Acute onset of tinnitus in patients with sudden deafness

Objective: We made hypotheses that tinnitus will appear more likely in patients with sudden deafness with superior hearing in unaffected ear or with more severe acute hearing loss. Methods: A retrospective cohort study was performed. Five hundred forty-one patients were identified with idiopathic sudden sensorineural hearing loss (ISSHL) from January 1995 to August 2006. The exclusion criteria for this study were as follows: bilateral sudden hearing loss and Meniere disease, previous tinnitus or bilateral tinnitus at initial evaluation, and onset of hearing loss less than 7 days. The cohort enrolled 454 patients. The enrolled patients were classified into two groups: patient with acute onset tinnitus in the affected ear and patients without tinnitus at initial visit. Main outcome measures were patient age, the presence or absence of vertigo and tinnitus, audiometric patterns, the severity of hearing loss, and hearing in the unaffected ear. Results: Better contralateral hearing (n = 220 versus n = 72, P < 0.001) and younger age (48 versus 55 years, P < 0.001) were independently associated with the acute onset of tinnitus in patients with ISSHL. The degree of asymmetry between the ears did not differ significantly between patients with and without tinnitus. The sex, presence of vertigo, shape of audiogram, and severity of hearing loss were not correlated with tinnitus occurrence. Conclusions: Tinnitus triggered by ISSHL was more frequent in patients with better contralateral hearing and of a younger age, irrespective of the severity of hearing loss on the affected side or the asymmetry between the ears

European association of urology risk stratification predicts outcome in patients receiving PSMA-PET-planned salvage radiotherapy for biochemical recurrence following radical prostatectomy

PURPOSE The European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET. METHODS For this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients. RESULTS The median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis-free survival (MFS) was 94.4 % in low-risk versus 87.6 % in high-risk patients (p = 0.005). The 3-year overall survival (OS) was 99.0 % in low-risk versus 99.6 % in high-risk patients (p = 0.925). In multivariate analysis, EAU risk group remained a statistically significant predictor of BPFS (p = 0.003, HR 2.022, 95 % CI 1.262-3.239) and MFS (p = 0.013, HR 2.986, 95 % CI 1.262-7.058). CONCLUSION Our data support the EAU risk group definition. EAU risk grouping for BCR reliably predicted outcome in patients staged lymph node-negative after RP and with PSMA-PET before SRT. To our knowledge, this is the first study validating the EAU risk grouping in patients treated with PSMA-PET-planned SRT

PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.

PURPOSE The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

PURPOSE Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

IMPORTANCE Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. OBJECTIVE To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. EXPOSURES Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. MAIN OUTCOMES AND MEASURES The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. RESULTS In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. CONCLUSIONS AND RELEVANCE This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study

BACKGROUND Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. CONCLUSIONS The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG