Rectal Toxicity Research Articles

Long-Term Anorectal Function in Rectal Cancer Patients Managed by a Watch-and-Wait Strategy after Neoadjuvant Therapy: A Cross-Sectional Study

Rectal cancer patients reaching complete clinical response (cCR) after neoadjuvant chemoradiotherapy can be offered a nonoperative watch-and-wait (W&W) strategy. As evidence of good oncological outcomes accumulates, the functional outcomes remain less explored. The aim of this study is to comprehensively assess the long-term rectal toxicity and anorectal function in patients managed by a W&W strategy and to investigate the clinical risk factors for anorectal dysfunction. Seventy W&W patients who were disease-free at the moment of recruitment were included. A minimum 2-year follow-up was considered. We graded late rectal toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and the Late Effects of Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system. Long-term anorectal function was assessed with the Wexner score, the Low Anterior Resection Syndrome score (LARS score), and the Memorial Sloan Kettering Bowel Function Instrument (MSK BFI). All patients received standard chemoradiotherapy consisting of a total dose of 5000 cGy in 25 fractions. The median tumor distance from the anal verge was 3 (IQR 2-4) cm. After a median follow-up of 43 (IQR 28-66) months, less than half of patients developed Grade 1 (40.0%) or Grade 2 (1.4%) late rectal toxicity, and no patients complained of higher grades. LENT/SOMA criteria also identified more patients with mild symptoms. The most frequent symptoms were sphincter control problems, mainly manifested as fecal urgency, reported by 60.0% of patients. For long-term anorectal function, the median LARS score was 16 (IQR 4-25). 17.1% of patients reported minor LARS and 15.7% reported major LARS. The median Wexner score was 2 (IQR 0-3). The median MSK BFI total score was 82 (IQR 77-86). Smoking history was an independent risk factor for anorectal dysfunction in multivariate analyses (OR = 6.491, 95% CI 1.536-27.432). Rectal cancer patients managed by a watch-and-wait strategy after neoadjuvant chemoradiotherapy have retained satisfactory anorectal function. However, fecal urgency might be a common problem. Smoking history was an independent risk factor for long-term anorectal dysfunction. Prospective studies with emphasis on bowel function outcomes containing a larger number of patients are needed.

Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Dismutase Mimetics and Pharmacological Ascorbate

Selective superoxide dismutase mimetics (DMs), including GC4419 and GC4711, are radiation (RT) modulators which induce opposite effects in tumors and normal tissues and may be ideally suited for locally advanced rectal cancer. However, their tumor radiosensitization effect is limited at RT doses relevant to rectal cancer (2-5 Gy). Over this dose range, they protect normal mucosal tissues, but we and others have shown they do not reliably enhance tumor radiosensitization at doses < 8-15 Gy. We hypothesize that combining DMs and other therapies which also target redox metabolism may effectively sensitize tumors to clinically relevant RT doses for rectal cancer while maintaining their normal tissue sparing effects. Like DMs, pharmacological ascorbate (P-AscH) selectively increases lethal hydrogen peroxide (H2O2) fluxes in tumors, but it does so through distinct mechanisms which are potentially complimentary with DMs (particularly at low RT doses). Human HCT116, SW480, and HT29 colorectal tumor models and non-malignant FHs74 intestinal epithelial cells were used. Clonogenic survival was assessed following single-fraction RT (2-5 Gy) +/- P-AscH (5 pmol/cell) +/- GC4711 (20 µM). Dependency on H202 fluxes was tested by adding bovine catalase with drug and RT treatments. Oxygen consumption in culture media was measured using a Clark electrode. Rectal toxicity was assessed in vivo using IHC in fixed rectal tissues following fractionated, image-guided rectal RT (5-9 Gy x 3). Tumor growth delay was assessed following RT (5 Gy x 3) +/- P-AscH (4 g/kg) +/- GC4419 (10 mg/kg) in animals with unilateral HCT116 flank tumors. Combination therapy with P-AscH and GC4711 potently radiosensitized all tumor lines in vitro whereas neither agent significantly decreased clonogenic survival as a monotherapy. Neither drug nor combination treatment sensitized FHs74 epithelial cells. P-AscH increased oxygen consumption and H2O2 production in culture media and the addition of GC4711 significantly increased both more than P-AscH alone. Co-treatment with exogenous catalase inhibited cancer cell killing with combination therapy +/- RT. In vivo, combination therapy significantly enhanced tumor growth delay and survival. Both agents significantly decreased markers of acute rectal RT injury as monotherapies. Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H202 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors.

Effect of Daikenchuto Therapy on Risk of Rectal Bleeding after IMRT for Prostate Cancer

Rectal bleeding due to radiation proctitis after treatment in radiation therapy for prostate cancer is a typical late toxicity symptom. The rate of rectal bleeding has been reduced by using IMRT, IGRT and peri-rectal hydrogel spacer. On the other hand, few reports have attempted to reduce the rate of rectal bleeding by medication. It has been reported that Daikenchuto (DKT), a traditional Japanese herbal medicine, has the effects of accelerating gastrointestinal motility and anti-fibrosis. We retrospectively investigated the rate of rectal bleeding in patients between concurrently administered and not administered DKT for bowel control during IMRT for prostate cancer. The subjects were 102 patients who underwent definitive IMRT for prostate cancer between 2014 and 2021 in our hospital. The DKT therapy concurrent use group were included 46 patients (45%), who were administered DKT per 10.0 g / day or 15.0 g / day. The irradiation was carried out, confirming the rectal volume every time by the image-guided radiotherapy using cone beam CT in all cases. The curative doses fractionation of IMRT were 78 Gy in 2 Gy per fraction (40%) or 70 Gy in 2.5 Gy per fraction (60%). We compared the rate of rectal bleeding after IMRT with and without DKT. Late rectal bleeding toxicity was scored using the Common Terminology Criteria for Adverse Events ver. 5.0 criteria. The associated factors of rectal bleeding were examined using the Cox proportional hazard model for multivariate analysis. In the DKT therapy group, the median follow-up period was 31 months (Range: 17-84 months), and the rectal bleeding rate was Grade 1 in 2 patients (4%) and Grade ≥ 2 in none. The median observation period in the non-DKT therapy group was 48 months (Range: 17-101 months), and the rectal bleeding rate was Grade 1 in 12 patients (21%), Grade 2 in 6 patients (10%), and there were no events of Grade ≥ 3. In univariate analysis, DKT therapy, dose fractionation and planned rectal doses (V50, V55, V60, V65, V70 and V75 converted to EQD23) were significant factors for rectal bleeding. Multivariate analysis showed that the DKT therapy was a significant independent factor in reducing the rate of rectal bleeding (HR: 0.105, 95% CI: 0.01-0.50, P = 0.003). It was statistically suggested in this study that the DKT therapy further reduced the rate of rectal bleeding in IMRT for prostate cancer.

Dose Escalation Using Magnetic Resonance Guided High-Dose-Rate Endorectal Brachytherapy to Enhance Clinical Response after Neoadjuvant Radiotherapy in Rectal Adenocarcinoma

To assess the proportion of patients with rectal adenocarcinoma achieving clinical complete response after neoadjuvant chemoradiation (NACTRT) and MR guided endorectal brachytherapy boost (MR-ERBT) MATERIALS/METHODS: Patients with rectal cancers (T2-T4/N0-N+) treated with concurrent chemoradiotherapy (50Gy/25# with Capecitabine) between June-2017 to April-2022. Post RT, patients having residual non-circumferential lesions <8cm in length were administered escalated-dose MR-ERBT with Ir192 HDR source. A median dose of 12Gy (8-15Gy) in 3 (2-3) fractions at 3-5 day intervals was delivered using MR-ERBT after external radiation. Data on near complete/complete clinical response (nCR/cCR) rates, local regrowth rates and clinical outcome were collected for analysis. Of the 145 patients who received MR-ERBT, majority were staged as T3(78.7%) and N1-2 (77.5%) rectal cancers. Median tumor length was 4cm and 123 (85%) of the tumors were located in the lower rectum (0-5cm from anal verge). Seventy-six (52%) patients achieved cCR or nCR (37 cCR, 39 nCR) and were advised observation or watch and wait (WW) management. The 69 patients having partial response were advised surgery. The patients having nCR 16 (29%) underwent resection, of these 10 (62%) had pathological complete response (pCR). The patients with partial or poor response, 57 underwent resection and of these 11 (19%) had pCR, 12 patients refused surgery due to fear of permanent stoma and continued to be on follow up. Of the 79 patients undergoing resection, 36 (45.5%) had sphincter preserving surgeries. At the median follow up of 30 months, local regrowth was seen in 8 (10.5%) of patients on WW and 6 were surgically salvaged while other 2 had synchronous metastatic relapse. Thus, 56 (41%) achieved organ preservation and continued to be on WW management. Twelve (8,2%) patients developed distant metastasis in the entire cohort, 3 in the WW group and 9 in the resected group. There were no pelvic recurrences seen in the resected patients. The disease-free survival at 3 years were (96.1% vs 89% Observation vs. resected (p_0.05) respectively. The overall survival at 3 years were (93% vs 98% Observation vs. resected (p_0.44) respectively. Late rectal toxicity was observed in 16(11%) patients on observation CONCLUSION: Dose Escalated MR-EBRT is an effective and safe method to enhance complete clinical response, thus improving the rate of organ preservation for distal rectal cancers.

A Hybrid Intelligence (HI) System for Segmenting Rectoprostatic Spacer Gel and Key OARs on CT Images for Prostate Cancer Radiation Therapy Planning

Our hybrid intelligence (HI) system, combining natural and artificial intelligence, is effective for auto-contouring H&N and thorax organs at risk (OARs) for radiation therapy (RT) planning with FDA 510(k) clearance. The purpose of this study is to test the HI system to segment a commercially available retroprostatic hyaluronic acid spacer gel (RSG) and pelvic OARs in planning CT images for prostate cancer RT. HI can achieve clinically acceptable auto segmentation for tissue-equivalent RSG in this domain. RSG is injected in the peri-rectal space in men with prostate cancer prior to RT to minimize rectal toxicity. 190 patients with prostate cancer were included in this post-hoc image analysis from a multi-center, prospective, randomized trial, with 136 in the spacer arm. The HI system has 3 steps: rough recognition from fuzzy model (FM) based automatic anatomy recognition (AAR-R), deep learning-based recognition (DL-R) refinement, and deep learning-based delineation (DL-D) to contour objects guided by the recognition results. FM encodes high level 3D anatomy knowledge of object shape and its relationship with other OARs; DL-R and DL-D focus on pixel-level details. The 190 studies are divided into disjoint training (100) and testing (90) subsets. 100 samples are used in DL-R and DL-D training, with 45 to build the FM for AAR-R. RSG and 4 other OARs (pelvic skin, prostate, bladder, rectum) are contoured. Location error (LE) is used to evaluate recognition; Dice coefficient (DC) and Hausdorff distance (HD) are employed to evaluate delineation. Acceptability scores (AS) (range 1-5, 1 for poor quality, 5 for best quality) from an observer study are recorded for HI-output and ground truth masks of RSG for assessing segmentation quality. The HI system achieves highest DC (0.94±0.07) and lowest HD (1.96±1.61 mm) for bladder, for rectum and prostate similar DC (0.82±0.08) and HD (2.62±1.65mm), for RSG, the most challenging object, a good DC close to 0.7 (0.67±0.10) and excellent HD (2.66±1.44mm). AS for auto-segmentations (3.86±0.85) were significantly better than those for ground truth segmentations (3.45±1.00) (p = 0.02, paired t-test). Table 1 summarizes results. The HI system achieves clinically acceptable segmentations for pelvic OARs and significantly better acceptability of segmentation of RSG compared to clinically performed ground truth segmentations. This has implications in improving efficiency and accuracy of CT-based RT planning in patients with prostate cancer.

Does Stereotactic Online Adaptive MRgRT to the Prostate Preclude the Need for Rectal Spacer

Historical prospective trials have shown that hydrogel rectal spacers can be very effective at decreasing rectal wall dose, and in turn rectal toxicity, in patients undergoing curative intent fractionated courses of radiotherapy for prostate cancer. However, in the modern era of stereotactic online adaptive MR guided radiation (MRgRT), it's not yet determined if rectal spacers improve the potential daily need for plan adaptation. A prospective database of MRgRT patients were queried for intact prostate cancer patients who received stereotactic online adaptive MR guided radiation. Patients were reviewed for the presence of a hydrogel rectal spacer present on the planning images. The number of adaptive fractions as well as the organs at risk out of tolerance were noted for each patient. Comparisons between number of fractions adapted as well as the number of fractions adapted for rectal constraints, were noted. For each case within this patient group that required plan adaptation, pre-specified dose constraints were finally met prior to treatment delivery. A total of 27 patients were treated with stereotactic online adaptive MRgRT from 2020 to 2022. 8 patients had a hydrogel rectal spacer placed prior to treatment. Out of the 95 fractions delivered to non-hydrogel patients, 78 were adapted, with 52 for urethra, 31 for bladder, 5 for bladder neck, and 35 for rectum. Of the 40 fractions delivered to patients with a hydrogel spacer, 20 were adapted. The corresponding reasons for adaptation in this group were 14 times for the urethra, 19 times for the bladder, 8 times for the bladder neck, and 8 times for the rectum. It was common for multiple at-risk organs to require adaptation for a single fraction within both cohorts. Although the percentage of patients requiring adaptation for rectal constraints was greater in the non-hydrogel patients (36.8% vs. 20%), this was not found to be statistically significant; p value greater than 0.1. The presence of a rectal spacer did not significantly reduce the need for online plan adaptation of the rectum for stereotactic online adaptive MRgRT. Furthermore, patients with a rectal spacer continued to often require adaptation to meet other prescription constraints. Further work is necessary to better select patients who would benefit from hydrogel spacers in the setting of online adaptive MRgRT. Additionally, longer follow-up of this patient population coupled with a larger patient cohort overall remains needed to increase the power of this analysis and to further explore the clinical outcomes of this patient group.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers

PurposeTo evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. Methods and MaterialsSeventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. ResultsMedian age at recurrence was 55 years (Range: 35–73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30–50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. ConclusionThe use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Comprehensive geriatric assessment predicts radiation-induced acute toxicity in prostate cancer patients.

The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by acomprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. Atotal of 314 prostate cancer patients (age ≥ 65years) undergoing definitive radiotherapy at atertiary academic center were included. Prior to treatment, patients underwent aGA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37patients (11.8%) and rectal toxicity in 8patients (2.5%), respectively. Multivariable analysis revealed asignificant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260-5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017-4.625; p = 0.045 and OR 7.220, 95%CI 1.227-42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004-0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028-0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045-20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Radiomics based predictive modeling of rectal toxicity in prostate cancer patients undergoing radiotherapy: CT and MRI comparison.

Rectal toxicity is one of the common side effects after radiotherapy in prostate cancer patients. Radiomics is a non-invasive and low-cost method for developing models of predicting radiation toxicity that does not have the limitations of previous methods. These models have been developed using individual patients' information and have reliable and acceptable performance. This study was conducted by evaluating the radiomic features of computed tomography (CT) and magnetic resonance (MR) images and using machine learning (ML) methods to predict radiation-induced rectal toxicity. Seventy men with pathologically confirmed prostate cancer, eligible for three-dimensional radiation therapy (3DCRT) participated in this prospective trial. Rectal wall CT and MR images were used to extract first-order, shape-based, and textural features. The least absolute shrinkage and selection operator (LASSO) was used for feature selection. Classifiers such as Random Forest (RF), Decision Tree (DT), Logistic Regression (LR), and K-Nearest Neighbors (KNN) were used to create models based on radiomic, dosimetric, and clinical data alone or in combination. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), accuracy, sensitivity, and specificity were used to assess each model's performance. The best outcomes were achieved by the radiomic features of MR images in conjunction with clinical and dosimetric data, with a mean of AUC: 0.79, accuracy: 77.75%, specificity: 82.15%, and sensitivity: 67%. This research showed that as radiomic signatures for predicting radiation-induced rectal toxicity, MR images outperform CT images.

Gastrointestinal Toxicity Prediction Not Influenced by Rectal Contour or Dose-Volume Histogram Definition

Rectal dose delivered during prostate radiation therapy is associated with gastrointestinal toxicity. Treatment plans are commonly optimized using rectal dose-volume constraints, often whole-rectum relative-volumes (%). We investigated whether improved rectal contouring, use of absolute-volumes (cc), or rectal truncation might improve toxicity prediction. Patients from the CHHiP trial (receiving 74 Gy/37 fractions [Fr] vs 60 Gy/20 Fr vs 57 Gy/19 Fr) were included if radiation therapy plans were available (2350/3216 patients), plus toxicity data for relevant analyses (2170/3216 patients). Whole solid rectum relative-volumes (%) dose-volume-histogram (DVH), as submitted by treating center (original contour), was assumed standard-of-care. Three investigational rectal DVHs were generated: (1) reviewed contour per CHHiP protocol; (2) original contour absolute volumes (cc); and (3) truncated original contour (2 versions; ±0 and ±2 cm from planning target volume [PTV]). Dose levels of interest (V30, 40, 50, 60, 70, 74 Gy) in 74 Gy arm were converted by equivalent-dose-in-2 Gy-Fr (EQD2α/β= 3 Gy) for 60 Gy/57 Gy arms. Bootstrapped logistic models predicting late toxicities (frequency G1+/G2+, bleeding G1+/G2+, proctitis G1+/G2+, sphincter control G1+, stricture/ulcer G1+) were compared by area-undercurve (AUC) between standard of care and the 3 investigational rectal definitions. The alternative dose/volume parameters were compared with the original relative-volume (%) DVH of the whole rectal contour, itself fitted as a weak predictor of toxicity (AUC range, 0.57-0.65 across the 8 toxicity measures). There were no significant differences in toxicity prediction for: (1) original versus reviewed rectal contours (AUCs, 0.57-0.66; P=.21-.98); (2) relative- versus absolute-volumes (AUCs, 0.56-0.63; P=.07-.91); and (3) whole-rectum versus truncation at PTV ± 2 cm (AUCs, 0.57-0.65; P=.05-.99) or PTV ± 0 cm (AUCs, 0.57-0.66; P=.27-.98). We used whole-rectum relative-volume DVH, submitted by the treating center, as the standard-of-care dosimetric predictor for rectal toxicity. There were no statistically significant differences in prediction performance when using central rectal contour review, with the use of absolute-volume dosimetry, or with rectal truncation relative to PTV. Whole-rectum relative-volumes were not improved upon for toxicity prediction and should remain standard-of-care.

Same-day versus delayed simulation imaging after placement of a perirectal hydrogel spacer for prostate radiotherapy.

Placement of a perirectal hydrogel spacer has been demonstrated to reduce the risk of rectal toxicity from prostate radiation. Practices vary regarding the timing of CT simulation after hydrogel placement, and the ideal schedule remains unknown. Thirty patients with localized prostate adenocarcinoma underwent transrectal ultrasound-guided placement of an iodinated SpaceOAR™ hydrogel prior to radiotherapy. Per evolving practice, 15 completed same-day simulation and 15 returned for simulation 1-2 weeks later. Hydrogel volume, perirectal distance, air-void volume, and rectal dosimetry per NRG GU005 were compared between CT simulation, 1st fraction Cone-Beam-CT (CBCT), and final CBCT. CT simulation occurred 8.8 ± 2.4 days after placement in the delayed group, with no significant difference in the interval between simulation and 1st fraction between groups (p = 0.165). Greater observed de-creases in hydrogel volume (0.57 cc vs. 0.04 cc, p = 0.0002), and perirectal distance at both mid-gland (1.32mm vs. 0.17mm) and tallest point (2.40mm vs. 0.04mm) were seen on 1st-fraction CBCT in the same-day group (p = 0.0039; p = 0.0002). Per dosimetry recalculated on 1st fraction CBCT, five (D3 cc and D50%) versus one (D50%) rectal dose parameters were exceeded in the same-day and delayed groups, respectively, and 10 versus one parameters had a relative increase of ≥ 20%. Due to the evolving anatomic changes in the days following hydrogel placement, same-day simulation scanning may introduce unintended variability in rectal dosimetry at the time of prostate radiotherapy.

Seminal Vesicle Treatment for Localized Prostate Cancer Treated with External Beam Radiotherapy.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010-2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with <15% risk. However, radiation oncologists still contour a high percentage of SVs in men with <15% risk of SV involvement, suggesting that there may be over-treatment of SVs that increases the risk of rectal or bladder toxicity.

A dosimetric analysis of rectal hydrogel spacer use in patients with recurrent prostate cancer undergoing salvage high-dose-rate brachytherapy

We hypothesize rectal hydrogel spacer (RHS) improves rectal dosimetry in patients undergoing salvage high-dose-rate brachytherapy (HDR-BT) for intact, recurrent prostate cancer (PC). A prospectively collected institutional database was queried for recurrent PC patients treated with salvage HDR-BT from September 2015 to November 2021. Patients were offered RHS beginning June 2019. Dosimetric variables were compared between RHS and no-RHS groups for the average of two fractions using Wilcoxon rank-sum tests. Primary outcomes were rectal volume receiving 75% of prescription dose (V75%) and prostate volume receiving 100% of prescription dose (V100%). Generalized estimating equation (GEE) model was used to evaluate the association between other planning variables and rectal V75%. Forty-one PC patients received salvage HDR-BT, of whom 20 had RHS. All patients received 2400cGy in 2 fractions. Median RHS volume was 6.2cm3 (Standard deviation [SD]: ± 3.5cm3). Median follow-up was 4 months and 17 months in the RHS and no-RHS groups, respectively. Median rectal V75% with and without RHS were 0.0cm3 (IQR: 0.0-0.0cm3) and 0.06cm3 (IQR: 0.0-0.14cm3), respectively (p<0.001). Median prostate V100% with and without RHS were 98.55% (IQR: 97.86-99.22%) and 97.78% (IQR: 97.50-98.18%), respectively (p = 0.007). RHS, rectum, and prostate volumes did not significantly affect rectal V75% per GEE modeling. There was 10% G1-2 and 5% G3 rectal toxicity in RHS group. There was 9.5% G1-2 and no G3+ rectal toxicities in the no-RHS group. Absolute improvement in rectal V75% and prostate V100% was significant with RHS in PC patients undergoing salvage HDR-BT, but clinical benefit is marginal.

Safety of Carbon-ion Radiotherapy for Prostate Cancer After Rectal Cancer Surgery.

The safety of carbon-ion radiotherapy (CIRT) for patients with prostate cancer after rectal cancer surgery remains unknown. This is a retrospective analysis of the safety of CIRT in patients with prostate cancer after rectal cancer surgery. The subjects were 13 consecutive patients with prostate cancer who underwent CIRT after rectal cancer surgery at the Kanagawa Cancer Center from December 2015 to April 2022. A total dose of 51.6 Gy (relative biological effectiveness) was administered in 12 fractions over 3 weeks. The criteria stated in the Common Terminology Criteria for Adverse Events, version 5.0, were used to assess toxicity. Fisher's exact test was performed to assess the associations between patient clinical factors and rectal toxicity. The median patient age was 71 years (range=66-83 years). The median observation period was 27.4 months (range=10.6-82.4 months). The median duration from rectal surgery to CIRT was 6.9 years (1.0-16.8 years). Five (38.5%) and six (46.2%) patients had a planning target volume (PTV)-adjacent rectal anastomosis and diabetes mellitus, respectively, and two (15.4%) patients had both. Grades 1 and 2 late gastrointestinal toxicities were observed in one case each. Development of gastrointestinal toxicity was significantly associated with both a PTV adjacent rectal anastomosis and diabetes mellitus (p=0.013). Late gastrointestinal toxicity was tolerable in patients with prostate cancer treated with CIRT after rectal cancer surgery. Patients with both a PTV adjacent rectal anastomosis and diabetes mellitus were more likely to experience late gastrointestinal toxicity.

OC-0454 Changes in prostate planning over a decade: radiobiological impact in rectum toxicity

OC-0454 Changes in prostate planning over a decade: radiobiological impact in rectum toxicity

Comparative Analysis of Dosimetry and Treatment Outcomes of Two Different Dose Fractionation Schedules of HDR Brachytherapy in Carcinoma Cervix Amid Covid-19 Pandemic

Background: Cervical carcinoma is the fourth most common cancer and leading cause of cancer related deaths in women worldwide. Brachytherapy is an important part in the treatment of cervical cancer. Delivering HDR Intracavitary Brachytherapy in the Covid-19 era is challenging. Objective: To compare the dosimetry and treatment outcomes between two fractionation schedules of 9Gy in 2 fractions v/s 7Gy in 3 fractions of high dose rate Brachytherapy in patients with locally advanced carcinoma cervix. Methods: A randomized observational study was carried out on 80 histopathologically proven squamous cell carcinoma patients of cervix. All patients were treated with EBRT 50Gy in 25 fractions over a period of 5 weeks (2Gy/#) with concurrent weekly cisplatin 30mg/m2. After assessing fitness for brachytherapy, patients in the study arm received HDR intracavitary brachytherapy in 9Gy for 2 fractions v/s 7Gy for 3 fractions in the control arm. Results: The median time of follow-up was 14 months for the study (range 7 – 20 months). Local control rate was 89.75% for study arm and 92.30% for control arm. One year disease free survival in the study arm was 76.92% as compared to 74.35% in the control arm. Median disease-free survival was better in the study arm (14 months v/s 12 months) with a trend of significant benefit. Rectal and bladder toxicities were comparable in both the arms. Median dose to ICRU bladder and rectal point, and EQD2 dose in both arms were not found to be statistically significant. Conclusion: Both the regimes were found to be safe. Disease response and toxicities were also similar in both the arms. There was a better patient compliance with 9Gy for 2 fractions schedule in view of lesser number of fractions resulting in less hospital visit in the Covid-19 pandemic.

Stereotactic focal radiotherapy as an alternative treatment for low-risk prostate cancer: Results of a single-arm monocenter Phase-II trial.

Since radical treatments in low risk prostate cancer do not improve overall survival in comparison to active surveillance, preserving quality of life (QOL) remains the key objective. Active surveillance of indolent prostate cancer avoids curative treatment side-effects but necessitates repeated biopsies. Focal stereotactic body radiation therapy (focal SBRT) may be an alternative. This non-randomized Phase-II trial examined the feasibility and safety of focal SBRT for low and favorable intermediate-risk prostate cancer. Patients were recruited in 2016-2019 if they had: localized CAPRA ≤ 3 prostate adenocarcinoma; an isolated PIRADS≥4 macroscopic tumor on MRI; WHO Performance Status 0-1; and no major urinary symptoms. 36.25 Gy (80% isodose prescription) were delivered in 5 fractions every other day. Primary outcome was delay between focal SBRT and salvage-treatment initiation. Secondary outcomes were: acute/late genitourinary/rectal toxicity; biological, clinical and MRI local control; and change in QOL measures. Over a median follow-up of 36 months, salvage prostatectomy in the 24 eligible patients was never required. Three-year biochemical progression-free survival was 96%. The single biochemical recurrence was a small (2-mm) Gleason 6 (3 + 3) lesion in the non-irradiated lobe. All 19 patients with ≥1 post-treatment MRI evaluations demonstrated complete radiological response. Acute/late grade ≥3 toxicities did not occur: all acute toxicities were grade-1 genitourinary (38% patients), grade-2 genitourinary (8%), or grade-1 rectal (13%) toxicities. There was one (4%) late grade-1 genitourinary toxicity. QOL was unchanged at last follow-up, as shown by IPSS (2.86 to 3.29, p>0.05), U-QOL (0.71 to 0.67, p>0.05), and IIEF5 (the 14 initially potent patients maintained potency (IIEF5 > 16)). Focal SBRT is feasible, well-tolerated, and preserves QOL. This innovative robotized approach challenges active surveillance.

V10-07 AUTOLOGOUS FAT TRANSFER AS A PROSTATE-RECTAL SPACER FOR PROSTATE BRACHYTHERAPY

You have accessJournal of UrologyCME1 Apr 2023V10-07 AUTOLOGOUS FAT TRANSFER AS A PROSTATE-RECTAL SPACER FOR PROSTATE BRACHYTHERAPY Ezequiel Becher, Juan Fernandez Long, Marcelo Bou, Edgardo F Becher, Luis Montes de Oca, and Marcelo Borghi Ezequiel BecherEzequiel Becher More articles by this author , Juan Fernandez LongJuan Fernandez Long More articles by this author , Marcelo BouMarcelo Bou More articles by this author , Edgardo F BecherEdgardo F Becher More articles by this author , Luis Montes de OcaLuis Montes de Oca More articles by this author , and Marcelo BorghiMarcelo Borghi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003328.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Implanted rectal spacers (IRS) have been developed to increase the distance between the prostate and the rectum, thus optimizing dose escalation in prostate brachytherapy (BT). Cost is a disadvantage and there is a lack of availability worldwide. We have developed an autologous fat transfer (AFT) technique to use as an IRS immediately after the implant of the seeds in low-dose-rate BT. We aim to present the feasibility and durability this technique. METHODS: A total of 120 patients underwent AFT (21 were treated with primary BT, 79 with a combined primary treatment of external beam radiotherapy and BT, 20 with salvage BT). The isodose used for primary BT was 14400 cGy, 11,000 cGy after 4600 cGy of external beam radiotherapy in the combined group, and 14400 cGy for the salvage group. Patients underwent a CT scan at 3, 6 and 12 months to measure the distance between the rectum and the prostate. RESULTS: An average of 18 cc (10-40) of fat was transferred successfully in 100% of cases.The mean distance to the rectum at the level of the base, middle, and apex at 1 and 6 months were 11.2, 9.7, and 7.6 mm; 8.3, 8.1, and 5.9 mm, respectively. No rectal toxicity or major complications were reported. CONCLUSIONS: The use of fat as an IRS seems to be a valid alternative to reduce rectal toxicity after BT, achieving equivalent distances to synthetic IRS. It is feasible, safe, and the loss of distance at 6 months is small. Cost is lower than other alternatives. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e928 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ezequiel Becher More articles by this author Juan Fernandez Long More articles by this author Marcelo Bou More articles by this author Edgardo F Becher More articles by this author Luis Montes de Oca More articles by this author Marcelo Borghi More articles by this author Expand All Advertisement PDF downloadLoading ...

PD15-09 REAL WORLD ASSESSMENT OF MRI PREDICTORS OF RECTAL COMPLICATIONS FOLLOWING TRANSPERINEAL SPACEOAR HYDROGEL INSERTION

PD15-09 REAL WORLD ASSESSMENT OF MRI PREDICTORS OF RECTAL COMPLICATIONS FOLLOWING TRANSPERINEAL SPACEOAR HYDROGEL INSERTION