Hearing loss among survivors of childhood brain tumors treated with an irradiation‐sparing approach

Orgel, Etan; Jain, Shveta; Ji, Lingyun; Pollick, Liora; Si, Stephanie; Finlay, Jonathan L.; Freyer, David R.

doi:10.1002/pbc.23275

Cited by 37 publications

(23 citation statements)

References 37 publications

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“…[11] Permanent sensorineural hearing loss (SNHL) has since become one of the principal late effects of irradiationsparing regimens, affecting over half of those exposed to the chemotherapy agent cisplatin. [12][13][14] In the general pediatric and non-brain tumor populations, even mild or unilateral hearing loss (HL) is associated with poorer academic performance, language acquisition, and quality of life. [15][16][17][18][19] Schreiber et al recently reported on SNHLassociated declines in intelligence and achievement in a pediatric brain tumor population.…”

Section: Introductionmentioning

confidence: 99%

Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors

Orgel

O’Neil

Kayser

et al. 2015

Pediatr Blood Cancer

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Background Intensified therapy with platinum-based regimens for pediatric brain tumors has dramatically increased the number of pediatric brain tumor survivors (PBTS) but frequently causes permanent sensorineural hearing loss (SNHL). Although neurocognitive decline in PBTS is known to be associated with radiation therapy (RT), SNHL represents a potential additional contributor whose long-term impact has yet to be fully determined. Methods The neurocognitive impact of significant SNHL (Chang Scale ≥2b) in PBTS was assessed through a retrospective cohort study of audiograms and neurocognitive testing. Scores for neurocognitive domains and subtest task performance were analyzed to identify specific strengths and weakness for PBTS with SNHL. Results In a cohort of PBTS (n=58) treated with platinum therapy, significant SNHL was identified in over half (55%, n=32/58), of which the majority required hearing aids (72%, 23/32). RT exposure was approximately evenly divided between those with and without SNHL. PBTS were 6.7±0.6 and 11.3±0.7 years old at diagnosis and neurocognitive testing, respectively. In multivariate analyses adjusted for RT dose, SNHL was independently associated with deficits in intelligence, executive function, and verbal reasoning skills. Subtests revealed PBTS with SNHL to have poor learning efficiency but intact memory and information acquisition. Conclusion SNHL in PBTS increases the risk for severe therapy-related intellectual and neurocognitive deficits. Additional prospective investigation in malignant brain tumors is necessary to validate these findings through integration of audiology and neurocognitive assessments and to identify appropriate strategies for neurocognitive screening and rehabilitation specific to PBTS with and without SNHL.

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Section: Introductionmentioning

confidence: 99%

Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors

Orgel

O’Neil

Kayser

et al. 2015

Pediatr Blood Cancer

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“…As reviewed by Rybak (2005), hearing loss occurs in 30 to 100% of patients treated with cisplatin. Hearing loss may occur during treatment (Knight et al, 2005(Knight et al, , 2007Orgel et al, 2012) or after discontinuation of chemotherapy (Al-Khatib et al, 2010;Kolinsky et al, 2010). Furthermore, patients treated with cisplatin exhibit severe difficulty in word recognition (Einarsson et al, 2011), suggesting a central component in their hearing loss.…”

Section: Introductionmentioning

confidence: 99%

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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Cisplatin is a platinum-based chemotherapeutic agent widely used for the treatment of various types of cancer. Patients undergoing cisplatin treatment often suffer from a condition known as "chemobrain", ototoxicity, peripheral neuropathy, weight loss, nausea, vomiting, nephrotoxicity, seizures, hearing loss and tinnitus.D-Methionine (D-Met), a sulfur-containing nucleophilic antioxidant, has been shown to prevent cisplatininduced side effects in animals without antitumor interference. In this study, we have used an in vitro model of cortical networks (CNs), enriched in auditory cortex cells; to quantify cisplatin neurotoxicity and the protective effects of D-Met. Dissociated neurons from auditory cortices of mouse embryos were grown on microelectrode arrays with 64 transparent indium-tin oxide electrodes, which enabled continuous optical and electrophysiological monitoring of network neurons. Cisplatin at 0.10-0.25 mM induced up to a 200% increase in spontaneous spiking activity, while concentrations at or above 0.5 mM caused irreversible loss of neuronal activity, accompanied by cell death. Pretreatment with D-Met, at a concentration of 1.0 mM, prevented the cisplatin-induced excitation at 0.10-0.25 mM, caused sustained excitation without occurrence of cell death at 0.5 mM, and delayed cell death at 0.75 mM cisplatin. L-Methionine, the optical isomer, showed lower potency and less efficacy than D-Met, was less protective against 0.1 mM cisplatin, and proved ineffective at a concentration of 0.5 mM cisplatin. Pre-exposure time of D-Met was associated with the protective effects at 0.1 and 0.5 mM cisplatin, with longer pre-exposure times exhibiting better protection. This study quantifies as a function of concentration and time that D-Met protects central nervous system tissue from acute cisplatin toxicity.

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“…At T1, the Parental Emotional Impact fell outside the average range, and at T2, survivors' General Health fell outside the average range. Auditory outcomes in survivors treated using similar protocols have been published [30,[34][35][36][38][39][40]. However, late effects data regarding physical outcomes from other initial irradiation-sparing/delaying studies are sparse [26][27][28][29][30][31][32][33][34][35][36][37][38].…”

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Late effects in survivors of childhood CNS tumors treated on Head Start I and II protocols

Saha

Salley

Saigal

et al. 2014

Pediatr Blood Cancer

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Background Due to the devastating late effects associated with cranial irradiation in young children with CNS tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. Objective This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. Methods Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. Results Twenty one survivors (medulloblastoma=13, sPNET=4, ATRT=1, ependymoma=3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included ≥ grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years) and dental (52%; 7.1 years) and no cases of secondary leukemia. Irradiation-free (versus irradiated) survivors reported low rates of hypothyroidism (0/10 vs 7/11; p=0.004) and GH deficiency (2/10 vs 8/11; p=0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation were associated with these scores. Conclusions Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.

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Hearing loss among survivors of childhood brain tumors treated with an irradiation‐sparing approach

Cited by 37 publications

References 37 publications

Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors

Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Late effects in survivors of childhood CNS tumors treated on Head Start I and II protocols

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