Body Radiation Therapy For Prostate Cancer Research Articles

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n=29) was significantly higher than that in group 2 (n=26), and Dmax , D0.03cc , D1cc , and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5±12.2%) in group 1 was significantly higher (p<0.05) than that in group 2 (74.7±10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

Dosimetric Predictors of Toxicities and Quality of Life Following Two-Fraction Stereotactic Body Radiotherapy for Prostate Cancer.

There is emerging interest in two-fraction stereotactic body radiotherapy (2#SBRT) for localized prostate cancer. However, there is limited data to guide organs at risk (OAR) dose constraints in 2#SBRT. We aim to identify dosimetric predictors of toxicities and quality of life (QoL) using real life patient data from two prospective 2#SBRT trials. We included 60 patients who had 2#SBRT in the 2STAR (NCT02031328) and 2SMART (NCT03588819) phase 2 trials. The prescribed dose was 26Gy to the prostate +/- focal boost of 32Gy to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC26 questionnaires. For QoL, we reported the minimal clinical important changes (MCIC), defined as changes in QoL score of >0.5 standard deviation from baseline QoL score. We evaluated the bladder, urethra, rectum, and penile bulb dosimetry (urethra dosimetry only available in 30 patients in 2SMART trial). Some of the dosimetric parameters were log-transformed to normalize the distribution. Cox regression was used to identify dosimetric predictors for acute and late grade ≥2 GU toxicities. Logistic regression was used to identify dosimetric predictors for late MCIC in urinary, bowel and sexual QoL domains. Backward stepwise selection was used to identify significant dosimetric parameters. For GU toxicities and urinary QoL, three additional clinical factors (age, prostate volume and IPSS) were included in the final model as confounding factors. Receiver operating characteristics curve was used to identify cut-off for significant dosimetric parameters. The median follow-up for the cohort was 56 months (range: 39-78 months). The cumulative acute and late grade ³2 GU toxicities were 62% (37/60) and 57% (34/60) respectively. No bladder or urethra dosimetric parameter was associated with acute grade ≥2 GU toxicities. Bladder D0.5cc was significant predictor of late grade ≥2 GU toxicities in univariate model (P = 0.05), but not in multivariate model. Baseline IPSS score was the single strongest predictor for late grade ≥2 GU toxicities (HR = 1.9; 95% CI = 1.1-3.4; P = 0.03). For late QoL outcomes, there were 36% (21/58), 28% (16/58), and 29% (17/58) of patients with MCIC in urinary, bowel and sexual QoL domains respectively. Bladder V10Gy was associated with late urinary MCIC in multivariate model after adjusting for clinical confounders (HR = 2.6, 95% CI = 1.1-6.6; P = 0.04). 48% (14/29) and 24% (7/29) of patients with bladder V10Gy>13.9% and V10Gy≤13.9% respectively had late urinary MCIC. No rectum and penile bulb dosimetry parameters was identified to be associated with late bowel or sexual QoL. Using real life patient data from prospective clinical trials with medium term follow-up, we identified statistically significant bladder dosimetry parameter predictive of late urinary QoL. This finding could be useful to guide OAR dose constraints in prostate 2#SBRT trials.

State of the art and future challenges of urethra-sparing stereotactic body radiotherapy for prostate cancer: a systematic review of literature

PurposeDoses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity.MethodA systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: “urethra-steering” SBRT (restriction of hotspots to the urethra) and “urethra dose-reduction” SBRT (dose reduction to urethra below the prescribed dose).ResultsBy limiting the urethra Dmax to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years.ConclusionUS-SBRT techniques limiting maximum doses to urethra below a 90GyEQD2 (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.

Energy use in moderate hypofractionation and stereotactic body radiotherapy for prostate cancer.

Energy use in moderate hypofractionation and stereotactic body radiotherapy for prostate cancer.

Optimization of Fluence Map for CyberKnife Raster Scanning Intensity Modulated Radiotherapy.

Stereotactic body radiotherapy for prostate cancer using CyberKnife with circular cone requires a long treatment time. Raster scanning intensity modulated radiotherapy (RS-IMRT) has a potential of improving treatment efficacy, introducing shorter treatment time, better target dose uniformity, and lower organ at risk (OAR) dose. The purpose of the study was to develop a fluence optimization system for RS-IMRT. RS-IMRT plans were created for five prostate cancer patients treated with the Novalis system and parameters were compared to the Novalis treatment plans. From 80 nodes available for the CyberKnife, twelve nodes were arbitrarily selected. On the beam's eye view of each beam, a 100×100 matrix of optimization points was created at the target center plane. The beam fluence map was optimized using the attraction-repulsion model (ARM). The beam fluence maps were converted to the scanning sequence using the ARM and a final dose calculation was performed. For planning target volume (PTV), RS-IMRT plans showed higher dose covering 2% of the volume (D2%) and lower D98% compared to the Novalis plans. However, the homogeneity was within our Institutional clinical protocol. The RS-IMRT plans showed significantly lower OAR dose parameters including bladder volume receiving 100% of prescribed dose (V100%) and dose delivered to 5 cm3 of rectum (D5 cc). We developed a fluence optimization system for RS-IMRT that performs the entire RS-IMRT treatment planning process, including scanning sequence optimization and final dose calculation. The RS-IMRT was capable of generating clinically acceptable plans.

Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer

Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial. To determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance. This phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up. Patients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions. The primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes. Between May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month. In this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist. ClinicalTrials.gov Identifier: NCT04384770.

Acute Gastrointestinal and Genitourinary Toxicity from Stereotactic Body Radiotherapy for Prostate Cancer following Continuous Tumour Tracking with the Micropos Medical RayPilot and RayPilot HypoCath System®

Purpose: Stereotactic body radiotherapy (SBRT) for prostate cancer is delivered over a shorter period than standard fractionation, with similar levels of post-treatment toxicity [1]. However, the greater dose per fraction delivered increases the significance of inter-fraction variability. The use of prostate tracking devices in planning and during treatment may help reduce variability and help develop more personalised radiotherapy plans. Here, we present acute toxicity data for patients treated with SBRT for prostate cancer where on-treatment prostate tracking was carried out.

1.5T MR-Guided Daily-Adaptive SBRT for Prostate Cancer: Preliminary Report of Toxicity and Quality of Life of the First 100 Patients.

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52-84). The median total dose delivered was 35 Gy (35-36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3-20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.

P038 - Toxicity patterns and preliminary clinical outcomes of 1.5T MR-guided stereotactic body radiotherapy for prostate cancer

P038 - Toxicity patterns and preliminary clinical outcomes of 1.5T MR-guided stereotactic body radiotherapy for prostate cancer

Magnetic Resonance Imaging-Guided vs. Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer (MIRAGE): Primary Endpoint Analysis of a Phase III Randomized Trial

<h3>Purpose/Objective(s)</h3> Magnetic resonance imaging (MRI) guidance offers multiple potential advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Herein we report the outcomes of a phase III randomized trial comparing acute grade ≥2 genitourinary (GU) toxicity after MRI- vs. CT-guided prostate SBRT. <h3>Materials/Methods</h3> Following stratification based on IPSS (≤15 or >15) and prostate volume (≤50 or >50 mL), patients were randomized to receive SBRT with CT- vs. MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary endpoint was the incidence of acute (i.e., within 90 days of SBRT completion) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). The trial had a superiority design, hypothesizing that 154 patients would provide 89% power to detect a 14% reduction in acute grade ≥2 GU toxicity with MRI-guidance with a one-sided significance level of 0.025. Changes in patient-reported outcomes were compared using a chi-square test with the same significance level. <h3>Results</h3> Between May 2020 and October 2021, 156 patients (n=77 CT and n=79 MRI) were randomized. 81% of patients had NCCN unfavorable intermediate-, high, or very high-risk disease, 44% had placement of a spacer and 27% had nodal radiation. Rates of acute grade ≥2 GU toxicity were significantly lower with MRI- vs. CT-guidance (24.4% [95%CI 15.4-35.4%] vs. 43.4% [95%CI 32.1-55.3%], p=0.01). Rates of acute grade ≥2 GI toxicity were also significantly lower with MRI-guidance (0.0% [95% CI 0-4.6%] vs. 10.5% [4.7-19.7%], p=0.003). On multivariable analysis adjusting for trial arm, age, IPSS, gland volume, spacer use, lymph node radiation, and use of a simultaneous integrated boost dose to gross disease, trial arm remained associated with a 60% reduction in odds of grade ≥2 GU toxicity (odds ratio 0.40 [95%CI 0.19-0.84], p=0.02). MRI-guidance was associated with a significantly smaller proportion of patients with a ≥15-point increase in IPSS approached (6.8% vs. 19.4%, p=0.011). MRI-guidance was associated with a significantly reduced proportion of patients with a clinically significant (>12 point) significant decrease in EPIC-26 bowel scores (25.0% vs. 50.0%, p=0.0013). <h3>Conclusion</h3> MRI-guidance significantly reduced acute grade ≥2 GU and GI toxicity. Patient-reported outcomes were also improved at 1 month with MRI-guidance, and trial arm was a significant predictor of lower odds of moderate GU toxicity after adjusting for other important covariates. Differences in late toxicity will take years to manifest, but in the interim, these data strongly suggest that MRI-guided prostate SBRT affords significantly reduced toxicity compared with CT-guided SBRT.

PSA Kinetics and Outcomes after Magnetic Resonance Image-Guided Stereotactic Body Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. Assessment of the efficacy of treatment response after radiotherapy relies heavily on the monitoring of prostate specific antigen (PSA) levels and PSA kinetics. The aim of our study was to evaluate tumor control outcomes with PSA response and toxicity after magnetic resonance image-guided adaptive radiotherapy (MRgRT) for prostate cancer patients. <h3>Materials/Methods</h3> A total of 95 prostate cancer patients treated with MRgRT were included in the study. Treatment was performed with IMRT (step and shoot) technique and daily plan adaptation using MRgRT. Patients received 36.25 Gy in 5 fractions, per institutional standards. Outcome measurements included tumor control evaluation with PSA levels, acute and late toxicities. Nadir PSA was defined as the lowest serum PSA value from the time of SBRT completion to date of last follow-up. Biochemical failure (BCF) was defined using the Phoenix definition (nadir + 2 ng/mL). <h3>Results</h3> The median follow-up for our cohort was 23.7 months (range; 3-41.4 months). The median age was 74 years (range; 50-87 years). The median initial PSA (iPSA) was 7.6 ng/mL (range; 2.7-44 ng/mL) for all patients. According to the NCCN guidelines, 13 (13.7%), 53 (55.8%) and 29 (30.5%) patients were in low-, intermediate- and high-risk group, respectively. Twenty-nine patients (30.5%) received androgen deprivation therapy (ADT). The median nadir PSA (nPSA) for all patients was 0.72 ng/mL (range, 0.01-4.96 ng/mL). For the entire cohort, 52.6% patients had an nPSA <1 ng/mL, with 35.8% of patients reaching an nPSA 0.5 ng/mL and 20% reaching an nPSA 0.2 ng/mL. For the patients who didn't receive ADT, median nPSA was 1.26 ng/mL (range; 0.16-4.96 ng/mL); 45.0% patients had an nPSA <1 ng/mL, with 21.3% of patients reaching an nPSA 0.5 ng/mL and 3.3% reaching an nPSA 0.2 ng/mL. For the patients who received ADT, median nPSA was 0.06 ng/mL (range; 0.01-1.55 ng/mL); 95.8% patients had an nPSA <1 ng/mL, with 87.5% of patients reaching an nPSA 0.5 ng/mL and 70.8% reaching an nPSA 0.2 ng/mL. A patient who did not yet meet the Phoenix criteria for biochemical recurrence but a PSA rising was diagnosed with two bone metastases with imaging evaluation and one patient with a nPSA and positive PSMA-PET had radical prostatectomy. MRgRT was well tolerated by all patients. There was no Grade ≥3 GU or GI toxicity. <h3>Conclusion</h3> In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation with MRgRT has an acceptable toxicity profile with favorable efficacy and PSA response. Further studies with longer follow-up time and larger cohorts are warranted.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. Accuray.

PD-0325 Feasibility and safety of MR-guided stereotactic ablative body radiotherapy for Prostate Cancer

PD-0325 Feasibility and safety of MR-guided stereotactic ablative body radiotherapy for Prostate Cancer

Stereotactic body radiotherapy of prostate cancer: influence of intrafraction motion of prostate on final dose distribution

Purpose: To determine impact of various planning tumour volume (PTV) margins on final dose distribution in patients with maximal intrafraction prostate displacement. Materials: We analyzed data of 15 prostate cancer patients with maximal (значения) prostate intrafraction displacement registered during stereotactic body radiotherapy (SBRT) — 5 fractions of 7.25 Gy. Prostate displacement was determined by cone beam CT that was performed before and after each fraction. Modeling of dose distribution considering prostate displacement was performed for every fraction by isocenter shift. Final dose distribution was calculated as the sum of all fractions and was evaluated for PTV with various margins: 5-5-5-3, 3-3-3-1, 5-5-5 and cropped rectum. Results: The dosimetric impact of maximal intrafraction prostate motion was minimal for target coverage even for PTV with minimal margins (3 in all directions and 1 mm — posterior): CTV V100% varied from 97.5 to 100%. Prostate displacement reduced the dose to the rectum in all but minimal doses were detected for PTV 3-3-3-1: average D2cc — 31.87 Gy (28.41–34.05). For PTV 3-3-3-1 average bladder V100% volume slightly increased from 3.67 (SBRT plan) to 4.87 cc (simulation of intrafraction prostate displacement). Conclusions: The dosimetric impact of maximal intrafraction prostate motion was minimal for target coverage and doses in rectum and bladder even for PTV with minimal (3-3-3-1) margins.

Magnetic resonance imaging-guided versus computed tomography-guided stereotactic body radiotherapy for prostate cancer (MIRAGE): Interim analysis of a phase III randomized trial.

255 Background: Magnetic resonance imaging (MRI) guidance offers several theoretical advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Here we report the results of an interim analysis of the phase III MIRAGE trial, which directly compared MRI- and CT-guidance with a pragmatic primary endpoint of acute grade ≥2 genitourinary (GU) toxicity. Methods: MIRAGE is a single center, randomized phase 3 trial. Men undergoing SBRT for localized prostate cancer were randomly assigned to either CT-guidance or MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary outcome was the incidence of acute (i.e., within 90 days of SBRT) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). Secondary outcomes of interest included the incidence of acute grade ≥2 GU physician-reported toxicity, changes in IPSS scores at 1 and 3 months, and changes in EPIC-26 bowel domain summary scores at 1 and 3 months. A pre-specified efficacy analysis was planned once the 100th patient was eligible for evaluation of the primary endpoint. Results: On 9/1/2021, 100 patients became eligible for evaluation for the interim analysis (51 CT arm, 49 MRI arm). Acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SBRT (incidence of 24 (47.1%) vs. 11 (22.4%), p = 0.01). Acute grade ≥2 GI toxicity was also significantly reduced in men receiving MRI-guided SBRT (incidence of 7 (13.7%) vs. 0 (0%), p = 0.01.). The increase in IPSS scores from baseline was significantly higher in men receiving CT-guided SBRT at 1 month post-SBRT (median change of 10 vs. 6, p = 0.03), but not at 3 months (median change of 3 vs. 2, p = 0.3). The decrement in EPIC-26 bowel domain scores was significantly greater at 1 month in men receiving CT-guided SBRT (median change of -8.3 vs. 0, p = 0.03), but not at 3 months (median change of -2.3 vs. 0, p = 0.4). Given the large primary endpoint signal seen, our protocol was amended to reduce the projected sample size to 154 while still maintaining 89% power to detect a difference. Conclusions: This interim analysis demonstrates a statistically significant reduction in acute grade ≥2 GU toxicity with MRI-guidance versus CT-guidance in the context of prostate SBRT. Patient-reported urinary and bowel function metrics are also better preserved at the 1 month time point with MRI-guidance, though this difference dissipates (potentially due to side-effect management) at the 3 month time point. Accrual has been completed as of October 2021 and a final analysis for the primary endpoint is anticipated in early 2022. Clinical trial information: NCT04384770.

Treatment Interruptions During Stereotactic Body Radiotherapy for Prostate Cancer.

BackgroundDuring the course of radiation treatment for prostate cancer, patients may have unintentional interruptions in their treatment course due to a wide variety of factors. Stereotactic body radiation therapy (SBRT) decreases the number of treatments compared to conventionally fractionated radiation; hence, it has the potential to decrease treatment delays and non-completion. This study sought to determine the incidence of treatment delay and characterize the etiology and length in a large cohort of men treated with SBRT for their prostate cancer.MethodsOne thousand three hundred and thirty-six patients treated with SBRT from 2008 to 2021 at the Georgetown University Hospital for prostate cancer were included in this retrospective study. A treatment delay was defined as a patient requiring longer than 14 days to complete 5 fractions of SBRT. Non-completion was defined as patients treated with less than 5 fractions. In the patients who experienced delays, chart review was performed to characterize the length and etiology of each delay. Multivariate analysis was performed via binary logistic regression modeling on PSPP.ResultsAll individuals in the cohort eventually completed the planned 5-fraction regimen. Thirty-three patients experienced a treatment delay. Median length of time to complete treatment was 11 days (range 5–155 days). In patients who experienced a delay, nearly half (45.5%) experienced only a one-day delay. The most common reason for a delay was a technical issue (48.5%), including the machine maintenance, fiducial misalignment, or inadequate pretreatment bowel preparation. Other reasons included unplanned breaks due to acute side effects (21.2%), logistical issues (18.2%), non-treatment related health issues (9.1%), and inclement weather (3.0%). There were no significant sociodemographic, oncologic, or treatment variables that predicted treatment interruption on multivariate analysis.ConclusionsThe incidence of treatment interruptions in patients undergoing SBRT for their prostate cancer was low. Most treatment delays were short.

EP014 - Preliminary report of toxicity and quality of life of the first 100 patients treated with 1.5T MR-guided stereotactic body radiotherapy for prostate cancer

EP014 - Preliminary report of toxicity and quality of life of the first 100 patients treated with 1.5T MR-guided stereotactic body radiotherapy for prostate cancer

Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis.

To provide an overview of the achievements and future research with stereotactic body radiotherapy (SBRT) in prostate cancer. SBRT publications for prostate cancer were retrieved from the Web of Science and Dimension database. Bibliometric analyses were performed using VOSviewer and Prism graph. Analysis of variance test was used to compare the publication, citation, and the mean citation between specialty journals. Network maps were produced to identify authors' and countries' collaboration clusters. Between 2006 and 2020, 574 publications fulfilling the inclusion criteria were identified, and a significant growth trend in publication (P<0.0001) and citation (P=0.001) number was recognized over the period. The United States was the most productive country with 253 (44.2%) articles. The RED Journal had the highest number of publications (14%) and citations (19%). Urology journals published (P=0.01) and cited significantly less than radiation oncology journals (P=0.01). All open access and non-open access number of publications increased over time, with a significant difference between non-open access and open access journals (P<0.0001). Two author clusters were identified, in the United States with the collaboration of Canadian and British authors, and in Italy with the participation of European authors. The number of publications and citations on SBRT for prostate cancer has grown linearly in the last decades. The United States is the leading country in this research field, and the use of SBRT in oligometastatic disease, reirradiation, and salvage seems to be hot topics in this research field.

Potential for focal magnetic resonance-guided stereotactic body radiotherapy for prostate cancer: A review

Prostate cancer is the most commonly diagnosed cancer among Australian men. Current whole gland radiotherapy treatment regimens are associated with known toxicities. The MR-Linac has the capability to deliver real-time visually guided radiation to enable focal therapy and reduce toxicity through decreasing radiation doses to organs at risk. This review article discusses the rationale, potential benefits and limitations of the MR-Linac in focal prostate stereotactic body radiotherapy (SBRT), in an effort to reduce toxicity-related side effects for men with low to favourable-intermediate risk prostate cancer. Pubmed was systemically for all published and ongoing trials using the search terms ‘Prostate’ and ‘MRI Linac or MR Linac’. 8 articles were reviewed, of those 1 was deemed relevant, additions were made and expert opinions in the field were sought regarding the most relevant research. Real-time MRI imaging during the delivery of each fraction with daily plan adaption is now a reality due to the development of the MR-Linac system. It is hoped that with improved real-time imaging, treatment accuracy can be improved, increasing the percentage of the planning target volume receiving the prescribed dose while reducing radiation to the surrounding organs at risk. Early results of prostate SBRT are promising but further research is needed into long term survival benefits and toxicity related outcomes. Focal stereotactic radiotherapy for low-risk intermediate prostate cancer using the MR-Linac has the potential to provide adequate tumour control while decreasing the toxicity and quality of life impact of whole gland treatment for men with localised prostate cancer.

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial

BackgroundStereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.MethodsThree hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator’s discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.DiscussionThe MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.Trial registrationClinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020.https://clinicaltrials.gov/ct2/show/NCT04384770Protocol versionVersion 2.1, Aug 28, 2020.