Epworth Collection:
http://hdl.handle.net/11434/126
2024-03-28T10:27:23ZComparison of perioperative outcomes following transperitoneal versus retroperitoneal robot-assisted partial nephrectomy: a propensity-matched analysis of VCQI database.
http://hdl.handle.net/11434/2124
Title: Comparison of perioperative outcomes following transperitoneal versus retroperitoneal robot-assisted partial nephrectomy: a propensity-matched analysis of VCQI database.
Epworth Authors: Moon, Daniel
Abstract: Objective: To compare perioperative outcomes following retroperitoneal (RPRAPN) and transperitoneal robot-assisted partial nephrectomy (TPRAPN).
Methods: With this Vattikuti Collective Quality Initiative (VCQI) database, study propensity scores were calculated according to the surgical access (TPRAPN and RPRAPN) for the following independent variables, i.e., age, sex, side of the surgery, RENAL nephrometry scores (RNS), estimated glomerular filtration rate (eGFR) and serum creatinine. The study's primary outcome was the comparison of trifecta between the two groups.
Results: In this study, 309 patients who underwent RPRAPN were matched with 309 patients who underwent TPRAPN. The two groups matched well for age, sex, tumor side, polar location of the tumor, RNS, preoperative creatinine and eGFR. Operative time and warm ischemia time were significantly shorter with RPRAPN. Intraoperative blood loss and need for blood transfusion were lower with RPRAPN. There was a significantly higher number of intraoperative complications with RPRAPN. However, there was no difference in the two groups for postoperative complications. Trifecta outcomes were better with RPRAPN (70.2% vs. 53%, p < 0.0001) compared to TPRAPN. We noted no significant change in overall results when controlled for tumor location (anteriorly or posteriorly). The surgical approach, tumor size and RNS were identified as independent predictors of trifecta on multivariate analysis.
Conclusion: RPRAPN is associated with superior perioperative outcomes in well-selected patients compared to TPRAPN. However, the data for the retroperitoneal approach were contributed by a few centers with greater experience with this technique, thus limiting the generalizability of the results of this study.2022-07-01T00:00:00ZTumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes.
http://hdl.handle.net/11434/2100
Title: Tumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes.
Epworth Authors: Moon, Daniel; Murphy, Declan; Lawrentschuk, Nathan; Bolton, Damian
Abstract: Background: Aberrations in homologous recombination repair (HRR) genes are emerging as important biomarkers for personalized treatment in prostate cancer (PCa). HRR deficiency (HRD) could affect the tumor immune microenvironment (TIME), potentially contributing to differential responses to poly ADP-ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors. Spatial distribution of immune cells in a range of cancers identifies novel disease subtypes and is related to prognosis. In this study we aimed to determine the differences in the TIME of PCa with and without germline (g) HRR mutations.
Methods: We performed gene expression analysis, multiplex immunohistochemistry of T and B cells and quantitative spatial analysis of PCa samples from 36 patients with gHRD and 26 patients with sporadic PCa. Samples were archival tumor tissue from radical prostatectomies with the exception of one biopsy. Results were validated in several independent cohorts.
Results: Although the composition of the T cell and B cells was similar in the tumor areas of gHRD-mutated and sporadic tumors, the spatial profiles differed between these cohorts. We describe two T-cell spatial profiles across primary PCa, a clustered immune spatial (CIS) profile characterized by dense clusters of CD4+ T cells closely interacting with PD-L1+ cells, and a free immune spatial (FIS) profile of CD8+ cells in close proximity to tumor cells. gHRD tumors had a more T-cell inflamed microenvironment than sporadic tumors. The CIS profile was mainly observed in sporadic tumors, whereas a FIS profile was enriched in gHRD tumors. A FIS profile was associated with lower Gleason scores, smaller tumors and longer time to biochemical recurrence and metastasis.
Conclusions: gHRD-mutated tumors have a distinct immune microenvironment compared with sporadic tumors. Spatial profiling of T-cells provides additional information beyond T-cell density and is associated with time to biochemical recurrence, time to metastasis, tumor size and Gleason scores.2022-06-01T00:00:00ZThe PRIMARY Score: Using intra-prostatic PSMA PET/CT patterns to optimise prostate cancer diagnosis.
http://hdl.handle.net/11434/2064
Title: The PRIMARY Score: Using intra-prostatic PSMA PET/CT patterns to optimise prostate cancer diagnosis.
Epworth Authors: Moon, Daniel; Murphy, Declan
Abstract: Background: Multi-parametric magnetic resonance imaging (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). 68Ga-PSMA -11 PET/CT (PSMA-PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post-hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intra-prostatic PSMA activity, proposing a 5- point PRIMARY score to optimise accuracy of PSMA-PET/CT for csPCa in a low prevalence population. Methods: The PRIMARY trial is a prospective multi-centre phase II imaging trial that enrolled biopsy-naïve men with suspected PCa, no prior biopsy, recent mpMRI (6 months) and planned for prostate biopsy. 291 men underwent mpMRI, PSMA-PET/CT and systematic +/- targeted biopsy. The mpMRI was read separately using PI-RADS (V2). PSMA-PET/CT (pelvic only) was acquired a minimum 60 minutes post injection. PSMA-PET/CT was centrally read for pattern (diffuse transition zone (TZ), symmetrical central zone (CZ), focal TZ or peripheral zone (PZ), and intensity (SUVmax). In this post-hoc analysis, a 5-level PRIMARY score was assigned based on analysis of the central read: 1. No pattern, 2. Diffuse TZ or CZ (no focal), 3. Focal TZ, 4. Focal PZ or 5. SUVmax ≥ 12. Two further readers independently assigned a PRIMARY score to 118 scans for inter-rater agreement. Associations between PRIMARY score and csPCa (ISUP≥2) were evaluated. Results: Of 291 men enrolled, 162 (56%) had csPCa. PRIMARY score-1 was present in 16% (47), score-2 in 19% (55), score-3 in 10% (29), score-4 in 40% (117) and score-5 in 15% (43). The proportion of patients with csPCa and PRIMARY score 1 to 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117) and 100% (43/43) respectively. Sensitivity, specificity, PPV and NPV for PRIMARY score 1,2 (low-risk patterns) vs PRIMARY score 3-5 (high-risk patterns) was 88%, 64%, 76% and 81%, compared to 83%, 53%, 69% and 72% for PI-RADS (2 vs 3-5) on mpMRI. The inter-rater agreements for PRIMARY score 1,2 vs. PRIMARY score 3-5 was 0.76 (CI: 0.64-0.88) and 0.64 (CI: 0.49-0.78). Conclusion: A PRIMARY score incorporating intra-prostatic pattern and intensity on PSMA-PET/CT shows potential with high diagnostic accuracy for csPCa. Further validation is warranted prior to implementation.2022-03-01T00:00:00ZFractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial
http://hdl.handle.net/11434/1773
Title: Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial
Epworth Authors: Moon, Daniel; Ruljancich, Paul; Grummet, Jeremy; Crosthwaite, Alan; Peters, Justin; McKenzie, Dean
Abstract: Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1-59.3%). The median length of treatment escalation-free survival over the entire follow-up period was 27.1 months (95% CI; 21.8-29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08-0.54, p = 0.001).2019-06-01T00:00:00Z