Simone Geiger de Almeida Selistre

Ototoxicity From Cisplatin Therapy in Childhood Cancer

Cisplatin has been associated with hearing damage. It is usually irreversible, bilateral, and characterized by high-frequency sensorineural hearing loss. This study was carried out to identify impairment of hearing function in children and adolescents with cancer after cisplatin therapy. Twenty-three survivors of childhood cancer treated with cisplatin at our Unit from 1991 to 2004 performed tympanometry, pure tone audiometry, transient otoacoustic emissions, and distortion product otoacoustic emissions (DPOAE). The median age at diagnosis was 12.3 years and the median total dose of cisplatin received was 406 mg/m2. Fifty-two percent of patients had bilateral and in the high frequencies range hearing loss on audiometry. Transient otoacoustic emission and DPOAE abnormalities were detected in 22% and in 71% of the patients, respectively. We found a high concordance between the findings of audiometry and DPOAE (P=0.01). There was no influence of sex and number of ototoxic drugs other than cisplatin on hearing loss. There was a trend for younger age and higher cumulative dose of cisplatin to be associated with greater severity of hearing damage. Our data provide further evidence on hearing damage due to cisplatin therapy in children. The high incidence of patients with hearing function abnormalities found in this study and in previous reports highlights the importance of monitoring hearing function in children and adolescents undergoing cisplatin therapy, or as early as possible at follow-up. This study also demonstrates that DPOAE should be used for screening of hearing abnormalities and, once hearing damage is identified, patients require expert audiologic pediatric evaluation and (where indicated) use of hearing aids and/or speech therapy.

Pediatric cancer and Li-Fraumeni/Li-Fraumeni-like syndromes: a review for the pediatrician

INTRODUCTION cancer is the second leading cause of death in children between the ages of 0 and 14 years, corresponding to approximately 3% of all cases diagnosed in Brazil. A significant percentage (5-10%) of pediatric cancers are associated with hereditary cancer syndromes, including Li-Fraumeni/Li-Fraumeni-like syndromes (LFS/LFL), both of which are caused by TP53 germline mutations. Recent studies have shown that a specific TP53 mutation, known as p.R337H, is present in 1 in 300 newborns in Southern and Southeast Brazil. In addition, a significant percentage of children with LFS/LFL spectrum tumors in the region have a family history compatible with LFS/LFL. OBJECTIVE to review clinical relevant aspects of LFS/LFL by our multidisciplinary team with focus on pediatric cancer. METHODS the NCBI (PubMed) and SciELO databases were consulted using the keywords Li-Fraumeni syndrome, Li-Fraumeni-like syndrome and pediatric cancer; and all manuscripts published between 1990 and 2014 using these keywords were retrieved and reviewed. CONCLUSION although LFS/LFL is considered a rare disease, it appears to be substantially more common in certain geographic regions. Recognition of population- specific risks for the syndrome is important for adequate management of hereditary cancer patients and families. In Southern and Southeastern Brazil, LFS/ LFL should be considered in the differential diagnosis of children with cancer, especially if within the spectrum of the syndrome. Due to the complexities of these syndromes, a multidisciplinary approach should be sought for the counseling, diagnosis and management of patients and families affected by these disorders. Pediatricians and pediatric oncologists in areas with high prevalence of hereditary cancer syndromes have a central role in the recognition and proper referral of patients and families to genetic cancer risk evaluation and management programs.