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Purpose/objectivesHigh-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure.Materials/methodsWe conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis.ResultsFrom 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%.ConclusionsTo our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

Purpose: Following radical prostatectomy, prostate bed radiotherapy (PBRT) has been combined with either long-term androgen deprivation therapy (LT-ADT) or short-term ADT with pelvic lymph node radiotherapy (PLNRT) to provide an oncological benefit in randomized trials. McGill 0913 was designed to characterize the efficacy of combining PBRT, PLNRT, and LT-ADT. It is the first study to do so prospectively.Methods: In a single arm phase II trial conduced from 2010 to 2016, 46 post-prostatectomy prostate cancer patients at a high-risk for relapse (pathological Gleason 8+ or T3) were assessed for treatment with combined LT-ADT (24 months), PBRT, and PLNRT. Patients received PLNRT and PBRT (44 Gy in 22 fractions) followed by a PBRT boost (22 Gy in 11 fractions). The primary endpoint was progression-free survival (PFS). Toxicity and quality of life (QoL) were evaluated using CTCAE V3.0 and EQ-5D-3L questionnaires, respectively.Results: Among the 43 patients were treated as per protocol, median PSA was 0.30 μg/L. On surgical pathology, 51% had positive margins, 40% had Gleason 8+ disease, 42% had seminal vesicle involvement, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there were no deaths or clinical progression. At 5 years, PFS was 78.0% (95% Confidence Interval 63.7–95.5%). Not including erectile dysfunction, patients experienced: 14% grade 2 endocrine toxicity while on ADT, one incident of long-term gynecomastia, 5% grade 2 acute urinary toxicity, 5% grade 2 late Urinary toxicity, and 24% long-term hypogonadism. No comparison between the average or minimum self-reported QoL at baseline, during ADT, nor after ADT demonstrated a statistically significant difference.Conclusions: Combining PBRT, PLNRT, and LT-ADT had an acceptable PFS in patients with significant post-operative risk factors for recurrence. While therapy was well-tolerated, long-term hypogonadism was a substantial risk. Further investigations are needed to determine if this combination is beneficial.Trial registration: NCT01255891.

We evaluated whether transcranial direct current stimulation (tDCS) in two different montages could improve picture naming abilities in participants with anomic Alzheimer Disease or Frontotemporal dementia.MethodsUtilizing a double-blind cross-over design, twelve participants were trained on picture naming over a series of 10 sessions with 30 min of anodal (2 mA) tDCS stimulation to either the left inferior parietotemporal region (P3), the left dorsolateral prefrontal cortex (F3), or sham stimulation. We evaluated performance on a trained picture naming list, an equivalent novel untrained list, and additional neuropsychological tasks.ResultsFor trained item picture naming, significantly larger improvement was seen for real stimulation vs. sham stimulation for both the DLPFC and left inferior parieto-temporal stimulation montages at the end of the stimulation sessions. The parieto-temporal montage remained superior to sham 2 weeks poststimulation. Significant improvement vs. sham was also seen for novel “untrained” item picture naming 2 weeks post-stimulation when the parieto-temporal montage was given, whereas no change was observed when the DLPFC montage was given. Finally, comparing groups when they received the parieto-temporal montage, participants with semantic variant Primary Progressive Aphasia (PPA) showed the least improvement for untrained items after their sessions. Scores on the additional neuropsychological tasks were unchanged.ConclusiontDCS stimulation has promise as a treatment for individuals with anomia arising from neurodegenerative disease, but its effectiveness can vary depending on the training given, the montage location used, as well as a participants’ diagnosis.

Purpose: Use of quantitative imaging features and encoding the intra-tumoral heterogeneity from multi-parametric magnetic resonance imaging (mpMRI) for the prediction of Gleason score is gaining attention as a non-invasive biomarker for prostate cancer (PCa). This study tested the hypothesis that radiomic features, extracted from mpMRI, could predict the Gleason score pattern of patients with PCa.Methods: This analysis included T2-weighted (T2-WI) and apparent diffusion coefficient (ADC, computed from diffusion-weighted imaging) scans of 99 PCa patients from The Cancer Imaging Archive (TCIA). A total of 41 radiomic features were calculated from a local tumor sub-volume (i.e., regions of interest) that is determined by a centroid coordinate of PCa volume, grouped based on their Gleason score patterns. Kruskal-Wallis and Spearman's rank correlation tests were used to identify features related to Gleason score groups. Random forest (RF) classifier model was used to predict Gleason score groups and identify the most important signature among the 41 radiomic features.Results: Gleason score groups could be discriminated based on zone size percentage, large zone size emphasis and zone size non-uniformity values (p < 0.05). These features also showed a significant correlation between radiomic features and Gleason score groups with a correlation value of −0.35, 0.32, 0.42 for the large zone size emphasis, zone size non-uniformity and zone size percentage, respectively (corrected p < 0.05). RF classifier model achieved an average of the area under the curves of the receiver operating characteristic (ROC) of 83.40, 72.71, and 77.35% to predict Gleason score groups (G1) = 6; 6 < (G2) < (3 + 4) and (G3) ≥ 4 + 3, respectively.Conclusion: Our results suggest that the radiomic features can be used as a non-invasive biomarker to predict the Gleason score of the PCa patients.