Prospective, Randomized, Controlled Pivotal Trial of Biodegradable Balloon Rectal Spacer for Prostate Radiation Therapy.

PURPOSE/OBJECTIVES: Rectal spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We evaluated efficacy and safety of a novel rectoprostatic spacer balloon which allows potential for controlled, adaptable deployment. This study tested co-primary hypotheses: 1) Balloon spacer would result in ≥ 25% reduction of rectal V70 in > 75% of subjects, and 2) Implantation procedure-related and rectal ≥ Grade 1 adverse events within 6 months (duration ≥ 2 days, CTCAE 4.0) would be non-inferior in balloon vs control subjects. MATERIALS/METHODS: 222 subjects were enrolled at 16 centers. All patients had T1-T3 prostate cancer without MRI evidence of posterior extraprostatic invasion. Randomization was 2:1 (balloon: control) and subject-blinded. Patients underwent transperineal TRUS-guided fiducial placement +/- balloon, followed by IMRT (81 Gy in 1.8 Gy fractions or biologically equivalent hypofractionated dose). For efficacy comparisons, plans were generated by a central core lab on pre- and post-implant CT scans. RESULTS: The primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction >25% (p<0.001). Mean V70 was 7.0 % pre- vs 1.1% post- implant. The primary safety endpoint was met with balloon subjects experiencing fewer ≥ Grade 1 events, 18% vs 23% (p < 0.001 for non-inferiority). On pre-defined secondary endpoint of ≥ Grade 2 events, rates trended lower in balloon subjects (4.3% vs 6.5%, p=0.527). Mean perirectal spacing was 19 ±3.7mm and maintained through radiation treatment (18 ±3.9mm). Balloon resorption was observed on 6-month CT in 98.5% (133/135) of subjects. The EPIC QOL instrument was collected throughout study, and did not differ statistically between the study arms. CONCLUSIONS: Biodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months.

Characterization of Treatments and Disease Course for Women with Breast Cancer Brain Metastases: 5-Year Retrospective Single Institution Experience.

PURPOSE: Around 30% of patients with breast cancer will develop brain metastases (BM). We sought to characterize the disease course, treatments and outcome for our patient cohort. MATERIALS AND METHODS: We extracted clinicopathological data from electronic records from January 2015 to December 2020. Results were generated using SPSS statistics v27. RESULTS: We identified 98 patients. Median overall survival (OS) from BM diagnosis was 3 months [hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-], 8 months [HR+/HER2+], 7 months [HR-/HER2+] and 2 months [triple negative breast cancer (TNBC)]. Whole brain radiotherapy (WBRT) (n=48, 70%) was most frequently used followed by surgery (n=15, 22%) and stereotactic radiosurgery (n=6, 8%). In patients who received WBRT alone (n=40) the median OS post WBRT was 2.6 months. CONCLUSION: After BM development, half of the patients had systemic therapy and 70% had local therapy, but only the HER2 subgroup had a prolonged OS likely reflecting central nervous system (CNS) activity of anti-HER2 drugs. TNBC patients had the worst prognosis. Although our cohort is small, OS was >1 year for 60% of HER2+ patients who received trastuzumab emtansine after BM development, which is encouraging for antibody drug conjugates and CNS activity. Patients who received WBRT had a higher burden of CNS disease and had an OS of less than 3 months.

Unexpected Seed Migration in Prostate Brachytherapy Implants Coincident with Change in Seed Stranding Product.

PURPOSE: This study was undertaken to determine if significant seed migration occurred when our institution changed seed products by comparing patterns of seed migration in implants containing different stranding material. METHODS AND MATERIALS: Day 0 and Day 30 CT scans were registered by the contoured prostate center of mass. An implant reconstruction program identified seeds on CT according to the pre-plan, enabling one-to-one correspondence between Day 0 and Day 30 seeds. Significant seed migration was defined by review of seeds that migrated > 2 cm outside the prostate or appearance in unexpected locations.   Results: Twenty-five (149, 16.8%) new strands displayed movement > 2 cm between Day 0 and Day 30 compared with just 2/118 (1.7%) of the standard strands. Six out of 26 (23%) patients with new strands displayed significant migration compared with 2/13 (14%) of patients with standard strands. In the six patients with new strands and significant migration, a mean of four strands (17%, range: 2-8 per patient) migrated significantly with 65% due to whole strand migration, 25% due to strand breakage, and 10% strand clumping. In the control group, only two strands (2%) migrated significantly, both due to strand breakage. Despite the greater seed movement with the new strands, Day 0 and Day 30 dosimetry was acceptable. CONCLUSION: In this short report, we identified that a change to a new strand type was associated with unexpected significant seed movement compared to our typical strands. Since seed movement can arise from unexpected causes, it is important to maintain quality assurance practices when a change in technique or infrastructure is instituted.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance.

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

Role for (11)C-choline PET in active surveillance of prostate cancer.

INTRODUCTION: Active surveillance (AS) is an increasingly popular management strategy for men diagnosed with low-risk indolent prostate cancer. Current tests (prostate-specific antigen [PSA], clinical staging, and prostate biopsies) to monitor indolent disease lack accuracy. (11)C-choline positron emission tomography (PET) has excellent detection rates in local and distant recurrence of prostate cancer. We examine (11)C-choline PET for identifying aggressive prostate cancer warranting treatment in the AS setting. METHODS: In total, 24 patients on AS had clinical assessment and PSA testing every 6 months and (11)C-choline PET and prostate biopsies annually. The sensitivity and specificity to identify prostate cancer and progressive disease (PD) were calculated for each (11)C-choline PET scan. RESULTS: In total, 62 biopsy-paired, serial (11)C-choline PET scans were analyzed using a series of standard uptake value-maximum (SUVmax) cut-off thresholds. During follow-up (mean 25.3 months), 11 of the 24 low-risk prostate cancer patients developed PD and received definitive treatment. The prostate cancer detection rate with (11)C-choline PET had moderate sensitivity (72.1%), but low specificity (45.0%). PD prediction from baseline (11)C-choline PET had satisfactory sensitivity (81.8%), but low specificity (38.5%). The addition of clinical parameters to the baseline (11)C-choline PET improved specificity (69.2%), with a slight reduction in sensitivity (72.7%) for PD prediction. CONCLUSIONS: Addition of (11)C-choline PET imaging during AS may help to identify aggressive disease earlier than traditional methods. However, (11)C-choline PET alone has low specificity due to overlap of SUV values with benign pathologies. Triaging low-risk prostate cancer patients into AS versus therapy will require further optimization of PET protocols or consideration of alternative strategies (i.e., magnetic resonance imaging, biomarkers).