Abstract Background: There is an unmet need in the treatment of triple negative breast cancer (TNBC) as recurrence rates remain a challenge. Indeed, the treatment of TNBC remains a challenge due to the paucity of targetable pathways as opposed to estrogen receptor-positive or Her2-positive breast cancers, thus novel treatment strategies are warranted to improve outcomes for patients. Smac mimetics (SMs) are FDA-approved small compound molecules that inhibit the inhibitors of apoptosis. In this study, we investigated the radiosensitizing properties of the SM compound Xevinapant (AT406) in a triple negative breast cancer model and potential therapeutic applications. Methods: A panel of TNBC cell lines were treated with increasing concentrations of Xevinapant (AT406) in the presence or absence of ionizing RT and cell viability and apoptosis measured in vitro using a live cell imaging system. Clonogenic assays were conducted in MDA-MB-231 with different Xevinapant and RT combinations. TNFα has been previously shown to enhance SM-induced apoptosis, thus we also evaluated the radiosensitizing properties of Xevinapant in combination with recombinant TNFα by clonogenic assays and evaluated apoptosis-mediated cell death by flow cytometry. Finally, a gene expression analysis was done to identify a potential TNFα gene signature Results: Xevinapant increased cell cytotoxicity in a panel of in irradiated TNBC cell lines. When assessed with the gold standard of clonogenic assays, we found that Xevinapant on its own is not a radiosensitizing agent in TNBC. However, when combined with a low dose of recombinant human TNFα, Xevinapant increased the sensitivity of MDA-MB-231 cells to RT with a dose enhancing factor (DEF) of 1.57. We also show that this radiosensitization effect is mediated by a cell cycle arrest in G2/M and an increase in apoptosis as evidenced by an increase in caspase-3/7 activity in irradiated cells treated with Xevinapant + TNFα and abrogation of the DEF by the pan-caspase inhibitor zVAD-fmk. Finally, a gene expression analysis of TNBC tumor samples suggests an immunogenic profile with a potential TNFα gene response signature. Conclusion: Xevinapant (AT406) synergizes with RT in the presence of TNFα to induce the death of triple-negative breast cancer cells. TNFα is central to this radiosensitization through activation of the programmed cell death. These results are promising, and investigations are underway to characterize a potential TNFα gene signature that could be used to identify patients that could respond to such a combination therapy. Citation Format: Mame Daro Faye, Julie Lafontaine, Philip Wong, Cynthia Menard, . The smac mimetic Xevinapant increases the efficacy of radiotherapy in triple negative breast cancer but only in the presence of tumor necrosis factor alpha [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6615.

Radiotherapy has achieved substantial progress often attributed to accelerated technological innovation over decades. However, randomized controlled trials (RCTs) are costly, difficult to fund and to conduct, such that the generation of quality evidence is outpaced by changes in practice. We sought to evaluate the implementation performance of a platform approach to the conduct of pragmatic RCTs in radiation oncology. We implemented PERa, a platform consisting of a prospective registry of patients receiving standard-of-care radiation therapy, designed to support pragmatic registry-based RCT (rRCT) methods and staged informed consent. Implementation performance metrics included rate of registry enrollment, acceptability of re-contact and/or serving as controls for interventional trials, activation and recruitment of embedded comparative effectiveness rRCTs, compliance to study arms, and completeness of ePRO data acquired at scale. Between January 1, 2018 and December 31, 2023, the registry accrued 1415 participants across 5 participating institutions. At time of stage 1 consent, 93

Background:Symptomatic posttreatment edema (SPTE) is a complication that may develop after radiotherapy for intracranial meningiomas. Our study aims at reviewing rates of SPTE in a large cohort of a single institution and identifying possible predictive factors. Methods:We retrospectively analyzed data of 293 patients with 304 intracranial meningiomas irradiated at our institution between 2005 and 2018. We evaluated rates of SPTE and investigated numerous factors by univariate and multivariate analysis. Kaplan Meier analysis was used for estimation of actuarial local control and overall survival. Results:Median age was 60 years. Meningiomas were treated with fractionated stereotactic radiation therapy (70 %), single fraction stereotactic radiosurgery (24 %) or fractionated stereotactic radiosurgery (6 %). Median imaging follow-up was 60 months, actuarial 10 year local control rate for patients with grade 1 meningiomas who received radiotherapy as definitive treatment was 99 %. Local control at 5 years was 94 % for grade 1 meningioma, 57 % and 53 % for grade 2 and 3 respectively. Sixteen patients (5.5 %) developed SPTE, median time to onset was 3 months (range 1-26 months). the higher rates of SPTE observed were in midline (13 %) and convexity (9 %), compared to skull base tumors (2 %). On univariate analysis, age > 60 years (p > 0.03), pretreatment peritumoral edema (p = 0.014), medline location (p = 0.018), tumor size > 30 mm (p = 0.015) and grade 2 histology (p = 0.03) were predictive of SPTE. On multivariate analysis, only tumor location and size remained statistically significant. Conclusions:Based on our results, patients at high risk of SPTE can be identified based on patient and tumor characteristics. The best treatment technique in high risk patients is yet to be defined.

BACKGROUND:The outcomes of radiosurgery for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) are not as extensively assessed as those for idiopathic or classical TN cases. OBJECTIVE:Evaluate the safety and efficacy of radiosurgery for TN in MS patients and identify potential predictors of successful outcomes. METHODS:A retrospective single-institution cohort study with patients treated between 2009 and 2022 was performed. Fifty patients were included, and a total of 68 radiosurgical interventions were delivered. Outcomes included the maintenance of pain relief assessed using Kaplan-Meier curves and treatment-related complications. Cox regression analyses were used to identify potential predictors of better pain relief. RESULTS:Following the first radiosurgical treatments, the initial pain relief rate was 86% after a median latency period of 14 days. Adequate pain relief rates at 6, 12, 36 and 60 months were 86%, 52%, 35% and 24%, respectively. Adequate pain relief was sustained for an actuarial median of 12.7 months. After initial relief, pain recurrence occurred in 68% of patients. No statistical difference was seen in the duration of pain relief after initial or repeat radiosurgery (p = 0.368). The most frequent complication was facial hypesthesia (Barrow Neurological Institute facial hypesthesia scale grade II: 10%; III: 6%; IV: 0%). Ipsilateral vascular compression was predictive of better efficacy (p = 0.024). CONCLUSION:Radiosurgery for TN in patients with MS appears to be safe and to provide effective pain relief. Notably, radiological identification of vascular compression may predict more sustained pain relief.

Importance:Prostate-specific membrane antigen positron emission tomography (PSMA-PET) offers superior accuracy in detecting prostate cancer lesions leading to intensified radiotherapy (RT), but its impact on patient outcomes is still undefined. Objective:To evaluate whether intensification of salvage RT (SRT) after radical prostatectomy (RP) guided by PSMA-PET (PSMAiSRT) is associated with improved failure-free survival (FFS). Design, Setting, and Participants:PSMAiSRT was a stratified cohort within a larger PSMA-guided intensification of radiotherapy (PSMAgRT) trial, a phase 2, two-center, registry-based randomized clinical trial. Patients with biochemical recurrence following RP who were eligible for standard-of-care (SOC) SRT from May 2018 to February 2021, were eligible for randomization in the PSMAiSRT stratum. A total of 130 patients were randomized, with 2 who did not proceed to radiotherapy (RT). The cutoff date for the primary analysis was October 26, 2023. Intervention:Patients were randomized in a 1:1 ratio to receive either SOC SRT to the prostate bed, with or without elective pelvic RT, with or without adjuvant hormonal therapy (HT), or PSMA-PET/CT-guided SRT, intensified to detected sites of disease. Main outcome and measures:The primary end point was FFS, defined as PSA progression (PSA nadir >0.2 ng/mL), radiological progression, next-line therapy initiation, or death. Results:Among 128 patients (median [IQR] age, 71 [64-74] years), median (range) PSA at enrollment was 0.3 (0.1-3.0) ng/mL. In the PSMAiSRT group, 33 of 64 patients (52%) received intensified SRT; with addition of pelvic RT (n = 16 [25%]), metastasis-directed RT (n = 2 [3%]), lymph node boost (n = 19 [30%]), or prostate bed boost (n = 15). Adjuvant hormone therapy was equally prevalent in both arms (55 [86%] control vs 54 [84%] PSMAiSRT). At a median (range) follow-up of 37 (7-60) months, PSMAiSRT improved FFS (hazard ratio [HR], 0.50; 95% CI, 0.27-0.94; P = .04) and eugonadal FFS (HR, 0.45; 95% CI, 0.21-0.96; P = .03), with its greatest benefit in the subgroup with PSA of 0.3 ng/mL or more (HR, 0.17; 95% CI, 0.04-0.79; P = .01). Fewer next-line treatment events occurred in the PSMAiSRT arm (4 vs 12; HR, 0.32; 95% CI, 0.11-1.02; P = .04). There were no significant differences in toxic effects or quality of life between arms. Conclusion and Relevance:This phase 2 trial demonstrated an isotoxic improvement in cancer control with PSMA-PET-guided intensification of SRT after RP. Confirmatory evidence is awaited from a subsequently accrued phase 3 trial. Trial Registration:ClinicalTrials.gov NCT03525288.

BACKGROUND:Multi-parametric MRI (mpMRI) datasets often vary between sites due to differences in acquisition protocols. PURPOSE:Evaluate adherence of multi-site mpMRI dataset to minimum technical standards (MTS) of PI-RADSv2.1. STUDY TYPE:Prospective. SUBJECTS:Six hundred patients (Age (years): ≤ 49 = 0.8%, 50-59 = 10.7%, 60-69 = 47.0%, ≥ 70 = 41.5%) with intermediate-risk prostate cancer (PCa) imaged across 124 institutions prior to radiotherapy. FIELD STRENGTH/SEQUENCE:3T, 1.5T, and 1.16T, T2-weighted (T2w): fast spin-echo, diffusion-weighted imaging (DWI): single-shot echo-planar imaging, and dynamic contrast-enhanced (DCE): T1-weighted 3D fast spoiled gradient echo. ASSESSMENT:Scanner vendors included Siemens, GE, Philips, Toshiba, and Hitachi. Degree of adherence to PIRADSv2.1 was determined as the proportion of datasets that met MTS. Mean and standard deviation of parameter values were calculated where applicable. Prostate imaging quality (PI-QUAL)v2 scores were assigned by one of three observers in 491 datasets. Evaluation of DICOM metadata consistency was performed. STATISTICAL TESTS:Fisher's exact test to assess changes in MTS adherence over time and by field strength; Harrel's C-index to compare MTS adherence to PI-QUAL score. A p value of < 0.001 is considered statistically significant after Bonferroni correction. RESULTS:Eighty-two percent of MTS showed greater than 75% adherence. Low adherence was found in the in-plane dimension (frequency-encoding direction) for T2w images (57%, mean = 0.45 ± 0.16 mm) and field of view (FOV) for DW images (62%, mean = 22.67 ± 4.70 cm). Only 50% of datasets used the recommended high b value image to compute the apparent diffusion coefficient map. Adherence improved significantly over time for one T2w and two DWI parameters; the adherence of FOV improved significantly at 3T for T2w and DWI sequences. C-index values for two T2w and two DWI parameters demonstrated a relationship between PI-RADS MTS and PI-QUAL score. Ten percent of anonymized datasets were stripped of some sequence information. DATA CONCLUSION:Results show promise for mpMRI standardization in characterization of PCa and identify key parameters that remain variable across datasets and institutions. EVIDENCE LEVEL:1. TECHNICAL EFFICACY:Stage 2. TRIAL REGISTRATION:ClinicalTrials.gov: NCT03367702.

PURPOSE/OBJECTIVES:Low Dose-Rate Brachytherapy (LDR) and High Dose-Rate Brachytherapy (HDR) are options for favorable risk prostate cancer. We hypothesized that HDR provides comparable disease control with less urinary toxicity. Primary objective was to determine prostate cancer control at 48 months, defined as a PSA < 0.4 ng/ml. MATERIALS/METHODS:Eligible patients had low and intermediate risk diseases. Randomization was to Arm 1 LDR with I-125 to 144 Gy, or Arm 2 HDR with 19 Gy x1 + intraprostatic boost. Follow-up included PSA, toxicity (CTCAE v 4.0), and Quality of Life (EPIC 26). Arm 2 was closed in May 2019 due to evidence of inferior outcomes, and a third arm (HDR 13.5 Gy x 2) was opened. We report outcomes of Arms 1 (LDR) and 2 (HDR single fraction) prior to study amendment. RESULTS:103 patients were randomized: 51 to LDR (Arm 1) and 52 to HDR (Arm 2). Median age 65 years; 76 % had Gleason 3 + 4, 90 % PSA < 10, and 80 % stage T1c. Median follow-up 53 months. PSA control at 4 years was 78.4 % for LDR, and 21.2 % for HDR. Local progression rates: 2 % LDR, 13.5 % HDR. Grade 3 toxicity occurred in 6 patients for LDR and 2 patients Arm 2. Urinary irritative and bowel symptoms were worse in the first 6 months for LDR. CONCLUSIONS:LDR brachytherapy has high prostate cancer disease control rate at 4 years, although with worse impact on urinary symptoms in the first 6 months. Single fraction HDR was associated with unacceptable cancer control.

Purpose Local recurrence of prostate cancer (PCa) after radiation therapy (RT) typically occurs at the site of dominant tumor burden, and recent evidence confirms that magnetic resonance imaging (MRI) guided tumor dose escalation improves outcomes. With the emergence of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), we hypothesize that PSMA-PET and MRI may not equally depict the region most at risk of recurrence after RT. Methods and Materials Patients with intermediate- to high-risk PCa and MRI plus PSMA-PET performed before RT were identified. The sextant most at risk of recurrence was defined as the pathologically dominant region with peak biopsy percentage core length involvement and any sextant with ≥ 40% percentage core length involvement (pathologic gross tumor volume [pGTV], per prior work). Imaging methods were reviewed independently to compare GTVs with pGTVs most at risk of recurrence. A paired chi-square test was employed for analysis. Results Eighty-eight patients (n = 88) were identified. Overall, there were no differences in the sensitivity of MRI and PSMA-PET for identifying the pGTV most at risk of recurrence. However, PSMA-PET demonstrated a trend of improved sensitivity for high-risk PCa compared with MRI (n = 46, 96% vs 87%, P = .06), while MRI outperformed PSMA-PET for the intermediate-risk group (n = 42, 93% vs 81%, P = .03). PSMA-PET showed lower specificity, misidentifying GTV in uninvolved pathologic sextants for 12% of intermediate-risk patients, whereas MRI was faultless (12% vs 0%, P = .03). MRI and PSMA-PET each misidentified uninvolved sextants for 9% of patients in the high-risk group. Conclusions MRI demonstrates superior sensitivity in identifying the region most at risk of RT recurrence for intermediate-risk PCa, whereas PSMA-PET may add value for some high-risk patients. Informed by sextant biopsy information and MRI, clinicians should consider integrating PSMA-PET for patients with high-risk diseases when delineating GTVs.

PURPOSE:This guideline presents evidence-based consensus recommendations for high-dose-rate (HDR) brachytherapy boost in combination with external beam radiotherapy (EBRT) for the primary treatment of localized prostate cancer. METHODS AND MATERIALS:The American Brachytherapy Society convened a task force for addressing key questions concerning prostate HDR brachytherapy boost with EBRT for the primary treatment of localized prostate cancer. A comprehensive literature search was conducted to identify prospective and large retrospective studies involving HDR brachytherapy combined with EBRT. Outcomes of interest included biochemical and/or disease control, toxicity, patient-reported quality of life, and the role of androgen deprivation therapy. RESULTS:HDR brachytherapy using Ir-192 in combination with EBRT is an appropriate treatment option for men with intermediate- and high-risk prostate cancer. CT, ultrasound, and/or MRI are imaging platforms that may be utilized for treatment planning and delivery. A single implant/fraction of 15 Gy or 2 implants/fractions of 9.5-11 Gy each are acceptable regimens in combination with EBRT at a dose equivalent of 45-50.4 Gy in 1.8-2.0 Gy fractions. The addition of HDR brachytherapy is expected to improve biochemical control compared with dose escalated EBRT alone. HDR brachytherapy boost is expected to achieve similar biochemical control outcomes as a low dose rate (LDR) brachytherapy boost. Androgen deprivation therapy is recommended for men with unfavorable intermediate and high-risk disease, with varying duration dependent on cancer risk. Use of an HDR brachytherapy technique, as opposed to LDR permanent seeds, has been shown to have less acute genitourinary (GU) and gastrointestinal (GI) toxicity following treatment. CONCLUSIONS:For men with intermediate- and high-risk prostate cancer, HDR brachytherapy boost is a safe and effective technique for dose-escalation that can achieve superior biochemical control compared with EBRT alone, possibly with an improved GU and GI side effect profile compared with an LDR brachytherapy technique.

Significance:Prostate cancer (PCa) confirmation during needle-based procedures is limited by the lack of intraoperative diagnostic tools. Raman spectroscopy (RS), combined with classification models, offers a promising solution for real-time tissue characterization, potentially improving sampling accuracy and therapy guidance. However, such models require tissue- and organ-specific data, making deployment in studies challenging due to limited data availability. Aim:The aim is to develop a one-dimensional convolutional neural network (1D-CNN) for real-time PCa detection using RS on prospectively collected ex vivo data, leveraging multi-organ pre-training and evaluating two domain adaptation strategies. Approach:A ResNet-based 1D-CNN was trained for binary cancer/normal tissue classification. We implemented a pre-training strategy using retrospective RS data from brain, breast, and prostate (202 patients), along with pre-trained bacterial models, followed by efficient fine-tuning and test-time adaptation (TTA) to adapt to unseen domains. Results:Prospective RS data were acquired using a robotic system from 10 PCa patients (two to five biopsies each). The fine-tuned model achieved 0.76 area under the receiver operating characteristic curve, 0.79 accuracy, 0.83 sensitivity, and 0.72 specificity, outperforming support vector machines. TTA improved predictions when labels were unavailable. Conclusions:Pre-trained 1D-CNNs combined with efficient fine-tuning or TTA enable accurate PCa detection in small-cohort settings using real-time RS.

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.

Purpose/Objective(s) The primary endpoint of our randomized trial was recently reported (Belliveau et al, EAU2024) and demonstrated that intensified salvage radiotherapy guided by PSMA-PET (PSMAiSRT) after radical prostatectomy (RP) resulted in improved failure free survival (FFS). The aim of the present study was to evaluate which subgroups most benefited from PSMAiSRT, evaluate treatment free survival (TFS) outcomes, and determine whether intensification led to heightened toxicity or impact on quality of life (QoL). Materials/Methods Between May 2018 and February 2021, there were 128 subjects with biochemical recurrence (BCR) after RP planned for salvage radiotherapy (SRT) were enrolled in the post-RP stratum of a phase II multicenter registry-based randomized controlled trial (RCT-NCT03525288). Patients were randomized 1:1 to standard of care SRT or 18F-DCFPyL PSMA-PET/CT with intensified SRT guided by newly identified disease sites. Secondary endpoints and subgroup analysis were analyzed using cox regression (Hazard Ratio (HR)) and Kaplan-Meier (survival curves and log-rank). Updated toxicity events (CTCAE version 5.0) grade ≥ 2 and minimal important decline (MID) quality of life (QoL) events based on EPIC-CP in 87 patients (n = 49 PSMAiSRT, n = 38 control) were analyzed. Results As recently published (Petit et al. IJROBP 2023), study arms were balanced with median PSA 0.3 ng/mL (range = 0.1-3) and intensified SRT was delivered in 33 of 64 imaged subjects (n = 16 addition of pelvic SRT, n = 2 addition of metastases-directed RT (MDRT), n = 19 lymph node boost, n = 15 prostate bed boost). The use of adjuvant hormone therapy (HT) was equally high in both arms (86% control vs. 84% PSMAiSRT). At median follow up of 37 months, PSMAiSRT most improved FFS outcomes in patients with PSA ≥ median 0.3 ng/mL (log rank P = 0.01, HR = 0.17, 95% CI = 0.04-0.79) and without adjuvant HT (log rank P = 0.01, HR = 0.009, 95% CI = 0.00-16.20). In secondary endpoint analysis, there was improved TFS with a higher rate of next-line HT events (+/- MDRT) in the control arm (PSMAiSRT 4 events vs. control 12 events, log rank P = 0.04, HR = 0.32, 95% CI = 0.11-1.02). There were no statistically significant differences in toxicity events at median follow up (grade ≥ 2 PSMAiSRT 35 events vs control 39 events, log rank P = 0.716, grade ≥ 3 PSMAiSRT 6 events vs. control 3 events, log rank P = 0.25). Two grade ≥ 3 events were found attributable to intensified RT. No significant differences were found in the rate of MIDs for all QoL domains at 12 and 24 months. (P = NS). Conclusion The results of this randomized trial demonstrate no significant differences in toxicities or impact in QoL with intensified SRT after RP informed by PSMA-PET/CT, with improved FFS leading to improved TFS. In subgroup analysis, there was a pronounced advantage favoring PSMAiSRT in patients with PSA ≥ median 0.3 ng/mL and without adjuvant HT. A Phase III RCT (NCT04557501) has completed accrual and will shed further light on those patients who benefit most from PSMAiSRT.

Purpose Focal recurrence (FR) in patients with prostate cancer (PCa) following first-line radiotherapy (RT) remains prevalent. Despite the advantages of focal HDR salvage regarding toxicity, achieving effective cancer control remains a challenge in patients at risk of distant prostate or regional failure, or those with lower tumor doses (<110 Gy EQD2).(1) Furthermore, PET-PSMA staging has resulted in increased detection of synchronous pelvic lymph node metastases amenable to salvage therapy. In order to improve cancer control outcomes while maintaining favorable toxicity profiles, we implemented a salvage approach combining tumor-targeted HDR brachytherapy and stereotactic radiotherapy (salvage HDR-BT/SRT). Materials and Methods Between May 2022 and October 2023, 11 patients were prospectively enrolled on registry (NCT03378856, PERa), had biochemical failure (PSA nadir + 2 ng/mL) along with MRI ± PSMA-PET (n=10) and histologically confirmed FR, occurring over 24 months after RT (51-114Gy EQD2) and M0. Figure 1 illustrates our approach for managing FR and identifies patients at higher risk of distant prostate and/or regional failure constituting the study cohort. For these patients, treatment consisted of salvage HDR-BT 13-15Gy in 1 fraction to the recurrent tumor followed by SRT delivered every other day, aiming for total prostate tumor EQD2 (ɑ/β 1.4) >120Gy, involved pelvic LNs >80Gy, and >66Gy and 46Gy elective prostate and/or pelvis, respectively. Patients also received adjuvant androgen deprivation therapy (6-18 months). Toxicity was assessed prospectively using CTCAEv5.0 criteria. Results At salvage HDR-BT/SRT, patients received a median dose (EQD2 ɑ/β 1.4) of 130Gy to recurrent prostate tumor (n=11, range 119Gy - 150Gy). Patients at risk of distant prostate failure received a median EQD2 to the whole prostate of 72 Gy (n=7, range 65-81Gy), while those with nodal disease received salvage elective pelvic EQD2 of 47Gy (n=4), and 87Gy to involved LNs. After a median follow-up of 8 months (range: 3-19 months), five grade 2 genitourinary irritative events associated with the experimental treatment were reported, impacting three patients. Among these events, three have resolved. No other grade ≥ 2 events occured. Conclusions We report promising toxicity in the salvage setting with a novel approach of intensified RT for at-risk patients. We now plan to expand to a larger cohort to further evaluate long-term toxicity and cancer control outcomes.