Effect of fractionated radiotherapy on the parotid gland: an experimental study in Brazilian minipigs

Summary

Introduction: Radiotherapy (RT) of head and neck neoplasms often damages the salivary glands.

Aim: To examine the pattern of morphologic changes resulting from RT of the head and neck region in minipig parotid glands in a clinical and experimental research setting.

Methods: Twelve 18-month-old male Brazilian minipigs weighing 30–40 kg were selected. Eight minipigs were assigned to the experimental group (group 1) and 4 to the control group (group 2). The RT was performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil, using an á/â ratio of 2.5. The minipigs from group 1 underwent 3 sessions of irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of 8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were sacrificed 12 weeks post-RT.

Results: The irradiated parotid glands displayed reductions in the size and number of acini as well as loss of secretory granules. The presence of fibrosis and loss of parenchyma relative to non-irradiated glands were observed, with an average reduction in volume of 54%.

Conclusions: Our results demonstrate that this model for parotid gland damage resulting from an RT regimen appears to be useful for preclinical large animal studies of RT-induced damage and testing novel potential treatment options. Although recent advances in radiation therapy, such as intensity-modulated radiation therapy, have reduced the dose and limited the field of radiation, considerable salivary gland injury still occurs and can greatly impact the patient's quality of life after cancer treatment.

Keywords

Head and Neck Neoplasms - Radiotherapy - Salivary Glands - Xerostomia - Swine - Miniature

• References

• 1 Ahlner BH, Hagelqvist E, Lind MG, Ruden BI. Irradiation of rabbit submandibular glands. Histology and morphometry after 15 Gy Acta Otolaryngol. 1993; Mar; 113 (2) 210-9
• 2 Bhide SA, Nutting CM. Advances in radiotherapy for head and neck cancer. Oral Oncol 2010; Jun; 46 (6) 439-41
• 3 Chambers MS, Garden AS, Kies MS, Martin JW. Radiationinduced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management. Head Neck 2004; Sep; 26 (9) 796-807
• 4 Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 2004; 73: 119-31
• 5 Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999; Oct 1; 45 (3) 577-87
• 6 English JA. Morphologic effects of irradiation on the salivary glands of rats. J Dent Res 1955; 34: 4-11
• 7 Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res 2009; Oct; 88 (10) 894-903
• 8 Li J, Shan Z, Ou G, Liu X, Zhang C, Baum BJ , et al. Structural and functional characteristics of irradiation damage to parotid glands in the miniature pig. Int J Radiat Oncol Biol Phys 2005; Aug 1; 62 (5) 1510-6
• 9 Lotz S, Caselitz J, Tschakert H, Rehpenning W, Seifert G. Radioprotection of minipig salivary glands by orciprenalinecarbachol. An ultrastructural and semiquantitative light microscopic study. Virchows Arch A Pathol Anat Histopathol 1990; 417 (2) 119-28
• 10 Marx R. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 1983; 41: 283-8
• 11 Nagler RM, Baum BJ, Miller G, Fox PC. Long-term salivary effects of single-dose head and neck irradiation in the rat. Arch Oral Biol 1998; Apr; 43 (4) 297-303
• 12 Nagler RM. Effects of head and neck radiotherapy on major salivary glands – animal studies and human implications. In Vivo 2003; 17: 369-75
• 13 Radfar L, Sirois DA. Structural and functional injury in minipig salivary glands following fractionated exposure to 70.  Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; Sep; 96 (3) 267-74
• 14 Sinn DP, Stoker NG, Epker BN. Effects of fractionated doses of cobalt 60 irradiation on rabbit submandibular glands: light microscopic studies. J Oral Surg. 1972; 30: 277-83
• 15 Stephens LC, King GK, Peters LJ, Ang KK, Schultheiss TE, Jardine JH. Unique radiosensitivity of serous cells in rhesus monkey submandibular glands. Am J Pathol 1986; Sep; 124 (3) 479-87
• 16 Veninga T, Visser AG, van den Berg AP, van Hooije CM, van Geel CA, Levendag PC. Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor model and remarkable effectiveness when preceded by external irradiation. Int J Radiat Oncol Biol Phys 2001; Apr 1; 49 (5) 1351-60
• 17 Verdonck HW, Meijer GJ, Nieman FH, Stoll C, Riediger D, de Baat C. Quantitative computed tomography bone mineral density measurements in irradiated and nonirradiated minipig alveolar bone: an experimental study. Clin Oral Implants Res 2008; May; 19 (5) 465-8
• 18 Vier-Pelisser FV, Amenábar JM, Cherubini K, Figueiredo MAZ, Yurgel LS. Microscopic analysis of the effect of fractionated radiation therapy on submandibular gland of rats. Radiol Bras 2005; 38 (6) 409-14
• 19 Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC , et al. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers. Int J Radiat Oncol Biol Phys 2010; Nov 15; 78 (4) 983-91
• 20 Wang SL, Li J, Zhu XZ, Sun K, Liu XY, Zhang YG. Sialographic characterization of the normal parotid gland of the miniature pig. Dentomaxillofac Radiol 1998; May; 27 (3) 178-81
• 21 Wang S, Liu Y, Fang D, Shi S. The miniature pig: a useful large animal model for dental and orofacial research. Oral Dis 2007; Nov; 13 (6) 530-7