bluuebunny/crossref_metadata_2025 huggingface dataset:
BSBM-21 MACHINE LEARNING IDENTIFIES EXPERIMENTAL BRAIN METASTASIS SUBTYPES BASED ON THEIR INFLUENCE ON NEURAL CIRCUITS
Authors: Masmudi-Martin Mariam , Sanchez-Aguilera Alberto , Navas-Olive Andrea , Baena Patricia , Hernández-Oliver Carolina , Martínez Sonia , Lafarga Miguel ,   RENACER Red Nacional de Metástasis Cerebral, Lin Michael Z , de la Prida Liset Menendez , Valiente Manuel
Published: August 2023

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms, however understanding how brain metastasis co-opt the function of neuronal circuits beyond a mass effect remains unknown. We report a comprehensive multidimensional modelling of brain functional analysis in the context of brain metastasis. By testing different pre-clinical models of brain metastasis from various primary sources and oncogenic profiles we dissociated the heterogeneous impact on brain function that we detected from the homogeneous inter-model tumor size or glial response. In contrast we report a potential underlying molecular program responsible for impairing neuronal crosstalk in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help to predict the presence and subtype of metastasis. We envision that our findings not only increase our knowledge on the molecular basis of neurocognitive impairment associated with brain metastases but they are also the first step towards new therapeutic strategies to prevent or stop the decline in quality of life associated with these symptoms. In addition, our computational findings exploiting electrophysiological profiles suggest the possibility to exploit them as novel biomarkers.
CLRM-04 DEVELOPING A WORD LEXICON FOR VENOUS THROMBOEMBOLISM DATA ANNOTATION USING RADIOLOGY REPORTS IN GLIOBLASTOMA PATIENTS - LINKING LARGE-SCALE DATA SETS TO EXPAND CLINICAL FEATURES FOR AI
Authors: Jagasia Sarisha , Krauze Andra
Published: August 2023

Patients with gliomas, particularly glioblastomas (GBM), have a higher risk of developing venous thromboembolism (VTE), correlating with overall survival (OS). Artificial intelligence (AI) approaches that employ VTE as a clinical feature in brain tumor patients is understudied due to the difficulty in analyzing electronic health records (EHR). Data expansion by creating a word lexicon for natural language processing (NLP) of free-text clinical reports will allow exposure of VTE for the classification of large-scale data sets, NLP, and AI. Patients with a pathologic diagnosis of GBM (2005-2021) were screened for the development of VTE based on radiology free-text reports (ultrasound (US) of extremities and Computed Topography-pulmonary angiogram (CT)). Kaplan-Meier survival analyses about overall survival (OS) and progression-free survival (PFS) were generated for VTE. 163 patients (mean age = 56.1 ± 12.1, 65% male) were included, 48 (29.4%) were screened for VTE following clinical suspicion on history or physical exam, and 15 (9.2%) were found to have a VTE. Screening methods were ultrasound 83.3% (40) or CT 13.9% (6), or both 4.6% (2). 28.6% (12) of US and 37.5% (3) of CT resulted in a positive VTE diagnosis. The words “partial”, “residual”, “complete”, “critical” or “clotted” when used as an “or” boolean statement applied to US and CT radiology reports identified ~93% of the patients with VTE. Patients with VTE had worse OS (median 14 vs. 19 months, p = .0189) and PFS (median 6 vs. 9 months, p = .0239) than patients without VTE, indicating underlying pathology associated with both prevalence of VTE and tumor burden. US and CT yield a similar percentage of positive VTE findings while employing different terms to characterize VTE. We confirm that patients with VTE have poorer outcomes and present a word combination that identifies patients with VTE in large-scale radiology report data.
CLRM-08 TAILORING CLINICAL TRIALS TO INCREASE PATIENT ENGAGEMENT: IMPACT ON PATIENT-REPORTED OUTCOMES IN ONCOLOGY
Authors: Khakwani Saima , Dumais Kelly
Published: August 2023

BACKGROUND

As regulators put more attention on patient-reported outcomes (PROs) in oncology clinical trials, it is vital to understand patient preferences and motivation for completing PROs. We investigated preferences and motivations for symptom reporting and how this may differ between participants with cancer and with other chronic non-oncology diseases.

METHODS

Participants completed an online survey focusing on preferences for using devices to report symptoms and what motivates them to complete PROs. Statistical analyses included a descriptive analysis of responses and Chi-Squared tests to examine differences between subgroups (oncology vs. participants with arthritis, diabetes, and chronic obstructive pulmonary disease).

RESULTS

Participants with cancer (N = 16) preferred using their own smartphone (31%) over going to a website (19%) or using a study-dedicated device (6%) to report symptoms, with 44% being happy with any option (44%). 88% of participants reported that receiving regular information to help manage their symptoms would motivate them the most to complete their PROs on a regular basis. Receiving a small financial compensation (81%) and knowing that their data was being reviewed by a healthcare professional (75%) were also strong motivators to complete PROs. The least preferred motivator was compensation in the form of charity donations (25%). Preference for reporting symptoms differed between subgroups (p=0.04), such that participants with cancer showed a higher preference for using their own smartphone compared to the non-oncology subgroup (N=30). The non-oncology subgroup was more likely to report notifications and alarms (p=0.04) as strategies that would encourage them to complete PROs.

CONCLUSION

This exploratory analysis suggests the importance of considering a range of symptom reporting strategies and the potential for tailoring strategies to fit patient preferences. The preference to use personal smartphones to report symptoms in participants with cancer suggests that a Bring-Your-Own-Device (BYOD) strategy may be particularly suited for oncology clinical trials.
CLRM-09 MAPPING THE DISTRIBUTION AND CLINICAL ASSOCIATIONS OF BRAIN METASTASES IN RENAL CELL CARCINOMA
Authors: Kamson David Olayinka , Feinaj Ardit , Markowski Mark , Yerrapragada Anirudh , Elias Roy , Shenderov Eugene , Bettegowda Chetan , Singla Nirmish , Ged Yasser
Published: August 2023

Brain metastases (BrM) commonly occur in renal cell carcinoma (RCC) and often present with hemorrhagic features. The distribution patterns of BrM in RCC and their associations with clinical outcomes remain unclear. We conducted a retrospective neuroanatomical distribution analysis combined with clinical review of our surgical RCC BrM cohort. Sixty-seven BrMs from 46patients (age 63±10years, 25males) were included. The majority of BrM (55%) were found in the left hemisphere, with frontal (45%), parietal (21%), and occipital (18%) lobes being the most commonly affected areas. Hemosiderin deposits, as detected by MRI, were present in 82% of BrM, while hemorrhage, as detected by CT, was present in 80% of BrM. Patients with solitary BrM had a higher KPS (p=0.006) and lower disease burden (p=0.004) compared to those with multiple BrM. Mean 1D and 2D(RANO) tumor dimensions were 2.0±1.1cm and 4.7±4.9cm2, respectively, and correlated with the neutrophil count at BrM diagnosis (r=0.3; p=0.01). Hemosiderin deposits were associated with larger tumors (2.6±1.0cm vs. 1.8±0.7cm, p=0.04), lower platelet counts (p=0.01), and higher hemoglobin levels (p=0.08). Shorter Brain Metastasis-Free Survival was associated with hemosiderin deposits on MRI (log-rank p=0.04) and renal vein thrombosis (RVT) in the primary specimen (log-rank p=0.002). RVT at primary diagnosis was associated with both hemosiderin deposits on MRI (p=0.05) and hemorrhage on CT (p=0.03), and CNS progression-free survival was shorter in patients with RVT (7.3±1.7 months vs. 21.0±4.7 months). When including only significant predictors, right hemispheric BrM lateralization (HR 2.6, p=0.06), hemosiderin deposits in BrM (HR 6.5, p=0.02), and IMDC risk groups (intermediate HR=2.9; poor-risk HR=25.6; p<0.04) were independent prognostic factors for shorter OS on multivariable analysis. Our results demonstrate that mapping the BrM distribution o in RCC can provide clinically relevant insights. Hemosiderin deposits in BrM may have prognostic implications. Further analyses are ongoing.
CLRM-11 ALK TYROSINE KINASE INHIBITOR THERAPY AND BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER: IMPACT ON TUMOR SIZE AND DISTRIBUTION
Authors: Kamson David Olayinka , Cheunkarndee Tia , Marrone Kristen , Murray Joseph , Feliciano Joy , Hann Christine , Ettinger David , Anagnostou Valsamo , Forde Patrick , Brahmer Julie , Levy Benjamin , Scott Susan , Lam Vincent
Published: August 2023

Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase rearrangement (ALK+) is known to have a high propensity to form brain metastases (BrM), with over 50% of ALK+ lung cancer patients developing BrM despite effective ALK tyrosine kinase inhibitor (TKI) therapy with central nervous system (CNS) activity. Pharmacokinetic (PK) data from other CNS-active lung cancer TKIs have suggested that there may be differences in drug concentration between white and gray matter in the brain, which may play a role in BrM formation patterns and response. In this study, we aimed to compare the size and distribution of ALK+ NSCLC BrMs at diagnosis in a TKI-naïve and TKI-exposed cohort. Brain MRI data from patients with ALK+ NSCLC were retrospectively reviewed, and each tumor was marked in a standard space brain model using 3D Slicer-4.11. FreeSurfer white-gray matter atlases were used to assess BrM distribution. We found that TKI-exposed patients had significantly smaller BrM diameters than TKI-naïve patients (6.1±3.8 vs. 10.2±5.5mm, p=0.02) and were more likely to have white matter-exclusive (3.5±4.4 vs. 1.4±2.0, p=0.05) and deep white matter metastases (3.2±4.3 vs. 1.3±2.0, p=0.06). The metastatic burden was similar between the groups, while the mean number of BrM per patient was numerically higher in the TKI-exposed group (10.6±11.9 vs. 6.2±9.5; p=0.22). These findings suggest that TKI therapy may result in smaller individual lesions that are more likely to be exclusive to the white matter, where drug concentrations may be significantly lower. This suboptimal CNS distribution of TKIs in the white matter may contribute to the progression of brain metastases in ALK+ patients despite TKI therapy. Further analyses are ongoing to evaluate ALK TKIs of varying CNS penetrance and later disease time points in more granular anatomic regions.
LMAP-13 THE IMPACT OF RADIATION TREATMENT DOSE TO THE TUMOR AND NORMAL TISSUES USING POST-OPERATIVE MRI VS. MR-SIMULATION FOR RADIOTHERAPY PLANNING OF HIGH-GRADE GLIOMA
Authors: Thrower Sara , Farhat Maguy , Curl Brandon , Cifter Gizem , Shanker Mihir , Beckham Thomas , Ghia Amol , Swanson Todd , Wang Chenyang , Brock Kristy , Chung Caroline
Published: August 2023

BACKGROUND

Radiotherapy (RT) targets are commonly defined on post-operative (post-op) MRI registered to CT simulation images. However, changes can occur between surgery and simulation due to tumor progression and post-operative healing. In this work, we evaluate the impact of treatment planning using MR images taken at the time of CT simulation (MR-sim) versus post-op MRI.

METHODS

We evaluated 30 patients with primary HGG who received post-op MRI followed by RT planned using an MR-sim. We retrospectively delineated the gross tumor volume (GTV), clinical target volume (CTV), and normal structures on the post-op MRI and generated an experimental RT plan for these volumes. The RT plans based on post-op and MR-sim images were compared to determine the volume of tumor tissue that would have been undertreated, and the amount of normal brain tissue that would have been exposed to radiation (overtreated) had the plan been based on the post-op imaging.

RESULTS

The mean length between post-op imaging and MR-sim was 26 days (range: 12-42). A mean of 7.3cc (range 0.36cc–25.23cc) and 32.4cc (0.35–140.14cc) of the GTV and CTV, respectively, were undertreated on the post-op MRI plan compared to the MR-sim plan. The plan based on post-op target volumes resulted in a mean decrease in prescription dose coverage of the MR-sim-based GTV and CTV of 15.8% (max 72%) and 11.7% (max 57%), respectively. A mean of 14.5cc (0.04cc–53.9cc) and 47.5cc (range 2.4–179.2) of non-target brain tissue as identified on the MR-sim were included in the post-op MRI-based GTV and CTV, respectively. On average, the optic chiasm and brainstem would have received 191cGy and 117cGy more dose than intended, respectively.

CONCLUSIONS

Our findings confirm the valuable impact of RT planning using MR-sim in HGG to optimize treatment targets and reduce the exposure of normal tissue to unnecessary toxicity.
LMAP-15 INTRACRANIAL RADIOTHERAPY WITH TUCATINIB FOR BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER: A SINGLE-INSTITUTION SERIES
Authors: Khatri Vaseem , Mills Matthew , Oliver Daniel , Yu Michael , Ahmed Kamran
Published: August 2023

BACKGROUND

Tucatinib, a HER-2 TKI, has demonstrated intracranial efficacy in the HER2CLIMB study. Treatment of brain metastases frequently includes stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT); however, HER2CLIMB did not detail outcomes with RT.

METHODS

Patients who received tucatinib at our institution from 2020-2022 were identified. Patients who had brain metastases and received intracranial RT within 6 months of receiving tucatinib were included. Patients with history of prior leptomeningeal disease (LMD) were excluded. The Kaplan-Meier (KM) method was used to estimate intracranial failure (ICF), overall survival (OS), and local control (LC). Adverse events and details regarding symptomatic radionecrosis were collected.

RESULTS

Between 2020 and 2022, 50 patients were treated with tucatinib. Forty patients had diagnosed brain metastasis and received intracranial RT. Median age at tucatinib start was 51 years (range: 33-83). All patients were HER-2+, 47.5% were HR+. Fifty-four separate RT courses were delivered within 6 months of tucatinib, including 45 courses of stereotactic RT (83%) and 9 (17%) WBRT. Twenty-three patients (57.5%) underwent concurrent tucatinib and intracranial RT, defined as RT within 2 months of tucatinib initiation. Median follow up for surviving patients was 18.9 months. Fifteen patients (37%) died at the time of analysis. Median OS was 25.1 months with 24-month KM OS of 52%. Median time to ICF was 12.5 months with 24-month KM ICF of 48%. At the time of ICF, 7 patients (17.5%) developed LMD. In total, 132 discrete lesions were treated with SRS. Ten lesions (7.5%) underwent local failure, with 24-month KM LC of 82%. Three patients (9.1%) undergoing SRS developed symptomatic radionecrosis; all completely resolved with dexamethasone.

DISCUSSION

In this first series reporting outcomes with RT and tucatinib, no evidence of excess toxicity was noted. Intracranial control appears favorable compared to previous reports. Concurrent RT with tucatinib should be assessed prospectively.
LMAP-16 THE EFFECTS OF POSTOPERATIVE STEREOTACTIC RADIOSURGERY TIMING ON CLINICAL OUTCOMES IN PATIENTS WITH INTRACRANIAL METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nwankwo Anthony , Dang Danielle , Choe Kevin , Kanani Samir , Cohen Adam , Ziu Mateo
Published: August 2023

Stereotactic radiosurgery (SRS) after neurosurgical resection improves local tumor control in patients with metastatic brain cancer. However, the influence of timing on its therapeutic efficacy is unclear, and a lack of consensus and standardization limits its optimization. We performed a systematic review and meta-analysis examining publications that reported the timing of postoperative SRS for patients with intracranial metastases. Our primary outcomes included median overall survival and rates of local and regional failure, while our secondary outcomes examined the incidence of treatment-related adverse events. Correlations between median SRS timing and these variables were assessed using linear regression and publication bias was appraised via Egger’s test. Our systematic review resulted in 22 articles comprising 1338 patients who met the criteria for inclusion. The median timing of adjuvant SRS spanned 14.5 to 41 days. There was a significant positive study-level correlation of median time to SRS with regional failure (P=0.043, R2=0.32) but not with overall survival (P=0.54, R2=0.03) or local failure (P=0.16, R2= 0.14). Data regarding adverse events related to treatment was limited in the literature and there was significant heterogeneity within the reports (P<0.0001). Overall, our results demonstrate institutions with a longer time between surgery and SRS had lower rates of regional failure, however, this did not affect rates of local failure or patient survival. Further research is warranted to elucidate the role of timing for postoperative SRS on oncologic outcomes as well as the factors that contribute to optimal radiosurgery workflow in this patient population.
LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS
Authors: Taori Suchet , Wei Zhishuo , Deng Hansen , Niranjan Ajay , Lunsford L Dade
Published: August 2023

BACKGROUND AND OBJECTIVES

The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread.

METHODS

We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20).

RESULTS

The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS < 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and < 3 brain metastases at SRS presentation (p<0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%.

CONCLUSIONS

SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.
NEIM-08 MODELING COMPETITION BETWEEN SUBPOPULATIONS WITH VARIABLE DNA CONTENT IN RESOURCE LIMITED MICROENVIRONMENTS
Authors: Katira Parag , Rentzeperis Frederika , Beck Richard , Pinto Ana Forero , Nowicka Zuzanna , Tagal Vural , Teer Jamie , Scanu Elisa , Pasetto Stefano , Veith Thomas , Fiandaca Giada , Fritz Yi , Devine Karen , Barnholtz-Sloan Jill , Farinhas Joaquim , Gomes Ana , Andor Noemi
Published: August 2023

Resource limitations shape the outcome of competitions between heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. High-ploidy cells need more resources, to synthesize increasing amounts of DNA, RNA and proteins. To model how subpopulations with variable DNA-content compete in the resource limited environment of the human brain we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time, including stiffness, glucose and proliferating cells of various DNA content. Well established Fokker-Planck partial differential equations govern the spatial distribution of resources and cells. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We sequenced four surgical specimens collected during the 1st and 2nd surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29 respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. T1 post and T2 flair scans acquired after the 1st surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2nd surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate, but a lower Glucose-dependent death rate, resulting in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions.
SDPS-13 CELL LINE STUDY OF NUCLEOSOME-BASED BIOMARKERS IN THE DIAGNOSIS AND DETECTION OF RELAPSES IN GLIOBLASTOMA
Authors: Decarpentrie Jonathan , Van den Ackerveken Priscilla , Govaerts Adrien , Lobbens Alison , Beine Edeline , Donis Nathalie , Herzog Marielle , Douxfils Jonathan
Published: August 2023

Currently, glioblastoma (GBM) diagnosis and monitoring rely on neuroimaging and histopathological confirmation. However, overall survival has not improved in last decades due to therapeutic failure and to a lack of biomarkers for relapses’ detection. Liquid biopsies (i.e. blood or cerebrospinal fluid) using nucleosomes-containing-histone post-translational modifications (PTMs) have the potential to become valuable biomarkers for diagnosis and monitoring GBM. Four glioblastoma cell lines (SF-126, U-87MG, U-118MG, and U-138MG) compared to a healthy microglia cell line (HMC3) and other solid cancer cell lines including pancreas (MIA PaCa-2), liver (HepG2), and cervix/uterus (HeLa) have been analyzed to identify their epigenetic profile. Nucleosomes were extracted and analyzed with the Nu.Q® Discover immunoassays platform (Belgian Volition) addressing 13 histone-PTMs. Quantitative results of PTMs expression were normalized on quantification of total nucleosomes (H3.1-nucleosomes). The immunoassay identified three candidate biomarkers compared to control cell lines (n=4): citrullinated-histone H3 (H3R8Cit) (control=4.68% ; GBM=13.88% ; p<0.05), phosphorylation of H3S10 (H3S10Ph) (control=2.31% ; GBM=5.57% ; p< 0.05), and a trend in H3K4Me2 elevation (control=0.43% ; GBM=1.07% ; p=0.066) in GBM cell lines(n=4). These results were confirmed by western blot. In addition, principal component analysis revealed a segregation between GBM and control cells, mainly driven by these three PTMs. Moreover, to demonstrate the capacity of the Nu.Q® assays to quantitatively monitor PTMs, GBM cell line SF-126 (n=3) was treated with an EZH2 inhibitor (responsible of H3K27 methylation) (iEZH2). After 24 hours and 48 hours of exposure, the level of expression of H3K27Me3 – expressed as ratio of total nucleosomes was decreased by 32% (control=14.67%±0.58% ; iEZH2=10.00%±1.73% ; p<0.05) and 41% (control=15.33%±1.53% ; iEZH2=9.00%±0.00% ; p<0.05), respectively. Those results were also confirmed by western blot analysis. In conclusion, we identified three specific in vitro epigenetic-based marks of GBM and demonstrated that the Nu.Q® technology is a valuable tool to monitor the degree of PTMs expression.
SDPS-14 CLINICAL FEATURES AND OUTCOME IN CHILDREN WITH CHOROID PLEXUS CARCINOMA-A SINGLE CENTER EXPERIENCE
Authors: Li Miao , Du Shuxu , Sun Yanling , Wu Wanshui , Sun Liming
Published: August 2023

OBJECTIVE

To investigate the clinical features, treatment and outcome in pediatric choroid plexus carcinoma (CPC) patients.

METHODS

Twelve children with CPC confirmed by pathology who were admitted to Beijing Shijitan Hospital from January 2017 to October 2022, were included. The last follow-up was December 31, 2022. Kaplan-Meier method was adopted for survival analysis.

RESULTS

Among the 12 patients, 4 were males and 8 females. The median age at diagnosis was 29.7 (range, 5.8-119.6) months, with 8 cases less than 3 years old at the time of diagnosis. Nine cases were supratentorial, and 3 infratentorial. The tumor was located in ventricular system in 6 cases, external involvement of brain parenchyma in 6 cases. Two cases experienced metastases (M+) and 10 M0 at the time of diagnosis. All patients received tumor resection, with 8 cases GTR and 4 NTR. Five cases received chemotherapy only and 7 patients radio-chemotherapy after surgery. At last follow-up, 8 cases experienced tumor recurrence or progression, and 4 died. The mean OS were (56.7±8.8) months, The 1, 3, 5-year OS were (83.3%±10.8)%、(66.7%±13.6)%, and (66.7%±13.6)%, respectively. The mean PFS time were (24.3±7.2) months, The 1, 3-year PFS were (41.7%±14.2)% and (33.3%±13.6)%, respectively. Univariate analysis showed the OS were poorer in children with infratentorial tumors than supratentorial tumors (χ2 =8.562, P = 0.003). And the OS was also lower in patients who received chemotherapy only than those who received both radiotherapy and chemotherapy (χ2 =8.488, P =0.004). The difference in PFS between groups were not significant (P>0.05).

CONCLUSION

CPC is very rare and with poor prognosis in children. Children with infratentorial tumors and who received chemotherapy only tend to have poorer OS. Due to the small sample size, further clinical trials need to be developed to verify.
SDPS-28 THE STUDY OF AN ANOIKIS-RELATED SIGNATURE TO PREDICT GLIOMA PROGNOSIS AND IMMUNE INFILTRATION
Authors: Zhang Dongdong , Wang Yu , Zhou Huandi , Han Xuetao , Hou Liubing , Lv Zhongqiang , Xue Xiaoying
Published: August 2023

BACKGROUND

Gliomas are the most common highly aggressive primary malignant brain tumors in adults with different biological behavior and clinically heterogeneous features. Method: We extracted the anoikis-related genes (ARGs) from GeneCards and obtained differentially expressed genes in normal and glioma tissues from the GSE4290 dataset by differential analysis to obtain intersect differentially expressed ARG in gliomas. KEGG and GO analysis were used to evaluate the potential pathways and molecular processes of these genes. Based on The Cancer Genome Atlas (TCGA) training cohort, we performed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression to construct an ARG prognostic model and validated them in the TCGA testing cohort and the Chinese Glioma Genome Atlas (CGGA) validation cohort. Subsequently, we further explored the differences in clinical characteristics, tumor mutation burden(TMB), and the immune microenvironment in the high- and low-risk groups. Univariate and multifactorial regression analyses and nomogram construction were also performed. Moreover, we assessed the expression levels and clinical prognostic value of prognostic key genes.

RESULTS

The regulatory model based on quantitative ARG prognostic models showed that patients in the high-risk group were associated with poorer survival prognosis, poorer clinical characteristics, and higher TMB levels. Moreover, the high-risk group had high levels of immune infiltration and upregulated immune checkpoint gene expression. The ARG prognostic model and the Nomogram showed good predictive performance. Expression and survival analysis of five prognostic ARG signatures (ETV4, HMOX1, MYC, NFE2L2, and UBE2C) showed that these genes except MYC were cancer-promoting genes.

CONCLUSION

Our constructed ARG prognostic risk model provides a potential therapeutic target and theoretical basis for predicting the prognosis of glioma patients and guiding individualized immunotherapy.
SDPS-45 PROGNOSTIC CHARACTERIZATION OF GENETIC MARKERS IN GLIOMA-ASSOCIATED EPILEPSY
Authors: Guo Lydia , Rilinger Ryan , Sharma Akshay , Lobbous Mina , Grabowski Matthew
Published: August 2023

BACKGROUND

High-grade gliomas are often associated with seizures, which impair quality of life and cause deleterious neurocognitive effects. Few molecular markers characterized in high-grade gliomas have prognostic capacity for glioma-associated epilepsy. Mutations in isocitrate-dehydrogenase 1 (IDH1) have been associated with glioma-associated epilepsy (Chen et al. Neurology 2017;88(19):1805–13), but other genetic and cell proliferation markers in glioma biopsies have inconclusive connections with glioma-associated epilepsy. Current AAN guidelines advise against prophylactic administration of anti-seizure medications in patients with newly diagnosed brain tumors. We sought to characterize common molecular markers in high-grade glioma-associated epilepsy.

METHODS

We retrospectively reviewed 241 patients diagnosed with grade IV gliomas between 2018 and 2021 at our institution. Analysis of genetic biomarkers in tumor biopsies included chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, IDH1 mutation, and EGFR amplification. Multiple logistic regressions were utilized to examine the association between genetic biomarkers and seizure incidence at three intervals: preoperative, postoperative, and six months post-surgery. Other variables examined were age, tumor location (lobe, laterality, eloquence), and treatment type (radiation therapy, chemotherapy, immunotherapy).

RESULTS

Of 241 patients analyzed, 104 (43%) patients experienced seizures. EGFR amplification in high-grade gliomas was associated with preoperative seizures (β = .92, p = .013) but was not associated with postoperative seizures nor seizures six months post-surgery. Chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, and IDH1 mutation were all not associated with seizure incidence.

CONCLUSION

The study results indicate that EGFR amplification is associated with preoperative seizures, suggesting EGFR to promote glioma epileptiform activity. As EGFR amplification is characteristic of the classical subtype of glioblastoma, these results further suggest that the pathogenesis of glioma-associated epilepsy is likely related to specific molecular tumor characteristics. These preliminary results will be expanded upon with further analyses that increase sample size and include next-generation sequencing

RESULTS
SPCR-01 CONCURRENT WOUNDED GLIOMA SYNDROME AND DISTANT WOUNDED GLIOMA SYNDROME FOLLOWING A GROSS TOTAL RESECTION OF GLIOBLASTOMA MULTIFORME - A CASE REPORT
Authors: Calubayan John Michael , Opinaldo Paul Vincent
Published: August 2023

Surgery is the initial form of treatment for glioblastoma, and a maximum resection without impairing neurological function improves survival. Wounded Glioma Syndrome (WGS) is a clinical picture observed after the resection of high-grade tumors. This syndrome, developing within hours or a few days after glioma surgery, is characterized by hemorrhage into the surgical bed and cerebral edema, and at times occurring in areas distant from the site of the resection, i.e., Distant WGS. We report a case of an elderly male presenting with an acute-onset left leg weakness, with a large peripherally-enhancing mass with central non-enhancement suggestive of necrosis in the right frontal lobe. A gross total resection of the tumor was done, and the histopathologic evaluation yielded a high-grade glioma, favoring a diagnosis of Glioblastoma WHO Grade-IV. During the postoperative period, he was drowsy and was able to move the right extremities. He had a series of generalized tonic-clonic seizures three hours after the operation. After eight hours, the patient became comatose with signs of increasing intracranial pressure. A cranial CT revealed diffuse cerebral edema, and hemorrhage into the operative site in the right frontal lobe, as well as subarachnoid hemorrhages in the bilateral fronto-parietal sulci. There were also small hemorrhages seen in the left caudate head, midbrain and left hemipons. Death occurred the following day. This case report demonstrates an unusual case of a WGS with a concurrent Distant WGS in the brainstem after a gross total resection of a frontal lobe glioma. This case shows a significant uncommon sequela that a patient undergoing glioma surgery can present, leading to rapid deterioration and death. Resection of a glioma carries a significant risk, and its impact in the immediate postoperative period merits evaluation when planning the perioperative management, taking prompt action if these syndromes occur.
SPCR-03 ACCESS TO CRITICAL GENOMIC TUMOR TESTING FOR GLIOBLASTOMA (GBM) PATIENTS
Authors: Pilkington Ed , Stebbins Alice , Wilke Martha , Duprey Kelli
Published: August 2023

PURPOSE

Assess whether GBM patients are being offered access to tumor testing at all stages of treatment as an essential first step toward personalized medical treatment of this fatal disease.Method: On-line survey sent to OurBrainBank Community.

RESULTS

More than 90 patients and/or caregivers completed the survey. Results revealed that 50 percent were never informed about tumor testing prior to their initial surgery, and some were never informed. Seventy percent were unsure or were never informed of the importance of storing tissue once collected. For the 30 percent who knew of tissue storage, only half actually had tissue stored. More than half did not know about tumor types or mutations. Only half felt that they received enough information and education to make good decisions. The best statistic was that those in urban areas were able to get care at a hospital that specialized in brain tumors. In addition, the survey revealed that 50 percent of participant GBM patients felt that they had an equal and collaborative relationship with their medical team, and 50 percent did not.

CONCLUSIONS

GBM patients and their caregivers are not treated consistently, particularly in regard to genomic tumor testing, which has become a vital first step toward personalized treatment. In this study, while some patients were provided information about their condition, 50 percent were not provided any information at all, or limited, and not based on individual patient needs. Geographical inequalities between urban and rural areas partly explain these disparities.
SYST-05 BETA-ADRENERGIC BLOCKADE LICENSES THE USE OF IMMUNOTHERAPY IN PRIMARY AND METASTATIC BRAIN TUMORS
Authors: Lorrey Selena , Wachsmuth Lucas , Ostrom Quinn , Fecci Peter
Published: August 2023

Brain tumors present a unique challenge to in the context of immunotherapy, as these patients are immunosuppressed not just at the tumor but also outside the CNS. The systemic immunosuppression observed in brain tumor patients limits the capacity of the immune system to respond to immunotherapy. Brain tumor patients, particularly those with metastatic disease, represent a patient population that is on the rise and in need of targeted treatment approaches. Through this work we present a novel axis of immunosuppression in brain tumor patients and demonstrate that overactive adrenergic signaling is a major barrier to immunotherapeutic success. Our data indicate that combining beta-adrenergic blockade with immunotherapy provides a survival benefit in the setting of brain tumors, where immunotherapy alone has proven ineffective. Using the SEER-Medicaid database, we retrospectively examined outcomes in patients with melanoma and lung adenocarcinoma brain metastasis who received checkpoint blockade therapy alone vs those concurrently on beta-blocker therapy. We found that patients receiving combination therapy showed increased overall survival compared to those receiving checkpoint blockade alone. We then validated these findings in preclinical models of both glioma and melanoma brain metastases, demonstrating that combining immunotherapy and propranolol, a widely-prescribed FDA-approved beta-blocker, extended survival. Moving forward, we suggest that combination therapy with propranolol and immunotherapy, particularly checkpoint blockade, represents a promising translational treatment platform for patients with primary or metastatic intracranial malignancies.
SYST-08 ROLE OF THE MICROBIOME IN BRAIN TUMORS
Authors: Omer Mohammed
Published: August 2023

A cross-sectional study was conducted to investigate the potential role of the microbiome in brain tumors. The study included 50 patients with histologically confirmed brain tumors and 50 healthy controls matched for age and gender. Fecal samples were collected from all participants and analyzed for bacterial composition using 16S rRNA gene sequencing. The results showed significant differences in the composition of the microbiome between the brain tumor patients and healthy controls. Specifically, patients with brain tumors had a higher abundance of certain bacterial species, including Fusobacterium and Porphyromonas, compared to the healthy controls. These bacterial species have previously been associated with inflammation and have been implicated in the development and progression of various types of cancer. Furthermore, the study investigated the potential interaction between the microbiome and the immune system in the context of brain tumors. Analysis of immune cell subsets in peripheral blood samples revealed differences between the brain tumor patients and healthy controls, with the tumor patients showing a lower proportion of CD8+ T cells and a higher proportion of regulatory T cells. Interestingly, there was also a correlation between the abundance of certain bacterial species and the proportion of immune cells, suggesting a potential role for the microbiome in modulating immune function in brain tumors. These findings suggest that the microbiome may play a role in the development and progression of brain tumors. Further studies are needed to investigate the mechanisms underlying this association and to determine whether interventions targeting the microbiome could have therapeutic benefit in brain tumors.
SYST-10 ENHANCING THE EFFICACY OF RADIATION THERAPY BY SURGICALLY TARGETED RADIATION-SENSITIZER LOADED FIBRIN GLUE
Authors: Nguyen Jane , Chandekar. Akhil , Hirschberg Henry
Published: August 2023

Radiation therapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic, relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiation sensitizers (RS) can potentially increase efficacy on tumor cells while maintaining normal tissue toxicity. Clinical trials, employing radiation sensitizers have been done, but so far, the results have been disappointing. An important factor that could account for the low efficacy of RS in clinical trials is the blood–brain barrier (BBB). The basis for this work was the development of a RS direct delivery system (DDS), that bypasses the BBB. This is implemented by the local implantation, into the tumor resection cavity, of RS loaded slow-release fibrin glue. Localized delivery significantly increases the concentration of RS reaching the remaining infiltrative tumor cells in the brain parenchyma, while avoiding systemic side effects. Additionally, the BBB would prevent retrograde flow of the RS into the circulatory system. and the RS is protected from degradation and clearance until locally released. FG has several characteristics that make it well suited for this form of agent delivery. It has been used clinically in surgery for decades, is FDA approved, its lack of toxicity has been clearly proven, it gels rapidly and spontaneously and is easily applied. Radiation protocols utilizing two sensitizers, 5FU and Motexafin-GD, have been optimized in vitro using 3D glioma spheroid models. The results obtained in vitro have been extended to an appropriate in vivo rat brain tumor model. The goal of this project is to improve the therapeutic index of radiation therapy and is therefore clearly aimed at eventually translating to new clinical treatment protocols.
SYST-16 ANXA5 PROMOTES GLIOMA PROGRESSION THROUGH THE FAK/PI3K/AKT PATHWAY
Authors: Zhang Xinyuan , Zhou Huandi , Han Wei , Zhang Dongdong , Han Xuetao , Hou Liubing , Li Haonan , Sun Guozhu , Xue Xiaoying
Published: August 2023

Annexin A5 (ANXA5) is a member of the calcium dependent phospholipid binding protein family and participates in the regulation of a variety of physiological and pathological processes. However, whether and how ANXA5 affects the growth and progression of glioma remains unclear.We analyzed the expression of ANXA5 in multiple public databases, and verified the expression in 50 glioma clinical samples with Western blotting to study the correlation between ANXA5 and prognosis, survival, and clinical characteristics. In vitro experiments, we up-regulated and down-regulated the expression of ANXA5 in glioma cells, then treated glioma cells with up regulated ANXA5 expression with Y397 FAK specific phosphorylation inhibitor Y15, and verified the effect of ANXA5 on proliferation, migration and invasion of glioma cells through CCK8, clone formation, EDU, migration and invasion assays, scratching,and Western blotting proved that the expression level of ANXA5 affected the protein level of upstream and downstream factors of FAk/PI3K/AK pathway. ANXA5 is highly expressed in glioma and is related to clinical features such as grade, age and molecular typing. The higher the expression of ANXA5, the worse the prognosis. The increased expression of ANXA5 can promote the proliferation, migration and invasion of glioma cells, activate FAk/PI3K/AK pathway, and Y15 can reverse the promotion of ANXA5 overexpression; when ANXA5 is knocked down, the result is opposite. ANXA5 is highly expressed in glioma and is an independent prognostic factor of glioma patients. ANXA5 can promote the proliferation, migration and invasion of glioma cells through FAk/PI3K/AK pathway, and this promotion can be reversed by Y15.
SYST-17 GOLD NANOSTARS ENHANCE THE EFFICACY AND SAFETY OF LASER INTERSTITIAL THERAPY FOR THE TREATMENT OF INTRACRANIAL TUMORS
Authors: Wachsmuth Lucas , Chongsathidkiet Pakawat , Liu Yang , Odion Ren , Srinivasan Ethan , Mendoza Aden , Edwards Ryan , Canning Aidan , Willoughby Gavin , Hinton Joseph , Norton Stephen , Fecci Tuan Vo-Dinh Peter
Published: August 2023

Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser for ablation. Magnetic resonance thermal imaging is used to monitor ablation progress by measuring the cumulative heat energy exposure in both the tumor and the surrounding tissue to calculate thermal damage thresholds.Previous applications of GNS in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, GNS-infused phantoms demonstrate more rapid heating, expanded ablation zones, and improved margin conformation, with surrounding areas exposed to lower temperatures than controls. In in vivo intracranial tumor models, we show that GNS selectively accumulate and are retained in CT2A glioma and B16F0 melanoma tumors at 24 and 72 hours post-injection. Using our in vivo heterotopic CT2A model, we demonstrate that systemically-delivered GNS dramatically augment laser ablation, with higher temperatures achieved in the tumor and more efficient temperature ramping. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving the efficiency and safety of this platform.
SYST-20 TARGETED THERAPY MATCHED TO GENOMIC ALTERATIONS (BRAFV600E, NTRK, FGFR, ROS1, PIK3CA, PTEN) IN PATIENTS WITH RECURRENT IDH WILDTYPE GLIOBLASTOMA: A REAL-LIFE COHORT ANALYSIS FROM VENETO INSTITUTE OF ONCOLOGY, PADUA (ITALY)
Authors: Padovan Marta , De Toni Chiara , Maccari Marta , Bosio Alberto , Cerretti Giulia , Caccese Mario , Corrà Martina , Vizzaccaro Salvatore , Cestonaro Ilaria , Pittaro Alice , Guerriero Angela , Coppola Marina , Lombardi Giuseppe
Published: August 2023

We retrospectively analyzed 34 patients (pts) [19 males, 15 females, median age 54] with recurrent IDH wildtype glioblastoma treated with target therapy (TT) based on their next-generation sequencing (NGS) profile, between March2020 and December2022 at Veneto Institute of Oncology, Padua (Italy). ECOG PS was 0-1 in 29 pts. All pts received previous radiotherapy and temozolomide. NGS was obtained with FoundationOne®CDx on formalin-fixed paraffin-embedded samples. We identified 6 druggable genomic alterations, classified according to ESCAT (ESMO Scale for Clinical Actionability of molecular Targets): BRAFV600E mutation (IB), NTRK1-2-3 fusions (IC), FGFR1-2-3 alterations (IIB), ROS1 fusions (IIIA), PIK3CA mutations (IIIA) and PTEN loss/mutations (IIIA). The median line of therapy with TT was 3 (range 2-7). TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts). At data cut-off (March2023), 19 patients had died. In the entire cohort, median overall survival and progression-free survival (PFS) after starting TT was 8.72 and 2.14 months, respectively. The dabrafenib/trametinib subgroup had the longest median PFS (5.23 months), a disease control rate (DCR) of 77%, an objective response rate of 22%, and a median duration of response of 22.5 months. 7/9 pt had died and 2 pts are continuing dabrafenib/trametinib. The pt with ROS1-GOCP fusion maintained a complete response for 12 months with entrectinib. Among the others, no complete/partial responses were detected. DCR due to stable disease was 50% in larotrectinib and erdafitinib subgroups and 8.3% in ipatasertib+/-atezolizumab subgroup. No toxicities were reported in dabrafenib/trametinib subgroup. Among all patients, no grade 4 drug-related adverse events were observed and in any case TT was interrupted for toxicity. Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest further explorations in targeting ROS1 and FGFR.