Randomized Clinical Investigation of Photobiomodulation (PBM) for the Management of Early Peripheral Neuropathy Related to Medical Oncologic Therapy

Overview

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the common complications of cancer treatment and involves paresthesia, numbness and/or burning pain in distal limbs. This condition has a high health impact because it is associated with psychological distress, fall risk, and poor sleep quality. Furthermore, it impairs patients' daily activities and thereby decreases their quality of life. The overall incidence of CIPN is approximately 68% in the first month after chemotherapy. The available evidence for preventive and therapeutic options for CIPN is limited. Therefore, only symptom management based on pharmacological and/or physical therapy is applied with limited success. Photobiomodulation (PBM) has the potential to reduce the development of CIPN in breast cancer patients. PBM uses visible and/or (near)-infrared light at a low power produced by laser diodes or light-emitting diodes (LED) to stimulate tissue repair and reduce inflammation and (neuropathic) pain. Additionally, research demonstrated that the use of PBM for three weeks in a curative setting reduces the CIPN symptoms, which is associated with a better QoL. According to the updated WALT 2022 recommendations it is most optimal for neuropathy patients to receive twelve PBM sessions. The aim of this project is to evaluate the role of PBM administered to patients with " de novo " early signs of Peripheral neuropathy (PN) that are supposed to be related to ongoing anti-cancer therapy.

Chemotherapy-induced peripheral neuropathy (PN) is a common side-effect of many anti-neoplastic agents; its prevalence is estimated to 20-50% but varies considerably according to many factors and might actually be underreported. PN is increasingly reported as a complication of cancer immunotherapy and various targeted therapies currently used for the treatment of cancer. PN typically causes disabling, sensitive (paresthesia, dysesthesia, allodynia, loss of sensation), but can also cause motor dysfunction (muscle weakness, fatigue) and autonomic dysfunction (digestive disorders, orthostatic hypotension); once established, regression of symptoms is slow. The pathobiology of chemotherapy-induced PN is mainly unknown despite the documented involvement of neuroinflammatory, mitochondrial, and vascular mechanisms. PN often compromises quality of life and is a frequent reason for dose reduction, treatment delay, or premature discontinuation of anticancer therapy. So far, no standard therapy has been recommended, with the possible exception of duloxetine, which has been associated with a modest symptom improvement in cisplatin-treated patients. In this context, innovative, non-pharmacological, and well-tolerated strategies are needed. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), uses specific wavelengths (red or near-infrared) to modulate cellular activity, promote nerve regeneration, reduce inflammation, and regulate pain. Already included in international recommendations for the management of oral mucositis induced by chemotherapy or radiotherapy, PBM is emerging as a potentially effective alternative for other cancer-related toxicities. A beneficial effect of PBM on diabetic PN and oxaliplatin-induced PN has been reported. Argenta et al. published a small randomized sham-controlled trial of PBM on chemotherapy-induced PN that indicated a significant reduction in neuropathy symptoms. They found a significant benefit already after 4 weeks of therapy and patients who crossed over from sham laser experienced similar benefits. In a pilot trial, Lodewijckx et al. found a considerable decrease in symptoms of chemotherapy-induced PN with PBM. The same group reported " promising " results with PBM for the prevention of chemotherapy-induced PN in breast cancer patients. Therefore, the investigator plan to evaluate the role of PBM administered to patients with " de novo " early signs of PN that are supposed to be related to ongoing neurotoxic anti-cancer therapy (Bortezomib, Cisplatin, Docetaxel, Enfortumag, Halaven, Oxaliplatin, Paclitaxel, Vinblastine, Vincritsine, Vinorelbine). The project is therefore part of a proactive approach to supportive care aimed at reducing the early symptoms of PN, improving patients' quality of life, and avoiding the interruption or reduction of cancer therapy doses, using a simple, non-invasive device that has the potential for widespread application.