Cisplatin may induce hearing loss in children and young adults

According to a recent large, multicentre cohort study published in The Lancet- Child and Adolescent Health Journal, benchmarks were established for the prevalence of CIHL in patients treated with cisplatin, where it was found out that Variations in cisplatin dosing confer the additive risk for developing CIHL.

Cisplatin is used to treat a wide range of childhood cancers and cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity.

Hence, Diana J Moke and colleagues from the Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA conducted this study to address persistent knowledge gaps in CIHL by establishing benchmarks for the prevalence of and risk factors for CIHL.

In this multi-institutional cohort study, children (age 0-14 years), adolescents, and young adults (age 15-39 years) diagnosed with a cisplatin-treated tumor from pediatric cancer centers, who had available cisplatin dosing information, and primary audiology data for central review from consortia located in Canada and the USA were eligible for inclusion. A total of 1481 patients received cisplatin was taken into the study. Audiology was centrally reviewed and CIHL graded using the consensus International Society of Pediatric Oncology (SIOP) Boston Ototoxicity Scale.

The authors assessed the prevalence of moderate or severe CIHL (SIOP grade ≥2) at the latest follow-up and end of therapy, in each demographic, diagnosis, and treatment group and their relative contributions to risk for CIHL. Secondary endpoints explored associations of cisplatin dose reductions and CIHL with survival. Cisplatin dose reductions and CIHL were also associated with survival outcomes.

The results showed that-

  1. Of 1414 (95·5%) participants who had audiometry at the latest follow-up (mean 3·9 years [SD 4·2] since diagnosis,), 620 (43·8%) patients developed moderate or severe CIHL.

  2. The highest prevalence of CIHL was seen in the youngest patients (aged <5 years; 360 [59·4%] of 606 patients) and those with a CNS tumor (221 [50·9%] of 434 patients), hepatoblastoma (110 [65·9%] of 167 patients), or neuroblastoma (154 [62·1%] of 248 patients).

  3. After accounting for cumulative cisplatin dose, higher fractionated doses were associated with risk for CIHL (for each 10mg/m2 increase per day, adjusted odds ratio [aOR] 1·15 [95% CI 1·07-1·25]; for each 50 mg/m2 increase per cycle aOR 2·16 [1·37-3·51]).

  4. Vincristine exposure was newly identified as a risk factor for CIHL (aOR 3·55 [2·19-5·84]).

  5. Dose reductions and moderate or severe CIHL was not significantly associated with survival differences.

  6. Therefore, the authors revealed that variations in cisplatin dosing confer additive risk for developing CIHL and warrant investigation as a potential approach to decrease the burden of therapy.

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