title: Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer.
abstract: Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. p.van.luijk@umcg.nl r.p.coppes@umcg.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pringle
authors.affiliation: Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Vitali V
authors.initials: VV
authors.lastname: Moiseenko
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, Netherlands.
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.affiliation: British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Hovan
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Baanstra
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
authors.forename: Hans P
authors.initials: HP
authors.lastname: van der Laan
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
authors.forename: Roel G J
authors.initials: RG
authors.lastname: Kierkels
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Schaaf
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Witjes
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Accelerator Department, Paul Scherrer Institut, CH-5212 Villigen, Switzerland.
authors.forename: Jacobus M
authors.initials: JM
authors.lastname: Schippers
authors.affiliation: KVI Center for Advanced Radiation Technology, University of Groningen, 9747 AA Groningen, Netherlands.
authors.forename: Sytze
authors.initials: S
authors.lastname: Brandenburg
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada.
authors.forename: Jonn
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands. Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, Netherlands. p.van.luijk@umcg.nl r.p.coppes@umcg.nl.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000818:Animals; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D010306:Parotid Gland / Q000378:metabolism / Q000528:radiation effects*; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D013234:Stem Cells / Q000166:cytology*; D014987:Xerostomia