Johanna M. Niers

Background: Knowledge about glioma patients’ physical functioning and physical fitness throughout the disease trajectory is limited. We analyzed self-reported functioning and fitness in a large sample of glioma patients preoperatively and after primary treatment. Methods: We used the physical functioning subscale of the 36-Item Short Form Health Survey (SF36) and three questions about physical fitness from the Checklist of Individual Strength (CIS20). Scores were compared to age-, sex-, and education-matched population controls, preoperatively and after treatment. In patients with repeated assessments, changes over time were analyzed. Correlations between patient, disease, and treatment characteristics and functioning and fitness at both time points, and with change over time, were explored. Analyses were performed separately for World Health Organization grade II, III, and IV glioma. Results: Grade III patients had significantly lower functioning than controls, both preoperatively and after treatment, and declined over time. No significant differences with controls were found for grade II and IV patients, or for fitness. Grade II patients reported better functioning than grade III and IV preoperatively and better than grade III after treatment. Lower Karnofsky Performance Status was generally related to lower functioning and fitness, while older age, female sex, and lower education appeared in subgroup analyses. Age, neurological disabilities and tumor histology were associated with changes over time. Conclusions: Grade III glioma patients showed poorer functioning than population controls, which declined over time. Grade II patients reported better outcomes than the other subgroups, although individual variability was high. These findings highlight the need for personalized approaches addressing functioning and fitness in glioma.

Table S1: GLASS surgery-level clinical and molecular characteristics (N=354)

Table S2: List of 132 pairs (ID of Initial and Recurrent samples)

Table S1: GLASS surgery-level clinical and molecular characteristics (N=354)

Table S3A/B/C/D: Clinical summary of GLASS epigenomic samples S3A: Clinical summary of IDHmut patients who switched from GCIMP-high to GCIMP-low S3B: Clinical summary of IDHmut and IDHwt patients with known hypermutator status S3C: Clinical summary of IDHmut and IDHwt patients with known treatment information S3D: Clinical summary of IDHmut patients with known treatment information

Table S4: Master regulators - list of samples and features (Related to Figure 2) S4A: List of sample profiled for ChIP-seq S4B: Results of H3K4me3 differential analysis S4C: Results of H3K27Ac differential analysis S4D: Results of gene expression differential analysis S4E: List of IDHmut non-codels samples profiled for both gene expression and DNA methylation S4F: List of hypomethylated probes between IDHmut non-codel initial and first recurrent pairs S4G: List of anticorrelated genes S4H: List of HOXD13 predicted targets

Table S5: Treatment-related probes and samples (Related to Figure 3) S5A: List of 69 IDHmut pairs with treatment information (ID of Initial and Recurrent samples and group assignment) S5B: List of differentially methylated probes associated with treatment in IDHmut gliomas S5C: List of differentially methylated probes associated with treatment in IDHmut astrocytomas S5D: List of CpG-gene pairs (epigenetic regulation associated with treatment)