Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma

J Neurosurg 141:673–683, 2024

Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma.

METHODS Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma.

RESULTS CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation.

CONCLUSIONS The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTMbased survival models can enable clinicians to evaluate patients’ response to surgery as well as their outcomes.

Blood-based biomarkers for malignant gliomas

Blood-based biomarkers for malignant gliomas

J Neurooncol (2013) 113:345–352

Malignant gliomas remain incurable and present unique challenges to clinicians, radiologists and clinical and translational investigators. One of the major problems in treatment of these tumors is our limited ability to reliably assess tumor response or progression.

The most frequently used neuro-imaging studies (contrast-enhanced MRI and CT) rely on changes of blood–brain barrier (BBB) integrity, providing only an indirect assessment of tumor burden. In addition, the BBB can be altered by commonly used interventions including radiation, glucocorticoids and vascular endothelial growth factor inhibitors, further complicating the interpretation of scans. Newer radiologic techniques including PET and magnetic resonance spectroscopy are theoretically promising but thus far have not meaningfully changed the assessment of patients with malignant gliomas. A tumor-specific, bloodbased biomarker would be of immediate use to clinicians and investigators if sufficiently sensitive and specific.

This review discusses the potential utility of such a biomarker, the general classes of tumor-derived blood-based biomarkers and it summarizes the currently available data on circulating tumor cells, circulating nucleic acids and circulating proteins in patients with malignant gliomas. It is unclear which marker or marker class appears to be the most promising for these tumors.

This article provides thoughts on how novel candidate blood-based markers could be discovered and tested in a more comprehensive way and why these efforts should be among the top priorities in neuro-oncologic research in the coming years.