## 2 Materials and Methods
### Procedures  
Ideally, patients were tested prior to chemotherapy infusions at the beginning of treatment (baseline; trial 1), during treatment, and following treatment (additional tests during or following treatment were performed as the schedule permitted). Baseline assessment was conducted for all participants prior to beginning treatment with the exception of one patient who had baseline testing completed at the first infusion. Due to variance in clinical treatment protocols, testing during treatment took place at different points in the treatment schedule for each patient. All testing was completed \begin{table}
\begin{tabular}{c c c c c c} \hline \hline  & & & \multicolumn{3}{c}{**Patient Demographics**} \\ \hline
**Patient** & **Gender** & **Age (years)** & **Platinum Agent** & \
\begin{tabular}{c} **Cumulative Dose** \\ **(mg)** \\ \end{tabular} &
\begin{tabular}{c} **Highest Frequency DPOAE** \\ **(kHz)** \\ \end{tabular} \\ \hline
9 & Female & 33 & Carboplatin & 1455 & 16 \\
16 & Female & 41 & Oxaliplatin & 1057 & 13.3 \\
4 & Female & 42 & Oxaliplatin & 873 & 16 \\
18 & Female & 44 & Carboplatin & 3907 & 13 \\
8 & Female & 45 & Carboplatin & 3779 & 10.6 \\
7 & Male & 47 & Oxaliplatin & 1079 & 7.3 \\
1 & Male & 49 & Oxaliplatin & 519 & 12 \\
12 & Male & 55 & Cisplatin & 163 & 6 \\
10 & Female & 56 & Oxaliplatin & 1202 & 9 \\
6 & Female & 59 & Carboplatin & 2412 & 8 \\
2 & Male & 61 & Oxaliplatin & 3669 & 5.3 \\
3 & Female & 79 & Carboplatin & Unknown & 3 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Patient number—sorted by age (in years), gender, platinum agent received, cumulative dose, and frequency of highest distortion product toacoustic emission (DPOAE) present at baseline determined from the gross frequency sweep data for all 12 patients included in this study. within approximately three months for each patient with baseline evaluations lasting approximately 2 h and 1.5 h for monitoring and post-treatment evaluations. During testing, patients were in a hospital bed either sitting or slightly inclined in a private room (in the infusion center) to reduce environmental noise from interfering with the measurements. The full test battery included middle ear reflectance, pure-tone behavioral hearing thresholds (1-16 kHz; [16]), spontaneous OAEs (i.e., SOAEs), and nine DPOAE paradigms for each session. The modification for monitoring sessions was that hearing thresholds at the 7 highest frequencies eliciting a response at baseline were evaluated [16]. In general, depending on time, cooperation by the patient and nursing staff, and environmental noise, some tests were not completed for some sessions. Prior to each test, patients were given instructions specific for that task. In this manuscript, data from patients with at least two testing sessions for two or more of the nine DPOAE paradigms were analyzed. Nine DPOAE paradigms were collected, which resulted in 11 analyses (refer to Section 3.4 Summary of Results). The first paradigm was a gross discrete frequency sweep: f\({}_{2}\) = 16-2 kHz; f\({}_{2}\)/f\({}_{1}\) = 1.2; L\({}_{1}\)/L\({}_{2}\) = 62/52 dB FPL where six points per octave were collected with three total octaves swept (18 points). The remaining eight paradigms were concentrated paradigms [21] based on the highest frequency with a present DPOAE from the gross discrete frequency sweep. The first of which were frequency sweeps (n = 2): f\({}_{2}\)/f\({}_{1}\) = 1.2; L\({}_{1}\)/L\({}_{2}\) = 62/52 dB FPL (mid-level) and L\({}_{1}\)/L\({}_{2}\) = 72/72 dB FPL (high level); spanning 2/3 of an octave in 1/48 steps (32 points) starting at the highest frequency with a present DPOAE from the gross sweep. Followed by level sweeps (n = 4): L\({}_{1}\) = 57, L\({}_{2}\) = 17-67 dB FPL; L\({}_{2}\) = 57, L\({}_{1}\) = 27-67 dB FPL (when varied L\({}_{1}\) or L\({}_{2}\) changed in 3 dB steps). Each level sweep (L\({}_{1}\) and L\({}_{2}\)) was completed at the two highest frequencies from the gross sweep with present DPOAEs.