bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMAP-12 TUMOR TREATING FIELDS (TTFIELDS) REAL-WORLD EXPERIENCE IN NEWLY DIAGNOSED GLIOBLASTOMA: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS OF OVERALL SURVIVAL
Authors: Ballo Matthew T , Conlon Patrick , Lavy-Shahaf Gitit , Kinzel Adrian , Vymazal Josef , Rulseh Aaron M 
Published: August 2023

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression by a multi-modal mechanism of action. TTFields therapy is FDA-approved for newly diagnosed glioblastoma (ndGBM) based on results from the randomized, phase 3 EF-14 study (NCT00916409). We assessed the overall survival (OS) benefit of adding TTFields therapy to standard of care (SOC) in ndGBM, as well as the relationship between OS and time using the device.

METHODS
A systematic literature review (PubMed, Embase, and Cochrane Library) identified single-cohort and comparative clinical studies that assessed survival in patients with ndGBM who received TTFields therapy. Inter-study heterogeneity was quantified using the Higgins I2 statistic and Cochran Q test. A distribution-free random-effects method was used to pool survival curves.

RESULTS
Nine studies were identified that evaluated survival with TTFields therapy in ndGBM. Of these, 7 studies (1430 patients) that compared TTFields therapy with SOC to SOC alone, were included in the pooled analysis for OS. The pooled data showed significantly longer OS with TTFields therapy/SOC versus SOC alone (HR: 0.63; 95% CI, 0.53-0.75; P&lt;0.001). A sensitivity analysis indicated that the effect was robust and independent of any individual study. In post-approval studies, pooled median OS was 22.2 months (95% CI, 17.3-42.6) for TTFields therapy/SOC and 17.3 months (95% CI, 13.6-22.0) for SOC alone. Gross total resection was generally more prevalent in the real-world setting, irrespective of TTFields therapy use. Average recommended device usage of ≥75% was associated with prolonged OS vs &lt;75% usage in 6 studies (pooled HR: 0.60; 95% CI, 0.48-0.73; P&lt;0.001).

CONCLUSIONS
Pooled analysis of comparative TTFields therapy studies suggests a significant survival benefit with TTFields added to SOC for patients with ndGBM, and that a recommended 75% usage rate may be clinically meaningful in the real-world setting.
LMAP-18 ADAPTING LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR TREATMENT OF INTRACRANIAL LESIONS IN CANINES
Authors: Mariani Chris , Wachsmuth Lucas , Ruterbories Laura , Tsvankin Vadim , Bramall Alexa , Tyc Richard , Fecci Peter 
Published: August 2023

Abstract
Malignant gliomas are devastating intracranial tumors with dismal prognoses that impose unique therapeutic challenges. Treatment options include surgical resection, radiation, and chemotherapy, but efficacy is limited and carries associated morbidity. Promise persists for newer modalities, such as immune-based platforms, but the blood-brain barrier (BBB) restricts intracranial therapeutic access, limiting success. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical intervention permitting thermal ablation of brain tumors and other intracranial lesions. During LITT, a laser probe is stereotactically introduced through a small skull burr hole into the lesion. Continuous MRI is used to conduct real-time temperature monitoring via software-based calculation of cumulative thermal dosage zones. LITT is not only capable of ablating neoplastic tissue, but can also open the BBB in peritumoral regions, and thus may synergize with other emerging therapies. We adapted a commercially available LITT system (Monteris Medical) for use in dogs with intracranial lesions. Canine cadavers were used to optimize LITT procedures before employing this platform in live dogs. Our approach consists of 1. obtaining volumetric, T1-weighted, MRI studies to plan trajectories to intracranial targets, 2. fixing canine patients to a surgical bed and registering them for surface matching to a volume rendered image, 3. using an integrated instrument holder (Varioguide, Brainlab) to guide drilling of 4.5 mm skull burr holes for placement of self-tapping titanium “mini-bolts” (Monteris Medical), and 4. introducing the laser catheter probe through the mini-bolts for lesion ablation in the MRI suite. This method allows for rigid stereotaxy, successful neuronavigation, and a minimally invasive approach. We have successfully performed LITT on four canine patients with spontaneously occurring intracranial gliomas and plan to treat additional canine patients with intracranial lesions. Future studies will explore combination therapeutic platforms, including immunotherapy and gold nanoparticles to improve the efficiency and specificity of tumor ablation.
NEIM-13 THE PROGNOSTIC ROLE OF VENTRICULAR SIZE AND ITS DYNAMICS IN PATIENTS WITH LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS
Authors: Le Rhun Emilie , Devos Patrick , Seystahl Katharina , Jongen Joost , Gramatzki Dorothee , Roth Patrick , van den Bent Martin , Brandsma Dieta , Weller Michael 
Published: August 2023

Abstract

BACKGROUND
Hydrocephalus is a common radiological sign in patients with leptomeningeal metastasis (LM) from solid tumors and can be assessed using the Evans index (EI) with high interrater agreement. Here we explored the prognostic value of ventricular size at diagnosis and during the disease course of LM.

METHODS
We assembled a cohort of 113 adult patients with a diagnosis of LM from solid extra-CNS tumors and explored the association of ventricular size assessed by the EI at diagnosis, of its modification between diagnosis and evaluation at first follow-up and at first progression, with outcome.

RESULTS
Median age was 58.2 years (interquartile range (IQR) 46.1-65.7), 41 patients (36%) were male, the most frequent cancers were lung cancer (n=39, 35%), breast cancer (n=36, 32%) andmelanoma (n=23, 20%). The median EI at baseline was 0.28 (IQR 0.26-0.31), the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median overall survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI of 0.26 or less had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, versus 1.3 months, IQR 0.6-4.1) (p=0.006). Among patients with follow-up scans available, median overall survival was 9.7 months (IQR 5.6-21.4) for patients with stable or decreased EI at first follow-up as opposed to 6.4 months (IQR 3.2-10.5) for those with an increase in the EI (p=0.292).

CONCLUSION
The EI at baseline is prognostic in LM. An increase of EI during the follow-up is associated with inferior LM-PFS. An independent validation cohort with larger sample size and evaluation of confounding factors will help to better define the role of EI assessments in LM.
SDPS-06 A 4 YEAR-OLD GIRL WITH EMBRYONAL RHABDOMYOSARCOMA IN RETROAURICULAR AND MIDDLE EAR : A RARE CASE REPORT FROM INDONESIA
Authors: Anugrah Diko , Rahmartani Ludy Dhyani 
Published: August 2023

Abstract
Rhabdomyosarcoma is the most common sarcoma of childhood, and this tumor is the third most common neoplasm after neuroblastoma and nephroblastoma. Rhabdomyosarcomas may originate in any anatomical site, occurring predominantly in head and neck regions, orbits, skull base, nasal cavity, and nasopharynx, where there is little or no musculoskeletal tissue. The involvement of the ear and mastoid bone in rhabdomyosarcoma is uncommon. The embryonal rhabdomyosarcoma includes about 60– 70% of rhabdomyosarcoma cases. A four years-old girl presented with pain in neck and difficult to moving, there was a mass in the left auricular that was getting bigger. 4 days prior to admission, there was a drooping mouth to the left, the voice sounds hoarse, but there was no weakness in the side and no loss of consciousness. On physical examination, there was a N.VII palsy, without hyperreflexia, paraplegia, and nystagmus. High resolution Mastoid CT-Scan showed a characteristic malignant solid mass involving the external acoustic canal and the left tympanic and mastoid cavities, destroying the auditory and temporal bones, involving the left internal acoustic canal, and reaching the left nasopharynx, extending into the intracranial region of the left cerebellopontine angle and left temporal duramater. In Pathology examination showed Tumor cells are spherical, spindle-shaped with pleomorphic nuclei, hyperchromatic, coarse chromatin, vesicular, some with real nuclear daughters, eosinophilic cytoplasm. Mitosis is discovered. eccentricallynucleated cells with eosinophilic cytoplasm, suggesting rhabdomyoblast differentiation, some with a "tadpole" appearance, and conclusion according to embryonal rhabdomyosarcoma. The patient is treated with chemotherapy using Vincristine, Actinomycin-D, and Ifosfamide.
SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS
Authors: Yu Nina , Lee Han Sung , Raslan Osama , Jin Lee-Way , Aboud Orwa 
Published: August 2023

Abstract
Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.
SDPS-16 CYTOLOGIC AND SEROLOGIC RESPONSE WITH INTRATHECAL METHOTREXATE IN A PATIENT WITH LEPTOMENINGEAL CARCINOMATOSIS FROM OVARIAN CANCER
Authors: Cordova Christine , Abdallah Kawther , Daniela Chiciuc , Tsay Jawad 
Published: August 2023

Abstract
Leptomeningeal Carcinomatosis (LMC) is a rare complication of ovarian cancer and there is no established first-line therapy. Treatment of LMC in general can include intrathecal chemotherapy and radiation as well as relevant systemic therapies with CNS activity. We employed the commercially available Biocept CNSide™ assay to detect, quantify, and molecularly characterize tumor cells in the cerebrospinal fluid (CSF). We report a 66-year-old female who was initially diagnosed with stage 3C serous ovarian carcinoma who developed brain metastases one year later, managed with resection and stereotactic radiosurgery. Serum CA-125 continued to rise despite local therapy and subsequent MRI demonstrated leptomeningeal enhancement of bilateral internal auditory canals and the cauda equine concerning for LMC. Exam was notable for a left cranial nerve VII palsy and gait instability. Lumbar puncture with CNSide quantified a baseline tumor cell count and identified HER2 amplification on tumor cells. She began intrathecal methotrexate (IT MTX), followed by decline in both CSF tumor cell count and serum CA-125. She demonstrated clinical benefit with improved imbalance. Over time, she experienced nausea and vomiting with IT MTX and was switched to anti-HER2 therapy with off-label lapatinib and she enjoyed improved quality of life. Notably, tumor cells lost HER2 amplification, raising possibility of clone selection. She later experienced focal progression of LMC and before other therapy could be offered, she succumbed to illness approximately one year from the initial radiographic finding of leptomeningeal enhancement, exceeding the average survival for LMC.Here we demonstrate the activity of IT MTX in ovarian LMC as well as the utility of serial CSF tumor quantification for disease monitoring in conjunction with imaging and the physical exam. Further studies are warranted to evaluate LMC therapy in a prospective setting as well as the possibility of clone selection in the CNS with targeted therapy.
SDPS-29 SERUM-DERIVED CD47 AS A MARKER OF TUMOR BURDENAND OUTCOME IN GBM PATIENTS – CORRELATIVE ANALYSISOF TUMOR LOCATION, RADIATION THERAPY VOLUMES,AND SURVIVAL
Authors: Jagasia Sarisha , Krauze Andra , Zhao Yingdong , Li Ming-Chung , Tasci Erdal , Zgela Theresa Cooley , Sproull Mary , Mackey Megan , Tofilon Philip , Camphausen Kevin 
Published: August 2023

Abstract
Glioblastomas (GBM) are the most aggressive central nervous system tumors exhibiting near universal recurrence following resection and chemoradiation (CRT). CD47 is an integrin-associated transmembrane protein associated with immunomodulation, invasion, and stemness that is highly expressed in GBM. We tested the hypothesis patient serum-derived CD47 measured pre vs. post-CRT may be related to tumor burden by exploring its association with tumor dissemination in the brain, RT volumes, and outcomes. CD47 was analyzed using an aptamer-based SOMAscan proteomic assay on serum collected pre and post CRT for 82 individuals with a pathologic diagnosis of GBM. Clinical features (tumor location (cortical/periventricular), gross tumor volumes (GTVT1, GTVT2), and outcome (overall survival (OS), progression-free survival (PFS)) were analyzed in conjunction with alteration in CD47 levels. Alteration in CD47 level was associated with OS (HR = 32.34 CI: 3.520 - 288.3, p = 0.0004053) and PFS (HR =8.5, p = .0008 CI: 0.2291-4.011). Expression of CD47 increased after CRT (p = .022). Patients with periventricular tumors had higher expression of CD47 pre vs. post CRT (p = 0.0188) and worse OS (median 13 vs. 25 months) and PFS (median 5 vs. 10 months) as compared to patients with strictly cortical tumor presence. A positive correlation was identified between GTVT1 and GTVT2 and CD47 expression levels (p = .0006). Lower CD47 expression values were associated with higher survival probability (p = .013). The stratification of CD47 expression levels yielded increasingly significant results with the separation of discrete survival groups (p = .00013), indicating clinically distinct subtypes of GBM. Tumor location (cortical vs. periventricular) and GTVT1 correlated with OS and PFS (p&lt;0.05), unlike GTVT2 in this cohort in the absence of CD47 expression level. CD47 expression levels correlate with tumor location, RT volumes, OS, and PFS with distinct GBM subtypes potentially stratified via serum CD47 expression levels.
SDPS-35 TUMOR-RELATED EPILEPSY IN HIGH-GRADE GLIOMA: A LARGE SERIES SURVIVAL ANALYSIS
Authors: Rilinger Ryan , Guo Lydia , Sharma Akshay , Grabowski Matthew , Lobbous Mina 
Published: August 2023

Abstract

BACKGROUND
Seizures are a common clinical occurrence throughout the disease course in glioblastoma (GBM). While many studies have explored the impact of surgical and medical treatment for GBM on seizure incidence and prevalence, limited study has been directed towards the prognostic effect of seizures occurring in the post-treatment setting.

METHODS
We retrospectively reviewed 238 patients with histologically-confirmed high grade glioma treated at our institution between 2018 and 2021. Seizure presentation was classified as early onset (occurring at the time of GBM presentation), or late onset (first seizure occurring after beginning standard surgical and medical treatment). Using a multivariate Cox proportional-hazards model, hazard ratios were assessed for timing of seizure presentation, as well as other clinical and tumor-associated variables.

RESULTS
Incidence of first seizure after the onset of treatment was found to be associated with improved overall survival (HR=0.66, p=0.03), while increasing age (HR 1.02, p=0.007) and deep/midline tumor location (HR 1.86, p=0.003) were associated with decreased overall survival.

CONCLUSION
While seizure at presentation may be associated with better survival in high-grade glioma, more analysis is underway to confirm the finding in a larger cohort and to evaluate the impact of molecular alterations in seizure incidence and management. Further study in this patient cohort utilizing detailed next-generation sequencing will evaluate the association of the patient-specific tumor profile on seizures and overall survival.
SDPS-38 A BRAIN METASTASES PREDICTION MODEL IN BREASTCANCER WOMEN
Authors: Cacho-Díaz Bernardo , Reynoso-Noveron Nancy 
Published: August 2023

Abstract

BACKGROUND
Breast cancer (BC) is a leading cause of mortality and the most frequent malignancy in women; most deaths are due to metastatic disease, expressly brain metastases (BM). Currently, there is no biomarker or a prediction model to accurately predict BM.

OBJECTIVE
To generate a BM prediction model from variables acquired at BC diagnosis.

METHODS
A retrospective cohort of BC women diagnosed from 2009 to 2020 at a single center was divided into training (TD) and validation datasets (VD). The TD was used to generate a multivariable prediction model. The modeĹs performance was measured applying the area under the curve (AUC), C-statistic, and the Akaike information criteria (AIC).

RESULTS
5,009 patients were divided into a TD (n 3339) and a VD (n 1670). In the TD, the model with the best performance (lowest AIC) was built with the following variables: Age, estrogen receptor status, tumor size, axillar adenopathy, AJCC anatomic clinical stage, Ki-67, and the Scarf-Bloom-Richardson score. This model had an AIC of 1241 and an AUC of 0.793 (95%CI 0.761 – 0.825) p &lt;0.0001 in the TD. A 10-fold cross-validation showed good stability of the model. In the VD, the model had an AUC = 0.812 (IC95% 0.774 – 0.850) P &lt; 0.0001 and an AIC = 644. Finally, we present with an online APP and an online calculator for its clinical use.

CONCLUSION
In a retrospective cohort of women with breast cancer, a prediction model built with clinical and pathological variables at diagnosis displayed a robust performance to measure the individual odds of BM. The model is currently considered for external validation in other institutions and countries.
SDPS-40 MEDULLOBLASTOMA MOLECULAR SUBTYPE PREDICTION USING PATHOMIC FEATURE ANALYSIS
Authors: Mahtabfar Aria , Familiar Ariana , Kazerooni Anahita Fathi , Kiani Mahsa , Khanna Omaditya , Viswanathan Karthik , Resnick Adam , Storm Phillip , Viaene Angela , Nabavizadeh Ali 
Published: August 2023

Abstract
The clinical course of pediatric medulloblastoma patients exhibits wide variability based on molecular subtype. The ability to predict medulloblastoma molecular subtypes (Group 3/4, WNT, SHH) based on histopathologic features alone has immense utility by providing clinicians insight into the molecular and biological underpinnings of the tumor. Although the use of computational pathology (“pathomics”) is expanding in multiple disciplines, its application in pediatric neuro-oncology has been limited. Our preliminary analysis highlights the potential for application in medulloblastoma and pediatric brain tumor research. Using the Children’s Brain Tumor Network database, pediatric patients with available clinical data, whole-slide images (WSI) and molecular subtyping were evaluated for inclusion. Regions-of-interest (ROI) on each H&E-stained WSI were selected for pathomic analysis, and features were extracted using a digital pathology software package (Qupath). 25 pathomic features capturing cellular and nuclear-level intensity and morphology properties were included. Subsequently, a histogram gradient boosting classifier was used to perform binary classification of Group 3/4 vs. SHH/WNT with leave-one-subject-out cross validation. A total of 68 subjects, with median age at diagnosis of 8.19 years (range 0.29-18.69), and median overall survival (OS) of 56 months (range 0.76-258.37) were identified. Our cohort included 44 and 24 subjects in Group 3/4 and SHH/WNT, respectively. Pathomic features classified subjects into Group 3/4 or SHH/WNT with a classification accuracy of 71% (SEM=0.06). A t-test against stratified chance accuracy (57%) showed significantly above-chance testing performance (p=.019). Inspection of the confusion matrix indicated better discrimination of Group 3/4 compared to SHH/WNT subjects, likely due to the larger number of these subjects in the dataset. Our preliminary analysis shows acceptable testing accuracy in distinguishing Group 3/4 from SHH/WNT medulloblastoma, and highlights the possibility of gaining molecular insight purely from histopathologic images. The potential of pathomic features should be considered an untapped resource.
SDPS-42 METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN EDEMA: A TOPOGRAPHICAL AND CLINICOPATHOLOGIC INVESTIGATION
Authors: Yun Jonathan , Kurker Kristina , Maragkos Georgios , Sutherland Grant , Farzad Faraz , Sukumar Rohit , Feng Xue , Yener Ulas , Patel Sohil , Schiff David , Lopes Beatriz , Askun Melike Mut 
Published: August 2023

Abstract
Tumor-associated vasogenic brain edema is a well-known contributor of morbidity and mortality in patients with metastatic disease to the brain. It is widely accepted that metastatic disease to the brain is associated with extensive edema and can cause increased symptomatology such as pain, neurologic deficit, and elevated intracranial pressure depending on extent and location. We present a retrospective artificial intelligence (AI) mediated analysis of radiological and clinicopathologic data including specific molecular markers, presenting symptoms, and tumor location of 86 patients with non-small cell carcinoma of the lung (NSCLC) and brain metastases who underwent surgical resection and were not previously on steroids. We found that overall, tumors in all locations demonstrated a mean 10:1 edema to tumor ratio (ETR) and an occipital tumor location was associated with a significantly elevated ETR. Within our cohort there were no other factors that were significantly associated with ETR. This study demonstrates a proof of concept that NSCLC is associated with significant peritumoral edema and that topographical factors may be associated with increased extent of edema.