Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience

Background: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. Methods: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Results: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. Conclusions: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations

INFLAMMATORY CYTOKINES ASSOCIATED WITH BLUNTED HYPOXIC PULMONARY VASOCONSTRICTION IN APNEA DIVERS

T. Kelly1, K. DiMarco1, Courtney Brown2, Mohini Bryant-Ekstrand1, Rachel Lord3, Tony Dawkins3, Aimee Drane3, Joel E. Futral1, Otto Barak4, Tanja Dragun5, Michael Stembridge3, Boris Spajić6, Ivan Drviš6, Joseph W. Duke7, Philip N. Ainslie2, Glen E. Foster2, Zeljko Dujic5, & A.T. Lovering1 1University of Oregon, Department of Human Physiology, Eugene OR, USA; 2University of British Columbia, Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Kelowna, BC, Canada; 3Cardiff Metropolitan University, School of Sport and Health Sciences, Cardiff, Wales, UK; 4University of Novi Sad, Department of Physiology, Novi Sad, Serbia; 5University of Split School of Medicine, Department of Integrative Physiology, Split, Croatia; 6University of Zagreb, Faculty of Kinesiology, Zagreb, Croatia; 7Northern Arizona University, Department of Biological Sciences, Flagstaff, AZ, USA PURPOSE: Our lab has previously reported blunted hypoxic pulmonary vasoconstriction in apnea divers (Kelly et al, Exp Physiol 2022). Why this occurs remains speculative but may relate to interactions between inflammatory cytokines and nitric oxide availability. We hypothesized that in apnea divers there would be a positive correlation between levels of inflammatory cytokines and degree of hypoxic pulmonary vasoconstriction. METHODS: 16 (4 women) apnea divers and 16 (4 women) non-diving age and sex-matched controls were recruited from diving camps in and around Split, Croatia and Eugene, Oregon. Serum was collected from each participant, then transthoracic ultrasound measures were made to calculate cardiac output (QT) and pulmonary artery systolic pressure (PASP). Total pulmonary resistance (TPR) was calculated as PASP/QT and converted to dynes/sec/cm-5. After baseline ultrasound measures, participants breathed on a dynamic end-tidal forcing machine targeting an end-tidal O2 ~50mmHg (corresponding to O2 saturation of ~80%) while clamping end-tidal CO2 at baseline value (~40mmHg). Ultrasound measures were repeated after 20 to 30-minutes of hypoxic breathing. ΔTPR was calculated as the change in TPR from baseline to the end of the hypoxic challenge. Serum was analyzed for cytokines using a flow cytometry bead-based multiplex assay. RESULTS: Data were analyzed by Pearson correlation. In apnea divers there were significant correlations between ΔTPR and levels of IL-8 (r = -.8151, r2 = .6644, p = .0481), IFN-a2 (r = -.8344, r2 = .6962, p = .0052), and IL-12p70 (r = -.9209, r2 = .8481, p = .0264). There were no significant correlations in Controls. CONCLUSION: We report strong negative correlations between ΔTPR in response to a 20 to 30-minute hypoxic challenge and several inflammatory cytokines. Our results suggest that apnea divers may have an altered inflammatory cytokine profile which is related to reduced hypoxic pulmonary vasoconstriction. US Fulbright Scholar’s Program # PS00273429, Burroughs Wellcome Fund # 101879

Development of a New Optical Device and Its Feasibility in Prostate Cancer Detection

Aim: To develop a new optical device (prostate optical device, POD) for assessment of prostate tissue stiffness and evaluate its sensitivity and specificity in prostate cancer detection. Patients and Methods: POD was tested in prostate phantoms and in patients with indications for prostate biopsy. Its sensitivity and specificity were compared to digital rectal examination (DRE) and transrectal ultrasonography (TRUS). Results: POD was able to identify stiffness differences on each prostate phantom. 45 patients were included in the study. Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%) (p = 0.000 and p = 0.003, respectively). There was no statistical difference between POD and DRE (p = 0.221). The combination of POD and DRE showed the highest sensitivity (88.6%), positive predictive value (81.6%), and negative predictive value (42.9%) among all diagnostic tests. Conclusions: POD identified prostatic stiffness differences with the same sensitivity of DRE performed by an experienced urologist providing an objective indication for prostate biopsy and early prostate cancer detection. Copyright (C) 2012 S. Karger AG, Base