Development and Validation of a Novel Prediction Model for Hearing Loss From Cisplatin Chemotherapy

Abstract

PURPOSE Cisplatin treats many common tumors but causes permanent and debilitating hearing loss (HL). The objective of this study was to develop and externally validate a predictive model of HL in cisplatin-treated children and adolescent cancer survivors. METHODS The Pediatric Holistic Evaluation of Auditory Risk (PedsHEAR) model architecture used several machine learning approaches followed by an ensemble predictor. The primary end point was post-treatment communication–affecting HL (International Society of Pediatric Oncology Ototoxicity Scale [SIOP] Grade ≥2). PedsHEAR was developed from a multicenter data set of cisplatin-exposed patients up to 21 years old (1984-2017) and externally validated using data from the Children's Oncology Group ACCL05C1 study (2007-2012) and two combined institutional cohorts (1988-2022). The model predicts post-treatment HL in each patient (probability [%], 95% CI) and classifies patients as low, intermediate, or high risk for HL (probability HL <0.33, 0.33-0.60, >0.60, respectively). RESULTS In the training data set (n = 1,115, median age 6.3 years, SIOP Grade ≥2 HL 44%), PedsHEAR demonstrated excellent discrimination (AUC, 0.93 [95% CI, 0.92 to 0.95]) and then successfully validated within the internal (testing; AUC, 0.79 [95% CI, 0.74 to 0.85]) and two external validation cohorts (AUC, 0.74 and AUC, 0.67). In an aggregate validation cohort (n = 631), the model predicted the probability of HL (AUC, 0.76 [95% CI, 0.72 to 0.79]) and classified 22% (141/631), 71% (447/631), and 7% (43/631) of patients as low, intermediate, or high risk for HL. CONCLUSION PedsHEAR predicted SIOP Grade ≥2 HL in pediatric cisplatin-treated patients. This is the first validated model to successfully predict cisplatin-induced HL in a broadly representative population treated with diverse regimens across a range of treatment settings.