bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMRK-08 TRENDS IN BREAST CANCER BRAIN METASTASES INCIDENCE AND MORTALITY: DISPARITIES BY MOLECULAR SUBTYPES, AGE, AND RACE
Authors: Thierheimer Marisa , Armashi Abdul Rahman Al , Martin James M 
Published: August 2024

Abstract
Brain metastases represent a critical complication of breast cancer, with a significant impact on patient prognosis. Understanding the variations in incidence and mortality across molecular subtypes, races, and age groups is crucial to enhance risk stratification and guide resource allocation. Identifying these trends can inform treatment and prognostication efforts. Utilizing the Surveillance, Epidemiology, and End Results 17 database, this study examined trends in synchronous breast cancer brain metastasis (BCBM) incidence and mortality from 2010-2020. The National Cancer Institute’s Joinpoint Regression Program was employed to estimate annual percent changes (APCs). Results were considered significant if the 95% confidence interval excluded zero, and trends were identified using JoinPoint software to delineate variations across demographic and molecular distinctions. There was a significant overall increase in BCBM incidence (APC=2.3%) between 2010-2020. Analysis by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status revealed incidence increases across all four subtypes, with Non-White patients experiencing a significant decrease in BCBM incidence in HR-/HER2+ tumors (APC=-7.7%). After accounting for observation-time bias, mortality rates demonstrated statistically significant upward trends overall (APC=4.0%) and across several biomarker groups, particularly HR+/HER2+ (APC=7.3%), HR-/HER2+ (APC=5.6%), and HR+/HER2- (APC=4.4%). While the increase in HR-/HER2- was more modest (APC=2.7%), it contributes to the evolving landscape of BCBM mortality. Disparities in mortality rates were also pronounced among age and racial groups within these individual subtypes. Representing the largest population-based study to evaluate trends in BCBM incidence and mortality, our analysis uncovers varying patterns across molecular subtypes, age, and race. These disparities suggest underlying biological differences and inherent healthcare barriers, highlighting the urgent need for targeted interventions in at-risk populations. Our findings lay crucial groundwork for further research into these disparities and tailored clinical and policy measures to improve BCBM outcomes.
BMRK-09 PROGNOSTIC ROLE OF TUMOR-INFILTRATING LYMPHOCYTES AND TERTIARY LYMPHOID STRUCTURES IN BRAIN METASTASIS
Authors: Mughal Sadaf Shabbir , Reiss Yvonne , Felsberg Jörg , Meyer Lasse , Macas Jadranka , Schlue Silja , Starzetz Tatjana , Köhrer Karl , Fehm Tanja , Müller Volkmar , Lamszus Katrin , Helfrich Iris , Wikman Harriet , Berghoff Anna , Brors Benedikt , Plate Karlheinz , Reifenberger Guido 
Published: August 2024

Abstract
Brain metastases (BrMs) constitute the most common type of brain cancer with abysmal prognosis. Given the high incidence and poor prognosis of BrM, understanding the tumor microenvironment (TME) architecture across BrM subtypes is increasingly crucial, especially with the emergence of novel immunotherapeutic agents like immune checkpoint inhibitors, which have demonstrated efficacy in melanoma and lung cancer BrM. Tertiary lymphoid structures (TLS) are spatially organized lymphoid aggregates in the TME that mediate antitumor immunity. Despite being established as prognostic and predictive markers in various cancers, their significance in BrM lacks extensive investigation. We performed gene expression profiling using paired-end RNA sequencing and multiplex immunofluorescence combined with spatial imaging on 149 human BrM samples. Cell type deconvolution analysis revealed that BrMs from non-small cell lung carcinoma (NSCLC) and malignant melanoma exhibited significantly higher immune cell infiltration compared to BrMs from breast carcinoma. Furthermore, B cell infiltration was detected in some patients, suggesting potential TLS formation. We created a metagene signature comprising TLS hallmarks in BrMs using transcriptomic profiling, allowing us to categorize BrM patients into TLS-positive and TLS-negative groups. This finding was corroborated by multiplex immunofluorescence staining of corresponding BrM tissue sections, which confirmed TLS-like aggregate formation in 40% of the BrM patients. Differential gene expression analysis highlighted the presence of activated lymphocyte-mediated immunity as well as increased immunoglobulin production signature in TLS-positive tumors. Additionally, a higher TLS signature score was associated with improved overall survival of lung carcinoma patients after BrM diagnosis. Our results underscore the heterogeneity of the tumor microenvironment in BrM, and the identification of intratumoral TLS may guide patient stratification for therapeutic interventions.
BMRK-12 THE CNSIDE CSF TUMOR CELL DETECTION PLATFORM IS A FEASIBLE, CLINICALLY RELEVANT AND SCALABLE PLATFORM FOR DISEASE MANAGEMENT FOR PATIENTS WITH LEPTOMENINGEAL DISEASE
Authors: Tripathy Arushi , Corkos Perry , Blouw Barbara , Moore Melissa , LaFrance Norman , Hedrick Marc , Kumthekar Priya 
Published: August 2024

Abstract
CNSide is a platform that analyzes Cerebrospinal Fluid (CSF) of patients with solid tumors having Leptomeningeal Disease for presence of tumor cells (CSF-TCs) and expression of different biomarkers via Fluorescent In Situ Hybridization (FISH), Next-Generation Sequencing (NGS) and Immunocytochemistry (ICC). CNSide was offered as a commercial test in a CAP accredited CLIA certified Laboratory and ordered at each physician’s discretion. Retrospective analysis of test results between January 2020 and October 2022 showed that the test was ordered by 19 physicians from 5 unique health systems totaling 613 tests on 218 individual patients. Of these, 162 (74.3%) were female; ages ranged from 19-99 years with a median age of 58. A range of cancer pathologies were sent for CNSide analysis, of which breast (n=105) and lung (n=65) were most common. CSF-TCs were detected in 67% (412/613) samples of which 66% (195/294) were from breast cancer patients and 76% (175/229) from lung cancer patients. In lung cancer patients, ALK was detected in 14% (17/118) and CMET in 61% (78/128). In breast cancer patients, HER2 was detected in 39% (65/168) patients, ER in 26% (44/168) and PR in 4% (5/120). Furthermore, 73% (16/22) lung cancer patients had HER positive CSF. Tumor cell detection with CNSide was more frequently seen than positive cytology and provided a more reliable quantitative measure of CNS malignant disease. This data shows that CNSide is viable from a feasibility perspective across many different tumor types. Furthermore, it is scalable and detects clinically relevant biomarkers. Analysis of the prospective FORESEE clinical trial to determine the impact of CNSide on clinical decisions is ongoing.
IMUN-03 IT-IO: INTRATHECAL ADMINISTRATION OF NIVOLUMAB AND IPILIMUMAB IN COMBINATION WITH SYSTEMIC COMBINATION OF NIVOLUMAB AND IPILIMUMAB IN PATIENTS WITH NSCLC OR MELANOMA AND NEWLY DIAGNOSED LEPTOMENINGEAL METASTASIS, A MULTICENTRIC PHASE I STUDY - PRELIMINARY DATA
Authors: Le Rhun Emilie , Dummer Reinhard , Gramatzki Dorothee , Kraehenbuehl Lukas , Britschgi Christian , Wicki Andreas , Migliorini Denis , Weindler Susanne , Weiss Tobias , Dafni Urania , Weller Michael 
Published: August 2024

Abstract
The EANO ESMO guidelines recommend the use of intrathecal pharmacotherapy in patients with leptomeningeal metastases with circulating tumor cells in the cerebrospinal fluid or linear leptomeningeal disease on MRI. Phase I studies have established that doses of intrathecal nivolumab of up to 50 mg Q2W combined with systemic nivolumab (240 mg Q2W) are safe (NCT03025256). The superiority of the combination of systemic nivolumab and ipilimumab over nivolumab alone or chemotherapy has been shown in patients with advanced NSCLC or melanoma. The objective of IT-IO is to determine the feasibility of intrathecal double immune checkpoint inhibition for patients with newly diagnosed LM from NSCLC or melanoma. IT-IO (NCT05598853) is a prospective phase I, multicentre, open label, interventional clinical study aiming at determining the recommended phase 2 dose (RP2D) of intrathecal nivolumab and ipilimumab. The diagnosis of LM must be confirmed or probable by EANO ESMO criteria, steroid dose must be stable or decreasing and &lt;4 mg dexamethasone equivalent per day in the last 7 days. Co-existing oligosymptomatic brain metastases are allowed if &lt;2 cm diameter or if planned to be treated by stereotactic radiosurgery. Planned whole brain radiotherapy and planned or prior craniospinal irradiation are not allowed. The treatment regimen within the IT-IO study consists of intrathecal administration of nivolumab/ipilimumab in combination with systemic nivolumab/ipilimumab. Patients are treated with a fixed dose of IT nivolumab (50 mg) and increasing doses of IT ipilimumab. Three dose levels of IT ipilimumab are planned: 5 mg at dose level 1, 10 mg at dose level 2 and 20 mg at dose level 3. The RP2D is determined in a 3 + 3 design. Secondary endpoints will explore compartmental efficacy and survival. The dose escalation phase has been completed without dose limiting toxicity. Enrolment in the expansion phase has started in January 2024
IMUN-05 PHASE II STUDY OF NIVOLUMAB (NIVO) IN COMBINATION WITH RELATLIMAB (RELA) IN PATIENTS WITH ACTIVE MELANOMA BRAIN METASTASES (MBM)
Authors: Phillips Suzanne , Burton Elizabeth , Oliva Isabella Claudia Glitza , McQuade Jennifer , Amaria Rodabe , Diab Adi , Wong Michael , Chung Caroline , Milton Denái , Malke Jared , Simon Julie , Wefel Jeffrey , Li Jing , Davies Michael , Tawbi Hussein 
Published: August 2024

Abstract

BACKGROUND
More than half of patients diagnosed with metastatic melanoma (MM) will develop brain metastases. Despite this prevalence, these patients are excluded from most clinical trials. The CheckMate 204 study combining ipilimumab (3mg/kg) plus nivo (1mg/kg) for patients with asymptomatic MBM revealed an intracranial (IC) response in 54% of patients. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 55% of patients. RELATIVITY-047, a global phase II/III randomized study, reported on the fixed-dose combination of nivo/rela (480 mg/160 mg) compared to nivo (480 mg) alone for patients with advanced unresectable and untreated melanoma. This combination demonstrated significantly improved PFS compared to anti-PD-1 monotherapy. Grade 3/4 TRAEs occurred in 21% of patients in the combination group compared to 11% in the monotherapy group with no new safety signals. The nivo/rela combination has FDA approval for the treatment of patients with MM but has not been studied in patients with MBM.

METHODS
This single arm, single center phase II trial evaluates the safety and efficacy of nivo/rela in patients with MBM. 30 MBM patients who are asymptomatic and treatment naïve to anti-PD-1 therapy will be enrolled. Patients are treated with nivo/rela (480 mg/160 mg) every 4 weeks for up to 25 cycles, disease progression, or unacceptable toxicity. The primary objective is to evaluate IC response (CR + PR) by MRI per modified RECIST 1.1 criteria. Monitoring for futility will be performed using the Bayesian Optimal Phase 2 design. Longitudinal research blood, tissue, and microbiome samples will be collected along with neurocognitive assessments and quality of life surveys.

RESULTS
This study is actively enrolling. Eight of planned 30 subjects have been treated. At a median follow-up of 8 months, IC response was seen in 43% of patients. Grade 3 TRAEs occurred in 12% of patients with no new safety signals.
IMUN-07 TIMING AND OUTCOME OF BRAIN METASTASES FOLLOWING FIRST-LINE IPILIMUMAB PLUS NIVOLUMAB THERAPY FOR METASTATIC MELANOMA IN A COMMUNITY ONCOLOGY PRACTICE
Authors: Victoria Ong Claire , Samlowski Wolfram 
Published: August 2024

Abstract
Melanoma brain metastases (MBM) are a frequent complication of advanced stage disease. MBM are an important cause of morbidity and mortality during disease progression. We report a retrospective cohort study of patients treated with combined ipilimumab and nivolumab as initial therapy for metastatic melanoma to identify and evaluate the clinical course of patients who developed brain metastases in the “real world setting.” The aim of our study was (1) to determine the frequency and timing of brain metastases onset and (2) to characterize the incidence and timing of brain metastases following first line combined ipilimumab-nivolumab therapy. We evaluated 73 patients. Only 20 (27.4%) patients developed MBM. The majority of these patients were identified at initial evaluation of metastatic disease (20.5%), while the rate of CNS progression during immunotherapy was low (6.9%). Patient treatment response, progression-free survival (PFS), overall survival, and neurologic progression-free survival (CNS PFS) were evaluated. We observed that patients with MBM at diagnosis of metastatic disease had improved PFS and CNS PFS, compared to patients who progressed in the CNS following treatment. Despite the presence of symptomatic MBM at diagnosis, 27% of patients with MBM at diagnosis achieved a durable complete remission (NED). Of note, all responding patients presented with neurologic symptoms associated with their brain metastases, and half of them were receiving systemic steroids at the time of treatment. In contrast, patients with delayed onset of brain metastases had an extremely poor outcome, with a median PFS of only 4.8 months. Thus, in patients presenting with MBM at diagnosis of metastatic disease, combined ipilimumab/nivolumab therapy has significant clinical activity. Furthermore, checkpoint inhibitor therapy appears to reduce the frequency of delayed onset brain metastases. However, novel treatment options need to be developed to more effectively treat patients who progress in the CNS following initial combination therapy.
MMOD-07 CONSORTIUM FOR INTRACRANIAL METASTASIS ACADEMIC RESEARCH (CIMARA): INTERNATIONAL INTERDISCIPLINARY COLLABORATIONS TO IMPROVE OUTCOMES OF PATIENTS WITH CNS METASTASES
Authors: Van Swearingen Amanda , Anders Carey , Tawbi Hussein , members CIMARa 
Published: August 2024

Abstract
Brain metastases, including both parenchymal lesions and leptomeningeal disease, impact hundreds of thousands of patients annually worldwide, and are increasing in incidence as systemic anticancer therapies, and thus survival, improves. While historically patients with brain metastases were excluded from clinical trials, after much advocacy by patients and physicians over the past decade this has changed. More effective design of clinical trials for patients with brain metastases is needed, and a multidisciplinary team spanning local and systemic therapies is critical. CIMARa (Consortium for Intracranial Metastasis Academic Research) was formalized in June 2021, and is now a multidisciplinary, international group of clinical investigators, research scientists, and advocates who share the collective goal of improving outcomes for patients with brain metastases. As of April 2024, CIMARa includes nearly 110 members from 50 institutions and 8 countries in North America and Europe. CIMARa aims to improve outcomes through the awareness and coordination of multi-institutional clinical trials testing novel therapeutic strategies for this unique patient population, as well as through retrospective clinical studies and translation of preclinical work to the clinical setting. CIMARa collaborations thus far have led to multi-institutional and international preclinical collaborations and clinical studies, including 2 retrospective case series already published. Several more initiatives and studies are in progress, including developing consensus language around symptomatic vs asymptomatic brain metastases, a multisite retrospective study on PARP inhibitors in patients with breast cancer CNS metastases, and a large multisite retrospective on the efficacy and safety of bevacizumab for radiation necrosis in patients with brain metastases. Anyone interested in CIMARa can reach out to cimarainfo@gmail.com for more information or to be added to the membership list and receive communications about meetings and studies. Patient and caregiver advocates are especially welcome and encouraged to participate in CIMARa.
MMOD-09 PINEAL GERMINOMA RECURRENCE AND DISTANT METASTASIS IN A POST-CHEMOTHERAPY AND POST-RADIOTHERAPY ADULT FILIPINO: A CASE REPORT
Authors: Balanquit Loiue Stihl , De Roxas-Bernardino Ranhel 
Published: August 2024

Abstract
Pineal Germinomas are rare tumors comprising approximately less than one percent of brain tumors seen mostly in children or young adults and in males. Its recurrence is even more rare especially with local recurrence or leptomeningeal dissemination which is around 15%. We report a case of a 25 year old female which initially presents as frontal headache with associated photophobia and doubling of vision. Persistence of symptoms prompted consult upon which an MRI was done revealing a mass lesion. Surgical biopsy was done with histopathology revealing germinoma. Four cycles of chemotherapy and one session of radiotherapy were done. Serial MRI showed regression in size and complete resolution of the initial symptoms hence patient was able to return to work. One month thereafter, patient had sudden onset left sided weakness hence readmission. Radiation Necrosis and Pineal Germinoma Recurrence were entertained. MRI perfusion revealed interval increase of the intracranial mass. Additionally, MRI of the whole spine with contrast revealed Multifocal intradural mass on the cervical, lumbar and sacral region upon which surgical removal was done. Histopathology revealed Germinoma. The patient was then also started on corticosteroid therapy and eventual Partial Laminectomy. After which, radiation therapy and other treatment modalities were also considered. Hence, in this paper, we aim to report an extremely rare case of Pineal Germinoma with recurrence and distant metastasis in a Female Adult Filipino and to provide novel insight on the treatment modalities for Pineal Germinoma Recurrence.
MMOD-10 BRAIN METASTASIS, MENINGIOMA, AND GLIOMA: A RARE CASE OF MULTIPLE PRIMARY MALIGNANCIES
Authors: Li Boyi , Higgins Dominique 
Published: August 2024

Abstract
Multiple primary malignancies is a rare occurrence in which a single patient has multiple tumors of different origins. This occurs more commonly in patients with genetic conditions such as Li- Fraumeni disease or NF1. Here we present a case of a 78 year-old woman with no known family history of cancer or underlying genetic condition, who was found to have three different types of brain tumors, two of which presented simultaneously. The patient initially underwent resection of a right frontal WHO grade 2 meningioma in 2021. She elected not to pursue adjuvant radiation and subsequent serial MRIs up to September 2023 showed no recurrence. The patient was also found to have stage IIIa serous endometrial carcinoma, with genetic profile revealing a TP53 mutation. She underwent a hysterectomy in March 2023 and 6 cycles of paclitaxel/carboplatin with good systemic control. She then presented in March 2024 with status epilepticus and was found on new MRI to have two new lesions: an irregular enhancing cortical right occipitotemporal lesion with leptomeningeal involvement and a small round well-circumscribed heterogeneously enhancing periventricular mass along the atrium of the left lateral ventricle. The patient was taken for stereotactic biopsy of both lesions given the difference in radiologic appearance. Pathology results revealed the left lesion to be metastatic high-grade serous carcinoma and the right lesion an infiltrating high grade glioma, positive for TERT promotor mutation and MGMT promotor methylation positive. Germline testing is pending. To our knowledge, this is the first case of a patient with three distinct types of brain tumors: meningioma, metastasis, and glioma. Further understanding of this patient’s unique presentation and genetic profile will contribute to our understanding of the diagnosis and treatment of patients with multiple brain tumors.
MMOD-16 THE CHALLENGES IN ASSIGNING THE PRIMARY SOURCE OF METASTATIC FOCUS: PATHOLOGY POINT OF VIEW
Authors: Almurshed Maryam 
Published: August 2024

Abstract
Metastasis to the central nervous system is the most common cause of brain lesions, mostly in adults and mostly in the posterior fossa. Assigning the primary source of metastasis in a patient as a first presentation/ unknown primary is challenging to the pathologist. The diagnosis, in pathology point of view depends primarily on three factors: tumour morphology, the immunohistochemical expression, and clinical correlation to definitely specify the primary site of the metastasis. Missing one of thses factors may mislead the final diagnosis. The morphology of the metastasis may differ from the primary site as the metastasis may include “only” the tiny aggressive variant in the primary site, leading to mis- directing the pathological investigation. In addition, the immuno-expression is highly overlapping over different pathological entities, not mentioning the lab quality of stain. In cases of complex tumors, only one component of the tumor can metastasis leading to mis-labelling of the tumor entity. In conclusion, precise pathological diagnosis on tumor metastatic focus as a primary diagnosis can not be achieved without minding these factors, which are essential information to be delivered to the assigning pathologist.
NIRL-01 DEEP LEARNING-BASED VOLUMETRIC SEGMENTATION ENABLES RESPONSE ASSESSMENT AFTER LASER INTERSTITIAL THERMAL THERAPY
Authors: Haskell-Mendoza Aden , Reason Ellery , Gonzalez Ariel , Jackson Joshua , Sankey Eric , Srinivasan Ethan , II James Herndon , Fecci Peter , Calabrese Evan 
Published: August 2024

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT) allows for definitive tissue diagnosis, surgical cytoreduction, and faster post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. Ablated tissue remains in situ following LITT, resulting in characteristic post-LITT lesion expansion. Post-LITT edema may be associated with transient clinical worsening and complicates subsequent response assessment.

METHODS
All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments.

RESULTS
Sixty-one LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed across 384 unique MRI exams. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and subsequently returned to baseline. Median overall survival (mOS) for LITT-treated patients was 39.1 (9.2 – 93.4) months. Using previously established volumetric thresholds, volumetric disease progression was defined as lesion expansion ≥ 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients with volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015).

CONCLUSION
We observed a nearly 70% increase in CeLV at 1 – 3 months post-LITT, which characteristically resolved within 6 months of the procedure. Development of response assessment criteria that account for transient post-LITT lesion expansion is feasible and should be considered for clinical trials. Automated lesion segmentation may facilitate adoption of volumetric response assessment into clinical practice.