivariate Cox proportional hazards regression. The performance of the nomogram was quantified using Harrell concordance index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, and a calibration curve. OS rates were established using the Kaplan-Meier method, and intersubgroup differences were examined by the log-rank test. Among the 8093 participants, 5688 (70.3%) were men, and the median age at diagnosis was 45 years (range, 7-85 years). Six variables (age, T stage, N stage, EBV DNA levels, LDH levels, and ALB levels) were identified through multivariate Cox regression and incorporated into a nomogram to estimate OS. The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating OS (C index, 0.716 [95% CI, 0.698-0.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; AUC, 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates. The validation cohort confirmed the results. Patients were stratified into 4 risk groups based on the 25th, 50th, and 75th percentile score values estimated from the nomogram. The 4 nomogram-defined risk groups demonstrated significantly different intergroup OS (3-year OS rates: risk group 1, 1328 of 1345 [98.7%]; risk group 2, 1289 of 1341 [96.1%]; risk group 3, 1222 of 1321 [92.5%]; risk group 4, 1173 of 1391 [84.3%]; P < .001). These risk groups were associated with the efficacy of different treatment regimens. For example, for risk group 4, induction chemotherapy with concurrent chemoradiotherapy was associated with a significantly better OS than concurrent chemoradiotherapy (log-rank P = .008) and intensity-modulated radiotherapy alone (log-rank P < .001). In this study, the proposed nomogram model enabled individualized prognostication of OS and could help to guide risk-adapted treatment for patients with nonmetastatic NPC.
Highlights
There is an unbalanced ethnic and geographic distribution in nasopharyngeal carcinoma (NPC) cases, with the highest incidences occurring in south China and Southeast Asia.[1,2] NPC cells are highly sensitive to irradiation, which has resulted in radiotherapy (RT) becoming the mainstay treatment modality for nonmetastatic NPC.[3]
The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating overall survival (OS) (C index, 0.716 [95% CI, 0.6980.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; area under the curve (AUC), 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates
Baseline Characteristics and Survival The baseline clinical and treatment characteristics of the 8093 eligible patients with nonmetastatic NPC are shown in eTable 1 in the Supplement, and the characteristics were well balanced between the training cohort and validation cohort
Summary
There is an unbalanced ethnic and geographic distribution in nasopharyngeal carcinoma (NPC) cases, with the highest incidences occurring in south China and Southeast Asia.[1,2] NPC cells are highly sensitive to irradiation, which has resulted in radiotherapy (RT) becoming the mainstay treatment modality for nonmetastatic NPC.[3]. Three published phase 3 randomized clinical trials[20,21,22] performed in endemic areas provide evidence that additional IC can significantly improve survival compared with treatment with CCRT alone in stage III to stage IVA NPC. With these encouraging results, the 2018 NCCN guidelines were upgraded to include the recommendation of IC with CCRT from category III to category IIA for patients with stage III to stage IVA NPC.[3] IC with CCRT is an increasingly important treatment regimen in managing stage III to stage IVA NPC in the IMRT era. There is still controversy regarding whether IC is applicable to all patients with stage III to stage IVA NPC.[20,21,22,23,24,25,26,27]
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