title: Parotid glands dose-effect relationships based on their actually delivered doses: implications for adaptive replanning in radiation therapy of head-and-neck cancer.
abstract: OBJECTIVE
  Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses.
  
  
  METHODS
  In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative delivered doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy.
  
  
  RESULTS
  Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were -4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose-effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments.
  
  
  CONCLUSIONS
  After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose-saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Klaudia U
authors.initials: KU
authors.lastname: Hunter
authors.forename: Laura L
authors.initials: LL
authors.lastname: Fernandes
authors.forename: Karen A
authors.initials: KA
authors.lastname: Vineberg
authors.forename: Daniel
authors.initials: D
authors.lastname: McShan
authors.forename: Alan E
authors.initials: AE
authors.lastname: Antonuk
authors.forename: Craig
authors.initials: C
authors.lastname: Cornwall
authors.forename: Mary
authors.initials: M
authors.lastname: Feng
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Schipper
authors.forename: James M
authors.initials: JM
authors.lastname: Balter
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D054893:Cone-Beam Computed Tomography / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects*; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010306:Parotid Gland / Q000378:metabolism / Q000528:radiation effects*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D061106:Radiotherapy Setup Errors / Q000517:prevention & control; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012463:Saliva / Q000378:metabolism; D012472:Salivation / Q000528:radiation effects*
chemical_list: D016190:Carboplatin; D017239:Paclitaxel
references.citation: Radiother Oncol. 2011 Dec;101(3):343-50
references.pmid: 21724283
references.citation: Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):924-32
references.pmid: 19801104
references.citation: Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):355-62
references.pmid: 16256277
references.citation: Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):986-93
references.pmid: 22138459
references.citation: Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):373-82
references.pmid: 18337023
references.citation: Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):695-704
references.pmid: 11395238
references.citation: Br J Radiol. 2012 Aug;85(1016):1070-7
references.pmid: 22815411
references.citation: Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S58-63
references.pmid: 20171519
references.citation: Int J Radiat Oncol Biol Phys. 2010 Apr;76(5):1360-8
references.pmid: 20338474
references.citation: Med Phys. 2008 Dec;35(12):5944-53
references.pmid: 19175149
references.citation: Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1220-8
references.pmid: 17336222
references.citation: Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1121-30
references.pmid: 17398025
references.citation: Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1451-60
references.pmid: 15050323
references.citation: Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):960-70
references.pmid: 15234029
references.citation: Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):659-64
references.pmid: 15936542
references.citation: Med Image Comput Comput Assist Interv. 2011;14(Pt 1):548-55
references.pmid: 22003661
references.citation: Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):1108-14
references.pmid: 21640505
references.citation: Int J Radiat Oncol Biol Phys. 1999 Oct 1;45(3):577-87
references.pmid: 10524409
references.citation: Int J Radiat Oncol Biol Phys. 2010 Oct 1;78(2):449-53
references.pmid: 20056347
references.citation: Radiother Oncol. 2013 Jan;106(1):85-9
references.pmid: 23337058
references.citation: Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1290-6
references.pmid: 17967319
references.citation: Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):1007-14
references.pmid: 22056067