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Application of optical coherence tomography in the diagnosis of mucositis in patients with head and neck cancer during a course of radio(chemo)therapy
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文摘

Objective

Mucositis is the most common oral complication of non-surgical therapy (chemotherapy, radiotherapy, and radio(chemo)therapy) in patients with head and neck cancer. Growing evidence indicates that more aggressive treatment regimens improve local tumor control and the survival of patients with locally advanced head and neck cancer. However combined therapy approaches are associated with higher acute toxicity. Currently there are no in vivo methods to visualize microscopic changes of mucosal structure during a course of radio(chemo)therapy and to assess the development and healing of oral mucositis. As a result it has been impossible to predict its severity before evident mucosal changes occurred.

The objective of this study was to visualize and quantify changes of normal oral mucosa in patients with oral and oropharyngeal cancer during a course of radio(chemo)therapy using a new non-invasive optical imaging modality – optical coherence tomography (OCT), which creates real-time cross-sectional microstructural images of tissues at depths of up to 2 mm and with a spatial resolution of 10–15 μm.

Materials and methods

Between November 2004 and June 2006, 18 patients with stage II–IV oral and oropharyngeal squamous cell cancer took part in the study. Patients were treated with external beam radiotherapy alone, or combined with chemotherapy. During the therapy we performed OCT imaging daily starting on the first day of irradiation or chemotherapy, at two sites on the right and left cheek, to evaluate normal oral mucosa toxicity. No OCT imaging was performed at the tumor site. We used a time domain OCT system operating at 1310 nm wavelength with a spatial resolution of 10–20 μm in depth. Epithelial thickness and contrast were measured in the OCT images and compared with clinical manifestations of the mucositis.

Results

The OCT images of normal buccal mucosa have a high-contrast stratified structure with well-delineated epithelium, lamina propria, and submucosa. Typical changes of OCT images during radio(chemo)therapy include a gradual loss of in the layer contrast, signs of edema, and epithelium thinning, eventually leading to its complete absence (erosion). Patients with severe reduction of OCT contrast between epithelium and lamina propria, a decrease in the epithelial layer thickness at a very early stage of the treatment (after a total cumulative dose of 2–4 Gy), and complete loss of contrast at the first day of clinical manifestation of mucositis (mild hyperemia, total cumulative dose 10–14 Gy), ultimately had severe mucositis. Patients with a visible, high-contrast interface between epithelium and lamina propria, on the first day of clinical symptoms, only had mild mucositis.

Conclusion

OCT is able to provide additional valuable information about the state of mucosa during a course of radio(chemo)therapy to complement visual evaluation. Typical OCT signs of mucositis appeared earlier and persisted longer than visual signs and the extent of OCT changes correlated with the severity of clinical manifestations of mucositis. Quantitative analysis of tissue layer contrast changes and epithelial thickness in OCT images provides an objective tool to assess mucosal damage and repair during and after the treatment. OCT images provide indirect information about radiosensitivity of oral and pharyngeal mucosa, serving as a predictor of the severity of radiation-induced mucositis during a course of radio(chemo)therapy.

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