Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study is to explore whether spacer hydrogel morphology changes during the course of stereotactic body radiation therapy (SBRT) radiation to the prostate. METHODS AND MATERIALS/METHODS:A total of 198 patients at our institution each received spacer gel before SBRT on magnetic-resonance-guided linear accelerator (MR-Linac) between October 2023 and March 2025. Each patient received at least 1 simulation magnetic resonance imaging and 5 on-treatment magnetic resonance imaging scans. Average time between simulation and first treatment and between simulation and final treatment was approximately 19.9 days and 31.1 days, respectively, with 2- to 3-day intervals between treatments. A U-Net deep learning model was implemented using nnUNetv2. This model was iteratively trained using inference images, resulting in a Dice similarity coefficient >0.98, and was then applied to detect changes in gel morphology over time. RESULTS:Longitudinal modeling of spacer gel radiomic shape features demonstrated a statistically significant change in flatness that remained significant over false discovery rate correction and all sensitivity analyses. This metric increased by 0.003 units per 10 days (95% CI, 0.001-0.005; false discovery rate q ≈ 0.02), implying a progressively rounder shape over the observation period. All other features showed minimal or inconsistent change. The hydrogel appeared larger on treatment imaging, with a mean percent change of 10.62% (95% CI, 8.68%-12.56%; P < .001). The corresponding absolute volume difference was 1.19 cm³ (95% CI, 1.00 cm³-1.39 cm³; P < .001). CONCLUSIONS:Because prostate SBRT planning assumes gel stability, interfractional changes could affect rectal dose estimates. In this cohort, the spacer hydrogel's overall geometry remained stable across the 5-fraction course, with no meaningful evidence of gel resorption. A small increase in the flatness metric was observed, but without a change in size or compactness. These findings indicate that the gel maintains its rectal-sparing configuration throughout SBRT.

BACKGROUND:Magnetic resonance (MR) imaging-linear accelerator-based real-time adaptive planning for delivering ultra-hypofractionated stereotactic body radiotherapy (SBRT) has advanced clinical accuracy yet added complexity to the radiotherapy workflow. We retrospectively evaluated whether the addition of a Parallel Automated Contouring module with Enhancement of AI (PACE-AI) reduced contouring time and overall SBRT duration, and its impact on intra-fractional target motion. METHODS:This study included 250 fractions from 90 prostate cancer patients from which fraction time were tracked. All patients received definitive SBRT to the prostate on the 1.5-Tesla Unity (Elekta©) system, through the Adapt-To-Shape (ATS) workflow, which required real-time re-contouring of the normal tissues by the dosimetrists and target contouring by the physician for each of the fractions. We compared the fraction durations for 125 consecutive fractions treated with the incorporation of PACE-AI with 125 fractions previously treated without PACE-AI to determine whether PACE-AI improved efficiency and reduced treatment session duration. RESULTS:For the cohort treated without PACE-AI, the overall median duration was 67.6 min, including 23.9 min contouring time. With the incorporation of PACE-AI, the overall median duration was 51.2 min, representing a 24.3% reduction. The average contouring time was reduced by 55% to 10.8 min. In addition, the extent of positional shifts prior to beam delivery was significantly reduced from an average of 1.8 mm to 1.3 mm (p < 0.001) in both superior/inferior (range reduced from 0 to 6.3 mm to 0-4.2 mm) and anterior/posterior directions (range reduced from 0 to 6.6 mm to 0-5.0 mm). CONCLUSIONS:The incorporation of PACE-AI improved workflow efficiency during SBRT. The reduction in treatment duration also helped reduce organ motion during real-time adaptive planning.

BACKGROUND:This is the quality of life (QOL) analysis of the SPPORT trial of men with a detectable prostate specific antigen (PSA) after prostatectomy for prostate cancer. Primary analysis established a benefit of adding pelvic lymph node radiotherapy (PLNRT) and short-term androgen deprivation therapy (STADT) to salvage prostate bed radiotherapy (PBRT) for biochemical progression-free survival. METHODS:Subjects were randomized to Arm 1, PBRT, Arm 2, 4-6 months of STADT + PBRT, and Arm 3, PLNRT + STADT + PBRT. QOL was assessed at baseline, 6 weeks after the start of RT, 1 and 5 years after the end of RT, including Expanded Prostate Cancer Index Composite (EPIC), Hopkins Symptom Checklist (HSCL-25), EuroQol (EQ-5D), and quality adjusted life years (QALYs). Statistical and clinical significance were calculated. Differences among arms were assessed using pairwise t-tests, Fisher's exact test, and mixed effects regression modeling, controlling for multiplicity. FINDINGS/RESULTS:644 patients consented to QOL; 81% white and 54% <65 years. EPIC, bowel and urinary scores decreased at 6 weeks then increased by years 1 and 5, although not to baseline. For sexual and hormonal domains, there were statistically significant differences between arms at 6 weeks and 1 year with STADT exhibiting poorer QOL scores, but no difference at 5 years. For HSCL-25, statistically significant differences at 6 weeks were not clinically significant. Comparisons of QALYs for overall survival showed no statistical significance. However, freedom from progression QALY means were 5.5, 6.2 and 6.6 years for Arms 1, 2, and 3, respectively, with Arms 3 and 2 indicating statistically significant improvement over Arm 1. INTERPRETATION/CONCLUSIONS:While QOL generally declined the most among all arms at 6 weeks post RT start, and remained lower than baseline at 5 years, there were no clinically significant differences in QOL among arms at 1 and 5 years. QALYs for freedom from progression favored STADT + PLNRT + PBRT for salvage treatment of prostate cancer.

RATIONALE/BACKGROUND:Ga-PSMA PET/CT in detecting biochemically recurrent prostate cancer and evaluate associations of PET imaging findings with alterations on genomic profiling. METHODS: RESULTS:Ga-PSMA PET/CT was 59.2% (357/603), with a positive predictive value of 0.98 (95% CI, 0.94-0.99), and a sensitivity of 0.60 (95% CI, 0.54-0.66). When analysed by PSA level, 43.8% of patients with PSA < 0.5 ng/mL, 64.1% with PSA 0.5-0.99 ng/mL, 73.6% with PSA 1.0-1.99 ng/mL, and 87% with PSA > 2.0 ng/mL were PET positive. Inter-reader agreement was excellent with κ-coefficient of 0.884. SUVmax was significantly higher in patients with higher PSA (P < 0.001), and extra-pelvic nodal metastases (P < 0.001). Patients with persistently elevated PSA, higher TNM stage, higher Gleason score, and without RT at baseline (all P < 0.001) had shorter time to PCBR. In patients with genetic alteration available, TP53 mutations were significantly associated with time to PCBR (alteration, n = 38; wildtype, n = 200; median time 4.3 versus 5.3 years, P = 0.04), and borderline significantly associated with SUVmax (median 11 versus 7, n = 33 and 121, P = 0.054). CONCLUSION/CONCLUSIONS:

PURPOSE/OBJECTIVE:This study evaluated the extent of prostate displacement during SBRT on an MRI Linac using comprehensive motion management (CMM) and identified variables associated with intrafraction motion (IFM). METHODS:212 patients with clinically localized prostate cancer were treated with 5-fraction SBRT on a 1.5 T MR-Linac where IFM was continuously tracked and gated by CMM. Pre-beam positional shifts were identified from MRI registration prior to beam delivery. Intrafraction positional variability during beam delivery was evaluated, and multivariable analysis identified variables associated with IFM. RESULTS:In 614 fractions (62.7%), a > 1.5 mm pre-beam positional shift led to an adapt-to-position (ATP) plan correction. Mean anterior-posterior and superior-inferior pre-beam shifts were 2.2 mm and 2.1 mm, respectively. For 962 evaluable fractions, the median beam-on-time was 13.7 min with a mean duty cycle of 95.8%. Sustained > 3 mm displacement was observed in 520 fractions (54.1%) with a median cumulative duration of 24 s; >5 mm displacement was observed in 209 fractions (21.7%) with a median duration of 12.4 s. The ATS + ATP workflow was associated with reduced odds of sustained > 3 mm motion (p = 0.035), while older age was associated with increased odds (p = 0.011). CONCLUSIONS:Significant prostate shifts can occur immediately prior to and during radiation beam delivery, frequently exceeding applied margins and potentially leading to tumor underdosage. Continuous motion tracking and gating during prostate SBRT is an important tool in reducing IFM and enhance treatment delivery accuracy.

INTRODUCTION/BACKGROUND:Focal dose intensification strategies targeting the dominant intra-prostatic lesion (DIL) improve outcomes of patients with prostate cancer. The purpose was to determine whether the 6-month multiparametric (mp)MRI response of the DIL is associated with post-treatment prostate-specific antigen (PSA) kinetics after MRI linear accelerator (LINAC) guided stereotactic body radiotherapy (SBRT) with focal dose intensification. METHODS:), and PSA ≤ 1.0 ng/mL. RESULTS:(100.0% vs 82.9%, p = 0.010) and PSA ≤ 1.0 ng/mL (45.9% vs 11.4%, p = 0.001) compared to those without mpMRI CR. In 10 patients without 6-month mpMRI CR but had further MRI follow-up (median 13 months), DILs either further decreased in size (30.0%) or resolved (70.0%). CONCLUSION/CONCLUSIONS:Initial 6-month mpMRI response correlates with PSA kinetics, which is associated with important clinical outcomes. mpMRI can be used for post-SBRT evaluation to gauge local tumor response of the DIL, where most recurrences occur.

OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.

PURPOSE/OBJECTIVE:Optimizing radiotherapy delivery for higher-risk prostate cancer often requires dose escalation while minimizing dose to surrounding normal tissues. We report on the feasibility of combining high-dose-rate (HDR) brachytherapy with dose intensification to the dominant intra-prostatic lesion (DIL) followed by magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT). METHODS AND MATERIALS/METHODS:Eighty-eight patients were treated with a single fraction of 15-Gy HDR brachytherapy boost followed by MRgSBRT to prostate, or prostate and pelvic lymph nodes, to a dose of 25 Gy in five fractions. The DIL noted on multi-parametric MR imaging was defined as a PIRADS-4/-5 lesion with an associated diffusion-weighted abnormality(s), and was intraoperatively boosted during brachytherapy to 120% of the prescription dose. Dosimetric objectives included D99% >120% to the DIL, D1% <120% for the urethra and D1cc <80% for the rectum. Real-time adaptive SBRT was delivered with a 1.5-T Unity MR Linac. RESULTS:For the HDR procedure, the mean prostate and DIL D90% were 108.3% ± 2.7% and 135.9% ± 12.2%, respectively. Mean urethra Dmax and D20% were 116.5% ± 4.5% and 108.2% ± 3.8%, respectively. Mean rectal V100 and D1cc were 0.0 ± 0.0cc and 73.6% ± 7.0%, respectively. DIL objective was not met in two lesions owing to proximity of the urethra and bladder neck. At a median follow-up of 6.8 months, Grade 2 genitourinary acute toxicity was observed in 33% of patients and Grade 2 acute gastrointestinal toxicity was observed in 1%. CONCLUSIONS:HDR boost with dose escalation to the DIL in combination with MRgSBRT is a feasible and effective treatment protocol. No significant genitourinary or gastrointestinal acute toxicity was observed.

Post-radiotherapy erectile dysfunction (ED) can significantly impact the quality of life of patients with prostate cancer (PCa). Critical anatomical structures, such as the neurovascular bundle (NVB), internal pudendal arteries (IPA), penile bulb, and corporal tissues track in close proximity to the prostate, making them susceptible to radiation-related damage. This study aimed to evaluate the anatomical patterns of these structures and their relationship with the prostate, and to provide comprehensive illustrative examples on MRI. Consecutive patients with PCa who underwent MRI-linear accelerator (LINAC)-based stereotactic body radiotherapy (SBRT) in January-December 2024 were included. NVB patterns were classified into 3 categories: (1) "classical" with discrete NVB elements, (2) "adherent", dispersed and adherent to prostatic capsule, and (3) "absent". The smallest distance between the IPA and the prostate capsule and membranous urethral length (MUL), serving as a surrogate for distance between corporal tissue and prostatic apex, were also measured. These MRI findings were compared between prostate volumes >40 and <40 ml and between MRI/pathological features of the dominant intraprostatic lesion. A total of 160 men (median age 70 years, interquartile range [IQR] 64-76) were included. The most common NVB pattern was "classic" (80.0-85.0%), followed by the "adherent" NVB pattern (13.8-18.1%). The median smallest distance between the IPA and prostate was 2.3 cm (IQR 1.8-2.8 cm), with 3.1-3.8% less than 1.0 cm. The median MUL was 1.5 cm (IQR, 1.2-1.8 cm), with 2.5% of patients less than 1.0 cm. No significant association was found between these MRI features and prostate volume or other variables (p = 0.09-0.99). In conclusion, most PCa patients demonstrated favorable anatomy for potential dose sparing of critical structures. Comprehensive MRI illustrations are provided to help radiation oncologists recognize the location, trajectory, and relationship of these structures, facilitating their contouring and ultimately aiding in achieving meaningful dose reductions to these erectile function structures.