Prostate Stereotactic Body Radiotherapy Research Articles

Stereotactic body radiotherapy with a focal boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 5-year efficacy and toxicity in the hypo-FLAME trial

BackgroundThe addition of an integrated focal boost to the intraprostatic lesion is associated with improved biochemical disease-free survival (bDFS) in patients with intermediate- and high-risk prostate cancer (PCa) in conventionally fractionated radiotherapy. Furthermore, whole gland stereotactic body radiotherapy (SBRT) demonstrated to be non-inferior to conventional radiotherapy for low- and intermediate-risk PCa. To investigate the combination of ultra-hypofractionated prostate SBRT with iso-toxic focal boosting for intermediate- and high-risk PCa, we performed the hypo-FLAME trial. MethodsPatients with intermediate- or high-risk PCa were enrolled in the phase II hypo-FLAME trial. All patients were treated with 35 Gy in 5 weekly fractions to the whole prostate gland with an iso-toxic integrated boost up to 50 Gy to the multiparametric MRI-defined tumor(s). If the dose constraints to the normal tissues would be exceeded, these were prioritised over the focal boost dose. The current analysis reports on the 5-year bDFS, late toxicity and health-related quality of life (HRQoL). ResultsBetween 2016 and 2018, 100 men were treated with a median follow-up of 61 months. The estimated 5-year bDFS (95 % CI) was 93 % (86 % to 97 %). At 5 years, the prevalence of grade 2 + genitourinary and gastrointestinal toxicity was 12 % and 4 %, respectively. ConclusionUltra-hypofractionated focal boost SBRT is associated with encouraging biochemical control rates up to 5-year follow-up in patients with intermediate- and high-risk PCa. Furthermore, prostate SBRT with iso-toxic focal boosting is associated with acceptable late genitourinary and gastrointestinal toxicity rates.

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

1368: Radiation-related lymphopenia post prostate stereotactic body radiation therapy ± pelvic irradiation

1368: Radiation-related lymphopenia post prostate stereotactic body radiation therapy ± pelvic irradiation

Clinical implementation of real time motion management for prostate SBRT: A radiation therapist’s perspective

Background and purposeThe adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial. Materials and Methods18 patients were investigated, nine were fitted with the Micropos RayPilotTM (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath TM (HC) system. 36.25 Gray (Gy) was delivered in 5 fractions over 7 days with daily pre- and post-treatment cone beam computed tomography (CBCT) images acquired. Acute toxicity was reported on completion of treatment at six- and 12-weeks post-treatment, using the Radiation Therapy Oncology Group (RTOG) grading system and vertical (Vrt), longitudinal (Lng) and lateral (Lat) transmitter displacements recorded. ResultsA significant difference was found in the Lat displacement between devices (P=0.003). A more consistent bladder volume was reported in the HC group (68.03 cc to 483.7 cc RP, 196.11 cc to 313.85 cc HC). No significant difference was observed in mean dose to the bladder, rectum and bladder dose maximum between the groups. Comparison of the rectal dose maximum between the groups reported a significant result (P=0.09). Comparing displacements with toxicity endpoints identified two significant correlations: Grade 2 Genitourinary (GU) at 6 weeks, P=0.029; and no toxicity, Gastrointestinal (GI) at 12 weeks P=0.013. ConclusionBoth the directly implanted RP device and the urinary catheter-based HC device are capable of real time motion monitoring. Here, the HC system was advantageous in the SBRT prostate workflow.

Intrafractional motion and dosimetric analysis in prostate stereotactic body radiation therapy with auto beam hold technique

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter. Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3–4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter. Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were −0.7 ± 2.5, 1.4 ± 2.9 and −0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (−1 ± 2%) and less than 10% for PTV (−10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:−206 ± 564 cGy, ΔD10%:−97 ± 426 cGy; ΔD20%:−50 ± 251 cGy). Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.

Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy

PurposeIn stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. MethodsA retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. ResultsAll treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (−46.1 %) and 1.3 min (−56.2 %) for 6 and 10 MV FFF respectively. ConclusionsThe high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC).The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal).During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy.The rates of late > Grade 3 GU toxicity and> Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities.Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral.Three underwent salvage cryotherapy and three received salvage ADT. In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT.However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hopethat recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

The Status and Challenges for Prostate Stereotactic Body Radiation Therapy Treatments in United States Proton Therapy Centers: An NRG Oncology Practice Survey

PurposeTo report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and MethodsA survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. ResultsWe received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. ConclusionProstate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

(016) Sexual Health Toxicity Following MRI-Guided versus CT-guided Prostate SBRT

Abstract Introduction Sexual health toxicities remain an under-reported but important health outcome for patients undergoing radiotherapy for localized prostate cancer. With the increasing adoption of higher daily doses of radiation over shorter timeframes delivered using stereotactic body radiotherapy (SBRT), the precision of radiation delivery remains an important factor that can reduce patient toxicity. MRI-guided SBRT (MRgRT) allows for improved image quality, treatment gating, and planning target volume margin reduction, offering improved radiation precision, which may translate to reduced treatment-related toxicity as compared to traditional CT-guided SBRT (CTgRT). Objective We sought to evaluate the effect of MRI-guidance on sexual health toxicity in patients following prostate SBRT for the treatment of localized prostate cancer. Methods We conducted a post-hoc analysis of patients enrolled on a phase III single-center randomized trial (MIRAGE: NCT04384770). The trial overall seeks to study the relative benefit of MRI vs CT guided SBRT (40 Gy/5 fractions) in patients with localized prostate cancer. Right and left neurovascular bundles (NVBs) and internal pudendal arteries (IPAs) were contoured on treatment planning images. Dosimetric parameters for these structures (Dmax, Dmin, Dmean, and V20Gy) were collected. Patient-reported sexual function outcomes (SHIM and EPIC-26 surveys) were also collected prior to treatment and at 1, 3, and 12 months following treatment. A clinically relevant decrement was defined as a ≥24 point decrease in the EPIC-26 sexual domain scores and a ≥9 point decrease on SHIM surveys. Unpaired t-tests and chi-square tests were used to evaluate for statistical significance. Results 152 patients received either MRgRT (n = 77) or CTgRT (n = 75). MRgRT resulted in a significant improvement in the volume receiving 20 Gy or less of radiation (V20Gy) in the left NVB (7.3cc vs 10.9cc, p = 4.4x10-8), right NVB (7.0cc vs 10.7cc, p = 2.8x10-7), and right IPA (0.42cc vs 1.35cc, p = 0.049), and trended towards significance for the left IPA (0.3cc vs 1.1cc, p = 0.066). Only 48 patients were not given hormonal therapy with radiotherapy. No statistically significant differences in clinically relevant decrements in patient-reported SHIM or EPIC scores were seen between MRgRT and CTgRT in these patients. No clear association between acute or chronic (12-months post-RT) sexual health toxicity and radiation exposure to the NVBs or IPAs was identified. Conclusions Patients treated with MRgRT had decreased radiation exposure to the bilateral NVBs and IPAs compared to patients treated with CTgRT. These data highlight the dosimetric benefits of MRgRT with regard to sexually relevant organs at risk. Power to detect associations between dosimetry and patient-reported sexual health outcomes will increase as the data matures and more patients have recovered testosterone after use of hormonal therapy. Future work will assess the impact on MRI-guided vs CT-guided radiation on sexual health outcomes at later time points. Disclosure No.

Clinical Outcomes of Prostate SBRT Using Non-adaptive MR-Guided Radiotherapy.

Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. Median follow up was 19.3months (3.8 - 36.6). Median BOT was 4.6min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

Treatment accuracy of standard linear accelerator-based prostate SBRT: the delivered dose assessment of patients treated within two major clinical trials using an in-house position monitoring system.

The purpose of this study was to assess the dosimetric improvements achieved in prostate stereotactic body radiotherapy (SBRT) treatment within the PROMETHEUS and NINJA trials using an in-house real-time position monitoring system, SeedTracker. This study considered a total of 127 prostate SBRT patients treated in the PROMETHEUS (ACTRN12615000223538) and NINJA (ACTRN12618001806257) clinical trials. The SeedTracker position monitoring system was utilized for real-time position monitoring with a 3-mm position tolerance. The doses delivered to the clinical target volume (CTV), rectum, and bladder were assessed by incorporating the actual target position during treatment. The dose that would have been delivered without monitoring was also assessed by incorporating the observed position deviations. Treatment with position corrections resulted in a mean (range) CTV D99 difference of -0.3 (-1.0 to 0.0) Gy between the planned and delivered dose. Without corrections, this difference would have been -0.6 (-3.7 to 0.0) Gy. Not correcting for position deviations resulted in a statistically significant difference between the planned and delivered CTV D99 (p < 0.05). The mean (range) dose difference between the planned and delivered D2cc of the rectum and bladder for treatment with position corrections was -0.1 (-3.7 to 4.7) Gy and -0.1 (-1.7 to 0.5) Gy, respectively. Without corrections, these differences would have been -0.6 (-6.1 to 4.7) Gy and -0.2 (-2.5 to 0.9) Gy. SeedTracker improved clinical dose volume compliance in prostate SBRT. Without monitoring and corrections, delivered dose would significantly differ from the planned dose.

Quantifying Intrafraction Motion and the Impact of Gating for Magnetic Resonance Imaging-Guided Stereotactic Radiation therapy for Prostate Cancer: Analysis of the Magnetic Resonance Imaging Arm From the MIRAGE Phase 3 Randomized Trial

Real-time intrafraction tracking/gating is an integral component of magnetic resonance imaging-guided radiation therapy (MRgRT) and may have contributed to the acute toxicity reduction during prostate stereotactic body radiation therapy observed on the MRgRT-arm of the MIRAGE (MAGNETIC RESONANCE IMAGING-GUIDED Stereotactic Body Radiotherapy for Prostate Cancer) randomized trial (NCT04384770). Herein we characterized intrafraction prostate motion and assessed gating effectiveness. Seventy-nine patients were treated on an MR-LINAC. Real-time cine imaging was acquired at 4Hz in a sagittal plane. If >10% of the prostate area moved outside of a 3-mm gating boundary, an automatic beam hold was initiated. An in-house tool was developed to retrospectively extract gating signal for all patients and identify the tracked prostate in each cine frame for a subgroup of 40 patients. The fraction of time the prostate was within the gating window was defined as the gating duty cycle (GDC). A total of 391 treatments from 79 patients were analyzed. Median GDC was 0.974 (IQR, 0.916-0.983). Fifty (63.2%) and 24 (30.4%) patients had at least 1 fraction with GDC ≤0.9 and GDC ≤0.8, respectively. Incidence of low GDC fractions among patients appeared stochastic. Patients with minimum GDC <0.8 trended toward more frequent grade 2 genitourinary toxicity compared with those with minimum GDC >0.8 (38% vs 18%, P = .065). Prostate intrafraction motion was mostly along the bladder-rectum axis and predominantly in the superior-anterior direction. Motion in the inferior-posterior direction was associated with significantly higher rate of acute grade 2 genitourinary toxicity (66.7% vs 13.9%, P = .001). Gating limited mean prostate motion during treatment delivery in fractions with a GDC <0.9 (<0.8) to 2.9 mm (2.9 mm) versus 4.1 mm (4.7 mm) for ungated motion. Fractions with large intrafraction motion were associated with increased toxicity and their occurrence among patients appears stochastic. Real-time tracking/gating effectively mitigated this motion and is likely a major contributing factor of acute toxicity reduction associated with MRgRT.

Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial

PurposeErectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiotherapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultra-hypofractionation as part of a phase II clinical trial of urethra-sparing prostate SBRT. Material and methodsAmong the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with CTCAE v4.03 grade 0-1 ED (ED-) at baseline treated with 36.25Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2-3 ED (ED+) development. The impact on QoL assessed by the EORTC PR-25 questionnaire was reported. ResultsAfter a median follow-up of 6.5 years, 43% (n=39) of the patients developed ED+, while 57% (n=51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 Gy vs 3.6 Gy (p=0.014) for the Dmean and 18.5 Gy vs 7.2 Gy (p=0.015) for the D2%, respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and the IPA. The median ED+ free-survival was worse in patients receiving a crura Dmean ≥ 4.7 Gy vs < 4.7 Gy (51.5% vs 71.7%, p=0.005), and a crura D2% >12 Gy vs ≤ 12 Gy (54.9% vs 68.9%, p =0.015). No ED+ free-survival differences were observed for doses delivered to PB and IPA. Decline in EORTC PR-25 sexual functioning was significantly more pronounced in patients with higher doses to the crura. ConclusionsBy keeping a Dmean and D2% to crura below 4.7 Gy and 12 Gy respectively, the risk to develop ED+ following prostate SBRT may be significantly reduced.

Performance characterization of a novel hybrid dosimetry insert for simultaneous spatial, temporal, and motion-included dosimetry for MR-linac.

Several (online) adaptive radiotherapy procedures are available to maximize healthy tissue sparing in the presence of inter/intrafractional motion during stereotactic body radiotherapy (SBRT) on an MR-linac. The increased treatment complexity and the motion-delivery interplay during these treatments require MR-compatible motion phantoms with time-resolved dosimeters to validate end-to-end workflows. This is not possible with currently available phantoms. Here, we demonstrate a new commercial hybrid film-scintillator cassette, combining high spatial resolution radiochromic film with four time-resolved plastic scintillator dosimeters (PSDs) in an MRI-compatible motion phantom. First, the PSD's performance for consistency, dose linearity, and pulse repetition frequency (PRF) dependence was evaluated using an RW3 solid water slab phantom. We then demonstrated the MRI4D scintillator cassette's suitability for time-resolved and motion-included quality assurance for adapt-to-shape (ATS), trailing, gating, and multileaf collimator (MLC) tracking adaptations on a 1.5 T MR-linac. To do this, the cassette was inserted into the Quasar MRI4D phantom, which we used statically or programmed with artificial and patient-derived motion. Simultaneously with dose measurements, the beam-gating latency was estimated from the time difference between the target entering/leaving the gating window and the beam-on/off times derived from the time-resolved dose measurements. Experiments revealed excellent detector consistency (standard deviation 0.6%), dose linearity (R2 = 1), and only very low PRF dependence ( 0.4%). The dosimetry cassette demonstrated a near-perfect agreement during an ATS workflow between the time-resolved PSD and treatment planning system (TPS) dose (0%-2%). The high spatial resolution film measurements confirmed this with a 1%/1-mm local gamma pass-rate of 90%. When trailing patient-derived prostate motion for a prostate SBRT delivery, the time-resolved cassette measurements demonstrated how trailing mitigated the motion-induced dose reductions from 1%-17% to 1%-2% compared to TPS dose. The cassette's simultaneously measured spatial dose distribution highlighted the dosimetric gain of trailing by improving the 3%/3-mm local gamma pass-rates from 80% to 97% compared to the static dose. Similarly, the cassette demonstrated the benefit of real-time adaptations when compensating patient-derived respiratory motion by showing how the TPS dose was restored from 2%-56% to 0%-12% (gating) and 1%-26% to 1%-7% (MLC tracking) differences. Larger differences are explainable by TPS-PSD coregistration uncertainty combined with a steep dose gradient outside the PTV. The cassette also demonstrated how the spatial dose distributions were drastically improved by the real-time adaptations with 1%/1-mm local gamma pass-rates that were increased from 8 to 79% (gating) and from 35 to 89% (MLC tracking). The cassette-determined beam-gating latency agreed within 12 ms with the ground truth latency measurement. Film and PSD dose agreed well for most cases (differences relative to TPS dose 4%), while film-PSD coregistration uncertainty caused relative differences of 5%-8%. This study demonstrates the excellent suitability of a new commercial hybrid film-scintillator cassette for simultaneous spatial, temporal, and motion-includeddosimetry.

Prostate volume variation during 1.5T MR-guided adaptive stereotactic body radiotherapy (SBRT) and correlation with treatment toxicity

IntroductionTo evaluate prostate volume change during daily-adaptive prostate SBRT on 1.5 T MR-linac and to correlate it with treatment toxicity. Methodsa series of patients affected by low-to-intermediate risk prostate cancer was treated by 5-fraction SBRT within a prospective study (Prot. n° 23748). Total dose was 35 Gy and 36.25 Gy delivered every day or on alternate days. Treatment toxicity was recorded with the following patient reported outcomes (PROMs): IPSS, ICIQ-SF, and EPIC-26. Results254 patients were included in the analysis. Baseline median CTV volume was 55 cc (range 15.3–163.3). Mean prostate volume were 58.9 cc, and 62.7 cc at first and last fraction respectively (mean volume increase 6.4 %; p = <0.0001). We observed prostate swelling (mean 15.4 % increase) in 50 % of cases, stable volume (≤5% volume change) in 39 % of patients, and prostate shrinkage in 11 % of cases (mean 12.2 % reduction). Baseline CTV > 55 cc showed a trend towards higher CTV shrinkage (-10.5 % versus −14.5 %; p = 0.052). We found no correlation between CTV change and PROMs. Prostate swelling was generally compensated by the planned PTV expansion, even though the mean setup volume dropped from 47.4 cc to 38.9 cc at last fraction, with few cases not covered by initial setup margins. ConclusionThe present study reported a significant prostate volume change during prostate SBRT on 1.5T MR-linac. We observed both prostate swelling in half of cases and few cases of prostate shrinkage. No correlations were found with PROMs in this population treatment with daily-adaptive strategy.

Patient adherence and early biochemical outcomes following relugolix with stereotactic body radiation therapy (SBRT) for unfavorable prostate cancer.

526 Background: Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventional radiotherapy. Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Methods: This prospective study sought to evaluate early testosterone suppression and PSA response following Relugolix and SBRT for unfavorable prostate cancer. Relugolix was initiated at least 2 months prior to SBRT. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone &lt; 20 ng/dL. Poor drug adherence was delineated as failure to reach profound castration. PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and &lt; 0.2 ng/mL during the first 4 months post SBRT. Results: Between July 2021 and January 2023, 52 men were treated at Georgetown with Relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were black and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were &gt; Grade Group 3. 44 patients were intermediate- and 8 were high-risk. The disease volume was high (mean 43.6% of total cores involved). Patients initiated Relugolix at a median of 3.6 months prior to SBRT with a median of 6.2 total months. 92.3%of patients achieved profound castration during Relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue Relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Conclusions: Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. Given the potential benefits of Relugolix over injectable GnRH receptor agonists, its usage may be preferred, especially in specific patient populations (fear of needles, prior cardiovascular events). We observed a 96% compliance rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients can consistently and successfully follow an oral ADT protocol in a real-world setting. Future studies should focus on barriers to medication access.

CT-based online adaptive radiotherapy improves target coverage and organ at risk (OAR) avoidance in stereotactic body radiation therapy (SBRT) for prostate cancer

IntroductionStereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. MethodsSeven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student’s t-test, with significance threshold of P < 0.05. ResultsSeven patients completed 35 Fx’s of adaptive RT. Daily adaptation resulted in a statistically significant mean improvement in PTV V100 for all targets: [21.4 % ± 4.3 % for PTV 4000 (p < 0.0001); 8.7 % ± 1.1 % for PTV 3625 (p < 0.0001); and 11.5 % ± 3.1 % for PTV 2500 (p = 0.0013)]. Mean rectal D0.03 was significantly reduced by 38.8 cGy ± 5.95 cGy (p < 0.0001) per fraction (194 cGy/5 fractions) compared to the initial plans. There was a modest increase in bladder dose of 10.9 cGy ± 4.93 cGy per fraction (p = 0.0424) for the adaptive plans. The adaptive plans met bladder constraints for every fraction. There were no statistically significant differences between sigmoid or bowel dose for adapted vs. initial plans. No patients experienced acute CTCAE grade ≥ 3 GI/GU adverse events (median F/U 9.5 months). All statistically significant differences were maintained in the presence and absence of rectal hydrogel spacer (p < 0.05). ConclusionsCT-based online adaptive SBRT resulted in statistically significant and clinically meaningful improvements in PTV coverage and D0.03 cc dose to the rectum. A trial evaluating CT adaptive whole-pelvis prostate SBRT is underway.

Impact of Interfractional Bladder and Trigone Displacement and Deformation on Radiation Exposure and Subsequent Acute Genitourinary Toxicity: A Post Hoc Analysis of Patients Treated with Magnetic Resonance Imaging–Guided Prostate Stereotactic Body Radiation Therapy in a Phase 3 Randomized Trial

PurposeEmerging data suggest that trigone dosimetry may be more associated with post-stereotactic body radiotherapy (SBRT) urinary toxicity than whole bladder dosimetry. Herein, we quantify the dosimetric impact of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pre-treatment 0.35T MRI images. MethodsSeventy-seven patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase III single-center randomized trial were included. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and five on-board pre-treatment MRIs. Dice Similarity Coefficient (DSC) scores and changes in volume between simulation and daily treatments were calculated. Dosimetric parameters including Dmax, D0.03cc, Dmean, V40Gy, V39Gy, V38Gy, and V20Gy for the bladder and trigone for the simulation and daily treatments were collected. Both physician-scored (CTCAE v4.03 scale) as well as patient-reported (IPSS and EPIC-26 scores) acute genitourinary (GU) toxicity outcomes were collected and analyzed. ResultsThe average treatment bladder volume was about 30% smaller than the simulation bladder volume; however, the trigone volume remained fairly consistent despite being positively correlated with total bladder volume. Overall, the trigone accounted for less than 2% of the bladder volume. Median DSC for the bladder was 0.79 while the median DSC of the trigone was only 0.33. No statistically significant associations between our selected bladder and trigonal dosimetric parameters and grade 2 or greater GU toxicity were identified, though numerically, patients with GU toxicity (grade ≥ 2) had higher intermediate doses to the bladder (V20Gy and Dmean) and larger volumes exposed to higher doses in the trigone (V40Gy, V39Gy, and V38Gy). ConclusionsThe trigone exhibits little volume change, but considerable interfractional displacement/deformation. As a result, the relative volume of the trigone receiving high doses during prostate SBRT varies substantially between fractions, which could influence GU toxicity and may not be predicted by radiation planning dosimetry.

Evaluation of kV Triggered Fiducial Tracking for Prostate SBRT Intrafraction Motion Management.

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment for localized prostate cancer. Given the high dose per fraction, a high degree of precision is needed during SBRT treatment delivery. Fiducial marker tracking is a means of monitoring intrafraction motion, ensuring precise treatment delivery and potentially allowing for decreased planning target volume (PTV) margins. We present a 5-year single institution experience to characterize the performance of fiducial tracking. We analyzed 132 consecutive patients treated at our institution with prostate SBRT between July 2017 and November 2022 using fiducial tracking with the TrueBeam Auto Beam Hold feature. Patients were treated using a 5-fraction dose escalation protocol, with many receiving a simultaneous integrated boost to the GTV up to 45 Gy. All patients underwent pre-treatment cone-beam CT and planar kV imaging with rigid registration to the fiducial markers. Cine kV images were acquired every 3-5 seconds during treatment delivery and the beam was paused when a fiducial deviated from a given 4 mm diameter tolerance region. Additional intrafraction 2D or 3D imaging techniques were then used to realign the fiducials. Data was retrieved from the record and verify system including: number and type of intrafraction images, number of treatment interruptions, number of and magnitude of shifts, and total treatment time. The average number of cine kV images acquired per fraction and for the total 5 fraction SBRT course were 86.6 ± 26.8 and 425.6 ± 136.8 respectively. Assuming 1.3 mGy/kV image, the fiducial tracking process delivered an average additional 55.3 cGy over the full treatment course. On average, the beam was paused 5.0 ± 2.5 times per fraction (range 1-21 interruptions) and shifts were applied 4.1 ± 2.1 times (range 0-10.2 times) per fraction. Over the 2560 total shifts applied for all the patients, the average(max) translations were 0.6 (12) mm vrt, 0.7 (22) mm lng, and 0.9 (5) mm lat and the average(max) rotations were 0.19 (5.9)° pitch, 0.01 (2.4)° roll, and 0.16 (6.4)° rtn. Overall, 2.4% of shifts were greater than the 4 mm PTV margin and 4.2% of vertical shifts were greater than the 2.5 mm posterior margin. Average fraction treatment time was 27 ± 9.7 minutes. Fiducial tracking affords the potential to increase daily treatment precision when delivering prostate SBRT. Our data indicate that the beam is typically paused several times during a prostate SBRT fraction, with occasional large shifts required, suggesting the importance of intrafraction motion management. Downsides of kV triggered fiducial tracking include extension of treatment times and delivery of additional radiation dose to the patient. We are investigating if this method of motion management might allow for a reduction in PTV margins to reduce normal tissue dosing.