RTID-06. TRENDS IN INTERNATIONAL INVESTMENT IN CHILDHOOD, ADOLESCENT AND YOUNG ADULT (CYA) BRAIN TUMOR RESEARCH 2006-2018, WITH A FOCUS ON DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Organizations funding brain tumor research want to identify gap areas for funding individually or in collaboration and want to better understand existing project focus to maximize new project investments. The International Cancer Research Partnership and the US Coalition Against Childhood Cancer used international research portfolio data to assess the landscape of CYA brain tumor research. From 2006-2018, investment for brain tumor research increased from $13m to $73m, and as a percentage of the CYA portfolio, brain tumor research received the highest percent investment (30%) in 2018. Research into treatment had risen (from $6m to $38m) as had research into biology (from $3m to $19m) - an essential foundation for more future personalized treatments. Given the lifelong impact on survivors it was encouraging that survivorship research investment had also started to increase. While 5-year survival for CYA cancers is now over 80%, survival for Diffuse Intrinsic Pontine Glioma (DIPG) remains very low. To assess capacity for future progress, several indicators were considered. The number of new DIPG projects per year increased from an average of 3 per year (2006-2012) to 11 (2013-2018) and funding increased from $0.5m (2006) to $10m (2018). Also, by 2018, 9 projects included a training component to build future research capacity. The number of laboratories researching DIPG increased from 2 in the US (2006) to 53 institutions in 6 countries (2018). Recent years had seen increased funding for pre-clinical models essential for identifying new targets. Collaborative initiatives such as DIPG-Open and DIPG-All had been funded to collect biological samples and accelerate translation of therapeutics to the clinic. Despite evidence that 5-year survival had improved from 1% to 2%, clearly major advances need to be made in new treatments, and monitoring the funding landscape carefully to make strategic investments will be essential.

The 1994 National Cancer Institute’s strategy to fund multi-institutional, multidisciplinary consortia to design and conduct early phase clinical trials in patients with high grade gliomas.

2003 Background: : In the early 1990’s, the NCI suspended activities of the Brain Tumor Study Group seeking to shift clinical brain tumor research from phase III trials to innovative and correlative rich phase I/II studies. In 1994, NCI funded three early phase brain tumor consortia, later reduced to two consortia in 1999 and one in 2009. In 2020, the NCI announced it would discontinue funding the brain tumor consortium and emphasize pre-clinical glioblastoma drug development (RFA-CA-20-047). Methods: The activities of the New Approaches to Brain Tumor Therapy (NABTT: 1994-2009) and Adult Brain Tumor Consortium (ABTC: 2009-2021) were summarized using data from the Central Operations Office that served the consortia for 27 years. Results: From 1994-2020, 48 consortium meetings were held to discuss, develop, conduct, and evaluate early phase clinical trials. These involved multidisciplinary brain tumor experts (neuro-oncologists, neurosurgeons, radiation oncologists, neuropathologists, statisticians, pharmacologists, imaging experts, immunologists, etc) from 27 US academic centers and hospitals. 85 clinical trials were written, approved by NCI and the Brain Malignancy Steering Committee, and conducted. Most trials evaluated NCI-provided therapeutic agents. 34 trials were conducted in collaboration with 27 pharmaceutical companies eager to develop malignant brain tumor therapeutics; for 9 of these the consortia held the IND. 4870 patients were accrued: 3375 to therapeutic and 1495 to non-therapeutic studies. 49 grant proposals were submitted to fund consortium activities with a 46% approval rate. 91 peer reviewed manuscripts were published, with 174 presentations and abstracts. 18 pharmaceutical symposia were conducted to attract new agents toward early phase brain tumor research. Consortia sponsored 34 Guest Lectureships and multidisciplinary symposia to focus on relevant critical research areas. Additionally, the consortia provided unique opportunities for young faculty to lead multicenter NABTT/ABTC trials with appropriate support and mentorship. Conclusions: Therapeutic progress for high grade gliomas has been slow for many reasons (95% of systemically administered agents do not penetrate the blood-brain barrier, inherent treatment resistance, immunologically “cold” phenotype, etc). NABTT/ABTC focused multidisciplinary, multi-institutional experts on major challenges unique to brain tumor research. The consortia developed innovative early phase clinical studies rich in correlative endpoints, fostered research grants, hosted relevant topical symposia, and provided leadership roles for young investigators while bringing together the NCI, industry, and committed multidisciplinary academicians to explore novel therapeutic options for patients with primary brain tumors.

COT-11 EFFECT OF PHYSICIAN SUPPORTS ON QUALITY CONTROL AND QUALITY ASSURANCE IN CLINICAL BRAIN TUMOR RESEARCH

BACKGROUND Clinical physicians have difficulties in conducting investigator-initiated-trials because of increasing clinical duties in Japan. Therefore, physician support can be one of the important factors for quality control and quality assurance. In Kyoto University Hospital, clinical research professional’s support for physician had started at November 2012. In this study, we evaluate effect of physician supports on quality control and quality assurance in clinical brain tumor research. METHODS Our department of Neurosurgery has been a member of Brain Tumor Study Group in Japan Clinical Oncology Group (JCOG) since 2007. The number of registered patients, the status of periodic monitoring, the occurrence of inquiries per case, and details of physicians’ support (items, frequency, methods, etc.) in each clinical trial were investigated. The factors affecting the audit results conducted by JCOG Audit Committee on January 2013 and February 2019 are examined. RESULTS There are seven trials have been ongoing on or started since November 2012. There are fifty patients registered in the clinical studies until July 2019. Periodic monitoring has been carried out in 214 patients of cumulative total number since 2012. Physicians’ support mainly involved the preparation of ethical review documents, CRF documentation, responses to data queries, preparation of SAE reports, study schedule check and monitoring of observation items. The audit results of site visit were acceptable, total evaluation score 68.80 on January 2013 and excellent, total evaluation score 99.9 on February 2019. CONCLUSION Clinical Trials Act has been implemented, and further improvement in the quality of clinical trials has been demanded. As the results of this study, we clarified the necessity for physician support and the contribution to quality improvement.

The ‘Ins and Outs’ of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?

In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models—a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly.

Brain tumor research in the United Kingdom: current perspective and future challenges. A strategy document from the NCRI Brain Tumor CSG

The National Cancer Research Institute (NCRI) is a partnership of charity and government research funders whose purpose is to improve health and quality of life by accelerating progress in cancer-related research through collaboration. Under this umbrella, the NCRI Brain Tumor Clinical Studies Group is focused on improving clinical outcomes for adult patients with brain and central nervous system tumors, including those with brain metastasis from other primary sites. This document discusses the current state of clinical brain tumor research in the United Kingdom and the challenges to increasing study and trial opportunities for patients. The clinical research priorities are defined along with a strategy to strengthen the existing brain tumor research network, improve access to tissue and imaging and to develop the future leadership for brain tumor research in the United Kingdom. This strategy document may serve as a framework for other organizations and countries.