Dose surface maps of the heart can identify regions associated with worse survival for lung cancer patients treated with radiotherapy

Alan McWilliam; Chloe Dootson; Lewis Graham; Kathryn Banfill; Azadeh Abravan; Marcel van Herk

doi:10.1016/j.phro.2020.07.002

Dose surface maps of the heart can identify regions associated with worse survival for lung cancer patients treated with radiotherapy

Phys Imaging Radiat Oncol. 2020 Jul 30:15:46-51. doi: 10.1016/j.phro.2020.07.002. eCollection 2020 Jul.

Authors

Alan McWilliam^{1

2}, Chloe Dootson³, Lewis Graham³, Kathryn Banfill^{1

2}, Azadeh Abravan^{1

2}, Marcel van Herk^{1

2}

Affiliations

¹ Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK.
² Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK.
³ Department of Physics and Astronomy, The University of Manchester, UK.

Abstract

Background and purpose: For lung cancer patients treated with radiotherapy, radiation dose to the heart has been associated with overall survival, with volumetric dose statistics widely presented. However, critical cardiac structures are present on the hearts surface, where this approach may be sub-optimal. In this work we present a methodology for creating cardiac surface dose maps and identify regions where excess dose is associated with in worse overall survival.

Material and methods: A modified cylindrical coordinate system was implemented to map the cardiac surface dose for lung cancer patients. Validation was performed by mapping the cardiac chambers for 55 patients, fitting a point spread function (PSF) to the blurred edge. To account for this uncertainty, dose maps were blurred by a 2D-Gaussian with width described by the PSF. Permutation testing identified regions where excess dose was associated with worse patient survival. The 99th percentile of the max t-value then defined a cardiac surface region to extract dose, from each patient, to be analysed in a multivariable cox-proportional hazards survival model.

Results: Cardiac surface maps were created for 648 lung cancer patients. Cardiac surface dose maps were blurred with a 2D- Gaussian filter of size σ_φ = 4.3° and σ_y = 1.3units to account for mapping uncertainties. Permutation testing identified significant differences across the surface of the right atria, p < 0.001, at all timepoints. The median dose to the region defined by the 99th percentile of the maximum t-value was 18.5 Gy. Multivariable analysis showed the dose to this region was significantly associated with survival, hazard ratio 1.01 Gy^-1, p = 0.03, controlling for confounding variables.

Conclusions: Cardiac surface mapping was successfully implemented and identified a region where excess dose was associated with worse patient survival. This region extended over the right atria, potentially suggesting an interaction with the hearts electrical conduction system.

Keywords: Cardiac toxicity; Dose surface maps; Lung cancer; Radiotherapy.