Rectal Hydrogel Research Articles

PO-0212 Use of rectal spacing hydrogel significantly reduces rectal dose in prostate LDR brachytherapy

PO-0212 Use of rectal spacing hydrogel significantly reduces rectal dose in prostate LDR brachytherapy

Dosimetric feasibility of neurovascular bundle-sparing stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer to preserve erectile function

Objective:We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy.Methods:Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%.Results:Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p < 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p < 0.01) and 25% with spacer (p < 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints.Conclusions:NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation.Advances in knowledge:This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.

The impact of a rectal hydrogel spacer on dosimetric and toxicity outcomes among patients undergoing combination therapy with external beam radiotherapy and low-dose-rate brachytherapy

PurposeRectal hydrogel spacers have been shown to decrease rectal radiation dose and toxicity. In this study, we compared prostate and rectal dosimetry and acute toxicity outcomes in patients who had and had not received a rectal hydrogel spacer prior to combination therapy with external beam radiotherapy and low-dose-rate brachytherapy. Materials and MethodsAll patients with intermediate-risk and high-risk prostate cancer who received combination therapy at our institution were identified between 2014 and 2019. Dosimetric outcomes of brachytherapy implants and quality of life (QOL) outcomes were compared between patients who had and had not received a hydrogel spacer. ResultsA Total of 168 patients meeting our inclusion criteria were identified. Twenty-two patients had received a rectal hydrogel spacer, among whom the mean separation between the rectum and prostate was 7.5 mm, and the V100rectum was reduced by 47% (0.09 cc vs. 0.17 cc, p = 0.04). There was no difference in the percentage of patients achieving a D90 of ≥100 Gy between those who had and had not received a spacer. The mean rate of change in I-PSS and SHIM scores did not differ between the two groups at 2 months after PID. ConclusionLDR brachytherapy appears feasible after the placement of a rectal hydrogel spacer. While there was a significantly reduced V100rectum among patients who had received a hydrogel spacer, there was no statistically significant difference in patients achieving a D90prostate of ≥100 Gy. Although there was no difference appreciated in QOL scores, the length of follow-up was limited in the rectal-spacer group.

Rectal spacer hydrogel in 1.5T MR-guided and daily adapted SBRT for prostate cancer: dosimetric analysis and preliminary patient-reported outcomes.

The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients. The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. 120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy >95% and planning target volume 37.5 Gy <2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy <1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group. These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs. This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.

Impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5\u2009T MR-guided stereotactic body radiotherapy

BackgroundThe assessment of organ motion is a crucial feature for prostate stereotactic body radiotherapy (SBRT). Rectal spacer may represent a helpful device in order to outdistance rectal wall from clinical target, but its impact on organ motion is still a matter of debate. MRI-Linac is a new frontier in radiation oncology as it allows a superior visualization of the real-time anatomy of the patient and the current highest level of adaptive radiotherapy.MethodsWe present data regarding a total of 100 fractions in 20 patients who underwent MRI-guided prostate SBRT for low-to-intermediate risk prostate cancer with or without spacer. Translational and rotational shifts were computed on the pre- and post-treatment MRI acquisitions referring to the delivery position for antero-posterior, latero-lateral and cranio-caudal direction, and assessed using the Mann-Whitney U-Test.ResultsAll patients were treated with a five sessions schedule (35 Gy/5fx) using MRI-Linac for a median fraction treatment time of 50 min (range, 46–65). In the entire study sample, median rotational displacement was 0.1° in cranio-caudal, − 0.002° in latero-lateral and 0.01° in antero-posterior direction; median translational shift was 0.11 mm in cranio-caudal, − 0.24 mm in latero-lateral and − 0.22 mm in antero-posterior. A significant difference between spacer and no-spacer patients in terms of rotational shifts in the antero-posterior direction (p = 0.033) was observed; also for translational shifts a positive trend was detected in antero-posterior direction (p = 0.07), although with no statistical significance. We observed statistically significant differences in the pre-treatment planning phase in favor of the spacer cohort for several rectum dose constraints: rectum V32Gy < 5% (p = 0.001), V28 Gy < 10% (p = 0.001) and V18Gy < 35% (p = 0.039). Also for bladder V35 Gy < 1 cc, the use of spacer provided a dosimetric advantage compared to the no-spacer subpopulation (p = 0.04). Furthermore, PTV V33.2Gy > 95% was higher in the spacer cohort compared to the no-spacer one (p = 0.036).ConclusionIn our experience, the application of rectal hydrogel spacer for prostate SBRT resulted in a significant impact on rotational antero-posterior shifts contributing to limit prostate intra-fraction motion. Further studies with larger sample size and longer follow-up are required to confirm this ideally favorable effect and to assess any potential impact on clinical outcomes.

Safety and outcome of stereotactic body radiation therapy (SBRT) with rectal hydrogel spacer for prostate cancer.

76 Background: Ultra-hypofractionated radiotherapy delivered using stereotactic body radiotherapy (SBRT) is a cost-effective treatment for localized prostate cancer. Optimal dosing remains unclear, as commonly used 30-40Gy/5fx regimens appear to overestimate hypofractionation’s control benefits. Here, we report the largest experience of 45Gy/5Fx of SBRT for prostate cancer patients treated with hydrogel peri-rectal spacer (‘hydrogel’). Methods: An IRB-approved retrospective protocol was used to conduct a registry search identifying all patients with prostate cancer who received 45Gy/5Fx between 2015-2019 with hydrogel. Genitourinary (GU) and gastrointestinal (GI) toxicities were defined using the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. The ASTRO-Phoenix failure definition of Nadir+2 ng/mL was used for biochemical failure. Results: We analyzed 250 low (9.2%), intermediate (85.2%), and high-risk (5.6%) prostate cancer patients with a median follow-up of 9.9 months (range: 0-45.7 months). Acute GU and GI grade ≥ II toxicities were noted in 15.2% and 7.2% of patients, respectively. Late GU grade II and III toxicities occurred in 24.0% and 1.2% of patients, respectively, while late GI grade II and III toxicities occurred in 4.0% and 0.4% of patients, respectively. In patients (N=44) with follow-up &gt;2 years, late GU and GI grade III toxicities occurred in 4.55% and 2.27% of patients, respectively. A significant correlation was noted for acute GI and GU toxicity predicting the respective late GI and GU toxicity (p-value &lt; 0.001 for both). Physician-reported Grade ≥ II new onset erectile dysfunction was 17.2%. A gradual decline in prostate-specific antigen with a mean nadir of 0.04 (95% CI: [0.018, 0.067]) at 36 months was noted. The actuarial freedom from biochemical failure was 96.33% at 3 years. Overall survival was 94.09% at 3 years with no deaths attributed to prostate cancer. Conclusions: SBRT treatment of 45Gy/5Fx with hydrogel is well tolerated with GU/GI toxicities comparable to those reported for conventional fractionation. Although short, the 3-year biochemical control rate is encouraging. Longer follow-up and prospective evaluation are warranted.

Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study

Our purpose was to compare dosimetric parameters and late gastrointestinal outcomes between patients treated with proton beam therapy (PBT) for localized prostate cancer with rectal balloon immobilization versus a hydrogel rectal spacer. Patients with localized, clinical stage T1-4 prostate adenocarcinoma were treated at a single institution using conventionally fractionated, dose-escalated PBT from 2013 to 2018. Patient-reported gastrointestinal toxicity was prospectively collected, and the incidence of rectal bleeding was retrospectively reviewed from patient records. One hundred ninety-two patients were treated with rectal balloon immobilization, and 75 were treated with a rectal spacer. Rectal hydrogel spacer significantly improved rectal dosimetry while maintaining excellent target coverage. The 2-year actuarial rate of grade 2+ late rectal bleeding was 19% and 3% in the rectal balloon and hydrogel spacer groups, respectively (P = .003). In univariable analysis, the probability of grade 2+ rectal bleeding was significantly correlated with increasing rectal dose. In multivariable analysis, only receipt of spacer hydrogel (hazard ratio, 0.145; P = .010) and anticoagulation use (hazard ratio, 5.019; P < .001) were significantly associated with grade 2+ bleeding. At 2-year follow-up, patient-reported Expanded Prostate Cancer Index Composite bowel quality of life composite scores were less diminished in the hydrogel spacer group (absolute mean difference, 5.5; P = .030). Use of rectal hydrogel spacer for prostate PBT is associated with a significantly lower incidence of clinically relevant, late rectal bleeding and lower decrement in long-term, patient-reported bowel quality of life compared with rectal balloon immobilization. Our results suggest that hydrogel spacer may improve rectal sparing compared with rectal balloon immobilization during PBT for prostate cancer.

What is the quality of hydrogel spacer insertions? and which patients will benefit? A literature review

AbstractAim:To evaluate the quality of rectal hydrogel spacer (HS) insertions from literature in patients undergoing radical radiotherapy for prostate cancer. The secondary aim is to assess the benefit of HSs in patients with risk factors more likely to have rectal complications, such as non-conventional radiotherapy dose fractionations and high-risk disease.Method and materials:A literature search of peer-reviewed electronic articles was carried out using Boolean connectors and Medical Subject Headings in the databases. Databases searched included ScienceDirect, Medline and Cinahl. The articles were assessed using relevant critical appraisal skills programme tools.Results:From the 26 studies used, HS showed a clinically significant relative reduction in rectal planning dose volumes for both high- and low-risk prostate cancer patients in a range of radiotherapy treatment modalities including volumetric modulated arc therapy, intensity-modulated radiotherapy, intensity-modulated proton therapy, stereotactic ablative body radiotherapy and brachytherapy. Spacer placements were successfully inserted in 99% of patients. However, rectal wall infiltration occurrence was 6% and ≥2 cm unsymmetrical placements in 2%.Findings:A spacer scoring system based on the HS symmetry has provided evidence of the quality of the position inserted, which was visually aided by T2-wieghted MRIs. Despite optimal HS placements ranging from 62 to 72%, HS had a clinically significant reduction of ≥25% in planned rectal V70 dose in 97% of patients.

Addition of Iodinated Contrast to Rectal Hydrogel Spacer to Facilitate MRI-Independent Target Delineation and Treatment Planning for Prostate Cancer

Rectal hydrogel spacers are increasingly used to reduce dose and thereby limit toxicity to the rectum during prostate radiotherapy. Commercially available products require magnetic resonance imaging (MRI) for hydrogel visualization and treatment planning, with only anecdotal reports of treatment planning with computed tomography (CT) alone. MRI-incompatible hardware, patient intolerance, and added cost provide incentives for MRI-independent alternatives for treatment planning. This case series evaluates the addition of iodinated contrast to spacer gel and assesses its impact on CT visualization. Three prostate cancer patients underwent contrasted rectal spacer placement in preparation for external beam radiotherapy. Standard low-osmolar iodinated contrast was added to a commercially available rectal hydrogel. 0.5cc of contrast was added to 4.5cc of accelerator and subsequently combined with 5cc of diluent. The resultant 10cc of hydrogel was injected into each patient as per standard procedure, utilizing transrectal ultrasound guidance. Two patients were simulated with MRI; a third with a non-MRI compatible pacemaker was planned with CT alone. CT was performed on the day of hydrogel placement within 2 hours of procedure and again 7-12 days later to account for fiducial migration and dissipation of injected air. The second CT was used for treatment planning. Hydrogel visibility was compared between CT and MRI through standardized symmetry scoring, volume calculation, and measurements taken at prostate base, mid-gland, and apex. Spacer contrast was visible only on the day of hydrogel placement by CT, allowing target delineation for treatment planning. On comparison to MRI delineation of spacer one week later, minimal changes in relevant spacer measurements were observed. In one patient, a significant amount of injected air dissipated between the time of hydrogel placement and repeat CT. CT visualization of rectal hydrogel with iodinated contrast on day of placement is feasible and allows MRI-independent treatment planning with spacer gel, but requires repeat CT on a subsequent day to allow for resolution of prostatic edema, fiducial migration, and air within the hydrogel spacer.Abstract 3673; Table 1PatientSimulation Type (Day)Spacer Volume (cc)CC Dimension (mm)AP Dimension (mm)TV Dimension (mm)Base Thickness (mm)Mid-gland Thickness (mm)Apex Thickness (mm)Symmetry Score1CT* (0)16.661.416.430.815.714.715.91CT (8)15.951.417.629.519.017.716.91MR (8)15.555.817.32616.516.816.212CT* (0)12.636.613.839.215.813.811.82CT (12)14.138.812.641.512.811.502MR (12)14.748.615.343.213.212.511.213CT* (0)18.1†58.7†11†40.5†11.8†12.3†15.7†3†CT (7)11.352.41030.411.910.59.52*Spacer contrast visible, †Includes injected air Open table in a new tab

Long-term Follow-up after Radiotherapy for Prostate Cancer with and without Rectal Hydrogel Spacer: A Pooled Prospective Evaluation of Sexual Function of Men with Good Baseline Sexual Function

Hydrogel spacers are a tool to improve dosimetry and overall quality of life with limited follow-up in men receiving radiotherapy for prostate cancer. This study is a pooled analysis of prospective cohorts with long-term quality of life (QOL) follow-up with or without a rectal spacer to minimize dose to rectum as well as other adjacent organs at risk. QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) and mean changes from baseline to EPIC domains were evaluated. A total of 126 patients with good pre-treatment sexual function (baseline EPIC >/=60) including 88 patients from a randomized multi-institutional trial of radiation with or without hydrogel rectal spacer with a QOL end-point were pooled with 38 non-randomized patients from a single institution with prospective QOL collection in patients with or without hydrogel spacer. The proportions of men with a predetermined minimally important differences (MIDs) relative to pre-treatment baseline (11 point decline from baseline = MIDx1 and 22 point decline from baseline = MIDx2) in sexual function were evaluated. A total of 126 men were evaluated (64% with spacer and 36% without) with QOL data being available for 68 men beyond 24 months of follow-up (median: 33 months, range: 2.5-69.4 months). MID was more common in men without a rectal spacer at 15 months (60.5% vs 44.4%) and at >/= 24 months (80% vs 55%). MIDX2 occurred at 15 months of 45% in men without rectal spacer vs 29% in men with rectal spacer and >/= 24months in 68% of men without rectal spacer vs 39% with rectal spacer. At >/= 24 months of follow up, men without spacer were more likely to have 1xMID in sexual QOL (11 point decline, p= 0.041, Fisher Exact) as well as 2xMID (22 point decline, p=0.025, Fischer Exact) declines. The use of rectal separation was associated with adequate erectile quality. In men with rectal spacer at late follow up, 63% of patients had firm enough erections for intercourse and 1% had no erectile function compared to 28% adequate erectile function for intercourse and 12% without any erectile function in patients without rectal spacer. In this pooled analysis of QOL after prostate radiotherapy with up to 5-years of follow-up, utilization of a hydrogel rectal spacer was associated with less MID per patient reported sexual QOL. This was especially important in patient reported adequate erectile function for intercourse.

Addition of Iodinated Contrast to Rectal Hydrogel Spacer to Facilitate MRI-Independent Target Delineation and Treatment Planning for Prostate Cancer

PurposeHydrogel spacers reduce rectal dose toxicity during prostate cancer radiation therapy. Current products require magnetic resonance imaging (MRI) for visualization during treatment planning, but MRI incompatibility and cost have prompted alternatives using computed tomography (CT). This case series evaluates the addition of iodinated contrast to hydrogel as such an alternative. Methods and materialsThree patients underwent rectal hydrogel spacer placement with iodinated contrast modification. CT was performed within 1 hour of injection and again 1 week later. MRI was obtained at the time of the second CT. Hydrogel delineation was compared between CT and MRI and between paired CT scans. ResultsSpacer enhancement was visible on CT immediately after hydrogel placement (mean Hounsfield units, 122; range, 52-193) but not at the second CT 1 week later (mean Hounsfield units, 8; range, −8 to 29). Delineated spacer volume did not significantly differ between immediate postprocedure CT and MRI ≥1 week later in 2 patients (patient 1: 16.6 vs 15.5 cm3; patient 2: 12.6 vs 14.7 cm3; paired t-test, P = .81). ConclusionsCT visualization of rectal hydrogel admixed with contrast is feasible and allows delineation of interface with rectum/prostate.

Rectal admission of chemotherapeutic drugs in neoadjuvant treatment schemes of locally advanced rectal cancer.

e15168 Background: High incidence and steady rise of rectal cancer morbidity, unsatisfactory treatment results, amount of disabling surgery, high rate of local recurrents advocate for searching for new methods of combined treatment of locally advanced rectal cancer. Methods: We had suggested to rectally install sterile hydrogel material based on sodium alginate with incorporated 5-FU for radio modification purposes during neoadjuvant chemo radiotherapy. 39 patients with histologically confirmed diagnosis were included into our study. 19 patients received preoperative radiotherapy with summary dose of 50-56 Gy and systemic chemotherapy with fluorpirimidines and rectally admitted hydrogel material with incorporated 5-FU twice per day. Control group consisted of 20 patients who had similar treatment, excluding rectal hydrogel installations. Results: There was no increase in early radiotherapy complications noticed. Three study group patients had complete response, 16 had partial response (versus 1 CR, 15 PR, 3 stabilization and 1 progression in control group). This allowed reduction of surgical assistance volume in seven patients - sphincter-preserving operations were performed. Grade 3-4 pathomorphosis by Dworak’s scale was identified in 17 out of 19 patients (13 out of 20 in control group). Conclusions: Use of hydrogel material based on sodium alginate with incorporated 5-FU does not increase amount and intensity of radiation induced complications, allows to improve patients quality of life and treatment results.

Impact of Rectal Hydrogel Spacer as Determined by CT Scan Dosimetry in Pd -103 Brachytherapy Patients

To assess the impact of rectal hydrogel spacer on prostate and rectal dosimetry as determined by CT Scan imaging for low-dose-rate brachytherapy.

Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: A pooled prospective evaluation of quality of life.

39 Background: Hydrogel spacers are a tool to improve dosimetry and overall quality of life with limited follow-up in men receiving radiotherapy for prostate cancer. This present study is a pooled analysis of a prospective cohorts with long-term follow-up quality of life (QOL) data with or without hydrogel spacers to minimize dose adjacent organs at risk. Methods: QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) to compare mean changes from baseline. A total of 215 patients from a randomized multi-institutional trial of radiation with or without hydrogel spacer with a QOL end-point were pooled with 165 non-randomized patients from a single institution with prospective QOL collection in both patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre-treatment baseline in each domain were tested using repeated measures logistic models with pre-specified thresholds for clinically significant decline. Results: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men beyond 24 months of follow-up (median: 39.5 months, range: 31-71.4 mo). Treatment with spacer was associated with less decline in average long-term bowel QOL (89.4 for control and 94.7 for experimental) with differences at &gt; 2 years meeting the threshold of MID difference between cohorts (Bowel Score Difference from baseline: control = -5.1 spacer = 0.3 Diff = -5.4 p = 0.0003). When evaluated over time men without spacer were more likely to have 1xMID (5 points) declines in bowel QOL (p = 0.01). At long-term follow-up 1xMID was 36% without spacer vs 14% with spacer (p = 0.0006 OR = 3.5) while 2x MID was seen in 19% vs 6% (p = 0.008 OR = 3.6). The use of spacer was associated with improved bowel frequency (p = 0.002), reduced bleeding (p = 0.005) and less overall bowel problems (p = 0.007). Conclusions: In this pooled analysis of QOL after prostate radiotherapy with up to 5-years of follow-up utilization of a hydrogel spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long-term follow-up.

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103

PurposeRates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity. Methods and MaterialsBetween January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance). ResultsOn average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V100%), dose to 1 cc of rectum (D1cc), and dose to 2 cc of rectum (D2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V100 and dose to 90% of gland (D90) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D20, D5cc, and D1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity—6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding. ConclusionsInjection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.

Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium

The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a non-steroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64–7.75) and gel strength (15.5–65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72–92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.

Placement of an Absorbable Rectal Hydrogel Spacer in Patients Undergoing Low-Dose-Rate Brachytherapy with Pd-103 Seeds

Placement of an Absorbable Rectal Hydrogel Spacer in Patients Undergoing Low-Dose-Rate Brachytherapy with Pd-103 Seeds

ANTIEPILEPTIC RECTAL HYDROGEL LOADED WITH CARBAMAZEPINE – RICE BRAN WAX MICROSPHERES

ABSTRACTObjectives: The objective behind the study is to develop a mucoadhesive rectal hydrogel from carbamazepine (CBZ) – rice bran wax (RBW)microspheres for the purpose of controlled release for the treatment of epilepsy.Methods: The study was conducted to formulate controlled release rectal hydrogel loaded with CBZ – RBW microspheres in two different natural polymers,RBW and collagen which are prepared by modified cooling induced solidification method and gel preparation along with their evaluation studies.Results: A thorough analysis of the optimized gel revealed that all the evaluation parameters evaluated are within the acceptable limits. Further, theoptimized microsphere formulation (M5) was used to formulate it as rectal hydrogel using polymer collagen and was characterized. The mucoadhesiontime of 25% w/w collagen hydrogel (H4) was 565 minutes, allowing the loaded microspheres to be attached on rectal mucosa. In vitro drug releasefrom the mucoadhesive hydrogel formulations showed controlled drug release pattern with a maximum drug release of 96.45±0.35% for optimizedH4 formulation after 12 hr, followed zero order release pattern with diffusion mediated Higuchi model. Ex vivo permeation studies using bovine rectalmucosa revealed that H4 formulation showed greater permeability compared to control. Histopathological findings revealed that H4 formulation issafer for rectal administration without any signs of rectal irritancy. The stability studies of optimized formulation (H4) proved that hydrogel remainedstable over a wide range of temperature condition.Conclusion: Hence, the developed rectal hydrogel formulation seems to be a viable alternative to conventional drug delivery system for the effectivemanagement of epilepsy.Keywords: Carbamazepine, Rice bran wax, Rectal hydrogel, Sustainability.

PREPARATION AND EVALUATION OF CHITOSAN SODIUM ALGINATE CARBAMAZEPINE MICROSPHERES

ABSTRACTObjective: The objective behind our study is that a mucoadhesive rectal hydrogel chitosan sodium alginate carbamazepine (CBZ) microspheres forthe purpose of controlled release for the treatment of epilepsy to avoid the possible side effects.Methods: The study was conducted to formulate controlled release chitosan sodium alginate CBZ microspheres with the dispersion of CBZ into thenatural polymers chitosan and sodium alginate forming microspheres conducting along with their evaluation studies.Results: The formulated microspheres were subjected to various evaluation parameters, and all the physical parameters examined are within theacceptable limits. Further, the optimized microsphere formulation (CM5) was characterized. Hence, the developed optimized microsphere formulation(CM5) seems to be a viable substitute to conventional drug delivery system for the effective management of epilepsy.Conclusion: The prepared formulation also provides a desired CBZ loaded sodium alginate microspheres with the controlled release drug delivery.Keywords: Carbamazepine, Sodium alginate microspheres, Particle size.

SU‐F‐J‐122: Rectal Sparing Reproducibility in Prostate Cancer Patients Treated with Hydrogel Spacer and Proton Therapy

Purpose:Rectal hydrogel spacer has been shown to improve rectal sparing in prostate radiotherapy. The purpose of this study was to determine the reproducibility of rectal sparing throughout treatment in patients undergoing proton therapy.Methods:At our facility, prostate cancer patients are treated with pencil beam scanning proton therapy, utilizing an endorectal balloon (ERB) or rectal spacer hydrogel (Gel) “SpaceOAR” implant. All patients were treated with a full bladder and empty rectum (low residue diet and stool softeners). A quality assurance CT (QACT) was performed periodically throughout treatment to ensure rectal filling consistency and sparing in 41 patients treated with Gel. The treatment planning (TP) dose was calculated on each QACT and the rectum V90%, V75%, V65%, V50%, and V40% were recorded. QACT scans were acquired on day 0, week 1, week 3, and week 5.Results:144 QACT scans were analyzed, each patient receiving 3–4 QACTs. Rectum V90% was within +/−1% of the TP dose in 70% of the QACTs and within +/−5% in 95% of scans. From previous data analyses, our ERB rectum V90% average is 6%. This value was used as an upper threshold for the Gel QACT analysis. 5 of the 41 patients (12%), corresponding to 7 QACTs, had a rectum V90% that exceeded 6% on one or more QACTs. However, the average rectal V90% measured over multiple QACTs never exceeded 6%. 55% of the QACTs had a rectum volume within 5cc of the TPCT volume, 68% were within 10cc.Conclusion:In this study, we have shown that a majority of our prostate patients can maintain consistent rectal sparing when treated with a hydrogel spacer. QACT rectal V90% exceeding our threshold was most often related to increased rectal filling and gas, which was addressed with improved dietary compliance and the intensification of stool softeners or laxatives.