Downloaded from http://journals.lww.com/amjclinicaloncology by BhDMf5ePHKbH4TTImqenVDZHALwmCBBpiLdeDzO2hVoVYb8XOC5nwiMIRtWXZoi3 on 09/16/2020 Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking A Phase II Study Giuseppe R. D’Agostino, MD, PhD,* Pietro Mancosu, PhD,* Lucia Di Brina, MD,* Ciro Franzese, MD,*† Luisa Pasini, MD,‡ Cristina Iftode, MD,* Tiziana Comito, MD,* Fiorenza De Rose, MD,* Giorgio F. Guazzoni, MD,†‡ and Marta Scorsetti, MD*† Objectives: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities. Materials and Methods: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0. Results: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir–prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year bio- chemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P = 0.042). Conclusion: Ultrahypofractionated radiotherapy, delivered with flat- tening filter free-volumetric modulated arc therapy and gated by elec- tromagnetic transponders, is a valid option for intermediate-risk prostate cancer. Key Words: SBRT, prostate cancer, Calypso, online tracking, beacon transponders (Am J Clin Oncol 2020;43:628–635) M odern external beam radiotherapy (RT), combining image- guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT), allow the delivery of an increased dose to the target while limiting toxicity to normal tissues. 1 These inno- vations have provided significant clinical benefits to all patients, especially those affected by prostate cancer. In fact, quality of life of these men could have been seriously compromised, in the past, by RT’s heavy side effects. 2,3 Presently, in the context of defin- itive local treatment of prostate cancer, exclusive RT represents a valid alternative to radical surgery, 4 offering comparable efficacy at the price of a minor toxicity, particularly with regard to urinary continence and erectile function. 5 Given the low α/β ratio (estimated to ∼1.5 to 3 Gy) of prostate tumors, in recent years, hypofractionated regimens of RT have been tested, obtaining the reduction of total treatment time, while maintaining the efficacy and an acceptable toxicity profile. 6 As an extreme hypofractionation, stereotactic body radiation treatment (SBRT) has also been explored in localized prostate cancer, exploiting the novel technologies that warrant an improved precision in radiation delivery and an increased protection of the organs at risk, with optimal results in terms of biochemical control and side effects. 7 Several studies suggest that a total dose between 35 and 50 Gy in 5 fractions is the recommended regimen for this treatment; nevertheless, the optimal schedule is still under investigation. 8–10 The recently published American Society for Radiation Oncology (ASTRO), American Society of Clinical Oncology (ASCO), and American Urological Association (AUA) evidence-based guidelines on hypofractionated RT for localized prostate cancer 11 recommend that a dose of 35 to 36.25 Gy in 5 fractions may be offered to low-risk and intermediate-risk patients with prostate sizes <100 cm 3 . Doses > 3625 cGy to the planning target volume (PTV), or a minor number of fractions, are not suggested outside the setting of a clinical trial or multi-institutional registry due to risk of late toxicity. 11 Recently, the first 2 randomized studies comparing SBRT to conventionally fractionated RT were also published, 12,13 report- ing nonsignificant differences in G2 or worse genitourinary (GU) or gastrointestinal (GI) late toxicity between the 2 treatment groups. In the HYPO-RT-PC trial, 12 a comparable 5-year bio- chemical recurrence-free survival (BRFS) was observed. Efficacy data for the PACE-B trial 13 are awaited in the next few years. Despite this consistent evidence, the major drawback in prostate cancer SBRT remains the prostate movement during the daily fraction RT, mainly due to rectal and bladder filling. 14 Another problem is represented by the shorter biochemical From the Departments of *Radiotherapy and Radiosurgery; ‡Urology, Humanitas Clinical and Research Center; and †Department of Bio- medical Sciences, Humanitas University, Rozzano—Milan, Italy. The authors declare no conflicts of interest. Reprints: Giuseppe R. D’Agostino, MD, PhD, Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano—Milan 20089, Italy. E-mail: giuseppe.dagostino@humanitas.it. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0277-3732/20/4309-0628 DOI: 10.1097/COC.0000000000000721 ORIGINAL ARTICLE 628 | www.amjclinicaloncology.com American Journal of Clinical Oncology  Volume 43, Number 9, September 2020 Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved.