A comprehensive assessment of mucositis due to radiation for head and neck cancer: Pathophysiology, clinical and patient-reported outcomes, and a proposal for a novel treatment based on ayurvedic medicine

Introduction: Head and neck cancers require aggressive multi-modal treatment, including a course of radiation therapy. Mucositis is a common side effect of radiation therapy with short- and long-term symptoms and disabilities. The objectives of this body of work were to characterize the myriad of clinical manifestations of mucositis and to describe patient-reported scales currently available to measure patients' symptoms (Manuscript ;Methods: In-depth reviews of articles published in PUBMED were done; articles were identified using the following search terms: radiation therapy; head and neck cancer; and patient symptoms/reported problems/subjective feelings/complications/side-effects. Review of traditional Ayurvedic texts was conducted to identify plant compounds effective for general stomatitis and, using a bio-prospecting methodology, recent literature was reviewed to ascertain mechanisms of action of these compounds.;Results: Multiple clinician-rated scales use inconsistent terminology and scoring rubrics to rate mucositis and often do not correlate with patient-reported symptoms. Only several patient-reported scales currently exist and they measure diverse and limited symptoms. However, multiple studies indirectly describe a plethora of acute and chronic symptoms resulting in marked disability and suffering. There are multiple metabolic pathways that drive the phases of radiation-induced mucositis and current medications are ineffective in controlling symptoms and progression. This results in patient suffering and cancer therapy protocol interruption. Using bio-prospecting, seven compounds met the following criteria for a novel treatment based on Ayurvedic medicine: can be used internally, daily, and as a mouthwash; has anti-bacterial and anti-fungal effects; and enhances saliva production, pH balance, and wound healing. Discussion: Radiation-induced mucositis is characterized by complex pathophysiology and clinical manifestations. There is a great need to develop uniform methods to describe symptoms, which would, in turn, enhance the assessment of new interventions to treat mucositis as well as enhance adherence to aggressive therapeutic protocols. Patient-reported scales should be developed and should capture the diverse experience of mucositis using patients' language (see poem below). In addition, clinicians' measurements should be standardized in terminology and content. A new mouthwash that is based on traditional Ayurvedic knowledge, supported by current scientific data, and targets multiple pathways, offers a new possibility to treat radiation-induced mucositis. This proposal is a paradigm shift in the drug discovery mechanism in that drug development need not always be confined to new molecular entities. Instead, bio-prospecting of plants utilized by ancient knowledge and gained from indigenous medicines may provide a new strategy for drug development. (Abstract shortened by ProQuest.).