A review on diffuse glioma and gene transfer technologies and the impact of COVID-19 on neurosurgical oncology service provision

1) Diffuse glioma is one of the most devastating cancers know in terms of morbidity and mortality. During the last decade, the mortality rate has seen a very modest change. Due to the rapid improvement in understanding the glioma-genesis, evolution, and genetic landscape, a new classification has emerged, improving the diagnostic accuracy. However, the new knowledge acquired has not been translated into novel therapeutic therapies. The treatment regime has mostly relied on maximal surgical resection and chemo/radiotherapy. Nevertheless, gross macroscopic surgical resection is allowing for a significant number of tumour cells to be left behind. Glioma Stem Cells (GSCs) left behind can acquire chemo-resistant properties and exhibit a plethora of characteristics that enable cell survival and growth, leading to an aggressive tumour recurrence. It is now increasingly recognised that IDH mutations are linked to the development of glioma and tumour reoccurrence. IDH mutations can lead to genetic and epigenetic changes promoting cell proliferation, tumour invasion and immune evasion as well as preventing differentiation. Understanding these pathways will allow for new rational therapeutic interventions in an attempt to improve patient outcomes. 2) Gene delivery is the process whereby foreign genomic material is inserted into a host cell or organism. A number of viral and non-viral gene transfer system have been developed in the last few decades. However, no system to date has been used without certain limitations. Here we critically appraise and outline, the advantages, disadvantages, and common uses of viral and non-viral methods. 3) The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic brings new challenges to the management of neuro-oncology patients. In the West Midlands (WM) a population of 5.7 million is served by three neuro-oncology centres. NHS service delivery was reconfigured to cope with SARS-CoV-2 infections. Here we report the impact at three centres with low (CLOW), medium (CMED) and high (CHIGH) levels of SARS-COV-2 mortality on referrals and diagnosis, surgical safety and quality and clinical management during the pandemic. Data were collected either prospectively or retrospectively using electronic clinical records from each centre during period 1 (before lockdown) and period 2 of SARS-CoV-2 (complete lockdown). Referral into specialist care pathways fell by 40% leading to reductions in diagnostic surgery of over 30% as a result of SARS-COV-2 related changes in healthcare provision and help-seeking behaviour. For SARS-COV-2 negative patients, surgical morbidity, 30-day readmission and 30-day mortality were unaffected by changes in management, but operations took longer, and there was an increase in patients with post-operative residual disease. There were no readmissions with SARS-COV-2 infection within 30 days of surgery. Access to radiotherapy and chemotherapy was reduced with patients suffering from the most aggressive cancers being more severely impacted. Future planning should consider accelerating access to advanced molecular diagnostic technologies to refine clinical decision making and the use of chemotherapy. Regional networking solutions could optimise the use of resources and maintain a higher standard of care, allowing patients to continue to receive the best possible care