Title: Validating Serum Diagnostics for Early Diagnosis and Stratification of Glioma
Funder: Cancer Research UK

Abstract: Brain tumours account for around 3% of all new tumours diagnosed in the UK, with over 10,500 cases each year. Glioma (grade III-IV) are the most common and most aggressive of these tumours is glioblastoma (GBM). They are incurable and the average survival for patients is only 14 months. Treatment involves surgery (biopsy or debulking) and combinations of radiotherapy and chemotherapy. Extent of tumour resection and a patient’s postoperative functional status are potentially modifiable if surgery can be performed earlier, where tumours are smaller and more safely removed. Unfortunately, there is often a delay in diagnosing gliomas. Greater than 38% of brain tumour patients will visit their primary care doctor more than 5 times prior to diagnosis, more than with any other cancer and 62% of patients are diagnosed only after emergency presentation, with larger tumours that may not be amenable to extensive surgical resection. Tumour molecular features (e.g. IDH status) which impact prognosis and treatment decision making cannot be discerned from the imaging and depend on tumour biopsy. Earlier identification of molecular features would shorten time to treatment and reduce potential harm from surgery. Following a study to examine the diagnostic pathway for brain tumours in adults. We assessed the utility of current referral guidelines and have validated a simple clinical tool that supports stratification of ‘at-risk’ patients for urgent brain imaging. To complement this work, we have been screening this cohort using our spectroscopic test. Blinded analysis of the first cohort of 104 prospectively collected patients has demonstrated 100% sensitivity for new GBM diagnosis and 92% sensitivity when including all primary brain tumours. This is combined with an 87% specificity demonstrates high sensitivity and specificity in a prospective cohort of patient samples. To extend the capabilities of our test to achieve molecular stratification of tumours we will use electrochemical sensors. Preliminary results are encouraging and show the detection of IDH1 using a simple label-free impedance measurement and an antibody modified electrode. We will further the clinical analytical research describe above in order to develop sensitive and specific tests to analyse the molecular content of human serum to enable 1) The early stratification of brain tumour status (low grade / high grade and tumour volume) for primary care 2) The identification of tumour molecular IDH status

Lay abstract: Brain tumours account for around 3% of all new tumours diagnosed in the UK, with over 10,500 cases each year. Glioma (grade III-IV) are the most common and most aggressive of these tumours is glioblastoma (GBM). They are incurable and the average survival for patients is only 14 months. Treatment involves surgery (biopsy or debulking) and combinations of radiotherapy and chemotherapy. Extent of tumour resection and a patient’s postoperative functional status are potentially modifiable if surgery can be performed earlier, where tumours are smaller and more safely removed. Unfortunately, there is often a delay in diagnosing gliomas. Greater than 38% of brain tumour patients will visit their primary care doctor more than 5 times prior to diagnosis, more than with any other cancer and 62% of patients are diagnosed only after emergency presentation, with larger tumours that may not be amenable to extensive surgical resection. Tumour molecular features (e.g. IDH status) which impact prognosis and treatment decision making cannot be discerned from the imaging and depend on tumour biopsy. Earlier identification of molecular features would shorten time to treatment and reduce potential harm from surgery. Following a study to examine the diagnostic pathway for brain tumours in adults. We assessed the utility of current referral guidelines and have validated a simple clinical tool that supports stratification of ‘at-risk’ patients for urgent brain imaging. To complement this work, we have been screening this cohort using our spectroscopic test. Blinded analysis of the first cohort of 104 prospectively collected patients has demonstrated 100% sensitivity for new GBM diagnosis and 92% sensitivity when including all primary brain tumours. This is combined with an 87% specificity demonstrates high sensitivity and specificity in a prospective cohort of patient samples. To extend the capabilities of our test to achieve molecular stratification of tumours we will use electrochemical sensors. Preliminary results are encouraging and show the detection of IDH1 using a simple label-free impedance measurement and an antibody modified electrode. We will further the clinical analytical research describe above in order to develop sensitive and specific tests to analyse the molecular content of human serum to enable 1) The early stratification of brain tumour status (low grade / high grade and tumour volume) for primary care 2) The identification of tumour molecular IDH status

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS