bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.18.B AIMING TOWARDS DIFFERENTIATING GLIOBLASTOMA PROGRESSION FROM PSEUDO PROGRESSION -PATIENTS COHORT ESTABLISHMENT AND PRELIMINARY RESULTS
Authors: Haisraely O , Taliansky A , Kaisman elbaz T , Abofani H , Siddeeq M 
Published: September 2023

Abstract

BACKGROUND
Longitudinal follow-up of glioblastoma patients includes advanced imaging modalities to identify tumor progression, which is of limited certainty and occasionally necessitates additional tissue sampling that has potential morbidity. Lately, the possibility of tumor-associated protein markers detection in patients' blood samples - liquid biopsies - has shown useful for this purpose in other cancers and has also gained significant interest in glioblastoma.

METHODS
This study presents data collected from 36histopathology-confirmed IDH-WT glioblastoma patientstreated in Sheba Medical Center between the years 2009 to 2021. Following their diagnosis, these patients were treated with radiation according to the Stupp protocol and subjected to repeated resection due to suspected tumor progressionbased on imaging studies. The data retrieved from patients' medical files include demographics, clinical outcomes, imaging characteristics, tumor molecular, andhistopathological markers. Notably, patients' selection and data retrieval were accomplished using a novel institutional AI algorithm software followed by complementary manual data retrieval of selected patients' medical files.

RESULTS
Patients demographics analysis showed that patientmedian age-at-diagnosis was 55.4 years (range, 21-82), and the male-to-female ratio was 3.5:1. The median overall survival (OS) was 25.1 months (range, 5.2-80.3) and the median follow-up duration was 23.1 months (range, 4.8-80.2).27 out of 36 patients had pathologically confirmed tumor progression while the remaining patients had post-radiation changes along with viable tumor or merely radiation necrosis identification. Pre-surgical resection blood samples were available for 27 out of 37 patients and will be used for a comprehensive glioblastoma-related proteins search using mass spectroscopy. In cases of patients' blood samples available both from the initial diagnosis surgical resection procedure and tumor progression surgical resection, a comparative analysis of those samples will be performed. The preliminary proteomics analysis and clinical outcomes measurements and volumetric tumor data will be presented.

CONCLUSION
s: Here, we present a glioblastoma patient cohort that was meticulously selected with the aim to examine our hypothesis that measuring glioblastoma-related proteins in patients' blood can be achieved and serve as a tool to distinguish between disease phases and monitor disease progression. Our comprehensive preliminary clinical, as well as proteomics data analysis, will be presented and discussed.
P11.30.A LONG-TERM SURVIVING GLIOBLASTOMA. CLINICAL, MOLECULAR AND SURVIVAL ANALYSES
Authors: Comas Antón S , Moreno S , Antelo M , Carrato C , Balaña C , Castañer S , Hernández A , Hostalot C , Domenech M , Villà S 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GB) has a poor prognosis with median overall survival of 12-14 months. According to literature, patients surviving more than two years has progressively increased since 2005 and represent approximately 18% of this population, being considered long-term survivors (LTS). The aim of this study is to retrospectively analyze GB LTS treated in our Neurooncology Unit.

MATERIAL AND METHODS
From December 2009 to March 2021, 49 GB LTS patients were identified in our oncology data base, representing 21,7% of GB patients electronically registered during the same period. Patients were diagnosed and treated for GB according to the current WHO CNS classification at the time of diagnosis. Clinical and molecular characteristics as well as treatment and survival data were analyzed. Classic prognostic factors were analyzed including contact with the subventricular zone (SVZ) which has been identified as prognostic factor in some previous studies.

RESULTS
Median age at diagnosis was 57 years (range: 30-75 years). Median overall survival (OS) and median time to first progression were 43.6 months and 20.7 months respectively, with 9 patients alive and 6 patients without recurrence at the time of analyses. Rate of patients surviving more than 3, 4, 5 and 7 years were 55,1%, 20,4%, 12,24% and 6,12% respectively. Patients received a median of 2 rescue treatments after first relapse (range: 0-6 lines), including systemic therapies, surgery and re-irradiation. Rates for gross total resection, subtotal resection and biopsy were 32,6%, 47% and 20,4% respectively. pMGMT methylated patients and lesions without SVZ contact rates were 73,5% and 42,8% respectively. IDH analyses was available for 61.22% of our GB LTS patients (90% were IDH wild type and 10% mutant IDH, which according to WHO CNS 2021 classification would actually be defined as Astrocytoma grade 4). No statistical differences for OS or time to first progression were found according to sex, age (&lt;55 years versus ≥55 years), pMGMT methylation status; Karnofsky performance status (≤70% versus &gt;70%) and contact or not with the SVZ.

CONCLUSION
Classical prognostic factors did not show statistical differences for OS and time to first recurrence in our GB LTS sample, which could be explained by the small number of patients in the sample and the absence of statistically comparable differentiated groups for some of the variables. Larger and prospective analyses of GB LTS are needed. Molecular analyses with next generation sequencing (NGS) technics and radiomics analyses could apport new information predicting GB LTS.
P11.38.A CYSTIC VESTIBULAR SCHWANNOMA - A SUBGROUP ANALYSIS FROM A COMPARATIVE STUDY BETWEEN RADIOSURGERY AND MICROSURGERY
Authors: Wang S , Naros G , van Eck A , Horstmann G , Tatagiba M 
Published: September 2023

Abstract

BACKGROUND
Some vestibular schwannoma (VS), show cystic morphology. It is known that these cystic vestibular schwannomas (cVS) bear different surgical risk profile compared to non-cystic VS (ncVS) in surgical treatment. This study aims to analyze the management of cVS compared to ncVS in a dual center study of surgically (SURG) and radiosurgically (SRS) treated VS patients.

MATERIAL AND METHODS
This is a retrospective multi-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of vestibular schwannomas for patients between 2005 und 2011 to enable long-term follow-up (FU). Tumor size was classified by Koos Classification. Previously treated VS and VS associated with Neurofibromatosis were excluded. Clinical state was reported by House and Brackmann (H&B) and Gardner-Robertson (G&R) scale (with H&B and G&R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. Data on VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected.

RESULTS
The study population included N=901 patients, who were treated in both centers. N=559 (62%) patients were treated by SRS, and N=342 (38%) patients by SURGERY. N=55 (6%) of all patients showed cystic MR-morphology. These were more often treated by SURG (N=31/55, 58%) compared to ncVS (N=311/845, 37%) (p=0.002). Patients with cVS were indifferent in mean age compared to ncVS. The rate of women was higher in cVS (64%), compared to ncVS (55%) (p=0.001). The overall incidence of recurrence was 16% in cVS (8% in ncVS). Tumor control was worse in cVS treated by SRS (N=6/24, 25%) compared to SURGERY (N=3/32, 9%). When surgically treated, gross total resection (GTR) was achieved in 87% in cVS, whereas this rate was higher in non-cystic VS at 96% (p=0.001). The number of patients N=5/32 (16%) with postoperative relevant facial palsy (HB&gt;2) was significantly higher in cVS (ncVS: N=28/310; 9%).

CONCLUSION
Tumor control in cVS is significantly worse in SRS compared to SURG and SRS-treated ncVS. However, when cVS is treated surgically, the rate of GTR is lower and the number of patients with relevant postoperative facial palsy higher compared to ncVS. Cystic morphology in VS poses a challenge in management (both SRS and SURG) compared to non-cystic tumors. Treatmend decision and patients' consultation should contemplate and address negative prognostic factor of cystic morphology in VS.
P11.39.B PREDICTING RESPONSE TO CHEMOTHERAPY IN RECURRENT HIGH GRADE GLIOMAS USINGEX VIVO 3D CELL CULTURE FUNCTIONAL PRECISION ONCOLOGY PLATFORM
Authors: Mrugala M M , Zimmerman R , Greene D , Fortin-Ensign S , Blomquist M , Swanson K , Bendok B 
Published: September 2023

Abstract

BACKGROUND
Treatment of recurrent high-grade glioma remains a clinical challenge. There are very few agents active in this disease and short of enrollment in a clinical trial, the choice of therapy for a patient at the time of recurrence remains challenging. Several groups, including our own have developed ex vivo drug sensitivity assays to evaluate susceptibility of the tumor tissue to specific chemotherapeutics. To our knowledge, there is only one commercially available platform from the US based company Kiyatec. This tool, in addition to the molecular analysis of the tumor might provide another layer of confidence in choosing treatments for patients with recurrent high-grade gliomas.

MATERIAL AND METHODS
We present the data from our initial experience with the 3D PredictTM platform (Kiyatec, Greenville, SC, USA). We used the platform for 6 patients with recurrent high-grade gliomas undergoing tumor resection at the time of recurrence. We followed the company protocol for obtaining, preserving and shipping the tissue.

RESULTS
Out of the 6 specimens shipped for analysis, 4 assays were completed with full results available for analysis and clinical use. In two cases, the ex vivo tissue expansion was unsuccessful and drug testing was not completed. For the remaining 4 cases, spheroids created from the expansion of the harvested tissue were exposed to 12 drugs (temozolomide, lomustine, procarbazine, abemaciclib, carboplatin, dabrafenib, etoposide, everolimus, irinotecan, osimertinib, rucaparib and trametinib). We have observed different levels of sensitivity to several agents graded as: NO RESPONSE, MODERATE RESPONSE and RESPONSE. In 3 cases the results were used for clinical decision making and 2 patients were started on temozlomidede and carboplatin respectively and remain on treatment. In one case where sensitivity to etoposide was detected, we were not able to proceed with therapy due to insurance denial for the chosen drug.

CONCLUSION
In our experience, this platform is easy to use in a standard clinical setting, the success rate for creating viable spheroids for testing is high and the information derived from the drug sensitivity testing can be useful in clinical practice. Large, prospective clinical trial is need to validate this approach for routine clinical use.
P11.40.A GLIOBLASTOMA WITH OSSEOUS METASTASES: A SINGLE INSTITUTION CASE SERIES
Authors: Webb L M , Webb M J , Campian J L , Caron S J , Sener U 
Published: September 2023

Abstract

BACKGROUND
Although glioblastoma (GBM) is the most common malignant primary brain tumor in adults, extracranial metastasis is rare, occurring in &lt;2% of cases. This rarity has been attributed to the blood brain barrier, immunologic factors, lack of traditional lymphatics in the brain, and the poor prognosis of GBM, limiting its opportunity to metastasize. When GBM does metastasize, bone is the most common destination. GBM may spread hematogenously to bone, especially to vertebral bodies via the surrounding venous plexus. In this single-institution study, we review the clinical characteristics of GBM patients with osseous metastases and evaluate potential risk factors and prognostic significance.

MATERIAL AND METHODS
Using an institutional database, we identified and retrospectively analyzed 6 GBM patients with osseous metastases and studied their demographics, tumor genetics, clinical courses, and outcomes.

RESULTS
Five of 6 (83%) GBM patients with osseous metastases were male, with a median age of 46 years at GBM diagnosis (range: 20-84). All patients had IDH wild type and MGMT unmethylated GBM with mutations in TP53. Two patients (33%) were initially diagnosed with gliosarcoma. All patients were treated with surgical resection followed by radiation with concurrent and adjuvant temozolomide. Five patients (83%) received bevacizumab for vasogenic edema (n=4) or intracranial tumor progression (n=1) prior to bone metastasis diagnosis. Bone metastases were diagnosed a median of 12.2 months (range: 5.3-35.2) after GBM diagnosis and 4.8 months after starting bevacizumab (range: 3.5-13.2). Two patients (33%) received immune checkpoint inhibitor therapy and two patients (33%) received tumor-treating fields prior to bone metastasis discovery. Bone metastases were symptomatic in 2 patients, presenting with back pain (n=1) and leg weakness and urinary incontinence (n=1). Three patients (50%) had concurrent metastases to other organs. Osseous metastases were biopsy-confirmed in 3 (50%) cases, while the other 3 patients had no known alternative malignancy to explain their bone metastases. After osseous metastasis discovery, the median survival was 27 days (range: 13-225).

CONCLUSION
Most of our GBM patients with osseous metastases were male and most, but not all, were young at GBM diagnosis. Tumor genetics common to all patients included IDH wild type, MGMT unmethylated status, and TP53 mutation, which may be important for osseous metastasis. Most patients received bevacizumab, which may be associated with earlier metastasis. While rare, metastatic GBM should be within the differential for GBM patients with bone pain or progressive neurologic symptoms, as osseous metastases portend a dismal prognosis in an already aggressive malignancy.
P11.41.B PHASE 2 STUDY OF VAL-083 AND RADIOTHERAPY IN NEWLY DIAGNOSED MGMT-UNMETHYLATED GBM: CASE STUDY REPORTS
Authors: Guo C , Yang Q , Li J , Wu S , Cao X , Deng M , Du X , Bacha J , Kanekal S , Kwan C , Johnson G , Schwartz R , Langlands J , Brown D , Chen Z 
Published: September 2023

Abstract

BACKGROUND
VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and cell death. In vitro and in vivo studies have demonstrated VAL-083 circumvents MGMT-mediated chemoresistance and differentiates it from other therapies used in the treatment of GBM, including temozolomide (TMZ). VAL-083 also acts as a radiosensitizer against GBM cancer stem cells in vitro.

MATERIAL AND METHODS
A Phase 2 study was conducted to evaluate the safety and tolerability of VAL-083 when administered concurrently with radiation therapy (RT) in newly diagnosed MGMT unmethylated GBM following surgical resection. Stage 1 was a dose-escalation phase to confirm the dose of VAL-083 in this setting. Patients received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days in combination with standard radiation treatment (RT) (2 Gy/day, 5 days/week for 6 weeks). Stage 2 was an expansion phase to enroll up to 20 additional patients at the 30 mg/m2/day of VAL-083 with RT.

RESULTS
A total of 29 patients were enrolled in the study and completed treatment, with 25 patients receiving 30 mg/m2/day VAL-083. The median number of cycles completed by all patients was 9 (range 2-13). Consistent with our prior experience, myelosuppression was the most common adverse event. In a sub-group of patients, levels of VAL-083 in CSF were found to be at least as high as those in plasma. At study completion, the median progression free survival (PFS) for all patients enrolled was 9.3 (95%CI: 6.4-12.0) months and median overall survival for all patients enrolled was 19.6 (95%CI: 14.0-22.4) months. Here we report on two patient cases. The first, a 32-yo woman, WHO Gr. 4 GBM (MGMT unmethylated), who received conventional radiotherapy with concurrent chemotherapy with VAL-083 followed by adjuvant VAL-083, for a total of 13 cycles of VAL-083. This patient is tumor free suvival more than 4 years till last follow-up (Mar 2023 ). The second, a 49-yo man, WHO Gr. 4 GBM (MGMT unmethylated), who received radiotherapy with concurrent chemotherapy with VAL-083 followed by adjuvant VAL-083, for a total of 12 cycles of VAL-083. Two years after initial treatment with VAL-083 was discontinued, a new lesion was found, and the patient had a second resection, which revealed WHO Gr. 3 astrocytoma. The patient was re-treated with VAL-083,and was stable till last follow-up(Mar 2023).

CONCLUSION
The results from the study and these patient cases, support the potential benefit of VAL-083 as a treatment alternative against GBM tumors with MGMT-mediated resistance to TMZ. Clinicaltrials.gov: NCT03050736.
P11.56.A MODIFIED FRAILTY INDEX (MFI) AS A SURVIVAL AND FUNCTIONAL OUTCOME PREDICTOR IN OLDER PATIENTS UNDERGOING SURGERY FOR BRAIN METASTASES
Authors: Ersoy T F , Brainman D , Coras R , Simon M 
Published: September 2023

Abstract

BACKGROUND
Surgical decision making in older patients with brain metastases (BM) is challenging. Frailty and comorbidities are often thought to limit therapeutic options as well as functional and survival outcomes.

MATERIAL AND METHODS
139 consecutive patients undergoing surgery 2017-2021 for BM were analyzed retrospectively. Cut-off for age was ≥60 yrs. in accordance with the graded prognostic assessment (GPA) index. Frailty was investigated using the mFI index, a compound measure assessing comorbidities and the patients’ functional health status.

RESULTS
Median age was 69.0 (IQR: 63.0-74.5) yrs. 55.4% had multiple metastases. We recorded 9.4% major (CTCAE III-V) surgical and 10.1% medical complications. 7.9% of patients had major new focal neurological deficits ≥30 days. Median overall survival (mOS) was 7.8 (IQR: 5.0-10.6) months. Frailer patients lived shorter (mOS for “least-frail”/mFl 0: 13.6 [IQR: 8.6-18.6], “moderately frail”/mFl 1-2: 9.0 [IQR: 4.9-13.0] and “frailest”/mFl ≥3: 2.7 [IQR: 0.9-4.5] months; p&lt;0.001). Multivariate analysis with all parameters correlating significantly with mOS in the univariate analysis (mFI, higher preop. KPS, younger age [&lt;69 yrs.], female sex) revealed a higher preop. KPS to be the only independent significant survival predictor (70 vs. 80-100; HR 2.1, p&lt;0.001). Frailer patients had poorer functional outcomes (patients w/ postop. KPS ≤70 vs. 80-100; mFI 0: 9/36 [25.0%], mFI 1-2: 20/65 [30.8%], mFI ≥3: 25/38 [65.8%]; p&lt;0.001). Multivariate analysis with all parameters correlating significantly with better functional outcome in the univariate analysis (mFI, higher preop. KPS, younger age, female sex and single metastasis) showed that a higher preop. KPS was the strongest prognostic parameter (RR 17.2, p&lt;0.001). The mFI was not an independent outcome predictor. In a ROC analysis the preoperative KPS proved a much better predictor of functional outcome than the mFI (AUC 92 vs. 71%; sensitivity/specificity optimum 80 vs. 2, resp.). mFI was not a predictor of complications (p=NS).

CONCLUSION
The mFI proved a strong survival and functional outcome predictor in older patients. However, this effect was no longer seen in multivariate analyses when the KPS was included as a covariate. This may suggest that surgical outcomes depend on the patients’ presurgical functional health status rather than comorbidities. The presence of comorbidities (if well treated) should therefore not deter from BM surgery in older patients.
P11.58.A CARDIOVASCULAR EVENTS AND VENOUS THROMBOEMBOLISM AFTER PRIMARY MALIGNANT AND NON-MALIGNANT BRAIN TUMOUR DIAGNOSIS: A POPULATION MATCHED COHORT STUDY IN WALES (UNITED KINGDOM)
Authors: Poon M T C , Brennan P M , Jin K , Sudlow C L M , Figueroa J D 
Published: September 2023

Abstract

BACKGROUND
Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the distribution of risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities.

MATERIAL AND METHODS
Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥18 years in the primary care database with first diagnosis of malignant and non-malignant brain tumour identified in the cancer registry in 2000-2014, and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any tumour diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour and follow-up period.

RESULTS
There were 2,869 and 3,931 people diagnosed with malignant and non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). Risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained to be higher than controls for those surviving one year. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.

CONCLUSION
The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.