Comparison of Topical Photodynamic Therapy With Topical Calcipotriol in Management of Oral Leukoplakia

(i)Rationale/ gaps in existing knowledge,: Oral cancer, one of the top three common cancers in India is usually preceded by Oral potentially malignant disorders in nearly two thirds of the cases like Oral leukoplakia. OL has a high prevalence and malignant transformation rates(0.13% - 40.8%). There are no universal protocols for management in OL ranging from preventive, conservative, medical and surgical interventions. They all have limitations and high recurrence rates requiring regular follow up. (ii)Novelty: Removal of pathological lesions are believed to reduce the risk of malignant transformation in OL. Surgical methods are associated with morbidity and high recurrence rates. Non -invasive methods (like Photodynamic therapy) that can remove the abnormal lesions would be preferred as they are cheaper, convenient, safe with less morbidity and better patient acceptability. They also have the advantage of repeatability with minimum morbidity and damage to adjacent normal tissues. Non -invasive medical management involves topical application of retinoids which are associated with systemic toxicity, recurrence and development of resistance. (iii)Objectives, Primary objective: To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy and topical calcipotriol (0.005%) on clinical response after completion of treatment at 4 weeks from baseline during management of Oral leukoplakia Secondary objectives: To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy with topical Calcipotriol (0.005%) on lesion size, lesion roughness/ whiteness, and oral health quality of life after completion of treatment at 4 weeks and 12 weeks from baseline during management of Oral leukoplakia To compare the effect of 2.5% Toluidine blue mediated topical photodynamic therapy with topical Calcipotriol (0.005%) on salivary molecular markers ( IL6, TNF-α, PCNA, Survivin and VEGF) after completion of treatment at 4 weeks from baseline To compare the adverse events, time to complete response and recurrence rates between the two groups (iv)Methods,: An open label randomized clinical trial where Group A (n=83) will receive 4 sessions of Toludine blue mediated photodynamic therapy (Fluence 15J/cm2); GroupB (n=83) will receive twice daily tropical application of Calcipotriol (0.005%) over a period of 4 weeks. The clinical response, lesion thickness/ whiteness, lesion size /area, OHIP-14 scores, adverse events and recurrence rates will be compared with baseline at 4 weeks and 12 weeks after completion of therapy. Sterile PVA ophthalmic sponges will be used to evaluate molecular markers ( IL6, TNF-α, PCNA, Survivin VEGF) from treatment site of lesion at baseline and 4 weeks after completion of treatment by ELISA. The data will be analyzed statistically using Intention to treat and as per protocol analysis at significance levels of p\<0.05. (v)Expected outcome.: The study will validate and verify the effectiveness of the TB mediated PDT protocol in the management of OL as compared to other non invasive method of topical Calcipotriol in terms of clinical response ( complete/ partial/ none), lesion thickness/ whiteness, lesion size and it's effect on oral health quality of life. Adverse events if any and recurrence rates or malignant transformation rates will also help in assessment of safety of the protocol. The molecular markers will help to monitor and determine prognosis of the lessons following treatment.

Sex

All

Minimum age

18 Years

Maximum age

99 Years

Inclusion Criteria:

* All diagnosed cases of Oral Leukoplakia with size ≥ 2 cm2 (Van der Waal classification ≥ L2) reporting to the department of OMR, CDER and willing to participate in the study will be included
* Subjects clinically and histologically diagnosed as Oral Leukoplakia.
* Subjects \> 18 years of age.
* Subjects willing to participate in the study and to complete the treatment sessions.

Exclusion Criteria:

* History of any topical and/or systemic therapy for Oral Leukoplakia other than general management in last 2 months.
* Subjects with current or past history of malignancy.
* Subjects with any lesion suspicious of malignancy requiring biopsy.
* Subjects with severe dysplasia and carcinoma in situ on biopsy of oral lesion
* Subjects with history of hyperphotosensitivity (genetic disorders, dermatological conditions, drug induced, systemic conditions)
* Subjects with calcium, Vit D metabolic and parathyroid disorders
* Pregnant and lactating females.

• BACKGROUNDPietruska M, Sobaniec S, Bernaczyk P, Cholewa M, Pietruski JK, Dolińska E, et al. Clinical evaluation of photodynamic therapy efficacy in the treatment of oral leukoplakia. PhotodiagnosisPhotodyn Ther. 2014 Mar;11(1):34-40. Bhandari A, Budakoti A, Chaudhary M. Methylene Blue-mediated Photodynamic Therapy for the Treatment of Oral Leukoplakia. Journal of the Scientific Society. 2023 Dec;50(3):394. Silva BS de F, Rocha RM, Prudente TP, Lenza MM de O, Ferraz DLF, Mezaiko E, et al. Efficacy of 5% methylene blue photodynamic therapy in the treatment of potentially malignant oral disorders: a randomized, double-blind, controlled trial. International Journal of Clinical Trials. 2024 Jul 25;11(3):207-14. Selvam NP, Sadaksharam J, Singaravelu G, Ramu R. Treatment of oral leukoplakia with photodynamic therapy: A pilot study. J Cancer Res Ther. 2015;11(2):464-7. Ghalwash D, Mahmoud E, Shaker O. Evaluation of the therapeutic effect of topical calcipotriol versus topical tretinoin in treatment of oral Leukoplakia and their effect on clinical improvement and salivary level of MMP-9, IL-6 and TGF-β: A Randomized Clinical Trial. Egyptian Dental Journal. 2017 Jul 1;63(3):2441-57. Femiano F, Gombos F, Scully C, Battista C, Belnome G, Esposito V. Oral leukoplakia: open trial of topical therapy with calcipotriol compared with tretinoin. Int J Oral Maxillofac Surg. 2001 Oct;30(5):402-6.