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Purpose Robotic systems to assist needle placements for low-dose rate brachytherapy enable conformal dose planning only restricted to path planning around risk structures. We report a treatment planning system (TPS) combining multiple direction needle-path planning with inverse dose optimization algorithms. Methods We investigated in a path planning algorithm to efficiently locate needle injection points reaching the target volume without puncturing risk structures. A candidate needle domain with all combinations of trajectories is used for the optimization process. We report a modular algorithm for inverse radiation plan optimization. The initial plan with V100 > 99% is generated by the “greedy optimizer”. The “remove-seed algorithm” reduces the number of seeds in the high dose regions. The “depth-optimizer” varies the insertion depth of the needles. The “coverage-optimizer” locates under-dosed areas in the target volume and supports them with an additional amount of seeds. The dose calculation algorithm is benchmarked on an image set of a phantom with a liver metastasis (prescription dose D p r = 100 Gy ) and is re-planned in a commercial CE-marked TPS to compare the calculated dose grids using a global gamma analysis. The inverse optimizer is benchmarked by calculating 10 plans on the same phantom to investigate the stability and statistical variability of the dose parameters. Results The path planning algorithm efficiently removes 72.5% of all considered injection points. The candidate needle domain consists of combinations of 1971 tip points and 827 injection points. The global gamma analysis with gamma 1 % = 2.9 Gy , 1 mm showed a pass rate of 98.5 % . The dose parameters were V 100 = 99.1 ± 0.3 % , V 150 = 76.4 ± 2.5 % , V 200 = 44.5 ± 5.5 % and D 90 = 125.9 ± 3.6 Gy and 10.7 ± 1.3 needles with 34.0 ± 0.8 seeds were used. The median of the TPS total running time was 4.4 minutes. Conclusions The TPS generates treatment plans with acceptable dose coverage in a reasonable amount of time. The gamma analysis shows good accordance to the commercial TPS. The TPS allows taking full advantage of robotic navigation tools to enable a new precise and safe method of minimally invasive low-dose-rate brachytherapy.

Purpose Low-dose-rate brachytherapy is a key treatment for low-risk or favorable intermediate-risk prostate cancer. The number of radioactive seeds inserted during the procedure depends on prostate volume, and is not easy to predict without pre-planning. Consequently, a large number of unused seeds may be left after treatment. The objective of the present study was to predict the exact number of seeds for future patients using machine learning and a database of 409 treatments. Material and methods Database consisted of 18 dosimetric and efficiency parameters for each of 409 cases. Nine predictive algorithms based on machine-learning were compared in this database, which was divided into training group (80%) and test group (20%). Ten-fold cross-validation was applied to obtain robust statistics. The best algorithm was then used to build an abacus able to predict number of implanted seeds from expected prostate volume only. As an evaluation, the abacus was also applied on an independent series of 38 consecutive patients. Results The best coefficients of determination R2 were given by support vector regression, with values attaining 0.928, 0.948, and 0.968 for training set, test set, and whole set, respectively. In terms of predicted seeds in test group, mean square error, median absolute error, mean absolute error, and maximum error were 2.55, 0.92, 1.21, and 7.29, respectively. The use of obtained abacus in 38 additional patients resulted in saving of 493 seeds (393 vs. 886 remaining seeds). Conclusions Machine-learning-based abacus proposed in this study aims at estimating the necessary number of seeds for future patients according to past experience. This new abacus, based on 409 treatments and successfully tested in 38 new patients, is a good alternative to non-specific recommendations.

BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1–31.3] and 24.2 (IQR 17.9–30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12–24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12–18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.

International audience; Low Dose Rate Brachytherapy (LDR-BT) is a technique for treating localized prostate cancer by implanting radioactive seeds. In conventional practice, the delivery of seeds is performed using transrectal ultrasonography (TRUS) imaging for implant guidance and checked using computed-tomography for post-implant dosimetry. In the case of TRUS, accuracy can be compromised due to sub-optimal imaging. Magnetic Resonance Imaging (MRI), however, is known to provide better soft-tissue contrast, therefore, increasing the ability to detect small lesions; for that reason, the integration of intraoperative MRI in BT workflows has been investigated over the last two decades. The fusion of preoperative MR-images during TRUS-brachytherapy is possible. However, the image registration process introduces a source of uncertainty. Manual, real-time intra-operative LDR-BT is challenging under MRI due to confined space and procedural workflows. This motivates the development of MRI-compatible robots for prostate BT, with potential advantages of improved source placement accuracy and final dosimetry. In this paper, the state-of-art of technological components in MRI compatible robots, especially for LDR-BT, has been presented. This systematic review helps us to position an ongoing Cooperative Brachytherapy project, developing a real-time MRI-guided robot for adaptive LDR-BT. The design approach includes integrating separate modules: imaging, dose planning, needles, and robot.

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

Purpose External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly. Methods and Materials This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer–specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function). Results Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively). Conclusions Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy.

Purpose Prostate cancer with nodular bladder invasion (stage T4 prostate cancer) is an extremely difficult clinical entity to achieve complete cure. So far, there has been no clear report demonstrating complete cure of prostate cancer with nodular bladder invasion, stage T4 prostate cancer. Case presentation In this case report, the author presents a 55-year-old man with a diagnosis of advanced prostate cancer invading into the bladder wall with pelvic lymph node metastasis (T4N1M0 disease). The patient was treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with whole pelvis (WP) external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT): neo-adjuvant six months plus adjuvant six months ADT. There was no grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity during follow-up. There was no evidence of hematuria, nor rectal bleeding in the follow-up. The patient stays healthy without biochemical failure and without bowel and urinary troubles at six years. Conclusions Along with previous outstanding data of BED ≥ 220 Gy LDR-based radiotherapy for high-risk and very high-risk prostate cancer patents, including pelvic lymph node metastasis, the present report, in which the patient was treated with BED ≥ 220 Gy of high-dose radiotherapy, LDR brachytherapy in combination with WP EBRT may be an optimal treatment for prostate cancer with nodular bladder invasion with lymph node metastasis (T4N1disease).

Purpose To verify the dose sparing effect of hydrogel spacer (SpaceOAR™) on rectal dosimetry for prostate brachytherapy, and to determine whether prostate and rectal dosimetry was affected by the time gap between hydrogel spacer injection and brachytherapy dosimetry. Material and methods The 103Pd brachytherapy dosimetry of 174 consecutive intermediate- and high-risk patients injected with hydrogel was compared with a dosimetry of 174 contemporaneous patients without hydrogel injections. Of the SpaceOAR™ patients, 91 had hydrogel injected upon completion of brachytherapy implant, while the remaining 83 patients had hydrogel placed prior to external beam radiation therapy (EBRT), followed 2-10 weeks later by brachytherapy. Brachytherapy implants were either planned with the prostate undistorted by any hydrogel or planned with hydrogel in place. Dosimetry of the prostate and tissues at risk was determined from CT imaging on the day of brachytherapy implant. Results SpaceOAR™ significantly reduced mean and maximum rectal doses as well as rectal wall V50, but there was a statistically significant reduction of planning target volume (PTV) D90 to 121.1% of the prescribed dose in hydrogel patients compared to 123.3% in the non-hydrogel patients. Rectal dosimetry was similar between patients injected with hydrogel after brachytherapy and those with spacer injected prior to EBRT. However, patients who had hydrogel placed prior to EBRT had statistically significantly higher dosimetry indices of PTV and urethra relative to those with spacer placed at the completion of brachytherapy. Conclusions There was a significant rectal dose sparing in the cohort with hydrogel spacer compared to a reference group without spacer injection. The rectal dose sparing effect was similar in the sub-group of patients injected with hydrogel prior to EBRT and the sub-group injected with hydrogel at the conclusion of brachytherapy.

Background Margin 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. Methods Eleven 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. Results One 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. Conclusion This 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.

Background/aim 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). Patients and methods 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). Results 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. Conclusion 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.

We aimed to investigate whether gold marker implantation in the tissue surrounding the prostate could accurately monitor setup errors during external beam radiation therapy (EBRT) following low-dose-rate (LDR) brachytherapy. Thirty-eight patients had confirmed intermediate- or high-risk prostate cancer and received EBRT following LDR brachytherapy. In >175 computed tomography imaging sessions, the average values of the weekly setup error during EBRT to the prostate centroid at the time of gold marker matching in the surrounding tissue of the prostate and pelvic bone matching were measured and then compared using the Wilcoxon signed-rank test. Gold marker matching in the surrounding tissue of the prostate estimated setup errors better than those estimated by bone matching (3D displacement = 2.7 ± 2.0 vs 3.8 ± 2.6 mm, P

Purpose The purpose of this study was to compare an isotropic three-dimensional (3D) T2-weighted sequence sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with an axial two-dimensional T2-weighted turbo spin echo (TSE) sequence with regard to overall image quality and the delineation of normal prostate and periprostatic anatomy for low-dose-rate prostate cancer brachytherapy planning evaluation. Methods and Materials Patients (n = 69) with prostate cancer who had pelvic magnetic resonance imaging (MRI) for low-dose-rate brachytherapy treatment planning were included. Three radiologists independently assessed the visibility of nine anatomic structures on each sequence by using a 5-point scale and overall image quality by using a 4-point scale. The significance of the differences in diagnostic performance was tested with a Wilcoxon signed rank test. Results No significant intersequence differences were found for most (7/9) anatomical structures and overall image quality. The mean scores for visibility of anatomical structures on the 3D SPACE and 2D TSE sequences, respectively, were as follows: the zonal anatomy (3.7; 3.9, p = 0.05), prostate capsule (3.9; 4.0, p = 0.08), neurovascular bundle (2.9; 2.9, p = 0.9), rectoprostatic angle (3.8; 3.8, p = 0.35), rectum (4.2; 4.3, p = 0.26), urethra (3.8; 3.9, p = 0.12), urinary bladder (4.6; 4.6, p = 0.61), and overall image quality (2.9; 2.9, p = 0.33). 3D SPACE was superior for delineation of the genitourinary diaphragm (3.8; 3.6, p = 0.003), whereas 2D TSE was superior for delineation of the seminal vesicles (3.5; 4.0, p Conclusions Anatomic delineation of the prostatic and periprostatic anatomy provided by the 3D SPACE sequence is as robust in quality as that provided by a conventional 2D TSE sequence with superior delineation of the genitourinary diaphragm. For MRI-based brachytherapy treatment planning, the 3D SPACE sequence with subcentimeter isotropic resolution can replace the 2D TSE sequence and be incorporated into standard MRI protocols.

Background As aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs). Methods During the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated. Results During the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively. Conclusion The crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

Aims To externally validate a proposed biochemical definition of cure following low dose rate (LDR) brachytherapy for prostate cancer - 4-year post-implant prostate-specific antigen (PSA) ≤0.2 ng/ml - in a UK population, and report the long-term (10- and 15-year) outcomes for patients stratified by National Comprehensive Cancer Network (NCCN) risk groups, through analysis of a large, prospectively collected, single-centre database. Materials and methods All patients treated with LDR brachytherapy for prostate cancer at a single UK centre between 2001 and November 2020 (n = 1142) were eligible; 632 patients met the inclusion criteria for the analysis. The primary end point was disease-free survival (DFS), defined as freedom from clinical, radiological or PSA progression requiring androgen deprivation therapy. Four-year PSA was categorised as ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml. Kaplan-Meier analysis to 15 years was undertaken for each group, and sensitivity and specificity of 4-year PSA as a surrogate for long-term cure were calculated. Kaplan-Meier analysis to 15 years was repeated, stratifying patients by NCCN risk groups. Results The median cohort age was 63 years; the median follow-up was 9.1 years (range 3.5-18.7). In total, 248 patients were available for analysis at year 10, 46 at year 15. Sixty-four patients (10.1%) relapsed during the study period. The 10-year DFS for 4-year PSA categories ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml (95% confidence intervals) were 97.5% (95.4-99.6), 89.0% (82.4-96.1), 81.5% (70.5-94.2) and 41.8% (29.7-58.9), respectively. The 10-year DFS results for NCCN low, favourable-intermediate and unfavourable-intermediate risk disease were 93.1% (89.6-96.7), 92.1% (87.6-96.9) and 75.9% (67.8-84.9), respectively. Conclusions Patients with 4-year PSA ≤0.2 ng/ml may be considered cured, and could be discharged to general practitioner follow-up. LDR brachytherapy is an excellent treatment option for patients with low and favourable-intermediate risk prostate cancer, but those with unfavourable-intermediate risk disease should be considered for treatment intensification strategies.

Background Radical prostatectomy and radiotherapy are standard treatments for localized prostate cancer. When making decisions about treatment, it is important to not only consider medical information such as the patient's age, performance status, and complications, but also the impact on quality of life (QOL) after treatment. Our purpose was to compare health related quality of life (HRQOL) after robot-assisted laparoscopic radical prostatectomy (RARP) versus radiation therapy in Japanese patients with localized prostate cancer retrospectively. Methods Patients with localized prostate cancer receiving RARP or radiotherapy at Tottori University Hospital between October 2010 and December 2014 were enrolled in a retrospective observational study with follow-up for 24 months to December 2016. The Medical Outcome Study 8-Item Short-Form Health Survey was performed before treatment and 1, 3, 6, 12, and 24 months post-treatment. Results Complete responses to the questionnaire were obtained from 154/227 patients receiving RARP, 41/67 patients receiving intensity-modulated radiation therapy, 35/82 patients receiving low dose rate brachytherapy, and 18/28 patients given low dose rate brachytherapy plus external beam radiation therapy. The median physical component summary score of the Medical Outcome Study 8-Item Short-Form Health Survey was significantly lower at 1 month after prostatectomy than radiotherapy, but was similar for both treatments at 3 months, and was significantly higher at 6, 12 and 24 months after prostatectomy. The median mental component summary score was also significantly lower in the prostatectomy group at 1 month, but not from 3 months onwards. Conclusion Our study suggested that HRQOL was inferior at 1 month after RARP, however, recovered at 3 months after RARP and was better than after radiotherapy at 6, 12, and 24 months.

Purpose:To monitor the outcomes for intermediate-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 200 Gy radiotherapy using low-dose-rate (LDR) brachytherapy., Material and methods:Between 2005 and 2016, a total of 397 patients with intermediate-risk prostate cancer were treated by LDR-based radiotherapy with a BED ≥ 200 Gy. Treatments consisted of LDR brachytherapy alone (177 cases) or LDR and external beam radiotherapy (EBRT) (220 cases). Short-term androgen deprivation therapy (ADT) was used in 186 patients (46.9%). The median follow-up period was 72 months (range 29-165 months). Dosimetric parameters and BED were studied in each case. The numbers of intermediate-risk features were: 163 patients with 1 intermediate-risk feature (41%), 169 patients with 2 intermediate-risk features (43%), and 65 patients with 3 intermediate-risk features (16%). A total of 145 cases were diagnosed as having primary Gleason pattern 4: Gleason score 4 + 3 (36.5%)., Results:Three patients developed biochemical failure, thus providing a 7-year actual biochemical failure-free survival (BFFS) rate of 99.1%. Biochemical failure was observed exclusively in cases with distant metastasis: two cases with lymph node metastasis and one case with bone metastasis, thus yielding a 7-year freedom from clinical failure (FFCF) rate of 99.1%. We observed eight deaths, but there was no death from prostate cancer, thus yielding a 7-year cause-specific survival (CSS) rate of 100%, and an overall survival (OS) rate of 98.4%., Conclusions:This study highlights excellent outcomes for intermediate-risk prostate cancer patients, including unfavorable intermediate-risk cases, treated with BED ≥ 200 Gy radiotherapy using LDR brachytherapy. LDR alone with a BED of 200 Gy may be an optimal treatment for both favorable and unfavorable intermediate-risk prostate cancer patients, although a longer follow-up is mandatory to confirm the present findings.

Highlights • Superior biochemical progression free survival for LDR in combination with EBRT. • On multivariable analysis, HDR and EBRT and Gleason ≥8 predicted for progression. • Low cumulative incidence of ≥grade 3 GU and GI toxicities., Introduction There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR–EBRT) and high dose rate brachytherapy (HDR–EBRT) to treat intermediate and high risk prostate cancer. Methods Men with intermediate and high risk prostate cancer treated using LDR–EBRT (treated between 1996 and 2007) and HDR–EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results 116 men were treated with LDR-EBRT and 171 were treated with HDR–EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR–EBRT cohort and 77.6% for the HDR–EBRT cohort. On multivariable analysis, patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT (HR 2.33, 95% CI 1.12–4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26–23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR–EBRT and HDR–EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. Conclusion LDR–EBRT may provide more effective PSA control at 5 years compared with HDR–EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further.

Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques.Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale.Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients.These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

This study aimed to evaluate the oncological outcomes and post-implantation complications of the concurrent androgen deprivation therapy (ADT) with I-125 low-dose-rate (LDR)-prostate brachytherapy (sparse implantation technique: SIT) in comparison with the conventional non-ADT using whole gland brachytherapy (CWT). 302 localized prostate cancer (PCa) patients were treated with CWT (implantation dose: 145 Gy) and 215 patients were treated with SIT, which applied reduced implantation dose of 123.5 Gy. SIT group had ADT consisting of bicalutamide 50 mg/day plus 3-month depot (11.25 mg) of leuprolide acetate subcutaneously on the post-implantation day-0. Post-implantation complications and biochemical-recurrence-free-survival (BCRS) were compared between the two groups. After ADT, SIT group had 40.9% patients (40.9%) with prostate volume reduction between 20–30%. At 3-months post-implantation, SIT group presented significantly better IPSS than CWT group (p = 0.038). Both groups showed decrease in IIEF-5 score at 3-months post-implantation, but ST group showed significantly better mean IIEF-5 scores (13.5) than the CWT group (11.1) (p = 0.045). For 3-months post-implantation dosimetry, both groups showed no significant differences regarding D90 (CWT 156 Gy vs. SIT 152 Gy). CWT group had 3 patients with rectal toxicity ≥radiation therapy oncology group (RTOG) grade 2 and 1 patient with urinary toxicity ≥RTOG grade 2 whereas SIT group had no patient with urinary or rectal toxicity ≥RTOG grade 2. Kaplan-Meier analyses showed no significant differences regarding PCSS were observed between the two groups (p = 0.350). The SIT group showed compatible oncological outcomes to the CWT and relatively smaller number of post-implantation complications within low- and intermediate-risk PCa patients.

Purpose The goal of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibitors on quality of life (QoL) of patients undergoing low-dose-rate (LDR) brachytherapy. Material and methods A total of 310 patients with prostate cancer who had undergone LDR brachytherapy were enrolled. The patients were randomized (1 : 1) to the monotherapy group (tamsulosin alone: 0.2 mg/day, n = 156) and the combination group (tamsulosin: 0.2 mg/day plus celecoxib: 200 mg/day, n = 154) without placebo. Using the expanded prostate cancer index composite (EPIC) and medical outcomes study 8-item short form health survey (SF-8) questionnaire, QoL was evaluated at baseline and at 1, 3, 6, and 12 months after seed implantation. Results The mean changes in scores from baseline to 1 and 3 months after seed implantation for the urinary (1M: -10.5, 3M: -10.9) and bowel (1M: -2.4, 3M: -4.2) domains of EPIC in the combination group were not significantly different from those (urinary 1M: -11.0, 3M: -11.4, bowel 1M: -2.3, 3M: -4.6) in the monotherapy group. The mean changes in scores from baseline to 1 and 3 months after seed implantation for the physical component summary (1M: 0.009, 3M: -0.32) and mental component summary (1M: 0.41, 3M: 0.36) of SF-8 in the combination group were not significantly different from those (physical component 1M: -0.89, 3M: -0.22, mental component 1M: 1.3, 3M: 1.1) in the monotherapy group. Conclusions Combination treatment with celecoxib and tamsulosin during the peri-operative period is not warranted for improving QoL in patients undergoing LDR brachytherapy.

Purpose To compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial. Methods and Materials Men with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant. Results LDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028). Conclusions HDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.

The history of prostate brachytherapy has passed one century. In 1983, modern low-dose-rate prostate brachytherapy using a transrectal ultrasound-guided procedure was introduced. In the early 1990s, low-dose-rate brachytherapy was introduced and rapidly spread across the USA due to its excellent oncological control, cost-effectiveness and technically easy procedure. Since low-dose-rate brachytherapy was introduced in Japan (2003), over 15 years have passed. More than 43 000 patients have undergone low-dose-rate brachytherapy. Japanese urologists and radiation oncologists are on course with leading brachytherapists in the USA. A nationwide prospective cohort study, J-POPS, was initiated in 2005. The J-POPS group also provides educational programs including an annual novel training course in low-dose-rate brachytherapy to familiarize urologists, radiation oncologists and pathologists with the procedure. Important information on Japanese patients has accumulated, especially by the J-POPS study group. The Japanese investigators reported excellent oncological outcomes of low-dose-rate brachytherapy, showing equivalent or superior efficacy to surgery in low- to intermediate-risk patients, and superior efficacy in high-risk patients using the surgery biochemical recurrence definition (prostate-specific antigen cut-off value of 0.2 ng/mL). Two randomized controlled studies (SHIP study: intermediate risk, and TRIP study: high risk) carried out by the J-POPS group are ongoing, and an additional follow-up study (J-POPS 2 study) has been started to evaluate survival outcomes over longer follow-up periods. Low-dose-rate brachytherapy is expected to provide a survival benefit, which must be confirmed by further studies with longer follow-up periods in the future.

Recurrence of prostate cancer after initial treatment with radiation therapy (RT) is highly dependent on pretreatment risk group and unfortunately, a proportion of patients fail primary treatment. The treatment of recurrence after primary radiation is rapidly changing with advances in imaging and it is important to distinguish those with a local failure from those with distant failure. If disease remains locally confined, salvage treatment with a variety of techniques can still provide a potential cure. Patients with distant failure are often treated with androgen deprivation, or in those with a shorter life expectancy, conservative management. In patients with a higher burden of metastatic disease, there is emerging evidence that chemotherapy and advanced androgen therapy can improve survival. We review the relevant literature on available salvage treatment options and appropriate patient selection for patients with recurrent prostate cancer after RT. We report on the efficacy and adverse effects of the currently available local salvage modalities including salvage radical prostatectomy, high dose rate and low dose rate brachytherapy, cryotherapy, high intensity focused ultrasound, and stereotactic body RT. We additionally discuss diagnosis of oligometastatic disease on imaging and current approaches to treatment with either radiation or surgery. While a full review of chemotherapy and advanced androgen therapies is beyond the scope of this article we briefly discuss their use in the treatment of newly diagnosed recurrence after radiation.

INTRODUCTION AND OBJECTIVE:There is currently insufficient evidence on the appropriate surveillance duration after low-dose-rate brachytherapy (LDR) with iodine-125 for localized prostate cancer (P...

OBJECTIVE To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p

PurposeWe report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up.Methods and materialsEligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen

Background Few studies have assessed hydrogel spacer shrinkage during external-beam radiation therapy following brachytherapy for localized high-risk prostate cancer. This case presentation evaluated the changes in hydrogel spacer appearance by magnetic resonance imaging during external-beam radiation therapy after brachytherapy for prostate cancer and analyzed the effect of this shrinkage on the dose distribution in four cases. Case presentation In all cases, we implanted 125I sources using a modified peripheral loading pattern for seed placement. The prescribed dose for each implant was 110 Gy. After delivering the sources, a hydrogel spacer was injected. All cases underwent external-beam radiation therapy approximately 1–2 months after brachytherapy. The prescribed dose of external-beam radiation therapy was 45 Gy in 1.8-Gy fractions. Magnetic resonance imaging was performed for evaluation on the day following seed implantation (baseline), at external-beam radiation therapy planning, and during external-beam radiation therapy. The median hydrogel spacer volume was 16.2 (range 10.9–17.7) cc at baseline, 14.4 (range, 9.4–16.1) cc at external-beam radiation therapy planning, and 7.1 (range, 2.0–11.4) cc during external-beam radiation therapy. The hydrogel spacer volume during external-beam radiation therapy was significantly lower than that at external-beam radiation therapy planning. The rectum V60–80 (rectal volume receiving at least 60–80% of the prescribed dose of external-beam radiation therapy) during external-beam radiation therapy was significantly higher than that at external-beam radiation therapy planning. Conclusions The potential reduction in hydrogel spacer size during external-beam radiation therapy following brachytherapy can lead to unexpected irradiation to the rectum. This case presentation would be helpful for similar cases.

PURPOSE The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen

Purpose/Objective(s) Low dose rate (LDR) brachytherapy alone or with external beam radiation (EBRT) results in excellent rates of biochemical control in patients (pts) with prostate cancer (PCa). Understanding failure patterns in pts with biochemical recurrence (BCR) may inform implant technique or pt selection. The primary objective of this study was to describe locations of recurrence on multiparametric MRI (mpMRI) and prostate specific membrane antigen (PSMA) imaging in pts with BCR after LDR brachytherapy. Materials/Methods Pts with BCR after definitive LDR (± EBRT, ± androgen deprivation therapy (ADT)) referred for IRB approved imaging protocols were included. All pts underwent 3T mpMRI (T2 weighted, dynamic contrast-enhanced, and diffusion-weighted imaging) prospectively reviewed by prostate-dedicated radiologists. A subset of pts underwent PSMA-PET/CT imaging. Pathologic confirmation was obtained unless contraindicated. Prostate lesions were categorized as left (L)/right (R)/midline (ML); transitional zone (TZ)/peripheral zone (PZ); apical/mid/base; and anterior/posterior/central. Locations of recurrence (prostate, seminal vesicles (SV), lymph nodes (LN) and distant metastases (DM)) were recorded and reported descriptively. Results Between Jan 2011 and Feb 2021, 57 pts with BCR after LDR underwent prostate mpMRI. Treatment was LDR (n = 39) or EBRT + LDR (n = 18), ± ADT (n = 12). At time of LDR, initial Gleason score was ≤ 6 (n = 29), 7 (n = 19), 8-9 (n = 8), unknown (n = 1) and median PSA was 6 ng/mL (3.4-49). Of dosimetry available (n = 27), 2 had D90 Conclusion In this cohort of pts with BCR following LDR, the predominant locations of local recurrence were in the anterior/central TZ and SV. PSMA corroborated the majority of mpMRI findings and often demonstrated LN and DM. These findings may inform LDR technique and impact patient selection or pre-treatment imaging evaluation; and should be confirmed in larger subsets and correlated with post-implant dosimetry.

To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.

Treatment planning in low-dose-rate prostate brachytherapy (LDR-PB) aims to produce arrangement of implantable radioactive seeds that deliver a minimum prescribed dose to the prostate whilst minimizing toxicity to healthy tissues. There can be multiple seed arrangements that satisfy this dosimetric criterion, not all deemed ‘acceptable’ for implant from a physician’s perspective. This leads to plans that are subjective where quality of treatment depends on the expertise of the planner. We propose a method that learns to generate consistent treatment plans from a large pool of successful clinical data (961 patients). Our model is based on conditional generative adversarial networks that use a novel loss function for penalizing the model on spatial constraints of the seeds. An optional optimizer based on a simulated annealing (SA) algorithm can be used to further fine-tune the plans if necessary (determined by the treating physician). Performance analysis was conducted on 150 test cases demonstrating comparable results to that of the manual plans. On average, the clinical target volume covered by \(100\%\) of the prescribed dose was \(98.9\%\) for our method compared to \(99.4\%\) for manual plans. Moreover, using our model, the planning time was significantly reduced to an average of 3 s/plan (2.5 min/plan with the optional SA). Compared to this, manual planning at our centre takes around 20 min/plan.

CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low–dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.

Background We report the first prostate brachytherapy in Nigeria, using low dose radioactive iodine 125 (I-125) permanent seeds implant. Case Presentation The 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. Conclusions The 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.

Background: Radiotherapy (RT) when combined with anti-PD-1 therapy can have a significant anti-tumor effect, but RT fractionation and dose impact the effects of this combined therapy. Iodine-125 particle implantation (125I RPI) is a hyperfractionated low-dose-rate brachytherapy. Its impact on the tumor immune microenvironment and the efficacy of 125I RPI combined with anti-PD-1 therapy are unknown. In this study, we evaluated the effectiveness of 125I RPI combined with anti-PD-1 therapy and their impact on tumor immunity. Methods: A Lewis lung cancer (LLC) mouse model was established in the right hindlimb and radioactive iodine-125 particles were implanted into the tumors. Tumor tissues were obtained six and 12 days after particle implantation, and the expression of PD-1/PD-L1 was detected by flow cytometry. LLC cells were injected subcutaneously into the right hindlimb (primary tumor) on day 0 and into the left flank (secondary tumor) on day 3 of mice. On day 10, the mice were randomly divided into PBS, α-PD-1, 125I RPI, and α-PD-1+125I RPI groups. On day 22, primary tumor tissues were extracted from the mice. The proportion of immune cell subsets in the tumor immune microenvironment was detected by flow cytometry, and the primary and secondary tumor volumes were monitored. Results: After 125I RPI, the expression of PD-L1 on tumor cells was upregulated (P < 0.0001), and the proportion of CD8+ PD-1+ T cells also increased (P = 0.0001). 125I RPI combined with anti-PD-1 therapy synergistically inhibited primary (P = 0.0139) and secondary (P = 0.0494) tumor growth. The flow cytometry results showed that the combination therapy could increase the proportion of CD8+ T cells (P = 0.0055) and decrease the proportion of T regulatory cells (P < 0.0227) in the tumor microenvironment. Survival analysis shows that the sequence of 125I RPI and α-PD-1 affects efficacy, and early initiation of 125I RPI is more beneficial. Conclusion: 125I RPI combined with anti-PD-1 therapy can significantly inhibit tumor growth and activate anti-tumor immunity, which presents a promising approach for the treatment of cancer.

Background Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy. Case presentation This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy. Conclusion Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer.

Background and purpose: Both multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) imaging have shown promise in early localization of prostate cancer (PCa) recurrence after primary external beam radiotherapy. Detecting recurrence after brachytherapy for PCa using MRI is significantly hampered by susceptibility artifacts secondary to brachy seeds. Here, we compare the efficacy of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET/CT versus mpMRI for detecting sites of local recurrence after low dose rate (LDR) brachytherapy for prostate cancer. Materials and methods: A total of 155 patients with a history of recurrent PCa who underwent mpMRI at 3 Tesla and 18F-DCFPyL PET/CT were retrospectively reviewed. Patients who underwent LDR brachytherapy for PCa and had subsequent biochemical recurrence (BCR) followed by mpMRI and 18F-DCFPyL PET/CT were included in this study. mpMRI was performed on a 3T scanner with endorectal and surface coils and images were prospectively read by a single expert radiologist. The 18F-DCFPyL PET/CT scan was prospectively interpreted by one of two nuclear medicine physicians. Patients underwent targeted biopsy when deemed clinically necessary and specimens were interpreted by an expert GU pathologist. Positivity rates (PR) from mpMRI and 18F-DCFPyL PET/CT were compared, and pathology results were used to calculate the positive predictive value (PPV) of each imaging modality for detecting PCa recurrence.Results: 14 patients who underwent LDR brachytherapy and had subsequent biochemical failure were imaged with mpMRI and 18F-DCFPyL PET/CT. 17 lesions were identified on at least one imaging modality. The PR for detection of intraprostatic lesions was 71% (10/14) for PET/CT and 64.3% (9/14) for mpMRI. 18F-DCFPyL PET/CT identified pelvic and extra-pelvic lymph nodes in 8 (57%) patients, while mpMRI noted positive lymph node findings in only 2 (14%) patients. A total of 14 lesions corresponding to 8 patients were targeted for biopsy and in these, 18F-DCFPyL PET/CT performed better than mpMRI for the detection of local recurrence with a PPV of 81.8% vs. 66.7%. For the detection of intraprostatic lesions, 18F-DCFPyL PET/CT and mpMRI had a PPV of 87.5% and 71.4%, respectively. Conclusion: Our findings suggest that 18F-DCFPyL PET/CT detects local and regional recurrent PCa after LDR brachytherapy at a higher rate than mpMRI and has a much higher detection rate of suspicious pelvic lymph nodes. Further studies are needed to validate these findings in larger cohorts.

Purpose We sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. Materials and methods We 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. Results 108 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. Conclusions Salvage 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.

Permanent and temporary implantation of I-125 brachytherapy sources has become an official method for the treatment of different cancers. In this technique, it is essential to determine dose distribution around the brachytherapy source to choose the optimal treatment plan. In this study, the dosimetric parameters for a new interstitial brachytherapy source I-125 (IrSeed-125) were calculated with GATE/GEANT4 Monte Carlo code. Dose rate constant, radial dose function and 2D anisotropy function were calculated inside a water phantom (based on the recommendations of TG-43U1 protocol), and inside several tissue phantoms around the IrSeed-125 capsule. Acquired results were compared with MCNP simulation and experimental data. The dose rate constant of IrSeed-125 in the water phantom was about 1.038 cGy·h−1U−1 that shows good consistency with the experimental data. The radial dose function at 0.5, 0.9, 1.8, 3 and 7 cm radial distances were obtained as 1.095, 1.019, 0.826, 0.605, and 0.188, respectively. The results of the IrSeed-125 is not only in good agreement with those calculated by other simulation with MCNP code but also are closer to the experimental results. Discrepancies in the estimation of dose around IrSeed-125 capsule in the muscle and fat tissue phantoms are greater than the breast and lung phantoms in comparison with the water phantom. Results show that GATE/GEANT4 Monte Carlo code produces accurate results for dosimetric parameters of the IrSeed-125 LDR brachytherapy source with choosing the appropriate physics list. There are some differences in the dose calculation in the tissue phantoms in comparison with water phantom, especially in long distances from the source center, which may cause errors in the estimation of dose around brachytherapy sources that are not taken account by the TG43-U1 formalism.

PURPOSE:To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) and low-dose-ratebrachytherapy (LDR-BT) as monotherapy for localized prostate cancer of low and intermediate risks progression. METHODS AND MATERIALS: The study included 165 patients with localized prostate cancer in low and intermediate progression risk groups. We compared 65 patients treated with HDR-BT and 100 patients with LDR-BT as monotherapy. LDR-BT treated advanced disease with more hormonal therapy than HDR-BT. All patients were in low and intermediate risk groups for prostate cancer progression. HDR-BT as monotherapy was delivered in 2 fractions of 15 Gy, two weeks apart. LDR-BT was performed in a standard mode of 145 Gy. The median observation was 32 months. All patients gave written informed consent. RESULTS: Overall biochemical free survival rate (BFSR) is 95,8%. There are 7 people having a growing prostatic specific antigen (PSA) while the case follow-up (in the group HDR-BT - 2 patients, LDR - 5 patients). Two recurrence cases with metastases in lymph nodes and bones were brought out as a result of 68Ga-PSMA PET examination in the group of HDR-BT. In 4 cases out of 5 LDR-BT, a local recurrence was detected (p=0,085). All cases of relapse were found in patients at intermediate risk (p = 0,041). LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade >2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Accumulated incidence of late grade >2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. CONCLUSION: HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT for low and intermediate risk patients. LDR-BT showed equivalent incidence of grade >2 late GU toxicities and higher grade >2 acute GU toxicity as that of HDR-BT as a monotherapy.

Background To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy (EBRT) for localized prostate cancer. Methods and materials We compared 352 patients treated with HDR-BT as monotherapy (median follow-up time 84 months, NCCN risk classification; low: intermediate: high = 28:145:179) and 486 patients with LDR-BT with or without EBRT (90 months, 194:254:38). HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. LDR-BT excluded patients with T3b–T4 tumor and initial PSA >50 ng/ml. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Results The actuarial 5-year biochemical failure-free survival rates (bNED) were 92.9% and 95.6% (p = 0.25) in the HDR-BT and LDR-BT groups, respectively, and it was 100% and 97.3% (p = 0.99) in the low-risk, 95.6% and 94.3% (p = 0.19) in the intermediate, 89.6% and 94.9% (p = 0.26) in the high-risk groups, and 93.1% and 94.9% (p = 0.98) in selected high-risk group excluding T3b-4 and initial PSA ≥50. IPTW correction also indicated no difference in bNED between LDR-BT and HDR-BT groups. LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade ≥2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Acute GU toxicity grade ≥1 predicted late GU toxicity grade ≥2. External beam radiotherapy plus LDR-BT elevated GI toxicity than LDR-BT only group. Accumulated incidence of late grade ≥2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. No grade 4 or 5 toxicities were detected in either modality. Conclusion HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT with or without EBRT for low-, intermediate- and selected high-risk patients. LDR-BT showed equivalent incidence of grade ≥2 late GI and GU toxicities and higher grade ≥2 acute GU toxicity as that of HDR-BT as a monotherapy.

Purpose To compare the outcomes of patients with intermediate risk prostate cancer (IR-PCa) treated with low-dose rate I-125 seed brachytherapy (LDR-BT) and targeted dose painting of a histologic dominant intra-epithelial lesion (DIL) to those without a DIL. Methods 455 patients with IR-PCa were treated at a single center with intra-operatively planned LDR-BT, each following the same in-house dose constraints. Patients with a DIL on pathology had hot spots localized to that region but no specific contouring during the procedure. Results 396 (87%) patients had a DIL. Baseline tumor characteristics and overall prostate dosimetry were similar between patients with and without DIL except the median number of biopsy cores taken: 10 (10–12) vs 12 (10–12) (p = 0.002). 19 (5%) and 18 (5%) of patients with and 1 (2%) and 0 (0%) of those without DIL experienced CTCAE grade 2 and 3 toxicity respectively. Overall, toxicity grade did not significantly correlate with presence of DIL (p = 0.10). Estimated 7-year freedom from biochemical failure (FFBF) was 84% (95% confidence interval: 79–89) and 70% (54–89) in patients with and without a DIL (log-rank p = 0.315). In DIL patients, cox regression revealed location of DIL (“Base” vs “Apex” HR: 1.03; 1.00–1.06; p = 0.03) and older age (70 vs 60 HR: 1.62; 1.06–2.49; p = 0.03) was associated with poor FFBF. Conclusions Targeting DIL through dose painting during intraoperatively planned LDR-BT provided no statistically significant change in FFBF. Patients with DILs in the prostate base had slightly lower FFBF despite DIL boost., Radiation physics; Surgery; Cancer surgery; Urology; Oncology; Prostate cancer; Brachytherapy; Low-dose-rate.

Background: To evaluate the occurrence of erectile dysfunction at 3 years (3yED) after prostate brachytherapy (BT) and to predict 3yED after treatment based on patients and treatments characteristi...

Background We describe two patients who underwent low-dose-rate prostate brachytherapy after embolization for pelvic arteriovenous malformation. Case presentation Case 1: A 76-year-old man was referred for definitive treatment of intermediate-risk prostate cancer (prostate-specific antigen 8.667 ng/mL, cT2aN0M0, Gleason score 3 + 4 = 7). We planned low-dose-rate brachytherapy. However, magnetic resonance imaging and computed tomography demonstrated a large pelvic arteriovenous malformation. We performed embolization of the arteriovenous malformation before initiating treatment to lower the risk of rupture of the arteriovenous malformation during low-dose-rate brachytherapy. Case 2: A 69-year-old man was referred for the definitive treatment of high-risk prostate cancer (prostate-specific antigen 5.81 ng/mL, cT2aN0M0, Gleason score 4 + 4 = 8) with a pelvic arteriovenous malformation. Similar to Case 1, we performed embolization of the arteriovenous malformation before initiating treatment. In both cases, low-dose-rate brachytherapy could be performed without complications. Conclusions Low-dose-rate brachytherapy after transcatheter embolization of pelvic arteriovenous malformations can safely and effectively treat localized prostate cancer with pelvic arteriovenous malformations.

Purpose To study the feasibility of hyaluronic acid (HA) injection to increase the distance between skin and radioactive sources, and dose reduction of skin during low-dose-rate (LDR) brachytherapy. Material and methods: A total of 11 patients with subdermal malignant tumors were enrolled in this study. HA was injected after I-125 seed implantation, and dosimetric parameters were calculated by a brachytherapy treatment planning system (BTPS). The distance of the new space between radioactive sources and skin was measured on computed tomography (CT) and magnetic resonance imaging (MRI). Clinical signs were observed and followed up for every patient. Results After HA injection, the average of newly generated maximum distance was 1.0 cm along the entire length of the tumor. The D90 and V100 did not significantly change for tumors before or after injection (p = 0.39, p = 0.50, respectively). The maximum dose to a relatively small volume (0.1 cc) of the skin (OAR-Max) decreased from 100.66 Gy to 61.20 Gy (p < 0.05), and the mean skin dose (OAR-Mean) decreased from 49.20 Gy to 17.27 Gy (p < 0.05) after injection. On follow-up CT and MRI, HA was quite stable in shape and position for nearly 6 months. Conclusions Our study results showed that an additional 1.0 cm distance between the radioactive source and skin could be induced by HA injection in patients with subdermal tumor, and this distance could significantly decrease the skin dose in LDR brachytherapy. In addition, no obvious toxicity and side effects were produced by HA injection. Therefore, hyaluronic acid injection is a safe and effective technique.