Document Type : Original Article

Authors

1 Department of Biochemistry, Father Muller Medical College, Mangalore, Karnataka, India

2 Father Muller Research Centre, Mangalore, Karnataka, India

3 Department of Radiation Oncology, Father Muller Medical College, Mangalore, Karnataka, India

4 Department of Community Medicine, Father Muller Medical College, Mangalore, Karnataka, India

Abstract

Background: Reports correlating changes in salivary flow rate and amylase with radiation dose to parotid glands and development of salivary dysfunction for Head and Neck cancers (HNC) are lacking. In the current study, an attempt was made at understanding this.
Method: This was a prospective study carried out on people newly diagnosed with HNC requiring curative radiotherapy of more than 60 Gy. The salivary flow rate and levels of salivary α-amylase were evaluated before the start of radiation [day 1, before exposure to the first fraction of 2 Gy radiation], after 2 Gy [24 hours after the 1st fraction of 2 Gy, before exposure to 2nd fraction of 2 Gy on day 2 of the treatment], and on the completion of 30 Gy [(15 fraction of 2 Gy), before start of the 16th fraction, at the start of the fourth week on day 22] of radiation and development of salivary dysfunction was evaluated on a weekly basis. The demographic data were subjected to frequency and percentage, while biochemical data were stratified depending on dose to parotids and subjected to unpaired “t-test”. We also employed chi square/Fishers exact test to ascertain changes in the number of patients developing various degrees of salivary dysfunction on a weekly basis. A P value of <0.05 was considered significant.
Results: Radiation decreased salivary flow rate from 0.29 ± 0.02 to 0.20 ± 0.04 (P = 0.0001) and amylase from 147.69 ± 11.15 to 109.07 ± 23.21 U/L (P = 0.0005). Both salivary flow rate and amylase was less in patients with severe salivary gland dysfunction (P = 0.014) and cumulative dose of radiation to the parotid glands (P = 0.014). The number of patients with a severe degree of salivary dysfunction was seen in people exposed to more than 25 Gy to the parotids (P = 0.04).
Conclusion: The results suggested that the evaluation of salivary amylase on day 22 could be a useful predictive marker to understand the development of radiation-induced dysfunction in patients with curative radiotherapy for their head and neck cancer.

Keywords

How to cite this article:

Shivashankara AR, Simon P, Pais S, Tonse R, Suresh S, et al. Salivary amylase as a predictive marker for radiationinduced salivary dysfunction in head and neck cancer: a pilot study. Middle East J Cancer. 2023;14(1):61-71. doi: 10. 30476/mejc.2022.90651.1585.

  1. Jaguar GC, Prado JD, Campanhã D, Alves FA. Clinical features and preventive therapies of radiation-induced xerostomia in head and neck cancer patient: a literature review. Appl Cancer Res. 2017;37:31. doi: 10.1186 /s41241-017-0037-5.
  2. Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr. 2019;2019(53):lgz016. doi: 10.1093/jncimonographs/ lgz016.
  3. Pinna R, Campus G, Cumbo E, Mura I, Milia E. Xerostomia induced by radiotherapy: an overview of the physiopathology, clinical evidence, and management of the oral damage. Ther Clin Risk Manag. 2015;11:171-88. doi: 10.2147/TCRM.S70652.
  4. Acauan MD, Figueiredo MA, Cherubini K, Gomes AP, Salum FG. Radiotherapy-induced salivary dysfunction: Structural changes, pathogenetic mechanisms and therapies. Arch Oral Biol. 2015;60(12):1802-10. doi: 10.1016/j.archoralbio. 2015.09.014.
  5. Dose AM. The symptom experience of mucositis, stomatitis, and xerostomia. Semin Oncol Nurs. 1995;11(4):248-55. doi: 10.1016/s0749-2081(05) 80005-1.
  6. Chitra S, Shyamala Devi CS. Effects of radiation and alpha-tocopherol on saliva flow rate, amylase activity, total protein and electrolyte levels in oral cavity cancer. Indian J Dent Res. 2008;19(3):213-8. doi: 10.4103/ 0970-9290.42953.
  7. Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res. 2009;88(10):894-903. doi: 10.1177/0022034509343143.
  8. Cheng SC, Wu VW, Kwong DL, Ying MT. Assessment of post-radiotherapy salivary glands. Br J Radiol. 2011;84(1001):393-402. doi:10.1259/bjr/66754762.
  9. Principe S, Dikova V, Bagan J. Salivary cytokines in patients with head and neck cancer (HNC) treated with radiotherapy. Clin Exp Dent. 2019;11:e1072– e1077. doi: 10.4317/jced.56318.
  10. Arrifin A, Heidari E, Burke M, Fenlon MR, Banerjee A. The effect of radiotherapy for treatment of head and neck cancer on oral flora and saliva. Oral Health Prev Dent. 2018;16(5):425-9. doi: 10.3290/j.ohpd. a41364.
  11. Leslie MD, Dische S. Changes in serum and salivary amylase during radiotherapy for head and neck cancer: a comparison of conventionally fractionated radiotherapy with CHART. Radiother Oncol. 1992; 24(1):27-31. doi: 10.1016/0167-8140(92) 90350-4.
  12. Lin CY, Ju SS, Chia JS, Chang CH, Chang CW, Chen MH. Effects of radiotherapy on salivary gland function in patients with head and neck cancers. J Dent Sci. 2015;10(3): 253-62. doi 10.1016/j.jds.2015.01.004.
  13. Javaid MA, Ahmed AS, Durand R, Tran SD. Saliva as a diagnostic tool for oral and systemic diseases. J Oral Biol Craniofac Res. 2016;6(1):66-75. doi: 10.1016/j.jobcr.2015.08.006.
  14. Awasthi N. Role of salivary biomarkers in early detection of oral squamous cell carcinoma. Indian J Pathol Microbiol. 2017;60(4):464-8. doi: 10.4103/ IJPM.IJPM_140_16.
  15. De Felice F, Tombolini M, Musella A, Marampon F, Tombolini V, Musio D. Radiation therapy and serum salivary amylase in head and neck cancer. Oncotarget. 2017;8(52):90496-500. doi: 10.18632/oncotarget. 18763.
  16. Vedam VKV, Boaz K, Natarajan S, Ganapathy S. Salivary amylase as a marker of salivary gland function in patients undergoing radiotherapy for oral cancer. J Clin Lab Anal. 2017;31(3):e22048. doi: 10.1002/ jcla.22048.
  17. Jayachander D, Shivashankara AR, Vidyasagar MS, Tonse R, Pais S, Lobo ADL, et al. Salivary parameters as predictive markers for radiation-induced treatment response in head and neck cancers: An investigational study. Middle East J Cancer. 2018;9(2):133-42. doi: 10.30476/mejc.2018.42115
  18. Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. Sobin LH, Gospodarowicz MK, Wittekind C, editors. 7th ed. WileyBlackwell, Chichester: UK; 2009.
  19. Hunt MA, Kutcher GJ, Burman C, Fass D, Harrison L, Leibel S, et al. The effect of setup uncertainties on the treatment of nasopharynx cancer. Int J Radiat Oncol Biol Phys. 1993;27(2):437-47. doi: 10.1016/ 0360-3016(93)90257-v.
  20. Hunt MA, Zelefsky MJ, Wolden S, Chui CS, LoSasso T, Rosenzweig K, et al. Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer. Int J Radiat Oncol Biol Phys. 2001;49(3):623-32. doi: 10.1016/s0360- 3016(00)01389-4.
  21. Eisbruch A, Marsh LH, Martel MK, Ship JA, Ten Haken R, Pu AT, et al. Comprehensive irradiation of head and neck cancer using conformal multisegmental fields: assessment of target coverage and noninvolved tissue sparing. Int J Radiat Oncol Biol Phys. 1998;41(3):559-68. doi: 10.1016/s0360-3016(98) 00082-0.
  22. Wu Q, Manning M, Schmidt-Ullrich R, Mohan R. The potential for sparing of parotids and escalation of biologically effective dose with intensity-modulated radiation treatments of head and neck cancers: a treatment design study. Int J Radiat Oncol Biol Phys. 2000;46(1):195-205. doi: 10.1016/s0360-3016(99) 00304-1.
  23. International Commission on Radiation Units & Measurements. International Commission on Radiation Units and Measurements Report 50: Prescribing, recording and reporting photon beam therapy. Washington DC: ICRU 1993 Available at: https://www.icru.org/report/prescribing-recording-andreporting- photon-beam-therapy-report-50/
  24. Lavertu P, Adelstein DJ, Saxton JP, Secic M, Eliachar I, Strome M, et al. Aggressive concurrent chemoradiotherapy for squamous cell head and neck cancer: an 8-year single-institution experience. Arch Otolaryngol Head Neck Surg. 1999;125(2):142-8. doi: 10.1001/archotol.125.2.142.
  25. Marcu LG. Improving therapeutic ratio in head and neck cancer with adjuvant and cisplatin-based treatments. Biomed Res Int. 2013;2013:817279. doi: 10.1155/2013/817279.
  26. Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993;694:72-7. doi: 10.1111/j.1749- 6632.1993.tb18343.x.
  27. Balkcom RM, O'Donnell CM, Amano E. Evaluation of the DuPont aca amylase method. Clin Chem. 1979;25(10):1831-5.
  28. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS; (http://ctep.cancer.gov), Published at: August 9, 2006. Available at: https://ctep.cancer.gov/protocolDevelopment/ electronic_applications/docs/ctcaev3.pdf
  29. Madan PD, Sequeira PS, Shenoy K, Shetty J. The effect of three mouthwashes on radiation-induced oral mucositis in patients with head and neck malignancies: a randomized control trial. J Cancer Res Ther. 2008;4(1):3-8. doi: 10.4103/0973-1482.39597.
  30. de Barros Pontes C, Polizello AC, Spadaro AC. Clinical and biochemical evaluation of the saliva of patients with xerostomia induced by radiotherapy. Braz Oral Res. 2004;18(1):69-74. doi: 10.1590/s1806- 83242004000100013.
  31. Leslie MD, Dische S. Changes in serum and salivary amylase during radiotherapy for head and neck cancer: a comparison of conventionally fractionated radiotherapy with CHART. Radiother Oncol. 1992;24(1):27-31. doi: 10.1016/0167-8140(92)90350- 4.
  32. Kashima HK, Kirkham WR, Andrews JR. Postirradiation sialadenitis: a study of the clinical features, histopathologic changes and serum enzyme variations following irradiation of human salivary glands. Am J Roentgenol. 1965;94:271-91.
  33. Borok TL, Cooper JS. Time course and significance of acute hyperamylasemia in patients receiving fractionated therapeutic radiation to the parotid gland region. Int J Radiat Oncol Biol Phys. 1982;8(8):1449- 51. doi: 10.1016/0360-3016(82)90599-5.
  34. Vineetha R, Pai KM, Vengal M, Gopalakrishna K, Narayanakurup D. Usefulness of salivary alpha amylase as a biomarker of chronic stress and stress related oral mucosal changes - a pilot study. J Clin Exp Dent. 2014;6(2):e132-7. doi: 10.4317/jced.51355.
  35. Arhakis A, Karagiannis V, Kalfas S. Salivary alphaamylase activity and salivary flow rate in young adults. Open Dent J. 2013;7:7-15. doi: 10.2174/18742106 01307010007.