Gilles Defraene1, Frank J W M Dankers2, Gareth Price3, Ewoud Schuit4, Wouter van Elmpt5, Soumia Arredouani6, Maarten Lambrecht6, Joost Nuyttens7, Corinne Faivre-Finn3, Dirk De Ruysscher8. 1. KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven, Belgium. Electronic address: gilles.defraene@uzleuven.be. 2. Radboud University Medical Center, Department of Radiation Oncology, Nijmegen, The Netherlands; Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands. 3. Division of Cancer Sciences, The University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. 4. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, The Netherlands. 5. Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands. 6. KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven, Belgium. 7. Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 8. KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven, Belgium; Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands.
Abstract
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.
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 NSCLCpatients. 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 NSCLCpatients. 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.
Authors: Adrian Thummerer; Carmen Seller Oria; Paolo Zaffino; Arturs Meijers; Gabriel Guterres Marmitt; Robin Wijsman; Joao Seco; Johannes Albertus Langendijk; Antje-Christin Knopf; Maria Francesca Spadea; Stefan Both Journal: Med Phys Date: 2021-11-16 Impact factor: 4.506