Frank J W M Dankers1, Robin Wijsman2, Esther G C Troost3, Caroline J A Tissing-Tan4, Margriet H Kwint5, José Belderbos5, Dirk de Ruysscher6, Lizza E Hendriks7, Lioe-Fee de Geus-Oei8, Laura Rodwell9, Andre Dekker6, René Monshouwer10, Aswin L Hoffmann11, Johan Bussink10. 1. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: frank.dankers@radboudumc.nl. 2. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Department of Radiation Oncology, Radiotherapiegroep, Arnhem, The Netherlands. 5. Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 6. Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. 7. Department of Pulmonary Diseases, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. 8. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Biomedical Photonic Imaging Group, MIRA Institute, University of Twente, Enschede, The Netherlands. 9. Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands. 10. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. 11. Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.
Abstract
BACKGROUND AND PURPOSE: We externally validated a previously established multivariable normal-tissue complication probability (NTCP) model for Grade ≥2 acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or volumetric-modulated arc therapy for locally advanced non-small cell lung cancer. MATERIALS AND METHODS: A total of 603 patients from five cohorts (A-E) within four different Dutch institutes were included. Using the NTCP model, containing predictors concurrent chemoradiotherapy, mean esophageal dose, gender and clinical tumor stage, the risk of Grade ≥2 AET was estimated per patient and model discrimination and (re)calibration performance were evaluated. RESULTS: Four validation cohorts (A, B, D, E) experienced higher incidence of Grade ≥2 AET compared to the training cohort (49.3-70.2% vs 35.6%; borderline significant for one cohort, highly significant for three cohorts). Cohort C experienced lower Grade ≥2 AET incidence (21.7%, p < 0.001). For three cohorts (A-C), discriminative performance was similar to the training cohort (area under the curve (AUC) 0.81-0.89 vs 0.84). In the two remaining cohorts (D-E) the model showed poor discriminative power (AUC 0.64 and 0.63). Reasonable calibration performance was observed in two cohorts (A-B), and recalibration further improved performance in all three cohorts with good discrimination (A-C). Recalibration for the two poorly discriminating cohorts (D-E) did not improve performance. CONCLUSIONS: The NTCP model for AET prediction was successfully validated in three out of five patient cohorts (AUC ≥0.80). The model did not perform well in two cohorts, which included patients receiving substantially different treatment. Before applying the model in clinical practice, validation of discrimination and (re)calibration performance in a local cohort is recommended.
BACKGROUND AND PURPOSE: We externally validated a previously established multivariable normal-tissue complication probability (NTCP) model for Grade ≥2 acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or volumetric-modulated arc therapy for locally advanced non-small cell lung cancer. MATERIALS AND METHODS: A total of 603 patients from five cohorts (A-E) within four different Dutch institutes were included. Using the NTCP model, containing predictors concurrent chemoradiotherapy, mean esophageal dose, gender and clinical tumor stage, the risk of Grade ≥2 AET was estimated per patient and model discrimination and (re)calibration performance were evaluated. RESULTS: Four validation cohorts (A, B, D, E) experienced higher incidence of Grade ≥2 AET compared to the training cohort (49.3-70.2% vs 35.6%; borderline significant for one cohort, highly significant for three cohorts). Cohort C experienced lower Grade ≥2 AET incidence (21.7%, p < 0.001). For three cohorts (A-C), discriminative performance was similar to the training cohort (area under the curve (AUC) 0.81-0.89 vs 0.84). In the two remaining cohorts (D-E) the model showed poor discriminative power (AUC 0.64 and 0.63). Reasonable calibration performance was observed in two cohorts (A-B), and recalibration further improved performance in all three cohorts with good discrimination (A-C). Recalibration for the two poorly discriminating cohorts (D-E) did not improve performance. CONCLUSIONS: The NTCP model for AET prediction was successfully validated in three out of five patient cohorts (AUC ≥0.80). The model did not perform well in two cohorts, which included patients receiving substantially different treatment. Before applying the model in clinical practice, validation of discrimination and (re)calibration performance in a local cohort is recommended.
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