Ultrahypofractionated Intensity Modulated Proton Therapy for Prostate Cancer: An Institutional Experience

Summary: Purpose: To describe our clinical experience and assess outcomes for patients treated with ultrahypofractionated intensity modulated proton therapy (IMPT). Background: Proton therapy is an accepted modality for the treatment of prostate cancer. Ultrahypofractionation, using 5 or fewer fractions, is a well-established treatment schedule for definitive treatment of prostate cancer and has several advantages compared to standard fractionation. Low fraction number greatly decreases patient treatment burden while simultaneously providing excellent disease control1, 2. The shortened schedule also provides a secondary benefit of increasing patient throughput for treating facilities. Compared to standard fractionation or moderately hypofractionated radiation therapy, ultrahypofractionation offers comparable 5-year bPFS and toxicity rates1, 2. Evidence also demonstrates similar cumulative late toxicity rates compared to traditional scheduling3. Methods and Materials: A retrospective analysis was performed of patient records who were treated with ultrahypofractionated IMPT at a single institution between July 2019 and August 2023. Kaplan-Meier analysis was used to estimate biochemical progression-free survival (bPFS). Toxicity data as described in the patient chart was collected and analyzed using Common Terminology Criteria for Adverse Events (CTCAE) criteria. Treatment Planning: All patients were treated using the Mevion S250i Proton Therapy System with HYPERSCAN and Adaptive Aperture (Mevion Medical Systems) and planned using the Raystation treatment planning system (RaySearch Laboratories). All patients underwent placement of carbon fiber fiducial markers, and the majority also received hydrogel rectal SpaceOAR (Boston Scientific). Our general treatment planning strategy is as follows. After CT simulation which was usually co-registered with same-day MRI, ultrahypofractionated intensity modulated proton therapy was planned to deliver 3625 cGy (RBE) to the prostate ± seminal vesicles with a 5 mm expansion to a planning target volume (PTV) with optional simultaneous integrated boost (SIB) to 4000 cGy (RBE) to the prostate without a margin, and 4500 cGy (RBE) to the tumor visible on MRI without a margin. While the majority of patients received simultaneous integrated boost, not all did. Dose constraints were consistent with current NRG protocols. Plans utilized left and right lateral beam angles, with an optional antero-posterior angle to meet femoral head dose constraints and improve dose conformality. Antero-posterior beams usually had a range margin of 2-3 mm applied to the rectum to avoid excess high linear energy transfer (LET) dose to this structure. Robust optimization was used with 2 mm geometric uncertainty and 3.5% range uncertainty as described by Kubes et al4. Some plans treated earlier in our experience did not include a 5 mm PTV expansion, but robust optimization was performed with 5 mm geometric uncertainty in these cases. For daily treatment, patients underwent repeat CT on the simulation unit to assess bladder and rectal filling as well as fiducial marker position. On the treatment unit, stereoscopic kV radiographs were obtained, and shifts were made using a 6-degrees-of-freedom robotic couch to match fiducial marker position. Translational shifts of up to 5 mm were allowed. Fractions were spaced at least 40 hours apart, typically delivered every other day on weekdays. Treatment courses were completed within 5 weeks of initiation. Results: 109 patients were identified for analysis, receiving treatment between July 2019 to August 2023. 7 patients (6%) had low risk disease, 40 (37%) had favorable intermediate risk disease, 40 (37%) had unfavorable intermediate risk disease, and 20 (18%) had high risk disease. 2 patients (2%) had metastatic disease. Patients received 5 fractions of ultrahypofractionated IMPT (modal peripheral dose of 36.25 Gy in 5 fractions typically delivered every other day). The median follow-up was 15.0 months. One patient experienced biochemical failure at 8.1 months. There were no observed deaths. The estimated bPFS was 98.7% at 2 years. Mean PSA nadir was 0.69. Acute grade 1-2 toxicity was experienced in 64 patients (59%). Late grade 1-2 toxicity was observed in 41 patients (38%). Neither acute nor late grade 3+ toxicity was observed in any patient. Conclusion: This retrospective study demonstrated excellent disease control with low associated toxicity in patients treated with ultrahypofractionated IMPT for all risk groups of prostate cancer. Toxicity rates in this study were comparable to those reported in similar studies, with acceptable rates of G1-2 acute and late toxicities, and no G3+ toxicities1, 2, 4. In this study, there was a single patient who experienced biochemical failure. While our median follow-up is currently only 15 months, this finding is consistent with other studies demonstrating excellent bPFS in patients treated with ultrahypofractionated RT for prostate cancer1,2,4.