bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-25. ASSESSING SLEEP AND CIRCADIAN RHYTHMS IN PRIMARY BRAIN TUMORS PATIENTS: AN OBSERVATIONAL STUDY
Authors: Wollet Alex , Leeper Heather , Vera Elizabeth , Mentges Kelly , King Amanda , Rogers James , Sass Dilorom (Delia) , Acquaye Alvina , Adegbesan Kendra , Boris Lisa , Burton Eric , Celiku Orieta , Chambers Claudia , Choi Anna , Christ Alexa , De Le Minyety Julianie Cruz , Evans Karen , Grajkowska Ewa , Komlodi-Pasztor Edina , Levine Jason , Lindsley Matthew , Lollo Nicole , Mendoza Tito , Miller Hope , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Polskin Lily , Reyes Jennifer , Roche Kayla , Sahebjam Solmaz , Stockdill Macy , Theeler Brett , Wall Kathleen , Wu Jing , Gilbert Mark , Armstrong Terri , Shuboni-Mulligan Dorela 
Published: November 2022

Abstract
Sleep-wake disturbances are among the most common and severe symptoms in primary brain tumor (PBT) patients. Currently, no studies have quantified their physiological sleep measurements or compared these assessments to established patient reported outcome measures (PROs). Smart wearable devices, such as Fitbits, continuously monitor patient behaviors at home and provide detailed physiological measurements of sleep, activity, and heart rate. We hypothesized that smart wearable devices can accurately determine physiological sleep disturbances and circadian disruptions and will complement established PROs in a PBT patient population. This observational, cross-sectional trial monitors sleep and circadian rhythm variables using Fitbit smart wearable devices worn for 1 month. Additionally, participants will answer PROs questionnaires (PROMIS Sleep Disturbance and Sleep Related Impairment-Short Forms, Sleep Hygiene Index, Morningness-Eveningness questionnaire, and Consensus Sleep Diary) at study entry and during the last week on-study. The present study is a planned interim analysis of 54 patients to assess feasibility, including evaluation of enrollment, attrition, study parameter completion and data missingness. 73 PBT patients were screened and approached. Of these patients, 54 (74%) were enrolled on study and 19 (26%) declined participation (8 lacked interest, 3 discomfort wearing watches, 3 lacked smart phone, 2 unable to wear device at work, 2 unable to attend consent calls, 1 pregnancy and 1 cognitive complication). The accrued patients were 56% male, 56%³ 50 years of age, and 81% had a KPS³ 90. Patients represented different stages of treatment: 6% of patients were newly diagnosed, 24% on active treatment (11% 1st recurrence, 13% 2nd recurrence), and 70% were on imaging surveillance. Feasibility was confirmed as there were no deviations reported and 100% of PROs and study timepoints completed. Quantified Fitbit data including percent time worn and physiologic sleep parameters will be reported. Study enrollment for efficacy measures continues.
INNV-27. SAFETY OF DIRECT ORAL ANTICOAGULANTS AS COMPARED TO LOW MOLECULAR WEIGHT HEPARIN IN TREATING VENOUS THROMBOEMBOLISM IN PATIENTS WITH PRIMARY BRAIN TUMORS AND BRAIN METASTASES
Authors: Ali Assad , Shah Nirja , Santiago Raphael Bastianon , Mandel Mauricio , Obrzut Michal , Borghei-Razavi Hamid , Adada Badih , Ranjan Surabhi 
Published: November 2022

Abstract

INTRODUCTION
Patients with brain tumors (PBTs) have a 20 to 30% incidence of venous thromboembolism (VTE) Recently, new direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, dabigatran and edoxaban, have gained popularity in treating VTE in cancer patients due to ease of administration and favorable safety profile. DOACs are also being used in treating VTE in in PBTs. While clinical trials have established the safety of DOAC use in systemic cancers, there is only limited literature on safety of DOAC in PBTs. In this review, we explore all prospective and retrospective studies to evaluate the safety of DOAC in comparison to LMWH in treating VTEs in PBTs.

METHODS
A search on PubMed database using keywords “Direct Oral Anticoagulant,” OR “Oral Anticoagulant,” AND “Cancer,” AND “Clinical Trial” was performed for clinical trials. Another search using keywords “Direct Oral Anticoagulants,” OR “Oral Anticoagulant,” AND “Brain Tumor,” AND “Retrospective.” was performed for retrospective studies.

RESULTS
Of 359 clinical trials in cancer patients, only 4 evaluating DOAC versus LMWH, included PBTs– Hokusai, Select D, ADAM VTE and EINSTEIN-DVT/PE. Four retrospective studies (Lee 2021, Carney 2019, Schwartz 2021 and Leader 2021) were identified.These four clinical trials enrolled a very limited number of PBTs (0.7, 1.5%, 2.7% and 6.8% of all patients). The risk of ICH with DOAC as compared to LMWH was low in Hokusai trial (OR = 0.93; CI=0.14-5.9) and uninformative in other 3 trials (0 episodes of ICH in either/both groups). All four retrospective studies showed no increase in incidence of ICH in the DOAC versus LMWH group in PBTs.

CONCLUSION
In the small number of prospective and retrospective studies which have evaluated the safety of DOAC in comparison to LMWH in brain tumors, the use of DOAC appears to be safe with no increase in the risk of ICH over LMWH.
INNV-28. A PILOT STUDY EVALUATING THE FEASIBILITY OF USING AN ULTRA-FAST DIGITAL CONFOCAL MICROSCOPY SCANNER FOR REAL-TIME INTRA-OPERATIVE BRAIN TUMOUR DIAGNOSIS
Authors: Bolton William , Ramakrishnan Piravin , Reveendran Dharsshini , Chakrabarty Arundhati , Mathew Ryan 
Published: November 2022

Abstract

INTRODUCTION
Real-time intra-operative brain tumour tissue analysis in the operating room (OR) can shorten turnaround times and facilitate repeated sampling; the latter can improve diagnostic accuracy and guide resection to maximise extent. We evaluated the feasibility of using an ultra-fast confocal microscopy scanner (Histolog®, SamanTree Medical SA) in the OR for real-time intra-operative brain tumour tissue diagnosis. This study is the first use of Histolog® on primary human brain tissue globally.

METHODS
An observational pilot study with varying brain tumour types was conducted in a tertiary UK brain tumour centre. Multiple, freshly excised tissue samples were stained with Acridine Orange, and images captured within 60 seconds on Histolog® in the OR in parallel to current diagnostic pathways. A Consultant Neuropathologist performed a blinded correspondence assessment between Histolog® and current gold standard histopathology. Qualitative logging of diagnostic features was performed.

RESULTS
Cases studied (n=12) included glioma, metastasis, meningioma, schwannoma, and pituitary adenoma. Concordance between Histolog® and traditional (frozen section) intra-operative histopathological diagnosis was 83% (10/12 cases). One Histolog® case demonstrated superior diagnostic accuracy to frozen section. Histolog® images demonstrated specific diagnostic features such as clusters of cohesive epithelioid cells (metastatic carcinoma), sheet-like variably cellular and pleomorphic cells (gliomas), diffuse sheet-like monomorphic round nuclei (pituitary adenoma), elongated spindle cells (schwannoma), and nodular architecture and oval nuclei (meningioma).

DISCUSSION
Ultra-fast confocal microscopy scanning with Histolog® is feasible in the OR and Histolog® image resolution is adequate to identify histopathological features necessary for intra-operative brain tumour diagnosis. Training and clinico-radiological details are important in minimising discordance. A larger study with greater numbers and tumour types will now be performed to define an optimal scanning protocol and determine the strengths and limitations of the technology. Future studies should investigate the effect of real-time margin zone analysis on extending resection.
INNV-30. RETROSPECTIVE ANALYSIS OF TTFIELDS IN PATIENTS WITH HGG BASED ON THE CRITERIA OF 2021 WHO CNS5
Authors: Yang Xiaoyan , Zhang Li , Ren Yanming , Mao Qing , Liu Yanhui , Wang Xiang , Chen Ni , Yue Qiang , Wu Xin , Liu Lei , Wang Feng 
Published: November 2022

Abstract

PURPOSE
High-grade glioblastoma (HGG) was highly malignant and had a poor prognosis, with an overall median survival time of only 15 months. Tumor-Treating Fields (TTFields) has been approved for the newly diagnosed glioblastoma (GBM), and more clinical evidence is needed for its use in HGG. The aim of this study was to analyze the efficacy and safety of TTFields in patients with HGG in our center.

METHODS
We analyzed baseline characteristics, efficacy, and safety data of 27 newly diagnosed HGG patients treated with TTFields for at least four weeks from January 2020 to February 2022 at West China Hospital of Sichuan University. All the pathological grades were diagnosed based on the 2021 World Health Organization Classification of Tumors of the Central Nervous System (2021 WHO CNS5) criteria.

RESULTS
Twenty-one patients (77.78%) were diagnosed as grade 4. Among them, the percentage of gross total resection was 81.48%, and MGMT promoter methylation was 51.85%. The median interval from surgery to TTFields initiation of treatment was 2.47 months (95% CI, 1.47-10.37). The median follow-up time was 12.47 months (95% CI, 8.6-15.03). The 12-month PFS rate and 12-month OS rate were 70.73% and 90.24%, respectively. Median PFS and OS have not been reached. The median compliance of patients wearing TTFields was as high as 95%, and their associated adverse events were patch-induced rash and ulcers, all of which were grade 1 ~ 2.

CONCLUSIONS
This study is the first to define HGG patients with the 2021WHO CNS5. TTFields were observed in this retrospective analysis to improve patients’ 12-month PFS rate and OS rate. Adherence was much higher than that reported in clinical studies, and safety remained good. More extended Survival data would be updated by further follow-up.
PATH-05. SEX-SPECIFIC HISTOLOGICAL FEATURES RELATED TO THE SPATIAL ORGANIZATION OF TUMOR-INFILTRATING LYMPHOCYTES PREDICT OVERALL SURVIVAL IN FEMALE GLIOBLASTOMA PATIENTS
Authors: Krebs Olivia , Corredor German , Tiwari Pallavi 
Published: November 2022

Abstract

PURPOSE
Epidemiological studies suggest that biological sex influences overall survival (OS) in Glioblastoma (GBM), possibly due to immunological variances between the sexes. Further, while prognostic in other cancers, the association of tumor-infiltrating lymphocytes (TILs) to OS in GBM requires additional exploration. We hypothesize that histological features corresponding to spatial organization of TILs from within the GBM microenvironment, when evaluated in a sex-specific manner, will be associated with OS.

METHODS
Digitized Hematoxylin-and-Eosin (H&E) slides of resected GBM tumors were collected to establish a multi-site cohort of Nf435 patients. The training set included Nf201 patients from eleven contributing sites of the Cancer Genome Atlas (TCGA). The validation set included Nf234 patients consisting of cases from two hold-out TCGA sites and the Clinical Proteomic Tumor Analysis Consortium. Each digitized H&E slide was assessed for quality, followed by employing a pre-trained classifier to label TIL and non-TIL cells. Spatial features related to the connectivity of nuclei centroids and corresponding cell cluster graphs were extracted for TILs, non-TILs, and between-group interactions. These TIL-centric histological features were fed into a Cox Hazard regression model with least absolute shrinkage and selection operator feature selection, to stratify patients as low or high-risk. Survival models were evaluated using Kaplan-Meier estimates, across male, female, and combined cohorts.

RESULTS
Selected features (i.e., measures of area and proximity across TIL clusters) were significantly associated with OS in the validation cohort (hazard ratio (HR)=1.95, confidence interval (CI)=1.19–3.2, p=0.00278), for the female cohort. For the male cohort, the selected spatial TIL features’ association with OS for the validation cohort yielded HR=1.43, CI=0.986–2.07, p=0.0667. The spatial TIL survival validation model on the combined cohort did not yield significant survival risk stratification.

CONCLUSION
Our findings suggest that sex-specific TIL organization histological features may be prognostic of OS in GBM tumors, specifically for the female cohort.
PATH-06. SURVIVAL ANALYSIS FOR ADULT MIDLINE GLIOMA: DO ADULT MIDLINE GLIOMAS WITH THE H3 K27M MUTATION REALLY HAVE POOR PROGNOSIS?
Authors: Choi Seonah , Jung In-Ho , Lim Jaejoon , Moon Ju Hyung , Kim Eui Hyun , Kim Se Hoon , Kang Seok-Gu , Chang Jong Hee 
Published: November 2022

Abstract

PURPOSE
Since it is known that midline located glioma with H3K27 mutation in children has a disastrous prognosis, in 2016 WHO classification, these tumors were defined as diffuse midline glioma (DMG) and classified as grade IV. A lot of papers about pediatric DMG have been published, but there are not many papers about adult DMG. In this study, we aimed to identify factors affecting the prognosis of adult midline glioma. This is the first paper to study the prognosis of adult DMG according to histological grade and is the largest study to investigate the survival of adult DMG.

METHODS
We reviewed the chart of adult patients diagnosed with midline glioma with H3K27M mutation after undergoing resection or biopsy among patients who visited our institution between January 2010 and December 2020. Survival analysis was performed according to tumor location, histological grading, Karnofsky Performance Scale (KPS), and age.

RESULTS
Among the 125 adult midline gliomas we identified, 45 (36.0%) had the H3K27M mutation. As a result of survival analysis performed on 125 adult midline gliomas, low histological grade, KPS ≥ 80, and age ≤ 60 showed significantly better survival. After adjusting for age, the difference in survival between H3K27M mutation and wildtype group was not significant. As a result of survival analysis performed on 45 DMG, low histological grade, KPS ≥ 80, total resection, and concurrent chemoradiation therapy group showed significantly better survival.

CONCLUSION
In adult midline glioma, disastrous prognosis due to H3K27M mutation was not observed as in children. The prognosis of adult midline gliomas is determined by histological grade, age, KPS, and extent of tumor resection. Therefore, the current WHO classification, which classifies all H3K27M mutant midline gliomas as grade IV regardless of histological diagnoses, is not suitable for adults.
PATH-13. IMAGE-BASED PHENOTYPING OF GLIOMAS FOR CLINICAL USE
Authors: Becker Aline , Casukhela Ishya , Chan Jany , McElroy Joseph , Eicher Tara , Fleming Jessica , Haque S Jaharul , Machiraju Raghu , Chakravarti Arnab 
Published: November 2022

Abstract
Adult-type diffuse gliomas have been classified according to histopathological characteristics only. Based on molecular profiles, the World Health Organization (WHO) classification defines three distinct biologic and prognostic types of diffuse gliomas: (i) IDH wild type (IDHwt), (ii) IDH mutant, 1p19q intact (IDHmut-non-codel), and (iii) IDH mutant, 1p19q codeleted (IDHmut-codel). Gliomas with missing molecular information are classified as “Not otherwise specified” (NOS). A histopathological signature that distinguishes IDH status in gliomas using hematoxylin & eosin (H&E)-stained whole slide images (WSIs) has yet to be developed to be used as proxy for molecular alterations. We employed WSIs with corresponding molecular data from The Cancer Genome Atlas (TCGA) and reclassified the gliomas according to the 2021 WHO guidelines. Weakly supervised deep learning approaches, i.e. the Uncertainty-Aware CNN (UA-CNN), and accompanying workflows developed by our group were successful in the segmentation and classification of other cancers. We used the weak labels of IDHwt or IDHmut for given WSIs and utilized an informative sampling algorithm to identify the most relevant tiles that are predictive of their WSI-level label. Next, a second UA-CNN was trained on the relevant subset of tiles determined from the screening stage. For inferencing, given a WSI, the trained UA-CNN model yielded both a predicted label and uncertainty measure for each tile. When reassembled into a WSI, an aggregated uncertainty classification map is formed, which will allow neuropathologists to more rapidly identify regions of interest. While molecular testing is indispensable for current glioma classification, our tool may help reduce the number of NOS diagnosis, mainly in smaller services, by identifying image features that can differentiate between IDHwt and IDHmut. We expect to develop and deploy a method to increase the amount of information extracted from the H&E stain, and help prioritize downstream molecular analyses mandatory for the layered diagnosis of gliomas.
PATH-15. THE PROGNOSTIC IMPLICATION OF MGMT PROMOTER METHYLATION IN IDH-MUTANT GLIOMAS
Authors: Youssef Gilbert , Aquilanti Elisa , Muzikansky Alona , Miller Julie , Vogelzang Jayne , Lapinskas Emily , Lim-Fat Mary Jane , Rahman Rifaquat , Beroukhim Rameen , Bi Wenya Linda , Chukwueke Ugonma , Castro Luis Nicolas Gonzalez , Lee Eudocia , McFaline-Figueroa J Ricardo , Nayak Lakshmi , Reardon David A , Ligon Keith , Wen Patrick Y 
Published: November 2022

Abstract

BACKGROUND
MGMT promoter methylation in IDH-mutant gliomas was associated with improved survival in a recent study (PMID 35386566) but did not account for the updated WHO classification of CNS tumors. We evaluated the prognostic value of MGMT methylation in IDH-mutant gliomas incorporating the 2021 WHO classification.

METHODS
We retrospectively identified 431 patients with IDH-mutant gliomas treated at a single institution from 2010-2020. Kaplan-Meier method was used to estimate OS and PFS rates. Log-Rank test was used to evaluate differences between groups.

RESULTS
Median age was 36.2 years. MGMT promoter was methylated in 49.6%, unmethylated in 17.2%, partially methylated in 6.7%, and untested in 26.5%. Histological diagnosis was consistent with astrocytoma in 45.7%, oligodendroglioma in 33.9%, glioblastoma in 16.4%, and oligoastrocytoma in 4%. After accounting for 1p/19q and CDKN2A statuses, 190 patients had an integrated diagnosis of astrocytoma, grade 2 or 3; 94 had astrocytoma, grade 4; and 147 had oligodendroglioma, grade 2 or 3. There were 101 death events. Median OS was 33.36 years and median PFS was 5.67 years in MGMT methylated gliomas, compared to median OS of 12.54 years (p=0.0064) and median PFS of 3.91 years (p=0.0034) in unmethylated tumors. Upon univariate subgroup analysis, MGMT methylation was associated with significantly longer OS in histological astrocytomas, grade 2 or 4. However, when stratifying patients according to 2021 WHO classification of CNS tumors, there was no significant difference in OS between MGMT methylated and unmethylated astrocytomas or oligodendrogliomas, irrespective of WHO grade.

CONCLUSION
MGMT promoter methylation was associated with prolonged OS in histological astrocytomas, IDH-mutant. However, MGMT status did not impact survival after incorporating 2021 WHO classification of CNS tumors, suggesting that 1p/19q co-deletion and CDKN2A homozygous deletion are stronger prognostic factors in our cohort. The number of survival events was limited; larger datasets are required for more definitive conclusions.
PATH-16. THRESHOLDS OF MITOTIC ACTIVITY AND POST-SURGERY RESIDUAL VOLUME ARE INDEPENDENT PROGNOSTIC FACTORS IN ASTROCYTOMA IDH-MUTANT
Authors: Tran Suzanne , Thomas Alice , Touat Mehdi , Karachi Carine , Dehais Caroline , Feuvret Loïc , Mokhtari Karima , Sanson Marc , Idbaih Ahmed , Carpentier Alexandre , Hoang-Xuan Khê , Capelle Laurent , Bielle Franck 
Published: November 2022

Abstract

BACKGROUND
The distinction between grade 2 and 3 is instrumental to choose between observational follow-up and adjuvant treatment in resected astrocytoma IDH-mutant. However, criteria for discriminating grade 2 and 3 tumors have not been updated since the WHO 2007 classification. There is no consensus on the method of evaluation of the mitotic activity or a mitosis cut-off for grading. The objectives were to evaluate the maximal mitotic activity on a series of resected astrocytoma IDH-mutant and assess its prognostic impact on survival.

METHODS
Maximal mitotic activity on consecutive high-power fields corresponding to 3 mm2 was examined in 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity as well as other prognostic factors (including age, performance status, presurgical tumor volume, plurilobar involvement, postsurgical residual tumor volume, midline involvement) was assessed in tumors with (i) ATRX loss, and (ii) without CDKN2A homozygous deletion, lesional enhancement, histological necrosis nor microvascular proliferation.

RESULTS
Among the 75 (64%) tumors which had gone through observational follow-up after resection, maximal mitotic activity, post-surgical residual volume and plurilobar involvement were independent prognostic factors of TTT (p &lt; 0.0001). A threshold of mitotic activity for grade 2 was fitted using TTT and OS parameters. Using this threshold, patients with “grade 2 tumors” had a median TTT of 55 months versus 19 months for “grade 3” (p= 0.0057) and a median OS of 102 months versus 73 months respectively (p= 0.001). Residual volume &lt; 1 cm3 was associated with longer OS (113 months versus 88 months, p= 0.0021).

CONCLUSIONS
The combination of mitotic activity and postsurgical residual volume improves prognostication in resected astrocytoma IDH-mutant. This novel risk assessment method could identify the best candidates for observational follow-up.
PATH-23. HIGHLY INFILTRATING OLIGODENDROGLIOMAS SHOW DIFFERENT MORPHOLOGY FROM TYPICAL OLIGODENDROGLIOMAS WHILE MAINTAINING GOOD RESPONSE TO CHEMO-RADIATION THERAPY
Authors: Higuchi Fumi , Uzuka Takeo , Sumi Takuma , Matsuda Hazuki , Iwata Kayoko , Shin Masahiro , Ueki Keisuke , Akutsu Hiroyoshi 
Published: November 2022

Abstract
Oligodendrogliomas are diffuse gliomas located in the cerebral hemisphere, and the MRI typically show swollen cortex and subcortical white matter by the tumor cells. IDH mutation and 1p/19q co-deletion define oligodendrogliomas in WHO classification, and these genetic alterations are associated with good response to chemo-radiation therapy and better prognosis compared to the IDH-mutant astrocytomas. We reviewed MRI findings of 60 oligodendrogliomas with 1p/19q co-deleted tumors which were diagnosed at Dokkyo Medical University since 1999. Of those, 3 cases showed highly infiltrating pattern in which tumors were more predominant in the white matter than the cortex and the infiltration involved multiple lobes. We retrospectively investigated those 3 cases for histological features, treatment, and clinical outcome. There were 2 males and 1 female. MRI showed faint-brushed Gd enhancement around the center of the tumor-infiltrated area in 1 case, while there was no enhancing lesion in other 2 cases. All three underwent stereotactic biopsy. Histologically, all 3 cases lacked typical oligodendroglioma morphology: the tumor cells have irregular round, oval to elongated nuclei without perinuclear halo and had dense, closed chromatin similar to astrocytoma. Two cases underwent chemotherapy (TMZ and PAV accordingly), without radiation and 1 case underwent chemotherapy with radiation as the primary treatment. Interestingly, all three tumors responded well not only to the primary treatments but also to the radiation therapy administered after recurrence, although all eventually succumbed to the tumor. PFS were 16, 37, 67 months and OS were 104, 70, 115 months for each, which were at the worse end as oligodendrogliomas but are apparently better than astrocytomas. Highly infiltrating oligodendrogliomas appeared to show significantly different MRI and histological features from typical oligodendrogliomas that primarily involve cerebral cortex. The underlying mechanism of such differences might involve specific genetic alterations and/or gene expression alterations that may not affect treatment response.