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

Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer.

BACKGROUND AND PURPOSE: A higher radiation dose to the heart is known to be associated with increased mortality in non-small cell lung cancer (NSCLC) patients. It is however unknown what the contribution of the heart dose is when other risk factors for mortality are also accounted for. MATERIALS AND METHODS: We constructed and externally validated prediction models of mortality after definitive chemoradiotherapy for NSCLC. Models were developed in 145 stage I-IIIB NSCLC patients. Clinical (performance status, age, gross tumour volume (GTV) combining primary tumour and involved lymph nodes, current smoker) and dosimetric (mean lung (MLD) and heart (MHD) dose) variables were considered. Multivariable logistic regression models predicting 12 and 24 month mortality were built in 5-fold cross-validation. Discrimination and calibration was assessed in 3 external validation datasets containing 878 (via distributed learning), 127 and 96 NSCLC patients. RESULTS: The best discriminating prediction models combined GTV, smoker and/or MHD: bootstrapping AUC (95% CI) of 0.74 (0.66-0.78) and 0.69 (0.55-0.74) at 12 and 24 months. At external validation, the 24 month mortality GTV-smoker-MHD model robustly showed moderate discrimination (AUC = 0.61-0.64 before and 0.64-0.65 after model update) with limited 0.01-0.07 improvement over a GTV-only model, and calibration slope (0.64-0.65). This model can identify patients for whom a MHD reduction may be useful (e.g. PPV = 77%, NPV = 52% (60% cut-off)). CONCLUSIONS: Tumour volume is strongly related to mortality risk in the first 2 years after chemoradiotherapy for NSCLC. Modelling indicates that efforts to reduce cardiac dose may be relevant for small tumours and that smoking has an important negative association with survival.status: publishe

Multifactorial risk factors for mortality after chemotherapy and radiotherapy for non-small cell lung cancer

BACKGROUND AND PURPOSE: A higher radiation dose to the heart is known to be associated with increased mortality in non-small cell lung cancer (NSCLC) patients. It is however unknown what the contribution of the heart dose is when other risk factors for mortality are also accounted for. MATERIALS AND METHODS: We constructed and externally validated prediction models of mortality after definitive chemoradiotherapy for NSCLC. Models were developed in 145 stage I-IIIB NSCLC patients. Clinical (performance status, age, gross tumour volume (GTV) combining primary tumour and involved lymph nodes, current smoker) and dosimetric (mean lung (MLD) and heart (MHD) dose) variables were considered. Multivariable logistic regression models predicting 12 and 24 month mortality were built in 5-fold cross-validation. Discrimination and calibration was assessed in 3 external validation datasets containing 878 (via distributed learning), 127 and 96 NSCLC patients. RESULTS: The best discriminating prediction models combined GTV, smoker and/or MHD: bootstrapping AUC (95% CI) of 0.74 (0.66-0.78) and 0.69 (0.55-0.74) at 12 and 24 months. At external validation, the 24 month mortality GTV-smoker-MHD model robustly showed moderate discrimination (AUC = 0.61-0.64 before and 0.64-0.65 after model update) with limited 0.01-0.07 improvement over a GTV-only model, and calibration slope (0.64-0.65). This model can identify patients for whom a MHD reduction may be useful (e.g. PPV = 77%, NPV = 52% (60% cut-off)). CONCLUSIONS: Tumour volume is strongly related to mortality risk in the first 2 years after chemoradiotherapy for NSCLC. Modelling indicates that efforts to reduce cardiac dose may be relevant for small tumours and that smoking has an important negative association with survival

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.status: publishe