PURPOSE:To evaluate the safety of moderately hypofractionated radiotherapy to the prostate and pelvic elective nodal irradiation (ENI) with intraprostatic and nodal boost in patients with high-risk prostate cancer. METHODS:In this prospective phase 2 single-arm study, patients with high-risk or node-positive prostate cancer received external beam radiotherapy to the prostate and ENI with moderate hypofractionation (60 Gy in 20 fractions to the prostate; 48 Gy ENI) with ADT. Simultaneous integrated boosts were allowed to 68 Gy to intraprostatic gross disease (MRI-defined) and 55 Gy to radiographically-involved nodes. The primary endpoint was acute gastrointestinal (GI) side effects (CTCAE v5.0) at 3 months following radiotherapy, with an a priori hypothesis that acute grade ≥ 2 GI side effects would not exceed 35%. Secondary endpoints included acute genitourinary (GU) side effects and quality of life (QoL) (EPIC-26 and IPSS). RESULTS:100 patients were enrolled; 97 completed treatment. Median age was 73, 49% had grade group 4-5 disease, median PSA was 22.2 ng/mL, 21% were cN1. 23 (24%) and 18 (19%) of patients received intraprostatic and nodal boosts, respectively. The rate of acute grade ≥ 2 GI side effects was 15.5% (one-sided 95% upper confidence bound22.8%). On univariable analysis, higher rectal and bowel D1cc and intraprostatic boost were significantly associated with increased acute GI side effects. The rate of grade ≥ 2 acute GU side effects was 26.8% (95% CI 18.3-36.8%). There was no statistically significant detriment to mean GI or GU QoL at 3 months post-treatment. CONCLUSIONS:Moderately hypofractionated radiotherapy to the prostate and ENI with boosts to gross disease was associated with lower-than-expected side effects and no statistically significant detriment to patient-reported mean GI or GU QoL at 3 months post-treatment.

Introduction Salvage radiotherapy (sRT) is an effective curative option for patients with biochemical recurrence following radical prostatectomy (RP). However, a subset of patients will develop local recurrence (LR) following treatment. Predictive factors and patterns of LR after sRT remain poorly defined. This study evaluates clinicopathological predictors of LR and characterizes failures anatomically relative to prior sRT fields. Methods Patients who received RP followed by sRT and subsequently underwent 18F-PSMA PET/CT for biochemical recurrence were identified from a prospective imaging registry. Logistic regression and Fine–Gray competing risks analyses were used to evaluate clinical, pathological, and treatment-related predictors of LR. Anatomical mapping localized LR relative to prior radiotherapy fields. Results Among 370 eligible patients, 68 (18.4%) had LR after sRT, including 34 (9.2%) with isolated LR. Median PSA at time of imaging was 0.77 ng/mL (IQR: 0.40-2.10 ng/mL) overall, and 0.83 ng/mL (IQR: 0.41-3.33 ng/mL) for patients with LR. On UVA, Gleason grade groups 1-3 and pN0 status were significantly associated with LR (p < 0.05). No variables remained significant on multivariable analysis. Fine–Gray analysis identified younger age and longer PSA doubling time as additional predictors of LR. Of all patients with LR, 35 had sRT plans available for spatial analysis, encompassing 39 discrete lesions. When mapped to the treatment-planned CTV, 29 lesions (74.4%) were in-field, 8 (20.5%) marginal, and 2 (5.1%) out-of-field. Marginal and out-of-field lesions commonly involved the posterior prostatic fossa and seminal vesicle bed. Conclusion PSMA PET/CT identified LR in nearly one-fifth of patients undergoing PSMA imaging for biochemical recurrence following sRT. Although most recurrences were within the treated volume, their distribution highlights anatomical regions that may benefit from additional attention at the time of planning.

Purpose/Aim A key barrier to widespread MRI-guided adaptive radiation therapy (ART) is the need for daily radiation oncologist (RO)-led re-contouring and evaluation. This has been addressed for prostate ART through radiation therapist (RTT)-led workflows.  This study evaluated the impact on toxicity and outcomes between RO- and RTT-led prostate treatment in an ART program Methods/Process All intermediate risk prostate ART patients treated on a 1.5T MR-Linac were retrospectively reviewed and grouped by workflow into consecutive cohorts: RO-led (September 2019 – November 2021) and RTT-led (April 2022 – October 2023), with a break during training. All patients were treated with 25 – 42.7 Gy in 5 – 7 alternate day fractions, 9-field IMRT using adapt to shape (ATS) workflow. Patients with 30Gy or less also received brachytherapy prior to EBRT. PTV margins were 5mm (all RO-led), 5mm (RT-led 25-30Gy) or 4mm (3mm left-right) (RTT-led 42.7Gy). Biochemical control was assessed using the Phoenix definition. Toxicity was quantified prospectively using CTCAE v3.0. Mean doses for each cohort PTV, bladder, urethra and rectum were summarized from summation of the adapted plan doses and normalized to prescription Results or Benefits/Challenges 166 prostate ART patients were reviewed: 78 RO-led and 88 RTT-led. Median (range) follow-up was 40 months (26-60) and 30 months (15-43) for RO-led and RTT-led patients, respectively. PSA at Nadir was similar between cohorts (0.28 vs 0.26) but mean(standard deviation) time to Nadir (TTN) in months was shorter in the RTT-led cohort (16.7 (±11.9) vs. 23.1 (±14.9), (p=0.005)). There were only 8 patients who developed biochemical failure at last follow up. Incidence of G2+ urinary toxicity was 9% vs 26% (p = 0.007) during RT, 14% vs 31% (p >0.05) at 1-month, 8% vs 14% (p>0.05) at 6-months, and 6% vs 3% (p>0.05) at 12-months for RO-led and RTT-led cohort, respectively. G2+ rectal toxicity was not significantly different between the cohorts during RT (0.6%), nor at 1-month (0.6%), 6-months (0.6%) or 12-months (1.2%). Mean PTV D95 coverage, bladder 1cc and mean urethra dose were all statistically significantly (p < 0.007) higher in the RO-cohort, but the magnitude of the differences was not clinically significant (0.99% vs 0.98%, 1.05% vs 1.02% and 1.06% vs 1.02%). Mean Rectum 1cc and D50 were similar in both cohorts Conclusions/Impact Acute G2+ GU toxicity was higher in the RTT-cohort, however late toxicity at 12-months was comparable to the RO-cohort. Overall, GI toxicity and incidence of BCR were low. Although shorter TTN could indicate poorer clinical outcomes, this finding may be related to 'PSA bounce' from the use of SBRT and brachytherapy, indicating longer follow-up is necessary. This work suggests that there was little clinical difference in dosimetry and toxicity. Further follow up will elucidate whether late toxicity continues to be comparable between the 2 cohorts and whether biochemical control is maintained

Purpose/Aim Interfraction bladder volume variation due to bladder filling poses challenges to the precision and efficiency of radiation therapy. Before the availability of a ConeBeamCT (CBCT) -guided adaptive radiation therapy (ART) platform, bladder patients at our institution were treated in two phases using CBCT for image guidance: Phase 1 used a 10mm planning target volume (PTV) margin for the first 7 fractions, and Phase 2 generated a patient-specific PTV (PS-PTV) using information from Day 1-4 CBCT. Despite this approach, some patients continued to have difficulty reproducing the bladder volume observed at simulation, resulting in longer appointment times and repeated CBCTs. Since implementing bladder treatments on the Ethos Adaptive platform in June 2025, our objective was to assess and compare treatment session durations between the IGRT and the ART workflow. Methods/Process Approval was obtained from the Quality Improvement Review Committee to retrieve data for comparison of radiation therapy workflows. All bladder patients were prescribed 55Gy in 20 fractions to the bladder, with or without pelvic lymph node (45Gy in 20 fractions). They were simulated and treated with a full bladder. For the IGRT workflow, a localization CBCT was acquired, and treatment was delivered using a 2-arc VMAT after correcting interfraction variation by couch shift based on image registration. If the anatomy is deemed unacceptable (e.g. bladder that was too small or extended outside of the PTV), patients were asked to wait for bladder filling or partially void, followed by acquisition of a repeat CBCT. Treatment proceeded once the anatomy met institutional imaging criteria. For the ART workflow, a localization CBCT was acquired and registered with the reference image. Autosegmentation of relevant volumes and target propagation were performed. The reference plan was re-computed to generate the Scheduled Plan, and an adapted plan was created by re-optimization based on the anatomy of the day. Both plans (9-field IMRT) were evaluated, and the clinically appropriate plan was selected. A physics quality check was performed, followed by a second CBCT to verify that the target was within the PTV before treatment delivery. For each fraction, timestamps for the initial CBCT and treatment beam delivery were collected. Treatment session duration was defined as the time interval between the first CBCT and the end of the beam delivery. Descriptive statistics were used to summarize the results. Results or Benefits/Challenges A total of 240 fractions from 12 IGRT patients and 195 fractions from 11 ART patients were analyzed. The average treatment session duration was 18 minutes (range: 5 – 186 minutes) for IGRT and 17 minutes (range: 11 – 29 minutes) for ART (p = 0.49). A total of 134 repeated CBCTs were acquired from 10 of the 12 IGRT patients. Overall, 88% of ART fractions were completed in less than 20 minutes compared to 75% for IGRT. Notably, 2% of IGRT fractions (10 fractions from 6 patients) exceeded 60 minutes, whereas no ART fractions required more than 60 minutes. Prolonged IGRT sessions were primarily associated with challenges in achieving the planned bladder volume. Conclusions/Impact The Ethos adaptive workflow demonstrated comparable average treatment session durations to the IGRT workflow while reducing variability and eliminating excessively prolonged sessions. ART offers greater workflow stability and efficiency in bladder radiation therapy. Future work will examine the dosimetric difference between the two workflows.

MR-guided adaptive radiotherapy (ART) enables daily plan optimization for prostate cancer but is resource-intensive. This study evaluated dosimetric and clinical outcomes following transition from radiation oncologist (RO)-led to radiation therapist (RTT)-led MR-guided ART. All prostate cancer patients treated with MR-guided ART on a 1.5T MR-linac were retrospectively reviewed. Consecutive RO-led (September 2019-November 2021) and RTT-led (April 2022-October 2023) cohorts were compared, excluding the actual transition period. Toxicities (CTCAE v5.0), dose-volume metrics from daily adapted plans, target volume variation, and biochemical recurrence-free survival (BRFS) were analyzed. A total of 166 patients were included (78 RO-led, 88 RTT-led; median follow-up 40 and 35 months). Dosimetric differences between the cohorts were statistically small (<1%). Rates of G2+ GI adverse events were similar across all timepoints. An increase in on-treatment GU events was observed in the RTT-led cohort (G2+ 27% vs. 9%, G3 incidence n = 2 vs. n = 0), likely reflecting higher baseline urinary dysfunction; no post-treatment differences persisted. Early biochemical outcomes were comparable, with 36-month BRFS of 93.5% (RO-led) and 95.0% (RTT-led). RTT-led MR-guided ART achieved comparable dosimetric quality and early biochemical outcomes to RO-led workflows with adverse advents that resolved in the long term. With structured training and a mature practice setting, RTT-led ART represents a scalable model to support future adaptive radiotherapy practice.

Purpose:Adaptive radiotherapy (ART) enhances treatment precision by adjusting for anatomical changes identified during a course of treatment. While ART is resource-intensive, non-adaptive workflows may also incur significant time and resource burden due to reactive interventions. This study aims to quantify the time-related burden of unplanned activities in non-adaptive CBCT-guided radiation therapy and assess their impact on patients and departmental efficiency. Methods and Materials:A retrospective analysis was conducted on 300 patients treated with CBCT-guided radiation therapy across 20 treatment techniques, encompassing 6,887 treatment fractions. Unplanned activities-including repeated CBCT acquisitions, aborted treatment sessions, additional CT scans, and mid-course replanning-were identified through electronic medical records and imaging logs. Time burden was estimated using electronic medical record timestamps. Results:Repeated CBCTs occurred in 55% of patients, contributing to 201.9 h of additional imaging time. Pelvic disease sites, particularly bladder and gynecologic cancers, exhibited the highest frequency of repeat imaging. Six patients required rescheduling due to unresolved anatomical discrepancies, and 15 underwent treatment plan modifications, with nine requiring repeat planning CTs. The average additional time per affected fraction was 13 min (range: 2-219 min), with some sessions extending beyond 3 h. Conclusions:Non-adaptive CBCT-guided workflows can lead to substantial time toxicity, comparable to or exceeding the resource demands of ART. These findings underscore the need for improved documentation, selective ART implementation, and workflow optimization to enhance patient experience and institutional efficiency.

Purpose/Aim Adaptive Radiation Therapy (ART) enhances treatment precision by accounting for anatomical and physiological changes throughout the treatment course. While ART is known to improve clinical outcomes, its implementation is resource-intensive, requiring frequent imaging, plan adaptation, and increased clinical oversight. In contrast, non-adaptive CBCT-guided workflows use static plans but often necessitate reactive interventions that also consume significant time and departmental resources. This study aims to quantify the time-related burden of unplanned activities in non-adaptive workflows and identify disease sites that may benefit most from planned ART, particularly in the context of limited ART-capable devices in Canada. Methods/Process A retrospective analysis was performed on 6,887 treatment fractions from 300 patients treated with CBCT-guided radiotherapy across 20 treatment techniques of various disease sites. Unplanned activities, such as repeated CBCT acquisitions, aborted sessions, additional planning CTs, and mid-course replanning, were identified through electronic medical records and imaging logs. Time burden was calculated using timestamp data from treatment management systems. The study was approved by the institutional Quality Improvement Review Committee. Results or Benefits/Challenges Repeated CBCTs were required in 55% of patients, resulting in 201.9 hours of additional imaging time. Each repeated CBCT added on average of 13 minutes (range: 2–219 minutes), impacting both patient experience and departmental throughput. Bladder and gynecologic cancers exhibited the highest frequency of repeat imaging, often due to organ filling variability. Six sessions were aborted and rescheduled due to unresolved anatomical discrepancies. Fifteen patients required plan modifications, including 9 repeat planning CTs, and 3 sarcoma cases with treatment interruption of 2-6 days. Conclusions/Impact Non-adaptive CBCT-guided workflows impose substantial resource burden, often comparable to or exceeding that of ART. These findings support a more strategic implementation of ART, particularly for bladder, cervix, and sarcoma cancers, where anatomical variability frequently disrupts standard workflows. Prioritizing ART for these high-burden disease sites may optimize resource utilization, reduce treatment delays, and improve overall patient care within current system constraints.

Objective: Quantify geometric and dosimetric accuracy of a novel prostate MR-to-MR deformable image registration (DIR) approach to support MR-guided adaptive radiation therapy dose accumulation. Approach: We evaluated DIR accuracy in 25 patients treated with 30 Gy in 5 fractions on a 1.5 T MR-linac using an adaptive workflow. A reference MR was used for planning, with three images collected at each fraction: adapt MR for adaptive planning, verify MR for pretreatment position verification and beam-on for capturing anatomy during radiation delivery. We assessed three DIR approaches: intensity-based, intensity-based with controlling structures (CS) and novel intensity based with controlling structures and points of interest (CS+P). DIRs were performed between the reference and fraction images and within fractions. We propagated CTV, bladder, and rectum contours using the DIRs and compared to manual contours using Dice similarity coefficient, mean distance to agreement (DTAmean), and dose-volume metrics. Results: CS and CS+P improved geometric agreement between contours over intensity-only DIR. DTAmean for reference-to-beam-on intensity-only DIR was 0.131+/-0.009cm (CTV), 0.46+/-0.08cm (bladder), and 0.154+/-0.013cm (rectum). For the CS, the values were 0.018+/-0.002cm, 0.388+/-0.14cm, and 0.036+/-0.013cm. For CS+P these values were 0.015+/-0.001cm, 0.025+/-0.004cm, and 0.021+/-0.002cm. Dosimetrically, comparing CS and CS+P for reference to beam-on DIRs resulted in a change of CTV D98 26cGy], rectum D1cc from [-106cGy, 72cGy] to [-52cGy, 74cGy], and bladder D5cc from [-51cGy, 544cGy] to [-79cGy, 36cGy]. Significance: CS improved geometric and dosimetric accuracy over intensity-only DIR, with CS+P providing the most consistent performance. However, session image segmentation remains a challenge, which may be addressed with automated contouring.

BACKGROUND AND PURPOSE:Changing to next-line systemic therapy is the standard-of-care for patients with progressive metastatic castrate-resistant prostate cancer. However, to preserve systemic therapy options and minimize toxicity, stereotactic body radiation therapy (SBRT) is being increasingly considered for patients with limited disease progression ('oligoprogression'). Herein, we report clinical, toxicity and quality of life (QOL) outcomes for an oligoprogressive prostate cancer cohort from a prospective trial. MATERIALS AND METHODS:RADIANT (NCT04122469) was a single-arm, phase-II basket trial which included patients with metastatic prostate cancer on any systemic therapy ≥ 3 months, with radiographic evidence of oligoprogression in ≤ 5 sites. Analysis by disease site was planned a priori. Patients received SBRT in 1-5 fractions to all progressive sites and were maintained on their current systemic therapy. The primary endpoint was cumulative incidence of change in systemic therapy. Key secondary endpoints included local control, toxicity and health-related (HR) QOL. RESULTS:Thirty-two patients were analyzed; median age was 74.0 years, median PSA 6.7 µg/L, 25% with visceral metastases and a median of 2 prior systemic therapy lines. Median follow-up was 14.1 months (range 4.8-51.9 months). At 1-year, 55.1% of patients remained on the same systemic line and local control was 84.0%. The cumulative incidence of grade 2 toxicity was 25.0% at 1 year, with no grade 3+ toxicities. HRQOL was maintained, with no detriment following SBRT delivery. CONCLUSION:Among patients with oligoprogressive prostate cancer, SBRT is an effective and safe intervention, including in patients with aggressive clinicopathologic features. Larger, randomized trials are needed to validate these findings.

INTRODUCTION:MRI-guided adaptive radiation therapy (ART) is the resource-intensive process of daily treatment plan modification. This study aims to demonstrate the feasibility of radiation therapist (RT)-led MRI-guided ART for oligometastatic disease (OMD) by comparing geometric accuracy and dosimetric differences between RT and radiation oncologist (RO) re-contouring. METHODS:Five RTs and five ROs retrospectively re-contoured gross target volumes (GTVs) and organs-at-risk (OARs) for eight OMD cases. RT and RO contours were compared against consensus RO Simultaneous Truth and Performance Level Estimation (RO-STAPLE) contours using the Dice similarity coefficient (DICE), mean distance to agreement (MDA), planning target volume (PTV) D95 and OAR D0.5cc using the Wilcoxon signed-rank test. Moreover, an RO qualitatively scored all contours using a 5-point Likert scale. RESULTS:We found very good geometric accuracy with average (±standard deviation) GTV DICE of 0.82 ± 0.06 for RTs and 0.85 ± 0.09 for ROs and MDA of 0.88 ± 0.03 mm for RT and 0.75 ± 0.05 mm for ROs relative to the RO-STAPLE. Qualitative GTV Likert scores were excellent, 4.8/5 for RTs and 4.7/5 for ROs. Mean percent difference in PTV D95 compared to RO-STAPLE was small but significantly higher for RTs (0.5% ± 1.5%) compared with ROs (-0.7% ± 1.9%, p < 0.05). Mean relative change in OAR D0.5cc results was small with -1% ± 6% for RTs and -1% ± 12% for ROs. CONCLUSIONS:Here we provide the first report of geometric and dosimetric contouring uncertainty for MR-guided online ART for OMD. Our results show that RT re-contouring maintains similar performance for eligible targets and OARs compared with RO contours, establishing the initial feasibility of an RT-led workflow.

PURPOSE:Stereotactic body radiation therapy (SBRT) represents a novel, efficacious treatment for patients with kidney tumors who are medically inoperable or decline surgery. There is limited prospective data on the impact of kidney SBRT on renal function. METHODS AND MATERIALS:This was a prospective phase 2 single-arm clinical trial (clinicaltrials.gov NCT03747133) of kidney-directed SBRT in patients with primary or metastatic renal lesions who were medically inoperable or declined surgery. The primary outcome was the change in kidney function, assessed by the change in eGFR (estimated glomerular filtration rate) over 2 years. The a priori hypothesis was that eGFR (mL/min/1.73 m2) does not decrease over time and was analyzed using a 1 sample t-test for noninferiority with a fixed margin of -6.974 based on published data at the time of trial design. RESULTS:Thirty patients with 32 renal tumors enrolled, with a median (IQR) age of 76 (73-82), a Charlson comorbidity index of 8 (7-9), 93% with chronic kidney disease stage ≥2 (eGFR ≤60 mL/min/1.73 m2), and the majority with cT1b disease with a median tumor size of 43 mm. Twenty-six patients (87%) had primary kidney cancer, and the remainder had metastatic lesions from non-kidney cancer histologies. Median radiation dose was 35 Gy in 5 fractions. Median follow-up was 24.5 months (IQR, 20-36.2). Median (IQR) eGFR levels (mL/min/1.73 m2) were 47.5 (37.8-64.0) at baseline, 42.0 (35.2-54.2) at 1 year, and 39.5 (25.5-54.8) at 2 years. Eighteen of 30 patients were evaluable for eGFR at 2 years. Noninferiority was not established based on a mean reduction in eGFR between baseline and 2 years of -8.7 mL/min/1.73 m2 (95% 1-sided CI, -14.1, ∞; P = .71). Renal function decline was significantly associated with time, increasing age, baseline chronic kidney disease stages 3-4, and larger baseline tumor size on multivariable analysis. Local control was 96.7% at 2 years. CONCLUSIONS:Kidney-directed SBRT results in modest clinical renal function loss up to 2 years following SBRT, based on evaluable patients in our study. Technical advances may further improve the therapeutic ratio.

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART. Twenty-one patients were treated with single-adaptation ART. Conventional treatments were delivered for fractions 1 to 6 and adapted plans for the remaining 27 fractions. Clinical target volumes (CTVs) and small bowel delineated on fraction 1 to 4 CBCT were used to generate adapted PTVs and planning organ-at-risk (OAR) volumes for adapted plans. PTV volume and OAR dose were compared between ART and conventional using Wilcoxon signed-rank tests. Weekly CBCT were used to assess the fraction of CTV covered by PTV, CTV D99, and small bowel D1cc. Clinical metrics were compared using a Student's t-test (p < 0.05 significant). Offline adaptive planning required 1.9 ± 0.4 days (mean ± SD). ART decreased mean adapted PTV volume 61 ± 37 cc and bladder wall D50 compared with conventional treatment (p < 0.01). The CTV was fully covered for 96% (97%) of fractions with ART (conventional). Reconstructing dose on weekly CBCT, a nonsignificant reduction in CTV D99 was observed with ART (94%) compared to conventional (96%). Reduced CTV D99 with ART was significantly correlated with large anterior-posterior rectal diameter on simulation CT. ART reduced the number of fractions exceeding our institution's small bowel D1c limit from 14% to 7%. This study has demonstrated the feasibility of offline ART for post-prostatectomy cancer. ART facilitates PTV volume reduction while maintaining reasonable CTV coverage and can reduce the dose to adjacent normal tissues.