Evaluating the tradeoffs between patient survival and treatment toxicity has been, and always will be, a major challenge to clinicians. Treatment options that improve the Disease Free Survival (DFS) rate are often accompanied by increased side effects whereas options with lower DFS rates are usually less toxic. The administration of Cisplatin to pediatric germ cell tumor patients entails a tradeoff between mortality and ototoxicity. Increasing the dose of Cisplatin from 100mg to 200mg raises the DFS rate from 82% to 92%, yet also results in an increased incidence of permanent hearing loss, from 20% to 76%. The primary goal of this project is to evaluate whether the increase in cancer survival is worth the increased risk of suffering the functional impacts of Cisplatin ototoxicity. The project will proceed in four sequential aims: (1) To understand the hearing impairments due to alternative Cisplatin dosages. Data available from a recent (unpublished) CCG protocol will be used for finding a probability distribution of hearing deficits as a function of dosage. (2) To study the Quality of Life (QOL) consequences and construct health vignettes for decision analysis. Specific hearing deficits will be mapped onto their corresponding patient functional states. This summarizes the real-life difficulties as a result of hearing loss from Cisplatin treatment. Functional status of the child will be assessed by validated inventories from parental ratings and child self-assessments (N = 60). (3) To elicit parental utilities on hearing vignettes constructed from functional results. Using the Standard Gamble and an analog rating scale, five groups of parents will be asked to assign utilities to various hearing vignettes constructed from aim 2 (N = 20 per group). Group differences will be compared. (4) Finally, to perform decision and sensitivity analyses to determine the normative Cisplatin dosage. Preliminary recommendations will be made involving the use of high dose Cisplatin in pediatric germ cell patients. A Markov model is proposed, which extends the time horizon of the analysis and considers hearing deterioration, cancer relapse, second cancer, pediatric cancer, late effects in other organ systems, and additional functional deficits due to salvage regimes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC004486-03
Application #
6628403
Study Section
Special Emphasis Panel (ZDC1-SRB-O (23))
Program Officer
Freeman, Nancy
Project Start
2001-02-15
Project End
2005-07-31
Budget Start
2003-02-01
Budget End
2005-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$85,000
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Li, Yuelin; Steinberg, Annie G; Bain, Lisa et al. (2007) Assessing parental attitudes toward genetic testing for childhood hearing loss: before and after genetic consultation. Am J Med Genet A 143A:1546-53
Li, Yuelin (2006) Using the open-source statistical language R to analyze the dichotomous Rasch model. Behav Res Methods 38:532-41
Li, Yuelin; Bain, Lisa; Steinberg, Annie G (2004) Parental decision-making in considering cochlear implant technology for a deaf child. Int J Pediatr Otorhinolaryngol 68:1027-38
Li, Y; Womer, R B; Silber, J H (2004) Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer 40:2445-51