Photodynamic therapy by curcumin vs. photo-bio-modulation therapy of oral mucositis in paedology patient undergoing anti-cancer non-invasive treatment

Background: The main objective of this study was to assess the impact of non-invasive photodynamic therapy by Curcumin and photo-bio-modulation low level (LL) laser treatment in managing oral mucositis induced by chemotherapy in pediatric patients. Methods: A cliinical trial was conducted involving 90 patients aged between 3 years and 15 years. The trial was open, controlled and blind. Patients were divided into two groups; Group A received photodynamic therapy, using Curcumin and a red laser at a wavelength of 450 nm, at 142 J/cm2, 100 mW. Group B received LL laser at a wavelength of 660 nm, delivering 1 joule of energy per point at 100 mW power output for 10 seconds. The results were assessed using both the World Health Organization (WHO) and Children’s International Mucositis Evaluation Scale (ChIMES). Statistical analysis included the Chi-square, Exact Fisher, Student’s t test and Mann-Whitney tests, as well as a mixed linear regression model for group comparisons, with a maximum allowable error of 5%. Results: There was no distinction observed between the groups in terms of the number of sessions required to achieve clinical resolution of oral lesions (p ≥ 0.05) or the reported reduction in patient pain (p ≥ 0.05). Nevertheless, within each group, a notable reduction in pain was evident (p ≥ 0.05). Conclusions: Photodynamic (PD)-and low level (LL) laser-therapy are viable options for managing oral mucositis (OM) in children and young patients. Both treatments were well-received and demonstrated positive outcomes in alleviating the pain associated with the condition. Clinical Trial Registration: A randomized clinical trial was register on ClinicalTrials.gov, ID NCT06044142. https://clinicaltrials.gov/study/NCT06044142.

Curcumin; Photodynamic therapy; Paedology; Photo-bio-modulation; Oral mucositis

[1] Zhang S, Li J, Zhang Y, Li X, Zhang Y, Li Y, et al. Efficacy of nonpharmacological interventions for severe radiation‐induced oral mucositis among head and neck cancer patients: a network meta-analysis of randomised controlled trials. Journal of Clinical Nursing. 2024; 33: 2030–2049.

[2] Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. International Journal of Surgery. 2012; 10: 28–55.

[3] Medeiros-Filho JB, Maia Filho EM, Ferreira MC. Laser and photochemotherapy for the treatment of oral mucositis in young patients: randomized clinical trial. Photodiagnosis and Photodynamic Therapy. 2017; 18: 39–45.

[4] Cheng KK, Chang AM, Yuen MP. Prevention of oral mucositis in paediatric patients treated with chemotherapy; a randomised crossover trial comparing two protocols of oral care. European Journal of Cancer. 2004; 40: 1208–1216.

[5] Pilas SA, Kurt S. Evaluation of oral mucositis level and affecting factors in cancer patients receiving chemotherapy. Supportive Care in Cancer. 2024; 32: 597.

[6] World Health Organization. World Health Organization handbook for reporting results of cancer treatment. World Health Organization: Geneva. 1979.

[7] Karlsson C, Bohm N, Andersson JS, Finizia C, Almståhl A. Prospective study on health-related quality of life, oral mucositis and oral health on during treatment of head and neck cancer. BMC Oral Health. 2024; 24: 697–706.

[8] Iovoli AJ, Turecki L, Qiu ML, Khan M, Smith K, Yu H, et al. Severe oral mucositis after intensity-modulated radiation therapy for head and neck cancer. JAMA Network Open. 2023; 6: e2337265.

[9] Nurhidayah I, Nurhaeni N, Allenidekania A, Gayatri D, Mediani HS. The effect of oral care intervention in mucositis management among pediatric cancer patients: an updated systematic review. Journal of Multidisciplinary Healthcare. 2024: 17: 3497–3515.

[10] Pinchaleaw D, Limlawan P. Oral chronic mucositis in a known lichen planus pigmentosus patient. Case Reports in Dentistry. 2024; 2024: 1975932.

[11] Ribeiro ILA, Caccia-Bava MDCGG, Sampaio MEA, Limeira RRT, de Carvalho LGA, dos Santos FG, et al. The implementation of an integrated oral care protocol for pediatric cancer patients: a qualitative study. Journal of Cancer Education. 2023; 38: 940–947.

[12] Franco R, Lupi E, Iacomino E, Galeotti A, Capogreco M, Santos JM, et al. Low-level laser therapy for the treatment of oral mucositis induced by hematopoietic stem cell transplantation: a systematic review with meta-analysis. Medicina. 2023; 59: 1413.

[13] Sung L, Robinson P, Treister N, Baggott T, Gibson P, Tissing W, et al. Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Support Palliat Care. 2017; 7: 7–16.

[14] Andriakopoulou CS, Yapijakis C, Koutelekos I, Perdikaris P. Prevention and treatment of oral mucositis in pediatric patients: systematic review and meta-analysis of randomized controlled trials. In Vivo. 2024; 38: 1016–1029.

[15] Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014; 120: 1453–1461.

[16] Kilic M, Gunen Yilmaz S, Kockopru ZM. Evaluation of oral health‐related quality of life in children with acute lymphocytic leukemia/acute myelocytic leukemia: a cross‐sectional study. Oral Diseases. 2024; 30: 2663–2669.

[17] Hosseini R, Brooks SP, Gadelha E, Schaap R, Cook J, Husan A. Effective treatment of methotrexate induced oral mucositis with a morphine mouthwash solution: a case report. Journal of Pharmacy Practice. 2024; 38: 212–216.

[18] Amadori F, Bardellini E, Conti G, Pedrini N, Schumacher RF, Majorana A. Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study. Lasers in Medical Science. 2016; 31: 1231–1236.

[19] Coppini M, Caponio VCA, Mauceri R, Bizzoca ME, Laino L, Lorenzo‐Pouso AI, et al. Efficacy of topical agents in oral mucositis prevention: systematic review and network meta‐analysis. Oral Diseases. 2024; 30: 4126–4144.

[20] Aygunes U, Karagun BS, Sasmaz I, Antmen B. The efficacy of three different oral hygiene regimens in preventing chemotherapy-induced oral mucositis in pediatric patients receiving hematopoietic stem cell transplantation. Klinische Pädiatrie. 2024; 236: 180–188.

[21] de Queiroz VG, da Silva ML, Xavier MG, de Moura MD, Ribeiro LN, da Silva Medeiros YH, et al. Effect of low-level laser therapy in the treatment of oral mucositis in patients with head and neck cancer: a scoping review. Arquivos em Odontologia. 2024; 60: 102–110.

[22] Shen B, Zhou Y, Wu D, Liu J. Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: a systematic review and meta‐analysis of randomized controlled trials. Head & Neck. 2024; 46: 936–950.

[23] de Górgolas Fernández-Chacón E, Fernández-Juárez A, Cobo-Vázquez CM, Sánchez-Labrador L, Pérez-González F, Meniz-García C. Treatment of oral mucositis in pediatric oncological patients using low power laser: a systematic review. Lasers in Dental Science. 2024; 8: 34.

[24] Ludovichetti FS, Costa G, Signoriello AG, Stellini E, Zerman N, Biffi A, et al. Evaluating high power laser therapy (HPLT) as treatment for chemotherapy‐induced oral mucositis in paediatric patients with oncohematological diseases. International Journal of Paediatric Dentistry. 2023; 33: 269–277.

[25] Cotomacio CC, Yshikawa BK, Calarga CC, Arana‐Chavez VE, Simões A. Red, infrared, and simultaneous laser‐wavelengths irradiation effects on 5‐fluorouracil‐induced oral mucositis in hamsters. Journal of Biophotonics. 2023; 16: e202300156.

[26] Gobbo M, Rico V, Marta GN, Caini S, Ryan Wolf J, van den Hurk C, et al. Photobiomodulation therapy for the prevention of acute radiation dermatitis: a systematic review and meta-analysis. Supportive Care Cancer. 2023; 31: 227.

[27] Aebisher D, Szpara J, Bartusik-Aebisher D. Advances in medicine: photodynamic therapy. International Journal of Molecular Sciences. 2024; 25: 8258.

[28] Qamar Z, Bamousa B, AlSheikh R, Ali S, Baeshen HA, Noushad M, et al. A bibliometric review of top 50 cited articles published in the photodiagnosis and photodynamic therapy from 2004 to 2019. Photodiagnosis and Photodynamic Therapy. 2020; 31: 101927.

[29] Longo M, Garcia VG, Ervolino E, Alves ML, Duque C, Wainwright M, et al. Multiple aPDT sessions on periodontitis in rats treated with chemotherapy: histomorphometrical, immunohistochemical, immunological and microbiological analyses. Photodiagnosis and Photodynamic Therapy. 2019; 25: 92–102.

[30] de Santana Cerqueira N, Vitória LA, da Silva VP, Rodriguez TT, Cangussu MCT, Ramalho LMP. Expression and degranulation of mast cells in laser photobiomodulated mucositis chemo-induced: pilot study in hamsters. Lasers in Medical Science. 2023; 38: 31.

[31] Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al.; Consolidated Standards of Reporting Trials Group. Erratum CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Journal of Clinical Epidemiology. 2010; 63: e1–e37.

[32] Jacobs S, Baggott C, Agarwal R, Hesser T, Schechter T, Judd P, et al. Validation of the children’s international mucositis evaluation scale (ChIMES) in paediatric cancer and SCT. British Journal of Cancer. 2013; 109: 2515–2522.

[33] Colella G, Boschetti CE, Vitagliano R, Colella C, Jiao L, King-Smith N, et al. Interventions for the prevention of oral mucositis in patients receiving cancer treatment: evidence from randomised controlled trials. Current Oncology. 2023; 30: 967–980.

[34] Soto M, Lalla RV, Gouveia RV, Zecchin VG, Seber A, Lopes NN. Pilot study on the efficacy of combined intraoral and extraoral low-level laser therapy for prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation. Photomedicine and Laser Surgery. 2015; 33: 540–546.

[35] Qamar Z, Abdul NS, Khan TA, Zeeshan T, Uddin AH, Albaqawi AH, et al. The effect of selected commercially available mouth-rinses vs. curcumin photosensitizers in an artificial mouth model mimicking their use before meals on early colonizers single species biofilm. European Review for Medical and Pharmacological Sciences. 2022; 26: 5466–5475.

[36] da Silva VC, da Motta Silveira FM, Monteiro MG, da Cruz MM, Júnior AD, Godoy GP. Photodynamic therapy for treatment of oral mucositis: pilot study with pediatric patients undergoing chemotherapy. Photodiagnosis and Photodynamic Therapy. 2018; 21: 115–120.

[37] Cruz LB, Ribeiro AS, Rech A, Rosa LG, Castro CG III, Brunetto AL. Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Pediatric Blood & Cancer. 2007; 48: 435–440.

[38] Moraes JJ, Queiroga AS, de Biase RC, Leite EP, Cabral Junior CR, Limeira Junior FA. The effect of low level laser therapy in different wavelengths in the treatment of oral mucositis—proposal for extra-oral implementation. Laser Physics. 2009; 19: 1912–1919.

[39] de Castro JF, Abreu EG, Correia AV, da Mota Vasconcelos Brasil C, da Cruz Perez DE, de Paula Ramos Pedrosa F. Low-level laser in prevention and treatment of oral mucositis in pediatric patients with acute lymphoblastic leukemia. Photomedicine and Laser Surgery. 2013; 31: 613–618.

[40] de Oliveira Mima EG, Pavarina AC, Dovigo LN, Vergani CE, de Souza Costa CA, Kurachi C, et al. Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2010; 109: 392–401.

[41] Javed F, Samaranayake LP, Romanos GE. Treatment of oral fungal infections using antimicrobial photodynamic therapy: a systematic review of currently available evidence. Photochemical & Photobiological Sciences. 2014; 13: 726–734.

[42] Aggarwal R, Bansal D, Naru J, Salaria M, Rana A, Minz RW, et al. HSV-1 as well as HSV-2 is frequent in oral mucosal lesions of children on chemotherapy. Supportive Care Cancer. 2014; 22: 1773–1779.

[43] Santos de Faria AB, Silva IH, de Godoy Almeida R, Silva SP, Carvalho AT, Leão JC. Seroprevalence of herpes virus associated with the presence and severity of oral mucositis in children diagnosed with acute lymphoid leukemia. Journal of Oral Pathology & Medicine. 2014; 43: 298–303.