Rapid Spectroscopic Liquid Biopsy for the Universal Detection of Brain Tumours

SIMPLE SUMMARY: Due to the non-specific symptoms of brain cancer (e.g., headaches or memory changes), gliomas will often remain undetected until they are larger or at a higher grade, reducing the patient’s likelihood of a good clinical outcome. Earlier detection and diagnosis of brain tumours is vital to improve patient outcomes, leading to safer surgeries and earlier treatments. A liquid biopsy for brain tumour would prove revolutionary however in order to detect disease earlier the liquid biopsy needs to be able to detect smaller tumours; and current liquid biopsies perform worse when detecting smaller or earlier stage tumours. Here, for the first time, we confirm the applicability of a validated spectroscopic liquid biopsy approach to detect both small and low-grade gliomas proving that the spectroscopic liquid biopsy approach is insensitive to tumour volume unlike other liquid biopsies. ABSTRACT: Background: To support the early detection and diagnosis of brain tumours we have developed a rapid, cost-effective and easy to use spectroscopic liquid biopsy based on the absorbance of infrared radiation. We have previously reported highly sensitive results of our approach which can discriminate patients with a recent brain tumour diagnosis and asymptomatic controls. Other liquid biopsy approaches (e.g., based on tumour genetic material) report a lower classification accuracy for early-stage tumours. In this manuscript we present an investigation into the link between brain tumour volume and liquid biopsy test performance. Methods: In a cohort of 177 patients (90 patients with high-grade glioma (glioblastoma (GBM) or anaplastic astrocytoma), or low-grade glioma (astrocytoma, oligoastrocytoma and oligodendroglioma)) tumour volumes were calculated from magnetic resonance imaging (MRI) investigations and patients were split into two groups depending on MRI parameters (T1 with contrast enhancement or T2/FLAIR (fluid-attenuated inversion recovery)). Using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy coupled with supervised learning methods and machine learning algorithms, 90 tumour patients were stratified against 87 control patients who displayed no symptomatic indications of cancer, and were classified as either glioma or non-glioma. Results: Sensitivities, specificities and balanced accuracies were all greater than 88%, the area under the curve (AUC) was 0.98, and cancer patients with tumour volumes as small as 0.2 cm(3) were correctly identified. Conclusions: Our spectroscopic liquid biopsy approach can identify gliomas that are both small and low-grade showing great promise for deployment of this technique for early detection and diagnosis.