New insights in cisplatin and radiation-induced ototoxicity: A French Childhood Cancer Survivors Study (FCCSS).

Authors

null

Brice Fresneau

Children and Adolescent Oncology Department, Gustave Roussy, Villejuif, France

Brice Fresneau , Felicia Santos , Rodrigue Allodji , Chiraz Fayech , Stephanie Bolle , Giao Vu-Bezin , Vincent Souchard , Nadia Haddy , Francois P. Doz , Delphine Berchery , Pierre Lemire , Neige Journy , Cristina Veres , Laurence Brugieres , Dominique Valteau-Couanet , Ibrahima Diallo , Christelle Dufour , Florent De Vathaire

Organizations

Children and Adolescent Oncology Department, Gustave Roussy, Villejuif, France, Inserm U1018, Gustave Roussy, Villejuif, France, INSERM Unit 1018/Gustave Roussy, Villejuif, France, Department of Radiation Oncology, Gustave Roussy, Villejuif, France, Institut Curie, Paris, France, Claudius Regaud, Toulouse, France, INSERM, VIMA: Maladies Chroniques Et Vieillissement. Approches Épidémiologiques Et Santé Publique, Paris, France

Research Funding

Other Foundation

Background: Platinum chemotherapy (CT) and cranial radiotherapy (RT) are risk factors of ototoxicity. Effects of RT dose at inner ear and of other CT were investigated. Methods: Of 7670 5-year childhood cancer survivors from the FCCSS treated before 20 years of age in 1942-2000 for solid cancer or lymphoma, 5243 with ototoxicity long-term follow-up data were included. Severe ototoxicity, defined as the need of hearing aids or Brock grade 3-4 hearing loss, was identified from self-administrated questionnaires, clinical visits and cohort linkage with the French Hospital Database and health insurance information system (SNIIRAM). The mean RT dose at inner ear was estimated using home-made software. Multivariable Cox models adjusted for gender, age at diagnosis, time period and social deprivation index was used to identify risk factors for severe ototoxicity. Results: After a mean follow-up of 30 years, 199 cases of severe ototoxicity were identified. Cumulative incidences at 30 and 50 years of age (30,50y-CumInc) were, 2.8% (95%CI = 2.4-3.3) and 5.5% (4.6-6.5), respectively. Mean RT dose at inner ear (Hazard Ratio HR = 1.6 (95%CI = 1.0-2.5), 4.5 (2.7-7.2), 5.7 (3.0-10.8) and 14.0 (9.2-21.2) for 0- < 5, 5- < 30, 30- < 40 and ≥40 Gy), as well as cisplatin (HR = 2.8, 95%CI = 1.9-4.0), melphalan (HR = 3.3, 95%CI = 1.9-5.7) and busulfan exposure (HR = 2.6, 95%CI = 1.6-4.4) were significantly associated with severe ototoxicity. Concerning melphalan (n = 199/5243 exposed), almost all cases were identified in neuroblostma patients (NBL), who also received cisplatin 200mg/m²/cycle (26/92 NBL, 30y-CumInc = 36.4% (95%CI = 25.9-48.4), vs. 3/107 non-NBL, 30y-CumInc = 1.6% (0.4-5.6)). Concerning busulfan (n = 131/5243 exposed), all cases were identified in NBL (n = 16/63, all treated with melphalan and cisplatin) and brain tumors (n = 13/28, all with RT at inner ear ≥5Gy). The 30y-CumInc in patients with RT at inner ear ≥5Gy was 7.4% (95%CI = 5.7-9.6) and 39.8% (22.5-60.0) respectively with and without busulfan. Conclusions: RT at inner ear has significant deleterious impact on audition, with cumulative incidence still worsening > 30years after RT, and with likely potentiation by busulfan. The deleterious effect of melphalan was related to previous treatment with cisplatin, either by interaction between these drugs, or by the high cisplatin dose by cycle used in NBL.

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Pediatric Oncology

Track

Pediatric Oncology

Sub Track

Survivorship

Citation

J Clin Oncol 37, 2019 (suppl; abstr 10061)

DOI

10.1200/JCO.2019.37.15_suppl.10061

Abstract #

10061

Poster Bd #

443

Abstract Disclosures