SP-0462: Do the current software solutions serve our needs?
Magnus Thor · Radiotherapy and Oncology · 2018
The risk of radiation-induced morbidity (RIM) in patients treated with radiation therapy (RT) for lung or head and neck (HN) cancer is historically estimated by condensing the 3D dose distribution into a monodimensional dosevolume histogram (DVH) that disregards spatial information of the dose.Increasing evidences, however, suggest that a voxel-based approach (VBA) allows to identify unprecedented correlations between RIM and local dose release, and accordingly unveils the spatial signature of radiation sensitivity in inhomogeneous organs -such as the lungs -or in composite regions -such as the HN district.A first key issue of any kind of VBA (ranging from neuroimaging to dose map processing) is represented by the spatial normalization of the analyzed patients to a common anatomical reference.In the context of lungs or HN RIM analyses, several studies showed the excellent performance of the inter-patient diffeomorphic log demons image registration, which allows for a robust match of anatomical structures both from a pure geometrical point of view and in terms of dose-organ overlap (see [Palma et al., Int J Radiation Oncol Biol Phys 2016] for the lungs and [Monti et al., Sci Rep 2017] for the HN).This appears particularly noteworthy in the HN district, due to the high number of elusive structures, whose contouring may be challenging even for an experienced radiologist.Of note, the B-spline parameterization approach was also exploited in the spatial normalization of a cohort of lung cancer patients included in a survival analysis [McWilliam et al., Eur J Cancer 2017].Next, the voxel-based statistical analysis to test regional dosimetric differences between patients with and without RIM can be performed according to different schemes, ranging from a classical voxelwise t-test to several methods counteracting the multiple comparison problem inherent in the task.In particular, our previous researches showed that a non-parametric permutation test [Holmes et al., J Cereb Blood Flow Metab 1996] based on the Threshold Free Cluster Enhancement [Smith & Nichols, NeuroImage 2009] of a maximum-T statistics allows for an excellent compromise between the sensitivity of the analysis and the control over imagewise Type I errors.The application of this pipeline to a cohort of Hodgkin Lymphoma survivors for the study of late radiationinduced lung damage led to the discovery that a significantly higher dose (~ 6 Gy) was consistently delivered to patients with RIM in voxel clusters near the peripheral medial-basal portion of the lungs in low dose parenchymal regions.Analogously, in a cohort of patients treated for HN cancer, two voxel clusters located in correspondence of the cricopharyngeus muscle and cervical esophagus were found to receive a significantly higher dose (~ 48 Gy) in patients developing severe radiation-induced acute dysphagia.Interestingly, in both cases, the mean dose released to the significant clusters was found to be a good classifier of RIM (AUC of 0.7-0.8).An effort to put the VBA in a clinical perspective has led to the definition of an avoidance region in correspondence of the significant clusters.In particular, Monti et al. proposed to constrain the mean dose to clusters not to exceed the first percentile of the corresponding doses received by RIM patients.It should be stressed, however, that neither the described voxel-based dose difference analysis nor the criterion proposed for the avoidance regions provide any