Supplementary Table 8 shows summary statistics of 16 SNPs associated with 23 concordant dQTLs across cohorts
Supplementary Table 6 displays the number of dQTLs identified for each somatic driver in each analysis strategy. Summary statistics from local dQTL associations. Statistics from logistic regression correcting for five genetic principal components, age and somatic mutation burden. OR = odds ratio; SE = standard error; L95 = lower 95% confidence interval; U95 = upper 95% confidence interval
Supplementary Table 9 summarizes the characterization of 16 SNPs associated with 23 concordant dQTLs.
Supplementary Table 1 shows a feature-by-patient summary matrix. For each patient, this table provides version information of bioinformatics tools, summary sequencing statistics, mutational density metrics, clinical information and driver mutation status for all drivers detected using GISTIC and ActiveDriverWGS as or identified in Armenia and colleagues 2018. Two additional tables are provided for the clinical and mutation data for the discovery and replication cohorts of dQTL discovery.
Supplementary Table 3 illustrates driver co-occurrence analysis, driver clusters, and associations of drivers with clinical features
Abstract Objectives To prospectively evaluate oncological control, pathological progression, and its predictors following focal low‐dose‐rate (LDR) brachytherapy for low‐intermediate risk prostate cancer (PCa). Patients and methods LIBERATE is a prospective, multi‐centre clinical registry of patients who have undergone focal LDR brachytherapy for low‐intermediate risk PCa since September 2019 (ACTRN:12619001669189). Unifocal ISUP GG1 (≥10 mm in ≥1 core), GG2 (any length) or GG3 (longest core<10 mm) were included. Follow‐up entailed serial PSA measurements, and surveillance mpMRI and repeat transperineal prostate biopsy at 18–24 months post‐treatment. Pathological control was achieved on repeat biopsy if there was no cancer or ISUP GG1 in <10 mm of core or GG2–3 grade cancer with radiation treatment effect. Progression was defined as no pathological changes from baseline or tumour upgrading. Results Of 120 men enrolled, 55 (45.8%) have completed repeat histopathological assessments with a median (IQR) follow‐up of 38 (33–45) months. Pathological control was reported in 42 (76.4%) patients, including 25 negative biopsies, 12 clinically insignificant disease, and five in‐field ISUP GG2–3 with radiation treatment effect. Pathological progression was observed in 13 patients (23.6%), with concurrent clinically significant in‐ and out‐of‐field progression in three cases (5.5%) and isolated clinically significant out‐of‐field progression in 10 cases (18.2%). Five (9.1%) patients underwent salvage treatment, including three robotic‐assisted radical prostatectomies, one contralateral lobe LDR brachytherapy and one external beam radiation therapy. The salvage‐free survival at 1, 2, 3 and 4 years were 98.2%, 96.4%, 94.2% and 87.0%, respectively. Mean PSA velocity >0.55 ng/mL/year was a strong predictor of pathological progression (OR 23.54, 95% CI 4.28–129.35, p = 0.001), with a sensitivity of 76.9% and specificity of 90.5%. Conclusion With a median follow‐up of 38 months, these early results suggest that focal LDR brachytherapy for low‐intermediate risk, single‐lesion, imaging‐visible PCa demonstrates satisfactory oncological control. However, further follow‐up is needed to assess long‐term oncological outcomes.
Supplementary Table 11 reports percentages of cross-individual contamination for each sample and sequencing lane.
Objectives:We aim to prospectively evaluate functional outcomes and toxicity following focal low-dose-rate (LDR) brachytherapy for low-intermediate risk prostate cancer (PCa). Patients and Methods:LIBERATE is a clinical registry of men treated with focal LDR brachytherapy for low-intermediate risk PCa since September 2019. Follow-up occurred at 6 weeks and every 3 months thereafter. Outcomes were assessed using validated patient-reported outcome measures (PROMs): IPSS, Expanded PCa Index Composite (EPIC) Bowel Assessment, and International Index of Erectile Function (IIEF-5). Adverse events (AEs) were clinically graded per Common Terminology Criteria for Adverse Events v5.0. Minimal important differences (MIDs) were defined as ±3.1 for IPSS, ±5 for EPIC bowel domain, and ±4 for IIEF-5. Results:Of 120 patients enrolled, 88/120 (73.3%) had ≥12 months follow-up, and 79/88 (89.7%) completed PROMs with a median (IQR) follow-up of 33 (26-41) months. At 6 weeks, a transient, statistically and clinically significant increase in IPSS was observed, which returned to baseline by 12 months (median IPSS: 6 at baseline, 12 at 6 weeks, 6 at 12 months). EPIC bowel scores showed no significant changes, with 72 (91.1%) patients having rectal spacer. Among 66 sexually active men, 40 (60.6%) had no or mild erectile dysfunction (ED) at baseline, with a median IIEF-5 score of 22.5, decreasing to 22 at 6 weeks and plateauing at 21 at 6 months, none meeting MID criteria. For the 26 patients with mild to severe ED at baseline, the median IIEF-5 score declined from 10 at baseline to 5 at 6 months, with partial recovery followed by a drop to 5.5 at 2.5 and 3 years. Declines at 6 months and beyond 2 years were both statistically and clinically significant. No Grade ≥3 AEs were reported. Conclusion:Focal LDR brachytherapy is associated with favorable functional outcomes and minimal toxicity. Further studies are required to evaluate long-term results.
We report a case of granulomatous prostatitis in a young male confirmed on histopathological examination. The case was initially presumed to be a case of prostate adenocarcinoma based on clinical, biochemical and imaging findings. To our knowledge, this is the second such reported case where there is a possible association between psoriasis and the subsequent development of granulomatous prostatitis and the only reported case of a patient on guselkumab immunotherapy.
Supplementary Table 5 displays summary statistics from PRS and HOXB13 associated with somatic drivers. β and P-value from logistic regression correcting for five genetic principal components, age and somatic mutation burden. FDR = false discovery rate.
Objectives To analyse the utility of adding multiparametric magnetic resonance imaging (mpMRI) with 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in detection of local recurrence (LR) and distant recurrence (DR) in patients with biochemical recurrence (BCR), by describing detection rates over time since radical prostatectomy (RP), describing detection rates at differing prostate-specific antigen (PSA) intervals, and identifying clinicopathological factors that predict detection of recurrence on imaging. Patients and Methods Patients with BCR after RP were identified from 2016 to 2020. Kaplan-Meier analysis was performed for LR and DR on mpMRI, 68Ga-PSMA PET/CT, and paired/combined scans, and multivariate regression was performed identifying predictors of LR and DR. Results A total of 117 patients underwent 150 sets of paired scans for BCR after RP, at PSA thresholds 0.2, 0.5, and 1.0 ng/mL. The 68Ga-PSMA PET/CT had higher detection rates of DR at PSA levels of <0.2, 0.2-0.5, 0.5-1.0, and >1.0 ng/mL vs mpMRI (6.1%, 10%, 25% and 36% vs 3%, 6.7%, 6.3%, and 24%, respectively). Meanwhile, mpMRI had higher detection rate of LR than 68Ga-PSMA PET/CT (30.3%, 33.3%, 40.6%, and 40% vs 0%, 13.3%, 18.8%, and 32%, respectively). The detection rate for LR was significantly higher on MRI compared to PSMA at PSA levels of <0.2 and 0.2-0.5 ng/mL (P < 0.001 and P = 0.001, respectively). The detection rate for DR was significantly higher on PSMA than MRI at PSA levels of 0.5-1.0 ng/mL (P = 0.039). On multivariate analysis, PSA velocity was a statistically significant predictor of both LR and DR on MRI alone, PSMA alone, and combined results of paired PSMA and MRI, and International Society of Urological Pathology grade was a statistically significant predictor of DR on MRI. Conclusion The mpMRI had a higher detection rate for LR, while 68Ga-PSMA PET/CT had a higher detection rate for DR. PSA velocity was a significant predictor of both LR and DR on both imaging modalities. In BCR after RP, addition of mpMRI with 68Ga-PSMA PET/CT may improve diagnosis of recurrent lesions and patient selection for treatment.
Supplementary Table 2 displays results from driver selection, driver groupings and driver associations.
[177Lu]Lu-PSMA radioligand therapy targets metastatic castration-resistant prostate cancer by delivering radiation to cells expressing prostate-specific membrane antigen (PSMA). While some patients show remarkable responses, up to 50
Supplementary Table 10 lists dQTL SNPs identified as eQTLs in prostate tissue in GTEx.
Supplementary Table 4 shows driver selection for dQTL nomination and prevalence of drivers in cohorts
Supplementary Figures & Figure Legends. Supplementary Figure 1 | Cohort Structure and Analysis. Supplementary Figure 2 | CNA Evolution & Transcriptomic Effects. Supplementary Figure 3 | Properties of Driver Mutations. Supplementary Figure 4 | Pathway & Signature Analysis of Driver Genes. Supplementary Figure 5 | Patterns of Mutational Drivers. Supplementary Figure 6 | Molecular Correlates of Clinical Behavior. Supplementary Figure 7 | Heterogeneity of Driver-Clinical Associations. Supplementary Figure 8 | Cohort Characteristics and Risk dQTL Replication. Supplementary Figure 9 | Local dQTLs Discovery. Supplementary Figure 10 | Replication of dQTLs. Supplementary Figure 11 | Enrichment of Sub-threshold dQTLs. Supplementary Figure 12 | Molecular Characterization of dQTLs. Supplementary Figure 13 | Association of dQTL Risk SNPs with eQTL and IMS. Supplementary Figure 14 | Clinical Characterization of dQTLs.