The Role of Post-Neoadjuvant Chemotherapy Tumor Volume for Prognostication and Treatment Guidance in Loco-Regionally Advanced Nasopharyngeal Carcinoma.

Fo-Ping Chen,Jia Kou,Feng Li,Ying Sun,Li Lin,Li Li,Guan-Qun Zhou,Wei-Hong Zheng,Dan-Wan Wen

doi:10.3390/cancers11111632

Abstract

The value of post-neoadjuvant chemotherapy (NACT) tumor volume for prognostication in loco-regionally advanced nasopharyngeal carcinoma (LA-NPC) is unascertained. Here, we recruited 4109 histologically proven LA-NPC (stage III-IVA) that were treated with radical chemo-intensive-modulated radiotherapy (IMRT). Post-NACT gross primary tumor (GTVp) and lymph node (GTVnd) volumes of each patient were calculated from planning computed tomography (CT). We observed similar linear association between GTVp/GTVnd and overall survival (OS); thresholds of 52 cm3 for GTVp and 12 cm3 for GTVnd were consistent for risk discretization for OS, disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). Recursive partitioning analysis (RPA) modelling incorporating T-/N-categories and GTVp/GTVnd yielded four T-N-volume (TNV) risk groupings with disparate OS (p < 0.001). TNV risk stratification outperformed GTVp/GTVnd and eighth edition TNM for predicting OS (AUC 0.643 vs. 0.541–0.591; p < 0.001), DFS (0.629 vs. 0.545–0.580; p < 0.001), and DMFS (0.652 vs. 0.522–0.621; p < 0.001). NACT + concurrent chemoradiotherapy (CCRT) over NACT + IMRT was not superior for low- and low–intermediate-risk groupings (p > 0.05 for both), but superior for intermediate- and high-risk groupings in terms of OS (HR 0.68 (95% CI 0.47–0.99) for intermediate risk, 0.73 (0.55–0.97) for high risk; both p < 0.05). Overall, GTVp/GTVnd represent effective indicators for prognostication and decision-making in LA-NPC after NACT.

Highlights

Nasopharyngeal carcinoma (NPC) arises from the nasopharyngeal epithelium and has an extremely unbalanced geographical distribution, with a high incidence in southern China and the surrounding areas [1]
The concurrent chemoradiotherapy (CCRT) followed neoadjuvant chemotherapy (NACT) is widely recognized as high toxicity and poor tolerance; only about 30–39% of patients could complete three cycles of concurrent chemotherapy after NACT [4,6]
The results of our study suggested that post-NACT tumor volume represented an independent prognostic factor of tumor relapse and death, and the tumor volume demonstrated a similar linear dose-response relationship for HROS, HRDFS, HRDMFS, HRLRFS

Summary

Introduction

Nasopharyngeal carcinoma (NPC) arises from the nasopharyngeal epithelium and has an extremely unbalanced geographical distribution, with a high incidence in southern China and the surrounding areas [1]. For patients with loco-regionally advanced NPC (LA-NPC), chemo-radiotherapy is essential because of the poor prognosis of these patients [3]. The concurrent chemoradiotherapy (CCRT) followed NACT is widely recognized as high toxicity and poor tolerance; only about 30–39% of patients could complete three cycles of concurrent chemotherapy after NACT [4,6]. This raises interesting questions regarding the necessity of concurrent chemotherapy for the patients with LA-NPC but having good response to NACT. Identification of an effective response evaluation index for NPC after NACT to inform on the risk of distant metastasis/loco-regional relapse for treatment intensification or de-intensification is essential

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Discussion

Conclusion