Alan McWilliam1, Jason Kennedy2, Clare Hodgson3, Eliana Vasquez Osorio4, Corinne Faivre-Finn5, Marcel van Herk6. 1. Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK. Electronic address: alan.mcwilliam@manchester.ac.uk. 2. Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK. 3. Clinical Outcomes Unit, The Christie NHS Foundation Trust, Manchester, UK. 4. Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK. 5. Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK. 6. Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK; NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
Abstract
BACKGROUND: Advances in radiotherapy (RT) have allowed an increased proportion of lung cancer patients to be treated curatively. High doses delivered to critical thoracic organs can result in excess mortality with tolerance doses poorly defined. This work presents a novel method of identifying anatomical dose-sensitive regions within the thorax. METHODS: A high-resolution, normal-tissue dosimetric analysis was performed to identify regions in the heart that correlate with poorer survival. A total of 1101 patients treated with curative-intent RT were selected and all computed tomography imaging and dose distributions were deformed to a reference. Mean dose distributions were created for patients who survived versus those who did not at a set time point. Statistical significance of dose differences was investigated with permutation testing. The dose received by the most statistically significant region of the thorax was collected in all patients and included in a multivariate survival analysis. RESULTS: The permutation testing showed a highly significant region across the base of the heart, where higher doses were associated with worse patient survival (p < 0.001). Cox-regression multivariate analysis showed region dose, tumour volume, performance status and nodal stage were significant factors associated with survival, whereas cardiac mean dose, V5 and V30 showed no significance. Survival curves, controlling for these factors, were plotted with patients receiving doses greater than 8.5 Gy to the identified region showing worse survival (log-rank p < 0.001, hazard ratio 1.2). CONCLUSION: The application of this novel methodology in lung cancer patients identifies the base of the heart as a dose-sensitive region for the first time.
BACKGROUND: Advances in radiotherapy (RT) have allowed an increased proportion of lung cancerpatients to be treated curatively. High doses delivered to critical thoracic organs can result in excess mortality with tolerance doses poorly defined. This work presents a novel method of identifying anatomical dose-sensitive regions within the thorax. METHODS: A high-resolution, normal-tissue dosimetric analysis was performed to identify regions in the heart that correlate with poorer survival. A total of 1101 patients treated with curative-intent RT were selected and all computed tomography imaging and dose distributions were deformed to a reference. Mean dose distributions were created for patients who survived versus those who did not at a set time point. Statistical significance of dose differences was investigated with permutation testing. The dose received by the most statistically significant region of the thorax was collected in all patients and included in a multivariate survival analysis. RESULTS: The permutation testing showed a highly significant region across the base of the heart, where higher doses were associated with worse patient survival (p < 0.001). Cox-regression multivariate analysis showed region dose, tumour volume, performance status and nodal stage were significant factors associated with survival, whereas cardiac mean dose, V5 and V30 showed no significance. Survival curves, controlling for these factors, were plotted with patients receiving doses greater than 8.5 Gy to the identified region showing worse survival (log-rank p < 0.001, hazard ratio 1.2). CONCLUSION: The application of this novel methodology in lung cancerpatients identifies the base of the heart as a dose-sensitive region for the first time.
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