bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIRL-07 DIAGNOSTIC AMBIGUITIES IN MRI CHANGES IN A PATIENT WITH BRAIN METASTASES AND RECURRENT STROKES
Authors: Prakash Neal , Chen Bihong , Fricke Jeremy , Babikian Razmig , Salgia Ravi 
Published: August 2024

Abstract
Brain magnetic resonance imaging (MRI) sequences, particularly gadolinium enhanced T1 images, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) are used frequently in clinical practice. These modalities can help distinguish ischemia from brain metastasis, leptomeningeal disease, hypoxic injuries, and other brain lesions. We present a case of a patient with metastatic lung cancer to the brain with progressive hemiplegia, tumor progression, recurrent strokes, hypoxic brain injury and leptomeningeal disease. Sequential MRIs showed chronic DWI hyperintensity that corresponded to metastatic tumor, with superimposed acute DWI hyperintensities at different time intervals that corresponded to either ischemic events, hypoxic events, and/or tumor progression. We highlight the strengths and limitations of current MRI imaging modalities, particularly DWI, in distinguishing tumor progression from acute ischemic events in a patient with metastatic brain cancer. The correct diagnosis is crucial in guiding treatment strategies as the clinical course progresses, particularly in regard to selecting more aggressive anti-thrombotics versus changing cancer treatment, and defining goals of care.
NVTG-04 REAL-WORLD OUTCOMES WITH SACITUZUMAB GOVITECAN AMONG BREAST CANCER PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) METASTASES
Authors: GRINDA Thomas , Morganti Stefania , Hsu Liangge , Kusmick Ross J , Aizer Ayal A , Giordano Antonio , Leone Jose P , Hughes Melissa , Tolaney Sara M , Lin Nancy U , Sammons Sarah L 
Published: August 2024

Abstract

Sacituzumab-govitecan (SG) demonstrated significant survival benefits over standard chemotherapy in pretreated triple-negative (TNBC) and hormone receptor-positive (HR+/HER2-) metastatic breast cancer (MBC) patients. Limited data on intracranial outcomes in MBC patients exist. We describe the real-world (RW) of intracranial efficacy and outcomes for SG in MBC patients with central nervous system metastases (CNS-mets).

METHOD
We retrospectively studied MBC patients with CNS-mets who began SG between 2018 and 2022, using an institutional MBC database. CNS involvement was subcategorized as active CNS-mets (new or progressive not yet treated with CNS-directed therapy) and leptomeningeal disease (LMD). An independent radiologist confirmed CNS response rates (rwCNS-RR) using RANO criteria. The Kaplan-Meier method estimated RW-CNS, bi-compartmental progression-free, and overall survival (rwCNS-PFS, rwBi-PFS, and OS).

RESULTS
33 women were included: 10 HR+/HER2- and 23 TNBC. 13/33 (39%) had active CNS-mets and 8/33 (24%) had LMD (2 HR+/HER2- and 6 TNBC). the median time from MBC diagnosis to SG initiation was 1.79 years (q1q3, 1.02-3.79), a median of 3 (q1q3, 2-6) prior lines received for MBC and 28/33 (84.8%) received prior brain radiotherapy. rwCNS-RR was 4/30 (13%; 1/9 HR+/HER2-; 3/21 TNBC). After a median follow-up of 20.70wks (95%CI 3.28-127.41) from SG initiation, median rwCNS-PFS, rwBi-PFS, and OS were 12.7 wks (95%CI 8.6–18.6), 11.3 wks (95%CI 8.3–17.6) and 29.1 wks (95%CI 13.6-43.3), respectively. Among patients with active CNS-mets, rwCNS-RR was 1/13 (8%). Among patients with LMD, rwCNS-RR was 1/7 (14.3%), and median OS was 15.8 wks (IC95% 7.4-47.6). The site of progression on SG was 1/33 (3%) CNS-only, 10/33 (30%) non-CNS only, 17/33 (52%) both, and 5/33 (15%) unknown because deceased.

CONCLUSION
In this RW analysis, SG was associated with modest clinical activity and intracranial response rates in heavily pretreated MBC patients with CNS metastases. Effective treatments demonstrated in prospective studies are needed for this patient.
NVTG-10 CLINICAL AND RADIOLOGICAL OUTCOMES OF ORBITAL METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY: A SINGLE INSTITUTION RETROSPECTIVE SERIES
Authors: Zamarud Aroosa , Hori Yusuke S , Kattaa Ahed H , Persad Amit R , Tayag Armine , Usttrzinsky Louisa , Emrich Sara Coleman , Soltys Scott G , Hancock Steven L , Park David J , Chang Steven D 
Published: August 2024

Abstract

INTRODUCTION
Orbital metastases (OM) are a rare complication of cancer that can result in visual impairment. Treatment options include surgery and radiotherapy, however, the optimal treatment for OM is unclear. The current evidence for stereotactic radiosurgery (SRS) is limited. We aim to report the efficacy and safety of SRS in patients with OM.

METHODS
The clinical and radiological outcomes of patients with OM treated with SRS between April 2006 and November 2023 were retrospectively reviewed. SRS was utilized to treat all the tumors. The post-treatment tumors were radiologically categorized to stable disease (SD), partial response (PS), and complete response per RECIST criteria.

RESULTS
We included 15 patients with 17 OM lesions in our study; 9 (60%) of whom were females, and their median age was 62 years (range: 21-82 years). The median overall survival was 6.5 months (range: 2-62 months). All these patients were treated with standalone CK SRS. The most common fractionation schedules were 24 Gy in 3 fractions (n=4). The median diameter of the lesions was 21 mm (range: 11-72 mm). The median volume treated was 2.6 cm3 (range: 0.3-78.8). At the last follow-up, 13 tumors (76.5%) showed SD, 2 tumors (11.8%) showed PR, 2 tumors (11.8%) showed CR, and no tumor (0%) showed PD. The lesions were followed for a median of 7 months (range: 2-62 months). The local control rates were 100% at 6-month and 12-month. No immediate or long-term radiation-induced necrosis was reported.

CONCLUSION
This is the largest series on OM treated with CK SRS with substantial follow-up data. Our study shows an excellent local tumor control with no immediate and long-term radiation induced necrosis.
OCTS-01 DOSE ESCALATION FOR PREOPERATIVE STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH LARGE BRAIN METASTASES
Authors: Murphy Erin S , Yang Kailin , Suh John , Yu Jennifer , Stevens Glen , Angelov Lilyana , Vogelbaum Michael , Barnett Gene , Ahluwalia Manmeet , Neyman Gennady , Mohammadi Alireza , Chao Samuel 
Published: August 2024

Abstract

PURPOSE/OBJECTIVE(S)
We conducted a prospective phase I preoperative radiosurgery dose escalation trial for brain metastases greater than 2 cm. We report updated results with known prognostic variables.

MATERIALS/METHODS
Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor diameter. Dose limiting toxicity (DLT) was defined as grade 3 or greater acute toxicity. Patients underwent surgical resection within 2 weeks and were followed with imaging and neurological evaluations every 3 months.

RESULTS
A total of 35 patients were enrolled. The most common histology was NSCLC (57.1%), followed by breast cancer (14.3%). Only 12 out of 35 patients had actionable mutations and received targeted therapy and/or immunotherapy. 13 (37%) underwent piecemeal resection. 7 (20%) were infratentorial. There were 3 DLTs: 2 in the &gt;3-4 cm cohort and 1 in the &gt;4-6 cm cohort. For &gt;3-4 cm, the maximum tolerable dose (MTD) was 18 Gy (2nd dose level), and for &gt;4-6 cm, 18 Gy (3rd dose level). Time to DLT occurred within 2 days to 2 months of surgery. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. The 6- and 12-month distant brain control was 63.1% and 55.3%, respectively. Overall survival at 6 and 12 months was 82.9% and 59.0%. The rate of leptomeningeal disease (LMD) at 2 years was 0%.

CONCLUSION
Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The Phase II portion of the trial is accruing patients with tumor size &gt;3-6 cm at 18Gy.
OCTS-02 ETOP 19-21 USZ-STRIKE: IMMUNOTHERAPY OR TARGETED THERAPY WITH OR WITHOUT STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES FROM MELANOMA OR NON-SMALL CELL LUNG CANCER
Authors: Weller Michael , Rhun Emilie Le , Giacomo Anna Maria Di , Mayinger Michael , Roschitzki Heidi , Guckenberger Matthias , Ruepp Barbara , Dummer Reinhard , Dafni Urania , Maio Michele , Stahel Rolf 
Published: August 2024

Abstract

BACKGROUND
Brain metastases may affect 30% of patients with metastatic cancer and are a major cause for morbidity and mortality. Treatment approaches include neurosurgical interventions, various approaches of radiotherapy, notably radiosurgery, and systemic pharmacotherapy. Encouraging response rates and response duration have been observed in patients with melanoma and non-small cell lung cancer (NSCLC) and asymptomatic or oligo-symptomatic brain metastasis treated with novel systemic therapies including immune checkpoint inhibitors and targeted therapy, challenging the need for immediate radiosurgery and introducing a change into clinical practice not supported by data from controlled clinical trials.

METHODS
ETOP 19-21 USZ-STRIKE (NCT05522660) is a randomized phase III study conducted by the ETOP IBCSG Partners Foundation. Patients with brain metastases from melanoma or NSCLC are treated systemically with the most appropriate pharmacotherapy. Randomization determines whether they receive pharmacotherapy alone or in combination with radiosurgery. The primary endpoint is CNS-specific progression-free survival (PFS), locally assessed per iRANO criteria. Secondary endpoints include CNS-specific PFS per tumor cohort, objective CNS response rate, duration of CNS response, pattern of CNS-specific progression, extra-CNS progression, incidence of radionecrosis and pseudoprogression, overall survival, neurocognitive function, quality of life and functional independence, and toxicity. We assume that the addition of radiosurgery to systemic treatment increases median CNS specific PFS by 62% from a median of 4 and 8 months for melanoma and NSCLC, respectively, corresponding to a hazard ratio 0.62 for time to CNS failure. According to the log-rank test, at a one-sided significance level of 5%, 138 observed events yield 88% power, for a sample size of 190 patients. The trial is supported by philanthropic funds from the USZ foundation and conducted at 11 sites in four countries. Accrual is slower than predicted mostly because of equipoise and patient, caregiver and notably physician bias.
OCTS-03 A MULTICENTER, OPEN-LABEL, SINGLE-ARM, MULTICOHORT PHASE II CLINICAL TRIAL OF TRASTUZUMAB DERUXTECAN IN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-POSITIVE AND HER2-LOW ADVANCED BREAST CANCER (ABC) WITH BRAIN METASTASES AND/OR LEPTOMENINGEAL CARCINOMATOSIS (LMC) – THE DEBBRAH STUDY
Authors: Vaz-Batista Marta , Pérez-García José Manuel , Cortez Patricia , Garrigós Laia , Ruiz-Borrego Manuel , de la Haba-Rodríguez Juan , de las Heras Begoña Bermejo , Servitja Sonia , Racca Fabricio , Fernández-Abad María , Blanch Salvador , Teurel Iris , Sáenz1 Jose Ángel Garcia , Ortega Adela Fernandez , Martrat Griselda , Shimizu Eileen , Alcalá-López Daniel , Pérez-Escuredo Jhudit , Braga Sofia , Llombart-Cussac Antonio , Cortes Javier 
Published: August 2024

Abstract
The DEBBRAH study (NCT04420598) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, in patients with HER2-positive and HER2-low ABC with brain metastases (BM) and/or LMC. Forty-one patients aged ≥18 years were enrolled in 5 cohorts: (1) HER2-positive ABC with non-progressing BM after radiotherapy and/or surgery (n=8); (2) HER2-positive or HER2-low ABC with asymptomatic untreated BM (n=10); (3) HER2-positive ABC with progressing BM after local treatment (n=9); (4) HER2-low ABC with progressing BM after local treatment (n=7); (5) HER2-positive or HER2-low ABC and pathologically confirmed LMC (n=7). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days until disease progression, unacceptable toxicity, or consent withdrawal. At the final analysis cut-off (4th April 2023), with a median follow-up of 15.2 months (range 2.1-30.1), three (7.3%) patients were still receiving T-DXd. In cohort 1, the 16-week progression-free survival rate was 87.5% (p&lt;0.001), meeting the primary endpoint, with seven out of eight patients alive without progressive disease 16 weeks after initiating treatment, demonstrating intracranial and extracranial activity. Among cohorts 2, 3 and 4, intracranial overall response rates ranged from 50% to 70%. In cohort 5, the median overall survival rate was 13.3 months, meeting the primary endpoint. The most common hematologic treatment adverse events (TEAEs) (≥10%) were anemia (31.7%; 0% G≥3), neutropenia (24.4%; 9.8% G≥3) and thrombocytopenia (17.1%; 4.9% G≥3). Fatigue (60.9%; 4.9% G≥3) and nausea (52.2%; 2.4% G≥3) were the most common non-hematologic TEAEs. One (2.4%) patient died due to drug-related pneumonitis. In conclusion, T-DXd showed impressive activity and was consistent with the known safety profile in patients with HER2-positive and HER2-low ABC with a history of BMs and/or LMC. These results justify Destiny Breast 12 and reinforce the need to include this patient population in clinical trials evaluating HER2-targeted agents.
OCTS-05 BRAIN BIOMARKER ANALYSIS OF LIKELY TUMOR ORIGIN (BALTO)- A PROSPECTIVE STUDY FOR THE DETECTION/DIAGNOSIS OF CNS TUMORS FROM CSF USING THE BELAY SUMMIT™ ASSAY
Authors: Holdhoff Matthias , Kumthekar Priya , Reddi Honey , Reiners Stephanie , Bettegowda Chetan 
Published: August 2024

Abstract
Currently, there is a lack of adequate sensitive and specific non- or minimally invasive molecular biomarker technologies to aid in the diagnosis of Central Nervous System (CNS) cancers in patients suspected of having disease based on clinical or radiological findings. Cerebrospinal fluid (CSF) cytology has low sensitivity, necessitating tissue sampling through invasive neurosurgical procedures in most cases. Tumor-derived DNA (ctDNA) has shown potential to detect brain and spinal cord neoplasms by evaluating CSF, offering promise in monitoring dynamic changes in disease burden and evolving mechanisms of resistance in patients undergoing treatment. In this study, we aim to bridge the gap in cytology by utilizing the Belay Summit™ assay, a next generation DNA sequencing-based platform, to identify and characterize tumor derived DNA in CSF across a diverse population in comparison to the current standard of care of histopathology and CSF cytology. Our objective is to demonstrate the performance of the Belay Summit™ assay to help clinicians diagnose and manage patients with suspected or known brain cancer by characterizing the ctDNA present in CSF based on methylation, mutation, and chromosomal copy number. The primary endpoint of this study is to assess the sensitivity and specificity of this novel assay as compared to the current standard of care. This is a multi-center study in patients with known or suspected CNS tumors, with a planned enrollment of 400 individuals. CSF will be collected as part of the standard clinical care in which 2-10 ml will be sent to Belay Diagnostics for testing using the Summit™ assay. Results will be returned to the investigator, and de-identified data will be evaluated to determine the sensitivity and specificity of the assay in the detection/diagnosis of CNS tumors from CSF.
OCTS-06 A PHASE II STUDY OF NIVOLUMAB WITH IPILIMUMAB AND CABOZANTINIB IN PATIENTS WITH UNTREATED RENAL CELL CARCINOMA BRAIN METASTASES
Authors: Wang Jianbo , Campbell Matthew , Shah Amishi Y , Goswami Sangeeta , Msaouel Pavlos , Alhalabi Omar , Hahn Andrew , Kovitz Craig , Bagi Jana , Araujo John , Gao Jianjun , Lin John , Zurita Amado , Jonasch Eric , Corn Paul , Tannir Nizar 
Published: August 2024

Abstract

BACKGROUND
The incidence of brain metastases(mets) at the diagnosis of renal cell carcinoma (RCC) is 1.51%, and around 12% of patients(pts) with advanced RCC (aRCC) had brain mets. Brain mets confer a poor prognosis. Although systemic therapies including tyrosine kinase inhibitors and immune checkpoint inhibitors have been explored in aRCC pts with brain mets, prospective data are lacking. Cabozantinib was FDA approved for pts with aRCC and retrospective studies have suggested activity in patients with intracranial tumors. The phase III COSMIC-313 trial recently evaluated cabozantinib in combination with nivolumab and ipilimumab and demonstrated significantly improved progression-free survival (PFS) in previously untreated pts with aRCC. However, the role of this combination in aRCC pts with brain mets remains undefined. We propose a study to assess the safety and efficacy of cabozantinib in combination with nivolumab/ipilimumab in RCC pts with untreated brain mets.

METHODS
This is a phase II study to assess the safety and efficacy of the combination of nivolumab with ipilimumab and cabozantinib in pts with untreated brain mets from RCC. Planned accrual is 40 pts. Pts will receive nivolumab (3mg/kg) and ipilimumab (1mg/kg) IV every 3 weeks for 4 doses and cabozantinib 40mg daily. Then pts will be treated with nivolumab 480mg IV Q 4 weeks and cabozantinib 40mg daily. A lead-in group of 6 pts will be closely monitored for dose limiting toxicities (DLT). If stopping criteria (&gt;3 patients develop DLTs) is met, then treatment will be switched to nivolumab plus cabozantinib omitting ipilimumab. The primary objective is intracranial progression free survival (PFS). Secondary objectives include intracranial safety, objective response rate (intracranial + extracranial) by modified RECIST v1.1 and RECIST v1.1, extracranial PFS, overall survival and correlative studies. As of 4/2024, Lead-in group has been completed with acceptable rate of DLT. Clinical trial information: NCT05048212.
OCTS-09 THE PROSPECTIVE PHASE II COG-SRS TRIAL: AN UPDATE ON COGNITIVE-SPARING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Puett Connor , Hopper Austin , Connor Michael , Karunamuni Roshan , Sanghvi Parag , Kim Grace , Bruggeman Andrew , Tringale Kathryn , Moiseenko Vitali , Farid Nikdokht , McDonald Carrie , Hattangadi-Gluth Jona 
Published: August 2024

Abstract
Stereotactic radiosurgery (SRS) plans that respect the neural correlates of cognition should result in better post-treatment cognitive outcomes compared to standard plans. The prospective phase II COG-SRS Trial is designed to test this hypothesis. To date, 92 treatment plans that ensure standard tumor coverage but also constrain doses to selected eloquent white matter tracts and the hippocampi have been developed for 70 patients with a total of 158 brain metastases arising from various cancer types. The most common primary malignancies were lung (40%) and breast (26%). Over 90% of plans treated 3 or fewer lesions. 80% of plans successfully met the 0.03cc dose (D0.03) constraint to all white matter tracts, and 95% met the D0.03 constraint to the hippocampi. Cognitive testing of immediate and delayed recall (Hopkins Verbal Learning Test-Revised) and letter and category fluency (Controlled Oral Word Association) is available in 66% (46/70) of patients to date, 76% (35/46) of whom had received systemic therapy and 20% (9/46) surgical resection prior to SRS. Comparing pre- and 3-month post-radiotherapy performance, 52% (24/46) had a significant decline in cognitive performance, defined as a decrease of at least 1 standard deviation in the score on one or more tests. In patients for whom the D0.03 constraint could not be met in white matter tracts, 70% declined significantly. In comparison, only 47% declined when the D0.03 constraint was met. Correlating associations between specific white matter tract doses, volumetric white matter tract changes assessed by serial MRI, and performance on the full battery of neuropsychological testing will be possible when trial data are finalized. These results should help in defining the radiosensitivity of distinct neuroanatomic regions and in guiding future dose-constraint planning protocols, as this new arena of cognitive-sparing SRS continues to be explored.
OCTS-10 PREOPERATIVE TUCATINIB IN PATIENTS WITH HER2 AMPLIFIED/MUTANT BREAST OR OTHER SOLID TUMORS WHO REQUIRE BRAIN METASTASIS RESECTION: A WINDOW OF OPPORTUNITY STUDY (WINHER2 STUDY, NCT05892068)
Authors: Ferraro Emanuela , Solomon Verna , Thompson Vanessa , Pollina Rachael , Pittner Brian , Moss Nelson , Seidman Andrew D 
Published: August 2024

Abstract

BACKGROUND
Tucatinib is a potent and selective HER2 tyrosine kinase inhibitor currently approved for patients with metastatic HER2-positive (+) breast (BC) or colorectal cancer (CRC). In combination, it has demonstrated significant intracranial activity in both preclinical and clinical studies. However, the variability of brain metastasis (BM) tucatinib uptake, and brain-specific mechanisms of resistance are unknown.

METHODS
WinHER2 is an ongoing investigator-initiated window of opportunity study of pre-operative tucatinib for patients with HER2+ or mutant BM requiring surgery. The objective is to identify mechanisms of resistance of tucatinib in the brain. With the hypothesis that reduced tucatinib tumor penetration may limit its therapeutic efficacy, the primary endpoint is tucatinib brain drug concentration in the resected metastases, blood, and cerebrospinal fluid. The secondary objectives are the characterization of resistance mechanisms using a multi-omics approach including proteomics by immunohistochemistry and electron microscopy (efflux pump and blood brain tumor barrier analysis), genomics, and transcriptomics of the tumor and its microenvironment. The study design includes three parallel cohorts: Cohort A: patients with HER2+ BC progressing while on tucatinib (n=10); Cohort B: patients with tucatinib-naïve HER2+ BC (n=10); Cohort C: patients with HER2-mutant BC, or HER2 amplified or mutant CRC/lung/gastroesophageal cancer (n=8). The main inclusion criteria are indication for craniotomy related to radiological/clinical BM progression and history of HER2+ or mutant disease. All patients receive 4 days of tucatinib at the standard dose pre-operatively. Preoperative perfusion brain MRI is included for correlations between perfusion parameters and tumor drug levels. Additionally, CNS-specific survival outcomes will be evaluated for cohorts B and C. Differences in cohorts A and B will be assessed by descriptive statistics for primary and secondary endpoints. This study aims to provide a biological basis for innovative future strategies to improve the prognosis of patients with HER2-altered BM, which currently remains poor.