In a groundbreaking study poised to revolutionize supportive cancer care in pediatric hematology, researchers have unveiled compelling evidence supporting the use of photobiomodulation (PBM) and photodynamic therapy (PDT) to prevent and treat chemotherapy-induced oral mucositis (OM). This debilitating condition, a frequent complication of chemotherapy protocols such as methotrexate (MTX) administration, inflicts painful ulcerations in the oral mucosa, profoundly impairing quality of life, nutrition, and treatment adherence for young patients battling hematologic malignancies.
The study, conducted as a dual-arm randomized clinical trial, addressed a critical gap in pediatric oncology by exploring non-pharmacologic interventions capable of both halting the onset of OM and expediting its resolution when lesions emerge. PBM, a form of low-level laser therapy, employs precise wavelengths of light to modulate cellular metabolism, mitigate inflammatory processes, and promote tissue repair. Complementing this approach, PDT was investigated using indocyanine green (ICG) dye activated by low-level laser, harnessing photochemical reactions to target and ameliorate affected oral tissues.
In the prevention arm of the clinical trial, an innovative intra-patient design was utilized, whereby patients initially undergoing chemotherapy without laser intervention constituted control cycles and subsequently experienced PBM during ensuing cycles. This within-subject comparison under uniform chemotherapy regimens yielded striking findings: the incidence of oral mucositis plummeted dramatically from two-thirds of cycles (66.67%) without intervention to a mere 6.67% with PBM application.
The therapeutic arm focused on children who had already developed OM, randomizing participants to receive either sham laser treatment or PDT using ICG combined with low-level laser exposure. Evaluation metrics spanned recognized clinical scales—including the World Health Organization (WHO) mucositis scale, the National Cancer Institute (NCI) grading, and the WCCNR assessment—to quantify lesion severity and healing progression. Results demonstrated statistically significant improvements in the PDT group at both three and five days after treatment initiation, encompassing reductions across all scoring systems relative to controls.
Notably, the NCI score exhibited more pronounced declines between days three and five post-treatment in the PDT cohort, suggesting accelerated mucosal healing kinetics potentially attributable to the photodynamic mechanism. This rapid amelioration is particularly salient in the pediatric context, where minimizing mucositis duration can translate into reduced analgesic requirements, enhanced nutritional intake, diminished infection risk, and uninterrupted chemotherapy dosing schedules.
Underlying the observed clinical benefits, photobiomodulation’s mechanism involves low-power laser light stimulating mitochondrial cytochrome c oxidase, fostering ATP synthesis, and activating transcription factors that upregulate growth factors conducive to epithelial regeneration. Additionally, PBM modulates inflammatory cytokines, attenuates oxidative stress, and enhances microcirculatory dynamics within mucosal tissues, collectively laying a biological foundation for mucositis prophylaxis.
In parallel, PDT leverages the photosensitizing properties of ICG, which upon laser activation generates reactive oxygen species that selectively disrupt pathological cellular elements and modulate local immune responses. This photon-activated cytotoxicity may accelerate lesion clearance and confine inflammatory damage, marking a sophisticated adjunct or alternative to conventional mucositis management strategies.
From a clinical translational perspective, these findings resonate powerfully with the urgent need to integrate low-risk, non-invasive interventions into pediatric oncology supportive care. Oral mucositis not only prolongs hospitalization and inflates healthcare costs but also undermines psychological well-being in vulnerable children. The data suggesting that PBM and PDT markedly diminish OM incidence and severity could prompt rapid adoption in hematology-oncology units worldwide.
Importantly, safety profiles reported in the trial were favorable, with no significant adverse effects attributable to either PBM or PDT observed, underscoring their tolerability in a pediatric cohort often sensitive to treatment-related toxicities. The laser parameters and ICG dosing were meticulously standardized, ensuring reproducibility and paving the way for broader multicenter trials and eventual clinical guidelines formulation.
Looking forward, the implications of this research extend beyond methotrexate-induced OM, potentially informing management of mucositis arising from other cytotoxic agents or radiation therapy. Furthermore, the synergistic potential of combining PBM and PDT warrants exploration, as well as the optimization of dosing schedules and laser parameters tailored to patient-specific factors.
The trial’s robust design, featuring intra-patient controls and randomization, lends credence to the validity of the conclusions while addressing confounders such as inter-patient variability and chemotherapy regimen consistency. Registration with an official clinical trial registry enhances transparency and facilitates future systematic reviews and meta-analyses.
In conclusion, this innovative investigation offers a beacon of hope for alleviating one of pediatric oncology’s most arduous side effects. By harnessing the subtle power of light-based therapies, clinicians may soon possess effective tools to prevent and treat chemotherapy-induced oral mucositis, safeguarding the welfare and resilience of children courageously fighting hematologic cancers.
Subject of Research: Photobiomodulation and photodynamic therapy for prevention and treatment of chemotherapy-induced oral mucositis in pediatric hematologic cancer patients
Article Title: Efficacy of photobiomodulation for the prevention and treatment of chemotherapy-induced oral mucositis in pediatric patients with hematologic cancers: a randomized clinical trial
Article References: Lavaee, F., Rezazadeh, F., Amanati, A. et al. Efficacy of photobiomodulation for the prevention and treatment of chemotherapy-induced oral mucositis in pediatric patients with hematologic cancers: a randomized clinical trial. BMC Cancer 25, 825 (2025). https://doi.org/10.1186/s12885-025-14213-w
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14213-w
