Multicenter, dual fractionation scheme, single core lab comparison of rectal volume dose reduction following injection of two biodegradable perirectal spacers.

PURPOSE: A multicenter, double-arm, central core lab, retrospective study was performed to compare the rectal dosimetry of patients implanted with two injectable, biodegradable perirectal spacers, in conventional fractionation (CF), as well as ultrahypofractionation (UH) treatment plans. METHODS AND MATERIALS: Fifty-nine patients were enrolled into the study in five centers: two centers in Europe, which implanted a biodegradable balloon spacer in a total of 24 subjects and three centers in the US, which implanted the SpaceOAR in 35 subjects. Anonymized CTs (pre and post-implantation) were reviewed by the central core lab. For VMAT CF plans rectal V50, V60, V70, and V80 were calculated. For UH plans, a corresponding rectal V22.6, V27.1, V31.37, and V36.25 were established representing 62.5%, 75%, 87.5%, and 100% of the 36.25 Gy prescribed dose. RESULTS: For CF VMAT, a comparison between the balloon spacer and the SpaceOAR revealed a significant difference of 33.4% decrease in mean rectal V50 (71.9% vs. 38.5%, p < 0.001), 27.7% in mean rectal V60 (79.6% vs. 51.9%, p < 0.001), 17.1% difference in mean rectal V70 (84.1% vs. 67.0%, p = 0.001), and a significant difference of 3.0% (p = 0.019) in mean rectal V80 (87.2% vs. 84.2%). With UH analysis, the mean rectal dose reduction for the balloon spacer compared to the SpaceOAR was 79.2% and 53.3% for V27.1 (p < 0.001), 84.1% and 68.1% for V31.71 (p = 0.001), and 89.7% and 84.8% for V36.25 (p = 0.012), respectively. CONCLUSION: Rectal dosimetry is more favorable for treatment with the balloon spacer compared with SpaceOAR. Further research, particularly in the context of a prospective randomized clinical trial design, is needed to assess the acute and late toxicity experience as well as physician satisfaction with achieving symmetrical implantation, and ease of use in light of increasing clinical use.

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial.

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT. Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT. Design, Setting, and Participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to µg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality. Main Outcomes and Measures: For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%. Results: Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01). Conclusions and Relevance: The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT. Trial Registration: ClinicalTrials.gov Identifier: NCT04189913.

The time gap between Pd-103 prostate brachytherapy and supplemental beam radiation does not impact on rectal morbidity or likelihood of cure.

OBJECTIVE: To determine whether treatment gap between supplemental beam radiation and brachytherapy implant affects rectal morbidity and likelihood of cure in the treatment of intermediate-risk prostate cancer. MATERIALS AND METHODS: Five hundred sixty-eight patients with AJCC clinical stage T1c-T2a prostate cancer, Gleason score 7 to 9 and/or prostate-specific antigen (PSA) 10 to 20 ng/mL, were randomized to implantation with Pd-103 (90 vs. 115 Gy) with 44 Gy versus 20 Gy preimplant supplemental beam radiation, respectively. Treatment-related morbidity was monitored by mailed questionnaires, using a modified Radiation Therapy Oncology Group rectal morbidity criteria at 1, 3, 6, 12, 18, and 24 months. Patients who reported grade 1 or worse rectal morbidity were interviewed by telephone to clarify details regarding their rectal bleeding. RESULTS: Persistent rectal bleeding occurred in 36 of the 548 evaluable patients (7%). The mean gap among rectal bleeders was 3.8 days and among nonbleeders was 4.8 days (P = 0.236). Higher R100 and external beam dose of 44 Gy were significant predictors of rectal bleeding on univariate and multivariate analysis. Log-rank analysis did not demonstrate any improvement in biochemical failure free survival (BFFS) with shorter gap interval. On univariate analysis, Gleason score >7, PSA >10, D90 <100%, and treatment gap were all predictive of biochemical failure. On multivariate analysis, only Gleason score, PSA, and D90 remained significant predictors of BFFS. CONCLUSION: Shorter gap intervals between supplemental beam radiation and brachytherapy implant are safe. Shorter gap intervals do not improve BFFS; however, they do allow for treatment completion in a more timely fashion.

Optimized prostate brachytherapy minimizes the prognostic impact of percent of biopsy cores involved with adenocarcinoma.

PURPOSE: A higher percent of positive biopsy cores predicts poor biochemical failure-free survival. The highest dose covering at least 90% of the prostate is a standard method of measuring implant quality. We tested the hypothesis that the percentage of positive biopsy cores loses its adverse prognostic impact in patients who receive implants with a highest dose covering at least 90% of the prostate of 100% or greater of the prescription dose. MATERIALS AND METHODS: A total of 568 patients with intermediate to high risk adenocarcinoma of the prostate who were previously treated with brachytherapy in a prospective, randomized study were evaluated. The relationship between the percentage of positive biopsy cores, the highest dose covering at least 90% of the prostate and biochemical failure was examined. RESULTS: At a median followup of 50 months the rate of 5-year biochemical failure-free survival was 87% for the entire group and 92% vs 81% for patients with less than 50% vs 50% or greater positive biopsy cores (log rank p = 0.009). The mean highest dose covering at least 90% of the prostate was statistically lower in failing vs nonfailing cases (p = 0.03). Gleason score, prostate specific antigen, 50% or greater positive biopsy cores and the highest dose covering at least 90% of the prostate were the only statistically significant predictive factors for biochemical failure-free survival on multivariate Cox regression analysis. When regression analysis was restricted to the 237 patients who received implants with a highest dose covering at least 90% of the prostate of 100% or greater, 50% or greater positive biopsy cores lost predictive value but prostate specific antigen and Gleason score remained independent prognostic factors. CONCLUSIONS: A total of 50% or greater positive biopsy cores is an independent predictor of poor biochemical failure-free survival in patients treated with brachytherapy. High quality prostate brachytherapy, defined by a highest dose covering at least 90% of the prostate of 100% or greater, minimize the adverse effect of 50% or greater positive biopsy cores on time to biochemical failure.