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 4.

Daily activity declined before clinical detection of GBM progression in patients.

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Daily activity declined before clinical detection of GBM progression in ...
(A) (Left) Patients with GBM continuously wearing wrist actigraphy watches characterized by sex, age, Karnofsky Performance Status (KPS) score, surgery type (STR, subtotal resection; GTR, gross total resection or biopsy), tumor location, months of TMZ treatment, dexamethasone (DEX) steroid dose, survival time, MGMT promoter methylation status (Unmet, unmethylated; Met, methylated), and ATRX and PTEN expression status. (Right) After surgery and radiation on day 0, wrist actigraphy (gray bars) was recorded for patients receiving TMZ for 5 days every 21 days while being monitored for tumor progression (circles). “A” indicates patient was alive when actigraphy data collection was finalized for all trial participants. (B) Representative actogram of a patient (#6) with stable disease (i.e., did not progress during study) and reliable daily activity pattern and level. Blue-yellow colors depict wrist activity counts and white indicates missing data (e.g., Actiwatch required battery replacement). (C) Representative actogram of patient (#1) with progressive dis¬ease (i.e., tumor size increased on scans during study) wearing actigraphy watch after completing surgery and during maintenance TMZ treatment. Note decline in daily activity. (D and E) Patients without disease progression showed stable daily locomotion (mean ± SEM, black line indicates 3-day running average of daily activity data, time series change point detection analysis; P > 0.05), while the 2 who progressed showed a sustained 10% decrease in wrist movements on days 33 (#1, 55 days before clinical detection of progression) and 98 (#2, 19 days before clinical detection of progression, asterisk indicates time-series change-point detection analysis, *P < 0.05). Arrows indicate times of activity decline and MRI detection of progression. Vertical lines show dates of MRI-based disease progression (red) or pseudo-progression (gray). See also Supplemental Figures 4 and 5.