Severe Hearing Loss From Ototoxic Cancer Therapies in Childhood Tied to Neurocognitive Deficits

By Linda Carroll

August 03, 2020

(Reuters Health) — Severe hearing impairment in childhood cancer survivors is associated with neurocognitive deficits, a new study suggests.

An analysis of data from more than 1,500 childhood cancer survivors who were tested a median 20 years after their original cancer diagnosis revealed that severe hearing loss linked to ototoxic therapies was associated with deficits in verbal reasoning skills, verbal fluency, visuomotor speed and mathematics skills, according to the results in JAMA Oncology.

"This is the first study to measure hearing impairment and neurocognition in a large cohort of long-term survivors," said Johnnie Bass, a research audiologist at St. Jude's Children's Research Hospital. "We found that hearing loss from ototoxic cancer treatment was prevalent - over a third of the children had severe hearing loss. And hearing loss was associated with an increased risk of neurocognitive deficits. The main take-home point is to underscore the importance of early identification and intervention in children with hearing impairment because it does help improve cognitive abilities."

Data for the study were collected between April 25, 2007 and June 30, 2017. Individuals were included in the study if they had survived a childhood cancer for five or more years after their original diagnosis and if they were eligible for audiologic and neurocognitive testing. Of the 1,678 survivors identified, 1,520 participated in the study, with 740 never exposed to an ototoxic therapy, 307 exposed to a platinum-based therapy only, and 437 exposed to cranial radiotherapy with or without a platinum-based therapy.

The participants, whose median age was 29 years (range 7.4-64.7), completed a standard battery of developmentally and age-appropriate neurocognitive assessments, which measured intelligence, attention, memory, executive function, processing speed and academic function. They also were assessed via otoscopy, tympanometry, pure tone audiometry and speech audiometry.

Survivors who were not exposed to either of the two ototoxic treatments did not differ from those who received platinum-based therapy, but were slightly younger at diagnosis than those treated with cranial radiotherapy.

Severe hearing loss occurred in 107 (84.9%) of those who received platinum-based therapy, 181 (38.3%), of those who received cranial radiotherapy and 65 (8.8%) of those who were not exposed to an ototoxic treatment.

Compared with those who had normal hearing or mild hearing impairment, survivors with severe hearing impairment in the platinum-based treatment and the cranial radiotherapy groups were more likely to have impaired focused attention (relative risks, 2.56 and 1.57, respectively) and impaired cognitive flexibility (RRs, 1.64 and 1.34).

The presence of severe hearing impairment in survivors was significantly associated with slower visuomotor speed among those with no exposure (RR 1.87), those treated with platinum therapy (RR 3.10) and those who received cranial radiotherapy (RR 1.40).

While it's been long known that these therapies can damage hearing, the new study provides information on how that hearing loss can negatively impact other aspects of learning, said Dr. Jean Tersak, a pediatric oncologist at the UPMC Children's Hospital of Pittsburgh.

"The impact of hearing impairment delineated in this article and the impact on medical late effects and quality of life are very significant," Dr. Tersak said in an email. "It is our obligation to understand these types of late effects to minimize adverse impacts of the therapy."

One of the strengths of the new study is the inclusion of cancer survivors who weren't treated with any known ototoxic agents, said Dr. Enrique Perez, an assistant professor of otolaryngology and director of otology at Mount Sinai in New York City.

That makes the connection between cognitive deficits and hearing loss due to the ototoxic agents stronger, Dr. Perez said.

Nevertheless, the study does have the limitation that it is it is cross sectional, Dr. Perez said. "So you can't really determine the temporal course of these things," he added.

"In the end, the take-home message is something we know even in the pediatric population that doesn't have cancer," Dr. Perez said. "It stresses the importance of early intervention in patients with known hearing loss. There is a potential for them to catch up or stay even with their peers and not have to fall way behind in the educational path."

SOURCE: and JAMA Oncology, online July 30, 2020.