Dose intensification in curative head and neck cancer radiotherapy—Linear quadratic analysis and preliminary assessment of clinical results

Abstract

Purpose : The feasibility of reducing overall treatment time by 2 weeks in the curative radiotherapeutic management of head and neck cancer patients is reported in a pilot trial of Hyperfractionated, Accelerated Radiotherapy with Dose Escalation (HARDE). This regimen prescribes 76 Gy in 5 weeks to definitive head and neck cancer patients, and 65 Gy in 5 weeks to high-risk postoperative patients. The linear quadratic model is used to compare predicted tumor cell kill with HARDE versus that expected with conventional fractionation (CF). Materials and Methods : Between January 1991 and March 1992, 40 head and neck cancer patients were treated with HARDE at the University of Wisconsin Comprehensive Cancer Center. Case-matched controls treated with CF were identified from patients treated at the same institution between 1980–1990, based on tumor site, stage, and extent of prior surgery. Individual patient treatment data (total dose, fraction size, overall time) rather than idealized schedule data from each group were analyzed using the linear quadratic model. Results : Seventy-nine case-matched controls were identified for comparison with HARDE patients. The predicted increase in log cell kill for HARDE patients over case-matched controls was 1.5 and 13 logs, respectively, in the definitive and postoperative settings. This difference in log cell kill projects an improvement in locoregional tumor control for HARDE patients of between 10–25%. HARDE patients experience very brisk acute mucosal reactions and moderately prolonged mucosal healing, however, 91% have completed therapy without a treatment break. Conclusion : A 2-week reduction in overall treatment time for curative head and neck cancer patients is feasible while maintaining doses > 70 Gy. Based on radiobiologic predictions, such treatment intensification may significantly improve rates of locoregional tumor control. However, intensified acute mucosal reactions accompany such accelerated therapy.