1106: Randomized Trial of Conventional Fractionated RT (CFRT) vs. Concomitant Chemo Radiotherapy (CTRT) and Accelerated Radiotherapy (ACRT) in Patients With Advanced, Non Nasopharyngeal, Squamous Cell Cancers of the Head and Neck Region

Abstract

Randomized trial comparing efficacy and sequelae of conventional fractionated RT (CFRT) vs. concomitant chemo radiotherapy (CTRT) vs. accelerated fractionated radiotherapy (ACRT) in patients with advanced HNSCC. Between April 2000 and Dec 2004, 150 untreated patients with Stage III and IV non nasopharyngeal, squamous cancers of the head and neck region were included in this 3 arm trial. Arms A: CFRT (66-70Gy in 6-7wks @ 5 fractions per week), Arm B: CTRT (66-70Gy in 6-7wks @ 5 fractions per week + concomitant weekly Inj. Cisplatin 30mg/m2), Arm C: ACRT (66-70Gy in 6.5wks @ 6 fractions per week). The sixth fraction was delivered using the reduced fields. For randomization patients were stratified by site and stage. The analysis was on an intention to treat basis. Response and toxicity were documented according to the WHO response assessment and RTOG criteria, respectively. Results were analysed after a median follow-up of 17 months (Range: 0-68months). Median age of patients was 53.6 years (range 20-70). Majority were males (95%) with a male: female ratio of 17:1. Oropharynx was the most commonly involved sub site (56%), followed by larynx (23.3%) and hypo pharynx (18%). Treatment was completed as per protocol in 94%, 90 % and 86% of patients in arms A, B and C respectively. The median duration of treatment was 49(31-68), 51(32-63), and 40(1-55) days for arms A, B, and C respectively. The median RT dose was 70Gy in each arm. In the CTRT arm the median weekly dose of Cisplatin was 45mg (range: 30-50mg). Seventy four percent received more than 5 cycles of Cisplatin. The overall CR rates were 43%, 53% and 31% in the three arms respectively. The 2yr DFS were 38%, 55% and 31% (p=0.07) for arms A, B, and C respectively and the 2yr OS were 44%, 58% and 44% (p=0.35). For each arm univariate analysis of all known prognostic factors was done to assess their impact on DFS and OS. There was a significant improvement in DFS for pts in the CTRT arm with oropharyngeal tumours (p=0.01). CTRT also resulted in improved DFS compared to CFRT and ACRT in pts with stage III disease (p=0.04) although it did not translate into a significant difference in OS, although the CTRT arm did better (p =0.09). When the DFS was analysed according to the T-stage, the benefit with chemotherapy was seen in patients with low primary tumor volume (T1-T2) which was statistically significant (p= 0.02). On further analysing patients in T1-2 subgroup, the results were in favour of the CTRT arm in the presence of nodal disease (p= 0.03), especially in patients with higher nodal involvement i.e. N2c (p = 0.03). These results did not translate into a benefit in OS. For larger tumours (T3-T4) with N0 status the DFS in the three arms was 71%, 58.9% and 39%, respectively (p= 0.12).The incidence of grade II skin reactions was higher in the accelerated arm (p = 0.482). Seventeen percent, 28%, 28.6% of patients on arm A, B and C respectively experienced grade III mucosal toxicity. CTRT resulted in superior DFS in pts. with advanced disease compared to CFRT & ACRT, especially for oropharyngeal tumors. This improvement did not translate into an improved OS and was associated with acceptable toxicity and compliance. The toxicity of CTRT is acceptable with a marginal increase in hospital support.