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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life

Supportive Care in Cancer volume 18, pages 1039–1060 (2010)Cite this article

Abstract

Purpose

This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies.

Methods

The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article.

Results

The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy.

Conclusions

Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

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References

  1. Pedersen AM, Bardow A, Jensen SB, Nauntofte B (2002) Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis 8:117–129

    Article  PubMed  CAS  Google Scholar 

  2. Schneyer LH (1956) Source of resting total mixed saliva of man. J Appl Physiol 9:79–81

    PubMed  CAS  Google Scholar 

  3. Dawes C, Ong BY (1973) Circadian rhythms in the flow rate and proportional contribution of parotid to whole saliva volume in man. Arch Oral Biol 18:1145–1153

    Article  PubMed  CAS  Google Scholar 

  4. Dawes C, Wood CM (1973) The contribution of oral minor mucous gland secretions to the volume of whole saliva in man. Arch Oral Biol 18:337–342

    Article  PubMed  CAS  Google Scholar 

  5. Ghezzi EM, Lange LA, Ship JA (2000) Determination of variation of stimulated salivary flow rates. J Dent Res 79:1874–1878

    Article  PubMed  CAS  Google Scholar 

  6. Dawes C (1987) Physiological factors affecting salivary flow rate, oral sugar clearance, and the sensation of dry mouth in man. J Dent Res 66(Spec No):648–653

    PubMed  Google Scholar 

  7. Sreebny LM (2000) Saliva in health and disease: an appraisal and update. Int Dent J 50:140–161

    PubMed  CAS  Google Scholar 

  8. Vissink A, Schaub RM, van Rijn LJ, Gravenmade EJ, Panders AK, Vermey A (1987) The efficacy of mucin-containing artificial saliva in alleviating symptoms of xerostomia. Gerodontology 6:95–101

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Jensen SB, Pedersen AM, Reibel J, Nauntofte B (2003) Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer 11:207–225

    PubMed  Google Scholar 

  11. National Institutes of Health Consensus Development Conference Consensus Statement (1989) Oral complications of cancer therapies: diagnosis, prevention, and treatment. Natl Inst Health Consens Dev Conf Consens Statement 7:1–11

    Google Scholar 

  12. National Institutes of Health Consensus Development Conference. Oral complications of cancer therapies: diagnosis, prevention, and treatment. Bethesda, MD, USA, April 17–19,1989 (1990) NCI Monogr 9:1–184

  13. Jensen SB, Pedersen AML, Vissink A, Andersen E, Brown CG, Davies AN, Dutilh J, Fulton JS, Jankovic L, Lopes NNF, Mello ALS, Muniz LV, Murdoch-Kinch CA, Nair RG, Napeñas JJ, Nogueira-Rodrigues A, Saunders D, Stirling B, von Bültzingslöwen I, Weikel DS, Elting LS, Spijkervet FKL, Brennan MT (2010) A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer (in press) doi:10.1007/s00520-010-0827-8

  14. Brennan MT, Elting LS, Spijkervet FKL (2010) Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO: Methodology and quality of the literature. Support Care Cancer (in press)

  15. Baccaglini L, Brennan MT, Lockhart PB, Patton LL (2007) World Workshop on Oral Medicine IV: process and methodology for systematic review and developing management recommendations. Reference manual for management recommendations writing committees. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(Suppl):S3–19

    PubMed  Google Scholar 

  16. Olver IN, Hughes PG, Smith JG, Narayan K, Bishop JF (1996) Concurrent radiotherapy and continuous ambulatory infusion 5-fluorouracil in advanced head and neck cancer. Eur J Cancer 32A:249–254

    Article  PubMed  CAS  Google Scholar 

  17. Harrison LB, Zelefsky MJ, Pfister DG, Carper E, Raben A, Kraus DH, Strong EW, Rao A, Thaler H, Polyak T, Portenoy R (1997) Detailed quality of life assessment in patients treated with primary radiotherapy for squamous cell cancer of the base of the tongue. Head Neck 19:169–175

    Article  PubMed  CAS  Google Scholar 

  18. List MA, Mumby P, Haraf D, Siston A, Mick R, MacCracken E, Vokes E (1997) Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer. Qual Life Res 6:274–284

    Article  PubMed  CAS  Google Scholar 

  19. Epstein JB, Emerton S, Kolbinson DA, Le ND, Phillips N, Stevenson-Moore P, Osoba D (1999) Quality of life and oral function following radiotherapy for head and neck cancer. Head Neck 21:1–11

    Article  PubMed  CAS  Google Scholar 

  20. Huguenin PU, Taussky D, Moe K, Meister A, Baumert B, Lutolf UM, Glanzmann C (1999) Quality of life in patients cured from a carcinoma of the head and neck by radiotherapy: the importance of the target volume. Int J Radiat Oncol Biol Phys 45:47–52

    PubMed  CAS  Google Scholar 

  21. List MA, Siston A, Haraf D, Schumm P, Kies M, Stenson K, Vokes EE (1999) Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination. J Clin Oncol 17:1020–1028

    PubMed  CAS  Google Scholar 

  22. Huang HY, Wilkie DJ, Schubert MM, Ting LL (2000) Symptom profile of nasopharyngeal cancer patients during radiation therapy. Cancer Pract 8:274–281

    Article  PubMed  CAS  Google Scholar 

  23. Hughes PJ, Scott PM, Kew J, Cheung DM, Leung SF, Ahuja AT, van Hasselt CA (2000) Dysphagia in treated nasopharyngeal cancer. Head Neck 22:393–397

    Article  PubMed  CAS  Google Scholar 

  24. Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L (2000) Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18:1458–1464

    PubMed  CAS  Google Scholar 

  25. Bjordal K, hlner-Elmqvist M, Hammerlid E, Boysen M, Evensen JF, Biorklund A, Jannert M, Westin T, Kaasa S (2001) A prospective study of quality of life in head and neck cancer patients. Part II: Longitudinal data. Laryngoscope 111:1440–1452

    Article  PubMed  CAS  Google Scholar 

  26. Magne N, Marcy PY, Chamorey E, Guardiola E, Pivot X, Schneider M, Demard F, Bensadoun RJ (2001) Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: a long-term quality of life analysis. Head Neck 23:678–682

    Article  PubMed  CAS  Google Scholar 

  27. Ohrn KE, Wahlin YB, Sjoden PO (2001) Oral status during radiotherapy and chemotherapy: a descriptive study of patient experiences and the occurrence of oral complications. Support Care Cancer 9:247–257

    Article  PubMed  CAS  Google Scholar 

  28. Morris MM, Schmidt-Ullrich RK, DiNardo L, Manning MA, Silverman L, Clay L, Johnson CR, Amir C (2002) Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 52:918–928

    PubMed  Google Scholar 

  29. Perlmutter MA, Johnson JT, Snyderman CH, Cano ER, Myers EN (2002) Functional outcomes after treatment of squamous cell carcinoma of the base of the tongue. Arch Otolaryngol Head Neck Surg 128:887–891

    PubMed  Google Scholar 

  30. Grotz KA, Genitsariotis S, Vehling D, Al-Nawas B (2003) Long-term oral Candida colonization, mucositis and salivary function after head and neck radiotherapy. Support Care Cancer 11:717–721

    Article  PubMed  CAS  Google Scholar 

  31. Pow EH, McMillan AS, Leung WK, Wong MC, Kwong DL (2003) Salivary gland function and xerostomia in southern Chinese following radiotherapy for nasopharyngeal carcinoma. Clin Oral Investig 7:230–234

    Article  PubMed  Google Scholar 

  32. Pow EH, McMillan AS, Leung WK, Kwong DL, Wong MC (2003) Oral health condition in southern Chinese after radiotherapy for nasopharyngeal carcinoma: extent and nature of the problem. Oral Dis 9:196–202

    Article  PubMed  CAS  Google Scholar 

  33. Tschudi D, Stoeckli S, Schmid S (2003) Quality of life after different treatment modalities for carcinoma of the oropharynx. Laryngoscope 113:1949–1954

    Article  PubMed  Google Scholar 

  34. Allal AS, Taussky D, Mach N, Becker M, Bieri S, Dulguerov P (2004) Can concomitant-boost accelerated radiotherapy be adopted as routine treatment for head-and-neck cancers? A 10-year single-institution experience. Int J Radiat Oncol Biol Phys 58:1431–1436

    Article  PubMed  Google Scholar 

  35. Bansal M, Mohanti BK, Shah N, Chaudhry R, Bahadur S, Shukla NK (2004) Radiation related morbidities and their impact on quality of life in head and neck cancer patients receiving radical radiotherapy. Qual Life Res 13:481–488

    Article  PubMed  CAS  Google Scholar 

  36. Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G (2004) Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22:69–76

    Article  PubMed  Google Scholar 

  37. Fang FM, Chien CY, Kuo SC, Chiu HC, Wang CJ (2004) Changes in quality of life of head-and-neck cancer patients following postoperative radiotherapy. Acta Oncol 43:571–578

    Article  PubMed  Google Scholar 

  38. Jereczek-Fossa BA, Morra A, DeBraud F, Alterio D, Mazzetta C, Rocca A, Catalano G, Bianchi L, Pasetti M, Chiesa F, Bruschini R, Orecchia R (2004) Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An analysis of 43 consecutive patients. Strahlenther Onkol 180:425–433

    Article  PubMed  Google Scholar 

  39. Levendag P, Nijdam W, Noever I, Schmitz P, Van de Pol M, Sipkema D, Braat C, de Boer MD, Jansen P (2004) Brachytherapy versus surgery in carcinoma of tonsillar fossa and/or soft palate: late adverse sequelae and performance status: can we be more selective and obtain better tissue sparing? Int J Radiat Oncol Biol Phys 59:713–724

    PubMed  Google Scholar 

  40. Moller P, Perrier M, Ozsahin M, Monnier P (2004) A prospective study of salivary gland function in patients undergoing radiotherapy for squamous cell carcinoma of the oropharynx. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:173–189

    Article  PubMed  Google Scholar 

  41. Palazzi M, Guzzo M, Tomatis S, Cerrotta A, Potepan P, Quattrone P, Cantu G (2004) Improved outcome of nasopharyngeal carcinoma treated with conventional radiotherapy. Int J Radiat Oncol Biol Phys 60:1451–1458

    PubMed  Google Scholar 

  42. Winter SC, Cassell O, Corbridge RJ, Goodacre T, Cox GJ (2004) Quality of life following resection, free flap reconstruction and postoperative external beam radiotherapy for squamous cell carcinoma of the base of tongue. Clin Otolaryngol Allied Sci 29:274–278

    Article  PubMed  CAS  Google Scholar 

  43. Fang FM, Tsai WL, Chien CY, Chiu HC, Wang CJ, Chen HC, Hsiung CY (2005) Changing quality of life in patients with advanced head and neck cancer after primary radiotherapy or chemoradiation. Oncology 68:405–413

    Article  PubMed  Google Scholar 

  44. Jellema AP, Doornaert P, Slotman BJ, Leemans CR, Langendijk JA (2005) Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy? Radiother Oncol 77:164–171

    Article  PubMed  Google Scholar 

  45. Petruson K, Mercke C, Lundberg LM, Silander E, Hammerlid E (2005) Longitudinal evaluation of patients with cancer in the oral tongue, tonsils, or base of tongue—does interstitial radiation dose affect quality of life? Brachytherapy 4:271–277

    Article  PubMed  Google Scholar 

  46. Ravasco P, Monteiro-Grillo I, Marques VP, Camilo ME (2005) Impact of nutrition on outcome: a prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy. Head Neck 27:659–668

    Article  PubMed  Google Scholar 

  47. Yeh SA, Tang Y, Lui CC, Huang YJ, Huang EY (2005) Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys 62:672–679

    PubMed  Google Scholar 

  48. Bensadoun RJ, Benezery K, Dassonville O, Magne N, Poissonnet G, Ramaioli A, Lemanski C, Bourdin S, Tortochaux J, Peyrade F, Marcy PY, Chamorey E, Vallicioni J, Seng H, Alzieu C, Gery B, Chauvel P, Schneider M, Santini J, Demard F, Calais G (2006) French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC). Int J Radiat Oncol Biol Phys 64:983–994

    PubMed  CAS  Google Scholar 

  49. Connor NP, Cohen SB, Kammer RE, Sullivan PA, Brewer KA, Hong TS, Chappell RJ, Harari PM (2006) Impact of conventional radiotherapy on health-related quality of life and critical functions of the head and neck. Int J Radiat Oncol Biol Phys 65:1051–1062

    PubMed  Google Scholar 

  50. Mowry SE, LoTempio MM, Sadeghi A, Wang KH, Wang MB (2006) Quality of life outcomes in laryngeal and oropharyngeal cancer patients after chemoradiation. Otolaryngol Head Neck Surg 135:565–570

    Article  PubMed  Google Scholar 

  51. Nordgren M, Jannert M, Boysen M, hlner-Elmqvist M, Silander E, Bjordal K, Hammerlid E (2006) Health-related quality of life in patients with pharyngeal carcinoma: a five-year follow-up. Head Neck 28:339–349

    Article  PubMed  Google Scholar 

  52. Braam PM, Roesink JM, Raaijmakers CP, Busschers WB, Terhaard CH (2007) Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy. Radiat Oncol 2:3

    Article  PubMed  Google Scholar 

  53. Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA (2007) 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 69:751–760

    PubMed  Google Scholar 

  54. Jensen K, Lambertsen K, Torkov P, Dahl M, Jensen AB, Grau C (2007) Patient assessed symptoms are poor predictors of objective findings. Results from a cross sectional study in patients treated with radiotherapy for pharyngeal cancer. Acta Oncol 46:1159–1168

    Article  PubMed  Google Scholar 

  55. Oates JE, Clark JR, Read J, Reeves N, Gao K, Jackson M, Boyer M, O'brien CJ (2007) Prospective evaluation of quality of life and nutrition before and after treatment for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 133:533–540

    Article  PubMed  Google Scholar 

  56. Thomson WM (2007) Measuring change in dry-mouth symptoms over time using the Xerostomia Inventory. Gerodontology 24:30–35

    Article  PubMed  Google Scholar 

  57. Yeh SA, Huang YJ (2007) Dose escalation for patients with locally advanced nasopharyngeal carcinoma treated with radiotherapy alone. Am J Clin Oncol 30:401–405

    Article  PubMed  Google Scholar 

  58. Dirix P, Nuyts S, Vander Poorten V, Delaere P, Van den Bogaert W (2008) The influence of xerostomia after radiotherapy on quality of life: results of a questionnaire in head and neck cancer. Support Care Cancer 16:171–179

    Article  PubMed  Google Scholar 

  59. Hauswald H, Lindel K, Rochet N, Debus J, Harms W (2008) Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary. Strahlenther Onkol 184:150–156

    Article  PubMed  Google Scholar 

  60. Jham BC, Reis PM, Miranda EL, Lopes RC, Carvalho AL, Scheper MA, Freire AR (2008) Oral health status of 207 head and neck cancer patients before, during and after radiotherapy. Clin Oral Investig 12:19–24

    Article  PubMed  Google Scholar 

  61. Nijdam WM, Levendag PC, Noever I, Schmitz PI, Uyl-de Groot CA (2008) Longitudinal changes in quality of life and costs in long-term survivors of tumors of the oropharynx treated with brachytherapy or surgery. Brachytherapy 7:343–350

    Article  PubMed  Google Scholar 

  62. Saunders M, Rojas AM, Dische S (2008) CHART revisited: a conservative approach for advanced head and neck cancer. Clin Oncol (R Coll Radiol) 20:127–133

    CAS  Google Scholar 

  63. Epstein JB, Robertson M, Emerton S, Phillips N, Stevenson-Moore P (2001) Quality of life and oral function in patients treated with radiation therapy for head and neck cancer. Head Neck 23:389–398

    Article  PubMed  CAS  Google Scholar 

  64. Franzen L, Funegard U, Ericson T, Henriksson R (1992) Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort. Eur J Cancer 28:457–462

    Article  PubMed  CAS  Google Scholar 

  65. Nishioka T, Shirato H, Arimoto T, Kaneko M, Kitahara T, Oomori K, Yasuda M, Fukuda S, Inuyama Y, Miyasaka K (1997) Reduction of radiation-induced xerostomia in nasopharyngeal carcinoma using CT simulation with laser patient marking and three-field irradiation technique. Int J Radiat Oncol Biol Phys 38:705–712

    Article  PubMed  CAS  Google Scholar 

  66. Someya M, Sakata K, Nagakura H, Nakata K, Oouchi A, Hareyama M (2003) The changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy. Jpn J Clin Oncol 33:336–340

    Article  PubMed  Google Scholar 

  67. Roh JL, Kim AY, Cho MJ (2005) Xerostomia following radiotherapy of the head and neck affects vocal function. J Clin Oncol 23:3016–3023

    Article  PubMed  Google Scholar 

  68. Wu Y, Hu WH, Xia YF, Ma J, Liu MZ, Cui NJ (2007) Quality of life of nasopharyngeal carcinoma survivors in Mainland China. Qual Life Res 16:65–74

    Article  PubMed  CAS  Google Scholar 

  69. Marunick MT, Seyedsadr M, Ahmad K, Klein B (1991) The effect of head and neck cancer treatment on whole salivary flow. J Surg Oncol 48:81–86

    Article  PubMed  CAS  Google Scholar 

  70. de Graeff A, De L Jr, Ros WJ, Hordijk GJ, Blijham GH, Winnubst JA (2000) Long-term quality of life of patients with head and neck cancer. Laryngoscope 110:98–106

    Article  PubMed  CAS  Google Scholar 

  71. Bhalavat RL, Pathak KA, Mahantshetty U, Jamema SV (2007) Brachytherapy boost: a novel approach for epiglottic carcinoma. Brachytherapy 6:212–217

    Article  PubMed  Google Scholar 

  72. Boscolo-Rizzo P, Maronato F, Marchiori C, Gava A, Da Mosto MC (2008) Long-term quality of life after total laryngectomy and postoperative radiotherapy versus concurrent chemoradiotherapy for laryngeal preservation. Laryngoscope 118:300–306

    Article  PubMed  Google Scholar 

  73. Spak CJ, Johnson G, Ekstrand J (1994) Caries incidence, salivary flow rate and efficacy of fluoride gel treatment in irradiated patients. Caries Res 28:388–393

    Article  PubMed  CAS  Google Scholar 

  74. Epstein JB, Chin EA, Jacobson JJ, Rishiraj B, Le N (1998) The relationships among fluoride, cariogenic oral flora, and salivary flow rate during radiation therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:286–292

    Article  PubMed  CAS  Google Scholar 

  75. Dawes C, Odlum O (2004) Salivary status in patients treated for head and neck cancer. J Can Dent Assoc 70:397–400

    PubMed  Google Scholar 

  76. Eliasson L, Almstahl A, Lingstrom P, Wikstrom M, Carlen A (2005) Minor gland saliva flow rate and proteins in subjects with hyposalivation due to Sjogren's syndrome and radiation therapy. Arch Oral Biol 50:293–299

    Article  PubMed  CAS  Google Scholar 

  77. Almstahl A, Wikstrom M, Fagerberg-Mohlin B (2008) Microflora in oral ecosystems in subjects with radiation-induced hyposalivation. Oral Dis 14:541–549

    Article  PubMed  CAS  Google Scholar 

  78. Chambers MS, Tomsett KL, Artopoulou II, Garden AS, El-Naggar AK, Martin JW, Keene HJ (2008) Salivary flow rates measured during radiation therapy in head and neck cancer patients: a pilot study assessing salivary sediment formation. J Prosthet Dent 100:142–146

    Article  PubMed  Google Scholar 

  79. Liu RP, Fleming TJ, Toth BB, Keene HJ (1990) Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. Oral Surg Oral Med Oral Pathol 70:724–729

    Article  PubMed  CAS  Google Scholar 

  80. Markitziu A, Zafiropoulos G, Tsalikis L, Cohen L (1992) Gingival health and salivary function in head and neck-irradiated patients. A five-year follow-up. Oral Surg Oral Med Oral Pathol 73:427–433

    Article  PubMed  CAS  Google Scholar 

  81. Valdez IH, Atkinson JC, Ship JA, Fox PC (1993) Major salivary gland function in patients with radiation-induced xerostomia: flow rates and sialochemistry. Int J Radiat Oncol Biol Phys 25:41–47

    PubMed  CAS  Google Scholar 

  82. Roesink JM, Moerland MA, Battermann JJ, Hordijk GJ, Terhaard CH (2001) Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region. Int J Radiat Oncol Biol Phys 51:938–946

    PubMed  CAS  Google Scholar 

  83. Beer KT, Zehnder D, Lussi A, Greiner RH (2002) Sparing of contralateral major salivary glands has a significant effect on oral health in patients treated with radical radiotherapy of head and neck tumors. Strahlenther Onkol 178:722–726

    Article  PubMed  Google Scholar 

  84. Jen YM, Lin YC, Wang YB, Wu DM (2006) Dramatic and prolonged decrease of whole salivary secretion in nasopharyngeal carcinoma patients treated with radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:322–327

    Article  PubMed  Google Scholar 

  85. Jensen K, Overgaard M, Grau C (2007) Morbidity after ipsilateral radiotherapy for oropharyngeal cancer. Radiother Oncol 85:90–97

    Article  PubMed  Google Scholar 

  86. Epstein JB, Gorsky M, Guglietta A, Le N, Sonis ST (2000) The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer 89:2258–2265

    Article  PubMed  CAS  Google Scholar 

  87. Burlage FR, Coppes RP, Meertens H, Stokman MA, Vissink A (2001) Parotid and submandibular/sublingual salivary flow during high dose radiotherapy. Radiother Oncol 61:271–274

    Article  PubMed  CAS  Google Scholar 

  88. Paulino AC, Simon JH, Zhen W, Wen BC (2000) Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 48:1489–1495

    PubMed  CAS  Google Scholar 

  89. Bieri S, Bentzen SM, Huguenin P, Allal AS, Cozzi L, Landmann C, Monney M, Bernier J (2003) Early morbidity after radiotherapy with or without chemotherapy in advanced head and neck cancer. Experience from four nonrandomized studies. Strahlenther Onkol 179:390–395

    PubMed  Google Scholar 

  90. Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Calais G (2003) Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA, RTOG/EORTC, and NCI-CTC scoring systems. Int J Radiat Oncol Biol Phys 55:93–98

    Article  PubMed  Google Scholar 

  91. Olmi P, Crispino S, Fallai C, Torri V, Rossi F, Bolner A, Amichetti M, Signor M, Taino R, Squadrelli M, Colombo A, Ardizzoia A, Ponticelli P, Franchin G, Minatel E, Gobitti C, Atzeni G, Gava A, Flann M, Marsoni S (2003) Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy—a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55:78–92

    Article  PubMed  Google Scholar 

  92. Hanna E, Sherman A, Cash D, Adams D, Vural E, Fan CY, Suen JY (2004) Quality of life for patients following total laryngectomy vs chemoradiation for laryngeal preservation. Arch Otolaryngol Head Neck Surg 130:875–879

    Article  PubMed  Google Scholar 

  93. Fallai C, Bolner A, Signor M, Gava A, Franchin G, Ponticelli P, Taino R, Rossi F, Ardizzoia A, Oggionni M, Crispino S, Olmi P (2006) Long-term results of conventional radiotherapy versus accelerated hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy in locoregionally advanced carcinoma of the oropharynx. Tumori 92:41–54

    PubMed  Google Scholar 

  94. Palazzi M, Tomatis S, Orlandi E, Guzzo M, Sangalli C, Potepan P, Fantini S, Bergamini C, Gavazzi C, Licitra L, Scaramellini G, Cantu' G, Olmi P (2008) Effects of treatment intensification on acute local toxicity during radiotherapy for head and neck cancer: prospective observational study validating CTCAE, version 3.0, scoring system. Int J Radiat Oncol Biol Phys 70:330–337

    PubMed  Google Scholar 

  95. Eisbruch A, Ship JA, Martel MK, Ten Haken RK, Marsh LH, Wolf GT, Esclamado RM, Bradford CR, Terrell JE, Gebarski SS, Lichter AS (1996) Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results. Int J Radiat Oncol Biol Phys 36:469–480

    Article  PubMed  CAS  Google Scholar 

  96. D'Hondt E, Eisbruch A, Ship JA (1998) The influence of pre-radiation salivary flow rates and radiation dose on parotid salivary gland dysfunction in patients receiving radiotherapy for head and neck cancers. Spec Care Dentist 18:102–108

    Article  PubMed  Google Scholar 

  97. Henson BS, Eisbruch A, D'Hondt E, Ship JA (1999) Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment. Oral Oncol 35:234–241

    Article  PubMed  CAS  Google Scholar 

  98. Henson BS, Inglehart MR, Eisbruch A, Ship JA (2001) Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy. Oral Oncol 37:84–93

    Article  PubMed  CAS  Google Scholar 

  99. Maes A, Weltens C, Flamen P, Lambin P, Bogaerts R, Liu X, Baetens J, Hermans R, Van den BW (2002) Preservation of parotid function with uncomplicated conformal radiotherapy. Radiother Oncol 63:203–211

    Article  PubMed  Google Scholar 

  100. Malouf JG, Aragon C, Henson BS, Eisbruch A, Ship JA (2003) Influence of parotid-sparing radiotherapy on xerostomia in head and neck cancer patients. Cancer Detect Prev 27:305–310

    Article  PubMed  Google Scholar 

  101. Braam PM, Roesink JM, Moerland MA, Raaijmakers CP, Schipper M, Terhaard CH (2005) Long-term parotid gland function after radiotherapy. Int J Radiat Oncol Biol Phys 62:659–664

    PubMed  Google Scholar 

  102. Braaksma MM, Wijers OB, van Sornsen de Koste JR, van der Est H, Schmitz PI, Nowak PJ, Levendag PC (2003) Optimisation of conformal radiation therapy by intensity modulation: cancer of the larynx and salivary gland function. Radiother Oncol 66:291–302

    Article  PubMed  Google Scholar 

  103. Ng MK, Porceddu SV, Milner AD, Corry J, Hornby C, Hope G, Rischin D, Peters LJ (2005) Parotid-sparing radiotherapy: does it really reduce xerostomia? Clin Oncol (R Coll Radiol) 17:610–617

    CAS  Google Scholar 

  104. Jen YM, Shih R, Lin YS, Su WF, Ku CH, Chang CS, Shueng PW, Hwang JM, Liu DW, Chao HL, Lin HY, Chang LP, Shum WY, Lin CS (2005) Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy. Radiother Oncol 75:204–209

    Article  PubMed  Google Scholar 

  105. Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ (2008) Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol 26:3770–3776

    Article  PubMed  Google Scholar 

  106. Rades D, Stoehr M, Meyners T, Bohlen G, Nadrowitz R, Dunst J, Schild SE, Wroblewski J, Albers D, Schmidt R, Alberti W, Tribius S (2008) Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer. Strahlenther Onkol 184:198–205

    Article  PubMed  Google Scholar 

  107. Portaluri M, Fucilli FI, Castagna R, Bambace S, Pili G, Tramacere F, Russo D, Francavilla MC (2006) Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: dosimetric and clinical evaluation. Int J Radiat Oncol Biol Phys 66:1036–1043

    PubMed  Google Scholar 

  108. Jellema AP, Slotman BJ, Doornaert P, Leemans CR, Langendijk JA (2007) Unilateral versus bilateral irradiation in squamous cell head and neck cancer in relation to patient-rated xerostomia and sticky saliva. Radiother Oncol 85:83–89

    Article  PubMed  Google Scholar 

  109. Louis CU, Paulino AC, Gottschalk S, Bertuch AA, Chintagumpala M, Heslop HE, Russell HV (2007) A single institution experience with pediatric nasopharyngeal carcinoma: high incidence of toxicity associated with platinum-based chemotherapy plus IMRT. J Pediatr Hematol Oncol 29:500–505

    Article  PubMed  CAS  Google Scholar 

  110. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, Leung WK (2006) 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 66:981–991

    PubMed  Google Scholar 

  111. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, Lai M, Ho R, Cheung KY, Yu BK, Chiu SK, Choi PH, Teo PM, Kwan WH, Chan AT (2007) Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 25:4873–4879

    Article  PubMed  Google Scholar 

  112. Chao KS, Deasy JO, Markman J, Haynie J, Perez CA, Purdy JA, Low DA (2001) A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. Int J Radiat Oncol Biol Phys 49:907–916

    PubMed  CAS  Google Scholar 

  113. Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA, Ship JA (2001) Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys 50:695–704

    PubMed  CAS  Google Scholar 

  114. Munter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, Huber P, Debus J, Karger CP (2007) Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine. Int J Radiat Oncol Biol Phys 67:651–659

    PubMed  Google Scholar 

  115. Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA (1999) 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 45:577–587

    PubMed  CAS  Google Scholar 

  116. Lin A, Kim HM, Terrell JE, Dawson LA, Ship JA, Eisbruch A (2003) Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study. Int J Radiat Oncol Biol Phys 57:61–70

    PubMed  Google Scholar 

  117. Blanco AI, Chao KS, El Naqa I, Franklin GE, Zakarian K, Vicic M, Deasy JO (2005) Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 62:1055–1069

    PubMed  Google Scholar 

  118. Saarilahti K, Kouri M, Collan J, Hamalainen T, Atula T, Joensuu H, Tenhunen M (2005) Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function. Radiother Oncol 74:251–258

    Article  PubMed  Google Scholar 

  119. de Arruda FF, Puri DR, Zhung J, Narayana A, Wolden S, Hunt M, Stambuk H, Pfister D, Kraus D, Shaha A, Shah J, Lee NY (2006) Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: the Memorial Sloan-Kettering Cancer Center experience. Int J Radiat Oncol Biol Phys 64:363–373

    PubMed  Google Scholar 

  120. Hsiung CY, Ting HM, Huang HY, Lee CH, Huang EY, Hsu HC (2006) Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy. Int J Radiat Oncol Biol Phys 66:454–461

    PubMed  Google Scholar 

  121. Liu WS, Lee SP, Lee JK, Su MC, Chen GD, Lee HS, Lee H (2006) Factors influencing the parotid function in nasopharyngeal carcinoma treated with parotid-sparing radiotherapy. Jpn J Clin Oncol 36:626–631

    Article  PubMed  Google Scholar 

  122. Liu WS, Kuo HC, Lin JC, Su MC, Lee JK, Chou MJ, Chou MC, Lee H (2006) Assessment of salivary function change in nasopharyngeal carcinoma treated by parotid-sparing radiotherapy. Cancer J 12:494–500

    Article  PubMed  Google Scholar 

  123. Li Y, Taylor JM, Ten Haken RK, Eisbruch A (2007) The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 67:660–669

    PubMed  Google Scholar 

  124. Munter MW, Karger CP, Hoffner SG, Hof H, Thilmann C, Rudat V, Nill S, Wannenmacher M, Debus J (2004) Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys 58:175–184

    Article  PubMed  Google Scholar 

  125. Dijkema T, Raaijmakers CPJ, Ten Haken RK, Roesink JM, Braam PM, Houweling AC, Moerland MA, Eisbruch A, Teerhard CHJ (2010) Parotid gland function after radiotherapy: the combined Michigan and Utrecht experience. Int J Radiat Oncol Biol Phys (in press) doi:10.1016/j.ijrobp.2009.07.1708

  126. Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, Spector G (2001) Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Radiother Oncol 61:275–280

    Article  PubMed  CAS  Google Scholar 

  127. Amosson CM, Teh BS, Van TJ, Uy N, Huang E, Mai WY, Frolov A, Woo SY, Chiu JK, Carpenter LS, Lu HH, Grant WH III, Butler EB (2003) Dosimetric predictors of xerostomia for head-and-neck cancer patients treated with the smart (simultaneous modulated accelerated radiation therapy) boost technique. Int J Radiat Oncol Biol Phys 56:136–144

    PubMed  Google Scholar 

  128. Chao KS, Ozyigit G, Blanco AI, Thorstad WL, Deasy JO, Haughey BH, Spector GJ, Sessions DG (2004) Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume. Int J Radiat Oncol Biol Phys 59:43–50

    PubMed  Google Scholar 

  129. Lu TX, Mai WY, Teh BS, Zhao C, Han F, Huang Y, Deng XW, Lu LX, Huang SM, Zeng ZF, Lin CG, Lu HH, Chiu JK, Carpenter LS, Grant WH III, Woo SY, Cui NJ, Butler EB (2004) Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 58:682–687

    PubMed  Google Scholar 

  130. Jabbari S, Kim HM, Feng M, Lin A, Tsien C, Elshaikh M, Terrel JE, Murdoch-Kinch C, Eisbruch A (2005) Matched case–control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report. Int J Radiat Oncol Biol Phys 63:725–731

    PubMed  Google Scholar 

  131. Nishimura Y, Nakamatsu K, Shibata T, Kanamori S, Koike R, Okumura M, Suzuki M (2005) Importance of the initial volume of parotid glands in xerostomia for patients with head and neck cancers treated with IMRT. Jpn J Clin Oncol 35:375–379

    Article  PubMed  Google Scholar 

  132. Pacholke HD, Amdur RJ, Morris CG, Li JG, Dempsey JF, Hinerman RW, Mendenhall WM (2005) Late xerostomia after intensity-modulated radiation therapy versus conventional radiotherapy. Am J Clin Oncol 28:351–358

    Article  PubMed  Google Scholar 

  133. Rosenbluth BD, Serrano V, Happersett L, Shaha AR, Tuttle RM, Narayana A, Wolden SL, Rosenzweig KE, Chong LM, Lee NY (2005) Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer. Int J Radiat Oncol Biol Phys 63:1419–1426

    Article  PubMed  Google Scholar 

  134. Lee NY, de Arruda FF, Puri DR, Wolden SL, Narayana A, Mechalakos J, Venkatraman ES, Kraus D, Shaha A, Shah JP, Pfister DG, Zelefsky MJ (2006) A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 66:966–974

    PubMed  Google Scholar 

  135. Meirovitz A, Murdoch-Kinch CA, Schipper M, Pan C, Eisbruch A (2006) Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys 66:445–453

    PubMed  Google Scholar 

  136. Nangia S, Chufal KS, Arivazhagan V, Srinivas P, Tyagi A, Ghosh D (2006) Compensator-based intensity-modulated radiotherapy in head and neck cancer: our experience in achieving dosimetric parameters and their clinical correlation. Clin Oncol (R Coll Radiol) 18:485–492

    CAS  Google Scholar 

  137. Vosmik M, Odrazka K, Dolezel M, Vaculikova M, Kordac P, Zouhar M, Petera J, Jansa J, Zoul Z, Paluska P, Vokurka J (2006) IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation. Acta Medica (Hradec Kralove) 49:167–173

    Google Scholar 

  138. Wendt TG, Abbasi-Senger N, Salz H, Pinquart I, Koscielny S, Przetak SM, Wiezorek T (2006) 3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing. Radiat Oncol 1:18

    Article  PubMed  Google Scholar 

  139. Wolden SL, Chen WC, Pfister DG, Kraus DH, Berry SL, Zelefsky MJ (2006) Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan–Kettering experience. Int J Radiat Oncol Biol Phys 64:57–62

    PubMed  Google Scholar 

  140. Daly ME, Lieskovsky Y, Pawlicki T, Yau J, Pinto H, Kaplan M, Fee WE, Koong A, Goffinet DR, Xing L, Le QT (2007) Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinoma. Head Neck 29:211–220

    Article  PubMed  Google Scholar 

  141. Fang FM, Tsai WL, Chen HC, Hsu HC, Hsiung CY, Chien CY, Ko SF (2007) Intensity-modulated or conformal radiotherapy improves the quality of life of patients with nasopharyngeal carcinoma: comparisons of four radiotherapy techniques. Cancer 109:313–321

    Article  PubMed  Google Scholar 

  142. Graff P, Lapeyre M, Desandes E, Ortholan C, Bensadoun RJ, Alfonsi M, Maingon P, Giraud P, Bourhis J, Marchesi V, Mege A, Peiffert D (2007) Impact of intensity-modulated radiotherapy on health-related quality of life for head and neck cancer patients: matched-pair comparison with conventional radiotherapy. Int J Radiat Oncol Biol Phys 67:1309–1317

    PubMed  Google Scholar 

  143. Rades D, Fehlauer F, Wroblesky J, Albers D, Schild SE, Schmidt R (2007) Prognostic factors in head-and-neck cancer patients treated with surgery followed by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or conventional radiotherapy. Oral Oncol 43:535–543

    Article  PubMed  Google Scholar 

  144. Anand AK, Chaudhoory AR, Shukla A, Negi PS, Sinha SN, Babu AA, Munjal RK, Dewan AK, Kumar K, Doval DC, Vaid AK (2008) Favourable impact of intensity-modulated radiation therapy on chronic dysphagia in patients with head and neck cancer. Br J Radiol 81:865–871

    Article  PubMed  CAS  Google Scholar 

  145. Huang K, Xia P, Chuang C, Weinberg V, Glastonbury CM, Eisele DW, Lee NY, Yom SS, Phillips TL, Quivey JM (2008) Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California–San Francisco experience. Cancer 113:497–507

    Article  PubMed  Google Scholar 

  146. Klem ML, Mechalakos JG, Wolden SL, Zelefsky MJ, Singh B, Kraus D, Shaha A, Shah J, Pfister DG, Lee NY (2008) Intensity-modulated radiotherapy for head and neck cancer of unknown primary: toxicity and preliminary efficacy. Int J Radiat Oncol Biol Phys 70:1100–1107

    PubMed  Google Scholar 

  147. Madani I, Vakaet L, Bonte K, Boterberg T, De NW (2008) Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 71:1158–1166

    PubMed  Google Scholar 

  148. Rusthoven KE, Raben D, Ballonoff A, Kane M, Song JI, Chen C (2008) Effect of radiation techniques in treatment of oropharynx cancer. Laryngoscope 118:635–639

    Article  PubMed  Google Scholar 

  149. Seung S, Bae J, Solhjem M, Bader S, Gannett D, Hansen EK, Louie J, Underhill K, Cha C (2008) Intensity-modulated radiotherapy for head-and-neck cancer in the community setting. Int J Radiat Oncol Biol Phys 72:1075–1081

    PubMed  Google Scholar 

  150. van Rij CM, Oughlane-Heemsbergen WD, Ackerstaff AH, Lamers EA, Balm AJ, Rasch CR (2008) Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life. Radiat Oncol 3:41

    Article  PubMed  Google Scholar 

  151. Sultanem K, Shu HK, Xia P, Akazawa C, Quivey JM, Verhey LJ, Fu KK (2000) Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California–San Francisco experience. Int J Radiat Oncol Biol Phys 48:711–722

    PubMed  CAS  Google Scholar 

  152. Kam MK, Teo PM, Chau RM, Cheung KY, Choi PH, Kwan WH, Leung SF, Zee B, Chan AT (2004) Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience. Int J Radiat Oncol Biol Phys 60:1440–1450

    PubMed  Google Scholar 

  153. Anand AK, Jain J, Negi PS, Chaudhoory AR, Sinha SN, Choudhury PS, Kumar R, Munjal RK (2006) Can dose reduction to one parotid gland prevent xerostomia?—A feasibility study for locally advanced head and neck cancer patients treated with intensity-modulated radiotherapy. Clin Oncol (R Coll Radiol) 18:497–504

    CAS  Google Scholar 

  154. Lee NY, O’Meara W, Chan K, la-Bianca C, Mechalakos JG, Zhung J, Wolden SL, Narayana A, Kraus D, Shah JP, Pfister DG (2007) Concurrent chemotherapy and intensity-modulated radiotherapy for locoregionally advanced laryngeal and hypopharyngeal cancers. Int J Radiat Oncol Biol Phys 69:459–468

    PubMed  CAS  Google Scholar 

  155. Saarilahti K, Kouri M, Collan J, Kangasmaki A, Atula T, Joensuu H, Tenhunen M (2006) Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer. Radiother Oncol 78:270–275

    Article  PubMed  Google Scholar 

  156. Murdoch-Kinch CA, Kim HM, Vineberg KA, Ship JA, Eisbruch A (2008) Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 72:373–382

    PubMed  Google Scholar 

  157. Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM (1998) Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med 39:1551–1554

    PubMed  CAS  Google Scholar 

  158. Solans R, Bosch JA, Galofre P, Porta F, Rosello J, Selva-O'Callagan A, Vilardell M (2001) Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J Nucl Med 42:738–743

    PubMed  CAS  Google Scholar 

  159. Mendoza A, Shaffer B, Karakla D, Mason ME, Elkins D, Goffman TE (2004) Quality of life with well-differentiated thyroid cancer: treatment toxicities and their reduction. Thyroid 14:133–140

    Article  PubMed  CAS  Google Scholar 

  160. Kim JW, Han GS, Lee SH, Lee DY, Kim YM (2007) Sialoendoscopic treatment for radioiodine induced sialadenitis. Laryngoscope 117:133–136

    Article  PubMed  CAS  Google Scholar 

  161. Hyer S, Kong A, Pratt B, Harmer C (2007) Salivary gland toxicity after radioiodine therapy for thyroid cancer. Clin Oncol (R Coll Radiol) 19:83–86

    CAS  Google Scholar 

  162. Walter MA, Turtschi CP, Schindler C, Minnig P, Muller-Brand J, Muller B (2007) The dental safety profile of high-dose radioiodine therapy for thyroid cancer: long-term results of a longitudinal cohort study. J Nucl Med 48:1620–1625

    Article  PubMed  Google Scholar 

  163. Caglar M, Tuncel M, Alpar R (2002) Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment. Clin Nucl Med 27:767–771

    Article  PubMed  Google Scholar 

  164. Lin WY, Shen YY, Wang SJ (1996) Short-term hazards of low-dose radioiodine ablation therapy in postsurgical thyroid cancer patients. Clin Nucl Med 21:780–782

    Article  PubMed  CAS  Google Scholar 

  165. Nederfors T, Isaksson R, Mornstad H, Dahlof C (1997) Prevalence of perceived symptoms of dry mouth in an adult Swedish population—relation to age, sex and pharmacotherapy. Community Dent Oral Epidemiol 25:211–216

    Article  PubMed  CAS  Google Scholar 

  166. Ish-Shalom S, Durleshter L, Segal E, Nagler RM (2008) Sialochemical and oxidative analyses in radioactive I131-treated patients with thyroid carcinoma. Eur J Endocrinol 158:677–681

    Article  PubMed  CAS  Google Scholar 

  167. Laupa MS, Toth BB, Keene HJ, Sellin RV (1993) Effect of radioactive iodine therapy on salivary flow rates and oral Streptococcus mutans prevalence in patients with thyroid cancer. Oral Surg Oral Med Oral Pathol 75:312–317

    Article  PubMed  CAS  Google Scholar 

  168. Chaillet MP, Cosset JM, Socie G, Pico JL, Grimaud E, Dubray B, Alapetite C, Girinsky T (1993) Prospective study of the clinical symptoms of therapeutic whole body irradiation. Health Phys 64:370–374

    Article  PubMed  CAS  Google Scholar 

  169. Buchali A, Feyer P, Groll J, Massenkeil G, Arnold R, Budach V (2000) Immediate toxicity during fractionated total body irradiation as conditioning for bone marrow transplantation. Radiother Oncol 54:157–162

    Article  PubMed  CAS  Google Scholar 

  170. Bagesund M, Winiarski J, Dahllof G (2000) Subjective xerostomia in long-term surviving children and adolescents after pediatric bone marrow transplantation. Transplantation 69:822–826

    Article  PubMed  CAS  Google Scholar 

  171. Dahllof G, Bagesund M, Ringden O (1997) Impact of conditioning regimens on salivary function, caries-associated microorganisms and dental caries in children after bone marrow transplantation. A 4-year longitudinal study. Bone Marrow Transplant 20:479–483

    Article  PubMed  CAS  Google Scholar 

  172. Jones LR, Toth BB, Keene HJ (1992) Effects of total body irradiation on salivary gland function and caries-associated oral microflora in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol 73:670–676

    Article  PubMed  CAS  Google Scholar 

  173. Chaushu G, Itzkovitz-Chaushu S, Yefenof E, Slavin S, Or R, Garfunkel AA (1995) A longitudinal follow-up of salivary secretion in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:164–169

    Article  PubMed  CAS  Google Scholar 

  174. Dens F, Boogaerts M, Boute P, Declerck D, Demuynck H, Vinckier F, Belgium B (1996) Caries-related salivary microorganisms and salivary flow rate in bone marrow recipients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:38–43

    Article  PubMed  CAS  Google Scholar 

  175. Coracin FL, Pizzigatti Correa ME, Camargo EE, Peterson DE, de Oliveira SA, Vigorito AC, Borba OG, de Brito Eid KA, Zulli R, De Souza CA (2006) Major salivary gland damage in allogeneic hematopoietic progenitor cell transplantation assessed by scintigraphic methods. Bone Marrow Transplant 37:955–959

    Article  PubMed  CAS  Google Scholar 

  176. Bagesund M, Richter S, Agren B, Ringden O, Dahllof G (2000) Scintigraphic study of the major salivary glands in pediatric bone marrow transplant recipients. Bone Marrow Transplant 26:775–779

    Article  PubMed  CAS  Google Scholar 

  177. Boguslawska-Kapala A, Cackowska-Lass A, Balon J, Hellmann A, Kochanska B (2006) Saliva secretion and abnormal moistening of oral mucosa after bone marrow transplantation. Bull Group Int Rech Sci Stomatol Odontol 47:1–5

    PubMed  Google Scholar 

  178. Dahllof G, Bagesund M, Remberger M, Ringden O (1997) Risk factors for salivary dysfunction in children 1 year after bone marrow transplantation. Oral Oncol 33:327–331

    Article  PubMed  CAS  Google Scholar 

  179. Wahlin YB (1991) Salivary secretion rate, yeast cells, and oral candidiasis in patients with acute leukemia. Oral Surg Oral Med Oral Pathol 71:689–695

    Article  PubMed  CAS  Google Scholar 

  180. Bergmann OJ (1991) Alterations in oral microflora and pathogenesis of acute oral infections during remission-induction therapy in patients with acute myeloid leukaemia. Scand J Infect Dis 23:355–366

    Article  PubMed  CAS  Google Scholar 

  181. Mansson-Rahemtulla B, Techanitiswad T, Rahemtulla F, McMillan TO, Bradley EL, Wahlin YB (1992) Analyses of salivary components in leukemia patients receiving chemotherapy. Oral Surg Oral Med Oral Pathol 73:35–46

    Article  PubMed  CAS  Google Scholar 

  182. Karolewska E, Konopka T, Pupek M, Chybicka A, Mendak M (2008) Antibacterial potential of saliva in children with leukemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:739–744

    Article  PubMed  Google Scholar 

  183. Harrison T, Bigler L, Tucci M, Pratt L, Malamud F, Thigpen JT, Streckfus C, Younger H (1998) Salivary sIgA concentrations and stimulated whole saliva flow rates among women undergoing chemotherapy for breast cancer: an exploratory study. Spec Care Dentist 18:109–112

    Article  PubMed  CAS  Google Scholar 

  184. Jensen SB, Mouridsen HT, Reibel J, Brunner N, Nauntofte B (2008) Adjuvant chemotherapy in breast cancer patients induces temporary salivary gland hypofunction. Oral Oncol 44:162–173

    Article  PubMed  CAS  Google Scholar 

  185. Wickham RS, Rehwaldt M, Kefer C, Shott S, Abbas K, Glynn-Tucker E, Potter C, Blendowski C (1999) Taste changes experienced by patients receiving chemotherapy. Oncol Nurs Forum 26:697–706

    PubMed  CAS  Google Scholar 

  186. Avsar A, Elli M, Darka O, Pinarli G (2007) Long-term effects of chemotherapy on caries formation, dental development, and salivary factors in childhood cancer survivors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:781–789

    Article  PubMed  Google Scholar 

  187. El-Housseiny AA, Saleh SM, El-Masry AA, Allam AA (2007) Assessment of oral complications in children receiving chemotherapy. J Clin Pediatr Dent 31:267–273

    PubMed  Google Scholar 

  188. Laine P, Meurman JH, Tenovuo J, Murtomaa H, Lindqvist C, Pyrhonen S, Teerenhovi L (1992) Salivary flow and composition in lymphoma patients before, during and after treatment with cytostatic drugs. Eur J Cancer B Oral Oncol 28B:125–128

    Article  PubMed  CAS  Google Scholar 

  189. Sepet E, Aytepe Z, Ozerkan AG, Yalman N, Guven Y, Anak S, Devecioglu O, Agaoglu L, Gedikoglu G (1998) Acute lymphoblastic leukemia: dental health of children in maintenance therapy. J Clin Pediatr Dent 22:257–260

    PubMed  CAS  Google Scholar 

  190. Blomgren J, Jansson S, Rodjer S, Birkhed D (2002) Secretion rate from minor salivary glands in patients with malignant haematological diseases receiving chemotherapy—a pilot study. Swed Dent J 26:75–80

    PubMed  Google Scholar 

  191. Nasman M, Bjork O, Soderhall S, Ringden O, Dahllof G (1994) Disturbances in the oral cavity in pediatric long-term survivors after different forms of antineoplastic therapy. Pediatr Dent 16:217–223

    PubMed  CAS  Google Scholar 

  192. Meurman JH, Laine P, Keinanen S, Pyrhonen S, Teerenhovi L, Lindqvist C (1997) Five-year follow-up of saliva in patients treated for lymphomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83:447–452

    Article  PubMed  CAS  Google Scholar 

  193. Meurman JH, Laine P, Lindqvist C, Pyrhonen S, Teerenhovi L (1994) Effect of anticancer drugs on patients with and without initially reduced saliva flow. Eur J Cancer B Oral Oncol 30B:204–208

    Article  PubMed  CAS  Google Scholar 

  194. Marmary Y, Shiloni E, Katz J (1992) Oral changes in interleukin-2 treated patients: a preliminary report. J Oral Pathol Med 21:230–231

    Article  PubMed  CAS  Google Scholar 

  195. Nagler A, Nagler R, Ackerstein A, Levi S, Marmary Y (1997) Major salivary gland dysfunction in patients with hematological malignancies receiving interleukin-2-based immunotherapy post-autologous blood stem cell transplantation (ABSCT). Bone Marrow Transplant 20:575–580

    Article  PubMed  CAS  Google Scholar 

  196. Nagler RM, Gez E, Rubinov R, Laufer D, Ben-Aryeh H, Gaitini D, Filatov M, Kuten A (2001) The effect of low-dose interleukin-2-based immunotherapy on salivary function and composition in patients with metastatic renal cell carcinoma. Arch Oral Biol 46:487–493

    Article  PubMed  CAS  Google Scholar 

  197. Cella DF, Cherin EA (1988) Quality of life during and after cancer treatment. Compr Ther 14:69–75

    PubMed  CAS  Google Scholar 

  198. Langius A, Bjorvell H, Lind MG (1993) Oral- and pharyngeal-cancer patients' perceived symptoms and health. Cancer Nurs 16:214–221

    PubMed  CAS  Google Scholar 

  199. Wijers OB, Levendag PC, Braaksma MM, Boonzaaijer M, Visch LL, Schmitz PI (2002) Patients with head and neck cancer cured by radiation therapy: a survey of the dry mouth syndrome in long-term survivors. Head Neck 24:737–747

    Article  PubMed  Google Scholar 

  200. Al-Nawas B, Al-Nawas K, Kunkel M, Grotz KA (2006) Quantifying radioxerostomia: salivary flow rate, examiner's score, and quality of life questionnaire. Strahlenther Onkol 182:336–341

    Article  PubMed  Google Scholar 

  201. Allal AS, Dulguerov P, Bieri S, Lehmann W, Kurtz JM (2000) Assessment of quality of life in patients treated with accelerated radiotherapy for laryngeal and hypopharyngeal carcinomas. Head Neck 22:288–293

    Article  PubMed  CAS  Google Scholar 

  202. Lin SC, Jen YM, Chang YC, Lin CC (2008) Assessment of xerostomia and its impact on quality of life in head and neck cancer patients undergoing radiotherapy, and validation of the Taiwanese version of the xerostomia questionnaire. J Pain Symptom Manage 36:141–148

    Article  PubMed  Google Scholar 

  203. Eisbruch A, Rhodus N, Rosenthal D, Murphy B, Rasch C, Sonis S, Scarantino C, Brizel D (2003) How should we measure and report radiotherapy-induced xerostomia? Semin Radiat Oncol 13:226–234

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Research Librarian Susie Andersen, Deputy Head of the Panum Library, Faculty of Health Sciences, University of Copenhagen, Denmark, for expert assistance with the systematic literature search. We also thank Tainika Williams, Department of Oral Medicine, Carolinas Medical Center, North Carolina, USA, for her overall skills with literature search.

Conflicts of interest

The authors declared that they have no potential conflicts of interests.

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Authors and Affiliations

  1. Department of Oral Medicine, Clinical Oral Physiology, Oral Pathology & Anatomy, Institute of Odontology, Faculty of Health Sciences, University of Copenhagen, Nørre Allé 20, 2200, Copenhagen, Denmark

    S. B. Jensen & A. M. L. Pedersen

  2. Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands

    A. Vissink & F. K. L. Spijkervet

  3. Department of Oncology, Herlev University Hospital, Herlev Ringvej, 2730, Herlev, Denmark

    E. Andersen

  4. School of Nursing, College of Health Sciences, University of Delaware, Newark, DE, 19716, USA

    C. G. Brown

  5. Department of Palliative Medicine, Royal Marsden Hospital, Sutton, SM2 5P5, UK

    A. N. Davies

  6. Dutilh Instituto de Reabilitação Facial e Oral, R. Paula Bueno 307, Taquaral, Brazil

    J. Dutilh

  7. Department of Adult Health, Indiana University School of Nursing, 1111 Middle Drive, Indianapolis, IN, 46202, USA

    J. S. Fulton

  8. Clinic for Periodontology and Oral Medicine, Faculty of Stomatology, University of Belgrade, P.O. Box 506, 11000, Belgrade, Serbia

    L. Jankovic

  9. Pediatric Dentistry, Service of Oral Medicine, IOP-Pediatric Oncology Institute/GRAACC, Federal University of São Paulo, Rua Botucatu 743, CEP 04023-062, São Paulo, Brazil

    N. N. F. Lopes

  10. Department of Endocrinology, Federal University of São Paulo, Medicine Paulista School, Rua Pedro de Toledo 910, São Paulo, Brazil

    A. L. S. Mello

  11. Department of Odontology, Associação do Combate ao Câncer do Centro Oeste de Minas Gerais, Instituto de Pesquisas Oncológicas Minas Gerais, IPOM, Hospital do Câncer Centro Oeste de Minas Gerais, Minas Gerais, Brazil

    L. V. Muniz

  12. Department of Oral and Maxillofacial Surgery/Hospital Dentistry, School of Dentistry, University of Michigan, 1011 North University Ave, Ann Arbor, MI, 48109-1078, USA

    C. A. Murdoch-Kinch

  13. Centre for Medicine and Oral Health, Griffith University, Gold Coast Campus, QLD, 4222, Gold Coast, Australia

    R. G. Nair

  14. Department of Oral Medicine, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC, 28232, USA

    J. J. Napeñas, B. Stirling & M. T. Brennan

  15. Department of Oncology and Research, Associação do Combate ao Câncer do Centro Oeste de Minas Gerais, Instituto de Pesquisas Oncológicas Minas Gerais, IPOM, Hospital do Câncer Centro Oeste de Minas Gerais, Minas Gerais, Brazil

    A. Nogueira-Rodrigues

  16. Department of Dentistry, Sudbury Regional Hospital Cancer Program, Hôpital régional de Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, ON, P3E 5J1, Canada

    D. Saunders

  17. Departments of Oral Immunology and Oral Medicine, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Medicinaregaten 12, 413 90, Gothenburg, Sweden

    I. von Bültzingslöwen

  18. Department of Pathology and Diagnostic Sciences, University of Maryland Dental School and Greenebaum Cancer Center, Baltimore, MD, 21201, USA

    D. S. Weikel

  19. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    L. S. Elting

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  1. S. B. Jensen
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  2. A. M. L. Pedersen
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  3. A. Vissink
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  4. E. Andersen
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  10. N. N. F. Lopes
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  15. J. J. Napeñas
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  18. B. Stirling
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  22. F. K. L. Spijkervet
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  23. M. T. Brennan
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Consortia

Salivary Gland Hypofunction/Xerostomia Section, Oral Care Study Group, Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO)

Corresponding author

Correspondence to S. B. Jensen.

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Jensen, S.B., Pedersen, A.M.L., Vissink, A. et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18, 1039–1060 (2010). https://doi.org/10.1007/s00520-010-0827-8

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  • DOI: https://doi.org/10.1007/s00520-010-0827-8

Keywords

  • Cancer therapy
  • Radiotherapy
  • Chemotherapy
  • Salivary gland hypofunction
  • Xerostomia
  • Quality of life