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Purpose To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. Methods ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Fifty-nine randomized trials focusing on therapeutic management were identified. Recommendations Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMTpromoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.

Objectives Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. Methods We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. Results Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. Conclusions PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.

Background Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. Methods In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population. Results The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field. Conclusions The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.

While immuno-oncotherapy (IO) has significantly improved outcomes in the treatment of systemic cancers, various neurological complications have accompanied these therapies. Treatment with immune checkpoint inhibitors (ICIs) risks multi-organ autoimmune inflammatory responses with gastrointestinal, dermatologic, and endocrine complications being the most common types of complications. Despite some evidence that these therapies are effective to treat central nervous system (CNS) tumors, there are a significant range of related neurological side effects due to ICIs. Neuroradiologic changes associated with ICIs are commonly misdiagnosed as progression and might limit treatment or otherwise impact patient care. Here, we provide a radiologic case series review restricted to neurological complications attributed to ICIs, anti-CTLA-4, and PD-L-1/PD-1 inhibitors. We report the first case series dedicated to the review of CNS/PNS radiologic changes secondary to ICI therapy in cancer patients. We provide a brief case synopsis with neuroimaging followed by an annotated review of the literature relevant to each case. We present a series of neuroradiological findings including nonspecific parenchymal and encephalitic, hypophyseal, neural (cranial and peripheral), meningeal, cavity-associated, and cranial osseous changes seen in association with the use of ICIs. Misdiagnosis of radiologic abnormalities secondary to neurological immune-related adverse events can impact patient treatment regimens and clinical outcomes. Rapid recognition of various neuroradiologic changes associated with ICI therapy can improve patient tolerance and adherence to cancer therapies.

Background Immuno-oncotherapy (IO) has revolutionized systemic cancer care but remains experimental in brain tumors. IO treatment risks multiorgan autoimmune inflammatory responses that limit its use. The central nervous system (CNS) is an immune-specialized compartment with restricted cellular access, thus fewer cases are reported for immune-mediated encephalitis. Interestingly, patients with history of blood–brain barrier compromise are potentially at higher risk for immune cell trafficking to the CNS. Case Description We report the first case, to our knowledge, of a 70-year-old man with clear cell renal cell carcinoma with pulmonary metastases treated with lung irradiation, nephrectomy, and chemotherapy prior to switching to single-agent nivolumab IO. The patient presented with new-onset generalized tonic-clonic seizure and left visual field-cut. Review of patient history revealed remote traumatic brain injury (TBI). Brain imaging noted a solid-enhancing right occipital mass that was presumed metastasis versus lymphoma. Cerebrospinal fluid cytology was negative for malignancy but concerning for lymphoproliferative process not determined to be malignant. The patient started steroids and anti-epileptic therapy. After negative systemic cancer re-staging, IO was discontinued and steroids were initiated with demonstrated patient clinical improvement. Conclusions We concluded the diagnosis of immune-mediated encephalitis secondary to IO with collection of reactive T-cells within the area of encephalomalacia. The area of encephalomalacia from prior TBI served to compartmentalize the reactive lymphocytes, giving the appearance of a mass. Taken together, new onset seizure in patients on IO might signal encephalitis and CNS metastatic mimicry should be considered in patients with a prior history of TBI and encephalomalacia.

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 .

While females make up almost 60% of all brain and spinal cord tumors in adults, guidelines that address women’s issues in neuro-oncology are lacking. This review sheds light on two common women’s issues in neuro-oncology. Neuro-oncology providers are often faced with patient questions about fertility and pregnancy maintenance or prevention and typically respond with generic cancer chemotherapy recommendations, based on the paucity of evidence on the use of common neuro-oncology chemotherapies and pregnancy. While these remain important gap issues, there are several other poorly researched issues in the Neuro-Oncology of Women (N.O.W.) including recommendations around endogenous and iatrogenic hormone exposure and female sexuality in cancer. As a significant percentage of cancers are hormone-dependent, it is important to understand how changes in hormone levels impact tumor biology over the course of a woman’s lifespan. Furthermore, greater attention should be given to the impact of tumors and tumor treatments on female sexuality. This article is intended to serve as an introduction to these two specific subjects within the vast expanse of N.O.W. subject matter.

BACKGROUND LMC is a rare complication of systemic cancer metastasis to the leptomeninges. Although first described in 1870 treatment options remain few for this rapidly fatal condition commonly excluded from clinical trials and disease site guideline updates. Whole brain radiation therapy (WBRT) and intrathecal (IT) chemotherapy are commonly employed and there is growing evidence for systemic therapies that cross the blood brain barrier. Disseminated necrotizing leukoencephalopathy (DNL) is a self-limited rare treatment-related radiographic finding variably associated with clinical decline and often misdiagnosed as progression or infection. DNL has been reported in patients exposed to IT chemotherapy and CNS irradiation. Our lab recently published improved LMC control with extended survival after standardization of Ommaya clinic IT treatment regimens, although with increased incidence of DNL. METHODS We retrospectively analyzed patients with LMC treated with IT chemotherapy after WBRT between 2017 – 2020. We reviewed sequential brain imaging over the treatment course to determine if there were predictive CSF markers associated with the development of DNL. RESULTS Of the 41 patients evaluated, 24% (n=10) developed DNL at a median 24-weeks after start of IT chemotherapy and WBRT. Of the patients with radiographically assessed DNL, 80% (n=8) experienced elevated CSF protein and 40% (n=4) had elevated white blood cells within 8-weeks prior to radiographic determination of DNL. Cytology remained benign and glucose was not significantly changed prior to DNL development. CONCLUSION Given the poor outcome of LMC, there is a need for treatment standardization and better understanding of treatment-associated radiographic changes. Evaluation of CSF markers to predict impending development of DNL in this treatment population might limit radiographic misdiagnoses and patient clinical decline as well as offer a potential window of opportunity for treatment de-escalation.

BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumor in adults with a slightly higher incidence and shortened survival in males as compared to females in the United States. Recently, there has been a focus on specific health disparities between rural versus urban populations. There is growing interest in these disparities as it pertains to CNS tumors. Here, we characterize a rural population of females diagnosed with GBM as part of an ongoing investigation to drive research and further discussion around this important topic. METHODS We performed a single institutional retrospective review of patients with GBM in rural Pennsylvania between 2006 and 2019. We collected clinical, demographic, and tumor specific data including chronic comorbid disease, marital status, age at diagnosis, obstetric history, BMI, and tumor location. RESULTS Of the 611 patients diagnosed with GBM from 2006–2019, 41% (n= 249) were female with a median overall survival of 9.5 months compared to 10.7 months in males. At diagnoses, 69% (n=173) of females had chronic comorbid allergy/immunology disorders, 41% (n=101) had endocrine disorders, 53% (n=132) had hypertension, and 43% (n=106) had mood disorders. Tumor laterality was predominantly right-sided (58%, n=145) and frequently involved the frontal lobe (38%, n=94). The temporal lobe was the second most commonly involved (32%, n=80). The median age at diagnosis was 65-years-old [range, 21–92]. Fifty-six percent (n=140) of women were married with an average of 2.27 childbirths. The median body mass index (BMI) was 27.5 [range, 16.3–64.9] with 66% of females classified as overweight/obese at diagnosis. Greater than 95% of females were insured. CONCLUSION There is a high incidence of chronic comorbid disease and obesity amongst females in this rural population, and females demonstrated a poorer overall survival as compared to males. Further comparisons are needed to characterize rural female GBM populations versus those in urban areas.

Coronavirus disease 2019 (COVID-19) has grossly affected how we deliver health care and how health care institutions derive value from the care provided. Adapting to new technologies and reimbursement patterns were challenges that had to be met by the institutions while patients struggled with decisions to prioritize concerns and to identify new pathways to care. With the implementation of social distancing practices, telemedicine plays an increasing role in patient care delivery, particularly in the field of neurology. This is of particular concern in our cancer patient population given that these patients are often at increased infectious risk on immunosuppressive therapies and often have mobility limitations. We reviewed telemedicine practices in neurology pre– and post–COVID-19 and evaluated the neuro-oncology clinical practice approaches of 2 large care systems, Barrow Neurological Institute and Geisinger Health. Practice metrics were collected for impact on clinic volumes, institutional recovery techniques, and task force development to address COVID-19 specific issues. Neuro-Oncology divisions reached 67% or more of prepandemic capacity (patient visits and slot utilization) within 3 weeks and returned to 90% or greater capacity within 6 weeks of initial closures due to COVID-19. The 2 health systems rapidly and effectively implemented telehealth practices to recover patient volumes. Although telemedicine will not replace the in-person clinical visit, telemedicine will likely continue to be an integral part of neuro-oncologic care. Telemedicine has potential for expanding access in remote areas and provides a convenient alternative to patients with limited mobility, transportation, or other socioeconomic complexities that otherwise challenge patient visit adherence.

Purpose To evaluate neuro-oncology clinician time utilization for medication management and identify a cost beneficial role for integration of a dedicated pharmacy specialists. Methods A pharmacist was temporarily integrated into a neuro-oncology clinic for a 30-day period to evaluate the clinical practice and perform a 14-day clinical chart evaluation and patient interactions as part of a single institutional exploratory analysis. The pharmacist completed screenings for drug-drug interactions, new therapies, medication reconciliation, and advanced interventions as part of a collaborative practice agreement for pharmacist autonomy. Pharmacist time spent was calculated and documented within the patient encounters to support physician decision-making. A comparative estimate of pharmacist versus physician time utilization and cost for each was completed to derive a savings analysis for integration of a dedicated clinic pharmacist. Result During the 14-day clinical assessment, the pharmacist completed 147 encounters with 338 interventions. Of the encounters, 90% (n = 132) were higher complexity requiring plan modification, and approximately 48% (n = 162) of all interventions required ≥10 minutes of the pharmacist’s time. Physician non-patient-facing time devoted to medication tasks was 5-hours weekly (0.125 FTE, full time equivalents), an estimated direct salary cost of $937/week ($45,000 yearly). Hire of a part-time pharmacist at 0.50 FTE would cover the clinical need with supported documentation and medication monitoring at a cost of $45,000/year. Conclusion Defining the roles for dedicated neuro-oncology clinic pharmacists allows for cost-savings through re-allocation of physician time and improves subspecialty clinic operations as well as patient care.

Background. The Congress of Neurological Surgeons (CNS) has developed a series of guidelines on 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 multi-disciplinary 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 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 upon the most relevant scientific evidence. ASCO/SNO endorsed these two CNS guidelines, with minor alterations. Conclusions. Key recommendations include: prophylactic anti-epileptic drugs were not recommended for routine use; corticosteroids (specifically dexamethasone) were recommended for temporary symptomatic relief in patients with neurologic symptoms and signs related to mass effect from brain metastases.

BackgroundTherapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure.Patients/MethodsA retrospective review of 622 GBM patients between 2006-2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2×2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI.ResultsSeventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥4 was the most significant prognostic indicator of death.ConclusionsImplications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.KEYPOINTSIncreased confidence in defining true tumor progression is of critical importance.Imaging markers preceding progression offer novel timepoints for salvage therapies.Earlier intervention might increase tumor therapy exposure and reshape clinical trial design.IMPORTANCE OF STUDYTherapeutic intervention at progression has failed to show benefit. Accurately defining progression impacts clinical decision-making, yet current response assessment criteria in glioblastoma remain unvalidated. The data presented identifies a highly sensitive brain tumor imaging biomarker, SI, which coincides with declining neurologic function and might supplement existing criteria to improve clinician confidence to declare GBM progression. Furthermore, as SI precedes current assessment guidelines by an average of 3.4 months, this finding might also offer an earlier window of opportunity for salvage therapeutic intervention and reshape glioma clinical trial design. This signal has been previously associated with glioma progression; however, prior studies were hampered by overly inclusive criteria and failed to make the innovative clinical and prognostic associations evidenced in our study. Prospective validation of the proposed imaging biomarker is currently underway as part of a centrally reviewed prospective interventional clinical trial for newly diagnosed GBM.

The COVID-19 outbreak is posing unprecedented risks and challenges for all communities and health care systems, worldwide. There are unique considerations for many adult patients with gliomas who are vulnerable to the novel coronavirus due to older age and immunosuppression. As patients with terminal illnesses, they present ethical challenges for centers that may need to ration access to ventilator care due to insufficient critical care capacity. It is urgent for the neuro-oncology community to develop a proactive and coordinated approach to the care of adults with gliomas in order to provide them with the best possible oncologic care while also reducing their risk of viral infection during times of potential health care system failure. In this article, we present an approach developed by an international multidisciplinary group to optimize the care of adults with gliomas during this pandemic. We recommend measures to promote strict physical distancing and minimize exposures for patients, address risk and benefit of all therapeutic interventions, proactively develop end-of-life plans, educate patients and caregivers, and ensure the health of the multidisciplinary neuro-oncology workforce. This pandemic is already changing neuro-oncologic care delivery around the globe. It is important to highlight opportunities to maximize the benefit and minimize the risk of glioma management during this pandemic and potentially, in the future.

Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer.To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19.This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021.Black and White race recorded in patient's electronic health record.An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death.Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]).These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

BACKGROUND Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers and clinicians led us to conduct a survey identifying opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals. METHODS Summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates (European Association of Neuro-Oncology, Asian Society for Neuro-Oncology, Society for Neuro-Oncology Latin America and Society for Neuro-Oncology Sub-Saharan Africa). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career success metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic and sexual identity. Standard descriptive statistics characterized the study population. RESULTS The 386 respondents were predominantly female (58%) with a median age range of 40-49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology community. CONCLUSIONS: The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.

Explanation of brain tumor imaging (BTI) complexities to patients is a challenge in neuro-oncology. With limited tools, neuro-oncologist attempt to demonstrate tumor volumes and anatomy, estimate surgical risks, and treatment responses. Arming clinicians with alternative BTI might help alleviate the stress of initial patient consults and follow-up surveillance visits. These interactions are critical to the physician-patient relationship, patient compliance, and satisfaction. Currently, 2D-MRI review is standard, often leaving the patient with a less-than-complete understanding of their tumor. Historically, 3D-Brain-Tumor-Modeling (3DBTM) has been used for neurosurgical simulation and planning. Here, we evaluated the use 3DBTM alongside routine MRI impact on patient health literacy and satisfaction. Our institution introduced 3DBTM as a best practice approach. Images were presented as 3D video or tangible 3D color renditions, or 2D MRI. We collected patient pre-visit and post-visit surveys to assess patient’s understanding of tumor features, opportunity to review images, and patient level of satisfaction. Data from 277 pre-visit and 159 post-visit surveys was collected from the Geisinger Neuro-Oncology Clinic over a six-month period. Post-visit survey categories included reviews of: 3DBTM (n=54), 2D-MRI (n=51), and no imaging (n=55). Patients without CNS tumors were excluded (n=101). Pre-visit surveys showed 30% (n=82) of patients had little-to-no prior understanding of their tumor location and size, and 53% (n=147) of patients believed that a 3DBTM would improve their understanding. Post-visit analysis demonstrated that only 21% (n= 29) of patients reported not seeing any imaging during the visit. Nearly 85% (n=46) of patients who had reviewed a 3DBTM noted improved tumor understanding. Of the patients who solely viewed 2D-MRI, 68% (n=35) reported improved understanding of their tumor but would like more advanced imaging teaching. In total, 84% of patients noted overall satisfaction with the clinic visit. These results support the use of 3DBTM in patient education and facilitating clinical interviews.

This year nearly 86,000 persons in the US will be diagnosed with a primary brain tumor. Glioblastoma (GBM) is the deadliest and most common of these tumors in adults with overall survival around 15mos. Disease progression is inevitable, and effective second-line therapies are few. Delays in identifying progressed GBM risks neurologic decline, continuation of ineffective therapies, and increased tumor-mutational-burden, potentially rendering treatment less-effective. Brain tumor imaging can be ambiguous and is an active topic in neuro-oncology as there are currently no validated approaches to assessment of tumor treatment response. We present a single institution database including 622 gross-totally-resected GBMs (2006–2018) to evaluate changes in T2/FLAIR signal intensity (T2FSI), diffusion restriction, and contrast enhancement both in and around the resection cavity (RC) to determine earliest indicators of tumor progression. Analysis of NANO score was completed to correlate with predicted tumor progression. This is an early data release of an ongoing two-phased retrospective/prospective study with findings that support a novel integration of radiographic sequences and NANO to supplement established RANO criteria in earlier detection of GBM progression. Of 622 confirmed GBMs, 158 fit the rigorous criteria – included here are 58 cases. We report 70% (n=41) of patients show RC T2FSI correlating with restricted diffusion and increasing NANO score (0.5–1.4) as early as 3.8mos prior to and at time of radiographic progression, respectively. Previous studies have reported similar T2FSI but without associated NANO, less rigid inclusion criteria, and limited MRI sequences. We also report imaging phenomena, not previously described, such as FLAIR migration and FLAIR coring timed closely with progression. The proposed technique uses routine MRI, therefore readily standardized in clinical practice. With further validation, this novel integration of imaging and neurologic assessment might serve to supplement existing response criteria in GBM and improve clinician confidence in earlier detection of progression.

BACKGROUND Disseminated necrotizing leukoencephalopathy (DNL) is a rare complication of intrathecal (IT) methotrexate administration with a previously reported incidence of 2.8%1 in patients undergoing treatment for central nervous system leukemia or lymphoma. The purpose of this study is to estimate the incidence of DNL in a series of patients undergoing treatment for leptomeningeal carcinomatosis (LMC) and to better characterize the radiographic findings associated with DNL. METHODS A retrospective review of a prospectively gathered database of 36 LMC patients was conducted. Patients were treated with whole brain radiation and a standardized regimen of twice-weekly IT methotrexate in the context of an established IT chemotherapy clinic. Data regarding the patients’ primary cancer pathology, time from initiation of IT methotrexate to onset of DNL, and radiographic characteristics of DNL were collected. RESULTS Six of 36 patients (16.7%) developed DNL. Mean time from initiation of IT treatment to development of DNL was 6.7 months. Primary pathologies of the DNL patients were breast (3), melanoma (1), GI (1), and pancreatic neuroendocrine (1). Radiologic presentation included areas of T2 hyperintensity, T1 hypointensity with contrast-enhancement, and restricted diffusion, all consistent with acute demyelination. These radiographic changes predominantly involved the catheter tract, periventricular and deep white matter, and grey-white interface. Interpretation of the magnetic resonance imaging by radiologists was highly inaccurate with the findings interpreted as catheter infection, progression of metastatic disease, stroke, or “possible treatment effect”, but never correctly identified as DNL. CONCLUSION DNL is a rare complication of intrathecal chemotherapy but may have a higher incidence in patients undergoing aggressive management of LMC than in those being treated for central nervous system lymphoma or leukemia. Although the imaging in DNL often exhibits characteristic findings, the rarity of this pathology leads to frequent misinterpretation, potentially complicating management of LMC.

Leptomeningeal carcinomatosis (LMC), first described in 1870, involves leptomeningeal and CSF invasion by neoplastic cells and portends poor survival. Among solid tumor LMC, breast cancer is the most common followed by lung and melanoma. With an estimated 100,000+ new cases yearly, the dual-edged sword of systemic treatment drives the increasing incidence as cancer patients live longer and on non-CNS penetrating therapies. Addition of immuno-oncotherapies has impacted LMC survival. At time of diagnosis, most patients have multiple neurologic disabilities. Multiple reports on the topic have not yielded consistent treatment standards to extend patient survival. Most agree that local CNS control coupled with systemic therapy offers the best survival. Still, there are few established Ommaya clinics (OC). Importantly, LMC is a common exclusionary criterion for clinical trials. A single institutional evaluation of 147 patients (2012–2019) with a diagnosis of LMC was completed. 69 of 147 were excluded, leaving 48 pre-OC and 30 OC patients. The mOS (weeks) of those treated with intrathecal chemotherapy (ITC) versus no ITC was compared between cohorts: pre-OC and OC (3.36, 15.29****). Average KPS at time of diagnosis in pre-OC and OC was 70–80 (ECOG 2–3). The mOS was compared between breast (5, 28*), lung (3, 3) and melanoma (5,10*) in the pre-OC and OC respectively. The treatment standardized for the OC includes whole-brain radiation, Ommaya reservoir placement, systemic treatment, treatment with ITC (2x weekly – q other month) and MR imaging every 3 months. Breast cancer patients fared the best followed by melanoma and lung patients in the OC. With use of advanced practitioners (APs), standardization of treatment and surveillance is achievable. Patients treated according to a standardized OC regimen experienced longer overall survival along with a 10% improvement in KPS after two months of treatment. Development of institutional OCs reduces treatment variability and increases clinical surveillance.

INTRODUCTION Meningioma is the most common benign primary brain tumor in adults comprising 37% of all primary CNS tumors. Approximately 81.1% of meningiomas are grade I, 16.9% - grade II, and 1.7% - grade III. While females are 2.5 times more likely to have meningiomas, males more commonly have aggressive grades. Loss of progesterone receptor (PR) and presence of androgen receptor (AR) are associated with tumor aggressiveness. We observed a declining sex-discrepancy with increasing tumor grade. We present an ongoing assessment of a rural population to define potential factors contributing to this observation. METHODS We completed a single institutional retrospective review of 406 pathology confirmed meningiomas in rural Northeast Pennsylvania. We compared WHO grade, hormone receptors, and proliferative indices between males and females. We further evaluated tumor location and comorbid endocrine disease for possible association. RESULTS Our patient cohort had a high frequency of aggressive tumors 73.5% (n= 297) grade I, 24% (n= 99) grade II, and 2.5% (n= 10) grade III. The ratio of females versus males was 3.1:1, 1.3:1, and 1:1 in grades I, II, and III respectively. Factors contributing to closing the sex-gap were: (1) grade II: males expressed less PR than females (76% vs 94%); (2) grade III: females expressed less AR than males (0% vs 100%), while PR expression remained equivalent; and (3) males had higher tumor proliferative indices compared to females (7% and 22% vs 2% and 14%), grades I and II respectively. There was no relationship determined for tumor location or comorbid endocrine disease between the sexes. CONCLUSION The association between declining sex discrepancy in meningioma with increasing tumor aggressiveness is potentially related to the expression PR, AR, and increased tumor proliferation indices with increasing meningioma grade.

Coronavirus disease 2019 (COVID-19) has grossly impacted how we deliver healthcare and how healthcare institutions derive value from the care provided. at increased infectious risk on immunosuppressive therapies and often have mobility limitations. Adapting to new technologies and reimbursement patterns were challenges that had to be met by the institutions while patients struggled with decisions to prioritize concerns and to identify new pathways to care. With the implementation of social distancing practices, telemedicine plays an increasing role in patient care delivery, particularly in the field of Neurology. This is of particular concern in our cancer patient population given that these patients are often at increased infectious risk on immunosuppressive therapies and often have mobility limitations. We reviewed telemedicine practices in neurology pre-/post-COVID-19 and evaluated the neuro-oncology clinical practice approaches of two large care systems, Barrow Neurological Institute and Geisinger Health. Practice metrics were collected for impact on clinic volumes, institutional recovery techniques, and task force development to address COVID-19 specific issues. Neuro-Oncology divisions reached >67% of pre-pandemic capacity (patient visits and slot utilization) within 3-weeks and returned to >90% capacity within 6-weeks of initial closures due to COVID-19. The two health systems rapidly and effectively implemented telehealth practices to recover patient volumes. While telemedicine will not replace the in-person clinical visit, telemedicine will likely continue to be an integral part of neuro-oncologic care. Telemedicine has potential for expanding access in remote areas and provides a convenient alternative to patients with limited mobility, transportation, or other socioeconomic complexities that otherwise challenge patient visit adherence.

BACKGROUND The COVID-19 pandemic has placed excessive strain on health care systems and this is especially evident in treatment decision-making for cancer patients. Glioblastoma (GBM) patients are among the most vulnerable due to increased incidence in the elderly (median age 64 years, peak between 75–84 years) and the short survival time. A virtual meeting was convened on May 9, 2020 with a panel of international neuro-oncology experts with hands-on experience using Tumor Treating Fields (TTFields). The objective was to assess the risk-to-benefit and to provide guidance for using TTFields in GBM during the COVID-19 pandemic. PANEL DISCUSSION Topics discussed included support and delivery of TTFields during the COVID-19 pandemic, concomitant use of TTFields with chemotherapy, and any potential impact of TTFields on the immune system in an intrinsically immunosuppressed GBM population. Special consideration was given to TTFields’ use in elderly patients and in combination with radiotherapy regimens (standard versus hypo-fractionated). Finally, we discussed the need to better capture COVID-19 positive brain tumor patients to analyze longitudinal outcomes and subtle changes in treatment decision-making during the pandemic. EXPERT CONSENSUS TTFields is a portable home-use device which can be managed via telemedicine and safely used in GBM patients during the COVID-19 pandemic. TTFields has no known immunosuppressive effects and is a reliable treatment modality with a relatively favorable side-effect profile. This is important during a crisis where other treatment methods might be limited, especially for elderly patients and patients with multiple co-morbidities. It is too early to estimate the full impact of COVID-19 on the global healthcare system and on patient outcomes and strongly recommended the need to collaborate with existing cancer COVID-19 registries (i.e. CCC19, ESMO-CoCARE, etc.) to follow CNS tumor patients. These efforts would have implications in assessing lessons-learned from this crisis and future guideline development.

Neuro-Oncology of Women (N.O.W.) is aimed to bring awareness to and increase research around pertinent neuro-oncology issues over the changing microenvironmental states over the female lifespan. Few neuro-oncologic diseases have validated clinical guidelines pertaining to pubescent, reproductive-aged, or peri/post-menopausal females. While some of the most common intracranial tumors predominantly affect women, guiding research on the use of hormone therapies, fertility, pregnancy, and tumor monitoring during pregnancy or perimenopausal stages are lacking. Questions about specialized tumor surveillance, pregnancy prevention/promotion, and fertility/pregnancy risks for tumor treating devices and immunotherapies are not confidently answered. As cancer therapies extend patient overall-survival, clinicians must be increasingly prepared to address brain tumors in women at various life-stages. Finally, the psycho-social impact on women and their families is discussed. Here, we feature neuro-oncology conditions in women and emphasize the common patient and clinician concerns.

PCNS-PTLD is a rare complication of solid organ transplantation (SOT) and is a distinct entity from primary CNS lymphoma (PCNSL). With fewer than 90 cases reported since 1970, there are no treatment standards. Existing data supports combining reduction of immunosuppression (RI), whole-brain radiotherapy, monoclonal antibody therapy, and systemic/IT chemotherapy. Treating kidney SOT PTLD is complicated by reduced renal clearance, contrast-dye restrictions, and nephrotoxicity. Treatment complications and allograft rejection cause early morbidity and mortality. Rapid identification of serum/CSF supporting diagnostic markers such as active EBV replication, elevated CSF protein, and positive cytology/flow cytometry is critical. We report three cases of B/T-cell PTLD in renal-SOT patients 1–27 years on immunosuppression (steroids, mycophenolate, tacrolimus/sirolimus) who presented with focal neurologic deficits and multifocal MRI lesions. After confirming CNS-isolated disease patients were treated with partial-RI, dexamethasone, and induction with rituximab weekly cycles. Patients had objective responses and underwent consolidative rituximab therapy q21-days with restaging. Residual enhancing lesions were treated by stereotactic radiosurgery and one year of temozolomide chemotherapy days 1–5 on a 28-day cycle. We monitored serum LD, drug levels, and serum EBV as indicators for progression/recurrence. Patients achieved complete responses and mOS has not been met. Long-term survival in PCNS-PTLD is one distinguishing feature from PCNSL. With multiple treatment obstacles in renal-SOT PT early recognition and minimally toxic regimens improve patient outcomes. This data challenges traditional paradigms in diagnosis and treatment of PTLD, specifically EBV+ disease occurring >6 years post SOT. We propose that the specialized CNS immune microenvironment permits EBV driving of neoplastic progression, which is exquisitely sensitive to B-cell targeting concurrent with partial restoration of host immunity. Furthermore, targeted radiotherapy, temozolomide, and partial immunosuppression maintains patient quality-of-life and reduce risk for allograft rejection.

In 2019, a projected 86,000 persons in the US will be diagnosed with a primary brain tumor, with an estimated prevalence of 700,000. Glioblastoma (GBM) is the deadliest and most common of these tumors in adults with an overall survival ~15 months. Exposure to ionizing radiation is the single known environmental risk factor for GBM. Most research in the field is directed at treatment and tumor biology/classification. There is growing interest in geodemographics, disease prevention, and measuring quality-survival in GBM. We evaluated 622 GBM patients (2006 to 2018) in Northeastern/Northcentral Pennsylvania treated at one of the nation’s largest rural hospital systems. Each patient was geocoded (plotted longitude/latitude) address at time of diagnosis and we used medical records, projected 2015 Census, and Environmental Protection Agency data to develop risk maps. Preliminary evaluation of overall survival (OS) and incidence related to distance from hospital, age, sex, level of education, insurance, income, and income disparity (Gini coefficient measure of income inequality) was completed. Interestingly, all significant clusters of high GBM incidence lay along water-ways or overlapped with high coal mine reprocessing. Contrary to recent studies, there was no significant sex or distance (0mi to 150mi) impact on survival. However, each age-decile increase resulted in an average 9mo decrease in OS (37mo[< 40yo], 26mo [41-50yo], 17mo [51-60yo], 12mo [61-70yo], and 3mo [>71yo]). Counties with the lowest OS shared geodemographic characteristics such as fewer insured and lower incomes (low income inequality), and counties with more college educated persons had longer survival. Counties with higher GBM incidences had better insured percentages, lower incomes (high income inequality), and large polarity between high school uneducated and college educated persons. Rural populations potentially demonstrate unique geodemographic characteristics that might better predict disease outcomes. Studies in this area could influence improvements in public policy and prevention-focused health literacy opportunities.

Meningiomas comprise 37% of primary brain tumors, arise extra-axially from the arachnoid cap cells, and are typically identified by classic imaging and histopathologic features. Blacks, females, and people age 65+ have higher incidence rate - partially correlated with hormonal states, high body mass index, and known genetic predispositions. Prognostication is otherwise based on histopathologic findings and 90% of meningiomas are classified as benign (WHO grade I). Despite use of these prognostic tools, clinicians often observe a more divergent post-operative clinical course. While several pre-clinical studies have identified putative oncogenic influencers, many have failed to show correlation in human trials. Here, we evaluate a single institutional meningioma database stratified by geodemographic and clinical data to identify novel integrated prognostic indicators for aggressive tumor natural history. Our database contains 3,528 image-confirmed meningiomas between 1992–2019. This report focused on 415 pathology-confirmed cases between 2006–2019: WHO grades I, II, III were 73% (n=303), 25% (n=103), and 2% (n=9) respectively, 71% female predominance (n=294), median age at diagnosis 57-years-old, and 97.5% were white race. Thus far, full exome sequencing has been completed on >50% of cases and >80% have available tumor tissue for future testing as part of this rural Pennsylvania database with high incident aggressive and/or multiply recurrent meningiomas. We selected four representative cases to compare post-operative prognostication to observed clinical outcomes and provide molecular/genetic, histopathologic, treatment modality, comorbid, and other clinical features associated with morbidity/mortality. Included in this patient review is the first reported case of a rare (< 1%) chordoid meningioma, multiply recurrent despite 8-years of aggressive treatment modalities, including surgery, radiation, chemotherapy and androgen-blockade, with eventual extracranial metastasis to the lung, a meningiocarcinoma, if you will. Thorough interrogation of the completed database could yield novel predictive indicators of clinically aggressive meningiomas and guide clinical decision-making for optimized surveillance in high-risk patients.

With the success of immuno-oncotherapy (IO) to treat systemic cancers came the risk for multi-organ autoimmune inflammation (esophagitis, colitis, hypophysitis, pneumonitis, etc.). Immune-mediated encephalitis, however, has been only rarely described in patients treated on IO. Here we present the first case of a 70-year-old male with history of clear cell renal cell carcinoma (CCRCC, Fuhrman grade 4, April 2017) post-nephrectomy with early progressive pulmonary metastases treated with pazopanib before switching to single-agent nivolumab (February 2018) with demonstrated early response. Further progression (March 2019) added body irradiation and continued systemic nivolumab with questionable medication-induced dermatitis. Patient presented to ED in May 2019 with new-onset generalized tonic-clonic seizure, left visual field cut, and 4.6cm heterogeneous enhancing right occipital mass with vasogenic edema on brain MRI, presumed metastasis. However, unknown to the patient was a remote area of right occipital encephalomalacia (found on skull-based portion of staging PET, July 2018) presumed silent stroke or TBI endorsed 20-years-ago. Patient started anti-epileptic therapy and underwent negative CSF evaluation before neurosurgical resection. Tissue pathology concerning for lymphoproliferative malignancy versus reactive lymphocytic infiltrate with perivascular distribution of monomorphic CD4+ T-cell predominance (97%) and positive T-cell receptor (gamma, beta) gene rearrangement. While clonal T-cell populations are highly suggestive of T-cell malignancies, reactive conditions can also rarely show clonal T-cell populations. Patient underwent a negative systemic staging for lymphoma and IO was discontinued without immediate initiation of steroids. Follow up clinical evaluation reveal patient improved off IO therapy. Patient was determined to have reactive immune-mediated encephalitis secondary to IO therapy causing seizure mimicking brain metastasis of primary CCRCC. Interestingly, the prior area of encephalomalacia allowed for a cellular bed to collect, resembling brain mass. Upfront staging brain MRI prior to starting IO might have revealed susceptible area and could be considered in these patients

There is no cure for glioblastoma (GBM), the most lethal primary brain tumor in adults. Despite decades of research aimed to improve outcomes, median survival is only 14–16 months. While promising discoveries in molecular genetics and immunotherapy continuously enhance our understanding of GBM and inspire new treatment approaches, challenges related to tumor-heterogeneity, inevitable recurrence, and poor patient tolerance limit treatment. The emergent need for paradigm-shifting approaches to to improve GBM-targeting is evident. Although never previously comprehensively reported, pregnancy/fetal-development shares striking similarities with gliobastomagenesis. Developing in an immune-deviated host, within an immune-privileged compartment, shielded and maintained by a proficiently adaptable microenvironment, both glioblastoma and fetal development thrive. After nine-months of pregnancy, biological and immune processes give-way to delivery (fetal-allograft rejection); however, GBM clearance is not so well orchestrated. By investigating the stages of these biologically reminiscent conditions, earlier events of glioblastomagenesis may be uncovered and potentially drive new treatment paradigms in neuro-oncology. While large cohort studies have not found a causal relationship between pregnancy and incidence of glioma, retrospective reviews of pregnancy concurrent with glioma consistently report increased aggressive glioma characteristics during the mid-late pregnancy period. These changes can in-part be ascribed to the influence of pregnancy hormones and growth factors accessing the CNS. In addition, (1) Pregnancy-mediated systemic immunosuppression and cellular re-education supporting glioma immune evasion; (2) Pregnancy hormones influence tumor-promoting cellular pathways; and (3) Fetal-maternal microchimerism allows for nesting of fetal cells within the glioma, offers local immunosuppression, and promotes glioma vascular neogenesis as quasi-stem-cells. Implementing the current knowledge of reproductive processes might offer new insight into GBM implantation and development. This abstract seeks a platform to discuss the potential to exploit overlapping concepts in reproductive immunology with that of neuro-oncology to develop clinical and biologic correlates between the two disciplines and drive innovative and paradigm-shifting multidisciplinary research.

In 2018 a projected 79,000 persons in the US will be diagnosed with a primary brain tumor. Glioblastoma (GBM) is the deadliest and most common of these tumors in adults with overall survival ~15 mos and >93% of patients deceased by 5-years. Disease progression is inevitable, and effective second-line therapies are few. Delays in identifying progressed GBM risks neurologic decline and increased tumor mutations that potentially renders treatment less-effective. Reliable brain tumor imaging can be ambiguous to distinguish true progression from treatment effect. Furthermore, inaccurate identification of tumor progression might result in continuation of ineffective treatment or premature discontinuation of effective therapies. This is an active topic in neuro-oncology as it applies to patient care and standardization of imaging techniques. Improved tumor imaging surveillance tools that supplement current standards and allow earlier detection of progression can improve clinician confidence and patient outcomes. This study collected 468 WHO grade IV astrocytomas with gross-total-resection within our institution between 2006 and 2017 to evaluate changes in T2/FLAIR signal intensity, diffusion restriction, and contrast enhancement both in and around the resection cavity to determine earliest indicators of tumor progression. Early data release of this ongoing retrospective study reveals encouraging findings that support a novel combination of radiographic biomarkers associated with GBM progression using standard brain tumor imaging. A feasibility study including 47 cases, thus far, support previously reported signal intensity changes within the resection cavity as well as specific phenomena that have not been previously described, such as FLAIR migration and signal coring. The proposed technique does not require advanced brain tumor imaging and can therefore be broadly employed and standardized in clinical practice. With further validation, this novel combination of imaging features that might serve to supplement existing response criteria.

Glioblastoma is the most deadly primary brain tumor in adults and has long represented a therapeutic challenge. Disease recurrence is inevitable, and the management of recurrent disease is complicated by spontaneous or induced tumor heterogeneity which confers resistance to therapy and increased oncogenicity. EGFR and the tumor-specific mutation EGFRvIII is commonly altered in glioblastoma making it an appealing therapeutic target. Immunotherapy is an emerging and promising therapeutic approach to glioma and the EGFRvIII vaccine, rindopepimut, is the first immunotherapeutic drug to enter Phase III clinical trials for glioblastoma. Rindopepimut activates a specific immune response against tumor cells harboring the EGFRvIII protein. This review evaluates the recently completed ReACT Phase II trial using rindopepimut plus bevacizumab in the setting of EGFRvIII-positive recurrent glioblastoma (Clinical Trials identifier: NCT01498328).

Rationale: Caspase-1 processes interleukin 1β (IL-1β) and IL-18 but may also contribute to apoptosis. In this context, caspase-1 knockout mice have been shown to be protected from endotoxin-induced mortality, whereas IL-1β knockout mice are not protected. Objectives: We therefore sought to delineate the mechanisms responsible for the differential responses between caspase-1 and IL-1β knockout mice. Methods: Caspase-1 knockout, IL-1β knockout, and IL-1β/IL-18 double knockout mice were compared with wild-type mice for survival after intraperitoneal challenge with live Escherichia coli. Measurements and Main Results: Caspase-1 knockout animals were protected from bacterial challenge, whereas wild-type, IL-1β knockout, and IL-1β/IL-18 double knockout animals were not. Wild-type animals and both IL-1β knockout and IL-1β/IL-18 double knockout mice demonstrated significant splenic B lymphocyte apoptosis, which was absent in the caspase-1 knockout mice. Importantly, IL-1β/IL-18 double knockout mice were protected from splenic cell apoptosis and sepsis-induced mortality by the caspase inhibitor zVAD-fmk. Furthermore, wild-type but not caspase-1 knockout splenic B lymphocytes induced peritoneal macrophages to assume an inhibitory phenotype. Conclusion: Taken together, these findings suggest that caspase-1 is important in the host response to sepsis at least in part via its ability to regulate sepsis-induced splenic cell apoptosis.

PCNS-PTLD is a rare complication following solid organ transplantation (SOT) and is a distinct entity from primary CNS lymphoma (PCNSL). With fewer than 100 cases reported since 1970, there is no standard of care for PCNS-PTLD. Existing data supports combining reduction of immunosuppression (RI), whole-brain radiotherapy, monoclonal antibody therapy, and systemic/IT chemotherapy. Treating kidney SOT (kSOT) PTLD is complicated by reduced renal clearance, contrast-dye restrictions, and nephrotoxicity. Treatment complications and allograft rejection cause early morbidity and mortality. Rapid identification of serum/CSF supporting diagnostic markers such as active EBV replication, elevated CSF protein, and positive cytology and flow cytometry is critical. We report two cases of mixed B/T-cell PTLD in kSOT patients >10 years on immunosuppression (steroids, mycophenolate, tacrolimus/sirolimus) who presented with focal and cognitive neurologic deficits. Brain MRI revealed multiple supra- and infratentorial lesions. Patients with confirmed CNS-isolated disease were treated with partial-RI (off mycophenolate) and dexamethasone prior to initiation of rituximab (375mg/m2) x4 weekly cycles. With objective response, patients underwent consolidative rituximab therapy q21-days x4 cycles and restaged. Residual enhancing lesions were treated by stereotactic radiosurgery along with 2-4 cycles of temozolomide chemotherapy (150mg/m2) days 1-5 on a 28-day cycle. With this strategy, both patients achieved a complete response. PCNS-PTLD long-term survival is one distinguishing feature from PCNSL. With multiple treatment obstacles in kSOT PTLD, maximized targeting and step-wise addition of minimally toxic regimens can improve patient outcomes. This data challenges traditional paradigms about diagnosis and treatment of PTLD, specifically EBV+ disease occurring >6 years post SOT. We propose that the brain’s specialized immune microenvironment permits EBV driving of neoplastic progression and that this process is particularly sensitive to B-cell targeting concurrent with partial restoration of host immunity achieved by minimal RI. Subsequent SRS, temozolomide therapy, and partial immunosuppression helps maintain patient quality-of-life and reduce risk for allograft rejection.

Glioblastoma (GBM) is the most lethal primary brain tumor in adults and is rarely identified concurrent with pregnancy. Several retrospective reports suggest that pregnancy promotes oncogenicity and ultimately tumor progression, although these mechanisms have not been clearly defined. Despite optimized multimodality treatment, median overall survival in GBM is 14-16 months. Tumor recurrence is inevitable and presents additional treatment challenges due to tumor heterogeneity which confers resistance to therapy and increased tumor oncogenicity. Treatment of recurrent disease in pregnant patients is further complicated by pregnancy-associated host immunosuppression, increased metabolic and vascular demands, restricted use of contrasted imaging modalities, and overall avoidance of risks to the fetus. Here, we offer the first report of a clinical case using laser interstitial thermal therapy (LITT) to manage progressed GBM during pregnancy. This work discusses the unique challenges related to determining the neurosurgical and medical treatment approaches, interpretation of neuroimaging post-LITT procedure, and appropriate multidisciplinary clinical follow-up. LITT was successfully used to offer a minimally invasive neurosurgical approach with reduced time of anesthesia to halt GBM progression and delay use of systemic chemotherapy in a second trimester pregnant patient. Standard temozolomide therapy was re-initiated after the birth of a healthy female singleton. Addition of chemotherapy timed with important post-partum immune profile changes facilitated continued tumor control and avoided risk to the fetus. Ultimately, research in this area offers potential indications and considerations for optimized timing for use of the LITT neurosurgical approach in pregnant GBM patients with progressed disease.

Background In addition to recreational tanning bed use, UV radiation exposures are sometimes sought to self-treat skin conditions. The ability of tanning bed radiation exposure to trigger toxic epidermal necrolysis has not been reported. Observations A young woman attempted to treat a self-limiting drug hypersensitivity reaction via tanning bed radiation exposure, which resulted in a systemic toxic epidermal necrolysis–like reaction. Studies with cultured keratinocytes and an epithelial cell line reveal that UV-A radiation can synergize with other stimuli such as phorbol esters or interleukin 1 to produce large amounts of tumor necrosis factor, providing a potential mechanism for this exaggerated reaction. Conclusion In addition to inducing photodamage and skin cancer, tanning bed radiation exposure can trigger a toxic epidermal necrolysis–like reaction, possibly via the exaggerated production of keratinocyte cytokines such as tumor necrosis factor.