Focal HDR brachytherapy boost to stereotactic radiotherapy (fBTsRT) for prostate cancer: a phase II randomized controlled trial.

BACKGROUND: For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. METHODS: 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing < 50% of the prostate gland. Those randomly selected will be offered the experimental treatment, consisting of focal HDR brachytherapy boost (fBT) of 13-15 Gy in 1 fraction followed by stereotactic radiotherapy (sRT) 36.25-40 Gy in 5 fractions to the prostate (+/- 25 Gy to the elective pelvis) delivered every other day. The primary endpoint is to determine if fBTsRT is superior to SOC by having fewer patients experience a minimally important decline (MID) in urinary function as measured by EPIC-26 at 1 and 2 years. Secondary endpoints include rates of toxicity measured by Common Terminology Criteria for Adverse Events (CTCAE), and failure-free survival outcomes. DISCUSSION: This study will determine whether a novel approach for the treatment of localized prostate cancer, fBTsRT, improves QoL and merits further evaluation. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04100174 as a companion to registry NCT03378856 on September 24, 2019.

Randomised Phase II Feasibility Trial of Image-guided External Beam Radiotherapy With or Without High Dose Rate Brachytherapy Boost in Men with Intermediate-risk Prostate Cancer (CCTG PR15/ NCT01982786).

AIMS: We conducted a multicentre feasibility study to assess the ability to randomise patients between image-guided radiotherapy (IGRT) and IGRT + high dose rate (HDR) brachytherapy boost and to adhere to appropriate radiation quality assurance standards. MATERIALS AND METHODS: The primary end point was to determine the ability to randomise 60 patients over an 18 month period. Arm 1 (IGRT) patients received 78 Gy in 39 fractions or 60 Gy in 20 fractions (physician's preference), whereas arm 2 (IGRT + HDR) received 37.5 Gy in 15 fractions with HDR boost of 15 Gy. The secondary end points included >grade 3 acute genitourinary and gastrointestinal toxicity, using Common Terminology Criteria for Adverse Events version 4.0 at 3 months, validation of a prospectively defined radiation oncology quality assurance to assess treatment compliance. All analyses were descriptive; no formal comparisons between treatment arms were carried out. RESULTS: Between April 2014 and September 2015, 57 National Comprehensive Cancer Network (NCCN)-defined intermediate-risk prostate cancer patients were randomised between IGRT alone (arm 1; n = 29) and IGRT plus HDR brachytherapy boost (arm 2; n = 28). Overall, 93% received the treatment as randomised. There were four patients (one on IGRT arm 1 and three patients on the IGRT + HDR arm 2) who were treated differently from randomisation assignment. For the 29 patients receiving IGRT (arm 1), there were 14 cases reported with minor deviations and three with major deviations. For patients on IGRT + HDR (arm 2), there were 18 cases reported with minor deviations and two with major deviations. At 3 months in the IGRT group (arm 1), one patient reported grade 3 diarrhoea, whereas in the IGRT + HDR group (arm 2), two patients reported grade 3 haematuria. No other gastrointestinal and genitourinary toxicities were reported. CONCLUSION: The pilot study showed the feasibility of randomisation between treatment with IGRT alone versus IGRT + HDR boost. Treatment compliance was good, including adherence to quality assurance standards.

Changes in periprostatic adipose tissue induced by 5α-reductase inhibitors.

There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer. The objective of the study was to determine the interaction between 5α-reductase inhibitors (5ARIs) and periprostatic adipose tissue (PPAT) and factors of prostate cancer aggressiveness. In this retrospective study, we identified 61 patients treated with 5ARIs for a period of ≥12 months before undergoing radiation therapy (brachytherapy or external beam radiotherapy). The control group consisted of 117 patients without any exposure to 5ARIs. Prior to being treated, all patients underwent abdominal computed tomography (CT). To measure PPAT, we defined the fat pad anteriorly to the prostate, as well as the intra-abdominal visceral adipose tissue (VAT) and subcutaneous tissue (SAT) at the level of L4/L5. All contours were performed manually. These adipose tissue measurements were correlated with the Cancer of the Prostate Risk Assessment (CAPRA) score using Pearson correlation coefficient. Differences in fat contents were evaluated using Student's t-test. Median time on 5ARIs for the 61 patients was 12 months (range 12-96). Patient on 5ARIs had a significantly (p < 0.001) smaller PPAT (0.4, SD 0.5) than patients without a 5ARI (0.6 cc, SD 0.4). There was no significant correlation between the CAPRA score and fat measurements when adjusted for 5ARI use (p = 0.18). In non-5ARI users, BMI was not correlated with PPAT but was correlated with SAT and VAT volume and its density. There were no significant differences in diabetics (p = 0.3), metformin users (p = 0.4) or statin users (p = 0.09) between both groups. 5ARIs taken for at least 12 months induce changes in PPAT volume. Whether these changes or the extent of changes will have an influence on outcome remains unknown.

The use of magnetic resonance imaging for image-guided brachytherapy.

Progress has been made in the delivery of brachytherapy, from low-dose rate (LDR) to high-dose rate (HDR) treatments, allowing for dose optimisation, conformal treatments, improved radiation protection, and improved accuracy and efficiency. Image-guided brachytherapy, incorporating spatial and temporal changes, is now possible with advanced imaging and treatment technology. This report reviews the evidence for the benefits of image-guided brachytherapy using magnetic resonance imaging (MRI), mainly for cervix and prostate cancer, but also possibilities for other tumour sites. It also emphasises the need for a dedicated MRI unit for brachytherapy.