330 - SOAR-HN: A Phase II Randomized Trial of Stereotactic Body Radiotherapy vs. Conventionally Fractionated Reirradiation for Previously Treated, Unresectable Head and Neck Cancer
Presenter(s)
L. F. Spurr1, A. Lee1, H. Wang2, A. S. Garden1, M. T. Spiotto1, J. P. Reddy1, S. J. Shah1, C. D. Fuller1, G. B. Gunn1, W. H. Morrison1, S. J. Frank1, A. C. Moreno1, G. M. Chronowski1, D. I. Rosenthal1, D. Swanson3, S. Y. Su4, N. D. Gross4, R. Ferrarotto5, and J. Phan1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Locoregional failure after prior RT for head and neck squamous cell carcinoma (HNSCC) remains a major cause of morbidity and mortality. Conventionally fractionated (CF) reirradiation (reRT) offers curative potential for unresectable patients but is limited by radioresistance and cumulative toxicity. Stereotactic body radiotherapy (SBRT) is a highly conformal hypofractionated technique increasingly used for reRT that may improve the therapeutic ratio, but prospective randomized data are lacking. We conducted a phase II randomized trial comparing SBRT to CF reRT, hypothesizing noninferiority of SBRT for grade =3 treatment-related adverse events (G3+ AEs).Materials/Methods:
Patients were randomized to SBRT (36.5-42.5 Gy in 3-6 fractions) or CF (66-70 Gy in 33-34 fractions) reRT and stratified by concurrent systemic therapy. Eligible patients had 1–3 select unresectable recurrent or second primary HNSCC tumors (<60 cc each with cumulative tumor volume <100 cc), treated with curative intent. The primary endpoint was time to first reRT-attributable G3+ AE (CTCAE v4.0), analyzed using cumulative incidence with death as a competing risk (Fine – Gray). Secondary endpoints were overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS; defined as failure within 2 cm of the treatment volume) and patient-reported outcomes, measured by composite MDASI-HN and longitudinally assessed using ANCOVA, adjusted for baseline score. Intention-to-treat (ITT) and as-treated (AT) analyses were performed.Results:
Sixty-seven patients were enrolled; 59 had evaluable outcomes (ITT: 32 SBRT, 27 CF; AT: 47 SBRT, 12 CF). Fifty-nine percent of CF-assigned patients crossed over to SBRT. Notably, no patients who experienced G3+ AE crossed over. Median follow-up was 28.3 months (range 0.7-85.5). GTVs were similar between arms but clinical target volumes were larger in the CF arm (53.0 vs 34.3 cc, Wilcoxon P=0.024). Thirteen G3+ AEs occurred in 8 (13.6%) patients, most commonly dysphagia (n=5) and pain (n=4); one G4 (oral bleeding) and no G5 events were observed; 75% occurred in patients treated to mucosal sites. The 2-year cumulative G3+ AE rates were 6.7% with SBRT vs 23.9% with CF (ITT, P=0.073) and 4.4% vs 51.4% (AT, P<0.001). Survival outcomes did not significantly differ between arms (ITT 2-year OS: 58.9% SBRT vs 62.4% CF, P=0.84; PFS: 53.0% vs 58.0%, P=0.97; LFFS: 35.9% vs 48.7%, P=0.69) overall or when stratified by concurrent systemic therapy, tumor site, or recurrence vs second primary. MDASI-HN scores were similar between arms except at 3 months in the ITT analysis (SBRT adjusted mean 49.5 vs CF 11.1, P=0.0017) and 6 months in AT (58.8 vs 22.0, P=0.048).Conclusion:
SBRT reRT is associated with fewer G3+ AEs and comparable survival to CF reRT for unresectable HNSCC. High CF-to-SBRT crossover limits survival comparisons and reflects the shorter SBRT treatment course. These data support testing SBRT reRT for previously treated, unresectable HNSCC in a phase III study.