A Single-Institution Prospective Study to Evaluate the Safety and Efficacy of Real-Time-Image Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Since 2014, RGPT that corrects the positional change of the prostate during treatment using gold fiducial markers placed in the prostate has been in use, but there are concerns about the effect of the metal marker on the proton dose distribution. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. <h3>Materials/Methods</h3> Prostate cancer patients with ECOG performance status 0 to 2 and no lymph node or distant metastasis were enrolled in this study. In all cases, 3-4 pure gold fiducial markers of 1.5 mm diameter were inserted in the prostate. To reduce the influence of the markers on the dose distribution, the proton beam was delivered from 3 or 4 directions. The prescribed dose was 70 Gy (RBE) in 30 fractions over 7.5 weeks, and 3 years of hormone therapy was recommended for patients with high or very high risk of recurrence according to the National Comprehensive Cancer Network classification. Adverse events (AE) were evaluated weekly during the treatment, and monthly after the treatment until 3 months and every 3 months thereafter. The primary endpoint was the frequency of an early AE of Grade 2 or higher within 90 days after the end of the proton therapy, and the secondary endpoint was the biological relapse-free survival rate (BRFS) and the frequency of late AE. Based on the previous report (Nihei et al., 2011) that the frequency of Grade 2 or higher AE was 12.6%, the frequency of early AE of RGPT was assumed to be 7.6% and the non-inferiority margin was set at 10%; the threshold AE occurrence rate was set at 22.6%. Since the required number of cases was calculated to be 43 using the one-sample binomial test by the SWOG statistical tools with the one-sided significance level of 2.5% and power 80%, the target number of cases was set to 45. Based on this assumption, the non-inferiority of early safety of RGPT would be verified if the number of Grade 2 or higher early AE occurrence cases is 5 or less. <h3>Results</h3> Forty-five cases were enrolled between March 2015 and May 2017. The number of patients with Low, Favorable intermediate, Unfavorable intermediate, and High/Very high risk was 9, 7, 12, and 17, respectively. Hormone therapy was used with 17 patients and all patients completed the treatment protocol. The frequency of a Grade 2 or higher early AE was 8.9% (4/45 cases), and the non-inferiority of early safety of RGPT was verified. The median follow-up period was 63.0 months (51.3 to 79.3 months) and the overall 5-year BRFS was 88.9%. As late AE: rectal bleeding (Grade 1 in 13 cases (28.9%), Grade 2 in 8 cases (17.8%)), and bladder bleeding (Grade 1 in 2 cases (4.4%)) were observed. <h3>Conclusion</h3> The results here allow the conclusion that the RGPT for prostate cancer was as safe as conventional proton beam therapy in early AE, and its efficacy was suggested to be comparable with previous studies.