Efficacy and Safety of CareMin650 Used for the Prevention of Oral Mucositis in Patients With Head and Neck Cancer Starting Radiotherapy: the PrOMiSE Study

Oral mucositis (OM) can affect up to 90% of head and neck cancer (HNC) patients treated with radiation therapy (RT) and/or chemotherapy (CT). It can be as severe as WHO grade 3 / 4 in 35% to more than 50% of cases. The pathobiology of OM relates to injuries that occur in the epithelial and connective tissues, as a response to a complex cascade of biological events, involving all the tissues and cellular elements of the mucosa (Sonis et al., 2004). OM may result in dysphagia, pain, risk of infection, weight loss, interruption or modification of anticancer therapy, or hospitalization.

As OM is a major and frequent side effect of RT, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) has published clinical practice guidelines for mucositis prevention secondary to cancer therapy. In addition to meticulous oral hygiene, MASCC/ISOO also suggests several therapeutic preventive strategies: growth factors, cytokines, anti-inflammatory agents, natural agents, ... In the 2020 guidelines, photobiomodulation (PBM) formerly known as Low-Level Laser Therapy (LLLT), has obtain a full recommendation for the prevention of OM in patients undergoing RT, with or without concomitant CT, for HNC.

PBM is the application of lasers or non-coherent light sources such as LEDs, to beneficially influence cellular metabolism. In a Cochrane review that included 32 clinical trials, PBM was the only treatment that demonstrated a reduction in the risk of severe mucositis. In 2011, a meta-analysis included 11 placebo-controlled randomized trials in 415 patients treated with CT or RT for head and neck cancer (HNC) or hematopoietic stem cell transplantation. According to MASCC/ISOO recommendations, PBM is now recommended to prevent OM in HNC patients receiving RT with or without chemotherapy . The 2014 recommendations have been endorsed by the AFSOS (Association Française pour les Soins de Support en Oncologie) in France. Finally, the National Institute for Health and Care Excellence (NICE) determined that PBM for OM shows no major safety concerns and that evidence on efficacy is adequate in quality and quantity.

Taken together, these data show that PBM is an efficacious and safe option to prevent and/or treat radiotherapy-related OM.

Even though PBM has proved its efficacy, delivery of PBM in OM is currently limited by lack of standardization, accuracy and reproducibility. In particular, the distance between the lighting source and the mucosa or skin is difficult to assess and control accurately. Therefore, the amount of energy delivered may vary from one session to another, as well as from one operator to another.