bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPID-10. MITOCHONDRIAL DNA SEQUENCE VARIATION AND RISK OF GLIOMA
Authors: Samanic Claudine , Teer Jamie , Thompson Zachary , Creed Jordan , Nabors Louis , Williams Sion , Egan Kathleen 
Published: December 2020

Abstract
Malignant gliomas are the most common primary adult brain tumors, with poor prognosis and ill-defined etiology. Mitochondrial DNA (mtDNA) sequence variants and haplogroups have been linked with certain cancers, but research on glioma is lacking. We examined the association of germline mtDNA variants and haplogroups with glioma risk in 1,654 glioma cases and 1,065 controls from a US case-control study, and 427 glioma cases and 1,541 controls from the UK Biobank, all genotyped using the UKBiobank array with 276 tiled mtDNA variants. The analysis was restricted to participants of European ancestry, and risk of glioblastoma (GBM) and lower grade glioma (LGG) was examined separately. Distribution of mitochondrial haplogroups (H/HV,I,J,K,R,T,U,V,W,X) were similar in both study populations, with 46.4% and 48.1% of controls in the US and UK studies respectively, identified as H/HV, the most common haplogroup. In the US study there was an inverse association between haplogroup W and glioma (OR=0.43, 95%CI: 0.23–0.79) when compared with the H/HV haplogroup, which was not seen in the UK study (OR=1.10, 95%CI: 0.49–2.49). In the US study, a significant inverse association was observed with the previously reported mtDNA variant m.14798T &gt; C (PMID: 31323957), resulting in the amino acid substitution F18L, for LGG (OR=0.73; 95%CI: 0.53–0.99) though not for GBM (OR=0.86; 95%CI: 0.66–1.11). In the UK study, the F18L substitution was associated with an increased risk of GBM (OR=1.48; 95%CI: 1.07–2.04), and no association was observed for LGG (OR=0.95; 95%CI: 0.53–1.68). Among cases in the US study with isocitrate dehydrogenase 1 (IDH1) status available (747 gliomas), a nonsignificant inverse association of the F18L substitution was observed in glioma cases with wild type (OR=0.72; 95%CI: 0.52–1.01) but not mutant (OR=1.08; 95%CI: 0.70–1.69) IDH1. No other common mtDNA variant (minor allele &gt; 5%) was associated with glioma risk in either study. These associations merit further study.
EPID-12. TREATMENT OUTCOMES OF MIDLINE GLIOMAS WITH H3K27 M: OUR BARROW NEUROLOGICAL INSTITUTE EXPERIENCE
Authors: Azadi Amir , Fonkem Ekokobe , Ranade Tejas 
Published: December 2020

Abstract

BACKGROUND
H3 K27M glioblastoma is an aggressive grade IV tumor located in midline structures, added in 2016 by the WHO. Current outcomes are poor. The rarity of these tumors presents a challenge for definitive research on developing optimal treatments.

METHODS
We conducted a case series of 12 patients at the Barrow Neurological Institute who were diagnosed with biopsy-proven H3 K27M glioblastoma. The clinical status of these patients was followed from dates of first and last contact. Factors included first line treatment, best response to first line treatment, recurrences, second line treatments, response assessment criteria for all treatment rounds, any discovered metastases, and vital status by date of last contact.

RESULTS
Of the initial 12 patients, 5 were lost to follow-up before meaningful clinical outcomes could be recorded. Of the remaining 7, all underwent temozolomide and radiation as components of first-line treatment. After first-line treatment, 1/7 (14.2%) had partial response, 3/7 (42.8%) had stable disease, and 3/7 (42.8%) had progressive disease. 4 patients elected to undergo second line treatment: 2 underwent bevacizumab with lomustine, 1 underwent bevacizumab and irinotecan, and 1 underwent surgery with carmustine. Of the 2 who underwent bevacizumab and lomustine, 1 (50%) improved from progressive to stable disease and 1 (50%) stayed at stable disease. Of the 1 patient who underwent bevacizumab and lomustine, outcome worsened from stable to progressive disease. Of the 1 patient who underwent surgery and carmustine, outcome improved from progressive to stable disease.

CONCLUSIONS
H3 K27M is a highly aggressive tumor with poor outcomes. This case series demonstrates that multiple treatment rounds with chemotherapy and radiation therapy may benefit patients, with bevacizumab/lomustine and surgery/carmustine appearing to lead to promising outcomes. Further research is needed to establish evidence-based protocols so quality of life and survival time in these patients may improve.
EPID-13. A RETROSPECTIVE ANALYSIS TO STUDY THE SURVIVAL CHARACTERISTICS OF PATIENTS WITH FIRST PROGRESSION OF GLIOBLASTOMA AT THE CLEVELAND CLINIC
Authors: Rauf Yasmeen , Yao Jimmy , Barnett Addison , Chen Yanwen , Hobbs Brian , Stevens Glen , Peereboom David , Ahluwalia Manmeet 
Published: December 2020

Abstract

BACKGROUND
Glioblastoma (GBM) is the most aggressive primary central nervous system malignancy. The median overall survival is 15 to 18 months with treatment and decreases to nine months after first progression.

METHODS
This is a retrospective study. Data was collected from all patients with first progression of GBM treated at CCF between Jan 2012 to Jan 2020. Eight cohorts of patients were evaluated: Group 1 received cytotoxic chemotherapy, Group 2 received bevacizumab alone, Group 3 received surgical or reirradiation alone, Group 4 were enrolled in clinical trials. Each group was divided into methylated and unmethylated cohorts.

RESULTS
Median overall survival was 12.4 months for patients with first progression of GBM (n= 248). Among the methlylated patients, the median overall survival was 16.5 months for group 1, 13.4 for group 2, 23.7 for group 3, and 17.3 for group 4. Among the unmethylated patients, the Median overall survival was 8.6 months for group 1, 7.7 months for group 2, 11.7 months for group 3 and 10.7 months for group 4. (p= 0.00016). Progression free survival (PFS) was 4.3 months for all patients with first progression of GBM. Among the unmethlylated patients, the PFS was 3.6 months for group 1, 15.3 months for group 2, 4.8 months for group 3, and 6.1 months for group 4. Among the unmethylated patients, the PFS was 2.3 months for group 1, 3.9 months for group 2, 3.8 months for group 3, and 4.4 months for group 4. (p &lt; 0.0001).

CONCLUSION
Patients with first progression of GBM had the best overall survival in the cohort that underwent a surgical or reirradiation. The best progression free survival was for patients who were treated with Bevacizumab if they were methylated and those enrolled in clinical trials if they were unmethylated. The study was statistically significant.
EPID-18. GLIOBLASTOMA CHARACTERIZATION IN FEMALES WITHIN RURAL PENNSYLVANIA: A SINGLE INSTITUTIONAL RETROSPECTIVE REVIEW
Authors: Giombetti Maia , Jakubek Emilia , Gatson Na Tosha , Bross Shane 
Published: December 2020

Abstract

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.
EPID-19. RACIAL/ETHNIC DISPARITIES IN TREATMENT PATTERN AND TIME TO TREATMENT FOR ADULTS WITH GLIOBLASTOMA IN THE US
Authors: Ostrom Quinn , Patil Nirav , Cioffi Gino , Barnholtz-Sloan Jill S 
Published: December 2020

Abstract

BACKGROUND
Race/ethnicity have been previously shown to significantly affect survival after diagnosis with glioblastoma, but the cause of this survival difference is not known. The aim of this study was to examine variation in treatment pattern and time to treatment by race/ethnicity, and the extent to which this affects survival.

METHODS
Data were obtained from the National Cancer Database (NCDB) for adults &gt;= 40 with glioblastoma (histologic codes 9440–9442 and topographical codes C71.0–C71.9) from 2004–2016 (N=117,710). Treatment patterns and time to treatment by race/ethnicity were compared using univariable and multivariable logistic and linear regression models, respectively. Models were adjusted for age, sex, insurance status, pre-existing comorbidities, type of treating institution, and distance to institution.

RESULTS
Black non-Hispanics (BNH) were 17% less likely to receive radiation (p=1.47x10-8) and 32% less likely to receive chemotherapy (p=1.10x10-31) than White non-Hispanics (WNH). Among those that did receive treatment, it took 3.3 additional days on average for BNH to receive radiation (p=2.12x10-11) and 4.6 additional days to receive chemotherapy in comparison to WNH (p=4.14x10-10). Hispanics were 21% less likely to receive radiation (p=4.79x10-12), and 23% less likely to receive chemotherapy (p=7.51x10-14) than WNH. Among those that did receive treatment, it took 3.3 additional days on average for Hispanics to receive radiation (p=4.07x10-9) and 4 additional days to receive chemotherapy in comparison to WNH (p=1.51x10-6). There were no significant differences in time to surgery, or in to treatment for Asian Pacific Islanders or American Indian/Alaska Natives.

CONCLUSIONS
Both likelihood of receiving treatment and time to radiation and chemotherapy vary significant between BNH and Hispanics as compared to WNH, and this difference is not fully explained by comorbidities or access to health care.
EPID-22. CHARACTERIZATION OF RADIATION-INDUCED MENINGIOMAS IN A BRAIN TUMOR DATABASE
Authors: Vaghjiani Nilan , Schwieder Andrew , Uppalapati Sravya , Kons Zachary , Kazarian Elizabeth , Sattiraju Srikar , Opalak Charles , Harris Timothy , Broaddus William 
Published: December 2020

Abstract

PURPOSE
Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs).

METHODS
1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics.

RESULTS
Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment.

CONCLUSION
RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.
EPID-25. SKULL BASE MENINGIOMAS ARE ASSOCIATED WITH OBESITY IN MALES
Authors: Shahin Maryam , Stedelin Brittany , Ramos Christian Lopez , Rae Ali , Edwards Jared , Bagley Jacob , Bowden Stephen , Bullis Carli , Wood Matthew , Cetas Justin , Han Seunggu 
Published: December 2020

Abstract

BACKGROUND
The female predominance of meningiomas may reflect hormonal influences on meningioma development, with known presence of estrogen and progesterone receptors. Progestin-associated meningiomas demonstrate a shift in the mutational landscape and are more frequently located at the skull base. Obesity and increased adipocytes increase aromatase and affect male hormone synthesis, thus increases circulating estrogen.

OBJECTIVE
Report prevalence of obesity in a consecutive series of male patients presenting with meningioma and the interaction with obesity.

METHODS
A retrospective review (20012019) was performed of male patients diagnosed with meningioma. Body mass index (BMI) &gt;30 kg/m2 was considered obese. Obese male meningioma patients were characterized and compared to nonobese male meningioma patients.

RESULTS
Of 239 male patients with meningioma, 97 (40.6%) were obese at the time of surgery with overall mean BMI (30.0 kg/m2). This is above the age-adjusted baseline prevalence of obesity for males in Oregon, which was 34.8% between 2015–2016. Mean age at diagnosis for obese males was 55.3 years and 57.0 years for nonobese males. Within the obese group, most lesions were located on the skull base (48.5% n=47) compared to 34.0% convexity (n=33), 15.4% falx (n=16) and 1.0% multiple (n=1). Tumors were WHO grade I (73.6%), grade II (25.6%) or grade III (1.2%). Of the men in our series, patients with skull base meningiomas were more likely to be obese (OR: 1.7, 95% CI: 1.01–2.9, p=0.0309).

CONCLUSIONS
There is likely a hormonal influence on the pathogenesis of meningioma, and many men diagnosed with this disease are obese. Of 239 male patients with meningioma in our series, 97 (40.6%) were obese which exceeds the 34% age-adjusted baseline prevalence of obesity for males in Oregon. Patients with skull base meningiomas were more likely to be obese, consistent with prior series and suggestive of a hormone-driven association with skull base meningioma.
EPID-28. THE IMPACT OF RITUXIMAB COMBINATION CHEMOTHERAPY ON THE CLINICAL OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): AN UPDATED META-ANALYSIS
Authors: Haddad Philip , Hammoud Dalia , Gallagher Kevin 
Published: December 2020

Abstract

BACKGROUND
PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2–5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory RESULTS: A small meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this updated meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab combination chemotherapy on the clinical outcomes of patients with PCNSL incorporating all available comparative studies.

METHODS
A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted.

RESULTS
Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HROS 0.75, 95%CI: 0.59–0.96, p=0.02; HRPFS 0.67, 95%CI: 0.53–0.85, p=0.001) with a heterogeneity estimate, I2=0%.

CONCLUSIONS
This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL.
EPID-29. CAUSES OF DEATH FOR PRIMARY BRAIN AND CNS TUMOR PATIENTS IN THE UNITED STATES (2001 – 2016): A POPULATION BASED STUDY
Authors: Penuela Maria , Patil Nirav , Cioffi Gino , Kruchko Carol , Barnholtz-Sloan Jill S 
Published: December 2020

Abstract

BACKGROUND
Population-based data on the various causes of death among Primary Brain and CNS tumor patients are lacking. We evaluated the causes of death for all eligible patients using the National Program of Cancer Registries (NPCR) data.

METHODS
The population-based cancer survival data collected by the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) were used to analyze the causes of death for patients of all ages with primary brain and CNS tumors diagnosed between 2001 and 2016. Patients for whom the cause of death was not listed on the death certificate or whose state death certificate was not available were excluded. Additional analyses to identify factors associated with brain tumor-specific mortality for the most common malignant (Glioblastoma) and non-malignant (Meningioma) were performed using univariable and multivariable logistic regression analysis.

RESULTS
Major cause of death for patients with malignant tumors was death due to brain and other CNS tumors (49.29%), and for non-malignant tumors were other benign and malignant tumors (31.5%) and heart disease (17.9%). Overall mortality was 36.4% (n=331,953) in patients with Primary Brain and CNS Tumors during the study period. Specifically, 163,621 (49.29%) patients died due to brain and other CNS tumors. A significant proportion of patients with malignant tumors had brain tumor-specific mortality compared to non-malignant tumors (75.4% in malignant vs 4.2% in non-malignant). The factors associated with brain specific mortality in Glioblastoma patients were Age (p&lt; 0.001), Race (p&lt; 0.001) and Primary Site (p&lt; 0.001). Further, the factors associated with brain specific mortality in Non-malignant Meningioma patients were Age (p&lt; 0.001), Sex (p&lt; 0.001), Race (p&lt; 0.001) and Primary Site (P&lt; 0.001).

CONCLUSION
Cause of death attributed to the brain tumor was significantly higher in malignant brain tumors compared to non-malignant brain tumors.
EXTH-02. TUMOR-HOMING INDUCED NEURAL STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER BRAIN METASTASIS AND LEPTOMENINGEAL CARCINOMATOSIS
Authors: Jiang Wulin , Valdivia Alain , Mercer-Smith Alison , Anders Carey , Hingtgen Shawn 
Published: December 2020

Abstract

INTRODUCTION
Breast cancer brain metastasis, including leptomeningeal carcinomatosis (LC), remains one of the most lethal CNS diseases. New therapies are urgently needed to treat this highly aggressive disease. Here we used models of both breast cancer brain parenchymal metastasis and leptomeningeal metastasis to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy.

METHODS
Personalized NSCs were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs), followed by genetic engineering to enable iNSCs to secrete cytotoxic TRAIL (iNSC-TRAIL). For the parenchymal metastasis study, iNSC-TRAIL therapy was infused intracerebroventricularly (ICV) into Nude mice bearing established intracranial MDA-MB-231-Br human breast cancer cells expressing fluorescent and bioluminescent reporters. For LC studies, we established the disease model by inoculating Nude mice with MDA-MB-231-Br tumor cells via intracisternal infusion. iNSC-TRAIL therapy was evaluated by infusing therapy ICV either 1 week prior to or 3 days after tumor inoculation to mirror prophylactic or established tumor treatment, respectively. Tumor progression in the brain and spine was monitored by serial bioluminescence imaging (BLI), and survival was analyzed.

RESULTS
Serial BLI showed ICV-infused iNSC-TRAIL reduced parenchymal tumor volumes by 72% 3 weeks post-ICV infusion, and extended median survival from 37 to 52 days. Testing iNSC-TRAIL therapy against established LC tumors, serial BLI showed ICV iNSC-TRAIL therapy reduced established tumors 196-fold in the brain and 500-fold in the spine within 2 weeks post-infusion, while extending median survival from 25 to 47 days. In the prophylactic LC model, iNSC-TRAIL therapy markedly delayed tumor development with tumors in the brain remaining &gt; 1000-fold smaller than control, and tumors in the spine below the limit of detection through 1 month post-treatment. The therapy also eliminated mortality through 50 days post-therapy.

CONCLUSION
These data suggest iNSC therapy could be a promising treatment option for breast cancer brain metastasis patients.