title: Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy.
abstract: OBJECTIVE
  Submandibular salivary glands (SMGs) dysfunction contributes to xerostomia after radiotherapy (RT) of head-and-neck (HN) cancer. We assessed SMG dose-response relationships and their implications for sparing these glands by intensity-modulated radiotherapy (IMRT).
  
  
  METHODS
  A total of 148 HN cancer patients underwent unstimulated and stimulated SMG salivary flow rate measurements selectively from Wharton's duct orifices, before RT and periodically through 24 months after RT. Correlations of flow rates and mean SMG doses were modeled throughout all time points. IMRT replanning in 8 patients whose contralateral level I was not a target incorporated the results in a new cost function aiming to spare contralateral SMGs.
  
  
  RESULTS
  Stimulated SMG flow rates decreased exponentially by (1.2%)(Gy) as mean doses increased up to 39 Gy threshold, and then plateaued near zero. At mean doses < or =39 Gy, but not higher, flow rates recovered over time at 2.2%/month. Similarly, the unstimulated salivary flow rates decreased exponentially by (3%)(Gy) as mean dose increased and recovered over time if mean dose was <39 Gy. IMRT replanning reduced mean contralateral SMG dose by average 12 Gy, achieving < or =39 Gy in 5 of 8 patients, without target underdosing, increasing the mean doses to the parotid glands and swallowing structures by average 2-3 Gy.
  
  
  CONCLUSIONS
  SMG salivary flow rates depended on mean dose with recovery over time up to a threshold of 39 Gy. Substantial SMG dose reduction to below this threshold and without target underdosing is feasible in some patients, at the expense of modestly higher doses to some other organs.
authors.affiliation: Department of Oral Medicine/Hospital Dentistry, University of Michigan, Ann Arbor, MI 48109-0010, USA.
authors.forename: Carol-Anne
authors.initials: CA
authors.lastname: Murdoch-Kinch
authors.forename: Hyugnjin M
authors.initials: HM
authors.lastname: Kim
authors.forename: Karen A
authors.initials: KA
authors.lastname: Vineberg
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ship
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D011832:Radiation Injuries / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated; D012472:Salivation; D013363:Submandibular Gland / Q000528:radiation effects*; D014987:Xerostomia / Q000209:etiology / Q000517:prevention & control