Document Type : Original Article(s)
Authors
1 Department of Radiation Oncology, Kidwai Memorial Institute of Oncology, Hombegowda Nagar, Bengaluru, Karnataka, India
2 Department of Radiation Oncology, Karnataka Cancer Therapy and Research Institute, Hubli, Karnataka, India
3 Department of Medical Physics, Kidwai memorial Institute of Oncology, Hombegowda Nagar, Bengaluru, Karnataka, India
Abstract
Background: Lacrimal gland forms the integral part of tear film production. In view of close proximity to treatment portals, the present study aimed to investigate the relationship between lacrimal gland radiotherapy dose and its toxicity among patients treated with volumetric modulated arc therapy for carcinoma nasopharynx.
Method: A total number of 50 nasopharynx cancer patients treated with 70Gray included in this mono-centric, prospective, observational study. The lacrimal glands contoured as part of organs at risk. Impact of planned target volume, distance of gland to this volume, dose received by glands and V30 are assessed. Slit-lamp examination and Schirmer-I test were used pre-treatment and post-treatment up to a period of 2-years. Radiation Therapy Oncology Group toxicity criteria were used to provide information on conjunctivitis, corneal ulceration, and sicca-keratitis. ‘R’ software v4.4 was used for statistical analysis and independent T-test to correlate the significance with P-value <0.05.
Results: The minimum, maximum, and mean dose (Gray) received by the right lacrimal gland, comparable with the dose delivered to left lacrimal gland, was 2.58, 17.44 and 10.01, respectively. The minimum, maximum and mean planned target volumes (cubic centimetre) were 188.12, 1612.33 and 893.45, respectively. The mean distance between lacrimal gland and planned target volume is 0.51 centimetre and found to be statistically significant with P-value <0.001. Ten Grade-I and three Grade-II toxicity were reported in the study.
Conclusion: Based on the findings of the present study, contouring lacrimal gland as organ at risk in carcinoma nasopharynx is recommended and dose constraints to be advised, to minimize the toxicity and to prevent dry eye syndrome.
Keywords
- Nasopharyngeal neoplasms
- Conformal radiotherapy
- Volumetric modulated arc therapy
- Lacrimal gland
- Dry eye syndrome
Main Subjects
Please cite this article as: Poojar S, Tejaswi Siddappa P, Desai V, Thimmaiah N. Evaluation of Toxicity Profiles of Lacrimal Glands in Nasopharyngeal Carcinoma Patients Treated with Volumetric Modulated Arc Therapy. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.106311.2263.
- Conrady CD, Joos ZP, Patel BC. Review: The lacrimal gland and its role in dry eye. J Ophthalmol. 2016;2016:7542929. doi: 10.1155/2016/7542929. PMID: 27042343; PMCID: PMC4793137.
- Masoudi S. Biochemistry of human tear film: A review. Exp Eye Res. 2022;220:109101. doi: 10.1016/j.exer.2022.109101. PMID: 35508212.
- Tariq F, Hehar NK, Chigbu DI. The Ocular surface microbiome in homeostasis and dysbiosis. Microorganisms. 2025;13(9):1992. doi: 10.3390/microorganisms13091992. PMID: 41011324; PMCID: PMC12472094.
- Zhang X, M VJ, Qu Y, He X, Ou S, Bu J, et al. Dry eye management: Targeting the ocular surface microenvironment. Int J Mol Sci. 2017;18(7):1398. doi: 10.3390/ijms18071398. PMID: 28661456; PMCID: PMC5535891.
- Alam J, Yu Z, de Paiva CS, Pflugfelder SC. Retinoid regulation of ocular surface innate inflammation. Int J Mol Sci. 2021;22(3):1092. doi: 10.3390/ijms22031092. PMID: 33499199; PMCID: PMC7866051.
- Xiao Y, de Paiva CS, Yu Z, de Souza RG, Li DQ, Pflugfelder SC. Goblet cell-produced retinoic acid suppresses CD86 expression and IL-12 production in bone marrow-derived cells. Int Immunol. 2018;30(10):457-70. doi: 10.1093/intimm/dxy045. PMID: 30010888; PMCID: PMC6153729.
- Chen CT, Yang SF, Chao SC, Lee CY, Huang JY, Lin HY. Nasopharyngeal carcinoma and its effect on dry eye disease: A nationwide cohort study. Int J Environ Res Public Health. 2022;20(1):387. doi: 10.3390/ijerph20010387. PMID: 36612710; PMCID: PMC9819044.
- Bin Sumaida A, Shanbhag NM, Balaraj KS, Puratchipithan R, Hasnain SM, El-Koha O, et al. Understanding the radiation dose variability in nasopharyngeal cancer: An organs-at-risk approach. Cureus. 2023;15(12):e49882. doi: 10.7759/cureus.49882. PMID: 38053989; PMCID: PMC10694485.
- Yip PL, You R, Chen MY, Chua MLK. Embracing personalized strategies in radiotherapy for nasopharyngeal carcinoma: Beyond the conventional bounds of fields and borders. Cancers (Basel). 2024;16(2):383. doi: 10.3390/cancers16020383. PMID: 38254872; PMCID: PMC10814653.
- Milner MS, Beckman KA, Luchs JI, Allen QB, Awdeh RM, Berdahl J, et al. Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment. Curr Opin Ophthalmol. 2017;27 Suppl 1(Suppl 1):3-47. doi: 10.1097/01.icu.0000512373.81749.b7. PMID: 28099212; PMCID: PMC5345890.
- Huang R, Su C, Fang L, Lu J, Chen J, Ding Y. Dry eye syndrome: comprehensive etiologies and recent clinical trials. Int Ophthalmol. 2022;42(10):3253-72. doi: 10.1007/s10792-022-02320-7. PMID: 35678897; PMCID: PMC9178318.
- Nuzzi R, Trossarello M, Bartoncini S, Marolo P, Franco P, Mantovani C, et al. Ocular complications after radiation therapy: An observational study. Clin Ophthalmol. 2020;14:3153-66. doi: 10.2147/OPTH.S263291. PMID: 33116366; PMCID: PMC7555281.
- Lin KT, Lee SY, Liu SC, Tsao CC, Hsu SD, Chien WC, et al. Risk of ocular complications following radiation therapy in patients with nasopharyngeal carcinoma. Laryngoscope. 2020;130(5):1270-7. doi: 10.1002/lary.28254. PMID: 31441954.
- Tiwari S, Bhatt A, Nagamodi J, Ali MJ, Ali H, Naik MN, et al. Aqueous deficient dry eye syndrome post orbital radiotherapy: A 10-year retrospective study. Transl Vis Sci Technol. 2017;6(3):19. doi: 10.1167/tvst.6.3.19. PMID: 28660094; PMCID: PMC5477619.
- Ting DSJ, Rana-Rahman R, Ng JY, Wilkinson DJP, Ah-Kine D, Patel T. Clinical spectrum and outcomes of ocular and periocular complications following external-beam radiotherapy for inoperable malignant maxillary sinus tumors. Ocul Oncol Pathol. 2021;7(1):36-43. doi: 10.1159/000511011. PMID: 33796515; PMCID: PMC7989770.
- Wang K, Tobillo R, Mavroidis P, Pappafotis R, Pearlstein KA, Moon DH, et al. Prospective assessment of patient-reported dry eye syndrome after whole brain radiation. Int J Radiat Oncol Biol Phys. 2019;105(4):765-72. doi: 10.1016/j.ijrobp.2019.07.015. PMID: 31351194; PMCID: PMC7384248.
- Akagunduz OO, Yilmaz SG, Tavlayan E, Baris ME, Afrashi F, Esassolak M. Radiation-induced ocular surface disorders and retinopathy: Ocular structures and radiation dose-volume effect. Cancer Res Treat. 2022;54(2):417-23. doi: 10.4143/crt.2021.575. PMID: 34176248; PMCID: PMC9016314.
- Albrecht F, Wolters H, Ziert Y, Timmermann B, Kortmann RD, Matuschek C, et al. Evaluation of treatment-associated eye toxicity after irradiation in childhood and adolescence-results from the Registry of the evaluation of side effects after radiotherapy in childhood and adolescence (RiSK). Strahlenther Onkol. 2021;197(8):700-10. doi: 10.1007/s00066-021-01793-2. PMID: 34100093; PMCID: PMC8292243.
- Lee AW, Ng WT, Pan JJ, Poh SS, Ahn YC, AlHussain H, et al. International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma. Radiother Oncol. 2018;126(1):25-36. doi: 10.1016/j.radonc.2017.10.032. PMID: 29153464.
- Lambrecht M, Eekers DBP, Alapetite C, Burnet NG, Calugaru V, Coremans IEM, et al. Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus. Radiother Oncol. 2018;128(1):26-36. doi: 10.1016/j.radonc.2018.05.001. PMID: 29779919.
- Westgaard KL, Hynne H, Amdal CD, Young A, Singh PB, Chen X, et al. Oral and ocular late effects in head and neck cancer patients treated with radiotherapy. Sci Rep. 2021;11(1):4026. doi: 10.1038/s41598-021-83635-w. PMID: 33597629; PMCID: PMC7889862.
- Ahmad I, Chufal K, Bhatt CP. Not all tears imply sadness: a concise review on the impact of modern radiotherapy techniques in preventing radiation induced xerophthalmia. J Nucl Med Radiat Ther S. 2018;9:2. doi: 10.4172/2155-9619.S9-001.
- Soni M, Walia S, Jain P. Dry eye disease in head and neck cancer patients undergoing radiotherapy. Indian J Ophthalmol. 2023;71(4):1556-60. doi: 10.4103/IJO.IJO_2673_22. PMID: 37026301; PMCID: PMC10276695.
- 24. Ma J, Pazo EE, Zou Z, Jin F. Prevalence of symptomatic dry eye in breast cancer patients undergoing systemic adjuvant treatment: A cross-sectional study. Breast. 2020;53:164-71. doi: 10.1016/j.breast.2020.07.009. PMID: 32836200; PMCID: PMC7451424.
)