Clinical Investigation Phase 1 Trial of SBRT to the Prostate Fossa After Prostatectomy Leslie K. Ballas, MD,* Chunqiao Luo, MS, y Eugene Chung, MD, PhD, JD, z Amar U. Kishan, MD, x Igor Shuryak, MD, PhD, k David I. Quinn, MD, { Tanya Dorff, MD, # Shamim Jhimlee, MBBS,* Raymond Chiu, BS, CMD,* Andre Abreu, MD,** Richard Jennelle, MD,* Monish Aron, MD,** and Susan Groshen, PhD y *Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California; y Department of Preventative Medicine, University of Southern California Keck School of Medicine, Los Angeles, California; z Rose Medical Center, Denver, Colorado; x Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California; k Center for Radiological Research, New York, New York; { Department of Medical Oncology, University of Southern California Keck School of Medicine, Los Angeles, California; # Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; and **Department of Urology, University of Southern California Keck School of Medicine, Los Angeles, California Received Aug 30, 2018. Accepted for publication Dec 26, 2018. Summary This phase 1 trial evaluated the tolerability of moderate to extreme hypofractionation to the prostate fossa, as measured by physician- scored toxicity and patient- reported outcomes. Given the similar equivalent dose in 2-Gy fractions of all dose levels, we hypothesized that prostate fossa stereotactic body radiation therapy would be well tolerated, with Purpose: The primary objective was to evaluate the maximum tolerated dose (within 10 weeks after treatment) associated with increasing hypofractionation to the prostate fossa (PF). We hypothesized that escalating the dose per fraction (fx) to the PF would have acceptable toxicity. Materials and Methods: Tested dose levels (DLs) were 3.6 Gy  15 fx (DL1); 4.7 Gy  10 fx (DL2); and 7.1 Gy  5 fx (DL3). Escalation followed a 6 þ 6 rules-based design with 12 patients required at the maximum tolerated dose. Dose- limiting toxicity was defined as grade (G) 3, gastrointestinal (GI) or genitourinary (GU) toxicity by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Patients completed quality-of-life questionnaires. Results: Twenty-four patients with indications for adjuvant or salvage radiation ther- apy (RT) enrolled (6 at DL1 and 2; 12 at DL3). All patients had at least 6 months of follow-up (median follow-up, 14.1 months). Four patients received concurrent androgen deprivation therapy. No G  3 GI or GU toxicity was seen at any DL; Reprint requests to: Leslie K. Ballas, MD, University of Southern California Keck School of Medicine, Department of Radiation Oncology, 1441 Easlake Ave, Norris G350, Los Angeles, CA 90033. Tel: (323) 865- 3050; E-mail: lballas@med.usc.edu This protocol is registered with ClinicalTrials.gov, NCT number: NCT02446366. Conflicts of interest: none. Supplementary material for this article can be found at https://doi.org/ 10.1016/j.ijrobp.2018.12.047. Int J Radiation Oncol Biol Phys, Vol. -, No. -, pp. 1e11, 2019 0360-3016/$ - see front matter Ó 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.ijrobp.2018.12.047 Radiation Oncology International Journal of biology physics www.redjournal.org