Ototoxicity after combined platinum and fractionated radiation in a novel guinea pig model

Miller, Matthew W.; Riedel, Gunther; Hoistad, Dick; Sutherland, Carolyn; Juhn, Steven K.; Adams, George L.; Griffin, Robert; Ondrey, Frank G.

doi:10.1016/j.amjoto.2007.12.003

« Previous Next »American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Volume 30, Issue 1 , Pages 1-7, January 2009

Ototoxicity after combined platinum and fractionated radiation in a novel guinea pig model

Portions presented at Annual Meetings of the AAO-HNS and an International Meeting of Otolaryngology Department, University of Minnesota/Karolinska Institutes, Minneapolis, MN.

Matthew W. Miller, MD, MS
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
Gunther Riedel, MD
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
Dick Hoistad, MD
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
Carolyn Sutherland, BS
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
Steven K. Juhn, MD
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
George L. Adams, MD
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
- Deceased.
Robert Griffin, PhD
- Radiation Physics Department, University of Minnesota, Minneapolis, MN, USA
Frank G. Ondrey, MD, PhD
- Otolaryngology Department, University of Minnesota, Minneapolis, MN, USA
- Corresponding author. Otolaryngology Department, University of Minnesota, MMC 396, Minneapolis, MN, USA. Tel.: +1 612 624 9449; fax: +1 612 625 2101.

Received 9 October 2007 published online 20 June 2008.

Abstract

Purpose

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.

Materials and 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.