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The DeEscalate study compared the use of Cisplatin and Cetuximab in combination with radiotherapy in the treatment of Human-Papillomavirus (HPV) positive cancer of the oropharynx. As part of the study the MD Anderson Dysphagia Inventory (MDADI) scores were collected at baseline and at time intervals up to two years post treatment. The degree of dysphagia was found not to be strongly affected by the treatment arm. This study seeks to determine anatomical locations associated with dysphagia as measured by the change in overall MDADI score relative to baseline. Approaches that do not rely on delineated structures were employed because various structures such as the oral mucosa, pharyngeal mucosa and constrictor muscles have all been identified as possible contributors to dysphagia. In this exploratory analysis we consider three possible approaches to this problem and explore the merits of each.

A total of 160 patients had all the required data available for analysis. Each patient CT scan was registered against a reference scan using deformable registration. Delineated contours and dose grids were subsequently propagated through the same deformation. Variation in structure position was used to quantify the registration uncertainty. We compared three approaches to image based outcomes analysis; a cluster detection approach, voxel-wise regression and a regression method based on Principal Component Analysis, Partial Least Squares (PLS) regression, controlled for tumour volume using the GTV volume.
The correlation between each dose voxel and the change in toxicity was calculated alongside the t-statistic. Permutation testing was used to identify statistically significant clusters. In parallel; two regression models were tried. A voxel-wise Huber regression was used to fit the change in outcome to dose, tumour volume and the volume of the 60 Gy isodose at each point in space.  The second method, a PLS regression, related to principal component regression, identifies the latent scores of the dependent and independent variables having maximum correlation, five components were used. GTV volume was used a surrogate measure of tumour burden.

Regions of correlation were identified close to the salivary glands and at the level of the larynx. These regions were significant with a t-test. After applying permutation testing due to the very large number of comparisons, these regions, although anatomically plausible, were found to not be statistically significant (p > 0.05). Regression identified similar regions as important.

Correlations between delivered dose and dysphagia in anatomical regions that may be expected to correlate were identified. However, these were not statistically significant either using a correlation cluster based approach or a partial least squares regression approach. The partial least squares method has the advantage of being able to decompose the image into only a few components rather than having to fit thousands of voxels individually.