bluuebunny/crossref_metadata_2025_split huggingface dataset:
OCTS-11 PHASE 1 DOSE ESCALATION OF RHENIUM (186RE) OBISBEMEDA (RHENIUM NANOLIPOSOME,186RNL FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES (LM): ONGOING CLINICAL STUDY UPDATE FOR INITIAL SAFETY AND FEASIBILITY
Authors: Brenner Andrew , Youssef Michael , Kumthekar Priya , Bao Ande , Michalek Joel , Phillips William , Patel Toral , Weinberg Jeffrey , Floyd John , Hedrick Marc , Juvierdianu Leonardo , Moore Melissa , Blouw Barbara , LaFrance Norman 
Published: August 2024

Abstract

BACKGROUND
Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, renal cell, and melanoma, with limited treatment options and poor survival. Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma-decay for imaging, and ~89.2-hour physical half-life for optimal radiation delivery. An ongoing clinical trial update for the Phase 1 dose escalation study (Cohorts 1-5) is presented.

METHODS
ReSPECT-LM is a Phase 1 dose escalation study for patients with LM from any primary cancer. Adult patients are given a single dose of 186RNL via intraventricular catheter (Ommaya reservoir) in an outpatient setting to determine the maximum tolerated/feasible dose (MTD/MFD), safety, and tolerability. Subjects received 6.6, 13.2, 26.4, 44.10, or 66.14 mCi of 186RNL (Cohort 1-5, respectively).

RESULTS
Doses were well-tolerated with no treatment-related serious adverse events (SAEs); the majority of AEs were Grade 1 and 2. The MTD/MFD has not been reached. CSF tumor cell enumeration assays (CNSide test) were performed with a maximum reduction over baseline seen at Day28. Radiation absorbed doses were calculated for the ventricles, cranial subarachnoid space, and spinal fluid and showed a linear increase with administered dose, with liver and spleen remaining low. To date, neurological signs and symptoms from LM were reported to improve by investigators and patients. Cohort 5 is completing its enrollment and subsequent analysis.

CONCLUSION
A single dose of 186RNL for patients with LM is well tolerated, has high absorbed doses to the treatment area with low organ dose, and shows promising positive clinical improvement and reductions in tumor cell count. Enrollment to Cohort 6 (87.97 mCi) will follow Cohort 5’s data safety review; the current development status of the Phase 1 study will be reported.
RADT-04 IMPROVED SURVIVAL IN PATIENTS WITH RADIONECROSIS VS. LOCAL RECURRENCE AFTER STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Leng Jim , Arshad Muzamil , Carpenter David , Qazi Jamiluddin , Huang Christina , Vaios Eugene , Reitman Zachary , Floyd Scott , Kirkpatrick John , Fecci Peter , Chmura Steven , Hong Julian , Sperduto Paul , Salama Joseph , Mullikin Trey 
Published: August 2024

Abstract
PURPOSE: Radionecrosis (RN) is a dose-limiting toxicity after stereotactic radiosurgery (SRS) for brain metastases. How RN affects patient outcomes following SRS is not well described. Therefore, we characterized survival outcomes of patients who develop RN versus treated tumor recurrence in the absence of out-of-field intracranial progression after SRS. METHODS: This cohort study included patients completing an initial course of SRS from 2015-2020 at two institutions. Primary outcome was overall survival (OS) by presence of RN or treated tumor recurrence (LR), analyzed via the Kaplan-Meier method. Binomial logistic regression tested parameters associated with RN or LR. RESULTS: 1383 patients were included, 55% were male and median age was 63.4 years. Common primaries were lung (55%), breast (15%), and melanoma (9%). At a median follow up of 8.7 months, concern for intracranial progression was limited to irradiated sites for 143 patients (10%) - 96 with RN and 47 with LR. LR was diagnosed sooner after SRS than RN (median 5.8 vs. 8.3 months, P=0.0087), and patients with LR had significantly worse OS compared to RN (median 15.2 vs. 40.4 months, P&lt;0.001). Patients who were symptomatic had LR and RN earlier than asymptomatic patients and had worse OS. On binomial logistic regression, RN was associated with single fraction SRS (odds ratio [OR] = 0.38, P = 0.012), receipt of immunotherapy after SRS (OR = 0.32, P &lt; 0.014), and a longer interval from SRS (OR = 0.94, P = 0.028). CONCLUSION: In this multi-institutional cohort study of patients with brain metastasis treated with SRS, those with RN had significantly better OS vs. those with LR, with a median OS of 40.4 months vs. 15.2 months (P&lt;0.001). This data informs the surveillance and prognosis of patients after SRS.
RADT-13 STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES SECONDARY TO PERIPHERAL NEURAL CREST TUMORS: A SINGLE INSTITUTION RETROSPECTIVE EXPERIENCE
Authors: Kattaa Ahed , Persad Amit , Park David , Hori Yusuke , Emrich Sara , Ustrzynski Louisa , Tayag Armine , Gu Xuejun , Rahimy Elham , Pollom Erqi , Soltys Scott G , Chang Steven D 
Published: August 2024

Abstract

BACKGROUND
Intracranial BM of peripheral neural crest tumors (PNCTs) are rare, and portent a poor prognosis. No standard treatment has been established to date, and only a few case reports describe the usage of stereotactic radiosurgery (SRS). This study aims to evaluate the efficacy of SRS for BM from PNCTs. Additionally, a comparison between SRS and other treatment modalities have been conducted.

METHODS
We retrospectively reviewed all patients diagnosed with BM from PNCTs between 2001 and 2024 at our institution. LTC was defined as a reduction/stable in tumor size, with no recurrence or hemorrhage as evidenced by radiological assessment.

RESULTS
Among the 8 patients (15 BM) identified, 3 with 6 BM underwent SRS, and 5 with 9 BM underwent other treatments (radiotherapy, craniotomy, or none). Amongst the patients treated with SRS, the median age was 4.0 years (IQR: 1.8-4.0 years) at diagnosis and 100% were male. The median follow-up was 5.5 months (IQR: 2-7 months). Amongst the patients not treated with SRS, the mean age was 2.5 years (Std. deviation: 1.4 years) at diagnosis and 60% were female. The median follow-up was 28 months (IQR: 1- 85 months). The group treated with SRS had LTC rate of 100% with no complications and a survival rate of 33.3% at one year follow up. LTC rate in the group treated with other modalities was 55.6%, with a survival rate of 60% for a one year follow up. There was no significant difference in LTC and survival between groups (p &gt; 0.05).

CONCLUSION
SRS provides a LTC rate of 100% within one year of follow up for BM from PNCTs. We do suggest that there is similarity of outcomes between SRS and other treatment modalities. SRS may be an alternative to more invasive treatments such as craniotomy or conventional radiation in these patients.
RMTD-02 PRACTICE VARIATION AND IMPACT OF PRE-OPERATIVE AND POST-OPERATIVE DEXAMETHASONE ON PATIENT OUTCOME IN THE RESECTED BRAIN METASTASIS – INSIGHTS FROM THE CLINDEXMET MULTICENTER REGISTRY
Authors: Wasilewski David , Tommaso Araceli , Rafaelian Artem , Demetz Matthias , Asey Benedikt , Ersoy Tunc-Faik , Dauth Alice , Peukert Ricarda , Poeser Paul , Jelgersma Claudius , Früh Anton , Xu Ran , Capper David , Ehret Felix , Frost Nikolaj , Schmidt Leon , Krenzlin Harald , Ringel Florian , Meyer Hanno , Gempt Jens , Kerschbaumer Johannes , Freyschlag Christian , Thomé Claudius , Simon Matthias , Dubinski Daniel , Freiman Thomas , Schmidt Nils Ole , Proescholdt Martin , Vajkoczy Peter , Onken Julia 
Published: August 2024

Abstract

BACKGROUND
Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate variation in pre- and post-operative dexamethasone dosing and whether perioperative dexamethasone in brain metastases is linked to patient outcome.

METHODS
This was a multicenter retrospective study collecting data on daily pre- and post-operative dexamethasone dosage over a period of 27 days in patients undergoing brain metastasis resection. Non arbitrary cutpoint selection was performed using maximally selected rank statistics to dichotomize patients. Propensity score matching served to reduce bias and adjust for potential confounders including tumor and edema volume, localization of the dominant brain metastasis, disease-specifc GPA score, presence of other non-oncological diseases.

RESULTS
988 patients were included. Median follow-up time was 55,2 months [95% CI: 50.7 – 61.5]. After propensity score matching patients below the determined cutpoint of 122 mg cumulative dexamethasone showed an overall survival of 16.0 months [95% CI: 13.3 – 21] vs. patients with more than 122 mg cumulative dexamethasone with a OS of 10.6 months [9.0 – 12.7], p=0.0022. No effect on extracranial or intracranial disease progression was observed. In a multivariable model for the matched data the cumulative peri-operative dexamethasone above the cutpoint remained independently associated with overall survival (HR: 1.3 [95% CI: 1.12 – 1.6], p=0.001).

CONCLUSION
Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases.
RMTD-03 USE OF A BRAIN-PENETRATING ANTHRACYCLINE IN ANTHRACYCLINE-SENSITIVE BRAIN METASTASES: THE PROMISE OF BERUBICIN
Authors: Silberman Sandra 
Published: August 2024

Abstract

BACKGROUND
Brain metastases are a common complication of cancer and also type of brain tumor: 10%-26% of patients develop brain metastases. Chemotherapy for these tumors is usually ineffective due to an intact blood-brain barrier (BBB). Anthracycline-sensitive cancers that metastasize to the brain do not receive anthracyclines which do not penetrate the brain. Triple-negative breast cancer (TNBC), which can be treated with doxorubicin (DOX) systemically has an incidence of brain metastases of approximately 25–46%; although lymphomas usually require an anthracycline as part of their chemotherapy, when they appear as a primary disease in the brain anthracyclines cannot be used. Berubicin is an analog of doxorubicin that appears to cross the BBB with significant central nervous system (CNS) uptake. A pivotal trial for patients with recurrent glioblastoma (GBM) after first-line therapy has finished enrollment with 252 patients in the US and Europe with evidence of efficacy and no impact on cardiac function.

METHODS
CNS Pharmaceuticals plans to evaluate Berubicin in patients with Primary CNS Lymphoma (PCNSL) who have never received an anthracycline and in TNBC with documented brain metastases. Patients will be enrolled if they have shown progression in the brain and have not undergone primary treatment. Outcome measurements will include efficacy in terms of overall response rates (ORR), progression-free survival (PFS), and overall survival (OS) as well as a continuing evaluation of Berubicin’s safety and tolerability.

CONCLUSIONS
The use of anthracyclines for the treatment of malignancy has encompassed 50 years of showing significant activity in certain diseases, however, use has been limited by both the risk of cardiotoxicity as well as the inability to penetrate the BBB, where these tumors tend to metastasize. This study offers the promise of using an anthracycline that can cross the BBB effectively for sensitive tumors and Berubicin becoming an important part of their therapy
RMTD-05 UNRAVELLING THE LANDSCAPE OF BRAIN METASTASES ACROSS PRIMARY CANCER TYPES: A PAN-CANCER STUDY UTILIZING THE SEER DATABASE
Authors: Dimou James , Stylli Stan , McCoy Patrick , Campbell Bethany , Corcoran Niall , Saunders Christobel , Drummond Kate , Hovens Christopher 
Published: August 2024

Abstract

INTRODUCTION
Brain metastases pose a formidable challenge in oncology. While certain cancers like lung, breast, and melanoma are known to commonly metastasize to the brain, comprehensive studies spanning cancer types that uncommonly or rarely spread to the brain are limited.

METHODS
This study employs data from the Surveillance, Epidemiology, and End Results (SEER) database to examine incidence, prevalence, and clinical characteristics of brain metastases across nearly all cancers. We conducted a detailed review of SEER-derived patient data, focusing on brain metastases. Statistical analyses, including Kaplan-Meier plots and Gehan-Breslow-Wilcoxon tests, were utilized to compare survival rates and clinical features between cancer types, integrating additional features such as staging. (i.e., T and N grades)

RESULTS
Lung cancer is the most common primary source of brain metastases. (~80.5% of cases) Furthermore, cancers traditionally associated with brain metastasis—lung, melanoma, breast, renal, and colorectal—comprise 93% of all brain metastasis cases in SEER. Further analysis showed that brain metastasis patients had worse five-year survival than patients who developed metastasis elsewhere, and those patients with high grade glioma. Recent advancements in treatment have improved survival rates for patients diagnosed with brain metastases between 2015-2019, compared to those diagnosed during 2010-2014. This improvement appears to be driven disproportionately by cancers commonly associated with brain metastasis. Moreover, it can be revealed that there are notable differences in T/N grades and clinical features of the cancers that uncommonly or rarely spread to the brain, compared to those that commonly do so.

CONCLUSIONS
This study suggests that the pattern of brain metastasis formation may differ between those primary malignancies that commonly, and uncommonly or rarely spread metastatically, highlighting the deficit of our clinical and scientific understanding of this pernicious cancer phenomenon, as well as the need to develop novel, innovative treatment paradigms for patients with brain metastases.
SPCM-02 ASSOCIATIONS BETWEEN INTRAOPERATIVE NEUROMONITORING USAGE AND CLINICAL OUTCOMES FOR SURGERIES AMONG PRIMARY NON-MALIGNANT SPINE TUMOR PATIENTS
Authors: Bishop Brandon , Woo Joshua , Rowe Dana , Luo Emily , Ndika Tobechukwu , Charles Antoinette , Arango Alissa , Yoo Seeley , Zachem Tanner , O’Callaghan Ellen , Owolo Edwin , Sperber Jacob , Crowell Kerri-Anne , Rivera Nicole , Nguyen Annee , Hockenberry Harrison , Reitz Kendall , Dalton Tara , Johnson Eli , Erickson Melissa , Goodwin C Rory 
Published: August 2024

Abstract

BACKGROUND
The use of intraoperative neuromonitoring (IONM) has recently increased in popularity among spinal surgery to reduce rates of postoperative neurological complications. However, its utility has been mixed, especially in elective surgeries, due to increased healthcare spending and limited guidelines. In this study, we investigated the associations between IONM and clinical outcomes, as well as both financial and demographic factors, for patients with primary non-malignant spine tumors (PNMT) undergoing surgery.

METHODS
A retrospective review was performed using the PearlDiver Patient Record Database to identify cases of PNMT patients who underwent surgery from 2011 to 2021. Rates of IONM usage were compared based on patient age, sex, family income, and region. Complications and 30-day readmissions were also assessed.

RESULTS
5,692 patients undergoing surgery with PNMTs were identified, with 1,914 (33.6%) of these utilizing IONM. Younger age (p &lt; 0.001) and male sex (p &lt; 0.05) were both significantly associated with IONM usage and there was significant regional variability in utilization observed (Midwest: 33.8%; Northeast: 24.6%; South: 29.0%; West: 12.6%; p &lt; 0.001). Among clinical outcomes, nerve injury (p &lt; 0.001), surgical complications (p &lt; 0.001), and 30-day readmission rates (p &lt; 0.001) were all significantly associated with IONM usage. Both mean family income (p &lt; 0.005) and reimbursement amounts were not clinically significant in association with IONM usage.

CONCLUSIONS
Among patients with PNMTs, this study demonstrates significant differences in IONM usage across geographic regions, sex, and age as well as a positive association with 30-day readmission rates with use. While associations between IONM and family income have been observed previously, neither income nor reimbursement measures were clinically significant in our cohort. Given the growing usage of IONM in spinal surgeries, these results provide important insights into the utility of IONM among patients with non-malignant spinal tumors.
QSPC-01 INVESTIGATING DISTRESS LEVELS IN PATIENTS WITH METASTATIC SPINE DISEASE UNDERGOING SURGICAL INTERVENTION
Authors: Rowe Dana , O’Callaghan Ellen , Barrett Connor , Owolo Edwin , Charles Antoinette , Luo Emily , Arango Alissa , Bishop Brandon , Yoo Seeley , Johnson Margaret , Erickson Melissa , Goodwin C Rory 
Published: August 2024

Abstract

INTRODUCTION
Cancer patients often experience high levels of distress, which are particularly pronounced in the perioperative period. However, there is a dearth of research on distress rates in patients with metastatic spine disease (MSD). This study aims to assess pre-operative and post-operative distress levels in patients with MSD undergoing surgical intervention.

METHODS/STUDY POPULATION
We retrospectively queried electronic medical records from a single institution for demographic and clinical data on patients with metastatic spine disease who underwent surgical intervention between 2015 and 2023. Data also included preoperative (within 60 days of surgery) and postoperative (within 30 days of surgery) National Comprehensive Cancer Network’s Distress Thermometer (NCCN-DT) scores.

RESULTS
We identified 222 patients with complete NCCN-DT questionnaires. Nearly half (46.4%) of the patients were female, with 71.2% identifying as White, and 68.5% being married or partnered. The median age at the time of spine metastasis diagnosis was 62.5 years (IQR: 53.0; 71.5). Preoperatively, the mean distress score was 3.5 (range 0-10), with 103 (46.4%) patients reporting moderate to severe distress (DT ≥ 4). The mean distress score at 30-days postop was 3.2 (range 0-10), with 43.75% of patients reporting moderate to severe distress. At 90-days post-op, the mean distress score was 2.3 (range 0-9) with 23.8% of patients reporting moderate to severe levels.

DISCUSSION/SIGNIFICANCE OF IMPACT
Distress is a common experience among patients with metastatic spine disease undergoing surgical intervention. Preoperatively, nearly half of these patients report moderate to severe distress. While distress rates generally decline postoperatively, a considerable proportion of patients continue to experience high levels of distress. These findings underscore the significance of addressing distress in this patient population.
QSPC-09 FACTORS IMPACTING QUALITY OF LIFE AFTER BRAIN METASTASES DIAGNOSIS: A MIXED METHODS STUDY OF PATIENTS AND THEIR CAREGIVERS
Authors: Porter Kathleen , Mulligan Caroline , Fadul Camilo , Bonilla Gloribel , You Wen , Anderson Roger 
Published: August 2024

Abstract
To provide optimal care after the diagnosis of brain metastases (BMETS), it is crucial to understand the factors that affect quality of life (QoL) from the patient and caregiver perspectives. We conducted a mixed-methods pilot study to gain initial insight into patients’ and caregivers’ reports on factors that affect patients’ QOL following initial brain-directed treatment of brain metastases. Within 4 months of BMETS diagnosis, eligible patients completed 2 surveys ~3 months apart, while they and their caregivers completed interviews at the same timepoints. Patient demographic, diagnostic, and treatment data were abstracted from the medical record. The surveys and the semi-structured interviews assessed patients’ QoL and explored contributing factors. Median QoL change scores (Timepoint 1 minus Timepoint 2) and effect sizes (Cohen’s d) were calculated. Interviews were analyzed using directed content coding. Patients (n=8) had a median age of 69 years and had ECOG and KPS scores of ≤1 and ≥70, respectively. 25%, 75%, and 75% had received whole brain radiation therapy, stereotactic radiosurgery, and systemic medical therapy, respectively. Caregivers (n=5) had a median age of 66 years and were 60% female and 80% a patient’s spouse/partner. QoL scores decreased among the 4 patients who completed both surveys [Fact-BR: median change score = 4.5, ES=0.28; Fact-G: median change score = 4.0, ES=0.34]. Interviews identified desirable features of and changes to patient QoL across 4 domains: physical, emotional, social, and spiritual. Six factors impacting patient QoL were identified, including BMETS diagnosis, care processes, treatment, alterations to daily activities and relationships, cancer-related life strain, and positive adaptations. This pilot study revealed that patients’ QoL decreased over time at a clinically relevant magnitude and identified some of the drivers of these changes. These preliminary findings support future research to address the persistent gaps related to supporting the QoL of patients with BMETS.
TRSC-07 COMBINATION OF ENDOCRINE THERAPY WITH RADIATION DECREASES BRAIN METASTASES THROUGH REACTIVATION OF EFFECTOR IMMUNE-CELL RECRUITMENT TO THE BRAIN
Authors: Contreras-Zarate Maria Jose , Alvarez-Eraso Karen , Goodspeed Andrew , Costello James , Jaramillo-Gomez Jenny , Koliavas Stella , Fox Morgan , Ormond Ryan , Kabos Peter , Karam Sana , Cittelly Diana 
Published: August 2024

Abstract
Younger women with breast cancer have increased risk of development of brain metastases (BM) irrespective of the tumor subtype. We have shown that pre-menopausal levels of 17-β-Estradiol (E2) promotes BM of estrogen receptor negative (ER¯) BC cells by inducing neuroinflammatory ER+ glial cells to secrete pro-metastatic factors critical for early brain colonization. Yet, the clinical translation of endocrine therapies (ET) to the management of BM requires a better understanding of its effectiveness at late stages of metastatic progression and its interactions with current standard of care (SOC). Using scRNAseq of brain immune cells isolated from E2 or E2-suppressed mice carrying BMs we show that pre-menopausal levels of E2 suppressed immune surveillance, activation, and IRF-7/interferon-driven anti-tumoral programs in microglia. Multiparametric flow cytometry show that E2 repressed recruitment of T, B and NK cells to the brain niche from early to late stages of BM progression and ET (ovarian suppression and aromatase inhibitors) restored recruitment of these effector immune cells to the brain. ET decreased BM progression when used in combination with brain radiotherapy (RT), but not when ET was used alone or in immunocompromised mouse models, suggesting ET-induced recruitment of interferon driven T, B and NK cells to the brain synergizes with radiotherapy to promote more effective anti-tumoral immune responses. Depletion of CD4+T, CD8+T, and NK1.1+ cells in E2-suppressed mice carrying BMs showed that anti-tumoral effects of RT and ET depend on CD4T and NK cells. Suppression of CD4+ T cells further increased the effectiveness of ET and RT and improved survival, suggesting that subsets of T cells, possibly Treg cells are critical to regulate BM antitumoral responses. While ET+RT were comparable to anti-PD-1+RT in decreasing BMs, their effects were not additive. Thus, our results suggest that FDA-approved ET synergizes with RT but not PD-1 inhibitors for treatment of BMs.