The Impact of Tumor Volume and Radiotherapy Dose on Outcome in Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck Treated With Stereotactic Body Radiation Therapy

Despite improvements in disease control and survival outcomes with modern advances in treatment of head and neck cancers,1,2 tumor recurrence remains a significant problem with approximately 15% to 50% locoregional recurrence rates.3–6 Surgical salvage remains the mainstay approach in the management of recurrent disease. Nonoperative approaches such as radiation therapy are alternatives to surgery when disease invades or surrounds major vessels in the head and neck or whenever the morbidity of surgical resection outweighs its benefits. When reirradiation is contemplated in this setting, treatment planning is frequently difficult because of the propensity for regional nodal spread and anatomic proximity to critical structures in the head and neck region, and requires integration of several factors such as extent of disease and overall patient performance status. Few studies have reported data on the use of stereotactic radiosurgery in head and neck cancers due to limited clinical experience. Recent studies by Siddiqui et al,7 Roh et al,8 and Unger et al9 recently reported data in 21, 36, and 65 patients, respectively, with recurrent head and neck cancers of mixed histologies. The current study is unique in that it includes a larger number of patients all with recurrent squamous cell carcinoma of the head and neck (SCCHN). Reirradiation in the setting of prior high-dose radiation with 3-dimensional or intensity-modulated radiation therapy remains a challenge because of the proximity of nearby critical structures and makes stereotactic radiotherapy the ideal treatment of choice due to its highly precise delivery of large doses to the disease site while minimizing toxicities to normal tissues. We have previously reported studies on the experience of our institution using this technique, first in 22 patients with recurrent nonmetastatic previously irradiated head and neck cancer treated with 10 to 25 Gy.10 Results of that study demonstrated the feasibility and safety of stereotactic body radiotherapy (SBRT) in these patients. The results of our prospective phase I dose escalation trial also supported these findings.11 Encouraged by these results, we previously performed a larger retrospective review of our 5-year experience with recurrent previously irradiated SCCHN demonstrating the evolution of this salvage program using SBRT.12 Results of this latter study showed improved locoregional control (LRC) with higher prescription dose while severe toxicities remained rare.12 In the current study, we sought to perform a thorough assessment of the relationship between radiation dose, volume, and treatment outcome. We performed a volumetric analysis for patients with recurrent previously irradiated SCCHN, who were treated with SBRT in a dose escalation program over several years. LRC has been shown to be dependent on tumor volume and prescription dose.13–15 However, dose response and volume response in SBRT for head and neck cancer have not been previously established. Therefore, we sought to establish such parameters for future clinical trials. Based on our previous results, we hypothesized that tumor volume was inversely correlated with LRC and increasing SBRT dose was directly correlated with locoregional tumor control probability, with larger tumor volume requiring higher prescription dose for LRC compared with smaller tumor volume.