Personalising Nasopharyngeal Cancer: Systemic Therapy and Radiotherapy Treatment Volumes

Nasopharyngeal carcinoma (NPC) is sensitive to chemotherapy and radiotherapy, with current treatment recommendations largely based on TNM-stage. Radiotherapy remains the backbone of treatment for NPC. Over the past decades, the addition of concurrent chemotherapy to radiotherapy for early-stage disease, and the combination of induction chemotherapy (IC) or adjuvant chemotherapy (AC) with chemoradiotherapy vs chemoradiotherapy alone for advanced disease have led to substantial improvements in survival of patients with NPC. Nonetheless, in the era of precision oncology, there is growing recognition that patients with NPC are clinically heterogeneous even within the same stage-group, and future advances must focus on individualisation of systemic therapy and radiotherapy. In this review, we summarised the published evidence on EBV DNA as a biomarker for clinical stratification and treatment response in NPC, and discussed some of the ongoing clinical trials of EBV DNA-directed personalisation of systemic therapy in locoregionally-advanced disease. Next, we assessed the evidence concerning individualised radiotherapy strategies for target volume delineation of the primary tumour and cervical nodes that ought to be based on individual tumour extent and IC response (for locoregionally-advanced NPC) as opposed to the historical one-size fits all approach. In the same vein, radiotherapy dose de-escalation may be considered in good responders to IC, whereas for the poor responders, altered fractionation or dose escalation may be required to target resistant disease. These concepts are particularly relevant in the era of combinatorial immune checkpoint blockade therapy with radiotherapy, where preservation of circulating immune cells is crucial to evoke immune-mediated antitumour cytotoxicity.