Preoperative brain irradiation in glioblastoma (POBIG)

"No significant scientific breakthroughs have occurred in the brain tumour sphere for decades", concluded the 2018 All-Party Parliamentary Group on Brain Tumours, which also highlighted the high socioeconomic costs of brain tumours.
Glioblastoma is the most frequent and aggressive type of brain cancer; only 25% of all patients survive >1 year. It affects more than 2500 patients in the UK per year, and the incidence is rising. Current treatment involves surgery followed by (chemo)radiotherapy, and this sequence has not changed or been challenged in decades. Inevitably after surgery, remnant tumour cells are left behind due to its invasive nature and the inability to remove all affected brain tissue. The postoperative radiotherapy regimen targets this remnant tumour contributing to the survival of our patients. Still, numerous efforts focussing on combining radiotherapy with new agents or applying a higher dose of radiotherapy have failed.
Surgery is of both diagnostic and therapeutic value. However, we know that the surgical procedures dramatically influence the tumour landscape as the postoperative tumour microenvironment exhibits increased hypoxia, tumour migration and proliferation. These negative factors directly limit the effectiveness of postoperative treatment and emphasise the clear clinical need for a breakthrough and trialling of preoperative interventions. For this, we need to diagnose glioblastoma without obtaining tissue via surgery. In clinical practice, we refer patients likely to suffer from a glioblastoma seen on an MRI scan for neurosurgical resection. Neuro-oncology radiologists are extremely good at diagnosing glioblastoma radiologically using MRI imaging. Moreover, current MRI scan techniques enable the stratification of glioma subtypes. In other words, MRI imaging techniques are paving the road to initiating preoperative interventions in glioblastoma patients.
Following the benefits of preoperative radiotherapy in other cancers, our Preoperative Brain Irradiation in Glioblastoma (POBIG) study will deliver radiotherapy before surgery. POBIG is the first experience worldwide of standalone contemporary preoperative radiotherapy for glioblastoma patients targeting the tumour in its potentially most treatment sensitive (i.e. preoperative) state. As our patients suffer from such a devastating prognosis, this is a disease with a high clinical need. The field needs, therefore, to deliver more than a clinical study with a strong rationale. Hence, we designed POBIG to fully characterise the radiation response in newly diagnosed glioblastoma patients initiating the development of the desperately needed paradigm shift in the treatment of our patients.
In POBIG, we will assess the safe dose and volume we can treat before surgery. In our study, we also collect unique information to study the radiotherapy response in-depth for each patient. To further improve the non-invasive tumour characterisation and response monitoring, we implement our advanced machine learning-based imaging analysis that will identify the regions of the tumour that are responsible for the poor prognosis. We will also collect different types of liquid biopsies to develop non-invasive tumour characterisation and treatment monitoring tools. All this information will be analysed to inform follow on studies and develop strategies to improve the outcomes for each patient.
In summary, POBIG is a high gain, safety and feasibility phase I dose-escalation study. POBIG is the first step towards the necessary paradigm treatment shift for a disease with a high unmet medical need.

"No significant scientific breakthroughs have occurred in the brain tumour sphere for decades", concluded the 2018 All-Party Parliamentary Group on Brain Tumours, which also highlighted the high socio-economic costs of brain tumours.
Glioblastoma is the most frequent and aggressive type of brain cancer, and only 25% of all patients survive >1 year. It affects more than 2500 patients in the UK annually, and the incidence is rising. Current treatment involves surgery followed by (chemo)radiotherapy, and this sequence has not been changed in decades. Inevitably after surgery, remnant tumour cells are left behind due to its invasive nature and the inability to remove all affected brain tissue. Furthermore, the surgical procedure dramatically influences the tumour landscape as the postoperative microenvironment exhibits increased hypoxia, tumour migration and proliferation. These factors emphasize the clear clinical need for a breakthrough and trialling of preoperative interventions in the tumour's potentially most treatment-sensitive state to improve treatment outcomes for glioblastoma patients. Following the benefits of preoperative radiotherapy in other cancers, our Preoperative Brain Irradiation in Glioblastoma (POBIG) study delivers for the first time single fraction radiotherapy before routine surgery and postoperative (chemo)radiotherapy.
As the field needs more than a clinical strategy with a strong rationale, we collect novel, unique and clinically relevant information at the individual patient level (e.g. sampling of paired irradiated and unirradiated tumour tissue, liquid biopsies and habitat-based imaging analysis). POBIG is a safety and feasibility phase I radiotherapy dose-escalation study. The innovative design of POBIG will contribute to personalized medicine and the necessary paradigm treatment shift for a disease with a high unmet need.