A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.

Characterization of rib fracture development following liver directed stereotactic body radiation therapy.

Purpose: Rib fractures are a well-described complication following thoracic stereotactic body radiation therapy (SBRT). However, there are limited data in the setting of liver-directed SBRT. Methods: Patients who underwent liver SBRT from 2014 to 2019 were analyzed. Logistic regression models were used to identify the demographic, clinical, and dosimetric factors associated with the development of rib fractures. Results: Three hundred and forty-three consecutive patients were reviewed with median follow-up of 9.3 months (interquartile range [IQR]: 4.7-17.4 months); 81% of patients had primary liver tumors and 19% had liver metastases. Twenty-one patients (6.2%) developed rib fractures with a median time to diagnosis of 7 months following SBRT (IQR: 5-19 months). Of those patients, 11 experienced concomitant chest wall pain, while 10 patients had an incidental finding of a rib fracture on imaging. On univariate analysis, female gender (odds ratio [OR]: 2.29; p = 0.05), V30 Gy (OR: 1.02; p < 0.001), V40 Gy (OR: 1.08; p < 0.001), maximum chest wall dose (OR: 1.1; p < 0.001), and chest wall D30 cm3 (OR: 1.09; p < 0.001) were associated with an increased probability of developing a rib fracture. On multivariate analysis, maximum chest wall dose (OR: 1.1; p < 0.001) was associated with developing a rib fracture. Receipt of more than one course of SBRT (p = 0.34), left versus right sided lesion (p = 0.69), osteoporosis (p = 0.54), age (p = 0.82), and PTV volume (p = 0.55) were not significant. Conclusions: Rib fractures following liver SBRT were observed in 6.2% of patients with the majority being asymptomatic. To mitigate this risk, clinicians should minimize dose delivery to the chest wall. Female patients may be at increased risk.

Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy.

BACKGROUND AND PURPOSE: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy. METHODS AND MATERIALS: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards. RESULTS: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy. CONCLUSIONS: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality.