Oral pathology following treatment of brain tumors in childhood

Relevance. The limited selectivity of antitumor therapy for central nervous system neoplasms entails the risk of dental morbidity in patients.

The aim of the study is to assess the severity of damage to the dental hard tissues in patients with tumors of the posterior cranial fossa (medulloblastoma, astrocytoma) and other tumors of the central nervous system.

Materials and methods. Three comparison groups were established based on the toxicity profiles of antitumor therapy among 251 patients at the "Russian Field" treatment and rehabilitation scientific center, to assess the characteristics of oral health status. The assessment of oral health status included diagnosing the carious process and calculating the DMFT index. The degree of damage to the dental hard tissues was evaluated on a four-point scale. The clinical manifestations of oral cavity pathology were compared using the Z-criterion for multiple pairwise comparisons of data, with adjustments for multiple testing (Multiple pairwise comparison Z-test for proportions with multiple testing correction) using the free R software version 3.5.2. The null hypothesis of equal indicators in the compared groups was rejected with a 95% confidence probability when comparing groups of patients.

Results. Dental hard tissue pathology was significantly more prevalent in patients with medulloblastoma compared to those diagnosed with astrocytomas and other central nervous system tumors. Additionally, the prevalence of dental hard tissue pathology progressively decreased as the observation period following the completion of antitumor remission was extended.

Conclusion. The most severe damage to dental hard tissues is observed in patients with medulloblastoma, who undergo more intensive antitumor therapy compared to those with CNS tumors of other histological types.

1. Parra JJ, Alvarado MC, Monsalve P, Costa ALF, Montesinos GA, Parra PA. Oral health in children with acute lymphoblastic leukaemia: before and after chemotherapy treatment. Eur Arch Paediatr Dent. 2020;21(1):129-136. doi: 10.1007/s40368-019-00454-4

2. National Cancer Institute. Cancer Therapy Evaluation Program. Common Toxicity Criteria. v2.0. [Internet]. Department of Health and Human Services: National Cancer Institute;1999. Available from: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcmanual_v4_10-4-99.pdf

3. Cammarata-Scalisi F, Girardi K, Strocchio L, Merli P, Garret-Bernardin A, Galeotti A, et al. Oral Manifestations and Complications in Childhood Acute Myeloid Leukemia. Cancers (Basel). 2020;12(6):1634. doi: 10.3390/cancers12061634

4. Najafi Sh, Tohidastakrad Z, Momenbeitollahi J. The long-term effects of chemo radiotherapy on oral health and dental development in childhood cancer. J Dent (Tehran). 2011;8(1):39-43. Available from: https://pubmed.ncbi.nlm.nih.gov/21998806/

5. Onile EA, Nechesnyuk AV, Obuchov YuА. Dental complications of radiotherapy in children with neoplasms of the head and neck. Pediatric bulletin of the South Ural. 2022;(1):39–45 (In Russ.). doi: 10.34710/Chel.2022.56.73.007

6. Tanem KE, Stensvold E, Wilberg P, Skaare AB, Brandal P, Herlofson BB. Oral and Dental late effects in longterm survivors of childhood embryonal brain tumors. Support Care Cancer. 2022;30(12):10233-10241. doi: 10.1007/s00520-022-07405-8

7. Proc P, Szczepańska J, Herud A, Zubowska M, Fendler W, Młynarski W. Dental caries among childhood cancer survivors. Medicine (Baltimore). 2019;98(6):e14279. doi: 10.1097/MD.0000000000014279

8. Obukhov AYu, Zhukovskaya EV, Spichak II, Kireeva GN. The oral cavity in children is normal and in the treatment of malignant neoplasms and blood diseases. 2021 (In Russ.). doi: 10.34710/e4565-3495-9660-v

9. Oskarsson T, Duun-Henriksen AK, Bautz A, Montgomery S, Harila-Saari A, Petersen C, et al. Skeletal adverse events in childhood cancer survivors: An Adult Life after Childhood Cancer in Scandinavia cohort study. Int J Cancer. 2021;149(11):1863-1876. doi: 10.1002/ijc.33741

10. Zhang W, Yelick PC. Tooth Repair and Regeneration: Potential of Dental Stem Cells. Trends Mol Med. 2021;27(5):501-511. doi: 10.1016/j.molmed.2021.02.005 11. Paulino AC Role of radiation therapy in parameningeal rhabdomyosarcoma. Cancer Invest. 1999;17(3):223-30. doi: 10.3109/07357909909021426

11. Othman N, Taib H, Mokhtar N. Root-crown ratios of permanent teeth in Malay patients attending HUSM Dental Clinic. Archives of Orofacial Sciences. 2011;6(1):21-26. Available from: https://www.researchgate.net/publication/228836061_Root-crown_ratios_of_permanent_teeth_in_Malay_patients_attending_HUSM_Dental_Clinic

12. Han X, Lin CC, Li C, de Moor JS, Rodriguez JL, Kent EE, et al. Association between serious psychological distress and health care use and expenditures by cancer history. Cancer. 2015;121(4):614-22. doi: 10.1002/cncr.29102.

13. Thesleff I. Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci. 2003;116 (Pt 9):1647-1648. doi: 10.1242/jcs.00410

14. Landier W, Skinner R, Wallace WH, Hjorth L, Mulder RL, Wong FL, et al. Surveillance for Late Effects in Childhood Cancer Survivors. J Clin Oncol. 2018;36(21):2216-2222. doi: 10.1200/JCO.2017.77.0180

15. Gawade PL, Hudson MM, Kaste SC, Neglia JP, Constine LS, Robison LL, Ness KK. A Systematic review of dental late effects in survivors of childhood cancеr. Pediatr Blood Cancer. 2014;61(3):407-16. doi: 10.1002/pbc.24842

16. Hong CH, Napeñas JJ, Hodgson BD, Stokman MA, Mathers-Stauffer V, Elting LS, et al. A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer. 2010;18(8):1007-21. doi: 10.1007/s00520-019-04848-4

17. Hudson MM, Ehrhardt MJ, Bhakta N, Baassiri M, Eissa H, Chemaitilly W, et al. Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort. Cancer Epidemiol Biomarkers Prev. 2017;26(5):666-674. doi: 10.1158/1055-9965

18. Kalinin AL, Strebkova NA, Zheludkova OG, Kareva MA, Mazerkina NA, Bezlepkina OB. Indicators of carbohydrate metabolism in children after complex treatment of medulloblastoma. Diabetes mellitus. 2021;24(6):529-535 (In Russ.). doi: https://doi.org/10.14341/DM12805

19. Salloum R, Chen Y, Yasui Y, Packer R, Leisenring W, Wells E, et al. Late morbidity and mortality among medulloblastoma survivors diagnosed across three decades: a report from the childhood cancer survivor study. J Clin Oncol. 2019;37(9):731–740. doi: 10.1200/JCO.18.00969

20. Nekhlyudov L, O'malley DM, Hudson SV. Integrating primary care providers in the care of cancer survivors: gaps in evidence and future opportunities. Lancet Oncol. 2017;18(1):e30-e38. doi: 10.1016/S1470-2045(16)30570-8