Hydrogel Spacer Research Articles

XIOSIS: An X-Ray-Based Intra-Operative Image-Guided Platform for Oncology Smart Material Delivery.

Image-guided interventional oncology procedures can greatly enhance the outcome of cancer treatment. As an enhancing procedure, oncology smart material delivery can increase cancer therapy's quality, effectiveness, and safety. However, the effectiveness of enhancing procedures highly depends on the accuracy of smart material placement procedures. Inaccurate placement of smart materials can lead to adverse side effects and health hazards. Image guidance can considerably improve the safety and robustness of smart material delivery. In this study, we developed a novel generative deep-learning platform that highly prioritizes clinical practicality and provides the most informative intra-operative feedback for image-guided smart material delivery. XIOSIS generates a patient-specific 3D volumetric computed tomography (CT) from three intraoperative radiographs (X-ray images) acquired by a mobile C-arm during the operation. As the first of its kind, XIOSIS (i) synthesizes the CT from small field-of-view radiographs;(ii) reconstructs the intra-operative spacer distribution; (iii) is robust; and (iv) is equipped with a novel soft-contrast cost function. To demonstrate the effectiveness of XIOSIS in providing intra-operative image guidance, we applied XIOSIS to the duodenal hydrogel spacer placement procedure. We evaluated XIOSIS performance in an image-guided virtual spacer placement and actual spacer placement in two cadaver specimens. XIOSIS showed a clinically acceptable performance, reconstructed the 3D intra-operative hydrogel spacer distribution with an average structural similarity of 0.88 and Dice coefficient of 0.63 and with less than 1 cm difference in spacer location relative to the spinal cord.

Patient factors affecting the distribution of hydrogel spacers in combination with permanent prostate brachytherapy

Patient factors affecting the distribution of hydrogel spacers in combination with permanent prostate brachytherapy

An optimal method of hydrogel spacer insertion for stereotactic body radiation therapy of prostate cancer.

This study aimed to explore an ideal method for hydrogel spacer insertion by analyzing the efficacy and safety of our originally developed apex expansion method. Overall, 100 patients with low- and intermediate-risk localized prostate cancer treated with stereotactic body radiation therapy were included. A hydrogel spacer was inserted in 64 and 36 patients using the conventional and apex expansion methods, respectively. For dosimetry, we trisected the rectum into the upper rectum, middle rectum, and lower rectum on the sagittal section of magnetic resonance imaging. We compared the dose to each part of the rectum between the two methods using dose-volume histograms. Genitourinary and gastrointestinal toxicity assessments were conducted until 3months of follow-up. The whole rectal dose in the apex expansion method group was lower than that in the conventional method group, which was significant in all dose regions (V5-V35). Similarly, in the apex expansion method group, the dose to the middle rectum was lower in the low- to high-dose region (V10-V35), and the dose to the lower rectum was lower in the middle- to high-dose region (V15-35). No Grade ≥ 3 toxicity or procedure-related complications were observed. Additionally, Grade 2 genitourinary and gastrointestinal toxicities during the treatment showed no significant differences between the two methods. The apex expansion method may be safe and effective in achieving a more efficient rectal dose reduction by expanding the anterior perirectal space in the prostatic apex area.

Increasing rectum–prostate distance using a hydrogel spacer to reduce radiation exposure during proton beam therapy for prostate cancer

SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level < 7.5 mm, n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30–60 Gy (RBE), was estimated and described as Rectal V30–60 (ml) in 10 Gy increments. The Rectal V30–60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate–rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

SpaceOAR hydrogel distribution and early complications in patients undergoing radiation therapy for prostate cancer.

Hydrogel spacers aim to separate the rectum from the prostate during radiation therapy for patients with prostate cancer to decrease the radiation dose and thus toxicity to the rectum. The aim of this study was to evaluate the distribution of the hydrogel spacer between the rectum and the prostate, to assess for hydrogel rectal wall infiltration and to assess for immediate complications. Retrospective study of 160 patients who had undergone hydrogel spacer placement. Distribution of the hydrogel was assessed on MRI. MRI images were reviewed for rectal wall injection or other malplacement of gel. Early post-procedure complications were recorded. 117 (73.1%) patients had a symmetrical distribution of the hydrogel spacer. The mean anteroposterior rectoprostatic separation was 10.2 ± 3.7 mm (range 0-27 mm). Seven (4.3%) patient had minimal rectal wall infiltration and one (0.6%) patient had moderate infiltration. One (0.6%) patient had an intraprostatic injection of hydrogel. Two (1.3%) patients required treatment in the emergency department: one for urinary retention and one for pain. Transperineal hydrogel placement separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy with a low rate of rectal wall injection and immediate complications. SpaceOAR hydrogel can be safely injected into radiation naive patients with low- or intermediate-risk organ-confined prostate cancer. The spacer separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy.

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

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

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life.

The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11-11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16-9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel. In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.

Effect of Transperineal Versus Transrectal Prostate Biopsy on the Quality of Hydrogel Spacer Placement in Men Prior to Radiation Therapy for Prostate Cancer

To determine whether prostate biopsy type affects spacer placement quality using a large sample of patients treated in the ambulatory setting. A retrospective cohort study was conducted on patients diagnosed with prostate cancer who underwent hydrogel spacer placement before primary radiation treatment between 2018 and 2023 after transperineal (TP) or transrectal (TR) prostate biopsy. Study outcomes were Spacer Quality Score (SQS) (0-2, with greater values indicating better placement), Rectal Wall Infiltration (RWI) (0-3, with lower values indicating lack of RWI), and the occurrence of other hydrogel complications. A total of 395 patients were included. A pre-hydrogel TR biopsy was performed in 273 patients (69.1%), while TP biopsy was performed in 122 (30.9%). A SQS ≥1 occurred in 308 (77.9%) patients. A greater proportion of TP patients had a favorable SQS (≥1) compared to those who underwent TR (87.7 vs 73.5%, P<.002). An RWI score ≥2 was found in 180 (45.6%) patients. The proportion of patients with an unfavorable RWI score (≥2) did not differ significantly by type of biopsy performed. Patients who had an interval of >70days between biopsy and hydrogel placement had significantly decreased odds of an RWI score ≥2 (odds ratio=0.42, 95% confidence interval: 0.21-0.83). Only one infection was found after hydrogel placement. The quality of hydrogel placement was significantly better in men who had undergone TP biopsy. Rectal wall infiltration was more common than previously reported but did not differ between TP and TR biopsies.

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiation Therapy: A Prospective Phase 2 Study

The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure, toxicity, treatment planning, image guidance, and imaging results up to 12 months after RT. RVS (median, 10 mL) was injected between prostate and rectal wall in 30 patients. Cone beam computed tomography (CT) was performed during the course of RT, a magnetic resonance imaging 3 and 12 months after RT. Injection and treatment tolerability were analyzed. The resulting distribution was compared with a control group of 30 patients with an initially fluid spacer. Procedure- or device-related adverse events were not observed. Signs of hydrogel migration were not found in any case. The volume decreased by 25% at 3 months after RT, and small residues were detected at 12 months after RT in 3 cases (10%). The median rectal volume percentage within the 90% isodose was 3.0% (interquartile range, 1.5%-4.5%). Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The median distance between prostate and rectum at the base/midplane/apex was greater for RVS in comparison to initially fluid spacer (14/12/11 mm vs 12/10/10 mm, respectively), the gel symmetry (right vs left from midline) was comparable. The application was assessed to be easier to control by the users, and visibility in cone beam CT as good. The injection of a radiopaque viscous hydrogel spacer resulted in a prostate-rectum distance of >10 mm in most cases. The resulting rectum volume within the high-dose region and RT toxicity were very low. Advantages in comparison to the conventional hydrogel spacer are predominantly an improved placement control during the injection process and good visibility on CT.

CT vs. MRI: Which is More Accurate in Grading Rectal Wall Infiltration after Hydrogel Spacer Placement for Prostate Cancer Patients?

The purpose of this study was to evaluate the incidence and severity of rectal wall infiltration (RWI) in prostate cancer patients after rectal hydrogel spacer implantation, a commonly used procedure to minimize rectal radiation exposure during prostate radiotherapy. The study aimed to determine correlation of RWI using computed tomography (CT) scans and magnetic resonance imaging (MRI) scans in order to determine the optimal post-placement imaging modality. This retrospective study was conducted on 370 patients diagnosed with localized prostate cancer who underwent rectal hydrogel spacer placement from 2020 to 2022. CT scans were performed on all patients, with a smaller subset also undergoing MRI scans. The images were independently evaluated by three radiation oncologists to grade RWI levels using a standardized scoring system based on CT and MRI images after hydrogel placement. The levels were categorized as 0 (no RWI), 1 (focal RWI), 2 (moderate RWI), and 3 (significant RWI). Any grade of RWI was identified in 79.8% of men with the majority (41%) being RWI grade 1. The median time for CT scans was 9 days after hydrogel spacer placement and 14.5 days for MRI scans. For the subset of patients with both CT and MRI scans after spacer (mostly SpaceOAR Vue), RWI was detected in 58.33% of patients based on CT and 61.11% of patients based on MRI. Table 1 shows the mean percentage of patients with each score of RWI for each imaging modality. MRI was more likely to lead to a designation of RWI of any grade compared to CT and more often led to detection of RWI grades 2-3. Our findings demonstrate that the incidence and severity of RWI may be higher than previously reported in clinical trials and that MRI may be a more sensitive imaging modality. Caution is needed in the utilization of rectal spacer gels given the potential for complications with misplacement prior to radiation therapy. Further study is warranted to determine the potential impact of low-grade RWI on the safety of subsequent treatment.

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiotherapy - A Prospective Multi-Institutional Phase II Study.

Rectal dose can be significantly decreased after spacer application. An initially fluid spacer (FS) spreads in a predetermined space, whereas the positioning of a viscous spacer is determined by needle guidance. The aim of this study was to evaluate the application a radiopaque viscous spacer (RVS) for prostate cancer radiotherapy (RT). In 30 patients including three centers, 10ml (median) of a RVS was injected between the prostate and anterior rectal wall. The resulting distance and distribution were determined in different planes and compared with a control group of 30 patients with a FS. A cone beam computed tomography (CBCT) was performed at least at the end of RT, a magnetic resonance imaging (MRI) 3 months and 12 months after RT. Injection and treatment tolerability were analyzed. With a median prostate volume of 40cm3, no overlap was found between planning target volume and rectal volume in most cases (median = 0cm3, interquartile range, IQR 0-0.6cm3). The median contoured RVS before, at the end and 3 months after RT was 8.5cm3, 8.7cm3 und 6.4cm3. Signs of hydrogel migration were not found in any case. Hydrogel visibility in CBCT was rated with "4" on a scale between 1 (poor) and 5 (excellent). Small residues were detected in the MRI 12 months after RT in 3 cases (10%). The median distance between prostate and rectum at the base / midplane / apex was 14mm / 12mm / 11mm. The median rectal volume percentage within the 90% and 80% isodoses was 3.0% (IQR 1.5-4.5%) bzw. 5.9% (IQR 3.0-10.6%). On a scale between 1 (difficult) and 5 (very easy), ease of application was rated with "3-4". Procedure- or device related adverse events have not been observed in any case. Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The control of gel distribution of RVS relative to FS was rated with "3-5" on a scale between 1 (much worse) and 5 (much better), the ease of application relative to FS with "2-3" on a scale between 1 (much harder) and 5 (much easier). With a median contoured FS volume of 9.9cm3, the prostate-rectum distance at the base / midplane / apex was 12mm / 10mm / 10mm (significantly smaller in comparison to RVS). However, the lateral gel extension of RVS was smaller in all planes, statistically significant for all comparisons (base: 28mm vs. 34mm, midplane: 28mm vs. 32mm, apex: 21mm vs. 26mm). The gel symmetry (right vs. left) was comparable. The application of a radiopaque viscous hydrogel spacer is harder in comparison to the initially fluid spacer. However, it can be better controlled and is achievable without any complications. Visibility in CBCT is good. The resulting prostate-rectum distance is >10mm in most cases and slightly larger at the base in comparison to FS. The resulting rectum volume within the high dose region and radiotherapy toxicity are very low.

Phase II Clinical Trial of Hypofractionated Image-Guided Proton Therapy with 12 Fractions for Prostate Cancer.

Towards hypofractionated proton therapy for prostate cancer for improving convenience for patients to receive treatment and improving therapeutic efficacy, image-guided technique with hydrogel spacer solved the late gastrointestinal toxicity, but it is unclear whether acute genitourinary (GU) toxicity is acceptable. The aim of this phase II study was to evaluate the safety and efficacy of hypofractionated image-guided proton therapy (IGPT) with 12 fractions for prostate cancer. Eligibility criteria were as follows: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by (UICC TNM8th); (3) ECOG-PS ≤ 2; (4) age ≥ 20 years; (5) no serious underlying disease or other cancers; (6) technically capable of proton therapy, and (7) written informed consent. Primary endpoint was the ratio of grade 2 or more acute genitourinary toxicity. We used the modified CTCAE grading of grade 2 GU toxicities, in which prescribing two and more types of drugs for dysuria within 3 months of the start of radiation was considered to indicate grade 2 GU toxicity. A phase II trial was planned based on the minimax Simon's two-stage design with a significance level of 0.05 and a power of 90%. The acceptable incidence is considered to be less than 5%, and the unacceptable incidence is considered to be more than 15%. A total of 83 patients is required for completion of the trial (7 patients or fewer). After evaluating the primary endpoint in 83 patients, 217 additional patients were registered and a total of 300 patients were registered in order to further examine the safety and efficacy. The prescribed dose to the isocenter was 51.6 GyRBE in 12 fractions (4 days a week). From January 2020 to March 2021, 30, 53, and 217 patients (total 300) were enrolled. The patient characteristics were as follows: median age, 70 (48-83) years; low/intermediate/high risk, 44/132/124. Forty-nine and 38 patients had benign prostatic hyperplasia and diabetes mellitus, respectively. Grade 2 acute GU toxicities were observed in 1, 5 and 13 patients, respectively (total 6.3%). No grade 3 or higher acute GU toxicities were observed. However, urinary retention during IGPT, which was not previously observed, was observed in 3 cases, and temporary urethral catheterization was performed (Grade 2). Most of the acute GU toxicity tended to improve at 1 month after IGPT, and almost improved at 3 months. Mean score deteriorations beyond the minimum clinically important difference threshold (1/2 SD) were observed only at 1 month in the following scales: summary (-6.0), bother (-7.0), and irritative/obstructive (-6.3). Hypofractionated IGPT with 12 fractions for prostate cancer is well tolerated in acute GU toxicities. Longer follow-up is necessary to evaluate the efficacy and late toxicities. Further investigation of hypofractionated IGPT with 12 fractions for prostate cancer is warranted. Since April 2021, an additional 1000 cases of prospective registration study have been conducted.

Biological Effective Dose (BED) in Evaluation of Rectal Dose in Prostate Cancer Patients with Hydrogel Spacer Who Underwent an EBRT with Different Fractionation Schemes

To evaluate rectal dose sparing in prostate cancer patients with hydrogel spacer who underwent an external beam radiotherapy (EBRT) with different fractionation schemes. In a previous study, we have reported that rectal sparing was achieved in prostate cancer patients with hydrogel spacer who underwent a combination therapy of EBRT and LDR brachytherapy (Zhang H, et al. J Appl Clin Med Phys, 2022). In this study, we focused on evaluation of spacer-related rectal sparing in patients who underwent an EBRT with conventional fractionation (81 Gy in 45 fractions), hypofractionation (70 Gy in 28 fractions), or stereotactic body radiotherapy (SBRT) for 40 Gy or 42.5 Gy in 5 fractions. In 172 patients, 119 patients were applied with injection of polyethylene-glycol hydrogel and others without the injection as control. In VMAT plans, doses to rectal wall were examined and converted to BED according to AAPM TG-137 (α/β ratio = 4 Gy). On average, an interspace of 1cm between prostate and rectum was achieved by spacer insertion. Rectal wall was defined as 0.4cm thickness inside the outer contour of rectum, and the volume ranged from 4.5 cm3 to 21.3cm3 for patients with spacer and from 8.2cm3 to 35.1cm3 for those with no spacer. In conventional scheme, an average rectal BED was 120.0 Gy, 116.9 Gy, 114.0 Gy, 108.6 Gy, 87.6 Gy and 55.6 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 55.3 Gy in patients with no spacer. The BED decreased to 105.1 Gy, 96.3 Gy, 86.1 Gy, 75.4 Gy, 51.7 Gy and 26.9 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), and BEDmean was 46.0 Gy in patients with spacer. In hypofractionation, rectal BED was in average of 115.8 Gy, 112.3 Gy, 109.8 Gy, 103 Gy, 81.6 and 52.8 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 48.6 Gy in patients with no spacer. Patients with spacer had significantly decreases of rectal BED, an average of 103 Gy, 91.7 Gy, 84.1 Gy, 72.8 Gy, 48.8 Gy and 26.0 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), BEDmean was 42.4 Gy. In SBRT, average rectal BED in patients with spacer decreased to 93.6 Gy, 78.4 Gy, 69 Gy, 57.5 Gy, 38.5 Gy and 21.5 Gy, in comparison of 124.1 Gy, 117,4 Gy, 110.9 Gy, 97.3 Gy, 59.7 Gy and 32.3 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3 in those without spacer, respectively (p <0.01). BEDmean decreased to 32.0 Gy in patient with spacer, compared with 43.2 Gy in those with no spacer. Insertion of hydrogel spacer significantly improved rectal dose sparing, about 11.1% to 50.8% in conventional scheme, 12.4% to 51.6% in hypofractionation scheme, and 24.6% to 40.9% in SBRT patients. Furthermore, relatively more dose sparing on rectum was seen on the volume from 0.1cm3 to 2cm3 in SBRT patients.

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.

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.

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.

Real-World Complications of the SpaceOAR Hydrogel Spacer: A Review of the Manufacturer and User Facility Device Experience Database

To characterize adverse events related to use of the perirectal spacing agent SpaceOAR, we examined the Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was queried for "SpaceOAR" and "Augmenix" from June 2015 (when SpaceOAR was approved by the Food and Drug Administration) to October 2022. Reports were reviewed for adverse events (AEs), operative procedures performed because of the AE, and changes to the radiation plan. AEs were categorized using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Six hundred fifty-four reports were reviewed. Eighty-four were excluded and 4 reports reviewed 2 separate cases of SpaceOAR administration. Five hundred seventy-four cases were ultimately included. Three deaths were reported (0.5% of all AEs). One point six percent of cases represented CTCAE grade 4 injuries (life-threatening consequences; urgent intervention indicated), 15.9% grade 3 (severe but not immediately life-threatening; hospitalization), 24.2% grade 2 (moderate; local/noninvasive intervention), and 57% of events were CTCAE grade 1 (mild; asymptomatic or mild symptoms). Bowel diversion occurred in 29 cases (9%). Both asymptomatic (n=311) and debilitating (n=12) complications of SpaceOAR hydrogel use were identified. Death, gel embolization, anaphylaxis, rectal ulcerations, and infections requiring bowel or urinary diversions were among the complications reviewed. Providers should consider these potential complications before perirectal spacer administration and during patient counseling.

PO64: Hydrogel Spacer Placement with HDR Prostate Brachytherapy: Does Time of Insertion Matter?

PO64: Hydrogel Spacer Placement with HDR Prostate Brachytherapy: Does Time of Insertion Matter?

PO70: Combining External Beam Radiation, Brachytherapy, and Rectal Hydrogel Spacer for Prostate Cancer: A Study of Gastrointestinal Toxicity and Implant Quality

PO70: Combining External Beam Radiation, Brachytherapy, and Rectal Hydrogel Spacer for Prostate Cancer: A Study of Gastrointestinal Toxicity and Implant Quality

Relationship between seminal vesicle displacement and distribution of hydrogel spacer within the perirectal space in prostate radiotherapy.

The influence of a hydrogel spacer (HS) on seminal vesicle (SV) displacement in prostate radiotherapy was examined in the present study. A total of 20 patients with prostate cancer, who received intensity-modulated radiation therapy (IMRT), were enrolled. Computed tomography and magnetic resonance imaging were performed before and after HS insertion within the peripheral space for IMRT planning. Before and after HS insertion, The SV was delineated, and the amount of SV displacement was evaluated. Large SV cranial displacements (≥0.50 cm) were observed in 25% of patients. A HS lateral distribution of ≥1.00 cm in the upper two slices (midgland + superior) influenced the SV cranial displacements (P<0.01) and was associated with large SV cranial displacements (≥0.5 cm) (P<0.01). The HS cranial distribution in the upper slices did not influence SV cranial displacements (P=0.16). In addition, any HS lateral distribution of ≥1.00 cm in all slices did not induce the SV lateral and anterior-posterior displacements (P=0.50 and 0.70, respectively). In conclusion, SV cranial displacement was influenced by HS lateral distribution of ≥1.00 cm in the upper two slices. Therefore, when the sigmoid colon or small bowel is depressed in rectovesical excavation and SV needs to be included in the target volume, HS insertion should be performed carefully.