title: Ototoxicity after combined platinum and fractionated radiation in a novel guinea pig model.
abstract: OBJECTIVE
  Cis-platinum and radiation in combination are current organ preservation treatment strategies for head and neck cancer. Their individual ototoxicity has been investigated, with recent demonstration of ototoxicity in clinical studies. Currently, no ototoxicity studies have been performed in animals receiving similar schedules of radiation or cis-platinum to those patients with head and neck cancer.
  
  
  METHODS
  In the present study, an animal model was developed to investigate the effects of combined modality therapy on hearing. Albino guinea pigs were given equivalent protocol dosages of cis-platinum (3 parenteral courses), fractionated radiation (25 fractions over 5 weeks), or both. Click and tone burst auditory brainstem response (ABR) measurements were performed before and 6 weeks after the completion of treatment.
  
  
  RESULTS
  Animals receiving radiation or cis-platinum and radiation experienced permanent significant ABR shifts at all frequencies, with 33% of the animals experiencing complete unilateral sensorineural hearing loss at 2 or more frequencies in the ear receiving the full radiation dose (7075 cGy over 25 fractions) (P < .05, paired t test analysis). The animals receiving 3 doses of cis-platinum had no significant ABR threshold shifts at 6 weeks. These data suggest that cis-platinum and radiation cause greater ototoxicity than cis-platinum alone. These findings correlate closely with sensorineural hearing loss in combined modality patients at our institution and in recent studies.
  
  
  CONCLUSIONS
  We conclude that the current animal results parallel those seen clinically and serve as a model for ototoxicity from combined modality therapies in future protocols.
authors.affiliation: Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Miller
authors.forename: Gunther
authors.initials: G
authors.lastname: Riedel
authors.forename: Dick
authors.initials: D
authors.lastname: Hoistad
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sutherland
authors.forename: Steven K
authors.initials: SK
authors.lastname: Juhn
authors.forename: George L
authors.initials: GL
authors.lastname: Adams
authors.forename: Robert
authors.initials: R
authors.lastname: Griffin
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D002945:Cisplatin / Q000633:toxicity*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000209:etiology*; D011336:Probability; D011829:Radiation Dosage; D011897:Random Allocation; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D002945:Cisplatin