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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

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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 1

Daily locomotor activity declines with tumor progression in GBM-bearing mice.

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Daily locomotor activity declines with tumor progression in GBM-bearing ...
(A) Schematic of locomotor activity recording before and through GBM progression. We recorded wheel-running activity continuously from mice for 7 days before and continuously through disease progression after GBM implant into the basal ganglia. (B) Daily locomotor activity of mice bearing patient-derived B165 tumors significantly declined 24 days after implant (mean ± SEM, n reported in figure, asterisk indicates day of 10% locomotion decline, time series change point detection analysis, *P < 0.05). Dotted lines on days 9–12 indicate dates of surgical recovery when locomotor activity was not recorded. (C) Daily locomotor activity of mice bearing syngeneic murine Nf1–/–DNp53 tumors significantly declined 37 days after implant (mean ± SEM, n reported in figure, asterisk indicates day of 10% locomotion decline, time series change point detection analysis, *P < 0.05). Dotted lines on days 9–12 indicate dates of surgical recovery when locomotor activity was not recorded. (D) Daily locomotor activity of mice bearing human LN229 tumors significantly declined 17 days after implant (mean ± SEM, n reported in figure, asterisk indicates day of 10% locomotion decline, time series change point detection analysis, *P < 0.05). Dotted lines on days 9–12 indicate dates of surgical recovery when locomotor activity was not recorded. (E) Daily locomotor activity of mice bearing murine GL261 tumors significantly declined 15 days after implant (mean ± SEM, n reported in figure, asterisk indicates day of 10% locomotion decline, time series change point detection analysis, *P < 0.05). Dotted lines on days 9–12 indicate dates of surgical recovery when locomotor activity was not recorded.

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