Results highlight the need for early screening, intervention

In childhood cancer survivors, severe hearing impairment (HI) is associated with neurocognitive deficits that are unrelated to the cancer treatments they received, according to a recent study in JAMA Oncology. Clinicians are encouraged to conduct early screening and HI interventions in these patients, in an effort to not only maintain their neurocognitive function, but to identify those who are at highest risk for impairment as well.

“Long-term survival from childhood cancers now exceeds 85% in the United States. Despite major advancements in cancer therapy and supportive care, childhood cancer survivors remain at risk for chronic morbidities associated with disease and treatment, such as HI and neurocognitive deficits. Among survivors, those who received cranial radiotherapy (RT) for central nervous system (CNS) malignant neoplasms experience the highest risk for neurocognitive dysfunction,” wrote lead author Johnnie K. Bass, PhD, of St. Jude Children’s Research Hospital, Memphis, TN, and colleagues.

“Treatment-induced HI is associated with platinum-based chemotherapy or [RT] directed to the cochlea and is typically bilateral, permanent, and progressive,” they added.

Bass and colleagues, therefore, undertook this cross-sectional study to assess the relationship between HI and neurocognitive function in a large cohort of long-term childhood cancer survivors stratified by treatment exposures. They also sought to determine what factors of HI affect neurocognitive outcomes in survivors of childhood cancers.

They included 1,520 patients (median age: 29.4 years; median time since diagnosis: 20.4 years; 53.6% male) treated at St. Jude Children’s Research Hospital for childhood cancers who had survived ≥5 years after the original diagnosis.

Patients were grouped according to their hearing sensitivities as measured by otoscopy, tympanometry, pure-tone audiometry, and speech audiometry. Chang grades for permanent conductive or mixed HI were determined via air conduction thresholds as follows:

  • Normal hearing: Chang grade 0.
  • Mild HI: Chang grades 1a, 1b, and 2a.
  • Severe HI: Chang grade ≥2b.

Patients were also stratified according to treatment exposure into a platinum-only group (n=307; cisplatin and/or carboplatin chemotherapy), a cochlear RT exposure group (n=473; cochlear RT with/without platinum-based chemotherapy), and a no exposure group (n=740; no platinum-based chemotherapy or cochlear RT). Patients treated with cochlear RT were older at diagnosis compared with those in the other two groups, and also had longer follow-up.

Mild HI was most prevalent in the cochlear RT exposure group (22.2%), followed by those in the platinum-only exposure group (20.2%), and the no exposure group (7.3%).

Compared with those in the no exposure group, those in the platinum-only and cochlear RT groups had a higher prevalence and risk of severe HI. In the platinum-only group, 34.9% (n=107) had severe HI (RR: 1.68; 95% CI: 1.20-2.37), while in the cochlear RT group, 38.3% did so, compared with 8.8% of those in the no exposure group.

Bass and fellow researchers also found that severe HIs were associated with verbal reasoning skill deficits, verbal fluency, visuomotor speed, and mathematics skills compared with survivors with only mild HI or normal hearing as follows:

  • Verbal reasoning skill deficits: No exposure group (RR: 1.11; 95% CI: 0.50-2.43), platinum-only exposure group (RR: 1.93; 95% CI: 1.21-3.08), cochlear RT exposure group (RR: 2.00; 95% CI: 1.46-2.75).
  • Verbal fluency: No exposure group (RR: 1.86; 95% CI: 1.19-2.91), platinum-only exposure group (RR: 1.83; 95% CI: 1.24-2.71), and cochlear RT exposure group (RR: 1.45; 95% CI: 1.09-1.94).
  • Visuomotor speed: Platinum-only exposure group (RR: 3.10; 95% CI: 1.92-4.99), no exposure group (RR: 1.87; 95% CI: 1.07-3.25), and cochlear RT exposure group (RR: 1.40; 95% CI: 1.11-1.78).
  • Mathematics skills: No exposure group (RR: 1.90; 95% CI: 1.18-3.04), platinum-only exposure group (RR: 1.63; 95% CI: 1.05-2.53), cochlear RT exposure group (RR: 1.58; 95% CI: 1.15-2.18).

Further, Bass and colleagues found that severe HI was also associated with patient performance in less language dependent measures—including attention, executive function, and processing speed. Patients in the platinum-only and cochlear RT exposure groups were more likely to have impaired focused attention compared with those with normal hearing or only mild HI (RR: 2.56; 95% CI: 1.45-4.52 and RR: 1.57; 95% CI: 1.16-2.14, respectively). They were also more likely to have impaired cognitive flexibility (RR: 1.64; 95% CI: 1.15-2.34 and RR 1.34; 95% CI: 1.06-1.68).

Those with severe HI also had a significantly higher risk for inadequate fine motor speed compared with those without severe HI, with a 55% higher risk (RR: 1.55; 95% CI: 1.14-2.10) in the platinum-only exposure group and a 25% higher risk (RR: 1.25; 95% CI: 1.04-1.49) in the cochlear RT exposure group.

“Even survivors with milder forms of HI showed a 110% to 247% increased risk for neurocognitive dysfunction in the domains of attention, executive function, processing speed, and intelligence compared with normal-hearing survivors,” added Bass and colleagues.

“To our knowledge, the present study is the first to objectively measure hearing sensitivity and task-specific neurocognitive function in a large cohort of long-term survivors of childhood cancer stratified by treatment exposures. Consistent with our expectations, survivors with severe HI demonstrated impaired function on 1 or more neurocognitive tests,” they concluded.

Limitations of the study include its cross-sectional design; the exclusion of cancer survivors with preexisting neurodevelopmental/genetic conditions, and neurological injuries not related to treatment; lack of pretreatment neurocognitive assessments; and the small number of patients who used hearing interventions despite recommendations to do so.

Wendy Landier, PhD, CRNP, of the University of Alabama at Birmingham School of Medicine, Birmingham, AL, provided an editorial comment on these results.

“[T]he clinically ascertained data from this large study shines new light on the important association between severe hearing loss and impaired neurocognitive functioning among long-term survivors of childhood cancer. These findings suggest that nearly 1 in 4 of these survivors—the majority of whom now face the responsibilities of adulthood—have severe hearing impairment that may also be associated with deficits in neurocognitive functioning, potentially affecting day-to-day functioning,” she wrote.

Landier also stressed the importance of the finding from Bass et al that few patients made use of the recommended and available audiologic interventions.

“[F]indings highlighted by this study regarding the poor uptake of audiologic interventions among childhood cancer survivors should speak volumes to the clinicians caring for them. 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. 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,” she concluded.

  1. Survivors of childhood cancers are at increased risk for severe hearing impairment, which affected over one-third of the patients in this cross-sectional study.

  2. Compared with survivors with normal hearing or only mild hearing impairment, those who sustained severe hearing impairment are at increased risk for neurocognitive deficits.

E.C. Meszaros, Contributing Writer, BreakingMED™

This study was funded by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities.

Bass reported receiving grants from the National Cancer Institute.

Landier reported no conflicts of interest.

Cat ID: 138

Topic ID: 85,138,730,935,130,138,192