Low Dose Rate Brachytherapy Research Articles

Impact of hydrogel and hyaluronic acid rectal spacer on rectal dosimetry and toxicity in low-dose-rate prostate brachytherapy: a multi-institutional analysis of patients' outcomes.

PurposeTo report on rectal dosimetry and toxicity outcomes in men with prostate cancer (PCa) treated with iodine-125 low-dose-rate brachytherapy (LDR-BT) with or without polyethylene glycol hydrogel (HS) or hyaluronic acid (HA) rectal spacer (RS) insertion.Material and methodsSeventy consecutive men treated with LDR-BT between December 2017 and July 2019 were included in this study, including twenty-eight (40%) men who had RS insertion according to the preference of referring urologist, compared to a group of forty-two men (60%) without RS. Descriptive statistics were used to compare RS safety, dosimetric effects on organs at risk (rectum and urethra), and gastrointestinal (GI) and genitourinary toxicities (GU) (assessed using the CTCAE v.4) between the two groups of patients.ResultsThe median prostate-rectal separation with RS at mid prostate was 10 mm (IQR, 8-11.5 mm). The median follow-up was 23.5 months. There were no post-operative complications for RS insertion. There was significantly reduced rectal dosimetry in RS-group vs. non-RS group; the median RV100 was 0.0 cc (IQR, 0.0-0.0 cc) vs. 0.4 cc (IQR, 0.1-1.1 cc) (p < 0.001), respectively. The mean rectal D1cc and D2cc were 52.4% vs. 84.2% (p < 0.001) and 45.7% vs. 70.0% (p < 0.001) for RS and non-RS group, respectively. There were no statistically significant differences in the mean urethral D20, D5, and D1. There were significantly less grade 1 acute and late GI toxicities in RS-group when compared to non-RS group (0% vs. 24%, p = 0.004 for acute GI toxicity; 4% vs. 33%, p = 0.003 for late GI toxicity). There were no reported acute or late grade 2 or above GI toxicities.ConclusionsInsertion of RS in men treated with LDR-BT is safe and resulted in a significant reduction in rectal dosimetry. The reduction in rectal dosimetry with RS insertion translates into significantly reduced acute and late GI toxicities.

Validation of American Association of Physicists in Medicine TG 43 Dosimetry Data in Commercial Treatment Planning System.

AimsThis study aimed to validate the dosimetric data of low-energy photon-emitting low-dose rate (LE-LDR) brachytherapy seed sources in commercial treatment planning system (TPS).Materials and MethodsThe LE-LDR seed sources dosimetric data were published in the American Association of Physicists in Medicine (AAPM) Task Group reports TG-43 (1995), TG-43U1 (2004), TG-43U1S1 (2007), and TG-43U1S2. The Bhabha Atomic Research centre (BARC) 125I Ocu-Prosta seed dosimetry data are also available in the literature. The commercially available TPSs are using both two-dimensional (cylindrically symmetric line-source) and one-dimensional (1D) (point source) dose-calculation formalisms. TPS used in this study uses only 1D dose-calculation formalism for permanent implant dosimetry. The point-dose calculation, dose summation, isodose representation, and dose–volume histogram quality assurance tests were performed in this study. The point-source dose-calculation tests were performed for all the available sources in the literature. The others tests were performed for the I-125 BARC Ocu-Prosta seeds. The TPS-calculated doses were validated using manual calculation.Results and DiscussionIn point-source calculation test, the TPS-calculated point-dose values are within ±2% agreement with manually calculated dose for all the seeds studied. The agreement between the TPS and manually calculated dose is 0.5% for the dose summation test. The isodose line pass through the grid points at an equal distance was verified visually on the computer screen for seed used clinically. In dose–volume histogram test, the TPS-determined volume was compared with the real volume.ConclusionMisinterpretation of the TPS test and/or misunderstanding of the TG-43 dose-calculation formalism may cause large errors. It is very important to validate the TPS using literature provided dosimetric data. The dosimetric data of BARC 125I Ocu-Prosta Seed are validated with other AAPM TG-43-recommended seeds. The dose calculation of Best® NOMOS permanent implant TPS is accurate for all permanent implant seeds studied.

Braquiterapia oftálmica de baja tasa de dosis en el Instituto Nacional de Cancerología, E. S. E.

La braquiterapia de baja tasa de dosis (LDR, por sus siglas en inglés), como opción de tratamiento contra el cáncer en el Instituto Nacional de Cancerología (INC), es una modalidad que usa radiaciones ionizantes para destruir células malignas y reducir el tamaño tumoral. Esta técnica de tratamiento consiste en la aplicación de semillas de iodo 125 (125I), elemento radiactivo que se dispone en una placa metálica de oro que se posiciona quirúrgicamente en la superficie del globo ocular en contacto con el tumor, con el fin de obtener un óptimo control local de los melanomas del cuerpo uveal y los retinoblastomas en pacientes pediátricos, cuando este tipo de neoplasias se encuentran en estadios tempranos, como una terapia alternativa a la enucleación (extirpación completa del globo ocular). En el presente artículo se describe la técnica usada en el INC, que se ha implementado desde el año 2006 empleando el software Plaque Simulator de BEBIG, se hace un barrido de la anatomía del globo ocular, las características físicas del radionúclido de 125I, el procedimiento clínico, la técnica, la planeación dosimétrica y la protección radiológica, dejando finalmente unos tópicos de discusión en las conclusiones.

First brachytherapy treatment of prostate cancer in Nigeria using low dose rate radioactive iodine 125

BackgroundWe report the first prostate brachytherapy in Nigeria, using low dose radioactive iodine 125 (I-125) permanent seeds implant.Case PresentationThe low dose rate brachytherapy using I-125 implants was performed in a private clinic in the city of Benin, Edo state of Nigeria. This pilot study reports the case of the first two patients with prostate cancer. The patients were treated under spinal anesthesia using 2 ml of heavy bupibacaine which is equivalent to 10 mg of bupibacaine. Biopsy, total blood count, electrolytes, urea, creatinine, urinalysis, electrocardiogram, chest X-ray, prostate-specific antigen and bone scan were checked prior to the procedure. The first two prostate cancer patients who were in low risk category successfully received the treatment in the first day of the clinic’s operations. This paper describes the settings in which these clinical operations occurred, detailing the type of technology used, the clinical procedure and the obtained dose distribution.ConclusionsThe paper ends with discussing the overall cost of the investment and the challenges encountered as well as the perspectives of extending the brachytherapy practice to treat other cancer diseases, such as breast and genealogical cancers.

Dose assessment in high dose rate brachytherapy with cobalt-60 source for cervical cancer treatment: a phantom study

Abstract Transition from low dose rate brachytherapy to high dose rate brachytherapy at our department necessitated the performance of dose verification test, which served as an end-to-end quality assurance procedure to verify and validate dose delivery in intracavitary brachytherapy of the cervix and the vaginal walls based on the Manchester system. An in-house water phantom was designed and constructed from Perspex sheets to represent the cervix region of a standard adult patient. The phantom was used to verify the whole dose delivery chain such as calibration of the cobalt-60 source in use, applicator, and source localization method, the output of treatment planning with dedicated treatment planning system, and actual dose delivery process. Since the above factors would influence the final dose delivered, doses were measured with calibrated gafchromic EBT3 films at various points within the in-house phantom for a number of clinical implants that were used to treat a patient based on departmental protocol. The measured doses were compared to those of the treatment planning system. The discrepancies between measured doses and their corresponding calculated doses obtained with the treatment planning system ranged from -29.67 to 40.34% (mean of ±13.27%). These compared similarly to other studies.

IJU this issue

This issue contains 15 Original Articles, three of which are excellent prospective clinical trials, and one Urological Note. Cabozantinib is a multiple receptor tyrosine kinase inhibitor targeting MET (c-MET), VEGFR2, RET, AXL, KIT and TIE-2. In the phase III, randomized, open-label METEOR study, cabozantinib was associated with a significant progression-free survival benefit and a greater objective response rate versus everolimus in patients with metastatic renal cell carcinoma who had progressed after VEGFR-TKI. Tomita et al. (Niigata, Japan) carried out a bridging study to METEOR to evaluate the efficacy and safety of cabozantinib in Japanese patients. This phase II, open-label, single-arm study showed that cabozantinib provided clinical benefits in Japanese patients with renal cell carcinoma, with similar efficacy and safety to the non-Japanese population. Medical lasers are increasingly used to treat benign prostatic hyperplasia. Shoji et al. (Isehara, Japan) carried out a randomized prospective study to compare functional outcomes and complications over a period of 12 months in benign prostatic hyperplasia treated with thulium laser enucleation of the prostate or bipolar transurethral resection of the prostate. This study showed that thulium laser enucleation of the prostate is superior to bipolar transurethral resection of the prostate in resected volume, resected rates per prostate volume and transition zone volume, hemostasis, catheterization and hospitalization time, and decrease in prostate-specific antigen. However, excessive laser irradiation time in thulium laser enucleation of the prostate has the possibility to delay improvement of overactive bladder symptoms and decrease sexual function. Loose seeds and stranded seeds are available for low-dose rate brachytherapy. Each method has its own advantages and disadvantages, such as flexibility and fixation. Tanaka et al. (Kashihara, Japan) carried out a randomized controlled trial to compare the post-implant dosimetric parameters between the conventional method (using only the loose seeds) and the hybrid method. This study showed that the hybrid method of low-dose rate brachytherapy can achieve a higher coverage of the periprostatic region compared with the conventional method, while maintaining an acceptable level of urethral and rectal doses. The intravesical recurrence rate after transurethral resection of bladder tumor carried out for non-muscle-invasive bladder cancer (NMIBC) is high, and some risk factors for recurrence have been identified. Sazuka et al. (Chiba, Japan) evaluated the risk of the residual urine volume and preoperative pyuria in intravesical recurrence after transurethral resection of bladder tumor among NMIBC patients. They found that the presence of residual urine and pyuria raised the risk of intravesical recurrence after transurethral resection of bladder tumor for NMIBC. Furthermore, especially in men, the recurrence-free survival was significantly higher in patients without than with residual urine by propensity score matching analysis. Iwasawa et al. (Tokyo, Japan) investigated the relationship between fluid intake and tumor recurrence in NMIBC patients by using urine-specific gravity as an indicator of daily fluid intake. They found that high urine-specific gravity was associated with tumor recurrence, especially in patients not receiving adjuvant bacillus Calmette–Guérin therapy. This showed that increasing fluid intake might prevent recurrence in relatively low-risk NMIBC patients. Testicular microlithiasis (TM) is a relatively rare condition occurring in the testicular parenchyma that is characterized by multiple bright and small foci without acoustic shadow limited to the testicle on scrotal ultrasonography. TM is a characteristic of testicular dysgenesis syndrome and was shown to be associated with infertility. Hiramatsu et al. (Tokyo, Japan) evaluated the correlation between the degree of severity in TM and several factors. This study showed the prevalence of TM in normal healthy Japanese men who are trying for first-time pregnancy. This also showed that men with TM might have poor semen findings, and that men with severe TM might have even worse semen parameters. None declared.

Longitudinal Changes in Health-related Quality of Life After 125I Low-dose-rate Brachytherapy for Localized Prostate Cancer.

The factors associated with longitudinal changes in health-related quality of life (HRQOL) are unclear. In this study we aimed to evaluate the longitudinal changes and predictors of HRQOL after 125I low-dose-rate brachytherapy (LDB) for localised prostate cancer (PCA). We evaluated 180 patients with localised PCA treated with LDB. The HRQOL was evaluated at 3 weeks before LDB and at 1, 3, 6, 12, 18, 24, 36, and 48 months after LDB using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8), and University of California Los Angeles Prostate Cancer Index (UCLA-PCI). All HRQOL scores, except for UCLA-PCI sexual function and SF-8 mental component summary (MCS), were improved to baseline after an early transient deterioration. In contrast, the sexual function did not return to baseline after early deterioration. Meanwhile, the MCS scores showed no significant decline after implantation and trended upward. The prostate V100 and baseline UCLA-PCI sexual function scores predicted a clinically significant decrease in sexual function in the late post-implantation period. Most aspects of the HRQOL of PCA patients who underwent LDB improved to baseline. The results that V100 and baseline sexual function were predictors of late post-LDB may provide more accurate information for patients with preserved sexual function before treatment and for their partners.

Treatment Outcome of Cervical Cancer Patients Treated with Low-Versus High Dose Rate Brachytherapy after Concurrent Chemo-Radiation

Cervical cancer (CC) is the commonest gynecological cancer seen in the Ghanaian woman. Majority of patients here present with locally advanced diseases due poor screening practices aimed at detecting and treating precancerous conditions. The current standard curative treatment for locally advanced CC is concurrent cisplatin-based chemo-radiation plus intracavitary brachytherapy. The brachytherapy (BT) component has been Low-Dose Rate (LDR) BT for almost a century now until a few decades ago when High-Dose Rate (HDR) BT was developed to overcome disadvantages of LDR BT such as long treatment duration. In October 2014, HDR BT was introduced as the BT technique for the management of CC patients at this Centre, after several years of using LDR BT. The hypothesis for this study was that there was no difference in the treatment outcomes of CC patients treated with HDR BT compared with those who received LDR BT at this center. The aim of this study was to compare the treatment outcomes and toxicity of CC patients treated with LDR BT versus HDR BT treated at this Centre. Patients with histologically confirmed CC treated from January 2008 to December 2017 were enrolled after applying the inclusion and exclusion criteria. Information regarding patient demographics, stage of disease, type of BT received, total radiation dose received, response to treatment and treatment related toxicities experienced were extracted from the medical records of the patients. The primary end points of the study included local control (LC), disease free survival (DFS) and overall survival (OS) all at 2 years. Toxicities were also assessed. Primary endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards models. Over the 10-year period, 284 LDR (2008 –mid-2014) and 136 HDR (mid-2014-2017) patients fit the inclusion criteria. The median follow-up was 22 months (1-132months) vs. 11 months (1-41months) in LDR vs. HDR group respectively. For stages IB, IIA, IIB, IIIA and IIIB disease, the 2-year LC rates for LDR vs. HDR were 63 % vs. 61% p = 0.348, 86% vs. 90% p = 0.680, 86% vs. 88% p = 0.829, 66% vs. 60% p = 0.556 and 77% vs. 40% p = 0.005 respectively. The 2-year DFS for LDR vs. HDR BT were 64% vs. 61% p = 0.495, 81% vs. 69% p = 0.179, 81% vs. 80% p = 0.540, 62% vs. 33%, p = 0.818, and 71% vs.30%, p = 0.001 for stages IB, IIA, IIB, IIIA and IIIB respectively. The OS were comparable in both treatment groups stage for stage. Frequencies of acute and chronic toxicities for LDR vs. HDR were 22.6 % vs. 23.5%, and 3.9% vs. 6.9%, respectively. Comparable LC, DFS and OS were observed for IB, IIA, IIB and IIIA patients treated with LDR vs. HDR BT. HDR BT for the treatment of CC is therefore an acceptable alternative to LDR BT. However, the poorer LC and DFS rates observed for IIIB patients, and the higher frequencies of toxicities in the HDR BT cohort highlights the need for refining the HDR BT techniques at the Centre.

Low Dose Rate Brachytherapy and Long-Term Treatment Outcomes In Patients Less Than 60 Years of Age

Low Dose Rate (LDR) brachytherapy in young men remains controversial amongst urologists due to their concerns regarding long term biochemical control and treatment related toxicities. The purpose of this study is to evaluate the treatment outcomes of men under 60 years of age who underwent LDR brachytherapy with Iodine 125 (125I) for clinically localized low to intermediate risk prostate cancer. A total of 156 patients with clinically localized prostate cancer were treated at our institution from 2003 to 2016 with 125I monotherapy. The prescription was 145.0Gy modified peripheral loading (MPD). Median age at implant was 56 years (range 42-60). Median PSA level at diagnosis was 4.5 ng/mL (range 0.3-13.9). Staging was T1 in 46% and T2 in 54% of patients. 62 patients (40.5%) underwent trans urethral resection of the prostate (TURP) prior to implant. All patients were assessed clinically for biochemical response based on Phoenix definition (nadir +2ng/ml), biochemical relapse free survival (bRFS), progression free survival (PFS), overall survival (OS) and any associated treatment toxicities. With median follow up of 6.7 years, bRFS at 10 years post LDR implant is 94% for the entire cohort; 99% and 82% for low and intermediate risk groups respectively. PFS at 10 years for the entire cohort is 94%; low and intermediate risk groups are 99% and 82% respectively. OS is 95% for our entire cohort. Late grade 2+ genito-urinary (GU) toxicities were reported in 5 patients (3.2%) with only one patient experiencing late grade 3 toxicity. Three patients (1.9%) developed secondary cancers, all considered unrelated to their LDR brachytherapy. Five (3.2%) deaths were reported but only 1 was secondary to prostate cancer. Four patients (2.6%) experienced late grade 2+ gastro-intestinal (GI) toxicity. No patients who underwent TURP prior to implant reported any late grade 2+ GU toxicity. With excellent long-term treatment outcomes and minimal associated toxicities, our results indicated that LDR brachytherapy is an effective treatment of choice for this younger cohort of men diagnosed with localized prostate cancer.

Biochemical Control and Toxicity Outcomes of SBRT vs LDR Brachytherapy in the Treatment of Low and Intermediate Risk Prostate Cancer

Abstract Purpose /Objective(s): Low dose rate (LDR) brachytherapy and Stereotactic Body Radiation Therapy (SBRT) have both shown acceptable outcomes in the treatment of low and intermediate risk prostate cancer. Minimal data has been published directly comparing rates of biochemical control and toxicity with these two modalities. We hypothesize that LDR and SBRT will provide similar rates of biochemical control. Materials/Methods All low and intermediate risk prostate cancer patients treated definitively with SBRT or LDR between 2010 and 2018 were captured. Phoenix definition was used for biochemical failure. Independent t-tests were used to compare baseline characteristics, while repeated measure ANOVA was used to compare AUA and EPIC scores between treatment arms over time. Biochemical control was estimated using the Kaplan Meier method. Differences in acute and late toxicity were assessed via Pearson chi-square. Results 219 and 118 patients were treated with LDR and SBRT. Median follow-up was 4.3 years (interquartile range:3.1-6.1). All patients treated with LDR received 125.0 Gy in a single fraction. SBRT consisted of 42.5 Gy in 5 fractions. 5-year biochemical control for LDR versus SBRT was 91.6% vs. 97.6% (p=.108). LDR patients had a larger increase in mean AUA scores at one month (17.2 vs. 10.3, p Conclusion Our data shows similar biochemical control and GU toxicity rates at 5 years for both SBRT and LDR, with slightly higher GI toxicity with SBRT and higher AUA and EPIC scores with LDR.

External Validation of Early Quality of Life (QOL) Declines Correlated with Late QOL after Intensity Modulated, Low Dose Rate Brachytherapy, or Stereotactic Radiation for Prostate Cancer within a Prospective Trial

There is data on early toxicity associated with late toxicity, but there is currently a lack of data on quality of life (QOL) outcomes and evaluation for possible surrogacy between early and late toxicity. This is an evaluation of early QOL for prostate cancer across RT options with a validation within QOL from a SBRT prospective trial. An initial cohort of 898 patients (PROSTQA study and 3 institutions with prospective QOL data were pooled for analysis for IMRT (n = 162), LDR brachytherapy (n = 271), or SBRT (Robotic n = 392 and Linac n = 72) to the prostate with or without seminal vesicles) were evaluated for patient reported outcomes. Expanded Prostate Cancer Index (EPIC) QOL data for urinary, bowel, vitality, and sexual function was evaluated by pre-specified relevant thresholds for meaningful clinical differences (MCD) compared to baseline. Patients were evaluated for QOL at 1-2 month from the start of radiotherapy and at 24 months from the start of radiotherapy. Multivariate analysis (MVA) used general linear models to assess the correlation between QOL changes. This was then externally validated with QOL analysis from a prospective trial of robotic SBRT to the prostate alone to 38 Gy in 4 fractions of 259 patients assessing QOL at 1-month post-radiotherapy to predict late declines QOL at 24 months. A total of 898 patients were within the initial cohort, 94% had evaluable QOL at 24 months. On MVA, after controlling for age, baseline function, PSA, Gleason score, T-stage, prostate volume, and RT technique, an early MCD was the strongest predictor of late MCD at 24 months in all assessed domains and radiation modalities: odds ratio (OR) 3.7 [95% CI 2.2-6.4] for urinary irritation, OR 4.5 [2.9-6.9] for urinary incontinence, OR 2.4 [1.6-3.5] for bowel, OR 3.7 [2.5-5.5] for sexual function, and OR 3.4 [2.3-4.9] for hormone. Within the validation cohort of 259 patients, 83% had evaluable QOL at 24 months. Early declines of a MCD were again associated with late declines noted across all domains of QOL: OR 3.1 [95% CI 1.7-5.8] for urinary irritation, OR 2.7 [1.5-4.8] for urinary incontinence, OR 2.0 [1.1-3.7] for bowel, OR 4.0 [2.1-7.7] for sexual function, and OR 3.0 [1.2-7.3] for hormone. Early QOL decline was the strongest predictor of QOL impacts at 2 years across all domains and this appeared consistent across standard radiation treatment modalities. This was externally validated within these domains suggesting early declines in QOL are surrogates and predict for late declines.Abstract 141; TableIncidence and Correlation of an MCD in Early and Late QOLEPIC DomainEPIC MCD ThresholdEarly Decline MCDLate Decline MCDOR [95% CI]Early Decline MCDLate Decline MCDOR [95% CI]Initial CohortValidation CohortUrinary Irritative678%36%3.7 [2.2-6.4]63%39%3.1 [1.7-5.8]Urinary Incontinence7.537%24%4.5 [2.9-6.9]32%41%2.7 [1.5-4.8]Bowel554%29%2.4 [1.6-3.5]41%26%2.0 [1.1-3.7]Sexual1136%41%2.9 [2.3-3.8]30%49%2.4 [0.89-6.6] Open table in a new tab

Analysis of PSA Kinetics and Late Treatment Related Toxicity in a Phase 2 Randomized Pilot Study Comparing High Dose Rate Brachytherapy and Low Dose Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

Analysis of PSA Kinetics and Late Treatment Related Toxicity in a Phase 2 Randomized Pilot Study Comparing High Dose Rate Brachytherapy and Low Dose Rate Brachytherapy as Monotherapy in Localized Prostate Cancer

Low Dose 125I Brachytherapy And Transpupillary Thermal Therapy (TTT) For Small To Medium Size Choroidal Melanoma

To evaluate our institutional outcomes after treatment of small to medium size choroidal melanoma with low dose COMS brachytherapy. Single center, retrospective review of small to medium size choroidal melanoma < 5 mm in apical height managed from 2005-2019 with 125I brachytherapy at prescribed dose < 80 Gy, using a homogeneous dose calculation methodology. Ocular outcomes included visual acuity, presence of ocular radiation side effects, and local tumor recurrence. The Kaplan-Meier method was used to estimate overall survival, and metastasis rates were reported using cumulative incidence with death as a competing risk. Univariable associations were analyzed using Cox proportional hazards regression. Radiation statistics were calculated using Monte Carlo dosimetry. There were 146 patients included. Patient demographics and presenting tumor features are described in Table 1. Patients were treated with 125I plaque radiotherapy at median dose 65 Gy (IQR: 65-65 Gy) to depth of 5 mm, with additional transpupillary thermotherapy (TTT) at the time of plaque removal in 140 (95.9%) cases. Median follow-up was 6.7 years (IQR: 2.7-9.3 years). At final follow-up, median logMAR visual acuity was 1.1 (IQR: 0.4-2.0) with Snellen acuity 20/15-20/40 (20%), 20/50-20/160 (26%), and 20/200 or worse (54%). Radiation complications were as follows: cystoid macular edema in 54 (38%), radiation maculopathy in 71 (50%), non-proliferative radiation retinopathy in 53 (38%), proliferative radiation retinopathy in 20 (14%), and radiation papillopathy in 53 (38%). There were 11 patients who required subsequent pan-retinal laser photocoagulation (8%). Radiation dose did not appear to impact radiation maculopathy or retinopathy, but radiation papillopathy was significantly associated with point dose, maximum dose, and mean dose to the optic disc (p < 0.05). Local tumor control was achieved in 145 (99.3%) patients with recurrence in 1 (0.7%) patient 6.5 years after plaque. The 5-year cumulative incidence of distant metastasis was 7.2% with 5-year overall survival of 96.2%. Low dose 125I plaque radiotherapy with TTT provided high rates of local tumor control. Radiation maculopathy, retinopathy, and papillopathy were still observed even with reduced radiation apex dose. Future studies are warranted to determine rates of tumor control and ocular toxicity in low dose brachytherapy without TTT.Abstract 3687; TablePatient CharacteristicsMedian age61 years (IQR: 51-68 years)SexFemale 58%ComorbiditiesAtherosclerotic disease 44%Diabetes 18%Hyperlipidemia 45%Hypertension 49%Tumor CharacteristicsMedian logMAR visual acuity0.18 (IQR: 0.0-0.4)Snellen acuity20/15-20/40 68%20/50-20/160 29%20/200 or worse 3%Tumor dimensionsLargest basal diameter (IQR) 8.0 mm (IQR: 6.7-10.0 mm)Thickness (IQR) 2.0 mm (IQR: 2.0-2.0 mm)Secondary retinal detachment18%Subfoveal/subretinal fluid88% Open table in a new tab

Assessing Clinical and Dosimetric Predictors For Low PSA Nadir after Stereotactic Body Radiation Monotherapy with Intraprostatic Dose Escalation

Definitive Stereotactic Body Radiation Therapy (SBRT) has become a standard treatment option for men with low to intermediate risk prostate cancer. Several studies have characterized the importance of low PSA nadir for sustained disease control post radiation. Dose response parameters are well-established for low dose rate (LDR) brachytherapy, and remain emerging for prostate SBRT. Due to heterogeneity of treatment platforms and prescription nomenclature, it remains challenging to apply dose-response data with SBRT in an ecumenical fashion. This study assesses clinical and dosimetric factors associated with a low PSA nadir post prostate SBRT. 852 patients with NCCN low (39.0%), favorable intermediate (26.6%) and unfavorable intermediate (34.4%) risk disease were treated with, inhomogeneous non-coplanar SBRT, allowing for intraprostatic dose escalation. Treatment was delivered at an academic institution from June 21, 2006 to January 3, 2018 and consisted of a 5-fraction regimen of 35.0-36.25 Gy. The mean age was 66.6 years (41-87). 77.9% of patients were Caucasian and 17.4% African American. The mean follow-up time was 46.3 months (24-155). In order to distill predictive correlates for post-treatment PSA decline, patients receiving ADT or who experienced biochemical failure were omitted a priori. Correlation analyses were performed using Pearson chi-square testing and odds ratios were assessed with binary logistic regression. After a minimum of 24 months post SBRT monotherapy, the mean PSA nadir was 0.39ng/ml (0-2.72), with 56.0% of patients experiencing a nadir ≤0.3ng/ml. Patients with a nadir ≤0.3ng/ml were more likely to be age ≥65 years (68.1% vs. 52.8%, p<.001), and to be Caucasian (80.7% vs. 74.4%, p = .007). They were more likely to have clinical T2b/T2c disease (11.6% vs. 6.7%, p = .031) and less likely to have a pre-treatment PSA >10ng/ml (9.6% vs. 15.2%, p = .014). They more often were treated with anti-coagulation medicine (12.0% vs. 6.5%, p = .01). Those with a nadir ≤0.3ng/ml had no difference in overall NCCN risk grouping, use of 5-alpha reductase inhibitor, metformin, or statin medication use. Dosimetric parameters that portended for nadir ≤0.3ng/ml included CTV D70 ≥37.75Gy (82.6% vs. 70.5%, p<.001), CTV D80≥ 37.5Gy (70.0% vs. 57.8%, p = .003), and CTV mean dose ≥38.5Gy (57.1% vs. 43.8%, p = .002). On multivariate analysis, predictors for long-term PSA nadir ≤0.3ng/ml were age ≥65 (OR 1.78, CI 1.20-2.64, p = .004) and CTV D70 ≥37.75Gy (OR 2.52, CI 1.10-5.79, p = .029). Patients with localized prostate cancer can experience low PSA nadirs post SBRT monotherapy. Consistent with previous studies, older age appears to correlate with lower nadir values. CTV D70 ≥37.75Gy predicts for PSA nadir ≤0.3ng/ml. Longer follow-up is warranted to assess for durability of these findings and future inquiry should involve correlation between D70 and long-term disease-free endpoints.

Salvage Low Dose Rate Brachytherapy for Intraprostatic Local Prostate Cancer Recurrence following Definitive External Beam Radiation Therapy

Salvage Low Dose Rate Brachytherapy for Intraprostatic Local Prostate Cancer Recurrence following Definitive External Beam Radiation Therapy

Clinical and Treatment Characteristics of Secondary Bladder Malignancies following Low Dose Rate Brachytherapy for Prostate Cancer

Clinical and Treatment Characteristics of Secondary Bladder Malignancies following Low Dose Rate Brachytherapy for Prostate Cancer

Clinical and Treatment Characteristics of Secondary Rectal and Anal Malignancies following Low Dose Rate Brachytherapy for Prostate Cancer

Clinical and Treatment Characteristics of Secondary Rectal and Anal Malignancies following Low Dose Rate Brachytherapy for Prostate Cancer

Salvage Low Dose Rate Prostate Brachytherapy: Clinical Outcomes of a Phase II Trial for Local Recurrence after External Beam Radiotherapy (NRG/RTOG -0526)

Prior studies of low dose rate (LDR) prostate brachytherapy (BT) for salvage of local recurrence (LR) of prostate cancer (PCa) after external beam radiotherapy (EBRT) are limited by retrospective reporting. We previously reported adverse events (AEs) of a prospective Phase II trial (NCT00450411) and now report efficacy outcomes with a minimum potential follow up of 5 yrs. Eligible patients had low or intermediate risk PCa prior to EBRT and biopsy-proven LR > 30 mos after EBRT, with PSA < 10 ng/mL and no regional or distant disease. Prescribed minimum target dose was 140 Gy with I-125, or 120 Gy with Pd-103. The primary endpoint, late GI/GU AEs occurring 9-24 mos after BT (CTCAE V3.0 > Grade 3; attributed to BT) was 14%. All eligible patients were followed for a minimum of 5 yrs after salvage BT and analyzed for secondary clinical outcomes. Disease-free (DFS), disease-specific (DSS), and overall (OS)survivals were estimated using the Kaplan-Meier method and 95% confidence intervals computed using Cox proportional hazards models. Local tumor progression (LR), distant failure (DF), and biochemical failure (BF) were estimated using nonparametric estimation of cumulative incidence accounting for competing risk events. Time to LR, DF and BF were modeled by cause-specific Cox proportional hazards regression and adjusted for clinical and treatment factors. From May 2007 – January 2014, 20 centers registered 100 patients with 92 analyzable. Median follow up is 6.9 yrs (range: 0.3-11.2); median age 70 (IQR: 66-74). Initial Gleason score was 7 in 48% and PSA >10 ng/mL in 16%. Median prior EBRT dose was 74 Gy (IQR: 70-76). Androgen deprivation was combined with salvage BT in 16%. Median interval from prior EBRT was 85 mos (IQR: 60-119). 10-yr OS is 70% (95% CI: 58 -83). Nineteen patients died (5 PCa, 10 other, 4 unknown). 4 had LR (one biopsy-confirmed). 10-yr LF rate is 5% (95% CI:1-11). 14 patients had DF (10-yr rate 19% (95% CI:10-29)). The 10-yr freedom from BF rate is 54% (95% CI:43-66). DFS is 61% at 5 yrs (includes death from any cause) but falls to 33% at 10 yrs. None of the baseline characteristics, including % of prostate covered by 100% of the prescription dose and interval from EBRT to BT were significantly associated with OS, DFS, local, distant, or biochemical failure. This is the first prospective multicenter trial to report outcomes of salvage LDR BT for LR after EBRT. We previously reported late grade 3 GU/GI adverse events occurring in14%. We now report 5-yr freedom from biochemical failure at 68%, comparable to other salvage modalities. Although further local LF is rare (5%), there is a continued toll of PCa recurrence such that freedom from biochemical failure at 10 yrs is 54%.

Salvage low dose rate brachytherapy for prostate cancer recurrence following definitive external beam radiation therapy

PurposeWe sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. Materials and methodsWe included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan–Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02–1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004–1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up. ConclusionsSalvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure.

First report on the feasibility of a permanently implantable uni-directional planar low dose rate brachytherapy sheet for patients with resectable or borderline resectable pancreatic cancer

BackgroundMargin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. MethodsEleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. ResultsOne patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. ConclusionThis is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.