Hydrogel Spacer Research Articles

Deep Rectal Ulceration Associated With Hydrogel Spacer for Prostate Radiation Therapy

The report highlights the importance of having a high suspicion of rectal ulceration in patients after radiation therapy. We present a case of 57-year-old man with a history of stage IIIc prostate cancer who developed a solitary rectal ulcer after radiation therapy with a hydrogel spacer. He was diagnosed during colonoscopy and responded well to a course of hyperbaric oxygen therapy.

Demonstrating the benefits of corrective intraoperative feedback in improving the quality of duodenal hydrogel spacer placement.

PurposePancreatic cancer is the fourth leading cause of cancer‐related death with a 10% 5‐year overall survival rate (OS). Radiation therapy (RT) in addition to dose escalation improves the outcome by significantly increasing the OS at 2 and 3 years but is hindered by the toxicity of the duodenum. Our group showed that the insertion of hydrogel spacer reduces duodenal toxicity, but the complex anatomy and the demanding procedure make the benefits highly uncertain. Here, we investigated the feasibility of augmenting the workflow with intraoperative feedback to reduce the adverse effects of the uncertainties.Materials and MethodsWe simulated three scenarios of the virtual spacer for four cadavers with two types of gross tumor volume (GTV) (small and large); first, the ideal injection; second, the nonideal injection that incorporates common spacer placement uncertainties; and third, the corrective injection that uses the simulation result from nonideal injection and is designed to compensate for the effect of uncertainties. We considered two common uncertainties: (1) “Narrowing” is defined as the injection of smaller spacer volume than planned. (2) “Missing part” is defined as failure to inject spacer in the ascending section of the duodenum. A total of 32 stereotactic body radiation therapy (SBRT) plans (33 Gy in 5 fractions) were designed, for four cadavers, two GTV sizes, and two types of uncertainties. The preinjection scenario for each case was compared with three scenarios of virtual spacer placement from the dosimetric and geometric points of view.ResultsWe found that the overlapping PTV space with the duodenum is an informative quantity for determining the effective location of the spacer. The ideal spacer distribution reduced the duodenal V33Gy for small and large GTV to less than 0.3 and 0.1cc, from an average of 3.3cc, and 1.2cc for the preinjection scenario. However, spacer placement uncertainties reduced the efficacy of the spacer in sparing the duodenum (duodenal V33Gy: 1.3 and 0.4cc). The separation between duodenum and GTV decreased by an average of 5.3 and 4.6 mm. The corrective feedback can effectively bring back the expected benefits from the ideal location of the spacer (averaged V33Gy of 0.4 and 0.1cc).ConclusionsAn informative feedback metric was introduced and used to mitigate the effect of spacer placement uncertainties and maximize the benefits of the EUS‐guided procedure.

Utilisation of a rectal hydrogel spacer for vaginoplasty in a cadaver model

Background: A major source of complications in vaginoplasty results from injury to the rectum during dissection of the neovaginal cavity. The SpaceOAR™ System is a rectal hydrogel spacer mostly used as a safety technique during prostate cancer treatment. Objective: This was a feasibility study performed in a single cadaveric perineum.Methods: Prior to standard cavity dissection, SpaceOAR was injected transperineally into the Denonvilliers’ fascia under guidance of transrectal ultrasound. Dissection of the neovaginal cavity with spacer gel was qualitatively assessed to be significantly easier, allowing for a blunt and quick approach. Results: A satisfactory vaginal length was achieved rapidly and safely. Conclusions: We show that transgender vaginoplasty using this adaptation of SpaceOAR is technically feasible in the cadaveric model and may reduce the incidence of rectal injury or rectovaginal fistula during neovaginal cavity creation. Future experimental endeavours should focus on the reproducibility of this approach and characterise the degree of rectal protection provided. Level of evidence: Not applicable

Finite Element-Based Personalized Simulation of Duodenal Hydrogel Spacer: Spacer Location Dependent Duodenal Sparing and a Decision Support System for Spacer-Enabled Pancreatic Cancer Radiation Therapy.

PurposePancreatic cancer is the fourth leading cause of cancer-related death, with a very low 5-year overall survival rate (OS). Radiation therapy (RT) together with dose escalation significantly increases the OS at 2 and 3 years. However, dose escalation is very limited due to the proximity of the duodenum. Hydrogel spacers are an effective way to reduce duodenal toxicity, but the complexity of the anatomy and the procedure makes the success and effectiveness of the spacer procedure highly uncertain. To provide a preoperative simulation of hydrogel spacers, we presented a patient-specific spacer simulator algorithm and used it to create a decision support system (DSS) to provide a preoperative optimal spacer location to maximize the spacer benefits.Materials and MethodsOur study was divided into three phases. In the validation phase, we evaluated the patient-specific spacer simulator algorithm (FEMOSSA) for the duodenal spacer using the dice similarity coefficient (DSC), overlap volume histogram (OVH), and radial nearest neighbor distance (RNND). For the simulation phase, we simulated four virtual spacer scenarios based on the location of the spacer in para-duodenal space. Next, stereotactic body radiation therapy (SBRT) plans were designed and dosimetrically analyzed. Finally, in the prediction phase, using the result of the simulation phase, we created a Bayesian DSS to predict the optimal spacer location and biological effective dose (BED).ResultsA realistic simulation of the spacer was achieved, reflected in a statistically significant increase in average target and duodenal DSC for the simulated spacer. Moreover, the small difference in average mean and 5th-percentile RNNDs (0.5 and 2.1 mm) and OVH thresholds (average of less than 0.75 mm) showed that the simulation attained similar separation as the real spacer. We found a spacer-location-independent decrease in duodenal V20Gy, a highly spacer-location-dependent change in V33Gy, and a strong correlation between L1cc and V33Gy. Finally, the Bayesian DSS predicted the change in BED with a root mean squared error of 3.6 Gys.ConclusionsA duodenal spacer simulator platform was developed and used to systematically study the dosimetric effect of spacer location. Further, L1cc is an informative anatomical feedback to guide the DSS to indicate the spacer efficacy, optimum location, and expected improvement.

Biological effective dose in analysis of rectal dose in prostate cancer patients who underwent a combination therapy of VMAT and LDR with hydrogel spacer insertion.

This study aimed to evaluate rectal dose reduction in prostate cancer patients who underwent a combination of volumetric modulated arc therapy (VMAT) and low‐dose‐rate (LDR) brachytherapy with insertion of hydrogel spacer (SpaceOAR). For this study, 35 patients receiving hydrogel spacer and 30 patients receiving no spacer were retrospectively enrolled. Patient was treated to doses of 45 Gy to the primary tumor site and nodal regions over 25 fractions using VMAT and 100 Gy to the prostate using prostate seed implant (PSI). In VMAT plans of patients with no spacer, mean doses of rectal wall were 43.6, 42.4, 40.1, and 28.8 Gy to the volume of 0.5, 1, 2, and 5 cm3, respectively. In patients with SpaceOAR, average rectal wall doses decreased to 39.0, 36.9, 33.5, and 23.9 Gy to the volume of 0.5, 1, 2, and 5 cm3, respectively (p < 0.01). In PSI plans, rectal wall doses were on average 78.5, 60.9, 41.8, and 14.8 Gy to the volume of 0.5, 1, 2, and 5 cm3, respectively, in patients without spacer. In contrast, the doses decreased to 34.5, 28.4, 20.6 (p < 0.01), and 8.5 Gy (p < 0.05) to rectal wall volume of 0.5, 1, 2, and 5 cm3, respectively, in patient with SpaceOAR. To demonstrate rectal sum dose sparing, dose‐biological effective dose (BED) calculation was accomplished in those patients who showed >60% overlap of rectal volumetric doses between VMAT and PSI. In patients with SpaceOAR, average BEDsum was decreased up to 34%, which was 90.1, 78.9, 65.9, and 40.8 Gy to rectal volume of 0.5, 1, 2, and 5 cm3, respectively, in comparison to 137.4, 116.7, 93.0, and 50.2 Gy to the volume of 0.5, 1, 2, and 5 cm3, respectively, in those with no spacer. Our result suggested a significant reduction of rectal doses in those patients who underwent a combination of VMAT and LDR with hydrogel spacer placement.

Efficacy of an Esophageal Spacer for Spine Radiosurgery: First Experience

This is the first study to investigate the use of an esophageal hydrogel spacer in spine stereotactic radiosurgery. The tolerability and the dose reduction to the esophagus are predicted to reduce the incidence of high-grade toxicities, which in turn can permit dose escalation to optimize tumor control.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

Injection of hydrogel spacer increased maximal intrafractional prostate motion in anterior and superior directions during volumetric modulated arc therapy-stereotactic body radiation therapy for prostate cancer

BackgroundThe aim of this study was to clarify the association between intrafractional prostate shift and hydrogel spacer.MethodsThirty-eight patients who received definitive volumetric modulated arc therapy (VMAT)-stereotactic body radiation therapy (SBRT) for prostate cancer with prostate motion monitoring in our institution in 2018–2019 were retrospectively evaluated. In order to move the rectum away from the prostate, hydrogel spacer (SpaceOAR system, Boston Scientific, Marlborough, the United States) injection was proposed to the patients as an option in case of meeting the indication of use. We monitored intrafractional prostate motion by using a 4-dimensional (4D) transperineal ultrasound device: the Clarity 4D ultrasound system (Elekta AB). The deviation of the prostate was monitored in each direction: superior-inferior, left–right, and anterior–posterior. We also calculated the vector length. The maximum intrafractional displacement (MID) per fraction for each direction was detected and mean of MIDs was calculated per patient. The MIDs in the non-spacer group and the spacer group were compared using the unpaired t-test.ResultsWe reviewed 33 fractions in eight patients as the spacer group and 148 fractions in 30 patients as the non-spacer group. The superior MID was 0.47 ± 0.07 (mean ± SE) mm versus 0.97 ± 0.24 mm (P = 0.014), the inferior MID was 1.07 ± 0.11 mm versus 1.03 ± 0.25 mm (P = 0.88), the left MID was 0.74 ± 0.08 mm versus 0.87 ± 0.27 mm (P = 0.55), the right MID was 0.67 ± 0.08 mm versus 0.92 ± 0.21 mm (P = 0.17), the anterior MID was 0.45 ± 0.06 mm versus 1.16 ± 0.35 mm (P = 0.0023), and the posterior MID was 1.57 ± 0.17 mm versus 1.37 ± 0.22 mm (P = 0.56) in the non-spacer group and the spacer group, respectively. The max of VL was 2.24 ± 0.19 mm versus 2.89 ± 0.62 mm (P = 0.19), respectively.ConclusionsOur findings suggest that maximum intrafractional prostate motion during VMAT-SBRT was larger in patients with hydrogel spacer injection in the superior and anterior directions. Since this difference seemed not to disturb the dosimetric advantage of the hydrogel spacer, we do not recommend routine avoidance of the hydrogel spacer use.

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer.

PurposeStereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.Methods and MaterialsThis study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally important difference (MID) assessing patient-reported quality of life was defined as greater than a one-half standard deviation increase in American Urological Association (AUA) symptom score after SAbR.ResultsTwo-hundred and forty-nine (249) low-, intermediate-, and high-risk PCa patients with median follow-up of 14.9 months for clinical toxicity were included. Acute urinary grade II toxicity occurred in 20.4% of patients. Acute grade II GI toxicity occurred in 7.3% of patients. For follow-up > 2 years (n = 69), late GU and GI grade ≥III toxicity occurred in 5.8% and 1.5% of patients, respectively. MID was evident in 31.8%, 23.4%, 35.8%, 37.0%, 33.3%, and 26.7% of patients at 3, 6, 12, 24, 36, and 48 months, respectively. The median follow-up for biochemical recurrence was 22.6 months with biochemical failure-free survival of 100% at 1 year (n = 226) and 98.7% for years 2 (n = 113) and 3 (n = 54).ConclusionsSAbR for PCa at 45 Gy in 5 fractions shows an encouraging safety profile. Prospective studies with longer follow-up are warranted to establish this dose regimen as standard of care for PCa.

Natural history of lower urinary tract symptoms among men undergoing stereotactic body radiation therapy for prostate cancer with and without a Rectal Hydrogel Spacer.

Stereotactic body radiation therapy (SBRT) is increasingly used for prostate cancer, but has morbidity as both the bladder and rectum are radiated during treatment. Our goal was to document and compare lower urinary tract symptoms (LUTS) among men who underwent SBRT with and without SpaceOAR hydrogel (Augmenix, Inc., Bedford, MA). We performed a retrospective analysis of 87 men (50 SpaceOAR and 37 non-SpaceOAR) who underwent SBRT. Primary outcomes were patient reported symptoms during radiation therapy, pharmacotherapy usage, and urologic and bowel survey scores up to 6-months post-SBRT. 78% of men were on α-inhibitors at the end of SBRT, an increase from 27.6% baseline usage (p < 0.001). Post-SBRT urinary frequency was more common in the non-SpaceOAR group versus the SpaceOAR group (68% versus 38%, p = 0.006), as was nocturia (35% vs. 8%, p = 0.002). Acute gastrointestinal symptoms did not differ. 58.8% of men were on α-inhibitors at 6-months of follow-up post-SBRT, an increase from 27.6% baseline usage (p < 0.001). Importantly, there was a difference of α-inhibitor use between non-SpaceOAR and SpaceOAR groups at the end of SBRT and at 1.5-, 3-, and 6-months follow up (86% vs. 53% [p = 0.002], 83% vs. 53% [p = 0.005], 72% vs. 49% [p = 0.038], respectively). LUTS after SBRT remains a significant problem for men undergoing treatment for prostate cancer. LUTS affects men during and up to 6-months following SBRT. Owing to these increased LUTS, preemptive minimally invasive solutions and their mechanisms of protection, including the SpaceOAR, should be further investigated.

Minimum Required Interval Between Hydrogel Spacer Injection and Treatment Planning for Stereotactic Body Radiation Therapy for Prostate Cancer

PurposeThe present study evaluated the short-term characteristics (<3 days) of a hydrogel spacer from the time of injection during stereotactic body radiation therapy (SBRT) for prostate cancer. Methods and MaterialsFifteen patients treated with SBRT via the CyberKnife system (36.25 Gy/5 fractions) were enrolled in this retrospective study. Two magnetic resonance (MR) images were obtained with a hydrogel spacer: one on a computed tomography (CT) simulation day (MR pretreatment [MRpre]) and the other on the last treatment day (MR posttreatment [MRpost]). Two medical physicists contoured the hydrogel spacer on each MR image. The changes of the shapes and the volume for the hydrogel spacer between 2 MR images were evaluated. ResultsThe median period between hydrogel spacer injection and CT simulation was 1 day (range, 1-9 days). The median period between CT simulation and the last treatment was 17 days (range, 14-25 days). Regarding the volume change of the hydrogel spacer, the 2 observers observed significant differences between the volumes of the hydrogel spacer on the MRpre and MRpost. However, the average volume difference between them was less than 1 cm3. The average dice similarity coefficient between the MRpre and MRpost to compare the shape was more than 0.83. In addition, no clear correlation was confirmed between the volume change and the period from hydrogel spacer injection to CT simulation. ConclusionsA single day is an acceptable interval between hydrogel spacer injection and treatment planning for SBRT for prostate cancer.

Rectal sparing in prostate radiotherapy with combination-brachytherapy and hydrogel spacer

BackgroundThough some techniques that facilitate rectal sparing such as brachytherapy and intensity modulated radiotherapy (IMRT) have been examined in detail, technical aspects of hydrogel spacer (HS) have been studied less exhaustively. We examined HS quality metrics and approaches to placement for superior dosimetric outcomes. Materials and methodsA single site retrospective review of radiation plans was conducted for patients who received combination-brachytherapy (CBT) with 90 Gy low-dose-rate implant followed by external beam radiotherapy (45 Gy/25 fractions) with operating room (OR) placed HS (2017–2021). A randomly selected set of patients that received CBT without HS over the same time period was used for comparison. Dosimetric outcomes included D1cc and D5% rectum. Dose gradients were quantified. Student's t-test was used for statistical comparisons. ResultsSixty patients (30 with and 30 without HS) who received CBT for prostate cancer were examined. Those with HS had lower mean D1cc [65.31 Gy (SD = 13.53)] and D5% [53.20 Gy (SD = 10.18)] compared to those treated without HS [91.67 Gy (SD = 8.31) and 75.00 Gy (SD = 8.45), respectively, p < 0.001]. Patients with superior HS (average thickness ≥1 cm; n = 12) had lower mean D1cc [58.49 Gy (SD = 13.25, p = 0.026)] and D5% [48.69 Gy (SD = 9.85, p = 0.049)] than those with thinner HS. When dose gradients were considered, HS spanning the interface between the prostate and perirectal tissues to a thickness ≥1 cm can reduce rectal maximum dose to 50–60 Gy. ConclusionsThrough effective use of CBT and HS, extreme rectal dose restriction is possible. The goal for HS placement should be thickness ≥1 cm from base to apex.

MRI-Based Radiotherapy Planning to Reduce Rectal Dose in Excess of Tolerance.

Materials and Methods This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test. Results For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001). Conclusions Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.

The dosimetric advantages of perirectal hydrogel spacer in men with localized prostate cancer undergoing stereotactic ablative radiotherapy (SABR).

To evaluate the dosimetric differences for patients receiving a perirectal hydrogel spacer (PR-HS) using SpaceOAR undergoing stereotactic ablative radiotherapy (SABR) for localized prostate cancer with the CyberKnife VSI system. Gold fiducial markers and a PR-HS was inserted in 22 consecutive patients with histologically confirmed localized prostate cancer. For planning comparison, dosimetry from the clinical plans was compared against replans based on a simulated rectum volume designed to recreate a clinically appropriate spacer-less anatomy for each patient. Both sets were planned to 36.25 Gy in 5 fractions using the treatment planning system associated with the CyberKnife VSI system. The aim was to ensure equivalent target coverage for both plans and to evaluate doses to the organs-at-risk (OARs): rectum, bladder and penile bulb. The median PR-HS implant volume was 11.2 cc (range 8.8 to 14.9 cc). The maximal median perirectal separation was 15.5 mm (10.5 to 20.7 mm). Statistically significant reductions were noted for the 3 OARs, with no statistically significant difference in planning target volumes or clinical target volume coverage. All rectal dose constraints were significantly improved in the PR-HS plans with a percentage dose difference of at least 24% (rectum V18.1Gy (%)) to 60.5% (rectum V36Gy (cc)). The bladder and penile bulb dose constraints parameters were also significantly improved: the bladder V37Gy was reduced by 17.1%, V18.1Gy was reduced by 4.2%; the penile bulb D50% was reduced by 7.7%. The use of PR-HS was able to significantly reduce planned dose to the rectum, bladder and penile bulb with SABR techniques associated with the CyberKnife VSI system.

SpaceOAR hydrogel spacer injection prior to stereotactic body radiation therapy for men with localized prostate cancer: A systematic review.

Background:Conventionally fractionated radiotherapy is a common treatment for men with localized prostate cancer. A growing consensus suggests that stereotactic body radiation therapy (SBRT) is similarly effective but less costly and more convenient for patients. The SpaceOAR hydrogel rectal spacer placed between the prostate and rectum reduces radiation-induced rectal injury in patients receiving conventionally fractionated radiotherapy, but spacer efficacy with SBRT is unclear. The purpose of this research was to assess the clinical utility of the hydrogel rectal spacer in men receiving SBRT for prostate cancer.Methods:We performed systematic searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies in men who received the SpaceOAR hydrogel spacer prior to SBRT (≥5.0 Gy fractions) for treatment of localized prostate center. Rectal irradiation results were compared to controls without spacer implant; all other outcomes were reported descriptively owing to lack of comparative data incuding perirectal separation distance, rectal irradiation on a dosimetric curve, gastrointestinal (GI) toxicity, and freedom from biochemical failure. GI toxicity was reported as the risk of a grade 2 or 3+ bowel complication in early (≤3 months) and late (>3 months) follow-up.Results:In 11 studies with 780 patients, SBRT protocols ranged from 7 to 10 Gy per fraction with total dose ranging from 19 to 45 Gy. Perirectal distance achieved with the rectal spacer ranged from 9.6 to 14.5 mm (median 10.8 mm). Compared to controls receiving no spacer, SpaceOAR placement reduced the radiation delivered to the rectum by 29% to 56% across a dosimetric profile curve. In early follow-up, grade 2 GI complications were reported in 7.0% of patients and no early grade 3+ GI complications were reported. In late follow-up, the corresponding rates were 2.3% for grade 2 and 0.3% for grade 3 GI toxicity. Over 16 months median follow-up, freedom from biochemical failure ranged from 96.4% to 100% (pooled mean 97.4%).Conclusions:SpaceOAR hydrogel spacer placed between the prostate and rectum prior to SBRT is a promising preventative strategy that increases the distance between the prostate and rectum, reduces rectal radiation exposure, and may lower the risk of clinically important GI complications.

Separation Effect and Development of Implantation Technique of Hydrogel Spacer for Prostate Cancers

PurposeThe purpose of this study is to improve the placement of a hydrogel spacer in patients with prostate cancer receiving radiation therapy. Methods and MaterialsA total of 160 patients with prostate cancer were classified into 3 groups: No spacer (group 1; n = 30), spacer placed using conventional technique (group 2; n = 100), and spacer placed using new technique (group 3; n = 30). When placing the spacer, the tip of the needle is placed at the middle of the prostate gland (group 2), or at a level corresponding to a cranial:caudal ratio of 6:4 and as close to the prostate gland as possible (group 3). The separation effect was examined and compared among the groups. ResultsThe separation in group 2 was larger than that in group 1 from the base to the apex level of the prostate (4 mm), but the separation in group 3 was larger than that in group 2 from the middle to the apex level of the prostate (4 mm). The separation values for the middle to the apex, the spacer thickness from the apex level to the apex (10 mm), the rectal exclusion from the middle to the apex, and the laterality were correlated with the 50 and 60 Gy relative biologic effectiveness (Gy[RBE]) rectal dose (P = 4.1 × 10−9 – .046). The separation vales were strongly correlated with the spacer thickness at the apex (10 mm) and the apex (4 mm; P = 1.1 × 10−18 – 1.8 × 10−17). The rectal volumes at 10 to 60 Gy(RBE) differed among the groups (P = 5.1 × 10−19 – 5.4 × 10−3). The rectal volumes in group 2 were smaller than those in group 1 at all dose levels, but those in group 3 were smaller than those in group 2 at dose levels of 30 to 50 Gy(RBE). ConclusionsThe separation, spacer thickness, and rectal exclusion from the middle to the apex of the prostate and the laterality of the hydrogel spacer affected the reduction in the rectal dose. The rectal dose can be further reduced by implanting a spacer on the caudal and prostate side.

SABR for High-Risk Prostate Cancer: A Prospective Multilevel MRI-Based Dose Escalation Trial

Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa. This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events. Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively. SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.

Radiotherapy-Induced Digestive Injury: Diagnosis, Treatment and Mechanisms.

Radiotherapy is one of the main therapeutic methods for treating cancer. The digestive system consists of the gastrointestinal tract and the accessory organs of digestion (the tongue, salivary glands, pancreas, liver and gallbladder). The digestive system is easily impaired during radiotherapy, especially in thoracic and abdominal radiotherapy. In this review, we introduce the physical classification, basic pathogenesis, clinical characteristics, predictive/diagnostic factors, and possible treatment targets of radiotherapy-induced digestive injury. Radiotherapy-induced digestive injury complies with the dose-volume effect and has a radiation-based organ correlation. Computed tomography (CT), MRI (magnetic resonance imaging), ultrasound (US) and endoscopy can help diagnose and evaluate the radiation-induced lesion level. The latest treatment approaches include improvement in radiotherapy (such as shielding, hydrogel spacers and dose distribution), stem cell transplantation and drug administration. Gut microbiota modulation may become a novel approach to relieving radiogenic gastrointestinal syndrome. Finally, we summarized the possible mechanisms involved in treatment, but they remain varied. Radionuclide-labeled targeting molecules (RLTMs) are promising for more precise radiotherapy. These advances contribute to our understanding of the assessment and treatment of radiation-induced digestive injury.

The Feasibility of Haar Feature-Based Endoscopic Ultrasound Probe Tracking for Implanting Hydrogel Spacer in Radiation Therapy for Pancreatic Cancer.

PurposeWe proposed a Haar feature-based method for tracking endoscopic ultrasound (EUS) probe in diagnostic computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans for guiding hydrogel injection without external tracking hardware. This study aimed to assess the feasibility of implementing our method with phantom and patient images.Materials and MethodsOur methods included the pre-simulation section and Haar features extraction steps. Firstly, the simulated EUS set was generated based on anatomic information of interpolated CT/MRI images. Secondly, the efficient Haar features were extracted from simulated EUS images to create a Haar feature dictionary. The relative EUS probe position was estimated by searching the best matched Haar feature vector of the dictionary with Haar feature vector of target EUS images. The utilization of this method was validated using EUS phantom and patient CT/MRI images.ResultsIn the phantom experiment, we showed that our Haar feature-based EUS probe tracking method can find the best matched simulated EUS image from a simulated EUS dictionary which includes 123 simulated images. The errors of all four target points between the real EUS image and the best matched EUS images were within 1 mm. In the patient CT/MRI scans, the best matched simulated EUS image was selected by our method accurately, thereby confirming the probe location. However, when applying our method in MRI images, our method is not always robust due to the low image resolution.ConclusionsOur Haar feature-based method is capable to find the best matched simulated EUS image from the dictionary. We demonstrated the feasibility of our method for tracking EUS probe without external tracking hardware, thereby guiding the hydrogel injection between the head of the pancreas and duodenum.

Effect of Hydrogel Rectal Spacer on Intrafraction Prostate Motion During Radiotherapy of Prostate Cancer Patients

<h3>Purpose/Objective(s)</h3> Insertion of hydrogel rectal spacer may potentially stabilize the prostate by reducing intrafraction prostate motion. The purpose of this study was to investigate the effect of hydrogel rectal spacer on intrafraction prostate motion. <h3>Materials/Methods</h3> A retrospective review was conducted of prostate cancer patients treated from September 2015 to November 2018 who underwent external beam radiation therapy (EBRT) with intrafraction motion management using implanted electromagnetic transponders. There were 87 patients (73%) who received conventional fractionation, 16 (13%) moderate hypofractionation, 10 (8%) stereotactic body radiation therapy (SBRT) and 7 (6%) EBRT plus brachytherapy. The threshold for gating was set at 4 mm for conventional fractionation, 3 mm for moderate hypofractionation, and 2 mm for SBRT. Maximum prostate motion was measured by displacement outside of the gating threshold during treatment per fraction. Independent samples t-test was performed to compare prostate motion with and without hydrogel rectal spacer. <h3>Results</h3> We identified 120 patients with a total of 4447 fractions eligible for analysis. 49 patients (41%) were treated with hydrogel spacer and 71 (59%) without hydrogel rectal spacer. Mean displacement of prostate outside of the gating threshold was 4.9 mm (range, 2.1 – 12.8) and 5.6 mm (4.1 – 14.6) anteriorly, 2.6 mm (1.1 – 7.6) and 19.4 mm (4.0 – 25.8) posteriorly, 4.7 mm (2.2 – 8.3) and 12.5 mm (4.0 – 20.8) superiorly, 3.1 mm (1.1 – 8.2) and 14.2 mm (3.7 – 22.7) inferiorly, 4.3 mm (3.0 -12.4) and 4.5 mm (4.2 -7.6) left and 3.1 mm (3.1 – 4.1) and 4.3 mm (4.1 – 11.6) right for patients treated with and without hydrogel rectal spacer, respectively. There was a significant reduction of mean displacement in the posterior (2.6 mm vs. 19.4 mm, <i>P</i> = 0.04) and inferior direction (3.1 mm vs. 14.2 mm, <i>P</i> = 0.04) in patients with hydrogel rectal spacer compared to those without hydrogel rectal spacer during "beam on time". <h3>Conclusion</h3> The use of hydrogel rectal spacer can mitigate intrafraction prostate motion in posterior and inferior directions, suggesting a potential dosimetric advantage with the use of hydrogel rectal spacer. However, longer follow-up may be needed to confirm whether this translates into significant clinical benefit outweighing potential risk.