Daily locomotor activity declines with tumor growth and disease progression in glioblastoma
Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog
Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog
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Research Article Clinical Research Neuroscience Oncology

Daily locomotor activity declines with tumor growth and disease progression in glioblastoma

Abstract

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2–3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the morning, but not evening, significantly reduced tumor size and restored daily locomotion in mice. In a pilot study of 6 patients with GBM wearing an actigraphy watch, wrist movement provided a feasible and continuous longitudinal indicator of daily activity with 1-minute resolution. After tumor resection and radiation, daily activity declined in 2 patients 19 and 55 days before detection of progression by MRI but did not change for the 4 patients with stable disease. These results suggest that daily activity tracking using wearable devices may serve as a real-time indicator and potential monitoring tool for GBM progression and treatment efficacy.

Authors

Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

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Figure 2

Daily locomotion declined with intracranial tumor growth.

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Daily locomotion declined with intracranial tumor growth. (A) We recorde...
(A) We recorded running-wheel activity for before and after implantation of GL261 or LN229 cells into basal ganglia. Representative locomotion in a sham mouse was stable throughout recording. Yellow and gray bars represent day and night (lights on 7 a.m. to 7 p.m.). (B) Actograms before and after GL261 (left) or LN229 (right) tumor implantation. Note daily locomotion declined as disease progressed. (C and D) Tumor bioluminescence increased 9-fold from 5 to 22 days after implant in mice bearing GL261 or LN229 tumors (mean± SEM, 1-way repeated-measures ANOVA with Tukey’s multiple-comparison test, **P < 0.01, ***P < 0.001). Dotted lines indicate surgical recovery (days 9–12). Inset images show tumor bioluminescence 22 days after implant. (E and F) Daily locomotion of GBM-bearing mice declined 15 or 17 days after implant compared with sham (mean ± SEM, 2-way repeated-measures ANOVA with Tukey’s multiple-comparison test, **P < 0.01 from days 25 to 33, ****P < 0.0001 from days 23 to 33). (G and H) Average daily locomotion declined as GBM tumors grew (GL261: Spearman’s correlation r = –0.92, 95% CI: –0.95 to –0.86, P < 0.0001, line shows nonlinear regression fit; LN229: r = –0.92, 95% CI: –0.97 to –0.84, P < 0.0001). (I and J) Body weight declined 22 days after implant in GL261-, but not LN229-, bearing mice compared with controls (mean ± SEM, 2-way ANOVA with Tukey’s multiple-comparison test, *P < 0.05). (K and L) Weight did not correlate with GL261 (r = –0.25, 95% CI: –0.50 to 0.03, P = 0.07) or LN229 tumor size (r = –0.15, 95% CI: –0.36 to 0.12, P = 0.06). Each dot represents average of all mice per recording day, excluding days of surgery and recovery.