Medical Student The Warren Alpert Medical School of Brown University Cranston, RI, US
Introduction: Glioblastoma (GBM) is a highly aggressive and heterogeneous primary brain tumor with limited survival despite surgery and chemoradiation. Immune-checkpoint blockade (ICB) has shown promise in solid tumors and has emerged as a therapeutic alternative in GBM. Traditional approaches to assess disease status, like cross-sectional imaging and biopsies, are invasive and carry important morbidity. Circulating tumor cells (CTCs) offer a non-invasive alternative for tracking GBM progression. The CTC-iChip, a tumor antigen-independent microfluidic technology, could help detect GBM CTCs, and, combined with primary lesion spatial biology, may offer a comprehensive biomarker for disease activity.
Methods: In this retrospective cohort study, we utilized multi-immunofluorescence (mIF) staining in archival tissue from six patients with GBM treated at Massachusetts General Hospital. Paired blood samples were prospectively collected before and during treatment and ran through the CTC-iChip. The panel identified tumor cells (SOX2), T cells (CD3), proliferative status (Ki67), cancer-associated myofibroblasts (α-SMA), macrophages (CD163), and immunomodulatory molecules (PD-1). Spatial metrics were obtained on a representative block from each patient's initial diagnostic material, and clinical outcomes were compared based on patients' CTC status.
Results: Of six tumors, five were IDH wild type. Three patients received temozolomide (TMZ), two durvalumab, and one TMZ plus a peptide vaccine. Four patients experienced recurrence, with a median survival of 17 months (range 5-54). Pre-treatment CTCs were present in 2/4 patients. CTCs were detected in 2/6 patients post-surgery and 2/4 patients post-systemic treatment. The tumor microenvironment (TME) primarily comprised SOX2+ (54%), CD163+ (34%), and α-SMA+ cells (6%). CTC presence post-treatment strongly correlated with the tumor area analyzed via mIF (R2=0.8). Patients with CTCs post-surgery had a shorter average five-year survival compared to those without CTCs detected (11 months [range 5-17] vs 21 months [range 6-47] respectively).
Conclusion : Tumor area analyzed using mIF is positively correlated with CTC presence after systemic treatment. Combining mIF and CTC detection offers a promising biomarker for tracking GBM disease progression. Larger studies are needed to further explore the impact of mIF paired with CTC detection on GBM.
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