Abstract
Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck cancer. Diagnostics, prophylaxis and correction of this condition demand new accurate and objective approaches. Here we report on an in vivo longitudinal monitoring of the oral mucosa dynamics in 25 patients during the course of radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional optical coherence tomography (OCT). A spectral domain OCT system with a specially-designed oral imaging probe was used. Microvasculature visualization was based on temporal speckle variations of the full complex signal evaluated by high-pass filtering of 3D data along the slow scan axis. Angiographic image quantification demonstrated an increase of the vascular density and total length of capillary-like-vessels before visual signs or clinical symptoms of mucositis occur. Especially significant microvascular changes compared to their initial levels occurred when grade two and three mucositis developed. Further, microvascular reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy offers a non-invasive, convenient, label-free quantifiable structural and functional volumetric imaging method suitable for longitudinal human patient studies, furnishing fundamental radiobiological insights and potentially providing useful feedback data to enable adaptive radiotherapy (ART).
Highlights
The painful inflammation and possible ulceration of the mucous membranes lining the digestive tract known as mucositis is most common limiting toxicity of radio(chemo)therapy of head and neck cancer[1,2]
Continued dose accumulation caused an increase in the clinical manifestations of radiation reaction, as seen by the 2D Optical coherence tomography (OCT) angiographic maps (Fig. 1c,e,g)
After start of anti-mucositis therapy (typically chamomile and antiseptic washes in case of grade 1 (Fig. 1d); washes and analgesics in case of grade 2 (Fig. 1f); analgesics, antibacterial and antifungal therapy in case of grade 3 (Fig. 1h)), only in the case of grade 3 mucositis, the anti-mucositis therapy tended to slow down the microvascular increase (Fig. 1h)
Summary
The painful inflammation and possible ulceration of the mucous membranes lining the digestive tract known as mucositis is most common limiting toxicity of radio(chemo)therapy of head and neck cancer[1,2]. Reactions before the onset of their clinical manifestations, offering the possibility of early intervention in suitable patients, (2) properly evaluating the effectiveness of different preventive measures and treatments of the mucositis, (3) monitoring of the radiobiological response of the different mucosal components such as small versus large vessels RT effects, their temporal dynamics relative to mucositis manifestation and relative to structural tissue changes (e.g., epithelium nature and thickness), and (4) possible alterations in the radiation treatment delivery in the context of ART (adaptive radiotherapy[13]) Such a method should be ideally noninvasive, contrast-agent-free, suitable for repeated in-vivo investigations, well tolerated by patients, and provide useful information in real-time; the ability to detect tissue functionality including mucosal microcirculation during the course and after irradiation would be desirable[14,15]. In addition to high-resolution microstructural tissue imaging, alternate OCT contrast mechanisms have enabled sensitive imaging of the microvasculature based on Doppler- and speckle-based OCT20,21
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