bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMD-10. The role of immune checkpoint inhibitors in leptomeningeal disease: a systematic review
Authors: Palmisciano Paolo , Haider Ali S , Nwagwu Chibueze D , Wahood Waseem , Sagoo Navraj S , Yu Kenny , Ene Chibawane I , O’Brien Barbara J , Cohen-Gadol Aaron A , El Ahmadieh Tarek Y 
Published: August 2021

Abstract

Background
Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown.

Methods
We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted.

Results
We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months.

Conclusion
ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.
LMD-17. Neoplastic meningitis in lung cancer: retrospective review of clinical features, diagnosis and outcome in adult patients
Authors: Yorio Florencia , Blaquier Juan Bautista , Calabrese Bernadette , Cerrato Sebastián , Diez Blanca , Muggeri Alejandro 
Published: August 2021

Abstract

Background
Neoplastic Meningitis (NM) is a lethal complication of cancer. Its incidence is rising and in 10% of the cases NM is the first manifestation of the disease. Diagnosis relies on the clinical manifestations, neuroimages, and finding of malignant cells in cerebrospinal fluid (CSF). Diagnosis is often challenging due to the low sensitivity of the different diagnostic modalities. The aim of this study is to identify the clinical features, diagnosis, treatment and outcome of lung cancer patients with NM.

Methods
Clinical records from patients with diagnosis of lung cancer and NM between 2011–2021 were retrospectively reviewed at a tertiary neurological center in Buenos Aires, Argentina.

Results
Twenty-seven patients were included. Median age was 58 years (IQR 52–64). 17 (65%) were female. Twenty-four patients had non-small cell lung cancer (91% adenocarcinoma), two had neuroendocrine lung cancer and one small cell lung cancer. In 19 (70%), meningeal involvement was a result of progressive disease from previously diagnosed cancer. In 12 (44%) patients meningeal disease developed posterior to parenchymal brain metastases surgical approach, 5 (41%) with posterior fossa craniotomy. Headache was the most frequent symptom (53%). CSF analysis was abnormal in 13 (48%) patients, with positive cytology in 10 (37%). Meningeal enhancement was detected with magnetic resonance imaging of brain or spine in 24 (92%) patients. Twenty-one (77%) patients received oncological treatment, 14 (51%) with chemotherapy (8 systemic, 3 intrathecal and 3 intrathecal plus systemic). Thirteen (48%) patients underwent treatment with either immunotherapy or target-therapy. 11 patients underwent whole brain radiotherapy. Median overall survival was 7 months (CI 95%: 3.5–10.4).

Conclusion
Headache was the most frequent symptom. Ninety-two percent of patients had meningeal pathological enhancement in high-quality MRI with gadolinium contrast of brain and spine. Despite median survival was poor (7 months), small subsets of these patients (22%) survived more than 2 years.
LMD-19. Anatomic and Surgical Factors Predict Development of Leptomeningeal Disease in Patients with Metastatic Melanoma
Authors: Lowe Stephen , Wang Christopher P , Brisco Amanda , Ahmed Kamran , Vogelbaum Michael A , Liu James K C 
Published: August 2021

Abstract

Background
Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, portending a poor prognosis with an estimated median survival of 4–6 weeks if left untreated. Several reports have suggested surgical resection, particularly piecemeal resection, as a potential causative factor. Herein, we explore if surgical and anatomical factors are correlated with development of LMD in patients with melanoma brain metastases.

Methods
Patients treated at our institution between 1999–2019 for primary melanoma with brain metastasis were compiled into a database based on ICD9/10 coding. 1,079 patients with melanoma brain metastases and appropriate imaging were identified, and 834 patients with a minimum of 3 months’ follow up were included. Patients were dichotomized by development of LMD or lack thereof. General demographic information, surgical and anatomic data, and ventricular access during surgery were investigated as possible correlative factors for the development of LMD.

Results
On univariate analysis, female gender (p=0.033), presence of dural metastasis (p=0.018), presence of periventricular lesions (p&lt;.001), presence of intraventricular lesions (p&lt;.001), and ventricular access during surgery (p&lt;.001) were significantly associated with LMD. Patients undergoing surgery, or those undergoing surgery without ventricular access, were not at higher risk of LMD. Administration of immunotherapy, either as first-line or salvage therapy, did not impact rates of LMD. On multivariate analysis, female gender (p=.033), presence of periventricular lesions (p&lt;.001), presence of intraventricular lesions (p&lt;.002), and presence of dural metastasis (p=0.032) were significantly associated with development of LMD. In patients who had surgery, iatrogenic ventricular access (p&lt;.001) was significantly correlated with LMD.

Conclusions
In a retrospective cohort of patients with melanoma metastatic to the brain, those patients with pre-existing lesions in contact with the CSF space are more likely to develop LMD than those who do not. In addition, iatrogenic access to the CSF space during surgery is highly correlated with LMD development.
LMD-21. Headache Improvement Predicts Survival after CSF diversion in Leptomeningeal Disease
Authors: Robin Adam , Haider Sameah , Distefano Natalie , Reiner Anne , Tabar Viviane , Pawloski Jacob 
Published: August 2021

Abstract

Background
Leptomeningeal carcinomatosis (LMD) is a seeding of the leptomeninges by malignant cells. Clinical, treatment and patient-related factors have been described in patients with LMD. Current data are limited by small sample size, particularly in patients undergoing ventriculoperitoneal shunting (VPS) as part of the treatment regimen.

Objective
This study presents the largest cohort of LMD patients in the literature undergoing cerebrospinal fluid (CSF) diversion and seeks to identify prognostic factors related to survival.

Methods
A retrospective review of patients diagnosed with LMD between 2010 and 2016 at a quaternary referral center was performed. Cox proportional hazards modeling was utilized to identify variables associated with improved overall survival from LMD diagnosis. Overall survival was depicted using Kaplan-Meier methodology. Competing risk methodology was used to identify variables associated with VPS, considering death as a competing event.

Results
Of the 314 patients identified, 112 underwent VPS placement. The median overall survival from LMD diagnosis was 3.9 months (95% CI: 3.2–4.4). The presence of headaches, increased opening pressure, and gait difficulty increased the likelihood of VPS placement (all p&lt;0.05). VPS, older age, lower Karnofsky Performance Status (KPS), higher opening pressure and CSF nucleated cell count (NCC) increased the risk of death (all p&lt;0.05). Patients reporting headache improvement after VPS had better survival (p&lt;0.05).

Conclusions
Headache, increased opening pressure and gait instability were associated with higher rate of VPS placement and may portend more aggressive disease. Headache improvement following VPS is a favorable prognostic sign, suggesting survival advantage for patients with hydrocephalus undergoing VPS. Age, KPS, VPS, opening pressure, CSF NCC, concomitant visceral metastases and histology-specific molecular profile impact survival.
THER-02. PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series
Authors: Mohler Alexander , Salinas Belkys , Nazur Karissa , Odia Yazmin , Lambrou Nicholas 
Published: August 2021

Abstract
Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis.
Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive.
Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1).
The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma.
MLTI-03. The relevance of the count of brain metastases for treatment and outcome in NSCLC
Authors: Reinecke David , Jünger Stephanie T , Kocher Martin , Ruge Maximilian , Ruess Daniel , Goldbrunner Roland , Grau Stefan J 
Published: August 2021

Abstract

Background and Purpose
While data reporting the number of brain metastasis as a prognostic factor for patients with NSCLC, we analyzed whether the prognostic importance of the mere count of brain metastasis in a modern, multimodal treatment setting.

Patients and Methods
We retrospectively analyzed patients treated for BM from non-small lung cancer between 2010 and 2020. Demographics, baseline characteristics, and tumor-associated parameters were retrieved from an electronic database. Prognostic factors for local cerebral control and survival were identified using the log-rank test and Cox regression analysis.

Results
We included 343 consecutive patients (male n=187, female n=156; median age 61 years). Histological subtypes were adenocarcinoma (n=283), squamous-cell carcinoma (n=42) and neuroendocrine carcinoma (n=18). The median number of BM was one (range 1–20). Single (n = 189), oligo (n=110) and multiple BM (n=44) showed in total a median follow up of 10 months (minimum 1, maximum 142). Treatment comprised surgical resection (n=218) with radiotherapy, stereotactic radiosurgery (n=125) and adjuvant systemic therapy (n=203). The median local cerebral control was 11 months (95%CI 8.5 – 13.5) and the median overall survival was 16 months (95%CI 12.8 – 19.2). The number of BM did not influence local control and overall survival rates (p = 0.234 and p = 0.210, respectively). Controlled systemic disease (HR 0.42; 95% CI 0.2284–0.633; p&lt;0.0001), clinical status (Karnofsky Performance Score &gt; 70; HR 0.41; 95% CI 0.265–0.661; p&lt;0.0001) and adjuvant systemic therapy (HR 0.38; 95% CI 0.279–0.530; p&lt;0.0001) were independent prognostic factors for survival.

Conclusions
The mere number of brain metastases is not a prognostic factor for survival and local cerebral control in a multimodal treatment setting.
MLTI-04. The Role of the Outpatient Registered Nurse in the care of Brain Metastases
Authors: Hernandez Juliana , Lavarco Amanda , David Kurt 
Published: August 2021

Abstract

Introduction
Brain metastases is a complex disease, requiring a skilled clinical team to deliver medical and surgical care. The nurse is an integral member of the interdisciplinary team. Despite this, the role of the nurse in brain metastasis care has been neglected in the literature. Moreover, while education for neurology nursing exists, there is a paucity of literature defining the nursing care specific to brain metastases. The aim of this study was to describe the essential nursing functions in brain metastases within medical and surgical clinics.

Methods
A working-group comprised of 2 registered nurses and a clinical nurse specialist in specialty brain metastases at Memorial Sloan-Kettering Cancer Center was formed. A KSA framework was used to develop a survey to assess nurses’ knowledge, skills, and attitudes regarding care of patients with brain metastases. 2 nurses were surveyed. Oncology nursing competencies were scored by medicine and surgical nurses for importance. Mean scores were calculated and ranked.

Results
Nurses consistently reported care coordination; symptom management and monitoring parameters; knowledge of treatment modalities; and referrals as key competencies. More variably endorsed competencies included access devices (implanted port and Omaya); managing immunocompromised patients; and legal issues (consent).
The nurses reported important knowledge includes screening and treatment guidelines; epidemiology; disease states including brain metastases and leptomeningeal disease; and tumor histology. Important skills include neurological exam; triage; critical thinking; and patient education. Important attitudes include being empathetic, communicative, positive, truthful, and realistic.

Conclusion
As the care of the patient with brain metastases evolves, interdisciplinary clinical practice models with advanced nursing training must occur. As the repertoire of clinical trials for patients with brain metastases continues to expand, future studies should assess the effects of specialized nursing training on clinical outcomes in patients with brain metastases.
MLTI-05. Adjuvant re-irradiation improves local control of surgically resected recurrent brain metastases
Authors: Wilcox Jessica , Brown Samantha , Reiner Anne , Young Robert , Chen Justin , Bale Tejus , Rosenblum Marc , Newman William , Brennan Cameron , Tabar Viviane , Beal Kathryn , Panageas Katherine , Moss Nelson 
Published: August 2021

Abstract

Background
The efficacy of salvage resection (SR) of recurrent brain metastases (BrM) post-stereotactic radiosurgery (SRS) is not well described. We sought to characterize the impact of adjuvant post-salvage radiation therapy (PSRT) in this setting and identify tumor-specific variables that influence local control.

Methods
Retrospective analysis of post-SRS recurrent BrM that underwent SR between 2003–2020 at Memorial Sloan Kettering Cancer Center was performed. Cases with histologically-viable malignancy were included and stratified by receipt of adjuvant PSRT within 60 days of SR (PSRT cohort) vs. observation (observation cohort). Resection-site outcomes were described using cumulative incidences and univariate and multivariate competing risks regression accounting for clustering.

Results
One-hundred fifty-five recurrent BrM in 135 patients were included. Thirty-nine (25.2%) of the post-operative cavities were treated with adjuvant PSRT, and the remaining 116 (74.8%) cavities were initially observed. Gross- or near-total resection was associated with significantly improved local control compared to subtotal resection (p=0.007). Adjuvant PSRT was associated with a reduced rate of LR at 6 months [18.0% (95%CI: 9.8–33.1%) vs. 35.9% (95%CI: 27.9–46.2%) with initial observation] and 12 months [28.8% (95%CI: 17.0–48.8%) vs. 43.9% (95%CI: 36.2–53.4%)]. On multivariate analysis, adjuvant PSRT (p=0.095), low tumor-viability within the resected BrM (p=0.17), and first-time resection (p=0.035) all independently trended towards improved local control. BrM size at SR (≥3cm vs. &lt;3cm, p=0.48), primary malignancy (p=0.35), and specific PSRT modality (whole or partial brain radiation vs. SRS, p=0.43) were not associated with differences in LR rate. Radiation necrosis (RN) was significantly increased in the PSRT cohort (HR 4.55, 95%CI: 1.26–16.39, p=0.02), though the total percentage with symptomatic RN remained low (PSRT cohort 5.1% vs observation cohort 0.9%).

Conclusions
Local control after SR of a recurrent BrM may be optimized with gross- or near-total resection and adjuvant post-operative re-irradiation, with low symptomatic RN.
OTHR-09. Accelerating Research for Breast Cancer Brain Metastasis and Leptomeningeal Disease through Patient-led Collaborations
Authors: Hodgdon Christine , Campbell Laurie 
Published: August 2021

Abstract

Patient-driven Initiative of the Metastatic Breast Cancer (MBC) Alliance
The Breast Cancer Brain Metastasis (BCBM) Initiative: Marina Kaplan Project launched in June 2020 as an official project of the MBC Alliance which includes 32 nonprofits, 12 industry partners, and 30 individual patient advocates. The Marina Project has grown to include 35members with representation from industry, research institutions, and individual patients. Nearly one-third of the group is comprised of patients living with brain metastases or leptomeningeal disease (LMD).

Disparities for Patients Living with BCBM & LMD
In the US, approximately 200,000 new cases of brain metastases are diagnosed each year[1]. Approximately 10–15% of patients with MBC will develop brain metastases, and may be as high as 30–50% for certain subtypes[2].
A diagnosis of central nervous system (CNS) metastasis often accelerates an already incurable diagnosis. CNS metastasis are difficult to image and detect, tend to have poorer prognoses with lower overall survival, and are treated with invasive therapies which can have lasting side effects. Furthermore, most clinical trials exclude patients with CNS metastasis which further hinders research.

Values and Objectives
The overarching goal of this initiative is to accelerate the scope and breadth of evidence-based CNS metastasis research by targeting entities conducting clinical trials and collaborating with them to do the following:
(i) Increase the quality and quantity of basic research;
(ii) Increase the number of clinical trials in areas where research is lacking;
(iii) Diversify the type of clinical trial interventions;
(iv) Eliminate restrictive eligibility criteria in clinical trials;
(v) Incorporate clinically meaningful trial endpoints
[1] Eichler, April F et al. The biology of brain metastases-translation to new therapies. Nature reviews. Clinical oncology vol. 8,6 (2011): 344–56. doi: 10.1038/nrclinonc.2011.58
[2] Brosnan EM, Anders CK. Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med. 2018;6(9):163. doi: 10.21037/atm.2018.04.35
OTHR-11. Comprehensive Analysis of Driver Mutation Profile in a Cohort of Lung Cancer Patients Using Targeted Gene Panel Analysis with Focus on Brain Metastatic Disease
Authors: Kazarian Marina , Cui Jin , Tocino Irena , Mahajan Amit , Aboian Mariam 
Published: August 2021

Abstract

Purpose
Approximately 228,820 people are diagnosed annually with lung cancer diagnosis and 135,720 die from their disease1. EGFR and KRAS targeted therapies have been shown to significantly improve treatment of non-small cell lung cancer (NSCLC), but they don’t apply to the majority of patients. There’s a critical need to characterize the molecular signature of patients with lung cancer and to define the proportion of patients eligible for novel targeted therapies.

Methods
IRB approval was obtained to retrospectively extract data from tertiary hospital tumor registry from 2011 to 2017. Data collected included patient demographics, targeted next generation sequencing results (50 and 150 gene panel), histology, and biopsy location in the final 2,203 patients, 715 of which were manually checked.

Findings
83.8% of patients in the lung cancer cohort that had targeted next-generation gene panel analysis demonstrated presence of at least one mutation. 50.9% of the patients in our cohort had a targetable mutation. There were 9.5% with hypermutated phenotype characterized as at least 5 mutations per sample. 1.3% of patients had at least 10 mutations per sample. We also characterize the distribution of mutations within brain metastatic lesions and demonstrate that brain metastases with hypermutated phenotype demonstrate larger volumes of edema and greater involvement of deep white matter than non-hypermutated brain metastases.

Conclusion
We present a comprehensive analysis of the molecular signature of lung cancer from a tertiary referral institution with focused analysis of brain metastases. Lung cancer brain metastases with greater than 5 mutations correspond to greater volume of edema and involvement of deep white matter.