bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-12. OUTCOMES IN A REAL-WORLD PRACTICE FOR PATIENTS WITH PRIMARY GLIOBLASTOMA: IMPACT OF A SPECIALIZED NEURO-ONCOLOGY CANCER CARE PROGRAM
Authors: Banerji Nilanjana , Hultman Meghan , Tipps Megan , Liu Minda , Bruns Patricia , Trusheim John 
Published: November 2019

Abstract

INTRODUCTION
Standard care for newly diagnosed glioblastoma consists of maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide. Prognosis for glioblastoma still remains poor, with a reported median survival of 14.6 months. Published data indicate that optimal outcomes in this population require involvement of an experienced team providing multidisciplinary care. We report here the outcomes in a real-world setting for glioblastoma patients treated at a specialized neuro-oncology cancer care program.

PATIENTS AND METHODS
Data from fifty consecutive patients with primary glioblastoma pursuing care at the Givens Brain tumor Center were analyzed. Coordinated medical care was provided by dedicated neuro-oncology and surgical clinicians, supplemented by care from nurse coordinators, social workers, care guides, genetic counselors, and other specialties. Demographic, pathologic, and clinical information was abstracted from electronic medical records.

RESULTS
Median patient age was 58 (range, 23–80) years and 26% were ≥65 years of age. Gross total resection was achieved in 91.5% patients, with 56% of resections performed in the Institution’s iMRI suite. A majority of patients received radiation and chemotherapy. In accordance with cancer program guidelines, 48% of the cases were presented at multidisciplinary tumor conferences. A LifeCourse™ care guide was utilized by 30% of the patients. Bevacizumab was used as second-line therapy with/without carboplatin in 63.2% patients. Optune treatment was administered to 27 patients. Additionally, eligible patients enrolled in clinical trials both at primary and recurrent stages. Median progression-free survival (PFS) and overall survival (OS) was 9.1 (range, 2.2–30.5) months and 19.4 (range, 4.6–31.8) months, respectively. End-of-life hospice care was elected by 48% patients.

CONCLUSION
PFS and OS in this real-world settings were comparable to outcomes noted in controlled clinical trials. These results indicate that efficient, quality care may be achieved with a multidisciplinary treatment approach, producing exceptional survival rates in patients with glioblastoma.
INNV-21. IN NEWLY-DIAGNOSED GLIOBLASTOMA, FRAILTY/SARCOPENIA PREDICTS 30D MORBIDITY & 30D, 90D, AND OVERALL MORTALITY AS ACCURATELY AS CURRENT STANDARDS
Authors: Zakaria Hesham , Chandra Ankush , Macki Mohamed , Robin Adam , Walbert Tobias , Chang Victor , Kalkanis Steven , Lee Ian 
Published: November 2019

Abstract

INTRODUCTION
Identification of novel prognostic biomarkers for glioblastoma (GBM) could stratify patients between aggressive or palliative treatments. Frailty, as measured by sarcopenia (lack of muscle mass), has been proven to predict survival in cancers. We evaluate whether the frailty/sarcopenia phenotype (FSP) predicts morbidity and mortality in GBM, and compare it to other survival markers.

METHODS
In 257 patients undergoing initial diagnostic surgery for GBM, FSP was defined by temporalis muscle thickness from preoperative MRI; patients were grouped into tertiles (thirds) based on size, which corresponded to the severity of FSP. Morbidity and mortality hazard ratios were calculated from surgery using multivariate analysis, accounting for age, gender, past medical history, tumor focality / laterality / eloquence / volume, extent of resection, MGMT / IDH status, and initiation of postoperative chemo/radiation. Morbidity was defined as any of these events within 30d: DVT, PE, SSI, UTI, MI, urinary retention, ileus, readmission.

RESULTS
FSP at diagnostic surgery predicted any morbidity (OR2.98, P= 0.005) at 30d. FSP at diagnostic surgery was the only risk factor associated with 30d mortality (OR10.0, P= 0.030), and was also strongly associated with 90d mortality (OR25.0, P= 0.003). FSP at diagnostic surgery was associated with decreased overall survival (OR0.41, P< 0.001) at a level comparable to other mortality predictors, including temozolomide/EBRT (OR0.27), gross total resection (OR0.54), favorable MGMT (OR0.44) or IDH (OR0.44) mutations. Kaplan-Meier curves display overall survival based on severity of FSP.

CONCLUSION
FSP is a preoperative, simple, accurate, and non-invasive methodology to predict 30d morbidity & 30-day, 90-day, and overall mortality from diagnosis in GBM. FSP is independent of age (not an age surrogate), demographic, oncologic, genetic, surgical, and therapeutic factors. Mortality prediction is comparable to temozolamid/EBRT, total resection, MGMT, and IDH. It is a low cost, intuitive, and potentially universal methodology to guide treatment decision making.
INNV-33. BARRIERS TO ACCRUAL AND ENROLLMENT IN BRAIN TUMOR TRIALS
Authors: Lee Eudocia , Chukwueke Ugonma , Hervey-Jumper Shawn , DeGroot John , Leone Pablo , Armstrong Terri , Chang Susan , Arons David , Oliver Kathy , Verble Kay , Musella Al , Willmarth Nicole , Alexander Brian , Bates Amanda , Doherty Lisa , Galanis Evanthia , Gaffey Sarah , Halkin Thomas , Friday Bret , Fouladi Maryam , Lin Nancy , Macdonald David , Mehta Minesh , Penas-Prado Marta , Vogelbaum Michael , Sahebjam Solmaz , Sandak David , van den Bent Martin , Weller Michael , Reardon David , Wen Patrick 
Published: November 2019

Abstract

BACKGROUND
A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual.

METHODS
We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual.

RESULTS
We described selected factors contributing to poor trial accrual and possible solutions. We focused on patient and community factors, disparities, physician and provider factors, clinical trial factors, and site and organizational factors

CONCLUSIONS
We will implement strategies with the intent to double accrual to neuro-oncology trials over the next 5 years.
INNV-34. PATTERNS OF FAILURE AND DEVELOPMENT OF A NOVEL PROGNOSTIC SCORING SYSTEM IN ELDERLY PATIENTS WITH GLIOBLASTOMA – FOLLOW UP ON 10 YEAR ANALYSIS OF THE BC CANCER AGENCY POPULATION
Authors: Zeng Jonathan , DeVries Kimberly , Krauze Andra 
Published: November 2019

Abstract

PURPOSE
Glioblastomas (GBM) are the most common primary brain tumour recurring in most patients despite maximal management. Patient selection for appropriate treatment modality remains challenging resulting in heterogeneity in management. We examined the patterns of failure and developed a scoring system for patient stratification to optimise clinical decision making.

METHODS
822 adults (BC Cancer Agency registry) diagnosed 2005–2015 age ≥60 with histologically confirmed GBM ICD-O-3 codes (9440/3, 9441/3, 9442/3) were reviewed. Univariate and Kaplan-Meier analysis were performed. Performance status (PS), age and resection status were assigned a score, cummulative maximal (favorable) score of 10 and minimum (unfavorable) score of 3. Patterns of failure were further analysed in the subset of patients with radiographic follow-up.

RESULTS
PS score of 3(KPS >80, ECOG 0/1), 2 (KPS 60–70, ECOG 2), 1 (KPS < 60, ECOG 3/4) (median OS 11, 6, 3 months respectively), age score and resection status were prognostic for OS with PS resulting in the most significant curve separation (p< 0.0001). Biopsy as compared to STR/GTR resulted in poorer OS in patients over 70 (age score 1/2) but had less impact in patients younger than 70 (age scores 3/4). The median OS for cumulative scores of 9/10 (123 patients), 7/8 (286 patients), 5/6 (313 patients), and 3/4 (55 patients) were 14, 8, 4 and 2 months respectively (p< 0.0001) allowing for stratification into 4 prognostic groups. 133 patients had >3 MRIs following diagnosis allowing for clinical and radiographic analysis of progression. Clinical/radiographic progression occurred within 3 months (29%/45%), 6 months (50%/66%), 9 months (70%/81%). Progression type (radiographic, clinical, both was not associated with OS.

CONCLUSION
Our novel prognostic scoring system is effective in achieving patient stratification and may guide clinical decision making. Early radiographic progression appears to precede clinical deterioration and may represent true progression in the elderly.
MNGI-05. COMBINED MULTIMODAL TREATMENT REGIMEN IN RECURRENT MENINGIOMAS
Authors: Carrillo Jose , Wagle Naveed , Barkhoudarian Garni , Kelly Daniel , Heng Annie , Gill Jaya , Juarez Tiffany , Kesari Santosh 
Published: November 2019

Abstract
Meningiomas are the most common primary brain tumor, subsequent tumor progression can be problematic for surgical treatment options based upon location. Currently there is limited activity of various single agent medical therapies. We evaluated a combined treatment modality in recurrent Meningiomas. Patients were consented to NOC study protocol JWCI-17–0401 in this retrospective analysis. Treatment consisted of combination Octreotide LAR, Everolimus, Hydroxyurea, and Mifepristone. Patient characteristics in the combined treatment meningioma group (n=12) had a median age 60, 50% male, 47% WHO grade I, 37% WHO grade II, 11% WHO grade III, 67% skull base location, median number of recurrences is 2.2, with median number of surgeries of 1.7. Total comparison meningioma patients (n=19) with median age 62, 42% male, 42% WHO grade I, 50% WHO grade II, 17% WHO grade III, 58% skull base location, median number of recurrences is 2.2, with median number of surgeries of 2.2. Median PFS in recurrence prior to initiation of multimodal combined therapy, mPFS=283 days. Median PFS with subsequent multimodal combined therapy, mPFS=318 days. Multimodal therapy may prolong mPFS in recurrent meningiomas. Our pilot data supports further clinical trials in combined multimodal treatments.
MNGI-08. PHARMACOKINETIC ANALYSIS OF 68GA-DOTATOC IN MENINGIOMAS USING PET/CT FOR ASSESSMENT OF SOMATOSTATIN RECEPTORS AND CORRELATION WITH ANGIOGENESIS, INFLAMMATION AND PROLIFERATION
Authors: Bashir Asma , Bitsch Vestergaard Mark , Binderup Tina , Broholm Helle , Marner Lisbeth , Ziebell Morten , Fugleholm Kåre , Kjær Andreas , Law Ian 
Published: November 2019

Abstract

BACKGROUND
A quantitative correlative analysis between 68Ga-DOTATOC accumulation using PET/CT and somatostatin receptor subtype 2 (SSTR2) in meningiomas was conducted. The possible contributions of angiogenesis and inflammation were investigated as well.

METHODS
Fifteen patients with newly (n = 12) and recurrent (n = 3) meningiomas were prospectively assigned to a 60-minute dynamic 68Ga-DOTATOC PET/CT scan prior to surgery. PET data included measurements of maximum and mean standardized uptake value (SUVmax, SUVmean) with/without normalisation to different reference tissues, and quantitative measures derived from kinetic modeling using a reversible two-tissue compartment model with the fractional blood volume (VB) included in the model. The SSTR2-expression was determined by immunohistochemistry and quantitative polymerase chain reaction (qPCR), while biomarkers of inflammation (macrophage-specific marker CD68, interleukin-18 [IL18]) and angiogenesis (endothelial marker CD34, vascular endothelial growth factor-A [VEGF-A]), were assessed by qPCR only.

RESULTS
Twelve patients (80%) were diagnosed with World Health Organization (WHO) grade I meningioma and three with WHO grade II (20%). No significant differences in SSTR2-expression was seen between WHO grades or subtypes (P ≥ 0.05; Mann-Whitney, Kruskal-Wallis). Upon stratification of patients based on the median SUVs (SUVmax, 20.9; SUVmean, 9.9), SSTR2-expression was seven-fold increased in patients with SUVs above the medians compared to patients with SUVs below the medians. Spearman’s rank correlation coefficient revealed significant correlations between SSTR2-expression, and SUVmean (r = 0.532, P = .041) and mean tumor-to-neck muscle ratio (TNMRmean) (r = 0.593, P = .020). 68Ga-DOTATOC uptake was additionally associated with VB and VEGF-A (P < 0.01), while no association with inflammatory biomarkers were found. In univariate linear regression analysis, SUVmean and TNMRmean remained the optimal surrogate biomarkers for SSTR2-expression (P < .0001).

CONCLUSIONS
68Ga-DOTATOC accumulation in meningiomas is more complex than previously reported, and may not be limited to the SSTR2-density but also be associated with the vascular component.
PATH-01. MGMT METHYLATION CUTOFF VALUE IN QUANTITATIVE ANALYSIS RELATED TO PROGNOSIS OF NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Adachi Jun-ichi , Shirahata Mitsuaki , Suzuki Tomonari , Mishima Kazuhiko , Nishikawa Ryo 
Published: November 2019

Abstract

BACKGROUND
MGMT promoter methylation is an important biomarker related to glioblastoma therapeutic response and prognosis. There are qualitative and quantitative methods as assays for MGMT methylation. Although the qualitative method is common, there is a disadvantage that low or high methylation cannot be distinguished. The quantitative method is an excellent method for evaluating methylation of tumors characterized by intratumoral heterogeneity like malignant glioma, but cutoff value of methylation that defines the prognosis of glioblastoma is unknown. Therefore, we examined the cutoff value of quantitative MGMT methylation assay determining the prognosis in glioblastoma.

METHODS
180 newly diagnosed glioblastoma which underwent radiotherapy and temozolomide treatment after tumor removal in our department were included. MGMT methylation was quantitatively analyzed by methylation-specific high resolution melting (MS-HRM) analysis. For each level of methylation, progression-free survival (PFS) and overall survival (OS) were calculated and statistically analyzed.

RESULTS
In the low MGMT methylation cases in which the proportion of methylation was 25% or less in PFS and 30% or less in OS, no difference was observed in PFS and OS as compared with those of unmethylated cases. The cutoff value of MGMT methylation most contributing to survival was calculated to be 35% by the survival classification and regression tree method.

CONCLUSION
The prognosis for MGMT hypomethylated group is as poor as unmethylated one. In the quantitative MS-HRM method, we found that the value of MGMT methylation of 35% is useful as a cut off determining the prognosis of glioblastoma.
PATH-02. A COMBINATION OF MGMT METHYLATION AND NFKBIA COPY NUMBER ALTERATION REFINES PROGNOSTICATION OF IDH-WT GLIOBLASTOMAS
Authors: Umehara Toru , Arita Hideyuki , Yoshioka Ema , Shofuda Tomoko , Kinoshita Manabu , Kodama Yoshinori , Kagawa Naoki , Okita Yoshiko , Nonaka Masahiro , Uda Takehiro , Fukai Junya , Sakamoto Daisuke , Mori Kanji , Kishima Haruhiko , Kanemura Yonehiro 
Published: November 2019

Abstract

INTRODUCTION
Recent studies have reported that NFKBIA deletion (dNFKBIA) was potentially associated with worse prognosis in glioblastoma (GBM) patients. However, no consensus has been reached to its universal prognostic value. Here, we investigated the survival impact of dNFKBIA using two primary IDH wild-type GBM cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). Additionally, prognostic impact of a combination of NFKBIA copy number and MGMT methylation status was evaluated.

METHOD
The Japanese cohort was collected from cases registered in Kansai Molecular Diagnosis Network for CNS tumors (KNBTG). The survival impact of dNFKBIA and/or unmethylated MGMT (uMGMT) were analyzed for 212 KNBTG cases and 265 TCGA cases. The hazard ratio (HR) and p-value were computed using Cox regression analysis.

RESULTS
dNFKBIA was less frequently observed in KNBTG (47 cases, 22.2%) than in TCGA (84 cases, 31.7%). dNFKBIA was associated with unfavorable prognosis in KNBTG (HR 1.52, p = 0.031), while this was not validated in TCGA (HR 1.14, p=0.406). uMGMT was a common adverse prognostic factor in KNBGT (HR 1.72, p = 0.001) and TCGA (HR 1.50, p = 0.008) cohort. When stratified by NFKBIA status, uMGMT was also associated with shorter survival in NFKBIA deleted cases both in KNBTG (HR 1.87, p = 0.002) and TCGA (HR 1.59, p = 0.014). On the other hand, MGMT status was not significantly associated with prognosis in NFKBIA intact cases in either KNBTG (HR 1.45, p = 0.279) or TCGA (HR 1.55, p = 0.131).

DISCUSSION
Although the prognostic value of dNFKBIA in IDH wild-type GBM patients was not validated in TCGA cohort, our results indicated that the prognostication based on MGMT methylation was potentially interacted by NFKBIA status.
PATH-07. MITOTIC INDEX THRESHOLDS DO NOT PREDICT CLINICAL OUTCOME FOR IDH-MUTANT ASTROCYTOMA
Authors: Yoda Rebecca , Marxen Troy , Longo Lauren , Ene Chibawanye , Wirsching Hans-Georg , Keene Dirk , Holland Eric , Cimino P J 
Published: November 2019

Abstract
Current histological grading recommendations for isocitrate dehydrogenase (IDH)-mutant astrocytoma are imprecise and not reliably predictive of patient outcome, while somatic copy number alterations are emerging as important prognostic biomarkers. One explanation for this relative underperformance of histological grading is that current criteria to distinguish World Health Organization (WHO) grade III anaplastic astrocytomas from lower-grade diffuse astrocytomas (WHO grade II) are vague (‘increased mitotic activity’). This qualitative approach ensures diagnostic uncertainty and a broad ‘gray zone’ where both diffuse and anaplastic designations can reasonably be assigned. Thus, we hypothesized that interobserver variability and lack of defined mitotic thresholds for IDH-mutant astrocytomas underlies poor predictive accuracy of current histologic grading approaches. To test this hypothesis, we quantified total mitotic figures and maximum mitotic activity per ten high-powered fields in an institutional cohort of IDH-mutant astrocytomas. In our cohort, there was no mitotic activity threshold that was reflective of clinical progression-free or overall survival. Furthermore, in a multivariate Cox regression model consisting of mitotic activity, molecular markers, and clinical characteristics, only CDKN2A deletion was identified as a relevant variant for poor overall survival. We conclude that lack of defined mitotic figure thresholds may not contribute to underperformance of histological grading for IDH-mutant astrocytomas. This study supports the shift towards ‘molecular grading’ to replace traditional histological grading for IDH-mutant astrocytomas.
PATH-20. INVESTIGATION OF CLINICALLY AGGRESSIVE SPINAL CORD EPENDYMOMA THROUGH METHYLATION ANALYSIS
Authors: Briceno Nicole , Abdullaev Zied , Vera Elizabeth , Blumental De Abreu Francine , Quezado Martha , Pack Svetlana , Xi Liqiang , Raffeld Mark , Gilbert Mark , Aldape Kenneth , Armstrong Terri 
Published: November 2019

Abstract
Spinal ependymoma is a rare, often low-grade tumor, for which the clinical course and prognosis has been poorly defined. Classification has relied on histological criteria, as there are few defining molecular mutations, causing controversy in diagnosis and grading. DNA methylation analysis with the brain tumor classifier was used on tumor tissue from 37 patients identified from the Neuro-Oncology Branch Natural History Study and selected Collaborative Ependymoma Research Network (CERN) Tissue Repository. These were histologically diagnosed with non-myxopapillary spinal ependymoma (92% grade II and 8% grade III), with 12 designated “poor performers” (50% male, median age 30 years) defined by a progression free survival of less than two years (median 7 months) with at least one recurrence. Alternatively, the 25 “good performers” (56% male, median age 43 years) had no progression with a follow-up time greater than 5 years (median 84 months). Methylation classification matched to “spinal ependymoma” in 33% of the poor performer cases while 8% matched myxopapillary or RELA-fusion ependymoma and 50% were no-match. For the good performers, 52% agreed with histological diagnosis, 28% matched myxopapillary and 20% were no-match. Interestingly, we noted high-level MYCN amplification by copy number analysis in two (17%) cases, neither of which matched to a defined methylation class, and both of which were in the poor performers group. Overall, methylation results reveal complex biology in conventional spinal cord ependymomas, most evident in an increase of no-match cases in the poor performers group. Of importance, the no-match cases contain evidence of a potentially new diagnostic entity characterized by both a poor prognosis and MYCN amplification. For further elucidation of this entity, a larger cohort of patients with expanded clinical criteria has been identified for further testing.
PATH-23. PROGNOSTIC AND RADIOGRAPHIC CORRELATES OF A PROSPECTIVELY COLLECTED MOLECULARLY PROFILED COHORT OF IDH-WILDTYPE ASTROCYTOMAS
Authors: Lin Andrew , Bale Tejus , Mellinghoff Ingo , Tabar Viviane , Schaff Lauren , Jonathan Yang T , Young Robert , Taylor Barry , Rosenblum Marc , Jonsson Philip 
Published: November 2019

Abstract

BACKGROUND
In the molecular era, the relevance of tumor grade for prognostication of IDH-wildtype (WT) astrocytomas has been debated. It has been suggested that lower-grade gliomas with molecular features of glioblastoma, IDH-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials.

METHODS
We integrated prospective clinical sequencing via the FDA-approved genomic sequencing assay MSK-IMPACT from 564 patients with IDH-WT astrocytomas (26 grade II, 71 grade III, and 467 grade IV) with clinical data.

RESULTS
Compared to grade III IDH-WT astrocytomas, grade II tumors harbor fewer chromosome 7/10 alterations and EGFR amplifications (p=0.07 and 0.03), but the same frequency of TERT promoter mutation. In contrast, there is no difference in the frequency of these canonical molecular features in grade III versus grade IV IDH-WT disease. Additionally, grade II astrocytomas harbor fewer cell cycle-pathway alterations than grade III tumors (p=6.9e-7). Progression-free (PFS) and overall survival (OS) for grade II astrocytomas were significantly longer than grade III tumors (p=0.02 and p=0.008, respectively), whereas there was no difference in PFS and OS for grade III compared to grade IV tumors. Median PFS for grade II vs. III vs. IV: 19 mo vs. 11 mo vs. 9 mo; median OS: 44 mo vs. 23 mo vs. 23 mo. In lower-grade IDH-WT astrocytomas, gliomatosis is associated with grade II histology (p=0.04), the absence of cell-cycle alterations (p=0.008), and more alterations in the PI3K-AKT pathway (p=0.09).

CONCLUSION
Histologic grade has genotypic and phenotypic associations, remains prognostically important in IDH-WT astrocytomas, and should be considered when enrolling patients to clinical trials.