Dysphagia at 1 year is associated with mean dose to the inferior section of the brainstem
Vasquez Osorio, Eliana Abravan, Azadeh Green, Andrew van Herk, Marcel Ganderton, D. McPartlin, Andrew J
Vasquez Osorio, Eliana
Abravan, Azadeh
Green, Andrew
van Herk, Marcel
Ganderton, D.
McPartlin, Andrew J
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Abstract
Purpose or Objective
Dysphagia is a common consequence of head and neck (HN) RT, which negatively affects quality of life. Voxel-wise image based data mining (IBDM) allows exploring the relation between RT dose and treatment outcome without prior assumptions.
Here, we used IBDM to explore the relation between RT dose to normal HN anatomy and dysphagia at 1 year after treatment,
assessed using three validated outcome measures: composite M.D. Anderson Dysphagia Inventory (MDADI), performance
status scale for normalcy of diet (HN-PSS), and water test (WT). Materials and Methods
IBDM was applied to data from 104 oropharyngeal cancer patients treated with definitive (Chemo)RT and assessed for
swallow function pre-treatment and at 1 year by a Swallow Assessment Specialist. We spatially normalised all patient’s
planning dose matrices (in equivalent dose at 2Gy/fraction, α/β=3Gy) to three arbitrary reference anatomies using a
combination of thin-plate splines deformation (for neck alignment) and NiftyReg. To reduce target laterality bias, all
patients were mirrored in the left-right axis and mapped twice to the reference patient. Regions where the dose was
associated with outcome at 1 year were found by performing voxel-wise statistics (t-test for WT, Spearman correlation for
MDADI/HN-PSS) and permutation testing (n=1000).
Mean and maximum doses of the overlap of the significant regions for all outcomes were averaged across the three
reference patients. Clinical factors, treatment variables and pre-treatment measures for WT, HN-PSS and MDADI (table 1)
were used in multivariable analysis to predict WT (logistic regression), HN-PSS and MDADI (linear regression) at 1 year. A
clinical model was found using backward stepwise selection for each outcome. Improvement of model discrimination after
adding the mean/max doses was quantified using Akaike information criterion (AIC). Results
IBDM revealed significant association between dose to distinct regions and the three outcomes tested (p<0.005), overlapping
around the inferior section of the brainstem (figure 1). Models for WT and HN-PSS at 1 year were significantly improved by
including mean dose to the overlap region (p=0.02); this was not the case for the MDADI model. Inclusion of max dose did
not significantly improve discrimination of any model. Conclusion
Mean dose to the inferior section of the brainstem is strongly associated with dysphagia at 1 year following HN RT. The
identified region is in proximity to swallowing centres in the medulla oblongata, providing a possible mechanistic
explanation. Unexpectedly, no significant region was found close to the pharyngeal constrictor muscles or salivary glands,
despite dose to these structures being predictive for dysphagia in previous studies. Mean, rather than max dose, was most
predictive, possibly indicating a parallel organ effect or a serial effect in small substructures (masked by imperfect
registration). Research is required to derive a dose constraint for RT planning.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Osorio EMV, Abravan A, Green A, van Herk M, Ganderton D, McPartlin A. Dysphagia at 1 year is associated with mean dose to the inferior section of the brainstem. Radiotherapy and Oncology. 2022 May;170:S212-S4. PubMed PMID: WOS:000806759200213.