(Pre)treatment risk factors for late fatigue and fatigue trajectories following radiotherapy for breast cancer

Breast cancer; Fatigue; RadiotherapyCáncer de mama; Fatiga; RadioterapiaCàncer de mama; Fatiga; RadioteràpiaFatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (ORGeneralFatigue = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered.We thank all patients who participated in the REQUITE study and all the REQUITE staff involved in this project. Belgium: Ghent University Hospital; KU Leuven. France: ICM Montpellier, CHU Nîmes (Department of Radiation Oncology, CHU Nîmes, Nîmes, France). Germany: Zentrum für Strahlentherapie Freiburg (Dr. Petra Stegmaier); Städtisches Klinikum Karlsruhe (Dr. Bernhard Neu); ViDia Christliche Kliniken Karlsruhe (Prof. Johannes Claßen); Klinikum der Stadt Ludwigshafen GmbH (PD Dr. Thomas Schnabel); Universitätsklinikum Mannheim: Anette Kipke and Christiane Zimmermann; Strahlentherapie Speyer (Dr. Jörg Schäfer). The researchers at DKFZ also thank Anusha Müller, Irmgard Helmbold, Thomas Heger, Sabine Behrens, Axel Benner, Nicholas Schreck. Petra Seibold is supported by ERA PerMed 2018 funding (BMBF #01KU1912) and BfS funding (#3619S42261). Italy: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Candiolo Cancer Institute – FPO, IRCCS. Tiziana Rancati was partially funded by Fondazione Italo Monzino. The Netherlands: Sylvie Canisius at Maastro Clinics, Maastricht. Spain: Barcelona: Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus; VHIO acknowledge the Cellex Foundation for providing research facilities and thank CERCA Programme/Generalitat de Catalunya for institutional support. Sara Gutiérrez-Enríquez is supported by ERAPerMed JTC2018 funding (ERAPERMED2018-244 and SLT011/18/00005). Santiago: Complexo Hospitalario Universitario de Santiago. Ana Vega: supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (PI22/00589, PI19/01424; INT20/00071); the ERAPerMed JTC2018 funding (AC18/00117); the Autonomous Government of Galicia (Consolidation and structuring program: IN607B), by the Fundación Mutua Madrileña (call 2018) and by the AECC (PRYES211091VEGA); UK: University Hospitals of Leicester NHS Trust; Theresa Beaver, Kaitlin Walker and Sara Barrows. Dr Tim Rattay was funded by a National Institute of Health Research (NIHR) Clinical Lectureship (CL 2017-11-002) and is currently supported by the NIHR Leicester Biomedical Research Centre. 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. Manchester: Catharine West and Rebecca Elliott are supported by NIHR Manchester Biomedical Research Centre and Catharine West is supported by Cancer Research UK (C1094/A18504, C147/A25254). USA: Mount Sinai Hospital, New York. Open Access funding enabled and organized by Projekt DEAL

Survivorship data in Prostate Cancer : Where are we and where do we need to be?

Funding/Support and role of the sponsor: PIONEER is funded through the IMI2 Joint Undertaking and is listed under grant agreement 777492. IMI2 receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The funding bodies played no direct role in this study. The views communicated here are those of PIONEER. Neither the IMI nor the European Union, EFPIA, or any associated partners are responsible for any use that may be made of the information contained herein.Peer reviewedPublisher PD

Health Policy for Prostate Cancer Early Detection in the European Union and the Impact of Opportunistic Screening:PRAISE-U Consortium

With the new policy recommendation in 2022 to explore the possibilities of screening for prostate cancer by the European Commission, the landscape for prostate cancer early detection is evolving. In line with this recommendation, the PRAISE-U project aims to evaluate the early detection and diagnosis of prostate cancer through customised and risk-based screening programmes, with the goal to align protocols across European Union member states. This systematic review is part of the PRAISE-U project, with the goal to review the policy, medical guideline recommendations, and the current level of opportunistic screening presented in the scientific literature on prostate cancer early detection from 2016 to 2023 in European Union member states. An extensive literature search was performed on 1 June 2023 in a large number of databases, including Embase.com, Medline (Ovid), Web of Science Core Collection, Google Scholar, and Policy Commons. We identified 318 articles (qualitative, quantitative, and reviews), of which 41 were included in the full-text screening. Seventeen articles were ultimately identified as eligible for inclusion. The included articles revealed significant variations towards PSA-based early detection policies for prostate cancer in nine European countries. Despite official recommendations, opportunistic screening was prevalent across all nine countries regardless of recommendations for or against PSA-based early detection. This systematic review suggests that the current early detection policies are not fit for purpose. High levels of opportunistic screening and overdiagnosis persist, prompting policy recommendations for standardised guidelines, informed decision making, and increased awareness to improve efficiency and effectiveness in early detection.</p

The Key Role of Patient Involvement in the Development of Core Outcome Sets in Prostate Cancer

Funding/Support and role of the sponsor: This research was supported by funding under the PIONERR Consortium. The Consortium played a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.Peer reviewedPublisher PD

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT.EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p &lt; 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.</p

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer : An International Multidisciplinary Systematic Review

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy

none38siContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).noneWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; MacLennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B LWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; Maclennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

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