Robert D Frisina1, Heather E Wheeler1, Sophie D Fossa1, Sarah L Kerns1, Chunkit Fung1, Howard D Sesso1, Patrick O Monahan1, Darren R Feldman1, Robert Hamilton1, David J Vaughn1, Clair J Beard1, Amy Budnick1, Eileen M Johnson1, Shirin Ardeshir-Rouhani-Fard1, Lawrence H Einhorn2, Steven E Lipshultz1, M Eileen Dolan1, Lois B Travis1. 1. Robert D. Frisina, University of South Florida, Tampa, FL; Heather E. Wheeler, Loyola University Chicago; M. Eileen Dolan, University of Chicago, Chicago, IL; Sophie D. Fossa, Oslo University Hospital, Radiumhospital, Oslo, Norway; Sarah L. Kerns, Chunkit Fung, and Eileen M. Johnson, J.P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester; Darren R. Feldman and Amy Budnick, Memorial Sloan Kettering Cancer Center, New York, NY; Howard D. Sesso, Brigham and Women's Hospital; Clair J. Beard, Dana-Farber Cancer Institute, Boston, MA; Patrick O. Monahan, Shirin Ardeshir-Rouhani-Fard, Lawrence H. Einhorn, and Lois B. Travis, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Robert Hamilton, Princess Margaret Cancer Centre, Toronto, ON; David J. Vaughn, University of Pennsylvania, Philadelphia, PA; and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI. 2. Robert D. Frisina, University of South Florida, Tampa, FL; Heather E. Wheeler, Loyola University Chicago; M. Eileen Dolan, University of Chicago, Chicago, IL; Sophie D. Fossa, Oslo University Hospital, Radiumhospital, Oslo, Norway; Sarah L. Kerns, Chunkit Fung, and Eileen M. Johnson, J.P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester; Darren R. Feldman and Amy Budnick, Memorial Sloan Kettering Cancer Center, New York, NY; Howard D. Sesso, Brigham and Women's Hospital; Clair J. Beard, Dana-Farber Cancer Institute, Boston, MA; Patrick O. Monahan, Shirin Ardeshir-Rouhani-Fard, Lawrence H. Einhorn, and Lois B. Travis, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Robert Hamilton, Princess Margaret Cancer Centre, Toronto, ON; David J. Vaughn, University of Pennsylvania, Philadelphia, PA; and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI. leinhorn@iupui.edu.
Abstract
PURPOSE: Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. PATIENTS AND METHODS: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. RESULTS: Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. CONCLUSION: Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing.
PURPOSE:Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. PATIENTS AND METHODS: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. RESULTS: Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. CONCLUSION: Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing.
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