Audiological Monitoring May Be Necessary in Very Young Children Receiving Cisplatin Treatment

Cisplatin-induced hearing loss (CIHL) incidence is higher in children either 5 or under the age of 5, compared with older children, according to findings from a study published in Cancer.¹

Although the mechanism of action still requires further investigation, study results indicated that close audiological monitoring is necessary after each cisplatin cycle for children who are very young in age.

The study assessed a total of 368 pediatric patients with cancer and conducted 2052 audiological assessments. Patients under the age of 5 demonstrated the highest level of CIHL 3 years after treatment (75%; 95% CI, 66%-84%). The audiological assessments concluded that at 3 months, the incidence increased to 27% (95% CI, 21%-35%), and, that by 1 year, the incidence had increased to 61%. In comparison, at 1 year, the incidence detected in children who were over the age of 5 during treatment was 48% (95% CI, 37%-62%; P < .001).

In addition, the cumulative treatment of cisplatin (per 100 mg/m2 increase: HR,1.20; 95% CI, 1.01-1.41), vincristine (HR, 2.87; 95% CI, 1.89-4.36), and concomitantly administered antibiotics (>30 days: HR, 1.85; 95% CI, 1.17-2.95) all contributed to the development of CIHL over time.

“If possible, audiological monitoring at each cisplatin cycle during childhood cancer therapy would be desirable, particularly in young patients,” the study authors wrote. “Many contemporary clinical protocols mandate audiological assessments every second cycle of cisplatin, which might delay the early detection of hearing loss and the application of interventions such as dose reduction of subsequent cisplatin administration. Close audiological monitoring enables timely counseling regarding implications of the loss and compensatory strategies to mitigate its adverse effects on communication and development.”

Participants included Canadian pediatric patients undergoing cisplatin treatment for cancer. Their autological function was measures from prior to, throughout, and following therapy. The median period between the baseline assessment and the start of treatment was 5 days, the median number of days between treatment initiation and the first assessment was 38 days, and 1.5 years was the median length between treatment initiation and the final assessment.

On average, participants were measured 5 times for audiological function. These assessments were conducted prior to initiation, throughout, and following treatment. The majority of assessments were conducted in the first 3 months of cisplatin treatment.

CIHL rapidly increased within the first 6 months of treatment in both patient cohorts (28.4%; 95% CI, 23.9%-33.4%). The steep increase rate continued throughout the year following treatment.

Notably, the cumulative incidence of CIHL differed greatly between tumor types. Patients with hepatic tumors experienced a 30.1% (95% CI, 18.7%- 46.2%) incidence rate at 3 months and 77.5% (95% CI, 62.3%-89.7%) at the 2-year follow-up. In comparison, patients with germ cell tumors experienced the lowest rate of CIHL incidence. At 3 months the incidence rate was 9.1% (95% CI, 4.2%-19.1%) and at 2 years the rate had increased 33.3% (95% CI, 16.8%-58.9%).

The univariate Cox regression analysis demonstrated that the greatest risk factors influencing CIHL over time included age (≤5 years: HR, 2.69; 95% CI, 1.98-3.67), sex (female: HR, 0.75; 95% CI, 0.56-1.02, TCD of cisplatin at 3 months during therapy (per 100 mg/m2 increase: HR, 1.17; 95% CI, 1.01-1.35). Vincristine treatment, total duration of ototoxic antibiotics administration, and furosemide administration also contributed to CIHL development. All of these risk factors remained independently associated with CIHL in the multivariate Cox regression as well.

Study strengths included the large number of audiological assessments. Each participant received at least 2 assessments from baseline to post-treatment. This allowed investigators to measure the direct impact of CIHL following treatment.

Study limitations included a lack of standardized time points for the audiological assessments. The authors noted that a standardized assessment plan should be incorporated into future clinical trials. The variation between cancer types was also a study limitation, particularly because it impacted the treatments administered. Finally, ototoxic antibiotic data was obtained retrospectively and information on total dose administration was mostly unavailable. Thus, researchers could not properly investigate the impact of these drugs on CIHL development and that association remains to be further understood.

Other areas of research that deserve to be explored include the relationship between vincristine and CIHL, as well as the effect of cranial irradiation in hearing loss in children.

“Cranial irradiation and subsequent carboplatin treatment have been associated with hearing loss in children with cancer, but these risk factors did not affect CIHL development over time in the current study. It might be possible that the numbers of children in our cohort who received these treatments were too small to report an association (24% and 20%, respectively) or that the strong ototoxic effect of cisplatin overruled that of cranial irradiation and subsequent carboplatin treatment. Furthermore, research has shown that, although hearing loss after cranial irradiation may develop as early as within the first 2 years post- treatment, it often develops at 3 to 5 years. Because this study focused on short-term occurrence of hearing loss in children with cancer, it might be possible that the ototoxic effect of cranial irradiation in our cohort had not yet developed,” the study authors concluded.

“Nevertheless, the development of radiation-induced hearing loss within 5 years after the end of treatment is still rather early. Therefore, it is recommended to monitor hearing function from baseline, every 6 months posttreatment for 5 years, and annually for 5 years thereafter.”

Reference:

Meijer AJM, Li KH, Brooks B, et al. The cumulative incidence of cisplatin-induced hearing loss in young children is higher and develops at an early stage during therapy compared with older children based on 2052 audiological assessments [published online ahead of print, 2021 Sep 7]. Cancer. 2021;10.1002/cncr.33848. doi:10.1002/cncr.33848