Brastianos, Priscilla K.

Abstract Craniopharyngiomas are surgically challenging brain tumors. Postoperatively, quality of life is often significantly impaired due to neurological and endocrinological complications. Currently, FDA approved systemic treatments are not available for patients in whom craniopharyngiomas recur after surgery and radiation. Papillary craniopharyngiomas are characterized by the presence of BRAFV600E mutations. To date, five case reports have been published on the treatment of BRAFV600E mutant papillary craniopharyngiomas with BRAF and/or MEK inhibitors. In this presentation, authors from all five previously published reports share their collective experience and provide updated follow-up on their patients, thus generating an overview of all currently available information on targeted therapy in patients with BRAFV600E mutant papillary craniopharyngiomas. We have also included information on an additional patient with a papillary craniopharyngioma recently treated with BRAF and MEK inhibitors after tumor biopsy alone, in the absence of recurrence, highlighting the potential for a neo-adjuvant therapeutic approach. All six cases in our series showed dramatic responses to targeted treatment with BRAF (and MEK) inhibitors. Collectively, our cases are highly promising and informative for patient treatment, although uncertainty remains with regards to the optimal timing, the specific agents (single agent or dual therapy) to be used and the duration of treatment. The ongoing multicenter phase II Alliance A071601 trial (NCT03224767) of vemurafenib and cobimetinib for patients with biopsy-proven residual or recurrent papillary craniopharyngiomas should provide additional information to help guide patient management.

Abstract BACKGROUND The face of neuro-oncology providers has evolved over the century. We sought to evaluate if its culture has evolved concurrently. Women in NeuroOncology (“WiN.”) is a SNO subcomittee that identifies the needs of women in neuro-oncology and promotes advancement of the careers of women in neuro-oncology. We created this survey to examine bias within our field with the goal to implement future change. METHODS Following IRB approval, we surveyed both male and female SNO members and analyzed de-identified responses. RESULTS Of the 206 respondents, 25% identified as male, 84.9% were in academics, 73.7% were primarily research focused (69% clinical), and 59% were medical neuro-oncology focused. The majority of respondents were 36–45 years old (47%), followed by 46–55 (32%), and 21% aged 56+. 69.8% self-identified as white, followed by 22% Asian, 7.8% Latin, and 2.9% Black. The majority reported general professional bias at least “not infrequently”, with 11.7% reporting it “very commonly.” 59.9% reported “not being invited to participate and or being considered for an opportunity”, followed by 46.1% “being minimized, teased or disrespected”, 44.3% “being passed over for professional opportunities”, and 41.9% salary disparity. Furthermore, of those reporting general professional bias, 42.9% reported a lack of effective mentorship and 94% reported some frequency of burnout, with 34% “commonly, very commonly”, followed by 28.3% “not infrequently.” Notably, although only 25% of responders were men, 82.4% of total respondents reported some frequency of gender bias in the workplace, with “not infrequently” being the most commonly reported (48%). CONCLUSIONS In this survey, we identified SNO members who have experienced bias. Based on quantitative and qualitative responses, many reported bias manifesting as missing academic opportunities, salary disparity, burnout, and lack of mentorship. As we cultivate the next generation, we will use these results to engage those in leadership to promote unbiased equality.

Papillary craniopharyngiomas (PCPs) are characterized by the presence of BRAF V600E mutations, which are emerging as a useful guide for diagnosis and treatment decision making. The ongoing multicenter phase 2 Alliance A071601 trial is evaluating the efficacy of BRAF and mitogen‐activated protein kinase kinase (MEK) inhibitors for patients with PCPs. With continued successful responses, it is proposed that BRAF (and MEK) inhibitors be evaluated for the neoadjuvant treatment of patients with PCPs.

AbstractAccurate pathologic diagnoses and molecularly informed treatment decisions for a wide variety of cancers depend on robust clinical molecular testing that uses genomic, epigenomic, and transcriptomic-based tools. Nowhere is this more essential than in the workup of brain tumors, as emphasized by the incorporation of molecular criteria into the 2016 World Health Organization classification of central nervous system tumors and the updated official guidelines of the National Comprehensive Cancer Network. Despite the medical necessity of molecular testing in brain tumors, access to and utilization of molecular diagnostics is still highly variable across institutions, and a lack of reimbursement for such testing remains a significant obstacle. The objectives of this review are (i) to identify barriers to adoption of molecular testing in brain tumors, (ii) to describe the current molecular tools recommended for the clinical evaluation of brain tumors, and (iii) to summarize how molecular data are interpreted to guide clinical care, so as to improve understanding and justification for their coverage in the routine workup of adult and pediatric brain tumor cases.

PURPOSE The Congress of Neurological Surgeons (CNS) has developed a series of guidelines for the treatment of adults with metastatic brain tumors, including systemic therapy and supportive care topics. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS Two CNS guidelines were reviewed for developmental rigor by methodologists, and an independent multidisciplinary Expert Panel was formed to review the content and assess agreement with the recommendations. The Expert Panel voted to endorse the two guidelines, and ASCO and Society for Neuro-Oncology (SNO) independently reviewed and approved the ASCO/SNO guideline endorsement. RESULTS The ASCO/SNO Expert Panel determined that the recommendations from the CNS anticonvulsants and steroids guidelines, published January 9, 2019, are clear, thorough, and based on the most relevant scientific evidence. ASCO/SNO endorsed these two CNS guidelines with minor alterations. RECOMMENDATIONS Key recommendations include the following: prophylactic antiepileptic drugs were not recommended for routine use; and corticosteroids, specifically dexamethasone, were recommended for temporary symptomatic relief in patients with neurologic symptoms and signs related to mass effect from brain metastases. Additional information is available at www.asco.org/neurooncology-guidelines .

Purpose of reviewMeningiomas, the most common primary brain tumor, have historically been managed with surgery and radiation. Traditional chemotherapy has not been effective. Fortunately, recent advances in genetic sequencing have led to an improved understanding of the molecular drivers in meningioma. This article aims to discuss the diagnostic and therapeutic implications of recently discovered genetic alterations in meningiomas.Recent findingsMany of the recently discovered genetic alterations correlate with distinct clinical phenotypes.SMO,AKTandPIK3CAmutations are enriched in the anterior skull base.KLF4mutations are specific for secretory histology, andBAP1alterations are common in progressive rhabdoid meningiomas. Alterations inTERT,DMDandBAP1correlate with poor clinical outcomes. Importantly, the discovery of clinically actionable alterations in a number of genes, includingSMO,AKT1andPIK3CA,has opened up novel potential avenues for therapeutic management of meningiomas. Overexpression of PD-L1 in higher grade meningiomas also provides preclinical support for the investigation of checkpoint blockade.SummaryThe discovery of genetic alterations has improved our understanding of the natural history and classification of meningiomas. Clinical trials with several novel agents targeting driver mutations are currently accruing patients and they can lead to better treatment strategies.