Abstract
Late side effects of radiotherapy (RT) in the treatment for head and neck (HN) malignancies involve an inadequate healing response of the distressed tissue due to RT-induced hypovascularity. The aim of this study was to develop a pilot model in which vascular alterations associated with the onset of late irradiation (IR) injury could be measured in rabbit oral mucosa and mandibular bone. Eight male New Zealand white rabbits were divided over four treatment groups. Group I-III received four fractions of RT (5.6 Gy, 6.5 Gy, and 8 Gy, respectively) and Group IV received 1 fraction of 30 Gy. Oral microcirculatory measurements were performed at baseline (before RT) and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI). Post-mortem histopathology specimens were analyzed. Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV (P<0.05). At T11, no lasting effect of decreased vessel density was observed. PPV and MFI remained unaltered at all-time points. Group IV showed a marked difference in scattered telangiectasia such as microangiopathies, histological necrosis, and loss of vasculature. No significant lasting effect in mucosal microcirculation density due to IR damage was detected. Observed changes in microcirculation vasculature and histology may align preliminary tissue transition towards clinical pathology in a very early state associated with late IR injury in the oral compartment. Enhancing knowledge on the onset of late vascular IR injury in the HN region could help the development, monitoring, and timing of therapies that act on prevention, discontinuation, or repair of radiation pathology.
Highlights
Radiotherapy (RT) has an essential role in the treatment of head and neck (HN) cancer patients
Oral microcirculatory measurements were performed at baseline and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI)
Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV (P
Summary
Radiotherapy (RT) has an essential role in the treatment of head and neck (HN) cancer patients. Experimental research fulfills an essential role in providing standardization of a model and controlled environments for studying pathophysiology and interventional responses associated with HN IR injury. Increased fibrosis and decreased vascularity in the soft tissues surrounding the irradiated mandible was observed after 5 fractions of 15 Gy in a rat IR model [4]. SDFI has extensively been used at the patient bedside and experimental setting to monitor and assess pathophysiological states associated with shock (e.g., cardiogenic, hypovolemic, and septic) [21,22], interventional endpoints and therapeutic responses associated with microvascular alterations in critical care patients, wound healing, and the side effects of cancer chemotherapy and RT [23,24,25].
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