Analysis of the Cancer Imaging Archive for Patterns of Locoregional Failure in Relation to the Mucous Membranes among Patients with Head and Neck Squamous Cell Carcinoma: Potential Organ at Risk that can be Spared?

Abstract

Radiation-induced oral mucositis (RIOM), a painful inflammation and ulceration of the mucous membranes (MM), occurs as a common and severe side effect of radiation treatment (RT) for head and neck cancers. It worsens significant quality of life leading to treatment interruption or cancellation. In RIOM, radiation injury of the MM basal epithelial cells may be one of the critical pathophysiological mechanisms. However, it is unclear if advanced radiation treatments could spare MM, without compromise on tumor control. The purpose of this study is to determine whether the MM that do not overlap with the prescription target volumes are a common site of locoregional recurrence in head and neck cancers. A de-identified data collection of 215 head and neck cancer patients stored within The Cancer Imaging Archive was downloaded for analysis. Imaging series both before and after RT were downloaded, as well as RT structures and RT dosimetric data. Diagnostic CECT and/or PET/CT and/or MRI scans documenting the initial evidence of recurrence were co-registered with corresponding original planning CTs. Radiologically evident recurrent gross disease (rGTV) was manually contoured, as well as the MM (defined as an approximately 3mm thick wall of mucosa tissue lining the oral cavity and pharynx and excluding any overlap with the radiation prescription targets). Contoured MM structures were cross-referenced with the sites of recurrence by examining the overlap of the MM volumes with the rGTV volumes. A total of 40 patients had documented evidence of recurrence; 38 of which had images available for analysis. Overall, 23 (60.5%) were oropharynx cancer. Of the 38 recurrences, 35 (92%) were locoregional: 23 with only local (60.5%) recurrences, 9 with only regional (23.7%) recurrences and 3 (7.9%) with both local and regional recurrences. One patient (2.6%) had distant recurrence, one patient had both regional and distant recurrences concomitantly, and one patient had local, regional and distant recurrences simultaneously. Overall, 30 patients (78.9%) had recurrences located exclusively within prescription PTV volumes/isodose lines. Four patients (10.5%) had recurrences located outside prescription PTV volumes/isodose lines, four patients (10.5%) had recurrences located both within and outside prescription PTV volumes/isodose lines (i.e., 2 sites of concomitant recurrence). Importantly, 0 patients (0%) had recurrences located in the contoured MM (excluding any overlap with the radiation prescription targets). Based on this retrospective series, the MM (excluding the areas of overlap with radiation prescription targets) are a rare location of locoregional recurrence. Hence, sparing the MM using radiation advanced dosimetry techniques could be a reasonable approach to reducing the incidence/severity of radiation-induced oral mucositis, without compromising tumor control. However, this requires further prospective investigation.