## 1 Introduction
### Advancing Distortion Product Otoacoustic Emission (DPOAE) Paradigms
To calculate a group delay value (referred to as group delay hereafter), the phase of the distortion product is plotted against the frequency of 2f\({}_{1}\)-f\({}_{2}\) and the slope of that curve is determined. This paradigm often involves fixing f\({}_{2}\) and varying f\({}_{1}\)[28; 29; 33]. In the conventional frequency range for DPOAEs \(\leq\) 8 kHz, group delay was more sensitive (by showing change sooner) than high frequency audiometry or frequency sweep DPOAEs at traditional frequencies (\(\leq\)8 kHz) when monitoring patients receiving tobramycin [33]. Additionally, group delay has been shown to be repeatable across testing sessions at high frequencies in normal hearing adult subjects and a patient population [29; 30]. Of note, the slope of the phase (used to calculate group delay) is not always consistent across frequencies [28; 29; 34]. There is a general trend of shorter group delays/travel times for higher frequencies [28; 29]. Thus, norms for group delay will be different at each frequency tested, so comparing across frequency (high to low) is not likely to lead to meaningful assessment of damage and should be considered during analysis of group delays. Although there are variations in group delays across frequencies, the results are repeatable within an individual over time [29; 30]. DPOAE group delay results tested at high frequencies, may give an earlier indication of cochlear damage than the traditional means of ototoxic monitoring (high frequency audiometry and DPOAEs \(\leq\) 8 kHz or high frequency DPOAEs with the commonly used frequency sweep paradigm), as has been shown in previous research [33]. [PERSON] et al. [33] reported prolonged DPOAE group delays in patients with cystic fibrosis (CF) receiving low and low-to-moderatecumulative doses of tobramycin regardless of age, but higher doses of tobramycin in older patients (15 to 23 years) resulted in a shorter DPOAE group delays. As DPOAE group delays change (longer or shorter compared to baseline) in the presence of cochlear damage, expectations may depend on the duration of exposure and/or the underlying physiologic consequences of the damage [33; 35; 36; 37]. Clinical practice may be enhanced by emerging DPOAE applications, including advanced calibration techniques to ensure stability of serial measurements, high-frequency stimuli to assess basal cochlear function, concentrated frequency monitoring protocols, detection thresholds, and group delays to gauge OHC function. These DPOAE applications may permit visualization and quantification of the earliest signs of underlying cochlear damage which may go undetected with conventional methods. This has the potential to facilitate more meaningful clinical interpretations. In a recent report, high-frequency DPOAE monitoring using frequency, level, and ratio sweeps resulted in clinically significant changes for patients receiving cisplatin, oxaliplatin, and carboplatin [16]. The current paper aims to elaborate on that work by assessing which of the three DPOAE paradigm categories is most sensitive to changes in the auditory system as a result of ototoxic therapies. It is hypothesized that significant changes in detection threshold and/or group delays may be seen before changes in the frequency sweep paradigm based on previous reports [33]. [PERSON] et al. [33] reported that changes were seen first for DPOAE thresholds and group delays compared to frequency sweeps in children with cystic fibrosis receiving antibiotic treatments versus controls. In addition, these paradigms have been reported to be repeatable over time and sensitive to platinum exposure [16; 29; 30]. The current report analyzes different DPOAE paradigms used in patients undergoing chemotherapy treatments with platinum derivatives. Individualized measurement protocols were assessed based on the highest frequencies with measurable DPOAEs, allowing exploration of potential opportunities for clinical translation in order to quantify cochlear dysfunction.