Conventional versus hyperfractionated radiotherapy in locally advanced head and neck cancer

ABSTRACT

Radiotherapy is often the primary treatment of locally advanced squamous cell carcinoma of the head and neck, but the optimal fractionation schedule has been controversial. The aim of this study was to examine whether, after preceeding induction chemotherapy, hyperfractionated radiotherapy [HFRT] is superior to conventional fractionated radiotherapy [CFRT]. Patients with locally advanced squamous cell carcinoma of the head and neck were treated with three cycles of cisplatin [100 mg/m[2] D1] and 5-fluorouracil [1000 mg/m[2] D1-4], repeated every 3 weeks. Then patients were randomized to receive either CFRT at 1.8-2 Gy/fraction /day, 5 day/week to 65-70 Gy/33- 35 fractions/7 weeks or HFRT at 1.2 Gy /fraction, twice daily with a 6-hours interfraction interval, 5 days/week to 76.8 Gy/64 fractions/7 weeks. All patients in both treatment arms received concomitant chemotherapy in the form of weekly bolus injection of cisplatin [20mg/m[2]]. Of the 60 patients entered, only 53 patients were evaluable for outcomes. The primary end points were local control and progression- free survival. Chemotherapy was well tolerated, the overall response rate after induction chemotherapy was 73.6%, including 13.2% complete response rate. After completion of radiotherapy, patients treated with HFRT had an overall response rate of 96.2% versus 77.8% in CFRT [P= 0.04] and complete response rate of 65.4% in HFRT versus 40.7% in CFRT [P=0.01]. After a median follow- up of 28 months, overall survival was 57.7% in HFRT versus 44.4% in CFRT [P= 0.07]. The 2-year progression-free survival was 44% in HFRT versus 23.8% in CFRT [P=0.03]. The 2- year locoregional control was significantly higher in HFRT [58.8%] than those with CFRT [36.4%] [P=0.02]. The incidence of local recurrence rate was 41.2% in HFRT versus 63.6% in CFRT [P=0.02]. However, the incidence of distance metastases was 7.7% in HFRT versus 11.1% in CFRT [P=0.4]. Patients treated with HFRT had significantly greater acute side effects compared to CFRT. However, there was no significant increase of late effects. After induction chemotherapy, hyperfractionated radiotherapy is more efficaceous than conventional fractionated radiotherapy in locally advanced squamous cell head and neck cancer. Acute but not late effects are increased, but it is tolerable and manageable