Reirradiation of Small Skull Base Tumors: A Comparison of Patient Outcomes after Stereotactic Body Radiotherapy, Intensity-Modulated Radiotherapy, and Proton Therapy

Objective Local disease recurrence or a second primary cancer in patients previously irradiated to the head and neck cancer poses a treatment challenge. In a subgroup of patients with small skull base tumors and no significant burden of distant disease, radiotherapy can potentially achieve good local control and maintain quality of life. To date, there are no reports comparing the effectiveness and toxicity of three commonly utilized highly conformal radiotherapy techniques: intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton radiotherapy (PRT). The aim of this study is to generate preliminary data for the development of a randomized clinical trial comparing SBRT and IMRT/PRT for recurrent small skull base tumors.

Methods Patients who received conformal reirradiation utilizing IMRT, SBRT, or PRT for recurrent or new small skull base tumors (<60 mL) between April 2000 and July 2016 were identified. Those with <3 months of follow-up were excluded. Patients' treatment details were recorded. Clinical outcomes and treatment toxicity were assessed. The Kaplan–Meier method was used to estimate the locoregional control (LRC), progression-free survival (PFS), and overall survival (OS).

Results Of the 49 patients who met the inclusion criteria, 17 (34.7%) received SBRT, 16 (32.7%) received IMRT, and 16 (32.7%) received PRT. The majority of patients had an ECOG performance status of 0 to 1 (95.9%), and 28 (57.1%) had squamous cell carcinoma histology. The median retreatment volume was 27 mL (range: 2.9–59.7 mL). The median re-irradiation dose was 66 Gy (range: 50–70 Gy) in 33 fractions for IMRT/PRT, and 45 Gy (range: 35 – 47.5 Gy) in 5 fractions every other day for SBRT. Thirty-four (69.4%) patients received concurrent chemotherapy. The median time to re-irradiation was 30 months (range: 3–246 months). With a median follow-up of 20 months (range: 3–153 months), the LRC, PFS, and OS rates were 80.6, 64, and 89.2% at 1 year, and 71.8, 53.1, and 73% at 2 years, respectively. Four patients developed Grade III late toxicity—one received SBRT (soft tissue necrosis), one received IMRT (dysphagia requiring feeding tube insertion), and two received PRT (trismus and glaucoma) [P1]. There were no Grade IV or V toxicities. The 1- and 2-year late Grade III toxicity rate was 7%. On correlative analyses, the use of concurrent chemotherapy (p = 0.0009), interval between radiotherapy courses (p = 0.004), and radiation treatment technique (p = 0.01) were associated with improved LRC. The use of concurrent chemotherapy was also associated with late Grade III toxicity (p = 0.01) but not overall survival.

Conclusion Hypofractionated short-course radiotherapy offers similar local control and toxicity rates as conventionally fractionated radiotherapy in the setting of reirradiation. A prospective clinical trial is needed to further guide selection of radiation treatment modalities.