Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy

Abstract

BACKGROUND:The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. METHODS: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m 2 /d on Days 1 and 22) was administered. RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with !4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.

Prognostic Significance of Maximum Primary Tumor Diameter in Nasopharyngeal Carcinoma

“…Although excellent local control can be achieved in NPC by IMRT, distant metastasis remains the major cause of disease failure [14,16,26]. Furthermore, most patients with advanced disease in this study received chemotherapy, though some patients with advanced disease did not receive chemotherapy (due to advanced age, heart disease, hepatitis, severe diabetes, inadequate renal function, patient refusal or economic problems).…”

“…The 5-year overall survival rate for NPC has increased from approximately 50% to 75% over the last ten years [13][14][15]. Advances in diagnostic technology, radiotherapy techniques and the introduction of combined chemotherapy are obvious, important contributors to this achievement [16][17][18][19].…”

Preliminary Results of a Phase I/II Study of Simultaneous Boost Irradiation Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

“…Li et al (2006) propose that radiosensibility could be divided into two biological behaviour types as the radiosensitive and the radioresistant.So during the process of treatment, to adjust total irradiation dose in time according to margins of pathological changes and sensitivity to treatment in order to avoid over-irradiation for sensitive patients and insufficient irradiation for resistant patients.This promises a stronger possibility and feasibility for increasing local control rate and general curative effect by further adjusting fraction dose and total dose of individualized treatment of irradiation. Xiao et al (2010) report that locally advanced nasopharyngeal carcinoma is treated by intensity modulated radiation therapy and simultaneous chemo and radiotherapy, the 3-year overall survival rate is 87.7%, local control rate is 94.9%, an retrospective analysis of simultaneous chemo and radiotherapy of cis-platinum complexes combined with IMRT for staged T3-4 nasopharyngeal carcinoma patients by Frank (Wong et al, 2010) shows that the 3-year DFSR is 91.8% for staged T3-4 patients, and the overall survival rate for staged IIIIVb patients is 64.2-87.4%.…”

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

“…The local area is one of the high incidence areas in China. The progress of radiotherapy technology increased the local control rate by 75-95% (Ng et al, 2010;Xiao et al, 2011;Abbasi et al, 2013). There were about 40% of patients with unsuccessful local therapy combined with distant metastasis; The distant metastasis still appeared on 18.5% of patients with local control (Kong et al, 2014); In addition, about 95% of NPC was undifferentiated non-keratinizing carcinoma.…”

“…Its biological characteristics are highly invasive and distant metastasis easily occurs (Lee et al, 2012). The distant metastasis occurred on about 20% of newly diagnosed 1 patients (Xiao et al, 2011). Chemotherapy is the main method for treating distant metastasis of NPC and various kinds of cytotoxic drugs have anticancer activity to NPC.…”