Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.

Background: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung).

Methods: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute).

Comparing symptom reporting by prostate cancer patients and healthcare professionals in the international multicentre REQUITE study.

Introduction: Previous studies showed that healthcare professionals and patients had only moderate to low agreement on their assessment of treatment-related symptoms. We aimed to determine the levels of agreement in a large cohort of prostate cancer patients.

Methods: Analyses were made of data from 1,756 prostate cancer patients treated with external beam radiotherapy (RT) and/or brachytherapy in Europe and the USA and recruited into the prospective multicentre observational REQUITE study.

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer.

Introduction: We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT).

Methods: The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index.

The correlation between pre-treatment symptoms, acute and late toxicity and patient-reported health-related quality of life in non-small cell lung cancer patients: Results of the REQUITE study.

Background And Purpose: To investigate the association between clinician-scored toxicities and patient-reported health-related quality of life (HRQoL), in early-stage (ES-) and locally-advanced (LA-) non-small cell lung cancer (NSCLC) patients receiving loco-regional radiotherapy, included in the international real-world REQUITE study.

Materials And Methods: Clinicians scored eleven radiotherapy-related toxicities (and baseline symptoms) with the Common Terminology Criteria for Adverse Events version 4. HRQoL was assessed with the European Organization for Research and Treatment of Cancer core HRQoL questionnaire (EORTC-QLQ-C30).

Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort.

Background: Circadian rhythm impacts broad biological processes, including response to cancer treatment. Evidence conflicts on whether treatment time affects risk of radiotherapy side-effects, likely because of differing time analyses and target tissues. We previously showed interactive effects of time and genotypes of circadian genes on late toxicity after breast radiotherapy and aimed to validate those results in a multi-centre cohort.

Overview of health-related quality of life and toxicity of non-small cell lung cancer patients receiving curative-intent radiotherapy in a real-life setting (the REQUITE study).

Objectives: Radiotherapy-induced toxicity may negatively impact health-related quality of life (HRQoL). This report investigates the impact of curative-intent radiotherapy on HRQoL and toxicity in early stage and locally-advanced non-small cell lung cancer patients treated with radiotherapy or chemo-radiotherapy enrolled in the observational prospective REQUITE study.

Materials And Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire up to 2 years post radiotherapy.

Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity.

Aim: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi).

Materials And Methods: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream.

External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort.

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. Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature.

A Deep Learning Approach Validates Genetic Risk Factors for Late Toxicity After Prostate Cancer Radiotherapy in a REQUITE Multi-National Cohort.

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. The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up.

Multi-centre technical evaluation of the radiation-induced lymphocyte apoptosis assay as a predictive test for radiotherapy toxicity.

Predicting which patients will develop adverse reactions to radiotherapy is important for personalised treatment. Prediction will require an algorithm or nomogram combining clinical and biological data. The radiation-induced lymphocyte apoptosis (RILA) assay is the leading candidate as a biological predictor of radiotherapy toxicity.

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.

ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers.

Background: Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia mutated and rad3 related (ATR) and DNA-dependent protein kinase catalytic sub-unit (DNA-PKcs) play critical roles in DNA damage response (DDR) by linking DNA damage sensing to DDR effectors that regulate cell cycle progression and DNA repair. Our objective was to evaluate if ATM, ATR and DNA-PKcs expressions could predict response to therapy and clinical outcome in epithelial ovarian cancers.

Methods: We investigated ATM, ATR, and DNA-PKcs expressions in ovarian epithelial cancers [protein expression (n = 194 patients), mRNA expression (n = 156 patients)] and correlated to clinicopathological outcomes as well as expression of X-ray repair cross-complementing protein 1 (XRCC1), cell division cycle-45 (CDC45), cyclin-dependent kinase 1(CDK1) and Ki-67 in tumours.

Degree of Rectal Distension Seen on Prostate Radiotherapy Planning CT Scan Is Not a Negative Prognostic Factor in the Modern Era of Image-Guided Radiotherapy.

Background: Studies have shown that rectal distension has a significant impact on treatment failure in patients receiving radical radiotherapy for prostate cancer. A distended rectum contributes to excessive organ movement during treatment, resulting in significant underdosing of the target volume and higher treatment failure rates. The increasing use of highly conformal, precise radiotherapy techniques places greater importance on reducing this risk.

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated breast cancers and metformin's ability to modulate Trx system expression and breast cancer radiosensitivity evaluated in vitro. AMPKα and pAMPKα(Thr172) expression was assessed using a discovery (n=166) and validation cohort (n=609).

Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer.

Oestrogen metabolites can induce oxidative DNA base damage and generate potentially mutagenic apurinic sites (AP sites) in the genomic DNA. If unrepaired, mutagenic AP sites could drive breast cancer pathogenesis and aggressive phenotypes. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA base excision repair (BER) protein and essential for processing AP sites generated either directly by oestrogen metabolites or during BER of oxidative base damage.