bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMRK-13 CSF TUMOR CELL (CSF-TC) DETECTION, QUANTIFICATION AND BIOMARKER ASSESSMENT HELPS IN CLINICAL MANAGEMENT OF BREAST CANCER AND NON-SMALL CELL LUNG CANCER PATIENTS HAVING LEPTOMENINGEAL DISEASE (FORESEE STUDY, NCT05414123)
Authors: Kumthekar Priya , Youssef Michael , Yang Jonathan , Piccioni David , Beruti Sue , Gillis Laura , Gordon Kelly , Blouw Barbara , Moore Melissa , LaFrance Norman , Hedrick Marc , Nagpal Seema 
Published: August 2024

Abstract
Leptomeningeal metastases (LM) in solid tumors is difficult to diagnose and treat, and occurs when there are cancer cells in the cerebrospinal fluid (CSF)/pia and arachnoid. Current standard of care methods to diagnose or assess treatment response of LM (Clinical Evaluation, MRI and Cytology) have limited sensitivity and specificity. This creates challenges for physicians to manage LM or determine the best course of treatment. The FORESEE Study was a multi-center, prospective clinical trial evaluating a novel diagnostic platform, CNSide, that aimed to overcome these challenges. The FORESEE study enrolled patients with breast or non-Small Cell Lung Cancer (NSCLC) with suspicion of or confirmed LM. CNSide can detect and quantify tumor cells in the CSF from patients with breast cancer or NSCLC having a suspicious or confirmed LM as well as identify actionable mutations in the CSF via Fluorescent In Situ Hybridization (FISH) and next-generation sequencing. The primary end point was to determine the impact of CNSide on physician treatment decisions. Secondary endpoints included evaluating the clinical performance of CNSide vs. cytology in tumor cell detection (sensitivity, specificity, PPV and NPV). The study enrolled 40 patients (22 breast cancer and 19 NSCLC). Each patient underwent standard of care diagnostic evaluations at baseline and at three follow up timepoints through their treatment. CNSide aided clinical decision making in 93% (50/54) of the clinical decisions. At baseline, 39 patients were assessed, showing that CNSide confirmed a positive LM diagnosis in 15% (6/39), a negative LM diagnosis in 8% (3/39), progression in 15% (6/39), resolution in 15% (6/39) and no progression, or resolution in 36% (14/39) of the patients. CNSide informed the specific drug selected for treatment in 26% (10/39) patients at baseline and demonstrated clinical high utility. The FORESEE data is undergoing ongoing analysis; full analysis will be presented at the meeting.
DSAI-02 AN AUTOMATED TRAJECTORY OPTIMIZATION ALGORITHM FOR LASER INDUCED THERMAL THERAPY (LITT) FOR BRAIN TUMORS
Authors: Lu Yonggang , Krucoff Max 
Published: August 2024

Abstract

PURPOSE
To plan laser probe trajectories for magnetic resonance imaging (MRI)-guided laser induced thermal therapy (MRIgLITT), current clinical practice relies on manual inspection on MRI images to find a path with minimum safety risk and maximal treatment impact. This process is empirical and time-consuming with potentially suboptimal solutions. The study aims to develop an automated trajectory optimization algorithm for reducing planning time and improving patient safety.

METHODS
Seven brain tumor cases treated with MRIgLITT were retrospectively reviewed. For each case, preoperative MRIs were auto-segmented for 16 brain tissue types (e.g., skull, artery, vein, etc.) using a deep learning-based head modeling algorithm (Sim4life v8.0, ZMT Zurich MedTech AG, Switzerland); Then an optimize trajectory was generated by searching potential trajectories based on a priori established criteria, such as trajectory feasibility (angle to the skull, not entering in the face or neck, etc.), safety risk (avoiding blood vessels and optical cranial nerves, etc.), and expected treatment efficacy (100% tumor coverage with assumed 1.5 cm laser radiation radius). The predicted optimal trajectories were finally compared with the trajectories prescribed from clinical procedures, and differences were analyzed descriptively.

RESULTS
For each case, the algorithm took approximately 4 minutes for brain tissue segmentation and 2 minutes for trajectory optimization on a desktop computer. The predicted trajectories from 7 cases were visually matched with prescribed trajectories with offsets of entry point (9.94±5.97 mm), target point (4.59±2.23 mm) and trajectory length (5.90±3.69 mm). Qualitative review of these trajectories confirmed their adherence to the above principles, meaning they would likely have been usable for their respective cases.

CONCLUSION
We demonstrated the feasibility and efficiency of an automated trajectory optimization algorithm for MRIgLITT. Future studies will improve the performance of brain tissue segmentation, assess anticipated versus achieved tissue treatment volumes, and prospectively evaluate application into case planning.
IMUN-04 COMBINING CHECKPOINT BLOCKADE AND LASER ABLATION FOR PROGRESSIVE NON-SMALL CELL LUNG CANCER BRAIN METASTASES
Authors: Haskell-Mendoza Aden , Srinivasan Ethan , Gonzalez Ariel , Reason Ellery , Jackson Joshua , Wachsmuth Lucas , Lerner Emily , Underwood Delaney , Buckley Evan , Zaidi Saif , II James Herndon , Fecci Peter 
Published: August 2024

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases (BM). Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB) and activate an anti-tumor immune response. However, LITT also disrupts the blood-brain barrier, causing transient peritumoral edema. Accordingly, information on safety and feasibility of this combination in BM is needed.

METHODS
All patients receiving LITT for radiographically progressive non-small cell lung carcinoma (NSCLC) BM at a single center from 2015 – 2023 were retrospectively reviewed. Combination therapy was defined as ICB within 6 weeks of LITT. Clinical data, post-LITT freedom from local progression (FFLP), and overall survival (OS) were collected. Adverse events (AEs) were evaluated according to Common Terminology Criteria.

RESULTS
Eighteen patients received LITT + ICB to a total of 19 lesions. Median time between therapies was 2.29 weeks (range 0.85 – 5.98). In comparison to NSCLC patients receiving LITT alone (n = 25), there was no decrement in % ablation (98 vs 95%, P = 0.1), length of stay (1 vs 1 days, P = 0.91), home discharge (100 vs 92%, P = 0.5), or 30-day readmissions (15.8 vs 16%, P = 0.99). Despite decreased preoperative steroid use (P = 0.0098), patients receiving LITT + ICB discontinued steroids at a median of 11 (4 – 147) days post-LITT vs. 24 (3 – 242) days for patients receiving LITT alone (P = 0.62). At study cutoff, 18/19 (94.7%) lesions in the LITT + ICB group and 22/25 (88.0%) in the LITT only group were locally controlled. There were 3 and 5 AEs ≥ Grade 3 in the LITT + ICB and LITT alone group, respectively.

CONCLUSIONS
Combination LITT and ICB does not compromise procedural outcomes and may favorably impact local control in NSCLC. Prospective studies are needed to assess biomarkers of immune response.
MMOD-03 CRANIOTOMY RATES FOR BRAIN METASTASES AFTER INTRODUCTION OF IMMUNOTHERAPY
Authors: Pelcher Isabelle , Begley Sabrina , Sreenivasan Sanjeev , Ziemba Yonah , Travaglia Isabella , Ratra Avi , Schulder Michael 
Published: August 2024

Abstract
Immunotherapy has been found effective for many patients with solid tissue cancers, with long-term remission of systemic disease and even of brain metastases from these treatments alone. We sought to determine whether the rates of craniotomies have changed since the introduction of immunotherapy. Institutional data of brain metastases incidence was gathered from 2011-2022 and included demographics and primary cancer information. A total of 885 samples from 789 unique patients were analyzed. National data were queried from the NSQIP database from 2011-2022 to include patients surgically treated for brain metastases for a total sample of 14,494 cases. A Craniotomy for Metastasis Index (CMI) was calculated and plotted over time. The most common institutional primary cancers were lung (46.1%), breast (17.4%), and gastrointestinal (10.1%) cancer. The most common lung cancer subtype was adenocarcinoma (57.11%) followed by non-small cell lung cancer (NSCLC) (11.52%). Institutionally, the CMI showed a non-significant decrease in craniotomies (R2=0.0545, p=0.46). When comparing the institutional CMI between 2011-2016 and 2017-2022, there was no significant change (p=0.37). Nationally, the CMI had a significantly positive slope of 0.03 (R2=0.544, p=0.006). When comparing the national CMI between 2011-2016 and 2017-2022, there was a significant increase in craniotomies (p=0.005). Despite the increasing efficacy of immunotherapy in the treatment of patients with brain metastases, the number of craniotomies remained constant institutionally and increased nationally. Possible explanations for these findings include improved surgical techniques that have made resection safer, along with longer survival of patients with systemic cancer who then develop metastatic brain tumors.
MMOD-06 IMPACT OF SYSTEMIC THERAPY TIMING AFTER STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN-ONLY METASTASES
Authors: Qazi Jamiluddin , Carpenter David , Broadwater Gloria , Van Swearingen Aamanda , Lent Jim , Arshad Muzamil , Chmura Steven , Bansal Rani , Fecci Peter , Kirkpatrick John , Alder Laura , Salama Joseph , Floyd Scott , Mullikin Trey , Anders Carey 
Published: August 2024

Abstract
The impact of systemic therapy (ST) on outcomes for patients with brain-only recurrence in the absence of extracranial disease (ECD) is not well established. We compared outcomes between patients with brain-only metastases (BrM) treated with stereotactic radiosurgery (SRS) who received ST ≤3 months (mos), &gt;3mos, or not at all after SRS. We identified patients completing a course of SRS, without ECD, across two institutions from 1/2015-12/2020. Intracranial progression after SRS was determined by radiographic recurrence on brain MRI. Overall survival (OS) and intracranial progression free survival (iPFS) estimates were generated via the Kaplan-Meier method. 342 pts with brain only metastases were identified. Primary sites included lung (73%), breast (12%), and additional sites (15%) including melanoma/skin, genitourinary, gastrointestinal, head/neck, and other/unknown. Almost half, 169 (49%), received no ST, 80 (23%) received ST ≤3mos, and 93 (27%) received ST &gt;3mos after SRS. Median age was younger in the ST &gt;3mos cohort (60.5yo versus overall median age 65.3yo, p=0.0002). Performance status, race, and gender were not significantly different between groups. Median OS differed significantly between groups: ST ≤3mos with 24.9mos (95%CI: 16.6-51.1), ST &gt;3mos with 27.9mos (95% CI: 20.6-37.5), and no ST after SRS with 11.0mos (95%CI: 8.9-17.5), p=0.002. Median iPFS differed significantly between groups: ST ≤3mos with 16.1mos (95% CI: 16.1-33.7), ST &gt;3mos with 8.9mos (95% CI: 6.9 – 13.5), and no ST after SRS with 10.0mos (95% CI: 6.7- 15.1). However, iPFS was non-significant in multivariate analysis adjusting for age, performance status, metastatic burden, tumor type, and prior ST. In a multi-institutional cohort of patients with BrM, ST after SRS improves OS regardless of timing. Additionally, ST ≤3mos appears to improve iPFS compared to ST &gt;3mos after SRS, which warrants further investigation. Appropriate patients with BrM should be routinely referred for a multi-disciplinary discussion of systemic therapy following SRS.
MMOD-08 REAL WORLD TREATMENT PATTERNS AND OUTCOMES FOR PATIENTS WITH MELANOMA BRAIN METASTASIS: A SINGLE CENTER EXPERIENCE
Authors: Ladwa Amrita , Elghawy Omar , Friedberg Jacob , Kaur Varinder 
Published: August 2024

Abstract

BACKGROUND
Traditionally, patients with melanoma brain metastasis (MBM) have poor survival outcomes. We investigated real-world treatment patterns and outcomes of patients with MBM.

METHODS
We conducted a retrospective, single-institution analysis of patients with malignant melanoma who received immunotherapy and developed synchronous or metachronous MBM. Real world treatment patterns, therapy sequencing and outcomes were analyzed in detail.

RESULTS
Of 453 patients with melanoma who received immunotherapy at our center, 138 developed brain metastases. Median age was 59 years, 63% were male, and 91% were white. 72% had cutaneous melanoma, 5% had mucosal, 4% had acral, and 19% had other subtypes. BRAF V600 mutation was positive in 36%. 44% had synchronous MBMs (within 30 days of diagnosis of unresectable/metastatic disease), and 56% had metachronous MBMs. 3% had solitary MBMs without concurrent extracranial disease. For patients with metachronous MBMs, median time to CNS metastasis from stage IV diagnosis was 11 months (range, 1 – 211 months). 69% of patients had 1 – 5 MBMs, 20% had 6 – 10 MBMs, and 11% had 11 or more MBMs. For first-line therapy, 66% received stereotactic radiosurgery (SRS) or gamma-knife radiosurgery (GKRS), 14% underwent surgical resection, 12% received whole-brain radiation therapy (WBRT), 88% received systemic therapy (with or without other therapy), and 72% received systemic therapy and loco-regional therapy. Systemic therapies included ipilimumab/nivolumab (36%), nivolumab alone (10%), pemboliaumab alone (20%), ipilimumab alone (23%), BRAF/MEKi (6%), or other (11%). 54% of patients who received treatment and/or were followed with imaging experienced disease progression. Median overall survival (OS) for the entire cohort was 66 months (range, 1 – 407 months).

CONCLUSION
Most patients with MBM receive a combination of loco-regional interventions and systemic therapy. Real-world outcomes for patients with MBMs have improved with newer treatments.
MMOD-12 PATHOLOGIC INCIDENCE OF TUMOR POSITIVITY VS ONLY NECROSIS AFTER PRIOR RADIATION IN PATIENTS UNDERGOING SURGICAL EXCISION FOR PRESUMED BRAIN METASTASIS RECURRENCE: INSIGHT FROM A PROSPECTIVE MULTICENTER REGISTRY
Authors: Kotecha Rupesh , McDermott Michael , Lee Stuart , Peach Matthew , Richardson Angela , Floyd John , Patel Toral , Wardak Zabi , Sloan Lindsey , Ferreira Clara , Neil Elizabeth , Hunt Matthew , Shen Colette , Wasilewski Andrea , Wanebo John , Smith Kris , Chamoun Roukoz , Robin Adam , Lee Ian , Leng Lewis , Patel Akash , Zhu James , Hanft Simon , Zeller Sabrina , Aizenberg Michelle , Rodriguez Analiz , Choutka Ondrej , Hoang Kimberly , Nowlan Adam , McCracken David , Dunbar Erin , Brachman David , Garcia Michael , Patel Sita 
Published: August 2024

Abstract

PURPOSE/OBJECTIVE(S)
Determining true recurrence versus necrosis alone after previous radiation therapy (RT) for brain metastasis based on imaging alone is difficult. Proper diagnosis is essential, as further radiation is contraindicated in the setting of radiation necrosis without tumor (TUM-). To better understand the rate of pathologic tumor positivity (TUM+) vs TUM-, we examined frozen section results from a cohort of patients with prior same-site RT undergoing resection of presumed recurrent brain metastasis (RBM).

MATERIALS/METHODS
Rates of intraoperative frozen section pathology disclosing tumor +/- necrosis (TUM+) or necrosis without tumor (TUM-) were examined in patients undergoing resection for presumed RBM after prior same-site RT. All cases had been prospectively enrolled on a multi-institution registry for patients undergoing resection and intraoperative cesium-131 collagen tile brachytherapy (NCT04427384)(GammaTile, GT Medical Technologies, Tempe AZ, USA). Preoperative evaluation varied by center, and patient demographics, primary site, lesion size, and prior therapies were also examined.

RESULTS
From 10/2020 to 2/2024 60 patients (64 lesions) underwent resection and intraoperative frozen section pathologic evaluation. Per patient, primary sites were 53% lung, 15% melanoma, 13% breast, 7% renal, and 10% other. F:M ratio was 31:29; median age 62, maximum preoperative diameter 2.9 cm, and median time from prior RT 15.4 months. Across all histologies TUM+ was seen in 88% (53/60) and TUM- in 12% (7/60). Rates of TUM- by primary type were highest for lung (16%), breast (13%), and melanoma (11%). The TUM- rate for lung metastasis was 16% vs 7% for non-lung origin. All TUM- patients received RT and prior chemotherapy, immunotherapy, or both.

CONCLUSION
For all previously irradiated metastasis, pathology demonstrated a 12% rate of TUM-. As all cases necessitated surgery, the adverse event grading would be ≥ Gr 4. These findings highlight the importance of pathologic confirmation before undertaking re-irradiation for presumed radiographic recurrence.
NIRL-09 PERI-AMPULLARY CARCINOMA METASTASIS TO THE BRAIN: A RARE CASE REPORT FROM INDIA
Authors: Sangwan Arushi , Mishra Saurabh , Rana Shaleen 
Published: August 2024

Abstract
Peri-ampullary carcinoma refers to a group of neoplasms arising from the head of the pancreas, the distal common bile duct (CBD), and the duodenum. It is typically associated with metastases to intra-abdominal sites, distant lymph nodes, lungs, and bone. Metastasis of peri-ampullary carcinoma involving the brain is extremely rare, with less than five reported cases in current literature. We present a case of a 77-year-old male patient, who presented with a two-week history of diffuse abdominal pain and distension associated with post-prandial vomiting. A comprehensive workup involving diagnostic imaging revealed moderate ascites, dilated CBD, splenomegaly, and a heterogeneously enhancing periampullary lesion. Multiple heterogeneously enhancing lesions in the lungs with metastatic features were also seen. Whole body PET-CT showed a hypermetabolic minimally enhancing nodular lesion at the distal CBD. Other lesions with metastatic features were also noted, including multiple retroperitoneal nodes, multiple lung masses, and a hypermetabolic mediastinal node. Bronchoscopy was normal, however, a side-viewing endoscopy biopsy of the peri-ampullary mass confirmed a high-grade malignancy. After counselling the patient at length regarding available treatment options, sphincterectomy and CBD stenting were performed. However, the patient returned after two weeks with confusion, slurring of speech, and worsening abdominal distension. MR imaging demonstrated a heterogeneously enhancing mass in the left frontotemporal region, associated with a disproportionate amount of surrounding edema and mass effect with a significant midline shift. The patient was admitted to the intensive care unit, and the CBD stent was switched with an uncovered self-expandable metallic stent. Unwilling to undergo further treatment, the patient was discharged with scheduled close follow-ups. Though metastasis of peri-ampullary carcinoma to the brain is uncommon, this case highlights the importance of being cognizant of its clinical and radiological features to ensure prompt diagnosis and treatment.
NIRL-14 RADIOGRAPHIC STUDIES ON THE THRESHOLD OF HUMAN CAPACITY IN EARLY DETECTION OF SMALL BRAIN METASTASES ESTABLISH A BASIS FOR DEVELOPING ARTIFICIAL INTELLIGENCE RECOGNITION TECHNOLOGY IN BRAIN MRI
Authors: Zhang Isabella , Burr Justin , Wang Shuo 
Published: August 2024

Abstract

BACKGROUND
Brain Metastases are the most common cancers in central nervous system and carry poor prognosis in cancer patients with their rapidly growing nature. Early identification of these tumors is crucial in improving patient survival. This investigation aims to study the rate of human error in missing early brain metastases and factors associated with the threshold of sensitivity of human eyes at the professional level.

METHODS
The ­database from a single institution was used which included patients with new brain metastasis diagnosed based on brain magnetic resonance imaging (MRI) who also had previous MRI scan(s) 1-6 months before diagnosis and no exposure to whole brain radiotherapy. The brain MRI used for diagnosis of brain metastasis and the MRI performed 1-6 months prior were reviewed. Based on the location of the newly diagnosed tumor, the corresponding location in the previous MRI was assessed for a missed incidence of a preexisting tumor. The sizes of the missed tumors were then measured to assess the threshold of human eyes in detecting metastases.

RESULTS
The percentage of missed metastases was 44% (56/126). The mean size of missed metastases was 3.0 millimeters (range 1.2 mm to 7.7 mm). No clinical factors were significantly associated with higher rate of missed diagnosis. The most likely reason for the missed diagnosis is the tiny size although visual distraction seems to play a role including adjacent contrast-enhancing structures such as blood vessels.

CONCLUSIONS
The results show a high rate of human error for missing small metastases even with high level of expertise indicating the limits of human capacity to reliably detect brain metastases at 1-2 mm in size. These results justify the development of artificial intelligence-based recognition to assist neuroradiologists in diagnosis. Our data support current standard practice of surveillance brain MRI every 3-6 months for patients with history of brain metastasis.
NVTG-03 IDENTIFYING THE DRIVERS OF EARLY BRAIN METASTASES ESTABLISHMENT IN BREAST CANCER PATIENTS
Authors: Ivanova Alyona , Cho Matthew , Wu Megan , Munoz David G , Das Sunit 
Published: August 2024

Abstract
Breast cancer is the most common type of cancer in women. It is also the 2nd most common cause of brain metastases (BrM), with 30-50% of breast cancer patients developing BrM over the course of their disease. Despite aggressive therapy and novel systemic treatment options, prognosis for these patients remains poor. The objectives of our work were to identify the underlying genomic and transcriptomic signatures that characterise early BrM establishment in patients with breast cancer, and to identify brain-intrinsic molecular mechanisms critical to BrM development. We performed transcriptomic and genomic profiling on fresh frozen (FF) brain metastases tumour samples of patients who required surgical resection of an intracranial metastatic early (&lt;3 years from initial diagnosis) or late (&gt;3 years from initial diagnosis) in the disease course. Findings were validated by immunohistochemistry and immunofluorescence staining for genes of interest in BrM, matched primary breast tumour samples, and healthy brain tissue. The findings were complemented with scRNA sequencing studies to resolve cellular contributions of individual cell types and subtypes and uncover specific cell-type interactions in BrM establishment. In patients with early metastatic disease, pathway enrichment analysis identified TGF-β pathway upregulation, which stimulates epithelial-to-mesenchymal transition, integrin-mediated invasion, recruitment and activation of cancer-associated fibroblasts. We identified collagen-extracellular matrix interactions as key oncogenic features of the metastatic tumour microenvironment. We have selected lead candidates that can play significant role in early colonisation of breast cancer cells to the brain from the primary breast tumour and enhance tumorigenesis. These markers will be challenged in an in vivo brain metastasis model to attenuate the establishment of metastatic disease. Our goal is to identify a modifiable marker that could be clinically targeted to prevent the establishment of brain metastases in patients diagnosed with breast cancer.