Biochemical control in intermediate- and high-risk prostate cancer after EBRT with and without brachytherapy boost.

PURPOSE: External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. METHODS: Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥ 76 Gy EQD2 (α/ß = 1.5 Gy) for IR and ≥ 78 Gy EQD2 (α/ß = 1.5 Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. RESULTS: Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49 and 51 months for HR and IR, respectively. BTB patients with ≥ 113 Gy EQD2Gy experienced a stable, good BC outcome compared with BTB at lower doses. Patients treated with ≥ 113 Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥ 113 Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5 and 20.8% for IR). CONCLUSIONS: In patients with IR and HR prostate cancer, BTB with ≥ 113 Gy EQD2Gy offered a BC advantage compared with dose-escalated EBRT and lower BTB doses.

Rectum and Bladder Toxicity in Postoperative Prostate Bed Irradiation: Dose-Volume Parameters Analysis.

Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 (p < 0.001 and p < 0.001) and rectum wall V46 (p = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 (p = 0.019 and p = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall (p = 0.004) and bladder (p = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.

Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients.

BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.

Ultra-Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer: Clinical Outcomes, Patterns of Recurrence, Feasibility of Definitive Salvage Treatment, and Competing Oncological Risk.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan-Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local-regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07-1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19-6.15). Definitive local salvage therapies were feasible in the majority of the patients with local-regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients' survival compared to primary disease recurrence.

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy.

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

The Prognostic Value of PI-RADS Score in CyberKnife Ultra-Hypofractionated Radiotherapy for Localized Prostate Cancer.

Prostate Imaging-Reporting and Data System (PI-RADS) has been widely implemented as a diagnostic tool for significant prostate cancer (PCa); less is known about its prognostic value, especially in the setting of primary radiotherapy. We aimed to analyze the association between PI-RADS v. 2.1 classification and risk of metastases, based on a group of 152 patients treated with ultra-hypofractionated stereotactic CyberKnife radiotherapy for localized low or intermediate risk-group prostate cancer. We found that all distant failures (n = 5) occurred in patients diagnosed with a PI-RADS score of 5, and axial measurements of the target lesion were associated with the risk of developing metastases (p < 0.001). The best risk stratification model (based on a combination of greatest dimension, the product of multiplication of PI-RADS target lesion axial measurements, and age) achieved a c-index of 0.903 (bootstrap-validated bias-corrected 95% CI: 0.848−0.901). This creates a hypothesis that PI-RADS 5 and the size of the target lesion are important prognostic factors in early-stage PCa patients and should be considered as an adverse prognostic measure for patients undergoing early treatment such as radiation or focal therapy.

Prostate-specific antigen kinetics and metastasis-free survival in patients treated with external beam radiotherapy combined with high-dose-rate brachytherapy boost and androgen deprivation therapy for localized prostate cancer.

PURPOSE: Serum prostate-specific antigen (PSA) kinetics has been linked to prognosis in prostate cancer (PCa) patients. Our goal was to analyze the association between PSA kinetics and metastasis-free survival (MFS) in patients with localized PCa treated with high-dose-rate (HDR) brachytherapy (BT) boost combined with external beam radiotherapy (EBRT). MATERIAL AND METHODS: We retrospectively analyzed multiple PSA kinetics related to PSA nadir (nPSA), PSA bouncing, and biochemical recurrence (BCR) in 186 PCa patients treated with neoadjuvant androgen deprivation therapy (ADT), followed by EBRT combined with HDR-BT boost. Uni- and multivariate Cox regression models were calculated to assess the value of PSA-related parameters for the prediction of MFS. RESULTS: 5- and 10-year MFS were 95% and 84%, respectively. Median nPSA was 0.011 (IQR, 0.007-0.057) ng/ml and predicted MFS in multivariable analysis. Implementation of nPSA improved c-index of baseline model from 0.8 to 0.68. nPSA of 0.2 ng/ml offered the most optimal discriminatory ability for identifying patients with better prognoses. Time to nPSA (median, 11 months; IQR, 8-18 months) and PSA bounce, which occurred in 12.4% of patients, were not significantly associated with MFS. CONCLUSIONS: Lower values of nPSA are significantly associated with decreased risk of developing metastases in patients treated with EBRT combined with HDR-BT boost and ADT, and improve the accuracy of a clinical model for MFS.

The survival impact of significant delays between surgery and radiochemotherapy in glioblastoma patients: A retrospective analysis from a large tertiary center.

The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unknown and the paradigm of 'the sooner, the better' has been challenged by many recent publications. In this study, we present unique data on the outcomes of patients with significant treatment delays. The study group consisted of 346 GBM patients (median age 56.8 years) who received surgical treatment (total or subtotal resection) and then underwent adjuvant concurrent RCT at one institution. The main endpoint was overall survival (OS). The Univariate and multivariate Cox Proportional-Hazard Model, log-rank test, and Kaplan-Meier method were used for the analysis. The median OS was 18.7 months and the 5-year overall survival was 8.5%. The median time interval from surgery to RCT was 9.8 weeks. The Cox regression showed that the time interval had no statistically significant impact on OS both in uni- and multivariate analysis. The explorative analysis suggested a positive trend for improved survival for patients in the 1st quartile of the time interval, especially for patients with residual disease or local recurrence prior to RCT, However, considering the 6.9 weeks median interval in the 1st quartile, this subgroup should still be regarded as 'moderate delay' compared with other literature data. The results indicate that the time interval is not a clear prognostic factor in the treatment of GBM. Prospective trials are highly warranted, as data suggest that moderate delays in the initiation of adjuvant treatment might be associated with survival benefit.

Effect of Ileal Transposition (IT) on Angiopoietin-Like Protein-8 (ANGPTL8) and Pentraxin (PTX3) Plasma Level in Sprague-Dawley Rats Fed High-Fat Diet (HFD).

BACKGROUND: Metabolic surgery procedures are designed not only for sustained weight loss but also for achieving positive metabolic changes, including improved glucose tolerance and insulin sensitivity, along with an increase in energy expenditure. Based on recent findings, the present study focuses on the relationship between the effects of ileal transposition (IT), high-fat diet (HFD), and selected markers of lipid metabolism and inflammation. METHODS: Forty-eight male rats were divided into two groups: HFD and control diet (CD) fed rats. After eight weeks, animals in each group were randomly assigned to two types of surgery: IT and SHAM. Thereafter, fifty percent of the animals in the HFD and CD groups had their diets changed, while the remaining half maintained their presurgery diets. Eight weeks after surgery, plasma levels of ANGPTL8, PTX3, leptin, and adiponectin were assessed. RESULTS: The IT group pre- and postoperatively maintained on the HFD showed higher ANGPTL8 level compared to SHAM operated animals (p=0.0041). The effect of IT on PTX3 level in the group pre- and postoperatively maintained on a CD was not significant, and there were no differences compared to SHAM. Only the postoperative diet change to HFD increased PTX3 level in the IT operated animals (p=0.0002). The IT group had increased plasma adiponectin (p=0.026) and leptin (p=0.0027) levels after dietary change to HFD compared to IT rats fed CD. CONCLUSIONS: This study indicates that the outcomes of metabolic surgery can be greatly modified by HFD. The effects of the IT procedure in this experiment are ambiguous and do not provide a clear answer as to whether or not they are beneficial.

Prognostic factors in postoperative radiotherapy for prostate cancer - tertiary center experience.

BACKGROUND: The aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS). PATIENTS AND METHODS: This retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development. RESULTS: The median follow up was 62.3 (interquartile range [IQR] 38.1-79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/. CONCLUSIONS: The Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4-5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.

The association between RDW and survival of patients with squamous cell carcinoma of the tongue. Simple, cheap and convenient?

AIM: The purpose of this study was to evaluate the prognostic impact of red-cell distribution width (RDW) on the overall survival (OS) of patients with squamous cell carcinoma (SCC) of the tongue. BACKGROUND: Development of cancer is connected with an ongoing inflammatory process which is reflected by laboratory indices, such as RDW that can be used as prognostic tools. MATERIAL AND METHODS: The study group consists of 74 consecutive patients treated with radical radiotherapy or chemo-radiotherapy for SSC of the tongue at one institution between 2005-2014. RDW was assessed based on routine blood tests done before the start of the treatment. ROC curve was applied to assess value of RDW in prediction of OS, and a cut-off value for further tests was obtained using the Younden index. The survival analysis was performed using the Kaplan-Meier method, log-rank testing and Cox regression model. RESULTS: The AUC for RDW in ROC analysis was 0.703, and the optimal cut-off value was 13.5%. 5-year OS was significantly lower in patients with RDW ≥ 13.5% compared with patients with RDW < 13.5% (67% vs. 26%, p-value = 0.0005). Additionally, high RDW was associated with a greater odds ratio for 5-year OS in a multivariate Cox proportional hazards regression analysis (3.43, 1.62-7.25; p = 0.001). CONCLUSION: Our study demonstrated that pre-treatment RDW ≥ 13,5% is an indicator of poor overall survival in patients with SCC of the tongue. Since RDW is a cheap and convenient marker, usually routinely assessed during complete blood count tests, it could be further used as an additional prognostic tool in patients with tongue cancers.