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Objectives: Investigating supportive care (SC) needs and utilization/willingness to use SC services from diagnosis to one year after radical cystectomy in bladder cancer (BC) patients. Materials & Methods: A longitudinal cohort study was conducted in 90 BC patients at Ghent/Leuven University Hospitals between April 2017 and December 2020. The Supportive Care Needs Survey-short form (SCNS-SF34) was used before radical cystectomy, one, three, six and 12 months after radical cystectomy. Additional questions assessed utilization/willingness to use SC services. Linear mixed models were performed. Results: The majority of BC patients report at least one moderate or high SC need at diagnosis (82%), month 1 (84%), month 3 (86%), month 6 (64%), and month 12 (60%). Significant decreases over time were seen for all domains (p

Contains fulltext : 238898.pdf (Publisher’s version ) (Closed access) BACKGROUND: Implant-supported overdentures (IOD) are becoming a more commonly used treatment in the dental practice and it risks causing speech problems. PURPOSE: The aim of this study was investigating the changes in speech, satisfaction with speech, and overall oral health-related quality of life (OHRQoL) in edentulous patients during and after treatment with maxillary IODs. MATERIALS AND METHODS: Twenty-one patients receiving an IOD participated in speech assessment. They were examined preoperatively with their conventional denture (CD) with full palatal coverage, after connection of the implant-bar connected denture, without palatal coverage, and 3 years thereafter. The examination included assessment of articulation in speech, OHRQoL based on total OHIP-14, and satisfaction with overall oral health and speech (visual analogue scale). RESULTS: There was a reduction in mean number of articulation disorders from 1.00 at baseline to 0.55 at connection, although statistically insignificant (p = 0.059). Especially the /s/ sound is vulnerable. At 3 years follow-up, still 6/16 (37.5%) of the patients suffered from this speech problem. Overall satisfaction improved from 64.05/100 at baseline to 82.95/100 at connection (p = 0.008) and remained unchanged with 81.69/100 after 3 years follow-up. Patients' satisfaction with speech increased from 70.62/100 with CD to 82.63/100, 3 years follow-up (p = 0.009). Total OHIP-14 decreased from 21.45/56 with CD to 8.00/56 (p

Purpose: To quantify the severity and location of corneal neovascularization (cNV) and its impact on the visual acuity and corneal sensitivity in a cohort of the patients referred to a specialist cornea clinic and also to describe the etiology of cNV in the cohort.Methods: We retrospectively evaluated the charts of 13,493 subjects referred to the San Raffaele Cornea Unit between January 2004 and December 2018 to search for cNV diagnosis. The corneal neovascularization severity was measured in the quadrants (range: 1–4) and location was defined as superficial, deep, or both. Best spectacle corrected visual acuity (BSCVA) was measured in logMar. We used the multiple regression analysis to identify the independent predictors of logMAR, after adjusting for age, gender, keratoconus, herpes keratitis, penetrating keratoplasty, trauma, and cataract surgery.Results: Corneal neovascularization was diagnosed in 10.4% of the patients analyzed. The most prevalent etiology of cNV in our population was non-infectious corneal dystrophies/degenerations followed by herpes simplex virus infection. cNV affected OD, OS, or both eyes in 35.6, 40.2, and 24.2 of cases, respectively. Mean BSCVA (SD) was 0.59 (0.76), 0.74 (0.94), and 1.24 (1.08) in cNV one, two, and three or four of the quadrant groups. Superficial, deep, or mixed cNV occurred in 1,029, 348, and 205 eyes. Severe cNV (three or four of the quadrants) was a significant predictor of low visual acuity (p < 0.001) and reduced corneal sensitivity (p < 0.05). cNV location and its severity were associated (p < 0.05). In addition, corneal anesthesia was associated with lower BSCVA (p < 0.001).Conclusion: Severe and deep cNV are associated with the reduced visual acuity and corneal sensitivity. Our data strongly support the relevance of appropriate follow-up as cNV is a major risk factor for graft rejection.

We aim to evaluate the diagnostic accuracy of PET–CT/MRI in the local and distant staging of patients with muscle invasive bladder cancer (MIBC). Medline, Pubmed and EMBASE were searched for studies evaluating the diagnostic performance of PET–CT/MRI in the primary staging of MIBC patients. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR, respectively) and diagnostic odds ratio (DOR = PLR/NLR) are reported. We retrieved 35 articles. For local staging, a pooled sensitivity and specificity of 88% (95% CI: 81–92%) and 68% (95% CI: 50–82%), respectively, were found. The PLR and NLR are 2.88 (95% CI: 1.71–4.73) and 0.19 (95% CI: 0.12–0.30) resulting in a DOR of 16.60 (95% CI: 5.98–37.50). For regional lymph node staging, the pooled sensitivity and specificity are 57% (95% CI: 5–63%) and 89% (95% CI: 83–3%). The PLR is 5.33 (95% CI: 3.44–8.09) and NLR is 0.48 (95% CI: 0.42–0.55). The corresponding DOR is 11.10 (95% CI: 6.62–17.60). For distant metastases, a pooled sensitivity and specificity of 89% (95% CI: 61–98%) and 95% (95% CI: 80–99%), respectively, were found. The PLR is 23.70 (95% CI: 4.19–72.10) and the NLR is 0.13 (95% CI: 0.02–0.36) with a DOR of 236.00 (95% CI: 38.00–871.00). PET–CT/MRI appears to have higher diagnostic accuracy than CT or MRI for local and distant staging of MIBC but it cannot (yet) be recommended in clinical practice because the quality of the evidence is insufficient and the effects on treatment decisions and patient’s outcome remain unclear.

This umbrella review aims to evaluate the quality, summarize and compare the conclusions of systematic reviews investigating the impact of curative treatment options on health-related quality of life (HRQoL) in muscle-invasive bladder cancer (MIBC). The Cochrane Library, MEDLINE, Embase and Web of Science were searched independently by two authors from inception until 06 January 2020. Systematic reviews and meta-analyses assessing the impact of any curative treatment option on HRQol in MIBC patients were eligible. Risk of bias was assessed using the AMSTAR 2 tool. Thirty-two reviews were included. Robot-assisted RC with extracorporeal urinary diversion and open RC have similar HRQoL (n = 10). Evidence for pelvic organ-sparing RC was too limited (n = 2). Patients with a neobladder showed better overall and physical HRQoL outcomes, but worse urinary function in comparison with ileal conduit (n = 17). Bladder-preserving radiochemotherapy showed slightly better urinary and sexual but worse gastro-intestinal HRQoL outcomes in comparison with RC patients (n = 6). Quality of the reviews was low in more than 50% of the available reviews and most of the studies included in the reviews were nonrandomized studies. This umbrella review gives a comprehensive overview of the available evidence to date.

PURPOSE: To determine the start exercise prescription dose in metastatic castrate-resistant prostate cancer (mCRPC) patients receiving second-line hormone treatment and recommended phase II exercise prescription. METHODS: Patients were enrolled in a 3 + 3 dose escalation phase I trial of aerobic, resistance, and flexibility exercises to evaluate dose-limiting tolerance and safety. Tolerance was defined as Borg score ≤ 16 and safety (pain) as a visual analogue scale score (VAS) ≤ 3 and CTCAE grade 3 during resistance training and/or flexibility training. No tolerance issues were observed in the two dosing cohorts. The optimal start exercise prescription dose was set at dose level 1 due to safety issues at dose level 2. CONCLUSION: Our findings suggest that exercise is perceived tolerable in mCRPC patients receiving second-line hormone therapy. Caution is indicated on safety during performance of the exercises.

Background: Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients. Objective: We aimed to identify the optimal candidates for early SRT after RP. Design, setting, and participants: The study included 925 node-negative patients treated with SRT after RP at seven institutions. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP that was defined as PSA level ≥0.1 ng/ml at 1 mo after surgery. All patients received local radiation to the prostate and seminal vesicle bed. Outcome measurements and statistical analysis: The primary outcome measured was distant metastasis after SRT. Regression tree analysis was used to develop a risk-stratification tool. Multivariable Cox regression analysis and nonparametric curve fitting methods were used to explore the relationship between PSA level at SRT and the probability of metastasis-free survival at 8 yr. Results and limitations: At a median follow-up of 8.0 yr, 130 patients developed distant metastasis. At multivariable analysis, pre-SRT PSA level was significantly associated with distant metastasis (hazard ratio: 1.06, p < 0.0001). However, when patients were stratified into five risk groups using regression tree analysis (area under the curve: 85%), early SRT administration provided better metastasis-free survival in three groups only: (1) low risk: undetectable PSA after RP, Gleason score ≤7, and tumour stage ≥pT3b, (2) intermediate risk: undetectable PSA after RP with Gleason score ≥8, (3) high risk: PSA persistence after RP with Gleason score ≤7. Conclusions: We developed an accurate risk stratification tool to facilitate the individualised recommendation for early SRT based on prostate cancer characteristics. Early SRT proved to be beneficial only in selected groups of patients who are more likely to be affected by clinically significant but not yet systemic recurrence at the time of salvage treatment administration. Patient summary: In patients affected by prostate cancer recurrence after radical prostatectomy, the early administration of salvage radiation therapy is beneficial only for selected subgroups of patients. In this study, these groups of patients were identified. In this multi-institutional study, we developed a prognostic tool to assess the risk of distant metastases after early salvage radiation therapy for prostate-specific antigen (PSA) rise after prostatectomy. Five distinct risk groups were identified based on clinical and pathological characteristics. Early salvage radiation therapy administration was noted to be associated with improved cancer control for low-, intermediate-, and high-risk patients. Conversely, very low-risk (undetectable PSA after radical prostatectomy, Gleason score ≤7, and tumour stage ≤pT3a) and very high-risk patients (PSA persistence after radical prostatectomy, and Gleason score ≥8) did not benefit from early salvage treatment. These findings facilitate the identification of optimal candidates for early salvage radiation therapy, and, pending validation, application into clinical practice will help to maximise cancer control while avoiding overtreatment.

Background The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome. Methods EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints. Discussion This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome. Trial registration The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.

INTRODUCTION AND OBJECTIVE:Radiotherapy to the prostate (RTp) has recently been shown to prolong survival in patients with low-volume newly-diagnosed metastatic prostate cancer (ndmPC). Therefore i...

A radical cystectomy (RC) is the mainstay of treatment for patients with muscle invasive bladder cancer (MIBC) (1). Despite improvements in surgical techniques and peri-operative management, the incidence of complications after RC remains significant. Even in contemporary series the incidence of grade 3–5 complications within 90 days after RC is high and occurs in up to 19% of the patients (2). The reported 90-day mortality rate varies between 1.2% and 8% (3,4).

Preclinical data indicate that radiotherapy works synergistically with pembrolizumab, but the effect and toxicity of this combination may depend on radiotherapy timing. We conducted a randomized phase 1 trial combining pembrolizumab with either sequential (A) or concomitant (B) stereotactic body radiotherapy (SBRT) in metastatic urothelial carcinoma (mUC). No dose-limiting toxicity occurred. Treatment-related adverse events (trAEs; Common Terminology Criteria for Adverse Events v4.0) of grade 1-2 occurred in six of nine and all nine patients in arms A and B, respectively. One grade 3 trAE occurred in arm B. No grade 4-5 trAEs occurred. Overall response rates of 0% and 44.4% were noted in arms A and B, respectively, as per Response Evaluation Criteria in Solid Tumors v1.1. The trial was not powered to compare efficacy between arms. Targeted sequencing of tissue DNA and circulating tumor DNA (ctDNA) revealed high genomic concordance. Treatment response was associated with ctDNA fraction decline. We conclude that sequential and concomitant SBRT can be safely combined with pembrolizumab in mUC and that the effect of SBRT timing on efficacy is worth exploring further. PATIENT SUMMARY: This study assessed the safety of pembrolizumab combined with radiotherapy at two different time points in metastatic bladder cancer. We conclude that the combination treatment was well tolerated.

PURPOSE/OBJECTIVE(S) Emerging data suggest that metastasis is a spectrum of disease burden rather than part of a binary state. Metastasis-directed therapy (MDT) such as radiation might improve outcomes in individuals with oligometastatic disease. Prospective data of MDT for metachronous oligometastatic or oligorecurrent prostate cancer (PCa) have been limited to single arm or small phase 2 randomized studies. We report an individual patient data meta-analysis to characterize the safety and clinical benefit of MDT in oligorecurrent PCa. MATERIALS/METHODS Individual patient data was submitted from trials published or in conference proceedings by January 2020. Included were single- or multi-arm prospective trials including only patients with recurrent prostate cancer and ≤5 sites of extracranial disease undergoing MDT (surgery or radiotherapy). We hypothesized that MDT improves ADT-free survival. ADT-free survival was analyzed as the primary outcome and biochemical relapse-free survival as secondary outcome. If hazard ratios (HR) were not constant across the different trials, we calculated standardized survival curves, analyzing the trials separately and pooling the adjusted log HR weighted by sample size. The following covariates were examined with the interaction test: PSA doubling time and localization of disease (nodal vs extra-nodal). RESULTS We identified 4 trials with published results, 2 single arm and 2 randomized trials, representing in total 174 patients (MDT: 72%, active surveillance (AS): 28%). Patient characteristics differed with respect to imaging at inclusion (conventional vs molecular imaging), PSA doubling time and localization of disease (nodal vs extra-nodal). Non-proportional hazards were detected for ADT-free survival but not for biochemical relapse-free survival. ADT-free survival is improved with MDT over AS (HR: 0.56, 95% CI 0.34 - 0.94, P = 0.03) across all covariates, as well as biochemical relapse-free survival (HR: 0.44, 95% CI 0.29 - 0.67, P < 0.01). Grade 2 and 3 toxicity were observed in 3% and 2%, respectively, of patients treated with MDT. CONCLUSION MDT improves both biochemical relapse-free and ADT-free survival as compared to active surveillance with low rates of grade 2 or higher toxicity.

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy.

Germ cell tumors (GCT), accounting for 95% of malignant testicular tumors, can be divided into two groups: seminoma (SGCT) and non-seminoma (NSGCT). Seminomas typically arise in men in the fourth decade of life, compromising 60% of the GCT. At diagnosis, approximately 75% present with local disease (Stage I); 15% is detected with metastatic regional lymph nodes (Stage II) and 5-10% present with juxtaregional or visceral metastasis (Stage III) . This article is protected by copyright. All rights reserved. ispartof: BJU INTERNATIONAL vol:124 issue:1 pages:35-39 ispartof: location:England status: published

External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with different treatment volumes have been described with similar tumour control and, so far, clear recommendations on the optimal radiotherapy regimen and treatment volume are lacking. The current review summarises EBRT literature on dose prescription, fractionation as well as treatment volume in order to guide clinicians in their daily practice when treating patients with muscle-invasive bladder cancer. Taking into account literature on repopulation, continuous-course radiotherapy can be used safely in daily practice where a split-course should only be reserved for those patients who are fit enough to undergo a radical cystectomy in case of a poor early response. A recent meta-analysis has proven that hypofractionated radiotherapy is superior to conventional radiotherapy with regards to invasive locoregional control with similar toxicity profiles. In the absence of node-positive disease, the target volume can be restricted to the bladder. In order to compensate for organ motion, very large margins need to be applied in the absence of image-guided radiotherapy (IGRT). Therefore, the use of IGRT or an adaptive approach is recommended. Based on the available literature, one can conclude that moderate hypofractionated radiotherapy to a dose of 55 Gy in 20 fractions to the bladder only, delivered with IGRT, can be considered standard of care for patients with node-negative invasive bladder cancer.

Contains fulltext : 229066.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Longitudinal evaluation of Oral Health-Related Quality of Life (OHRQoL) during treatment of flaplessly placed, one-piece mini-dental-implants (MDIs) for maxillary overdentures is rarely investigated, nor is the impact of MDI failures. MATERIAL AND METHODS: This multicenter prospective cohort study evaluated the 3-year outcome of 5-6 MDIs in the edentulous maxilla in patients above 50 years with dentate mandible. Provisional dentures were provided before final prosthetic connection was established at 6 months. Postoperative discomfort was assessed using a visual analogue score (VAS). OHRQoL was investigated using the Oral Health Impact Profile (OHIP)-14 at baseline (preoperatively), postoperatively, post-prosthetic connection and after 3 years in function. RESULTS: 164 (78.4%) of the 204 placed MDIs were still in situ after 3 years, in 29/31 patients. Two patients lost 5/6 MDIs resulting in two prosthetic failures (6.45%). With regard to pain, a score of 4.1/10 (SD 2.8) was recorded on day 1, and 1.1/10 (SD 1.7) on day 7. A decrease in total OHIP-14 scores was observed postoperatively (15.6; SD 12.8) as compared to baseline (21.3; SD 13.1), with improvement of OHRQoL. Furthermore, this was statistically significant at connection of the final prosthesis (7.3; SD 6.7) (p = .006). The OHIP-14 improved less (p = .011) when experiencing one or more implant losses (9.5; SD: 9.85), in comparison with no implant loss (20.7; SD: 13.97). A failure of one MDI did not affect OHIP-14 score (p = .658); however, multiple failures did (p = .007). CONCLUSION: Maxillary MDI overdenture treatment yields significant OHRQoL improvement when at least 5 MDIs survive, preserving functional comfort.

Background Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). Objective to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. Design, setting, and participants A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16–49). Intervention cRP was compared with RTp and NLT. Outcome measurements and statistical analysis Overall survival (OS), cancer-specific survival (CSS), and local event–free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. Results and limitations The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. Conclusions For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. Patient summary Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression., Take Home Message In selected patients, cytoreductive radical prostatectomy is able to achieve similar overall survival and cancer-specific survival to radiotherapy.

Highlights • Single fraction radiotherapy is feasible for uncomplicated bone metastases. • Four-week mortality was similar between single fraction and multiple fraction. • Our paper has the highest rate of reported single fraction radiotherapy in literature. • Re-irradiation were higher for single fraction radiotherapy in uncomplicated bone metastases., Background Single-fraction radiotherapy (SFRT) offers equal pain relief for uncomplicated painful bone metastases as compared to multiple-fraction radiotherapy (MFRT). Despite this evidence, the adoption of SFRT has been poor with published rates of SFRT for uncomplicated bone metastases ranging from

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning. ispartof: FRONTIERS IN ONCOLOGY vol:10 ispartof: location:Switzerland status: published

Càncer de mama; Model de predicció; Radioteràpia Cáncer de mama; Modelo de predicción; Radioterapia Breast cancer: Prediction model; Radiotherapy Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study. Methods: Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature. These predictors were used to develop risk models for acute erythema and acute desquamation (skin loss) in three Radiogenomics Consortium cohorts of patients treated by breast-conserving surgery and whole breast external beam radiotherapy (n = 2,031). The models were externally validated in the REQUITE breast cancer cohort (n = 2,057). Results: The final risk model for acute erythema included BMI, breast size, hypo-fractionation, boost, tamoxifen use and smoking status. This model was validated in REQUITE with moderate discrimination (AUC 0.65), calibration and agreement between predicted and observed toxicity (Brier score 0.17). The risk model for acute desquamation, excluding the predictor tamoxifen use, failed to validate in the REQUITE cohort. Conclusions: While most published prediction research in the field has focused on model development, this study reports successful external validation of a predictive model using clinical risk factors for acute erythema following radiotherapy after breast-conserving surgery. This model retained discriminatory power but will benefit from further re-calibration. A similar model to predict acute desquamation failed to validate in the REQUITE cohort. Future improvements and more accurate predictions are expected through the addition of genetic markers and application of other modeling and machine learning techniques. TRat is currently an NIHR Clinical Lecturer. He was previously funded by a National Institute of Health Research (NIHR) Doctoral Research Fellowship (DRF 2014-07-079). This publication presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The REQUITE study received funding from European Union's 7th Framework Programme for research, technological development and demonstration under grant agreement no. 601826. The ISE study was supported by the German Office for Radiation Protection, project number St. Sch. 4116 and 4233. The LeND study received funding from Breast Cancer Now (formerly Breast Cancer Campaign) under grant ref. 2007NovPR45.

Introduction Uptake of sufficient physical activity before and after radical cystectomy is important to improve physical and psychosocial outcomes in bladder cancer (BC) patients. Methods In this paper, we describe the development of an evidence-based and theory-informed intervention, guided by the steps of the Intervention Mapping approach, to promote physical activity before and after radical cystectomy in patients with BC. Results The intervention is a home-based physical activity program. The preoperative timeframe of the intervention is 4 or 12 weeks, depending on administration of neoadjuvant chemotherapy. Postoperatively, the intervention will last for 12 weeks. The intervention consists of a digital oncological platform (DOP), several consultations with healthcare professionals, personal booklet and follow-up phone calls. DOP includes information, diaries, visual representation of progress, mailbox, videos of peers and treating physician explaining the benefits of physical activity, photo material of exercises and a walking program with an activity tracker. Individual goals will be set and will be self-monitored by the patient through DOP. Patients will receive alerts and regular feedback. Conclusions Intervention Mapping ensures transparency of all intervention components and offers a useful approach for the development of behaviour change interventions for cancer patients and for translation of theories into practice.

Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT. ClinicalTrials.gov identifier: NCT03899077.

After breast conserving surgery (BCS) for breast cancer, radiotherapy (RT) reduces the risk of locoregional recurrences and improves overall survival [1,2]. Despite the benefits, late toxicity may ...

Objectives Contemporary research on the impact of dental rehabilitation scarcely focuses on the role of personality and social relationships in QoL related to dental implant treatment. To overcome biases related to evaluation with self-reports, descriptions provided by informed external observers are recommended. Aims To investigate the impact of implant-supported rehabilitation on quality of life and social participation taking into account patient’s personality. Materials and methods Fifty-four patients were included in this study and assigned to either a single unit group (n = 15) or a complete jaw restoration group (n = 39). Of the 54 participants, 49 nominated an external observer who can evaluate the daily behavior of the patient. Before and after treatment patients and their external observer completed the OHIP-14, the NEO-FFI and the MSPP questionnaires respectively focusing on Oral Health related Quality of Life, Personality and Social participation. Results and conclusion The correlations between self- and observer ratings on pre and post treatment outcomes on were insignificant (QoL pre: p = 0.086, post: p = 0.115, freq. soc. part pre: p = 0.944, post: p = 0.876, div. soc. part pre: p = 0.798, post: p = 0.167), suggesting considerable differences in observer perspectives. The traits Neuroticism, Extraversion and Agreeableness were associated with QoL. Openness, Conscientiousness and Agreeableness were associated with social participation. Patients in the complete jaw restoration group reported more impact of the implant treatment on quality of life as compared to the single unit group (p = 0.007). The complete jaw restoration group reported an improved quality of life after treatment and significant increases of both frequency (p = 0.001) and diversity of social participation (p = 0.036). In conclusion there was a minor impact of treatment with single crowns on quality of life and social participation compared to the full denture group. The role of personality and the use of multi-informants in evaluating dental treatment was found important.

To evaluate the morbidity of different surgical approaches for pelvic lymph node dissection (PLND), to evaluate the influence of morbidity on radiotherapy (RT) planning and to evaluate a possible therapeutic effect of a more extensive yield of PLND.From 2000-2016, 228 patients received staging PLND before primary RT in a single tertiary care center. Nine patients were excluded for the evaluation of morbidity. Fifty patients were operated in an open approach, 96 laparoscopic and 73 robot-assisted (RA). Clavien-Dindo classification was used for evaluating complications. Predictors of biochemical recurrence (BCR), clinical relapse (CR), cancer-specific survival (CSS) and overall survival (OS) were evaluated by regression analyses to determine a possible therapeutic effect.Minimal invasive surgery (laparoscopic or RA) caused five times less major complications (22% vs. 4.3%, p = .001) and a median 3 days shorter hospital stay (5 days versus 2 days, p .001). Major complications resulted in a delayed (23 days, p .001) RT start but no oncological effect was seen. Independent oncological predictors were the number of positive nodes (BCR, CR, CSS, OS), a lower age (CR), a higher level of initial prostate-specific antigen (PSA) (BCR) and post-RT PSA (BCR).Minimal invasive surgery can diminish major complications which delay RT start. Nodal staging proved to be of importance for prognosis but no therapeutic effect was seen of performing PLND as such.

Purpose Hypofractionated radiation therapy (HFRT) for localized prostate cancer is safe and effective. The question that remains is which hypofractionation schedule to implement. We compared 2 different HFRT regimens in the present study. Methods and Materials From June 2013 to July 2016, 160 patients with prostate cancer were randomly assigned (1:1), within this single-center phase III trial, to 56 Gy (16 fractions of 3.5 Gy; arm A) or 67 Gy (25 fractions of 2.68 Gy; arm B). Randomization was performed using computer-generated permuted blocks, stratified by previous transurethral resection of the prostate and the presence of a dominant intraprostatic lesion. Treatment allocation was not masked, and the clinicians were not blinded. The primary endpoint was acute gastrointestinal (GI) toxicity, assessed using the Common Terminology Criteria for Adverse Events, version 4.0, and Radiation Therapy Oncology Group toxicity scale. An interim analysis of acute toxicity was planned at 160 patients to prove the safety of both treatment regimens. If ≥22 of 72 patients had grade ≥2 GI toxicity, the study arm would be rejected. The study is registered at ClinicalTrials.gov ( NCT01921803 ). Results In arm A, 20 patients (26%) and 1 patient (1%) developed acute grade 2 and grade 3 GI toxicity. In arm B, 16 patients (20%) reported acute grade 2 GI toxicity. In arm A, 42 (55%) and 5 (6%) patients developed acute grade 2 and grade 3 urinary toxicity. In arm B, 40 (49%) and 7 (9%) patients reported acute grade 2 and grade 3 urinary toxicity. Toxicity peaked during radiation therapy and resolved in the months after radiation therapy. Conclusions With acute grade ≥2 GI toxicity reported in 21 of 77 patients in arm A and 16 of 82 patients in arm B, both treatment arms can be considered safe.

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Objectives To explore patient perspectives of muscle-invasive bladder cancer (MIBC) on how the health care team and their social network can support them during their cancer trajectory. Data sources Sixteen semi-structured interviews were conducted with MIBC survivors who underwent radical cystectomies at Ghent University Hospital. The interviews were audiotaped, transcribed verbatim, and analyzed with an iterative content analysis approach. Conclusion Information to support people affected by bladder cancer (BC) in several aspects of their disease trajectory (eg, shared decision-making and self-management of their urinary diversion) was most important throughout the interviews (although type and source of required information varied). The clinical nurse specialist was important for informational and emotional support because receiving sufficient information might help patients reduce emotional stress. People affected by BC are still reluctant to consult a psychologist, and several barriers were indicated for this. Also physical needs in the early postoperative phase could be reduced with appropriate information. Communication skills of clinicians in the hospital and knowledge of general practitioners about the important aspects of BC care are also important aspects that should be further optimized. Furthermore, peer support groups and family members can offer important support throughout the BC pathway. Implications for nursing practice This study provides an overview of how people affected by BC want to be supported by their health care team and their social network. This overview can serve as a basis to develop educational interventions for both patients and health care professionals to guide restructuring of BC pathways and can also be used to develop future intervention studies to improve BC outcomes.

Context: There is uncertainty regarding the oncologic effectiveness and the survival advantage of local treatment (LT) in men with clinically lymph node-positive (cN+) prostate cancer (PCa). Objective: To systematically review the current literature comparing oncologic outcomes associated with the use of any form of LT for PCa patients with cN+ disease. Evidence acquisition: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of LT ± androgen deprivation therapy (ADT) versus ADT alone. LT included both radical prostatectomy (RP) and radiotherapy (RT). Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we identified five nonrandomized comparative retrospective studies published between 1999 and 2018, which were eligible for inclusion in this systematic review. A narrative review and risk-of-bias assessment were performed to determine the impact of LT on recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). Evidence synthesis: Four studies compared the use of RT ± ADT versus ADT alone, whereas one study compared any form of LT ± ADT versus ADT alone. Different statistical strategies were used in the included studies to account for baseline measured and unmeasured confounders. Overall, the use of RT and, generally speaking, any form of LT was associated with an OS as well as a CSS benefit over ADT alone, without any clear superiority shown either by RP ± ADT or by RT ± ADT. Conclusions: Our systematic review suggests an advantage in terms of both OS and CSS for men with cN+ PCa receiving LT. However, these results should be interpreted with caution due to the low level of evidence of available reports. Patient summary: We reviewed the studies that assessed the role of local treatment in men with prostate cancer and with clinical evidence of lymph node involvement at diagnosis. We found that local treatment was constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the included studies. Local treatment for clinically lymph node-positive prostate cancer is constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the studies included in this systematic review.

Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1 ng/ml at 1 mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8 yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9 mo. At median follow-up of 93 mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p = 0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p = 0.001; 0 vs ≥2, p < 0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36 mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (

Objective To prospectively evaluate patients with newly diagnosed metastatic prostate cancer in the context of the LoMP trial (which investigates the role of cytoreductive radical prostatectomy [cRP] in addition to standard of care [SoC]) and to provide a preliminary analysis of patient's characteristics, safety of cRP, and early local symptoms. Patients and Methods cRP was performed in asymptomatic patients with a resectable tumor and who were fit to undergo surgery (group A, n = 17). Only SoC was administered to patients with metastatic prostate cancer ineligible or unwilling to undergo cRP (group B, n = 29). At 3 months, surgical complications related to cRP and local symptoms for both groups were evaluated. Results Median operation time, blood loss, and hospital stay for cRP were 215 minutes (150-290), 250 mL (100-900), and 4 days (2-7), respectively. Respectively 5 (29.4%) and 2 (11.8%) patients suffered grades 1 and 2 complications within 3 months postoperatively. When compared with Group B, patients in group A were younger (64 vs 72 years, P = .005), had lower initial prostate-specific antigen (15.9 vs 156 µg/L, P = .002), and less high-volume metastatic disease (5.9% vs 69%, P Conclusion In a group of well-selected patients, cRP is safe. These patients have more favorable characteristics compared with patients treated with only SoC. If only SoC can be offered, patients are at risk to suffer from local symptoms.

Objectives To describe the anatomical patterns of PCa recurrence following primary therapy and investigate if patients with low-volume disease have a better prognosis as compared to their counterparts. Material and methods Patients eligible for a F18-choline PET-CT were entered in a prospective cohort study. Eligible patients had an asymptomatic biochemical recurrence following primary PCa treatment and testosterone levels >50 ng/ml. The number of lesions were counted per scan. Patients with an isolated local recurrence or with up to 3 metastases (+/- local recurrence) were considered “low-volume” and patients with >3 metastases as high-volume. Descriptive statistics were used to report recurrences. Cox-regression analysis investigated the influence of prognostic variables on the time to developing castration resistant PCa (CRPC). Results In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed) (11%), viscera (4%) or a combination of any of the previous (37%). In total, 153 patients (74%) had a low-volume recurrence and 55 patients (26%) had a high-volume recurrence. The 3-year CRPC-free survival for the whole cohort was 79% (95% CI: 43 – 55%) and 88% for low-volume recurrences and 50% for high-volume recurrences, respectively (p

Background Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. Methods The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon’s two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. Discussion The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy. Trial registration this trial is registered on clinicaltrials.gov (NCT02826564). Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1251-3) contains supplementary material, which is available to authorized users.

• The most common treatment for non-metastatic muscle invasive bladder cancer (MIBC) is radical cystectomy with pelvic lymph node dissection. For selected patients, trimodal therapy (TMT) consisting in a maximal transurethral resection of the bladder, followed by a concurrent chemotherapy and radiotherapy, spread over 5 to 7 weeks, is considered as an acceptable option. We aimed to perform a systematic review to report the current results of curative hypo-fractionated radiotherapy in terms of oncological outcomes and toxicity. In total, 5 phase III and 13 phase II trials were retained. Our review shows that TMT using hypo-fractionated radiotherapy allows a 2-year recurrence free survival rate between 43% and 83%, a 5-year OS rate going from 36% to 58%. Less than 12% of late grade ≥3 gastro-intestinal toxicities and between 4 to 46% grade ≥3 genito-urinary late toxicities were observed. This approach must be evaluated with prospective trials including quality of life scales.

PURPOSE: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. METHODS: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. RESULTS: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). CONCLUSION: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. PATIENT SUMMARY: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity. ispartof: RADIOTHERAPY AND ONCOLOGY vol:138 pages:59-67 ispartof: location:Ireland status: published

INTRODUCTION AND OBJECTIVES:Previous studies defined biochemical response (BR) to salvage radiotherapy (SRT) as a first PSA after SRT

INTRODUCTION AND OBJECTIVES:The use of concomitant hormonal therapy (HT) in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP) has shown to be beneficial on stro...

INTRODUCTION AND OBJECTIVES:Salvage radiation therapy (SRT) represents a potential curative treatment option for prostate cancer (PCa) patients with rising PSA after radical prostatectomy (RP). How...

INTRODUCTION AND OBJECTIVES:Salvage radiation therapy (SRT) represents a potential curative treatment option for patients affected by PSA rising after radical prostatectomy (RP). However, little is...

The present study assessed the efficacy of hyperbaric oxygen therapy in reducing symptoms of radiation cystitis, a specific type of iatrogenic injury to the bladder, by systematic review of recent literature. The MEDLINE, Embase and Web of Science databases were searched using combinations of the terms "radiation," "cystitis" and "hyperbaric oxygen" to identify articles evaluating patients with radiation cystitis, treated with hyperbaric oxygen therapy. Only recent (

Up to 50% of patients recur after salvage radiation therapy (sRT) for prostate-specific antigen (PSA) rise following radical prostatectomy (RP). Notably, the importance of lymph node dissection (LND) at the time of RP with regard to recurrence risk following sRT has not been previously determined. Therefore, we evaluated the association between nodal yield at RP and recurrence after sRT. We performed a multi-institutional review of men with a rising PSA after RP treated with sRT. Clinicopathologic variables were abstracted, and the associations between lymph node yield and biochemical (BCR) as well as clinical recurrence (CR) after sRT were assessed using multivariable Cox proportional hazards regression models. In total, 728 patients were identified; of these, 221 and 116 were diagnosed with BCR and CR, respectively, during a median follow-up of 8.4 (interquartile range: 4.2–11.2) yr. On multivariable analysis, the risk of BCR after sRT was inversely associated with the number of nodes resected at RP (hazards ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96–0.99; p =0.049). Increased extent of dissection was also independently associated with a decreased risk of CR after sRT (HR: 0.97; 95%CI: 0.94–0.99; p =0.042). These data support the importance of an extensive LND at surgery and may be used in prognosis assessment when sRT is being considered. Patient summary We found that patients who had increased number of lymph nodes resected at surgery had improved outcomes after the receipt of salvage radiation therapy. These findings support the use of the extended lymph node dissection at initial surgery and should serve to improve counseling among patients who require salvage radiation therapy.

The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors. All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2–3 years of androgen deprivation therapy (ADT). Kaplan–Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors. Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25–87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17–1.54) and OS (HR 1.22, 95% confidence interval 1.10–1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%). Patients with pN1 PCa treated with wpRT and 2–3 years ADT have an encouraging 5‑year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

Background Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. Objective To test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. Design, setting, and participants A total of 525 patients received SRT at PSA levels ≤2ng/ml. Outcome measurements and statistical analyses Multivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. Results and limitations Median PSA and radiotherapy dose were 0.42ng/ml and 66Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01–3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51–4.52), and dose (HR: 0.82; 95% CI: 0.76–0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p=0.01). This was confirmed when considering patients treated with early SRT (p=0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4ng/ml). Conclusions The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. Patient summary The oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features.

Renal-cell carcinoma is considered to be a radioresistant tumour, but this notion might be wrong. If given in a few (even single) fractions, but at a high fraction dose, stereotactic body radiotherapy becomes increasingly important in the management of renal-cell carcinoma, both in primary settings and in treatment of oligometastatic disease. There is an established biological rationale for the radiosensitivity of renal-cell carcinoma to stereotactic body radiotherapy based on the ceramide pathway, which is activated only when a high dose per fraction is given. Apart from the direct effect of stereotactic body radiotherapy on renal-cell carcinoma, stereotactic body radiotherapy can also induce an abscopal effect. This effect, caused by immunological processes, might be enhanced when targeted drugs and stereotactic body radiotherapy are combined. Therefore, rigorous, prospective randomised trials involving a multidisciplinary scientific panel are needed urgently. © 2014 Elsevier Ltd.

Background and purpose Local recurrences after radiotherapy are dose-dependent and occur in the dominant intraprostatic lesion (DIL). The purpose of this study was to evaluate the impact of a simultaneous integrated boost (SIB) to the magnetic resonance imaging (MRI)-defined DIL on toxicity. Materials and methods Four-hundred and ten patients were treated with intensity-modulated radiotherapy. A median dose of 78Gy was prescribed to the prostate. A SIB of 82Gy to the DIL was performed in 225 patients (SIB+). Genitourinary and rectal toxicity on fixed time points up to 8years were compared between SIB− (185 patients) and SIB+ patients. Chi-square, Fisher's exact and Kaplan–Meier statistics were applied. With a median follow up of 72months, the six-year actuarial risk of genitourinary and rectal toxicity grade⩾2 was 31% and 12% respectively. The actuarial risk of developing toxicity and incidence of symptoms at fixed time points were not increased with a SIB. Conclusion Performing a SIB did not increase genitourinary or rectal toxicity up to 8years' follow-up.