Hearing Loss Deepens Cognitive Deficits in Pediatric Cancer Survivors

Childhood cancer survivors who experienced severe treatment-related hearing impairment had a greater risk for neurocognitive deficits, independent of whether they had received neurotoxic treatment, a cross-sectional study found.

In an analysis of over 1,500 survivors, those with severe hearing loss were more likely to suffer deficits in verbal fluency and reasoning, visuomotor speed, and math skills compared to those with mild hearing loss or normal hearing, reported Johnnie Bass, PhD, of St. Jude Children's Research Hospital in Memphis, Tennessee.

As described in JAMA Oncology, compared to patients who did not receive potentially ototoxic therapies, severe hearing impairment was significantly associated with exposure to cochlear radiotherapy (relative risk 2.69, 95% CI 2.02-3.57) or platinum-based chemotherapy (RR 1.68, 95% CI, 1.20-2.37).

"There has been a lot of research on how children who are born deaf can be affected academically and psychosocially, but far less for kids who acquire hearing loss at some point during their childhood," Bass said in a statement. "Our goal was to report on the prevalence, severity and risk of hearing loss in a large cohort of cancer survivors to assess the impact of hearing impairment on neurocognitive function."

Among those with severely impaired hearing, exposure to platinum-containing chemotherapy was significantly associated with deficits in multiple cognitive domains, including:

• Reading skills (RR 3.47, 95% CI 1.56-7.73)
• Math skills (RR 1.63, 95% CI 1.05-2.53)
• Verbal reasoning (RR 1.93, 95% CI 1.21-3.08)
• Verbal fluency (RR 1.83, 95% CI 1.24-2.71)
• Visuomotor speed (RR 3.10, 95% CI 1.92-4.99)

Similarly, exposure to cochlear radiation therapy was significantly associated with deficits in:

• Verbal reasoning (RR 2.00, 95% CI 1.46-2.75)
• Verbal fluency (RR 1.45, 95% CI 1.09-1.94)
• Reading (RR 2.31, 95% CI 1.36-3.92)
• Math (RR 1.58, 95% CI 1.15-2.18)
• Visuomotor speed (RR 1.40, 95% CI 1.11-1.78)

Patients not exposed to these ototoxic treatments, but with severe hearing loss, still had neurocognitive deficits in the domains of attention, memory, executive function, processing speed, and academic function, the researchers found.

"Even patients not exposed to neurotoxic therapies who develop mild hearing deficits can have problems with their neurocognitive skills," co-author Kevin Krull, PhD, also of St. Jude Children's Research Hospital, said in a statement. "This makes it important to identify these patients early and suggest interventions to help improve their hearing and thus their neurocognitive outcomes."

As part of their study, the researchers performed a mediation analysis to examine the association between cranial radiation and neurocognitive outcomes and found that severe hearing impairment accounted for 36% of the observed deficits in reading, 33% for verbal fluency, 20% for verbal memory, 27% for cognitive flexibility, 25% for fine motor speed, and 17% for visuomotor speed.

"The investigators demonstrated, for the first time to my knowledge, that severe hearing impairment mediates much of the association between CRT [cranial radiotherapy] and neurocognitive deficits among childhood cancer survivors treated with CRT," wrote Wendy Landier, PhD, CRNP, in an accompanying JAMA Oncology editorial. "This is a finding of particular importance given the potential for remediating the hearing impairment."

Landier noted several limitations of the study, including the lack of pretreatment neurocognitive assessments, a lack of data on factors that might have impaired patients' hearing, and on their frequency of hearing aid use (for those that used them at all).

The study also found that only 22.7% of survivors with severe hearing loss used a hearing aid or cochlear implant when indicated.

"These findings underscore the importance of providing parents with anticipatory guidance regarding the necessity of audiologic monitoring and management of children receiving potentially ototoxic agents," said Landier. "Pediatric oncology clinicians can foster parental understanding of the critical consequences of hearing loss for a young child's development, and set expectations for ongoing audiologic monitoring and early audiologic rehabilitation -- beginning during therapy and continuing throughout recovery. Audiologic intervention can be depicted as an essential component of the child's care and deemed part of the child's 'new normal.'"

For their study, Bass and colleagues examined outcomes in 1,520 childhood cancer survivors who were treated at St. Jude Children's Research Hospital and took part in the St. Jude Lifetime Cohort Study. Overall, 62.2% of the cohort had normal hearing following treatment, as defined by the Chang Ototoxicity Grading Scale, 14.5% had mild hearing impairment, and 23.2% had severe impairment.

The cohort included 307 patients who received platinum-based chemotherapy, 473 who received cranial radiation therapy, and 740 whose treatment was not considered ototoxic. Among these groups, 34.9%, 38.3%, and 8.8%, respectively had severe hearing loss.

Data were collected from 2007 to 2017, and included only patients who survived at least 5 years from their initial cancer diagnosis and had audiologic and neurocognitive testing. Slightly more of the participants were male (53.6%), the median patient age was 29.4 years (interquartile range 7.4-64.7), and the median time since diagnosis was 20.4 years (IQR 6.1-53.8).

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