## 2 Results
### Univariate Statistical Analyses  
Prior to undertaking approaches 1 and 2, PH Weeks 1-3 and PL Weeks 1-3 were compared relative to cancer weeks 1-3 using all 212 VOCs. The Student's _t_-test was undertaken to identify statistical significance between each treatment and cancer. A volcano plot was generated by plotting the \(-\log_{10}\) (_p_-value) against the \(\log_{2}\) fold change (FC) for both treatments to visualize which treatment had more differences in VOC expression relative to cancer. Most VOCs were upregulated in both the PH samples and in the PL samples when compared to cancer samples. This is interesting, as the majority of VOCs were downregulated in cancer weeks 1-3 compared to control samples. There is a handful of VOCs that are downregulated in PL samples and show high absolute FC values relative to cancer; however, many of these VOCs did not display statistical significance (relatively high _p_-values). Moreover, the volcano plot demonstrates that PH presents more considerable differences in VOC expression relative to PL when compared to cancer (VOCs here have relatively lower _p_-values in PH relative to PL), which is initially indicative that PH treatment is more effective when compared to PL treatment (Figure 1). Approach 1 was then undertaken to screen for differences between PH and cancer in a time-dependent fashion. Upon implementation of two-tailed Student's _t_-tests between PH week 1 vs. cancer week 1, PH week 2 vs. cancer week 2, PH week 3 vs. cancer week 3, and PH weeks 1-3 vs. cancer weeks 1-3, a total of eight VOCs (Supplementary Table S1) were statistically significant (_p_-value < 0.05) across two or more comparisons. Two VOCs (2-nonanone (2-NON) and dicyclohexylmethanone (DCHM)) were significant between PH week 3 and cancer week 3, whereas five VOCs (2-hexanone (2-HEX), 2-heptanone (2-HEP), 5-methyl-2-hexanone (5M2H), 2-NON, and DCHM) were significant for PH weeks 1-3 vs. cancer weeks 1-3 after adjusting _p_-values for false discovery rate (FDR). A hierarchical heatmap was generated using these eight VOCs (the five noted above, along with 3,3-dimethyl-2-butanone (DMB), 2,4-di-tert-butylphenol (DTB) and safranal (SAF)) (Figure 2). VOCs within cancer weeks 1-3 are mostly downregulated upon tumor injection and throughout progression (compared to control samples). Some VOCs displayed low intraclass variation across all weeks of cancer, and other feat dysegulated from cancer week 1 to cancer week 3. Control samples for all VOCs presented in the heatmap have high reproducibility between replicates. The heatmap also shows that VOCs within PH weeks 1-3 appear to be expressed at similar levels as the control class, which is seen as early as the first week of treatment. On the other hand, the PL treatment sample class shows that VOCs are downregulated when compared to control samples and showed a high degree of similarity to cancer weeks 1-3 samples. There are limited differences in VOC expression between the weeks within the PH and PL treatment samples. Approach 2 was then undertaken to screen for univariate differences in PH relative to cancer week 3 and highlighted 30 VOCs (Supplementary Table S2) differentially expressed across two or more of the following comparisons: control vs. cancer week 3, PH week 1 vs. cancer week 3, PH week 2 vs. cancer week 3, and PH week 3 vs. cancer week 3. VOCs found to be significant by FDR have an underlined asterisk in Supplementary Table S2; 3 VOCs were found to be significant between PH week 1 vs. cancer week 3, 12 VOCs between PH week 2 and cancer week 3, and 2 VOCs were significant between PH Week 3 and cancer Week 3. VOCs in Supplementary Table S2 were utilized for multivariate analysis. Overall, the univariate statistical analyses showed that VOCs had higher statistical significance between pita high and cancer samples when compared to pita low and cancer samples.