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Future Prevention and Treatment of Radiation-Induced Hyposalivation

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Dry Mouth

Abstract

Radiation-induced hyposalivation and consequential xerostomia have devastating effects on the quality of life of patients treated for head and neck cancer. Regretfully, currently there are no adequate or safe treatments. This chapter describes the mechanism of radiation-induced salivary gland damage and current and potential treatments. The reduced function of the salivary gland after irradiation is mainly due to loss of acinar cell function and number. Therefore, future strategies are aimed to restore saliva flow through manipulation of the remaining cells through gene therapy or by stimulation of the generative potential of the glands. The latter can be induced by stimulation of proliferation of remaining cells through the administration of cytokines or transplanted mesenchymal cells. Stem cell therapy seems to have the highest potential as in preclinical studies it has been shown to restore glandular homoeostasis and long-term regenerative capacity. However, less radiation dose as possible with proton therapy may be the best way to prevent hyposalivation.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Hunter KD, Parkinson EK, Harrison PR. Profiling early head and neck cancer. Nat Rev Cancer. 2005;5(2):127–35.

    Article  PubMed  Google Scholar 

  3. Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med. 2003;14(3):199–212.

    Article  PubMed  Google Scholar 

  4. Sciubba JJ, Goldenberg D. Oral complications of radiotherapy. Lancet Oncol. 2006;7(2):175–83.

    Article  PubMed  Google Scholar 

  5. Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA. Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;69(3):751–60.

    Article  PubMed  Google Scholar 

  6. Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol. 2008;26(22):3770–6.

    Article  PubMed  Google Scholar 

  7. Burlage FR, Roesink JM, Kampinga HH, Coppes RP, Terhaard C, Langendijk JA, et al. Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized, placebo-controlled study. Int J Radiat Oncol Biol Phys. 2008;70(1):14–22.

    Article  PubMed  Google Scholar 

  8. Eisbruch A. Intensity-modulated radiation therapy in the treatment of head and neck cancer. Nat Clin Pract Oncol. 2005;2(1):34–9.

    Article  PubMed  Google Scholar 

  9. Vergeer MR, Doornaert PA, Rietveld DH, Leemans CR, Slotman BJ, Langendijk JA. Intensity-modulated radiotherapy reduces radiation-induced morbidity and improves health-related quality of life: results of a nonrandomized prospective study using a standardized follow-up program. Int J Radiat Oncol Biol Phys. 2009;74(1):1–8.

    Article  PubMed  Google Scholar 

  10. Vissink A, Burlage FR, Spijkervet FK, Jansma J, Coppes RP. Prevention and treatment of the consequences of head and neck radiotherapy. Crit Rev Oral Biol Med. 2003;14(3):213–25.

    Article  PubMed  Google Scholar 

  11. Zajicek G, Yagil C, Michaeli Y. The streaming submandibular gland. Anat Rec. 1985;213(2):150–8.

    Article  PubMed  Google Scholar 

  12. Nagler RM, Baum BJ, Fox PC. Acute effects of X irradiation on the function of rat salivary glands. Radiat Res. 1993;136(1):42–7.

    Article  PubMed  Google Scholar 

  13. Burlage FR, Coppes RP, Meertens H, Stokman MA, Vissink A. Parotid and submandibular/sublingual salivary flow during high dose radiotherapy. Radiother Oncol. 2001;61(3):271–4.

    Article  PubMed  Google Scholar 

  14. Coppes RP, Zeilstra LJ, Kampinga HH, Konings AW. Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists. Br J Cancer. 2001;85(7):1055–63.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Konings AW, Coppes RP, Vissink A. On the mechanism of salivary gland radiosensitivity. Int J Radiat Oncol Biol Phys. 2005;62(4):1187–94.

    Article  PubMed  Google Scholar 

  16. Abok K, Brunk U, Jung B, Ericsson J. Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(4):443–60.

    Article  PubMed  Google Scholar 

  17. Nagler R, Marmary Y, Fox PC, Baum BJ, Har-El R, Chevion M. Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper. Radiat Res. 1997;147(4):468–76.

    Article  PubMed  Google Scholar 

  18. Zeilstra LJ, Vissink A, Konings AW, Coppes RP. Radiation induced cell loss in rat submandibular gland and its relation to gland function. Int J Radiat Biol. 2000;76(3):419–29.

    Article  PubMed  Google Scholar 

  19. Stephens LC, Schultheiss TE, Price RE, Ang KK, Peters LJ. Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer. 1991;67(6):1539–43.

    Article  PubMed  Google Scholar 

  20. Stephens LC, Schultheiss TE, Small SM, Ang KK, Peters LJ. Response of parotid gland organ culture to radiation. Radiat Res. 1989;120(1):140–53.

    Article  PubMed  Google Scholar 

  21. Takahashi S, Nakamura S, Shinzato K, Domon T, Yamamoto T, Wakita M. Apoptosis and proliferation of myoepithelial cells in atrophic rat submandibular glands. J Histochem Cytochem. 2001;49(12):1557–64.

    Article  PubMed  Google Scholar 

  22. Denny PC, Chai Y, Klauser DK, Denny PA. Parenchymal cell proliferation and mechanisms for maintenance of granular duct and acinar cell populations in adult male mouse submandibular gland. Anat Rec. 1993;235(3):475–85.

    Article  PubMed  Google Scholar 

  23. Denny PC, Ball WD, Redman RS. Salivary glands: a paradigm for diversity of gland development. Crit Rev Oral Biol Med. 1997;8(1):51–75.

    Article  PubMed  Google Scholar 

  24. Man YG, Ball WD, Marchetti L, Hand AR. Contributions of intercalated duct cells to the normal parenchyma of submandibular glands of adult rats. Anat Rec. 2001;263(2):202–14.

    Article  PubMed  Google Scholar 

  25. Konings AW, Faber H, Cotteleer F, Vissink A, Coppes RP. Secondary radiation damage as the main cause for unexpected volume effects: a histopathologic study of the parotid gland. Int J Radiat Oncol Biol Phys. 2006;64(1):98–105.

    Article  PubMed  Google Scholar 

  26. Ihrler S, Zietz C, Sendelhofert A, Lang S, Blasenbreu-Vogt S, Lohrs U. A morphogenetic concept of salivary duct regeneration and metaplasia. Virchows Arch. 2002;440(5):519–26.

    Article  PubMed  Google Scholar 

  27. Roesink JM, Konings AW, Terhaard CH, Battermann JJ, Kampinga HH, Coppes RP. Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: radiation dose dependency and compensatory mechanisms. Int J Radiat Oncol Biol Phys. 1999;45(2):483–9.

    Article  PubMed  Google Scholar 

  28. Liu RP, Fleming TJ, Toth BB, Keene HJ. Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. Oral Surg Oral Med Oral Pathol. 1990;70(6):724–9.

    Article  PubMed  Google Scholar 

  29. Lombaert IM. Regeneration of irradiated salivary glands by stem cell therapy. PhD thesis ed. Groningen: University of Groningen; 2008.

    Google Scholar 

  30. Baum BJ. Gene therapy. Oral Dis. 2014;20(2):115–8.

    Article  PubMed  Google Scholar 

  31. Delporte C, O’Connell BC, He X, Lancaster HE, O’Connell AC, Agre P, et al. Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc Natl Acad Sci U S A. 1997;94(7):3268–73.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Shan Z, Li J, Zheng C, Liu X, Fan Z, Zhang C, et al. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol Ther. 2005;11(3):444–51.

    Article  PubMed  Google Scholar 

  33. Zheng C, Goldsmith CM, Mineshiba F, Chiorini JA, Kerr A, Wenk ML, et al. Toxicity and biodistribution of a first-generation recombinant adenoviral vector, encoding aquaporin-1, after retroductal delivery to a single rat submandibular gland. Hum Gene Ther. 2006;17(11):1122–33.

    Article  PubMed  Google Scholar 

  34. Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, et al. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci U S A. 2012;109(47):19403–7.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Cotrim AP, Hyodo F, Matsumoto K, Sowers AL, Cook JA, Baum BJ, et al. Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res. 2007;13(16):4928–33.

    Article  PubMed  Google Scholar 

  36. Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010;15(4):360–71.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Utley JF, Marlowe C, Waddell WJ. Distribution of 35S-labeled WR-2721 in normal and malignant tissues of the mouse1,2. Radiat Res. 1976;68(2):284–91.

    Article  PubMed  Google Scholar 

  38. Yuhas JM, Spellman JM, Culo F. The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin Trials. 1980;3(3):211–6.

    PubMed  Google Scholar 

  39. Konings AW, Faber H, Vissink A, Coppes RP. Radioprotective effect of amifostine on parotid gland functioning is region dependent. Int J Radiat Oncol Biol Phys. 2005;63(5):1584–91.

    Article  PubMed  Google Scholar 

  40. Jensen SB, Pedersen AM, Vissink A, Andersen E, Brown CG, Davies AN, et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer. 2010;18(8):1061–79.

    Google Scholar 

  41. Paardekooper GM, Cammelli S, Zeilstra LJ, Coppes RP, Konings AW. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function. Int J Radiat Biol. 1998;73(6):641–8.

    Article  PubMed  Google Scholar 

  42. Coppes RP, Vissink A, Zeilstra LJ, Konings AW. Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage. Int J Radiat Biol. 1997;72(5):615–25.

    Article  PubMed  Google Scholar 

  43. Coppes RP, Zeilstra LJ, Vissink A, Konings AW. Sialogogue-related radioprotection of salivary gland function: the degranulation concept revisited. Radiat Res. 1997;148(3):240–7.

    Article  PubMed  Google Scholar 

  44. Bentzen SM, Harari PM, Bernier J. Exploitable mechanisms for combining drugs with radiation: concepts, achievements and future directions. Nat Clin Pract Oncol. 2007;4(3):172–80.

    Article  PubMed  Google Scholar 

  45. Coppes RP, van der Goot A, Lombaert IM. Stem cell therapy to reduce radiation-induced normal tissue damage. Semin Radiat Oncol. 2009;19(2):112–21.

    Article  PubMed  Google Scholar 

  46. Braam PM, Roesink JM, Moerland MA, Raaijmakers CP, Schipper M, Terhaard CH. Long-term parotid gland function after radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62(3):659–64.

    Article  PubMed  Google Scholar 

  47. Coppes R, Stokman M. Stem cells and the repair of radiation-induced salivary gland damage. Oral Dis. 2011;17(2):143–53.

    Article  PubMed  Google Scholar 

  48. Lombaert IM, Brunsting JF, Wierenga PK, Faber H, Stokman MA, Kok T, et al. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One. 2008;3(4):e2063.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Pringle S, Van Os R, Coppes RP. Concise review: adult salivary gland stem cells and a potential therapy for xerostomia. Stem Cells. 2013;31(4):613–9.

    Article  PubMed  Google Scholar 

  50. Peter B, Van Waarde MA, Vissink A, ‘s-Gravenmade EJ, Konings AW. Radiation-induced cell proliferation in the parotid and submandibular glands of the rat. Radiat Res. 1994;140(2):257–65.

    Article  PubMed  Google Scholar 

  51. Coppes RP, Vissink A, Konings AW. Comparison of radiosensitivity of rat parotid and submandibular glands after different radiation schedules. Radiother Oncol. 2002;63(3):321–8.

    Article  PubMed  Google Scholar 

  52. Lombaert IM, Brunsting JF, Wierenga PK, Kampinga HH, de Haan G, Coppes RP. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells. 2008;26(10):2595–601.

    Article  PubMed  Google Scholar 

  53. Ohlsson B, Jansen C, Ihse I, Axelson J. Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands. Pancreas. 1997;14(1):94–8.

    Article  PubMed  Google Scholar 

  54. Limesand KH, Said S, Anderson SM. Suppression of radiation-induced salivary gland dysfunction by IGF-1. PLoS One. 2009;4(3):e4663.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Thula TT, Schultz G, Tran-Son-Tay R, Batich C. Effects of EGF and bFGF on irradiated parotid glands. Ann Biomed Eng. 2005;33(5):685–95.

    Article  PubMed  Google Scholar 

  56. Hai B, Yang Z, Shangguan L, Zhao Y, Boyer A, Liu F. Concurrent transient activation of Wnt/beta-catenin pathway prevents radiation damage to salivary glands. Int J Radiat Oncol Biol Phys. 2012;83(1):e109–16.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kojima T, Kanemaru S, Hirano S, Tateya I, Suehiro A, Kitani Y, et al. The protective efficacy of basic fibroblast growth factor in radiation-induced salivary gland dysfunction in mice. Laryngoscope. 2011;121(9):1870–5.

    PubMed  Google Scholar 

  58. Martin KL, Hill GA, Klein RR, Arnett DG, Burd R, Limesand KH. Prevention of radiation-induced salivary gland dysfunction utilizing a CDK inhibitor in a mouse model. PLoS One. 2012;7(12):e51363.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Gorjup E, Danner S, Rotter N, Habermann J, Brassat U, Brummendorf TH, et al. Glandular tissue from human pancreas and salivary gland yields similar stem cell populations. Eur J Cell Biol. 2009;88(7):409–21.

    Article  PubMed  Google Scholar 

  60. Lombaert IM, Wierenga PK, Kok T, Kampinga HH, deHaan G, Coppes RP. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res. 2006;12(6):1804–12.

    Article  PubMed  Google Scholar 

  61. Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood. 2012;120(15):3142–51.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Tran SD, Sumita Y, Khalili S. Bone marrow-derived cells: a potential approach for the treatment of xerostomia. Int J Biochem Cell Biol. 2011;43(1):5–9.

    Article  PubMed  Google Scholar 

  63. Tran SD, Liu Y, Xia D, Maria OM, Khalili S, Wang RW, et al. Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation. PLoS One. 2013;8(4):e61632.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Lombaert IM, Brunsting JF, Wierenga PK, Kampinga HH, de Haan G, Coppes RP. Cytokine treatment improves parenchymal and vascular damage of salivary glands after irradiation. Clin Cancer Res. 2008;14(23):7741–50.

    Article  PubMed  Google Scholar 

  65. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  PubMed  Google Scholar 

  66. Kawakami M, Ishikawa H, Tachibana T, Tanaka A, Mataga I. Functional transplantation of salivary gland cells differentiated from mouse early ES cells in vitro. Hum Cell. 2013;26(2):80–90.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Vissink A, van Luijk P, Langendijk J, Coppes R. Current ideas to reduce or salvage radiation damage to salivary glands. Oral Dis. 2014. doi 10.1111/odi.12222epubahead.

  68. Lombaert IM, Knox SM, Hoffman MP. Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration. Oral Dis. 2011;17(5):445–9.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Pringle S, Nanduri LS, Marianne Z, Ronald O, Coppes RP. Isolation of mouse salivary gland stem cells. J Vis Exp. 2011;(48). pii: 2484. doi(48):10.3791/2484.

  70. Feng J, van der Zwaag M, Stokman MA, van Os R, Coppes RP. Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation. Radiother Oncol. 2009;92(3):466–71.

    Article  PubMed  Google Scholar 

  71. Nanduri LS, Lombaert IM, van der Zwaag M, Faber H, Brunsting JF, van Os RP, et al. Salisphere derived c-Kit cell transplantation restores tissue homeostasis in irradiated salivary gland. Radiother Oncol. 2013;13:240.

    Google Scholar 

  72. Nanduri LS, Maimets M, Pringle SA, van der Zwaag M, van Os RP, Coppes RP. Regeneration of irradiated salivary glands with stem cell marker expressing cells. Radiother Oncol. 2011;99(3):367–72.

    Article  PubMed  Google Scholar 

  73. Palmon A, David R, Neumann Y, Stiubea-Cohen R, Krief G, Aframian DJ. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells. Methods. 2012;56(2):305–9.

    Article  PubMed  Google Scholar 

  74. Beetz I, Schilstra C, Burlage FR, Koken PW, Doornaert P, Bijl HP, et al. Development of NTCP models for head and neck cancer patients treated with three-dimensional conformal radiotherapy for xerostomia and sticky saliva: the role of dosimetric and clinical factors. Radiother Oncol. 2012;105(1):86–93.

    Google Scholar 

  75. van de Water TA. Potential benefits of intensity-modulated proton therapy in head and neck cancer. PhD thesis, ed. Groningen: University of Groningen; 2013.

    Google Scholar 

  76. Jereczek-Fossa BA, Orecchia R. Radiotherapy-induced mandibular bone complications. Cancer Treat Rev. 2002;28(1):65–74.

    Article  PubMed  Google Scholar 

  77. Nguyen NP, Frank C, Moltz CC, Vos P, Smith HJ, Karlsson U, et al. Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;61(3):772–8.

    Article  PubMed  Google Scholar 

  78. 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;78(4):983–91.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function. J Prosthet Dent. 2001;85(2):162–9.

    Article  PubMed  Google Scholar 

  80. van Nieuw Amerongen A, Veerman ECI, Vissink A. Samenstelling en eigenschappen van speeksel: van dun-vloeibare tot viskeuze mondvloeistof. In: Speeksel, speekselklieren en mondgezondheid. 2nd ed. Houten: Bohn Stafleu Van Loghum bv; 2008. p. 37–51.

    Chapter  Google Scholar 

  81. Cooper JS, Fu K, Marks J, Silverman S. Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys. 1995;31(5):1141–64.

    Article  PubMed  Google Scholar 

  82. Eisbruch A, Ship JA, Dawson LA, Kim HM, Bradford CR, Terrell JE, et al. Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer. World J Surg. 2003;27(7):832–7.

    Article  PubMed  Google Scholar 

  83. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol. 2007;25(31):4873–9.

    Article  PubMed  Google Scholar 

  84. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006;66(4):981–91.

    Article  PubMed  Google Scholar 

  85. Slater JD, Yonemoto LT, Mantik DW, Bush DA, Preston W, Grove RI et al. Proton radiation for treatment of cancer of the oropharynx: Early experience at Loma Linda University Medical Center using a concomitant boost technique. Int J Radiat Oncol Biol Phys. 2005;62(2):494–500.

    Article  PubMed  Google Scholar 

  86. Tokuuye K, Akine Y, Kagei K, Hata M, Hashimoto T, Mizumoto T, et al. Proton therapy for head and neck malignancies at Tsukuba. Strahlenther Onkol. 2004;180(2):96–101.

    Article  PubMed  Google Scholar 

  87. Brada M, Pijls-Johannesma M, De Ruysscher D. Current clinical evidence for proton therapy. Cancer J. 2009;15(4):319–24.

    Article  PubMed  Google Scholar 

  88. Chan AW, Liebsch NJ. Proton radiation therapy for head and neck cancer. J Surg Oncol. 2008;97(8):697–700.

    Article  PubMed  Google Scholar 

  89. Schulz-Ertner D. The clinical experience with particle therapy in adults. Cancer J. 2009;15(4):306–11.

    Article  PubMed  Google Scholar 

  90. van de Water TA, Lomax AJ, Bijl HP, Schilstra C, Hug EB, Langendijk JA. Using a reduced spot size for intensity-modulated proton therapy potentially improves salivary gland-sparing in oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):e313–9.

    Article  PubMed  Google Scholar 

  91. van de Water TA, Lomax AJ, Bijl HP, de Jong ME, Schilstra C, Hug EB, et al. Potential benefits of scanned intensity-modulated proton therapy versus advanced photon therapy with regard to sparing of the salivary glands in oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2011;79(4):1216–24.

    Article  PubMed  Google Scholar 

  92. van de Water TA, Bijl HP, Schilstra C, Pijls-Johannesma M, Langendijk JA. The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature. Oncologist. 2011;16(3):366–77.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Liu X, Su Y, Jha N, Hong M, Mai H, Fan W, et al. Submandibular salivary gland transfer for the prevention of radiation-induced xerostomia in patients with nasopharyngeal carcinoma: 5-year outcomes. Head Neck. 2010;33(3):389–95.

    Google Scholar 

  94. Saarilahti K, Kouri M, Collan J, Kangasmaki A, Atula T, Joensuu H, et al. Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer. Radiother Oncol. 2006;78(3):270–5.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology and Cell Biology, University Medical Center Groningen, Internal Zipcode DA30, 30001, Groningen, 9700 RB, The Netherlands

    Robert P. Coppes PhD

  2. Department of Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands

    Tara A. van de Water PhD

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  2. Tara A. van de Water PhD
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Correspondence to Robert P. Coppes PhD .

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  1. Department of Salivary Research, Kings College London Dental Institute, London, United Kingdom

    Guy Carpenter

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Coppes, R.P., van de Water, T.A. (2015). Future Prevention and Treatment of Radiation-Induced Hyposalivation. In: Carpenter, G. (eds) Dry Mouth. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55154-3_13

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