Non-randomized comparison between definitive concurrent chemoradiotherapy and pre-operative radiotherapy followed by surgery in patients with hypopharyngeal squamous cell carcinoma

Abstract

A standard therapy for clinical stage III and IV hypopharyngeal carcinoma is surgery combined with pre- or post-operative radiotherapy (RT) until now. Few randomized control studies comparing standard surgical treatment to neo-adjuvant chemotherapy followed by RT have been presented in hypopharyngeal carcinoma, but none to concurrent chemoradiotherapy (CRT). To compare the outcomes between concurrent CRT and preoperative radiotherapy followed by radical surgery (RT-S) in the patients with respectable stage II to IV hypopharyngeal carcinoma, and to demonstrate the feasibility of laryngeal preservation approach. Seventy-one patients with Stage II to IV hypopharyngeal squamous cell carcinoma were treated with radical intent for two definitive protocols between April 1992 and December 2001 in Hokkaido Cancer Center Sapporo, Japan. Thirty-four out of the 71 patients were treated with radiotherapy concurrent to chemotherapy using cisplatin (20mg/m2/day) single agent 4 days a week and 3–4 weeks interval between 2 cycles. This study was designed as a phase II clinical trial. The records of other 37 patients treated with RT-S in the same period as the prospective study were retrospectively analyzed to address the results of standard treatment. A nonrandomized comparison was done between concurrent CRT group and RT-S group after having considered selection bias enough (Table 1). Planned total RT dose was 66Gy/ 30F/ 7.5 wks for CRT group. Pre-operative RT dose was 40-44Gy/16-20F/5wks for RT-S group. All patients in CRT group, except 2 cases, completed full CRT. There is no significant difference in patients backgrounds and clinical TNM stage between two groups. A complete response was noted in 29 (85%) of the 34 patients treated with CRT. The 5-year over all survival (OAS) rate, the 5-year disease specific survival(DSS) rate, the 5-year local recurrence free survival (LRFS) rate and the 5-year disease free survival (DFS) rate, for CRT group vs. RT-S group were 60% vs. 30 %, 68% vs. 35%, 63% vs. 54% and 54% vs. 39%, respectively. We could totally realize larynx preservation at a rate of 54% by induction of concurrent CRT. The 5-year DSS rate in T1 through T3, and T4 stage of disease in CRT group was 81% and 25%, and in RT-S group each for 34% and 36%, respectively. There was a significant difference (p = 0.0123) between CRT and RT-S groups in T1 through T3. However, there was no significant difference in T4. Concurrent CRT using cisplatin was effective to preserve larynx and prolong survival in the patients with T1-3 hypopharyngeal cancer. Development of more intensive CRT protocol is expected from these outcomes to improve treatment outcomes of T4. View Large Image Figure ViewerDownload (PPT)