Low Dose Rate Research Articles

PO02: Survey of Radiotherapy Technologists on Their Attitude and Involvement in Brachytherapy in India

<h3>Purpose</h3> Radiotherapy Technologists (RTTs) in India are mostly involved in external beam radiation therapy (EBRT) treatments. Their involvement in brachytherapy is relatively less. The aim of this study was to study the level of awareness, their attitude, interest and involvement in the practice of brachytherapy in India. <h3>Material and Methods</h3> A web based 22-points questionnaire (Fig. 1) was designed for the survey of RTTs. (https://docs.google.com/forms/d/e/1FAIpQLSd9EejaRj9m_GtcBKRotr4hMLtu1fuSD2vJBAnNuCQ6Xw8wNg/viewform?usp=sf_link). The questionnaire was e-mailed to participants in December 2021 and a 3 months time period was given to submit responses. The multiple choice questions (MCQs) format was used in the questionnaire and each question had 2-5 choices depending upon the nature of question. It included questions related to the level of awareness, the attitude, interest and involvement in the practice of brachytherapy. One of the questions (Question no-22) was descriptive type where the participants could give suggestions on how to improve their involvement in brachytherapy practice. The data provided by the respondents was analyzed statistically. <h3>Results</h3> Of a total of 220, 106 responded to the survey (response rate: 48%). Fifty nine of the respondents belonged to academic institutions (65%) while 47 belonged to non-academic and other types of institutions. Eighty-nine respondents (83%) claimed to have one or more brachytherapy units in their centers. Seventy percent had high dose rate (HDR), 2% -low dose rate (LDR), 6% had both LDR and HDR systems. Remote after loading was the most common mode of treatment (77%).Of all the eighty-nine respondents that had brachytherapy available at their centres, only 59 (56%) were involved in different phases of brachytherapy treatment. Forty-three (45%) were actively involved in both the phases (i.e., simulation and treatment delivery) while rest were either involved in imaging only (26%) or treatment delivery only (7%).Seventy-one RTTs (68%) felt that their current knowledge is adequate to work as brachytherapy technologist. Seventy-eight percent expressed their willingness to work in brachytherapy. Sixty-three (68%) RTTs attributed their non-involvement to the departmental policies and 13% to the lack of awareness and interest. Sixty-five percent RTTs felt that brachytherapy is being represented well in the academic meeting but 42% expressed the need of more awareness programs. Thirty-five percent respondents suggested that improved curriculum at training level can enhance their involvement in brachytherapy practice. Majority (89%) of the respondents are not involved in any kind of research in brachytherapy. In response to descriptive type question no: 22, shortage of staff was cited as one of the reasons for less involvement. <h3>Conclusion</h3> The survey emphasized that majority of RTTs in India have adequate level of knowledge about brachytherapy. However, despite interest, their involvement in brachytherapy practice is significantly low due to their departmental policies and shortage of staff. This could be improved by addressing these factors.

PSOR6 Presentation Time: 11:55 AM: A Scoping Review of Immune Changes After Prostate Brachytherapy

<h3>Purpose</h3> Prostate brachytherapy (BT), with either low-dose-rate (LDR) or high-dose-rate (HDR), delivers a highly conformal and heterogeneous dose, allowing for dose escalation beyond external beam radiotherapy (EBRT). Whether this different dose deposition results in opportunistic biological changes that could be harnessed to improve outcomes is not well studied. Given the increasing interest in incorporating immunotherapy into prostate cancer treatment, we sought to investigate the impact of prostate BT on the immune system. <h3>Materials Methods</h3> A scoping review was performed using PubMed and Scopus for papers published between 2011-2021. Search terms used were "brachytherapy" AND "immune" AND "prostate". A total of 62 records were identified. After review, 6 studies were identified for review that included information an immune assessment on patient samples (tissue and/or blood) after prostate BT. <h3>Results</h3> 2 LDR studies (N=68) evaluated changes in the peripheral blood following I-125 BT monotherapy. Both studies demonstrated significant increases in peripheral CD3+ T cells and CD4+ T cells post-BT. However, increased circulating CD8+ T cells were observed in only one study. One study also demonstrated significant increases in Treg subsets up to 150 days post-treatment, which may be compensatory to increased cytotoxic T cell titers. 4 HDR studies (N=37) were identified (HDR fraction sizes 10-15 Gy), and all were done in combination with EBRT. Androgen deprivation therapy was included, for select patients, and one study included nivolumab. Three looked at changes in tissue immune infiltrates seen in post-BT biopsies and 1 looked at changes in both tissue and blood. The largest study (N=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature, when comparing a pre-BT biopsy to a biopsy done prior to HDR fraction 2. In another study (N=6) a significant correlation between increased pathologic response (no tumor in ≥ 4/6 cores) and increased CD4+ and CD8+ T cells in prostate tissue as well as CD4+ T cells in the blood was seen (p values not reported). Tumor infiltrating lymphocyte recruitment may be context dependent given a case report demonstrated decreased T cell infiltration post BT+EBRT. Finally, in a separate study (N=6), peripheral blood analysis demonstrated increased CD8+ T cells with an activated phenotype, decreased CD4+/CD8+ T ratio, decreased CD4+ helper T cells, and increased CD4+PD1+ cells at 3 months post-treatment when compared to baseline levels EBRT. Patients with PSA<0.02 at 3 months were also more likely to have increased CD4+ PD1+ T cells. <h3>Conclusion</h3> Both LDR and HDR BT can invoke an immune activating phenotype in prostate cancer; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to better promote synergy between these changes and improving clinical outcomes.

PO48 Presentation Time: 10:00 AM: Clinical Implementation of an In-House Made Perineal Template for Low Dose Rate Prostate Brachytherapy Treatment

<h3>Purpose</h3> An in-house perineal needle-template device was developed to improve the interactive¹ low-dose-rate (LDR) brachytherapy treatment planning process for patients with small prostate volume size. One of the side effects of external beam radiation and androgen deprivation therapies is the significant reduction of the prostate gland volume (target) which can be challenging to plan with a standard 5mm hole spacing template. The new perineal needle template (new template) has additional rows with holes placed in a 2.5mm off-set grid pattern which provided more hole locations to place seeds inside the small prostate periphery region for a more conformal plan while meeting all dosimetric planning goals. <h3>Methods and Materials</h3> Thirty patients with different prostate gland volumes size were selected for this study. These thirty patients received either external beam radiation alone or external radiation combined with androgen deprivation therapy. Patients had LDR interactive planning performed using the new template, BARD I-125 seed model STM1251 (USA, IL), BARD QuickLink Delivery System for the seed train assembly, Oncentra - Prostate (Elekta, Sweden) for the treatment planning software (TPS) and the B-K Medical Ultrasound 3000 (USA, MA) for the internal organs imaging. On implant day (DAY 0), the radiation oncologist (physician) contoured target, urethra and rectum on TPS. The medical physicist proceeded to start the planning on the TPS using the inverse planning option to create plan and dose volume histogram (DVH) as the first iteration. Then, manually adjusted and customized the seeds locations with the MD input for a final DVH evaluation in order to proceed and deliver the implant. The AAPM TG-64² dosimetric guidelines were followed and reported. All patients had CT and MRI imaging studies performed approximately 30 days after the implant for a DAY 30 post implant evaluation. Using the Oncentra TPS, both imaging studies were fused, and the prostate, urethra and rectum were contoured. The implanted seeds were registered, and the DAY 0 prescription was used for the post-plan evaluation following the AAPM TG-64 dosimetric guidelines. <h3>Results</h3> Thirty patients were successfully treated using the new template. The new template was modeled in TPS and the ultrasound system. The new template did not affect the calculating time in the TPS and the increased amount of hole locations provided more options for an easier manual optimization "tweaking" to achieve a final plan, especially in the apex location where the target tapers down in size. Initially, physician adaptation to the new template was challenging for the first few cases but rapidly improved as the physician became more familiar with the new hole patterns. <h3>Conclusion</h3> We have successfully designed, built and implemented a new template for brachytherapy LDR treatments of small sizes targets (≤20 cc). The new template has provided a viable option to implant the seeds inside or closer to the target periphery thus improving the interactive planning process significantly.

PO51 Presentation Time: 10:00 AM: Permanent I-125 Seeds Prostate Cancer Mono-Brachytherapy: Outcomes in 273 Patients

<h3>Purpose</h3> Report outcomes of patients undergoing I-125 seeds permanent low-dose-rate (LDR) mono-brachytherapy (mBT) in terms of OS, biochemical failure-free survival (BFFS), recurrence-free survival (RFS) and GU-GI toxicities in localized prostate cancer (LPC). <h3>Materials and Methods</h3> Between 2001 and 2015, 273 patients, undergoing I-125 LDR mBT with no prior curable treatment, with a prostate volume (pV) ≤50cc, cT1 à cT2c (NCCN classification) et iPSA ≤ 20 ng/ml were included and examined. <h3>Results</h3> With a median followup of 68 months, a biochemical failure occurred in 8 patients (4%) patients. The 5 and 8y-BFFS, defined by the Phoenix criterion, were 98.2% and 88.9%, worse for intermediate risk (IR) as compared with low risk (LR), with a 8y-BFFS of 85.7% and 91.5% respectively (p-value=0.01). The 8y-RFS were 96% and 90% for LR and IR respectively. The only factor statistically significant on OS was the age ≤ 65y with a 5 and 8y-OS of 93%/83% vs 89%/73% for ≤ 65y or >65y patients (p-value: 0.031). Surprisingly, we found in a sub-group analysis that 8y-OS for Gleason score 7 disease (GS 4+3 or 3+4) was higher than ≤ Gleason score 6 (83% vs 62%). No difference in outcomes between IR vs LR and ≤ 65y vs >65y patients was observed in terms of 8y-distant metastasis-free survival (DMFS) and prostate cancer specific survival (pCSS). The toxicity profiles suggested, from a follow-up of at least 2 years, that ≥ G3 urinary, GI and sexual toxicities were 5.5%,0.7%, 0% respectively. <h3>Conclusion</h3> I-125 permanent seeds LDR mBT provided excellent outcomes in this study. 8y-local recurrence was 6.5%. Therefore, LDR brachytherapy can be considered and still proposed as an effective treatment option for IR and LR LPC patients.

Sunday, June 19, 202210:00 AM - 10:15 AMPO47 Presentation Time: 10:00 AM: Dose Distribution of Permanent Interstitial Brachytherapy (Iodine-125) in Comparison to Temporary Interstitial Brachytherapy (Iridium-192) with a Hydrogel Spacer for Prostate Cancer

<h3>Purpose</h3> Brachytherapy (BT) for prostate cancer can be applied as permanent interstitial brachytherapy BT (LDR, low dose rate) and temporary interstitial brachytherapy BT (HDR, high dose rate), applied also alternatively in many centers. The aim of the study was to analyze the dose distribution in- and outside the prostate. <h3>Methods</h3> The intraoperative dose distribution of 102 LDR-BT patients was compared with the dose distribution of 109 HDR-BT patients (232 HDR-BT fractions). A hydrogel spacer (HS) (10ml) was only applied before HDR-BT. For the analysis of the dose coverage outside the prostate, a 5mm margin was added to prostate volume (PV+). Prostate V100 and V150 denote the PV covered by 100% and 150% of the prescription dose, while prostate D90 and urethra D30 denote the minimum dose in 90% of the PV and 30% of the urethral volume. <h3>Results</h3> The comparison of volume and dose values is shown in the table. HDR-BT patients had on average a slightly larger PV, but considerably larger PV+. The only not significantly different value comparing both methods was prostate V100. LDR-BT was characterized by a considerably more inhomogeneous dose distribution and higher doses to the urethra. However, the minimum dose in 90% of PV+ was lower. As a consequence of the HA in HDR-BT patients, the dose to the rectum was considerably lower. <h3>Conclusion</h3> In comparison to HDR-BT, LDR-BT is characterized by a more inhomogeneous dose inside the prostate, a higher dose to the urethra and a slightly less steep dose drop-off around the prostate. The dose to the rectal wall can be considerably reduced applying the HS.

MSPP06 Presentation Time: 4:50 PM: Price Availability for Prostate Brachytherapy, External Beam Radiation Therapy, and Radical Prostatectomy

<h3>Purpose</h3> For patients with low to favorable-intermediate risk prostate cancer (PC), management with active surveillance, radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT) are all National Cancer Center Network-supported monotherapy options. Because therapy is non-urgent and choosing between these options can be complex, patients routinely seek second opinions. Expectedly, the cost of therapy can be an important consideration. Recent federal price transparency (PT) guidance requires hospitals to provide payer-negotiated prices for at least 300 common services in a "shoppable," user-friendly, online format. Seventy services, including RP, are specified, while the remainder are left to the discretion of each institution. Even though there is equipoise between radiation therapy (RT, inclusive of EBRT and BT) and RP in definitive treatment for PC, inclusion of prices for RT is optional. National Cancer Institute (NCI)-designated cancer centers (NCI-CC) are referral centers catering to high volumes of patients with cancer. Although NCI-CC have the option to volunteer prices for RT, the rate at which these institutions choose to report payer-negotiated price estimates for prostate-directed RT is unknown. We hypothesize that reporting rates for BT and EBRT may substantially trail rates of mandatory price reporting for RP. <h3>Materials and Methods</h3> Through online query, we identified "shoppable" price tools for NCI-CC in December 2021. Using Current Procedural Terminology billing codes and keyword searches, we queried these price tools for cost estimates for RP, EBRT (delivered using intensity modulated radiation therapy), and BT. Both high dose rate (HDR) and low dose rate (LDR) BT were considered. NCI-CC were stratified by Medicare Prospective Payment System(PPS)-exempt status; these 11 NCI-CC are exempt from standard Medicare fee for service reimbursement caps. Descriptive statistics, include frequency counts and proportions, were performed. The rate of reporting of "shoppable," negotiated prices for each therapy was assessed. These rates were compared using the chi-squared test at a significance level of α=0.05. <h3>Results</h3> Of the 63 NCI-CC offering clinical care, 58 (92%) published "shoppable" tools. Seven (11%), 6 (10%), and 51 (81%) published "shoppable" prices for BT, EBRT, and RP, respectively (Figure 1), translating to a significantly higher rate of publication of prices for RP than for EBRT or BT (<i>P</i> < 0.001). All of the published prices for BT were for HDR-BT and none were for LDR-BT. PPS-exempt cancer hospitals had the highest rates of reporting "shoppable" prices at 91%, with 64%, 27%, and 36% including prices for RP, EBRT, and BT, respectively. <h3>Conclusions</h3> Under current federal guidance, patients with PC can obtain online payer-negotiated price estimates for BT and EBRT from just roughly 10% of NCI-CC, while price estimates for RP are offered by more than 80% of these institutions. For patients with PC, this represents a potential obstacle to informed decision making, undermines the stated goals of US PT health policy, and the impact of this unintended effect of PT laws on BT utilization rates (or patient choice of therapy) is unknown. Moving forward, mandating the inclusion of common radiotherapy services (EBRT and BT) in "shoppable" price tools is a straightforward intervention that may be highly beneficial to this patient population.

MSS12 Presentation Time: 4:40 PM: A Proposed Formalism for Postoperative Dosimetry Evaluation for Permanently Implanted Collagen Tile Embedded Cs-131 Brachytherapy in the Brain

<h3>Purpose</h3> To propose a standardized formalism for delineating target volume contours and evaluating dose on postoperative imaging for patients receiving permanent low dose rate (LDR) brachytherapy (BT) in the brain. The BT applicator considered for this work consists of a 20 × 20 × 4 mm collagen tile embedded with four 3.5 U Cs-131 seeds with a 10 mm inter-seed spacing (GammaTile®, GT Medical Technologies, USA). Following maximum safe resection, multiple tiles are used to line the cavity and deliver a nominal dose of 60 Gy to a depth of 5 mm from the operative bed surface. The tiles are designed to limit the maximum dose to brain tissue via a 3 mm seed offset from brain surface that functions as an implanted internal compensator (Fig 1A). <h3>Materials and Methods</h3> Collagen tiles are placed by neurosurgeons under surgical visualization on resection the surfaces suspected to harbor subclinical disease; in this setting the Clinical Target Volume (CTV) is defined as the region of parenchyma adjacent to tile placement to a depth of 5 mm. As illustrated in Fig 1B-D, the algorithm proposed to generate a CTV is): 1) outline the brain, 2) outline all seeds using a Hounsfield Unit-based threshold tool, 3) expand the seed contour by 3 mm to approximate the tile/brain interface, 4) outline the cavity visualized on a registered MRI using the seeds+3 mm contour as a guide, 5) use a Boolean operation to obtain the intersection of the cavity contour expanded by 5 mm, the seed contour expanded by 0.94 mm, and the brain contour, and 5) subtract the cavity. Manual adjustments to ensure only areas with suspected subclinical disease may be required. Postoperative dose was calculated as per the AAPM TG43 3D formalism using the consensus dataset for the Cs-131 seed model utilized in the GammaTile device. Dose statistics pertaining to the CTV, including the mean isodose values covering 90% and 95% of the volume (D90% and D95%), the volume receiving at least 90% and 95% of the prescription 60 Gy (V90% and V95%), minimum dose, and maximum dose were tabulated for 11 patients using a commercial Treatment Planning System (MIM, MIM Software, USA). <h3>Results</h3> Volumes (cc) of cavity contours across all patients ranged from 3.3 to 49.9 and the CTVs ranged from 6.9 to 27.1. Mean D90% and D95% (Gy) to the CTV was 55.8 (45.5 - 73.8) and 49.4 (36.3 - 67.1), respectively. Mean V90% and V95% (% of total volume) to the CTV was 88.7 (77.6 - 99.8) and 85.5 (72.6 - 99.4), respectively. Mean minimum and maximum doses (Gy) to the CTV were 36.3 (19. - 64.7) and 426.3 Gy (265.6 - 573.9), respectively. Note, the maximum dose to the <i>cavity</i> is not accurately calculated by the TPS but is estimated to be in the range of 800 - 1500 Gy, indicating the tiles reduce maximum dose to brain by ∼28-53%. <h3>Conclusions</h3> A formalism to 1) generate a CTV representing brain containing subclinical disease following gross tumor resection and collagen tile BT implant and 2) obtain dose statistics is proposed. The contouring algorithm utilizes the surgical cavity (well-seen on MRI), LDR seeds (placed with direct surgical guidance, and well-seen on CT) and Boolean operations, resulting in a straightforward and reproducible CTV. The proposed dose statistics (D90%, D95%, V90%, V95%, min, and max) proved to be useful metrics for dose review. The standardized formalism for contouring CTV and its use in dose evaluation will be further tested to determine its utility in minimizing interobserver variability. Once fully validated, this formalism will be used to generate recommendations for quantitative evaluation GammaTile implant dosimetry.

PO49 Presentation Time: 10:00 AM: Prevalence of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy

<h3>Purpose</h3> QTc has been associated not only with a higher risk of Torsade de Pointes (TdP), sudden cardiac arrest but also with general cardiac mortality, including cardiovascular and coronary death. We examined the prevalence of prolonged QTc interval in prostate cancer patients undergoing brachytherapy in general and in patients with more aggressive cancers who may be exposed to ADT and compared them to patients who underwent prostatectomy. <h3>Materials and Methods</h3> We randomly selected 1094 patients treated with either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy between August 2010 and February 2022 from our internal database. All patients had an ECG as part of the preoperative work-up. The QTc was automatically calculated using the Bazett formula. Excluded were patients with left or complete bundle branch block, ventricular extrasystoles, atrial fibrillation, presence of a pacemaker or a QRS ≥ 120 ms. .As primary outcome, a QTc ≥450ms was considered abnormal. Chi-square or Fisher's exact test, when appropriate was used to compare groups. Pearson correlation coefficient and binary multivariable regression analysis was used to evaluate correlations between QTc and clinical values. <h3>Results</h3> A total of 6.2% (n=68) had a QTc ≥450ms. Patients with a Cancer of the Prostate Risk Assessment (CAPRA) high risk disease (score 6-10) were significantly more likely to have a QTc ≥450ms than patients with low-or intermediate risk (9.7% vs. 5.5%, p=0.039). QTc as a continuous variable correlated weakly with the neutrophil count (r=0.13, p<0.001), age (r=0.08, p=0.009) and inversely with testosterone (r=-0.17, p=0.002). On binary multivariable regression analysis including neutrophils, testosterone and age, only testosterone [nmol/L] was predictive of a QTc ≥450ms, OR 0.9, 95% CI 0.82-0.98, p=0.02. We then compared the patients treated with brachytherapy to 178 patients who underwent prostatectomy. The latter had a non-significantly smaller portion of patient with a QTc ≥450ms: 4.5% vs. 6.2%, p=0.5. <h3>Conclusions</h3> Our data show that about 10% of patients with high-risk prostate cancer are at increased risk of TdP. Treating physicians should be aware of this and monitor the QTc during ADT to possible decrease cardiac mortality in these patients who require ADT. The correlation between increasing age, neutrophil count and low testosterone with QTc prolongation links inflammation and hypogonadism.

PP06 Presentation Time: 9:50 AM: Biochemical Failure-Free Survival Rates After Brachytherapy with I-125, Pd-103, or Cs-131 for Intermediate-Risk Prostate Cancer: Phase II Trial

<h3>Background</h3> Iodine (I)-125 is traditionally used for low-dose-rate (LDR) brachytherapy for prostate cancer, but emerging data support the use of cesium (Cs)-131 or palladium (Pd)-103 as well. Although the safety and effectiveness of these three isotopes for intermediate risk prostate cancer have been established, the relative efficacy of each is unknown. <h3>Purpose</h3> To compare biochemical outcomes after I-125, Pd-103, or Cs-131 brachytherapy as definitive treatment for intermediate-risk prostate cancer. <h3>Materials and Methods</h3> This prospective phase II trial evaluated ultrasound-guided LDR brachytherapy monotherapy as definitive treatment for intermediate-risk prostate cancer at a single institution in 2006-2013. The choice of isotope and corresponding prescribed dose was made sequentially (starting with I-125, D=144 Gy; followed by Pd-103, D=125 Gy; then Cs-131, D=115 Gy. Patients had intermediate-risk disease (Gleason score [GS] 6 or 7 [3+4 or 4+3]), no evidence of nodal or metastatic disease, and no prior hormonal or radiation therapy. Follow-up visits were every 4 months for the first year after the implant, every 6 months for the next 5 years, and yearly thereafter, with prostate-specific antigen (PSA) levels measured at each visit. Biochemical failure (BCF) was defined per the Phoenix criteria as an increase in PSA value to nadir +2 ng/dL or radiologic or histologic evidence of recurrence with increasing PSA value. Patients were considered to have no evidence of disease (NED) if the PSA was <0.2 ng/dL at the specified time. Treatment efficacy was defined as time to BCF and the presence or absence of NED at a given time. Kaplan-Meier analysis was used to estimate BCF-free survival rates by isotope, with between-group differences assessed with log-rank tests. One-way analysis of variance was used to compare time to BCF between groups. Simple linear regression was used to determine the influence of isotope on achieving NED. <h3>Results</h3> Of the 300 patients in this trial (median age 64.9 years), 100 were treated with Cs-131, 98 with I-125, and 102 with Pd-103. Eleven patients (3.7%) had GS 6 disease, 236 (78.7%) had GS 7 (3+4) disease, and 53 (17.7%) had GS 7 (4+3) disease; 195 (65.0%) had favorable intermediate-risk, and 105 (35.0%) had unfavorable intermediate-risk disease. The median follow-up time was 8.7 years. During follow-up, 27 patients (9.0%) experienced BCF, 7 (7%) in the Cs-131 group, 13 (13.3%) in the I-125 group, and 7 (7.1%) in the Pd-103 group. Among those 27 patients with BCF, 10 (37.0%) received salvage therapy with surgery, brachytherapy, radiation therapy, or cryotherapy. The BCF-free survival rates were 93% for those treated with Cs-131, 86.7% for I-125, and 93.1% for Pd-103 (p=0.86) (Figure); the median time was not reached because of the short follow-up and the limited number of events. Follow-up data were available for 101 patients at 8.7 years; 100 patients (99%) had NED. Although 36 patients (12%) died during the study, only 1 death (0.3%) was related to prostate cancer. <h3>Conclusions</h3> No significant differences in efficacy were found among Cs-131, Pd-103, and I-125 for LDR brachytherapy monotherapy for intermediate-risk prostate cancer. The choice of isotope should be based on dosimetric advantages, estimated risk of toxicity, and quality-of-life profile. A larger randomized trial is needed to assess potential differences in efficacy among isotopes.

EP016 - Re-irradiation for recurrent prostate cancer after low dose rate brachytherapy: A new option of care?

EP016 - Re-irradiation for recurrent prostate cancer after low dose rate brachytherapy: A new option of care?

PP11 Presentation Time: 11:10 AM: Assessment of Brachytherapy-Induced Prostate Edema on Post-Implant Dosimetric Analysis in MRI-Assisted Radiosurgery

<h3>Purpose</h3> Prior studies have shown that brachytherapy-induced prostate edema (PE) results in altered target dose coverage on post-implant CT dosimetry in prostate cancer patients treated with low dose rate brachytherapy (LDR). The pre-plan target volume (PTV) accounts for PE by adding 1-5mm margins to the prostate for calculation of the goal dose coverage on the day of the implant (day zero, D0). However, visualization of PE on CT is limited, diminishing PE measurement accuracy. MRI-based LDR (MRI-assisted radiosurgery, MARS) improves accuracy through better delineation of target, normal structures, and seeds compared to CT. Thus, MARS may improve the accuracy of PE measurements. We investigated PE using MARS to analyze its effect on D0 dosimetry and determine if current pre-plan PTV margins are adequate in all isotopes. <h3>Materials and Methods</h3> We identified 346 patients with low to intermediate-risk prostate cancer treated with Cesium-131 (Cs-131, 15 [4.3%] patients, prescription dose (PD)=115 Gy), Iodine-125 (I-125, 83 [23.9%] patients, PD=144 Gy), or Palladium-103 (Pd-103, 248 [71.7%] patients, PD=125 Gy) MARS as definitive LDR from 2016-2021. Patients treated with hormone therapy, as a boost with external-beam RT, or for salvage were excluded. Implants were pre-planned using MRI (MIM Symphony treatment planning system) and our published nomograms verified the activity per volume within 5%. PE was measured as the change in prostate volume from the pre-plan to D0 based on physician contours. Post-implant dosimetry was performed using MRI on D0. Treatment characteristics, including pre-plan and D0 prostate volumes, prostate volumes receiving 100%, 150%, and 200% of the PD (V₁₀₀, V_150, V₂₀₀), percent of the PD going to 90% of the prostate volume (D₉₀), rectum volume receiving 100% of the PD (V₁₀₀), and external urethral sphincter (EUS) volume receiving 200% of the PD (V₂₀₀), were extracted from MIM. Simple linear regression with Pearson's correlation analysis was used to assess the effect of PE on post-implant D0 prostate V₁₀₀, V₁₅₀, V₂₀₀, and D₉₀, rectum V₁₀₀, and EUS V₂₀₀. Ordinary one-way ANOVA analysis was used to compare PE between categorical variables. <h3>Results</h3> Median age at diagnosis was 63 years. Median PSA at diagnosis was 6. 24 (6.9%) patients had GS 6 and 322 (93.1%) had GS 7. On the pre-plan, 55 (15.9%) patients had a prostate size of 0-20 ccs, 222 (64.2%) had 20-40 ccs, 63 (18.2%) had 40-60 ccs, 6 (1.7%) had 60+ ccs. On D0 analysis, the median [IQR] change in prostate volume was +28% [15-42%] as compared to the pre-plan. There was no significant difference in magnitude of PE by isotope (median change in prostate volume: +22.6% for Cs-131, +27.3% for I-125, +29.5% for Pd-103, p=0.33). There was no difference in PE by increasing number of needles (R²=0, p=0.70). PE decreased with increasing pre-plan prostate size (R²=0.05, p<0.001). Greater PE was associated with decreased post-implant D0 V₁₀₀ (<b>Graphic</b>, R²=0.08, p<0.001), V₁₅₀ (R²=0.03, p<0.001), and D₉₀(R²=0.12, p<0.001); there was no association with D0 V_{200 (}R²=0.01, p=0.06). Greater PE was associated with decreased D0 rectum V₁₀₀ (R²=0.02, p=0.02) and trended toward decreased EUS V₂₀₀ (R²=0.01, p=0.05). <h3>Conclusions</h3> MARS confirmed that patients undergoing LDR experienced PE. PE was uniform between isotopes, supporting the use of the same pre-plan PTV margins among isotopes. There was decreased D0 prostate V₁₀₀, V₁₅₀, and D₉₀ in patients with greater PE. We suggest pre-plan PTV margins as follows: 3mm laterally, 2mm anteriorly/cranially/caudally, and 0mm posteriorly. These PTV margins can help ensure adequate D0 dosimetry. <b>Graphic:</b> Correlation of post-implant D0 prostate V₁₀₀ with the magnitude of prostate edema (PE). PE was calculated as the percent change in prostate volume from the pre-plan to post-implant D0.

Detection accuracy of I-125 seeds and needle tips, in MRI prostate tissue mimicking material: Phantom design, fabrication, and testing

• Novel phantom design provides a method of verifying geometric brachytherapy seed and needle tip positions in MRI. • Tests clinically relevant arrangements for seed placements in T1 MRI sequences within prostate tissue mimicking material. • Tests performed with Nitinol needles. • Demonstrates challenges meeting the required accuracy of seed and needle tip detection for brachytherapy in MRI. • Identifies seed placements to be avoided to improve overall accuracy in seed localisation. Accurately identifying needle tip and seed positions for low dose rate prostate brachytherapy on MRI images is challenging. Uncertainties in locating needle tip positions can lead to misplacement of seeds compared to planned coordinates. Furthermore uncertainty in establishing true seed positions on the images, leads to uncertainty in the dose distributions. In this study, a novel phantom has been designed for the analysis of I-125 seed and needle tip detection and tip image distortion. The phantom utilises a gel that mimics prostate tissue in MRI, to evaluate the uncertainty in establishing seed and needle tip positions. Reults are reported for the IsoSeed (Bebig) source, in clinically relevant seed arrangements, and for a novel nitinol needle. The choice of MRI sequence impacts the accuracy of detecting the needle tips and seeds. This is most prevelant when the seeds are in clusters, at the boundary of the prostate and at 90˚ to the long axis of the scanner. Detected needle tip position, when the MRI metal artefact correction algorithm was used, was measured consistently inferior to the actual position (mean tip at -2.3 ± 1.5 mm (k = 2), p = 0.03). We have demonstrated the design of a phantom that can be used to quantitatively assess seed and needle tip positions simultaneously, to establish the accuracy of detection, or presence of artefacts on MRI.

A study on the influence of dose rate on total ionizing dose effect of anti-fuse field programmable gate array—The irradiation damage is attenuated at low dose rate

The TID (total ionizing dose) in-situ experiments of LC1020B, an anti-fuse FPGA (Field Programmable Gate Array) device, were designed and carried out under different dose rates, and the influence of dose rate on the TID effect of FPGA was studied. The experimental results show that: 1) the TID irradiation failure of the FPGA under different dose rates has nothing to do with the input voltage parameter exceeding the standard. 2) with the decrease of cobalt source irradiation dose rate [171, 26.83, and 2.68 mGy(Si)/s], the TID effect failure dose threshold [168, 229, and 334 Gy(Si), respectively] of the FPGA gradually increased, showing obvious attenuation of low dose rate damage. Theoretical analysis suggests that, compared with the space charge limitation effect, the oxide charge annealing effect plays a dominant role, and longer irradiation time is beneficial to the oxide charge annealing. And based on the experimental data, an FPGA TID analytical model with power consumption current as the damage characterization parameter is established, which lays a foundation for scientific evaluation of radiation effect of anti-fuse FPGAs.

BODY WEIGHT KINETICS OF F1 GENERATION IRRADIATED In-utero

To investigate radiation risks associated with a low dose and low dose rates, pregnant Swiss albino mice were exposed to 0.20 Gy, 0.40Gy and 0.80 Gy of gamma rays from a Cobalt-60 source at two different dose rates (0.0584 Gy/min and 0.00091 Gy/min) on 18-day post conception. Irradiated as well as control animals were allowed to reach term and to deliver normally. Post irradiation variations in the body weight of mice were studied in the F1 generation at 0 days and 1,2,3,4,5,6 and 12 weeks of postpartum age. Bodyweight at both and at different postnatal ages was found to be influenced by the exposure dose as well as by the dose rate. The higher the dose, the greater is the weight loss. Moreover, at different postnatal age’s body weight was less in the High dose rate (HDR) subgroup than in the Low dose rate (LDR) subgroup. This holds true for all the exposed dose groups. In all the dose groups ratio of LDR to HDR, values for the bodyweight revealed the following relation: 0.20 Gy &lt; 0.40Gy &lt; 0.80 Gy.

Combined Brachytherapy and Ultra-Hypofractionated Radiotherapy for Intermediate-Risk Prostate Cancer: Comparison of Toxicity Outcomes Using a High-Dose Rate (HDR) vs. Low-Dose Rate (LDR) Brachytherapy Boost

<h3>Purpose/Objective(s)</h3> Combined brachytherapy and external beam radiotherapy is an accepted treatment for unfavorable intermediate-risk and high-risk prostate cancer. We compared genitourinary and gastrointestinal toxicity of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy boost when combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT) for prostate cancer. <h3>Materials/Methods</h3> 99 intermediate-risk prostate cancer patients underwent UH-EBRT (5 Gy x 5) combined with brachytherapy HDR (n=59) or LDR (n=40) boost. HDR brachytherapy consisted of 15 Gy using Iridium-192, and LDR brachytherapy consisted of Palladium-103 seed implantation (prescription dose=100 Gy). Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3 months. Toxicity assessment included Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, International Prostate Symptom Score (IPSS), and bowel symptom assessment. Cumulative incidences were calculated for toxicity outcomes. Fisher exact tests were used to evaluate associations. <h3>Results</h3> Overall incidence of grade 2 genitourinary toxicity at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% versus 5.1%, and 55% versus 11%; p<0.001). No grade ≥3 or 4 toxicities were observed. On MVA, only treatment regimen (LDR versus HDR) was significantly associated with grade ≥2 genitourinary toxicity (p<0.001). Two patients had grade 2 rectal toxicity in each cohort. No grade ≥ 3 or 4 toxicities were observed. <h3>Conclusion</h3> Both LDR and HDR brachytherapy combined with UH-EBRT were associated with favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR compared with LDR brachytherapy.

A Randomized Phase III Trial Comparing Health-Related Quality of Life after Low Dose Rate (LDR) or High Dose Rate (HDR) Prostate Brachytherapy Boost Combined with External Beam Pelvic Radiotherapy (EBRT)

<h3>Purpose/Objective(s)</h3> This randomized phase III trial compared health related quality of life (HRQOL) in urinary, bowel, and sexual domains in men with intermediate (IR) and high-risk (HR) prostate cancer treated with combined EBRT and prostate brachytherapy (BT) using either LDR or HDR. <h3>Materials/Methods</h3> Eligible men receiving pelvic EBRT (46 Gy/23F) combined with prostate BT were randomized to either an LDR (110 Gy) or HDR (15 Gy) boost. HDRBT preceded EBRT by 1 week while LDRBT followed. Time 0 for QOL evaluations was day 1 of any radiotherapy. The Expanded Prostate Cancer Composite (EPIC) questionnaire was used to evaluate HRQOL q3 months for the first year, q6 months to 3 years and then annually. The Mann-Whitney U test was used to compare mean EPIC scores for urinary, bowel and sexual summary domains. <h3>Results</h3> From 01/2014 to 01/2020, 191 men were randomized: 42% IR and 58% HR. Median age was 71 years. T stage was T1c/T2a:34%, T2b:28%, T2c:24% and T3:13%. 57% had Gleason 7, 13% Gleason 8 and 30% Gleason 9. 74% received ADT with at least 3 months neoadjuvant and for a median duration of 12 mo. Median follow-up was 48 mo. HDR patients had higher (better) HRQOL urinary domain scores at 3 mo (79.0 vs. 69.4; p<.001) and 6 mo (84.0 vs. 76.9; p<.001), and higher bowel domain scores at 3 mo (87.0 vs. 82.1; p=.005) and 6 mo (88.7 vs. 82.8; p=.023). Better bowel domain scores were sustained at 24, 36, and 48 mo. In contrast, HDR patients had worse HRQOL urinary domain scores at 1 month (73.6 vs. 80.7; p=.003). There was no statistically significant difference in HRQOL sexual domain scores between the two arms. <h3>Conclusion</h3> The effect of HDRBT on urinary and bowel domains was evident 1 mo post implant but had recovered at 3 and 6 mo, while LDR patients were still experiencing significant QOL impact of their ongoing LDRBT. Although HDR patients sustained an advantage in long term bowel function compared to LDR, there was no difference in long term urinary QOL between the 2 types of BT after the acute phase subsided. The patient treatment experience of combined EBRT/BT is improved with HDR.

Prostate Brachytherapy Utilization in the COVID-19 Era: A Cross-Sectional Study of Radiation Oncologists in the United States

Purpose/Objective(s)Brachytherapy (BT) is indicated as monotherapy for lower risk prostate cancer (PC) or to boost external beam radiation therapy (EBRT) for higher risk disease. Despite its advantages, such as decreased treatment time and cost, BT utilization in the United States (US) is declining. We surveyed US radiation oncologists (ROs) to determine the proportion of providers who offer BT for PC, by risk group, and whether the COVID-19 pandemic influenced practice patterns. We hypothesized that rates of utilization would continue to lag EBRT.Materials/MethodsFrom July-October 2021, an anonymized survey was distributed to currently practicing US ROs. Demographic and practice characteristics were collected. Questions assessing utilization of BT and EBRT for patients of varying risk group and the effect of the pandemic on practice patterns were administered. The primary endpoint was the rate of BT utilization by risk group. Descriptive statistics were performed. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using 2-sided chi-squared tests (α=0.05).ResultsOf 203 respondents (72% male, 72% white, 53% non-academic, 69% >10 years in practice), 156 (77%) treated PC. For low (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) and favorable intermediate (FI) (37% total; 21% LDR, 10% HDR, 6% both) PC, BT was less commonly offered then stereotactic body (SBRT – 54% and 48%), moderately hypofractionated (MHFRT – 83% and 87%), and conventionally fractionated (CFEBRT – 37 and 38%) radiation therapy. For unfavorable intermediate PC, BT alone (7%) and BT+EBRT (37%) were less offered then moderately HFRT (82%) and CFEBRT (46%). For high and very high-risk PC, BT boost was not routinely offered (44% and 37%, respectively). For every risk group, academic ROs were more likely to offer BT (50-60% vs. 29-46%, all p < 0.05) (Table 1). For FI only, ROs treating both urban and rural patients were less likely to offer BT than those in an urban or rural setting (p=0.045). No other characteristics were associated with offering BT. <1% of respondents reported increased BT usage due to the pandemic.ConclusionDespite its advantages for patients, BT remains underutilized, particularly in non-academic settings, with <1/2 of surveyed ROs offering BT monotherapy for low to FI risk PC or to boost higher risk disease. Practice patterns were unaffected by COVID-19 likely due to barriers to starting a BT program. Provider retraining may be critical to increasing utilization rates.

A Proposed Formalism for Target Volume Delineation for Permanently Implanted Collagen Tile Embedded Cs-131 Brachytherapy in the Brain

<h3>Purpose/Objective(s)</h3> To propose and establish the utility of a standardized formalism for delineating target volume contours on postoperative imaging to evaluate dosimetry for patients receiving permanent low dose rate (LDR) brachytherapy (BT) in the brain. The BT applicator considered for this work consists of 4 mm thick collagen tiles embedded with evenly spaced 3.5 U Cs-131 seeds designed to deliver a nominal dose of 60 Gy to a depth of 5 mm from the operative bed surface. The tiles feature a designed seed offset from brain surface of 3 mm, introduced with the intention of reducing maximum dose to brain tissue. <h3>Materials/Methods</h3> Collagen tiles are placed by neurosurgeons under surgical visualization on the resection surfaces known or suspected to harbor subclinical disease; in this setting the Clinical Target Volume (CTV) is defined as the region of parenchyma adjacent to tile placement to a depth of 5 mm. The algorithm proposed to generate a CTV is: 1) outline the brain tissue, 2) outline all seeds using a Hounsfield Unit-based threshold tool, 3) expand the seed contour by 3 mm to approximate the tile/brain interface, 4) outline the cavity visualized on a registered MRI using the seeds+3 mm contour as a guide, 5) use a Boolean operation to obtain the intersection of the cavity contour expanded by 5 mm, the seed contour expanded by 0.94 mm, and the brain contour, and 5) subtract the cavity. Manual adjustments to ensure only areas with suspected subclinical disease may be required. For 11 patients, a commercial Treatment Planning System was used to generate CTVs, calculate implant dose distributions, and obtain CTV dose statistics. <h3>Results</h3> Volumes (cc) of cavity contours across all patients ranged from 3.3 to 49.9 and the CTVs ranged from 6.9 to 27.1. Mean isodose value (Gy) covering 90% of the CTV (D90%) was 55.8 (45.5 – 73.8) and 95% of the CTV (D95%) was 49.4 (36.3 – 67.1). Mean minimum and maximum doses (Gy) to the CTV were 36.3 (19. – 64.7) and 426.3 Gy (265.6 – 573.9), respectively. Note, the maximum dose to the cavity is not accurately calculated by the TPS but is estimated to be in the range of 800 – 1500 Gy, indicating the tiles reduce maximum dose to brain by ∼28-53%. <h3>Conclusion</h3> A formalism to generate a CTV representing brain containing subclinical disease following gross tumor resection and collagen tile BT implant is proposed. The contouring algorithm utilizes the surgical cavity (well-seen on MRI), LDR seeds (well-seen on CT) and simple Boolean operations, resulting in a straightforward and reproducible CTV structure. The corresponding dose statistics (D90%, D95%, min, and max) proved to be useful metrics for dose review. The proposed standardized formalism for contouring CTV and its use in dose evaluation will be further tested to determine its utility in minimizing interobserver variability to evaluate the dosimetry of collagen tile BT implants in brain.

Toxicity Outcomes at 18 Months for Cs-131 Low-Dose-Rate Prostate Brachytherapy Compared to I-125 and Pd-103

<h3>Purpose/Objective(s)</h3> Low dose rate prostate brachytherapy is an established component of definitive radiotherapy options for localized prostate cancer. As the utility of LDR brachytherapy (LDRB) has evolved, the focus has shifted to improving the side effect profile while maintaining oncologic outcomes. Most prior efficacy and toxicity data were gathered using I-125 and Pd-103, but due to the shorter half-life and slightly higher average energy of Cs-131, several institutions have adopted its use in an attempt to improve outcomes and decrease toxicity. To report the toxicity outcomes up to 18 months after Cs-131 LDR brachytherapy at our institution, compared to our experience with I-125 and Pd-103. <h3>Materials/Methods</h3> A retrospective review was performed on the first 50 patients treated with Cs-131 LDRB for localized prostate cancer at our institution. Patients receiving either a full or partial implant were included. Prescription doses of 100Gy and 80Gy were utilized, respectively. Patients receiving partial implants generally received 45Gy external beam radiotherapy starting 6-8 weeks after implant. Data regarding AUA prostate symptom score, sexual health inventory for men (SHIM) score, and RTOG GI toxicity score were assessed pretreatment, at 1 month, and at each subsequent follow up. Demographic and clinical data were also collected. The data was compared to cohorts of the last 50 patients treated I-125 and the last 50 patients treated with Pd-103, to standard doses. Descriptive statistics were used to summarize variables. A linear mixed model was used to compare means and to identify variables as prognostic for toxicity (p≤0.05). <h3>Results</h3> The mean AUA scores prior to brachytherapy were similar for patients in all groups (p=1.00), while at 1-month post-treatment, mean AUA score was significantly higher for patients treated with Cs-131 and Pd-103 compared to I-125 (p<0.001). Mean AUA scores were not significantly different at longer follow-up (p>0.50). The need for a catheter post-brachytherapy occurred in 8% of patients and was not associated with type of isotope on multivariate analysis (MVA). Prostate volume, numbers of seeds, and prostate D90% were significant predictors for the need for a catheter on MVA. The use of ADT and the total activity were significant predictors on MVA for a decrease in SHIM score over time. The type of isotope used did not predict for erectile dysfunction (ED) as measured by SHIM score on MVA. Overall rates of GI toxicity were low with only 3 patients developing RTOG grade 2 toxicity or greater without any obvious difference between isotopes. <h3>Conclusion</h3> In patients treated with Cs-131 or Pd-103 LDRB, acute GU side effects peaked higher at 1 month than with I-125, but rapidly decreased to similar levels with longer follow-up. The type of source used did not predict for need for catheterization, ED, or GI toxicity at any time point.

A Prospective Analysis of Toxicity Associated with Intraoperative, Real-Time Planned Low Dose Rate Brachytherapy or Intensity-Modulated Radiotherapy Boost for High/Intermediate Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> The ASCENDE-RT trial which used pre-planned brachytherapy boost (BT) reported worse treatment-related morbidity with BT vs dose-escalated intensity-modulated radiotherapy boost (DE-IMRT) for prostate radiation therapy (RT). However, toxicity is technique dependent and the outcomes of real-time intraoperative BT have not been well studied. We evaluate the toxicity profile of intraoperative, real-time planned BT vs DE-IMRT. <h3>Materials/Methods</h3> 402 patients treated from 2010-18 at our institution were included. Median dose for DE-IMRT was 79Gy. BT included IMRT to a median of 45Gy plus BT boost of 110 Gy. Patient-reported outcomes using the validated Prostate Cancer Symptom Indices and physician-graded CTCAE toxicity were prospectively collected from baseline to 2yrs post-RT. Clinically meaningful symptoms were defined as ≥Grade 2. Per institutional practice, an α-1 blocker is started prior to BT but not DE-IMRT boost. We report acute (0-6 months) & late (1 & 2yr) toxicity. Multivariable logistic regression calculated odds ratios (OR) for symptoms & controlled for hormone therapy, image guidance modality, risk category & age. <h3>Results</h3> At acute, 1-, & 2-yr time points 148, 108, 54 & 254, 214, 162 patients were available for BT & DE-IMRT analysis, respectively. Baseline and acute genitourinary (GU) or gastrointestinal (GI) symptoms did not differ between cohorts. For both modalities, PRO GI and GU symptom prevalence peaked acutely, declined over 1yr and returned near baseline by 2yrs (Table). At 2yrs, a difference in ≥Grade 2 CTCAE GU toxicity persisted (19% vs 2%, p = <0.001); urinary frequency (6% vs 0%, p = 0.02), & incontinence (9% vs 2%, p = 0.02) differed most. On MVA, BT had higher 2-yr GU symptoms for PRO (OR 32.0, 95%CI: 6.2-165, p < 0.0001) & CTCAE (2.2, 1.4-3.6, p = 0.0006). Cumulative incidence of CTCAE ≥Grade 3 events at 2yr were GU 3.4% vs 0%, p = 0.007 & GI 2.0% vs 2.0%, p = 1.0 for BT & DE-IMRT. <h3>Conclusion</h3> This large single institution series with prospectively collected PRO & CTCAE toxicity is one of the first to report outcomes for intraoperatively, real-time planned BT. Odds of GU symptoms ≥Grade 2 are elevated with BT but cumulative incidence of GU/GI CTCAE ≥Grade 3 toxicity at 2yr was <4% for BT & DE-IMRT. Our results may assist in counseling and suggest that among appropriately selected patients a BT boost with intraoperative planning is reasonably well tolerated.