Oral mucositis (OM) is a common and severely debilitating side effect of non-surgical cancer treatments. Painful mouth sores, redness, and damage to the mucosal lining are the hallmarks of OM. OM is often underreported, particularly in patients undergoing chemotherapy [19]. Effective supportive care is crucial for managing oral mucositis, as it typically develops early after chemotherapy, often within one to two days. OM is associated with severe pain, taste alterations, dysphagia, nutritional deficiencies, secondary fungal infections, bacterial infections, and changes in speech. These side effects significantly impact patients’ quality of life and may necessitate dose adjustments or early discontinuation of anticancer treatment [20,21,22].

The most effective strategy for managing mucositis is prevention rather than mitigation or repair. Once lesions develop, management becomes increasingly complex due to the clinical complications they cause and the impaired healing process, which is often exacerbated by systemic debilitation from chemotherapy and the risk of secondary infections. Additionally, even after healing occurs, the affected tissues do not fully return to their pre-mucositis state. This is attributed to residual angiogenesis, which results in weakened tissue that is more susceptible to recurrence [23].

Since ancient times, preconditioning tissues and organs before medical intervention has been a well-established practice. This approach aims to enhance the stress tolerance of cells, including their ability to withstand oxidative stress and treatment-related damage. Research has demonstrated that prior exposure to light can increase cellular flexibility and resistance to chemical and radioactive damage [24,25,26].

The data supporting the potential therapeutic and preventive effects of photobiomodulation (PBM) on the side effects of cancer therapy was detailed by the World Association of Photobiomodulation Therapy (WALT) [27].

A literature review revealed several trials, the vast majority of which assessed the efficacy of PBM in patients with head and neck cancer receiving radiotherapy or in those undergoing hematopoietic stem cell transplantation (HSCT). This focus persists despite the fact that certain chemotherapy regimens—such as 5-fluorouracil, docetaxel in combination with capecitabine, pralatrexate, and cyclophosphamide with etoposide—can induce mucositis in a significant number of patients. Moreover, the incidence rates of mucositis in chemotherapy patients are comparable and very close to those observed in patients with head and neck cancer and HSCT recipients [28,29,30,31,32,33].

In the current study, we applied PBM before the start of the chemotherapy session, which aligns with WALT recommendations to administer PBM within 30–120 min prior to tumor treatment. We used a 635 nm wavelength for intraoral irradiation, consistent with WALT recommendations to use an LED/laser device with a visible wavelength (630–680 nm) for the prevention of mucositis [27]. The power settings were within the range suggested by Bensadoun et al. [34] The energy density employed was within the range recommended by Cronshaw et al. in their systematic review, which advocates using a lower energy density (2–5 J/cm²) for the prevention and healing of lesions, and a higher energy density (10–15 J/cm²) for OM-associated analgesia rather than biostimulation [26].

We used the Oral Mucositis Assessment Scale (OMAS) to evaluate the presence and severity of oral mucositis because it is an objective, quantitative measure suitable for research purposes. The OMAS primarily relies on measuring the dimensions of ulceration and erythema in nine different locations within the oral cavity [17].

According to our study, the incidence of mucositis was 100% in the first group, which appears to be higher than the rates reported in the literature [2]. This discrepancy may be attributed to the fact that 86.7% of our patients presented with mild erythema, a degree of oral mucositis that is typically not reported by patients but is detected during clinical examination by the clinician. It is important to consider that most incidence rates of oral mucositis are underestimated because patients tend to report it only when it reaches more severe degrees.

Through our review of the literature, we identified six studies evaluating the role of Photobiomodulation (PBM) in preventing oral mucositis. All these studies confirmed the positive impact of PBM, except for one study by Cruz et al., which found no benefit from laser application. Our study supports the significant role of photobiomodulation in preventing oral mucositis. We concur with most previous studies, including the research by Arbabi-Kalati et al. [14], who used a laser with the following parameters: 630 nm, 30 mW, and 5 J/cm², applied to ten sites within the oral cavity of patients with hematological and solid tumors. Likewise, Rozza-de-Menezes et al., who applied the intraoral laser to patients with solid tumors undergoing chemotherapy with fluorouracil and/or doxorubicin according to the following parameters: 660 nm, 4 J/cm2 and 50 mW, found that PBM has a noticeable role in preventing OM, with patients showing only 75% erythema [35]. There was also alignment with the results of de Castro et al., who compared the efficacy of a 660-nm red laser and an 830-nm infrared laser for the prevention and treatment of oral mucositis in children receiving high-dose methotrexate for acute lymphoblastic leukemia and found that prophylactic laser therapy resulted in better outcomes compared to patients who did not receive any preventive intervention [36]. Similarly, the Malta study observed a lower incidence of oral mucositis in the PBM group, which used 660-nm and 808-nm lasers, among stage II-IV breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide [37] The positive role of PBM in the prevention of oral mucositis, as observed in our study and most other studies, is due to its ability to favorably influence cellular metabolism. This occurs when light energy is transferred to the mitochondria, leading to an increased production of adenosine triphosphate (ATP) and nitric oxide, which subsequently triggers complex effects on gene expression. These effects result in many beneficial changes, such as enhanced production of collagen, growth factors, and an increased rate of cell division, all of which contribute to the healing process. Additionally, PBM plays a role in eliminating mediators of acute inflammation and modulates cytoplasmic reactive oxygen species, thus enhancing the immune response in targeted areas [38, 39].

Our only disagreement concerns the study by Cruz et al., which attributed the ineffectiveness of PBM to the increased susceptibility of children to mucositis. This contrasts with the numerous studies conducted in pediatric populations that have demonstrated positive outcomes of PBM in preventing mucositis [40,41,42]. A more plausible explanation for the findings of Cruz et al. is that some participants in their study had previously developed mucositis due to prior chemotherapy regimens, which may have rendered their mucosa more susceptible to further damage because of residual blood vessel formation. This highlights the importance of administering PBM to healthy tissue before the initiation of any anticancer therapy [43].

Several studies have demonstrated the superiority of red light in preventing mucositis, including the study by de Castro et al., which compared red light with infrared light in children with leukemia receiving high doses of methotrexate [36], as well as the study by Schubert et al. on hematopoietic stem cell transplantation patients [44]. However, this does not preclude the use of infrared light, which can be effectively combined with red light due to its deeper penetration. This allows infrared light to reach difficult-to-access areas, such as the oropharyngeal region, helping to prevent lesion development and thereby improving swallowing and quality of life [16]. For the above-mentioned reasons, we combined infrared with red light. In fact, the proportion of patients without OM in the infrared laser plus red laser group was higher compared to the intraoral red laser alone group, but the differences were not statistically significant. This may be attributed to the fact that extraoral infrared laser has a positive effect in preventing OM but the greater effect is due to intraoral red laser. We agree with the study of Malta et al., which shared red light with infrared light in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide and found that the incidence of OM was significantly reduced in these patients [37].

Chemotherapy also causes dysfunction of the salivary glands by inhibiting the lubricating, moisturizing, and antibacterial activities of saliva. Chemotherapy appears to have different effects on basal and stimulated saliva. While the basal pH of saliva remains unchanged, the pH of stimulated saliva becomes acidic. This acidity, combined with decreased saliva flow, leads to changes in beneficial flora. In addition, electrolyte modifications have been observed. During ion rearrangement, increases in Na + and K + disrupt salivary duct transport systems, causing damage [6, 7]. So far, there is no conclusive evidence on the effect of PBM on the salivary glands, but many studies and reviews have suggested the benefit of applying PBM to enhance the function of the salivary glands. For example, Golez et al. highlighted the role of the laser in alleviating dry mouth and hyposalivation [45]. Similarly, Sousa et al. observed an increase in the rate of saliva production in patients undergoing PBM [46]. In our study, we observed that PBM significantly reduced the incidence of xerostomia in patients undergoing chemotherapy, which is consistent with the findings of Arbabi Kalati et al. [14] The most likely explanation for this effect may be the role of PBM in stimulating the submandibular gland, which is responsible for producing the majority of saliva (about 70%) in the unstimulated state [47]. However, there was no significant difference between the two PBM protocols applied.

Several studies have evaluated the impact of PBM on patients’ quality of life. For instance, Gautam et al. studied patients with head and neck cancer undergoing combined chemotherapy and radiation, and found that PBM was effective in improving patients’ subjective experiences of OM and overall quality of life [48]. Likewise, Silva et al. found that PBM improved quality of life in patients with head and neck cancer treated with radiotherapy [49]. In our study, we observed that the Oral Health Impact Profile (OHIP-14) scores were better in the PBM group, whether intraoral alone or combined with extraoral application. This improvement is attributed to PBM’s role in reducing the incidence of OM and dry mouth, which subsequently alleviates symptoms such as pain, difficulty eating, dysphagia, taste changes, and other physical and psychological consequences that affect patients’ quality of life. These findings are consistent with the study by Malta et al., which demonstrated that PBM enhanced overall health status and quality of life in patients with breast cancer undergoing chemotherapy [37].