Nasopharyngeal Carcinoma – a rare but potentially curable disease

Michalis Karamouzis

Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial, published in the Journal of the National Cancer Institute in November 2011 (Chen QY, et al.)

Nasopharyngeal carcinoma (NPC) has a high endemic incidence (more common in eastern Asia, northern Africa and Alaska), is pathogenetically correlated with Epstein-Barr Virus (EBV) and is usually appreciated as a separate clinical entity. The histological classification of nasopharyngeal carcinoma proposed by WHO in 1978, categorized tumours into three groups: type I included typical keratinising squamous-cell carcinomas, similar to those found in the rest of the upper aerodigestive tract; type II included non-keratinising squamous carcinomas; and type III included undifferentiated carcinomas. An alternative classification has divided tumours into two histological types, namely squamous-cell carcinomas and undifferentiated carcinomas of the nasopharyngeal type. The second classification is correlated with EBV serology: patients with squamous-cell carcinomas have a reduced EBV titre, whereas those with undifferentiated carcinomas of the nasopharyngeal type have raised titres.

Radiotherapy (RT) is the standard treatment for NPC, although it can produce undesirable complications after treatment because of the location of the tumour at the base of skull, closely surrounded by and in close proximity to radiation dose-limiting organs. In RT a dose of 65–75 Gy is normally given to the primary tumour and 65–70 Gy to the involved neck nodes, whereas the dose for prophylactic treatment for a node-negative neck is 50–60 Gy. Because of the high incidence of occult neck node involvement, prophylactic neck RT is usually recommended. Several prospective randomized trials and meta-analyses have demonstrated that concurrent chemo-radiotherapy (CRT) with or without adjuvant chemotherapy is superior to RT alone in the treatment of locoregionally advanced NPC. The prognosis of patients with stage I-II NPC is generally favourable, and this group of patients has largely been excluded from clinical trials with CRT.

This randomized clinical trial is the first one reported to compare the clinical impact of CRT over radiotherapy alone in early-stage NPC patients. Totally 230 patients were randomized to RT alone versus CRT (RT plus weekly cisplatin 30mg/m2).The primary objective of the study was overall survival and secondary endpoints were progression-free survival, distant metastasis-free survival and locoregional relapse-free survival. With a median follow-up of 60 months, CRT improved the 5-year overall survival rate (94.5% vs 85.8%, P=0.007), the progression-freezer survival (87.9% vs 77.8%, P=0.017) and distant metastasis free-survival (94.8% vs 83.9%, P=0.007). No statistically significant difference was observed regarding locoregional relapse-free survival (93% vs 91.1%, P=0.29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with overall survival, progression-free survival and distant control of the patients. The CRT patient group experienced statistically significantly more acute (and not late) side effects.

Although there are some limitations in this study (e.g. use of two-dimensional RT technique instead of IMRT, lower than previously used in other clinical trials cisplatin dose), it brings significant clinical data regarding the utility of CRT in early-stage NPC patients. These data should be taken into serious account since distant metastases remain the major cause of treatment failure and the outlook for stage IV NPC patients remains poor.

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