Acute GU Toxicity Research Articles

Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial

Purpose: Dose escalated radiotherapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiotherapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease whilst limiting toxicity. This study evaluated the toxicity and quality of life (QOL) with CyberKnife-based SBRT and simultaneous integrated boost in localised prostate cancer. Methods and Materials: Eligible participants included newly diagnosed, biopsy-proven unfavourable intermediate to high risk localised prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI defined T3a N0, PSA ≥ 20) with up to two MRI-identified DILs. Participants received 36.25Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 + genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D QOL outcomes were assessed. Results: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 + genitourinary and gastrointestinal toxicity was 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. IPSS score and urinary QOL scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D QOL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. Conclusions: CyberKnife SBRT delivered dose of 36.25Gy to the prostate with a simultaneous integrated boost up to 47.5Gy is well tolerated. Acute and late GU and GI toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer

PurposeHigh-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. MethodsPatients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. ResultsWe recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. ConclusionSIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Conditional Risk and Predictive Factors Associated with Late Toxicity for Prostate Cancer Patients Treated with External Beam Radiotherapy Alone on Randomized Trial RTOG 0126

Patients with localized prostate cancer (PCA) treated with RT alone have excellent outcomes, making quality of life and minimization of toxicities of great concern. The risk of developing toxicity may evolve with time from treatment which is of interest to patients seen in follow up. The primary objective of this study is to determine the conditional risk of grade 2+ GI or GU toxicity for patients treated with RT. A secondary objective is to determine risk factors associated with the development of late toxicities. We performed a post-hoc analysis of RTOG 0126, which enrolled patients with intermediate risk PCa who were randomized to receive standard dose RT of 70.2 Gy in 39 fractions vs dose escalated dose RT (DE-RT) of 79.2 Gy in 44 fractions. Cumulative incidence was used to calculate risk of grade 2+ GU and grade 2+ GI toxicity at initial time points, as well as for patients who survived 2 years and 5 years without respective grade 2+ toxicity. Risk factors of age, race, urinary incontinence, baseline urinary frequency, acute GU toxicity, treatment arm, RT method (3DCRT vs IMRT), and OAR contouring protocol violation were analyzed using univariate and multivariate Cox proportional hazards modeling for late GU toxicity. Risk factors of age, race, RT method, acute GI toxicity, DE-RT, RT method, and OAR contouring protocol violation were analyzed for late GI toxicity. One thousand four hundred ninety-nine patients with a median follow up of 8.4 years (range 0.02-13 years) were included for analysis. The conditional cumulative 5-year risk of late grade 2+ GI toxicity at enrollment, 2-, and 5-years of grade 2+GI toxicity free survivorship was 14.7%, 6.2%, and 1.8% respectively. The cumulative 5-year risk of late grade 2+ GU toxicity at enrollment, 2-, and 5-years of late grade 2+ GU toxicity free survivorship was 7.9%, 4.7%, and 2.7% respectively. Initially DE-RT (HR 1.401, 95% CI 1.099-1.787; p = 0.0066), acute GI toxicity (HR 1.962, 95% CI 1.271-2.616; P<0.0001), and black race (HR 0.630, 95% CI 0.4-0.993; p<0.0463) were predictive of late GI toxicity. After two years of 2+ GI toxicity free survivorship, only acute GI toxicity (HR 2.015, 95% CI 1.238-3.279, p<0.0048) remained predictive of late GI toxicity on MVA. DE-RT (HR 1.616, 95% CI 1.187-2.2, p<0.0023), IMRT (HR 0.559, 95% CI 0.389-0.804, p = 0.0017), and urinary frequency at baseline (HR 1.377, 95% CI 1-1.895 p<0.0498) were predictive of late GU toxicity at enrollment. This data suggests that as patients proceed further from completion of EBRT, the conditional risk of late toxicity decreases. The majority of grade 2+ GI and GU toxicities occur in the first two years of treatment and patients who have not had a grade 2+ GU or GI toxicity within the first five years are likely to remain toxicity free. Factors such as presence of baseline urinary dysfunction, presence of acute toxicities, DE-RT, and radiation modality predict for late toxicity. These findings are of relevance for clinicians and patients in the post treatment setting.

Focal Boosted IMRT Treatment of Prostate Cancer to 84 Gy in 28 Fractions: Preliminary Clinical Outcomes and Dosimetry

The FLAME trial reported that focal boosting of prostate tumor to 95 Gy in 35 fractions improves biochemical control. However, this treatment is not commonly used in the United States. We investigated a focally boosted treatment of 84 Gy in 28 fractions (EQD2 108 Gy, BED 252 Gy). Between 2019-2022, men with unfavorable intermediate risk (uIR) and high risk (HR) prostate cancer were enrolled on a prospective registry and received a novel IMRT regimen. The dose levels were 84 Gy to the gross tumor volume (GTV) as defined on mpMRI (T2W and ADC) with no added margin, 70 Gy to the prostate and proximal seminal vesicles, and optional 50.4 Gy to elective pelvic lymph nodes (all 28 fractions). Patients received fiducial markers and hydrogel spacer. The treatment planning goal was to cover 95% of the GTV at 84 Gy, and also meet the target and normal tissue dosimetry criteria of the hypofractionated treatment arm of NRG-GU005. VMAT was used for treatment delivery. ADT was given at the discretion of the treating physician. A total of 20 men were included in the study, 2 (10%) uIR and 18 (90%) HR. 9 (45%) tumors were GS 7, 7 (35%) were GS 8, and 4 (20%) were GS 9. There were 13 (65%) stage cT1, 4 (20%) cT2 and 3 (15%) cT3. One (5%) patient received short term ADT, 18 (95%) long term ADT, and 1 (5%) refused ADT. 18 (90%) men received elective nodal radiation. The mean baseline PSA was 25.1 (range 4.2-73.4). The median baseline IPSS score was 11.1 (IQR 4.5-12), and 4 patients had severe baseline urinary symptoms (IPSS ≥20). The mean baseline prostate volume was 57.4 cc (range 26.8-198.3). The mean volume of the 84 Gy boost target was 7.1 cc (range 2.3-15.0) and the mean proportion of the prostate boosted was 14.8% (range 2% - 47%). There were 10 (50%) men with 1 boost target, 6 (30%) with two, 3 (15%) with three, and 1 (5%) had 4 boost targets. Targets were located in peripheral zone (85%), transition zone (30%), and central zone (5%). Patients met all per-protocol normal tissue criteria of NRG-GU005, except for bladder D0.03cc. The mean±SD (Gy) rectum D15%, D25%, and D30% were 51±5, 45±5, 42±4. The mean±SD (Gy) bladder D0.03cc, D30%, D50% were 79±4, 50±8, 38±10. At a median follow up time of 21.3 months (range 7.1-38.2), no patients have developed biochemical progression, local recurrence, distant progression, or death from prostate cancer. One patient died at 18 months from metastatic colorectal cancer, unrelated to prostate cancer treatment. Acute grade 1-2 GU toxicity occurred in 13 (65%) patients, and acute grade 1-2 GI toxicity occurred in 4 (20%) patients. No patients developed grade 3+ acute or late GU or GI toxicity. Two patients required temporary foley catheter for obstruction during RT, and both had IPSS >20 at baseline. The patient who refused ADT had a PSA bounce of magnitude 2.2 ng/mL at 14 months, PSA values declined without additional treatment. A novel 28-fraction focal boosted IMRT treatment is feasible and has an acceptable early toxicity profile. Oncologic results are promising but require longer follow up.

Comparison of chronic gastrointestinal and genitourinary toxicities between brachytherapy and external beam radiotherapy for patients with prostate cancer: A systematic review and meta-analysis.

125I BT is an effective radiotherapy for prostate cancer. However, comparison data of GI and GU toxicities between BT, BT + EBRT, and EBRT-alone patient groups is limited. To define the GI and GU toxicities in prostate cancer to prevent adverse events after treatment. We searched published studies in PubMed, Cochrane, and Embase databases up to December 31, 2022. The endpoints were the RRs of GI and GU toxicities. Pooled data were assessed using a random-effects model. Fifteen eligible studies were included into this analysis. LDR-BT had significantly lower RRs than LDR-BT + EBRT for acute GI (2.13; 95% CI, 1.22-3.69; P= 0.007) and late GI toxicities (3.96; 95% CI, 1.23-12.70; P= 0.02). Moreover, EBRT had significantly higher RRs than LDR-BT for acute GU (2.32; 95% CI, 1.29-4.15; P= 0.005) and late GU toxicities (2.38; 95% CI, 1.27-4.44; P= 0.007). HDR-BT had significantly higher RRs for acute GU toxicities than LDR-BT alone (0.30; 95% CI, 0.23-0.40; P< 0.00001). The results implied that BT with and without EBRT can result in both GI and GU toxicities in patients with prostate cancer, with LDR-BT leading to a poorer urinary function than EBRT.

Outcome of the first 200 patients with prostate cancer treated with MRI-Linac at Assuta MC.

We present our experience with MR-guided stereotactic body radiotherapy (SBRT) for 200 consecutive patients with prostate cancer with minimum 3-month follow-up. Treatment planning included fusion of the 0.35-Tesla planning MRI with multiparametric MRI and PET-PSMA for Group Grade (GG) 2 or higher and contour review with an expert MRI radiologist. No fiducials or rectal spacers were used. Prescription dose was 36.25 Gy in 5 fractions over 2 weeks to the entire prostate with 3-mm margins. Daily plan was adapted if tumor and organs at risk (OAR) doses differed significantly from the original plan. The prostate was monitored during treatment that was automatically interrupted if the target moved out of the PTV range. Mean age was 72 years. Clinical stage was T1c, 85.5%; T2, 13%; and T3, 1.5%. In addition, 20% were GG1, 50% were GG2, 14.5% were GG3, 13% were GG4, and one patient was GG5. PSA ranged from 1 to 77 (median, 6.2). Median prostate volume was 57cc, and 888/1000 (88%) fractions required plan adaptation. The most common acute GU toxicity was Grade I, 31%;dysuria and acutegastrointestinal toxicity were rare. Three patients required temporary catheterization. Prostate size of over 100cc was associated with acute fatigue, urinary hesitance, and catheter insertion. Prostate Specific Antigen (PSA) decreased in 99% of patients, and one patient had regional recurrence. MR-guided prostate SBRT shows low acute toxicity and excellent short-term outcomes. Real-time MRI ensures accurate positioning and SBRT delivery.

5-Year result of single-institute cohort study in single-fraction HDR monotherapy for localised prostate cancer.

362 Background: The aim if this single institute UK-based study was to look at 3-year and 5-year bRFS and toxicity profiles. Methods: It is a prospective data study with a total number of 174 patients who were treated with single-fraction HDR monotherapy between July 2014 and February 2017. Biochemical recurrence is defined using Phoenix criteria. Results: The median age was 67.5 years with the median presenting PSA of 8. Majority of patients were lower risk group with 55% for combined low and favourable intermediate risks. 81 patients had Gleason score 6(3+3) and 77 patients had GS 7(3+4). Total hormone duration was 8 months and median duration of hormone prior to HDR monotherapy was 4 months. Overall bRFS at 3 years was 96% and 5 years was 88%. 5-year bRFS as per risk stratification was 100% in low risk, 92% in favourable intermediate risk, 83% in unfavourable intermediate risk and 79% in high-risk groups. This study had better 5-year overall bRFS compared to published data in single fraction HDR monotherapy (88% vs 73.5%, p value 0.001) (Morton et al., 2020). Despite inferior 5-year overall bRFS in compared to 2-fractionated HDR monotherapy (88% vs 95%) (p value 0.001), no difference in 5-year bRFS noted in low and favourable intermediate risk groups (100% vs 100% and 92% vs 93% respectively) (Morton et al., 2020). Two-thirds (71%) of biochemically recurred patients found to have local recurrence disease. The median time of biochemical recurrence was 47 months. Higher risk groups had higher 5-year biochemical recurrence risk. Acute and late toxicity profiles were minimum with acute G2 GU toxicity (2%) and GI toxicity (1%); late G2 GU toxicity (2%) and GI toxicity (0%) with no G3, G4 GU or GI toxicities. Conclusions: This prospective study had shown better overall 5-year bRFS especially in low and favourable intermediate risk groups with minimal toxicities. Therefore, single-fraction HDR monotherapy could be considered for elderly or patients with significant co-morbidities who are more suitable for single treatment rather than 2 fractions in these risk groups. Further randomised multicentre studies in these risk groups are suggested.

Effects of gold fiducial marker implantation on tumor control and toxicity in external beam radiotherapy of prostate cancer.

Evidence regarding the effects of fiducials in image-guided radiotherapy (IGRT) for tumor control and acute and late toxicity is sparse. Patients with primary low- and intermediate-risk prostate cancer, 40 with and 21 without gold fiducial markers (GFM), and treated between 2010 and 2015 were retrospectively included. The decision for or against GFM implantation took anaesthetic evaluation and patient choice into account. IGRT was performed using electronic portal imaging devices. The prescribed dose was 78 Gy, with 2 Gy per fraction. Biochemical no evidence of disease (bNED) failure was defined using the Phoenix criteria. Acute and late gastrointestinal (GI) and genitourinary toxicity (GU) were assessed using the Radiation Therapy Oncology Group criteria. Most patients did not receive GFM due to contraindications for anaesthesia or personal choice (60% and 25%). Regarding tumor control, no significant differences were found regarding bNED and overall and disease-specific survival (p = 0.61, p = 0.56, and p > 0.9999, respectively). No significant differences in acute and late GI (p = 0.16 and 0.64) and GU toxicity (p = 0.58 and 0.80) were observed. We were unable to detect significant benefits in bNED or in early or late GI and GU side effects after GFM implantation.

PO35 Presentation Time: 10:30 AM: Initial Outcomes for Utilization of the Venezia Hybrid High-Dose Rate Brachytherapy Applicator in Definitive Treatment of Locally-Advanced Cervical and Endometrial Cancer

<h3>Purpose</h3> The Venezia gynecological applicator (Elekta) is a hybrid interstitial/intracavitary brachytherapy applicator used to treat cervical cancers. Previous data supporting the use of hybrid brachytherapy comes mainly from the EMBRACE cohort showing increased coverage of the high-risk CTV (HR-CTV) with decreased toxicity. Single-institution data, further supports this technique. We undertook this study to report our initial experience with the Venezia applicator for treatment of locally advanced cervical and endometrial cancers. <h3>Materials/Methods</h3> We retrospectively reviewed 21 patients who received brachytherapy using the Venezia applicator for definitive treatment of cervical or endometrial cancer, treated from June, 2021 to March, 2022. All patients completed chemoradiotherapy followed by brachytherapy boost. For each brachytherapy fraction, patients received sedation and the Venezia applicator was placed. Radiation treatment planning was performed on CT imaging fused to daily MRI, using the Oncentra® treatment planning system. If needles were required for hybrid interstitial brachytherapy, the plan was optimized first without utilizing the needles, to meet constraint to organs at risk (OARs). Subsequently, planning was performed considering the interstitial needles with a focus on optimizing the balance of target coverage and dose to organs at risk. Radiation dose to target volumes and organs at risk were recorded as equivalent dose in 2Gy fractions (EQD2). <h3>Results</h3> Median age was 54 years. Ninety percent of patients were treated for a primary cervical cancer and 10% for primary endometrial cancer. Twenty-nine percent of patients had T1 primary tumor, 48% had a primary T2 tumor and 24% had a primary T3 tumor. The most common histology was squamous cell carcinoma (SCC) in 76% of patients, with adenocarcinoma in 10% and the remaining being undifferentiated or endometrioid. Median follow up was 4.3 months. Thirty-three percent of patients experienced acute toxicity with brachytherapy, all of which were grade 1-2. Twenty-nine percent experienced acute GI toxicity, 10% experienced acute GU toxicity and 10% experienced bleeding. Median brachytherapy dose and fractionation was 28Gy delivered over 4 fractions. Sixty-two percent of patients required hybrid interstitial brachytherapy and the median number of interstitial needles placed was 4. Median volume of the Gross Tumor Volume (GTV) and HR-CTV at first fraction were respectively 5.22cm³(IQR 4.26cm³-10.28cm³) and 27.84cm³(IQR 24.71cm³-40.36cm³⁾. Median HR-CTV D90 and D98 were respectively 85.3Gy(IQR 83.1Gy-88.8Gy) and 76.8Gy (IQR 74.2Gy-79.6Gy). Median GTV D98 was 98.4Gy (IQR 94.3Gy-116.3Gy). Regarding OARs, median D2cc dose to the rectum, sigmoid and bladder were respectively 56.9Gy (IQR 53.7Gy-59.1Gy), 60Gy (IQR 55.9Gy-63.7Gy) and 75.3Gy (IQR 72.3Gy-77.6Gy). Median D1cc dose to the bowel was 50Gy (IQR 46.6Gy-56.8Gy). Median D0.1cc dose to the left and right ureter were respectively 71.8Gy (IQR 62.6Gy-85Gy) and 67.5Gy (IQR 61.6Gy-89.1Gy). <h3>Conclusions</h3> Brachytherapy using the Venezia hybrid applicator was implemented with good dosimetry and sparing of organs at risk. Procedure related complications were mild.

MR Guided SBRT for Early Prostate Cancer: Initial Experience with 270 Consecutive Patients

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is a recommended treatment for localized prostate cancer. We present our experience with the first consecutive 270 patients (8.2019-11.2022) treated with MR-guided SBRT with minimum 3 months follow-up and acute side effects. <h3>Materials/Methods</h3> This IRB approved series includes histologically confirmed prostate cancer patients, consecutively treated with MR-guided SBRT. Staging included diagnostic MRI (86%) and PET-PSMA (78.5%) for patients with grade >1 disease. No fiducials or rectal spacers were used. Treatment planning included fusion with pre-treatment imaging and contour review with an expert MRI radiologist. Prescription dose was 36.25Gy in 5fx delivered over 2 weeks to the entire prostate with 3mm margins. High-risk area identified on MRI (PIRADS4-5) or PET received 40Gy. On each fraction, MRI was performed and plan adapted if tumor and OAR doses differed significantly from the simulation-based plan. During radiation, the prostate was monitored and treatment automatically interrupted if the target volume moved out of the PTV range. <h3>Results</h3> Mean age was 71.2(35-90) years. Clinical stage was I-85.5%, II-13%, III-1.5%. MRI showed suspected ECE- 12.5%, NVB involvement-9.5%, SV involvement-1.5%. Group grade was 1-20.5%, 2-52.0%, 3-13.5%,4-13.5%, 5-0.5%. 77 (38%) patients had involvement of ≥50% cores. Pre-treatment PSA ranged from 1-to 77, PSA was>10 in 53 patients (26.5%). Median prostate volume-57cc (16-171). Sixteen (36%) received adjuvant hormone therapy. 739/1000 (73.9%) daily treatments required plan adaptation. Significant prostate movement during treatment noted in 7 patients. Acute GU toxicity was Grade I-21%, II-14% (4 patients required temporary catheter). Acute GI toxicity was grade I-7.5%, II-1.5%. All grade II and 95% of grade I toxicities resolved by 3 months follow-up. No grade III toxicity reported. Three-month post-treatment PSA decreased in 99% of patients, range 0.14-23 (median 2.87). 99.5% are disease free with median follow up of 14 months. Four patients required a temporary catheter during treatment, one following a previous event unrelated to radiation and the other three following radiation. Two of them after three fractions and one after two fractions of radiation. The catheter was removed after 5-7 days except in one patient who was weaned after 3 weeks. Age was significantly associated with acute nocturia, (p=0.005). Number of adapted fractions, catheter insertion was not associated with age, PSA at dx, prostate volume and BMI. Prostate size was not associated with either ISUP or Gleason. <h3>Conclusion</h3> MR guided prostate SBRT shows very low risk of transient's acute toxicity, little long-term toxicity and excellent response (median 14 months). Real-time MR imaging and plan adaptation when required is important for ensuring accurate positioning and SBRT delivery, and prevents geographical miss and inadvertent dose delivery to OAR.

HDR Focal Boost with Whole Gland SBRT in Localized Prostate Cancer: Assessment of Acute Toxicity and Early Quality of Life

<h3>Purpose/Objective(s)</h3> The dominant intraprostatic lesion (or GTV) is recognized as a possible site of radioresistance, potentially increasing the risk of relapse following prostate radiotherapy. We evaluated an approach of HDR focal boost to the GTV followed by dose-adjusted whole gland SBRT, and report the acute toxicity and early quality of life (QoL). <h3>Materials/Methods</h3> Patients with intermediate- to high-risk localized prostate cancer with GTV(s) identified on MR were enrolled into this non-randomized phase II trial. All patients received MR-guided HDR focal boost to the GTV(s), 15 Gy in single fraction, and whole gland prostate SBRT (33 Gy in 5 fractions to CTV; 30 Gy in 5 fractions to PTV). SBRT was delivered on conventional Linac (CL) or MRLinac (MRL). Rectal spacer was placed at the discretion of the treating physician. Toxicity and QoL assessments included CTCAE v4.0 and EPIC questionnaire at baseline, 1, 3 and 6 months, and 1, 2, 3, and 5 years. <h3>Results</h3> Ninety-five patients enrolled between 2016 and 2021 with ≥6-month follow-up were included in this analysis. Majority (83%) had intermediate-risk; 17% had high-risk disease. Median age was 70 years (range; 56 – 79). Seventy-five patients were treated on CL and 20 on MRL. Rectal spacer was placed in 68 patients. Acute G1 and G2 GU toxicity were 53% and 25%, respectively; G1 and G2 GI toxicity was 24% and 4%, where 74% had a rectal spacer. Mean percentage change in EPIC urinary score at 1 month was -9.3; -11.8 on CL and 0.5 on MRL. At 6 months this improved to -0.6. Mean EPIC bowel score reduced by -4.4 at 1 month; -5.3 on CL and -0.5 on MRL. Six-month bowel score was 0.7. Presence of rectal spacer did not appear to influence the bowel score. <h3>Conclusion</h3> An approach of HDR focal boost with whole gland prostate SBRT was well tolerated with minimal acute toxicity, and recovery by 6 months. Further follow up will determine the study primary endpoint of local control, and late toxicity and QoL outcomes, using this treatment approach.

The Use of HA as Rectal Spacer in Prostate Cancer Patients Undergoing Hypofractionated RT: An Australian Experience

<h3>Purpose/Objective(s)</h3> To report the feasibility, post-operative complications and recto-prostatic separation achieved with hyaluronic acid (HA) inserted into the perirectal fat before definitive prostate radiotherapy (RT). <h3>Materials/Methods</h3> Fifty-seven patients with clinical stage T1-3 prostate cancer underwent transrectal ultrasound guided transperineal insertion of fiducial markers and HA into the perirectal space before volumetric arc RT between 7/2020 to 7/2021. Post insertion computerized tomography (CT) and magnetic resonance imaging (MRI) scans were obtained for treatment planning. HA feasibility, safety and recto-prostatic separation were assessed. The prescribed dose to the planning target volume (PTV) ranged from 60-62Gy in 20 fractions. <h3>Results</h3> The mean age was 74.7 years. The median PSA was 8.1 [Interquartile range (IQR)6.2-10.0]. The majority of patients had ISUP 2 adenocarcinoma (60%). The rest had ISUP 1 (11%) and ISUP 3 (30%). The disease risk was staged as early in 11%, favorable intermediate in 30%, unfavorable intermediate in 58% and high in 2%. Androgen deprivation therapy was delivered in 63%. HA insertion was completed with a 100% success rate. This was rated as ‘easy' to ‘very easy' 100% of the time. There were no device related complications, rectal perforation, serious bleeding, infections or allergic reactions. The mean prostate size was 43cc (IQR 30-55cc). Recto-prostatic separation at the base (measured 5mm below the prostate base), mid gland and apex (measured 5mm above the prostate apex) were 12mm (0.2), 11mm (0.2) and 0.9mm (0.1) respectively. The HA was also symmetrically placed in breadth at the mid gland in all patients. The mean rectal volume receiving 53Gy (rV53) was 3.2% (IQR 1.3-5.5) for patients receiving 60-62Gy. The median follow up was 13.5 months (IQR 9.5-17.5). The risk of any acute GU toxicity was 81%. The majority had grade 1 GU toxicity at 67% with urinary frequency, urgency and obstruction being the commonest reported side effects. The risk of any grade 2 GU toxicity was 14% with urinary obstruction (13%) and urgency (7%). The risk of any acute GI toxicity was 2%. Only 1 patient developed grade 1 GI toxicity with diarrhea. The risk of any late GU toxicity was 43%. The majority had grade 1 GU toxicity at 32% with urinary frequency, urgency and obstruction. The risk of any grade 2 GU toxicity was 11% with urinary obstruction (5%), urgency (5%) and incontinence (2%). The risk of any late GI toxicity was 2%. Only 1 patient had grade 1 GI toxicity with diarrhea. <h3>Conclusion</h3> HA was successfully inserted in all patients and was well tolerated. Recto-prostatic separation was symmetrical in length from the base to the apex and in breadth at the midgland. The risk of developing any acute GI toxicity was minimal at 2% with the use of HA. In addition, the risk of late GI toxicity was 2%, albeit with short follow up.

Hypofractionated Radiotherapy in Intermediate-Risk Prostate Cancer Patients: Long-Term Results.

Background: To evaluate outcomes in terms of survival and toxicity in a series of intermediate-risk prostate cancer (PCa) patients treated with hypofractionated radiotherapy (HyRT) + hormonal therapy (HT) with or without image guidance (IGRT) and to investigate the impact of different variables. Methods: This is a multi-centric study. From January 2005 to December 2019, we treated 313 intermediate-risk PCa patients (T2b–T2c, Gleason score 7, or pre-treatment PSA 10 to 20 ng/mL) with HyRT. Patients received 54.75 Gy in 15 fractions in 5 weeks plus 9 months of neo-adjuvant, concomitant, and adjuvant HT with or without IGRT. Results: Median follow-up was 91.6 months (range 5.1–167.8 months). Median OS was not reached, and the 8- and 10-year OS was 81.9% and 72.4%, respectively. Median CSS was not reached, and the 8- and 10-year CSS was 97.9% and 94.5%, respectively. PSA at first follow-up <0.8 ng/mL was significantly related to better oncological outcomes (CSS, bRFS, LRFS, cPFS, and MFS) in both univariate and multivariate analysis. After Propensity Score matching, grade 2–3 acute and cumulative late GU (p = 0.153 and p = 0.581, respectively) and GI (p = 0.196 and p = 0.925, respectively) toxicity were not statistically different in patients treated with or without IGRT. Conclusions: HyRT is effective and safe regardless of the use of IGRT. PSA at first follow-up is an easily accessible prognostic factor that may help the clinicians to identify patients who require a treatment intensification.

Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: A secondary analysis of the NRG oncology RTOG 0415 randomized clinical trial.

243 Background: While intensity-modulated radiotherapy (IMRT) is commonly used to deliver moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC), IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in the context of MHRT. This secondary analysis of the phase III RTOG 0415 trial compares survival outcomes and toxicity across RT technique between IMRT and 3D-CRT for low-risk PC. Methods: The phase III, non-inferiority trial RTOG 0415 randomized patients with low risk PC to either MHRT (70Gy at 2.5Gy/fraction) or conventionally fractionated radiation (CFRT; 73.8Gy at 1.8Gy/fraction) with stratification by RT technique. A secondary analysis for differences in overall (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. For patient and tumor characteristics, continuous data were compared with Wilcoxon rank sum test and categorical data with Chi-squared test, as appropriate. Rates of BRFS and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 1079 patients received the allocated intervention with a median follow up of 5.8 years. RT technique was balanced between treatment arms, with 79.1% of patients receiving IMRT. RT protocol compliance was &gt; 95% for both IMRT and 3D-CRT. There were no significant differences in BRFS between patients treated with 3D-CRT versus IMRT for all patients (p = 0.33), those randomized to CFRT (p = 0.78), or those randomized to MHRT (p = 0.24). Overall survival did not differ by RT technique as well. For all patients, there was no difference in acute and late GI and GU toxicity rates across RT technique. For patients treated with MHRT, late grade 2 GU toxicity was more common with IMRT than 3D-CRT (31.3% vs 23.4%; p = 0.004). On logistic regression analysis, only poor baseline urinary function, defined as an EPIC score of 90 or below, correlated with acute (p &lt; 0.001) or late (p &lt; 0.001) GU toxicity. Baseline bowel function did not correlate to GI toxicity. Conclusions: RT technique did not impact survival outcomes or toxicity rates following MHRT for low risk PC. Higher rates of late CTCAE grade 2+ GU and GI toxicity observed within the RTOG 0415 MHRT arm were not disproportionally observed following 3D-CRT than IMRT. These data highlight the need for careful consideration of target delineation and normal tissue constraints in the selection and delivery of appropriate RT technique.

Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study.

BackgroundIntensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.Material and MethodsWe used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.ResultsThe mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.ConclusionUse of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

One Fraction Size Does Not Fit All: Patient Preferences for Hypofractionated Radiation Therapy From a Discrete Choice Experiment

PurposeHypofractionated external beam radiation therapy (EBRT) is a standard of care option for localized prostate cancer. To inform clinical practice we quantified patients’ preferences for convenience, efficacy, and toxicity risks, of conventional, moderate hypofractionation, and stereotactic radiation therapy regimens. Methods and MaterialsWe used a discrete choice experiment with a voluntary sample consisting of patients treated with EBRT for localized prostate cancer at our academic cancer center. In 2019, 58 participants, mean (SD) age of 72.9 (7.1) years, agreed to complete an in-person 1:1 discrete choice experiment. Each participant made 12 choices between 2 unique EBRT scenarios, each described by 5 attributes: (1) treatment time; (2) fiducial markers; and risk of (3) prostate specific antigen recurrence; (4) acute and (5) late GI or GU toxicity. Patient preferences were estimated using mixed multinomial logistic regression, and prespecified subgroups with conditional logistic regression. ResultsAll attributes were statistically significant, thus influenced participants’ choices. Risks of prostate specific antigen recurrence (β = −2.581), late (β = −1.854), and acute (β = −1.005) toxicity were most important to participants (P < .001 for each), followed by EBRT length (β = −0.728; P = .017) and fiducial marker implantation (β = −0.563; P = .004). Older (β = −0.063; 95% confidence interval, −0.12, −0.01) and rural (β = −0.083; 95% CI -0.14, −0.02) participants significantly preferred shorter EBRT and were less willing-to-extend treatment to reduce toxicity risk. ConclusionsPatients with prostate cancer place importance on EBRT attributes, and some are willing to trade-off increased risk of toxicity for improved convenience. Our findings promote shared clinical decision-making because patients are interested in learning about the trade-offs involved.

Metastasis-Directed Therapy for Oligoprogressive Castration-Resistant Prostate Cancer ― Preliminary Results of the Prospective, Single-Arm MEDCARE Trial

In metastatic castration-refractory prostate cancer (mCRPC), clinical progression usually implies the start of a new systemic treatment-line. When clinical progression is limited to a few new and/or progressive lesions, while all other lesions are still responsive to ongoing treatment, the term 'oligoprogression' is used. Retrospective data demonstrated that metastasis-directed therapy (MDT) to the oligoprogressive lesions substantially postponed the start of next-line systemic treatment (NEST). Based on these results, the prospective, single-arm MEDCARE trial was initiated.MEDCARE is a prospective, single-arm, monocentric pilot-study, investigating the use of MDT in oligoprogressive mCRPC. Oligoprogression was defined as ≤3 new and/or progressive metastatic lesions or local progression (counting as 1 new lesion) diagnosed on CT or bone scan. Additional MRI was allowed for confirmation. All patients also underwent an 18F PSMA PET-CT as investigational imaging, to assess its predictive value and impact on treatment policy. Ongoing systemic treatment at the time of oligoprogression was continued. MDT consisted of stereotactic body radiation therapy (SBRT) or metastasectomy. The primary endpoint of the trial was NEST-free survival, calculated from the last day of MDT until the start of NEST. Clinical progression-free survival (cPFS) and toxicity scoring with CTCAE v4 scoring were secondary endpoints.Between January 2020 and January 2021, 20 patients were included in the trial. Median age at time of inclusion was 74 years (IQR 67-78). Median PSA and PSA doubling time were 4 ng/ml (IQR 2-11) and 4 months (IQR 3-5), respectively. Eleven patients had 1 progressive lesion on conventional imaging, 7 patients had 2 progressive lesions and 2 patients had 3 progressive lesions. The most frequent location of progressive lesions was the bone (16/20). One patient was treated for a progressive liver metastasis, and one patient presented with progression in the prostatic fossa. Two more patients had a combination of progression in pelvic and retroperitoneal lymph nodes (N1/M1a disease). All patients with progressive metastatic lesions were treated with SBRT (30 Gy in 3 fractions (BED 130 Gy for a/b = 3). The patient with local progression was treated with conventional radiotherapy (77 Gy in 35 fractions (BED 133 Gy for a/b = 3)). At a median follow-up of 6 months (IQR 2-9), 8 patients experienced clinical progression, and five patients were started on NEST. Median NEST-FS was 12 months. Three patients died, 2 deaths were prostate cancer related and 1 patient died of small cell lung cancer. MDT was well tolerated, with 3 patients experiencing grade 1 toxicity, and two patients grade 2 toxicity (acute GU toxicity). There were no patients with grade 3 or higher toxicity.The first results of the MEDCARE trial (NCT04222634) investigating MDT in oligoprogressive CRPC are promising, with negligible toxicity.

A Phase I Trial of Highly Conformal, Hypofractionated Post Prostatectomy Radiotherapy

Increasingly hypofractionated dose schedules for post prostatectomy radiotherapy to the prostate bed were investigated on a phase I trial. The final toxicity results for patients treated on Arm 2 (no visible recurrence on pelvic MRI) are reported here. The primary objective of this trial was to determine the maximal tolerated hypofractionated dose (MTHD) regimen.Patients were treated on 1 of 3 dose levels (DL): 56.4 Gy in 20 fractions (DL1), 51.2 Gy in 15 fractions (DL2), and 44.2 Gy in 10 fractions (DL3). Patients underwent treatment to the prostate bed (RTOG Consensus); pelvic nodal irradiation was not allowed. Concurrent androgen deprivation therapy (ADT) was used at the discretion of the treating physician. Dose escalation followed a standard 3+3 design with an expansion for 6 additional patients at the maximal tolerated dose (MTHD). Dose limiting toxicity (DLT) was defined as grade 3 (G3) toxicity lasting > 4 days that occurred during or up to 21 days following RT. Toxicity was scored during RT and for 2 years following completion using the CTCAE v4.0. Toxicity was considered acute within 90 days of RT and late after 90 days.Between 01/2018 and 08/2019, 15 patients with a median age of 70 (47-76) underwent RT. Nine patients (60%) underwent concurrent ADT. Patients were classified as NCCN favorable-intermediate (n = 3), unfavorable-intermediate (n = 2), high-risk (n = 9), and very-high risk (n = 1). Three patients were treated at DL1, 3 at DL2, and 9 at DL3. Median follow up was 24 months (9.7-24.0). One patient was removed from study at 9.7 months for PSA progression. There were no DLTs, and no patients required a treatment break. Nine patients (60%) experienced a maximum acute G2 GI toxicity. Within these 9 patients there were 11 total acute G2 GI events consisting of diarrhea in 1 patient (duration: 37 days), proctitis in 5 patients (median duration: 25 days), and worsening hemorrhoids in 5 patients (median duration: 17 days, all occurred in patients with baseline G1 hemorrhoids). One patient developed acute G3 GI toxicity (proctitis) on DL3 which resolved to G2 with medical management in < 4 days. No acute G2 or G3 GU toxicities were observed, however acute G1 dysuria was common (n = 6). Late G2 GI and GU toxicity each occurred in 3 patients respectively. Late G3 GU toxicity occurred in 2 patients (self-limited hemorrhagic cystitis in a patient on DL2, worsening of baseline incontinence in a patient on DL3). There were no ≥ G4 acute or late toxicities.The MTHD for hypofractionated post-operative radiotherapy to the prostate bed was 44.2 Gy in 10 daily fractions. Consistent with recent reports on hypofractionation in the intact prostate setting, acute ≥G2 GI toxicity was observed frequently. Late toxicity rates were similar to rates reported in these prior studies.