Solitary Brain Lesion Research Articles

An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis—A Case Report and Review of the Literature

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5×3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

The Eye as a Window to the Brain: Prominent Retinal Vasculopathy Points to Neuro-Behcet Diagnosis for an Undifferentiated Solitary Brain Lesion

Objective To report a perplexing case of Behcet disease (BD) presenting as a focal parenchymal lesion that reached a diagnosis after noting a prominent retinal vasculopathy, highlighting the importance of ophthalmologic evaluation in undifferentiated CNS disease. Background BD can have variable systemic manifestations driven by a vasculitis, including oral or genital ulcers, pulmonary aneurysms, and uveitis. Neurologic involvement is present in less than 10% of patients, most commonly as a meningoencephalitis. Design/Methods We present the case of a woman who developed asymmetric sub-acute sensorineural hearing loss at age 31 followed by transient right facial weakness at age 40, and most recently presented with right facial numbness and arm weakness at age 47. Brain MRI revealed a left frontal enhancing lesion with associated T2/FLAIR hyperintensity extending from the periventricular to the juxtacortical area with a thin rim of a reduced diffusion. CSF and serum studies were negative for inflammation, infection and malignancy except for elevated ESR and CRP. Brain biopsy revealed non-specific gliosis. Persistent enhancement on MRI was noted over 3 months, with spontaneous clinical improvement. Patient endorsed insidious vision changes over recent years, and visual testing was performed. Results Dilated ophthalmic examination demonstrated striking peripheral attenuation and sclerosis of retinal vasculature, with evidence of nonperfusion and skip lesions on retinal fluorescein angiography (FA). Findings of occlusive retinal peripheral vasculopathy suggested an underlying vasculitis as the etiology of the brain lesion and prior deficits, raising the likelihood of BD. Patient was homozygous for HLA-B*51, further supporting this diagnosis even with lack of mucosal ulcers and negative history of pathergy. Conclusions Neurologic manifestations of BD can be diverse including retinal occlusive vasculopathy; ulcers are not universally present. Ophthalmologic examination, even when minimally symptomatic, can inform the diagnosis of CNS lesions. Patient was started on Prednisone, Infliximab and Methotrexate, achieving disease remission.

ODP503 Non-Small Cell Lung Cancer Metastatic to the Thyroid Gland

Abstract Introduction Metastatic disease affecting the thyroid gland is an uncommon phenomenon, with the most common primary sites being kidney, breast, lung and gastrointestinal tract. Thyroid metastases frequently occur simultaneously with spread to other sites and are rarely symptomatic. Clinical case: 73-year-old female with remote history of stage IA (T1c, N0, M0) invasive lobular carcinoma of the right breast treated with lumpectomy, radiation and tamoxifen, previous tobacco use, remote exposure to radiation during Chernobyl nuclear accident, developed progressive dyspnea on exertion. She was found to have a large left-sided pleural effusion. Thoracentesis was performed, and the cytology revealed adenocarcinoma with features favoring lung primary. Further imaging showed a left lower lobe mass with central necrosis and left hilar adenopathy, multiple pleural masses, and a small solitary brain lesion. PET-CT also demonstrated, amongst other findings, an FDG avid left lower pole thyroid nodule. Thyroid ultrasound was obtained to further characterize the lesion, which demonstrated a 0.8×1.3×1.3 cm solid hypoechoic nodule in the left mid lobe, which was thought to be corresponding to the PET avid nodule. Two additional nodules, a mixed cystic and solid measuring 1.7×2.1×2.9 cm on the right lobe, and another left-sided solid isoechoic measuring 0.8×0.7×0.9 cm, were noted. Thyroid FNA of the 1.3 cm PET avid nodule revealed rare cells in clusters, with large pale nuclei and prominent nucleoli, some with intracytoplasmic vacuoles, morphologically similar to those seen in the prior pleural fluid. Thin prep was stained with antibody to thyroglobulin, and the malignant cells showed lack of staining, supporting the diagnosis of metastatic lung cancer. Thyroid function tests were normal. Given lack of compressive symptoms, patient was maintained on her primary oncologic treatment with carboplatin and pemetrexed, and stereotactic radiation for the brain metastasis. Repeat PET-CT, performed approximately 8 months after the initial scan, showed mildly decreased focal FDG activity in the thyroid lesion. Discussion In this scenario, a patient with primary lung malignancy was found to have an FDG avid thyroid nodule which on FNA proved to be a metastatic lesion. Per some studies, such lesions can be seen in 1.4%–3% of patients who undergo surgery for suspected malignancy in the thyroid gland. Management of metastatic thyroid cancers depends on multiple factors including the primary malignancy location and staging, patient comorbidities, compressive symptoms, etc. Surgical management may be of benefit in isolated lesions in the thyroid. Conclusion When evaluating thyroid nodules in patients with known history of malignancy, it is important to consider the differential of metastatic lesions and to perform a thorough evaluation including fine-needle aspiration for clinical elucidation and management. Presentation: No date and time listed

S2429 A Rare Case of Esophageal Adenocarcinoma Presenting as an Isolated Brain Lesion 6 Years After Treatment

Introduction: Esophageal adenocarcinomas account for ∼1% of all cancers in the U.S. The prevalence of central nervous system (CNS) metastases associated with these cancers is around 1.8%. Response rates to standard of care are poor and prognosis is dismal. Often CNS involvement is associated with widely metastatic disease, herein, we present a case of a solitary brain lesion from esophageal adenocarcinoma at first recurrence. Case Description/Methods: A 72-year-old-male with a 40 pack-year smoking presented with progressive dysphagia in March 2015. Contrast enhanced CT of the chest, abdomen and pelvis revealed a constricting mass at the esophagogastric junction that led to endoscopy guided biopsy revealing esophageal adenocarcinoma. He underwent neoadjuvant chemotherapy (cisplatin/5-fluorouracil) and radiation therapy followed by esophagogastrectomy in July of 2015 where diagnosis of stage IIIBT3N2cM0 esophageal adenocarcinoma was confirmed. Clinical and imaging surveillance for 6 years had not shown any progression of cancer. However, in June of 2021, he presented with altered mental status that led to contrast enhanced brain MRI showing a T2 hyperintense left parietal lobe mass with an 8 mm midline shift and surrounding vasogenic edema (Figure). FDG PET-CT head to toes did not show extracranial recurrence. He underwent left posterior temporal craniotomy for resection of tumor confirming the diagnosis of metastatic esophageal adenocarcinoma. IHC showed positivity of cytokeratin7, CDX2 and SATB2. Whole exome sequencing revealed mutations in ARID1A, FH, and TP53 with variants of unknown significance of ATM and CDH. Tumor displayed proficient mismatch repair protein, a combined positive score of 15 for PD-L1, and negative Her2/Neu. Further sequencing showed tumor mutational burden of 4, no genomic loss of heterozygosity, and stable microsatellite repeats. He received gamma-knife radiation to the solitary left temporal lobe lesion. Patient continues to maintain his quality of life with no evidence of clinical and radiographic recurrence. Discussion: Isolated brain metastasis from esophageal adenocarcinoma is a very rare phenomenon. Limited data suggests that the survival of patients with isolated CNS lesions is < 1 year, however, achieving pathologic complete response after neoadjuvant chemo-radiation therapy has shown to improve survival. These esophageal cancers with isolated CNS metastases may share a unique genomic profile and more research is required to understand their alterations.Figure 1.: MRI of the brain. 1A- Pre-op axial OLEA of L. temporal lobe tumor (06/2021), 1B- Pre-op axial coronal T1 (06/2021), 1C- Follow-up T2 MRI.

Clinical Profile and Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Brain Metastases: Real-World Experience.

There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.

64-Year-Old Woman With Aphasia and Troponin Elevation

64-Year-Old Woman With Aphasia and Troponin Elevation

Clinical and molecular characteristics of advanced esophageal/GEJ cancer with brain metastasis.

e16092 Background: Brain metastasis (BRM) in gastroesophageal (GE) cancer is uncommon, but contributes to poor prognosis and significant symptom burden. While HER2 overexpression has been suggested as a potential driver of BRM, clinicopathologic and molecular determinants of BRM in GE cancer and their impact on clinical outcome remain incompletely understood. Methods: We retrospectively analyzed clinicopathologic data from 323 advanced esophageal/GEJ patients (pts) at Johns Hopkins from 2003 to 2021. Univariate and multivariate logistic regression were performed to investigate the association between several clinical and molecular features and the occurrence of BRM, with particular focus on HER2 overexpression (by IHC and FISH) and PD-L1 expression (by IHC) as measured by the combined positive score (CPS). Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 64 and most pts were white (90.4%). Tumors were 73.7% esophageal primary, 82.7% adenocarcinoma, 43.8% HER2+, and 11.1% CPS ≥ 1. Cumulative incidence of BRM in overall cohort and within HER2+ subgroup was 14.6% (47 pts) and 25.4% (16 pts), respectively. Pts with BRM (not already present at time of stage IV diagnosis) had median onset of 10.8 months. Seventeen (36.2%) pts had a solitary brain lesion and 10 (21.7%) were asymptomatic. On univariate analysis, adenocarcinoma and HER2 overexpression were associated with increased risk of BRM (OR 3.45; 95% CI 0.09-0.96; p = 0.043 and OR 2.72; 95% CI 1.11-6.67; p = 0.028, respectively). Notably, the HER2 association was strengthened when HER2 equivocal tumors were re-classified as positive in an exploratory analysis (OR 3.55; 95% CI 1.38-9.14; p = 0.009). Adenocarcinoma and HER2 overexpression were collinear in the multivariate model. In pts with BRM, OS was improved in HER2+ pts (16.72 months; 95% CI 12.3-21.1 months; log-rank p = 0.039 and OR 0.33; 95% CI 0.11-0.99; Cox regression p = 0.049). CPS and primary tumor location were not associated with increased BRM. Conclusions: HER2 overexpression identifies an esophageal/GEJ molecular subtype that is significantly associated with increased risk of BRM; though with improved OS (compared to non-HER2+ BRM) and later onset CNS progression, likely reflecting durable extra-CNS control on targeted systemic therapy and a potential HER2+ subgroup with relatively indolent biology. Prevalence of asymptomatic and solitary brain lesions supports increased brain surveillance for this population.

Performance of Conventional and Machine-Learning Approaches for the Diagnosis of Tumor Recurrence on MRI after Radiation Therapy of Brain Metastases

Objective: To compare the performance of conventional and machinelearning approaches for the diagnosis of tumor recurrence after radiation therapy of brain metastases. Methods: 184 symptomatic patients with solitary metastatic brain lesions treated with radiation therapy were enrolled in a monocentric retrospective study from June 2013 to May 2018. The diagnosis was tumor recurrence (n=71) and radiation necrosis (n=113) using as reference standard expert-consensus derived from pathology and long-term follow-up. 37 potential predictors were recorded at the time of radiological progression (7-15 months after therapy): 6 clinical features and 31 imaging features including 20 radiomics features derived from standard of care 3D T1-gadolinium sequences. We compared four approaches (A, B, C, D): expert report using MRI sequences without (A) and with delayedcontrast MRI (TRAM) sequences (B), 11 non-Radiomics imaging features alone (C) and a signature combining variables selected using unsupervised machinelearning algorithms (D), training:validation sets: n=144:40 pts). Results: Overall (n=184), approaches B and C (using TRAM sequence alone) reached comparable performances with respective AUCs [95% CI] of 78.7% [72.3%-85.1%] and 76.8% [70.3%-83.3%]. Both significantly outperformed approach A with AUC [95% CI] of 57.4% [50.7%-64.1%] (DeLong’s test, p-value=10-7). In the validation set (n=40), the signature reached an AUC [95% CI] of 92% [87%-97%]. Conclusion: A quantitative analysis of TRAM sequence seems the best approach for the diagnosis of recurrent tumor after radiation therapy. It is parsimonious, objective and less time-consuming than interpreting all sequences. A signature derived from the analysis of standard of care 3D T1- gadolinium sequence showed promising results that warrant prospective validation.

Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report

BackgroundAnti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a severe autoimmune encephalitis mediated by anti-NMDA receptor antibodies. Brain MRI manifestations vary and are non-specific. If there are any lesions, they tend to be diffusely or multifocally distributed. Solitary lesion is relatively rare.Case presentationWe report a 16-year-old girl who initially presented with focal seizures but developed severe psychiatric and extrapyramidal symptoms later on. Brain MRI revealed a solitary juxtacortical demyelinating lesion in the left frontal lobe. No enhancement was noted. Electroencephalogram captured epileptiform discharges in the same region. NMDAR IgGs were tested positive in the serum and cerebrospinal fluid. Corticosteroid and intravenous IgG were administered and the patient completely recovered. Brain MRI revealed a fainter lesion in the left frontal lobe.ConclusionIn very rare instances, anti-NMDA receptor encephalitis can present with a solitary brain lesion. A full panel of antibodies for autoimmune encephalitis is the key leading to the diagnosis.

Radiosurgery for small-cell lung cancer brain metastases: a review.

First-line stereotactic radiosurgery (SRS) is now considered the preferred treatment over whole brain radiation therapy (WBRT) for limited brain metastases arising from most tumor histologies. This standard was reached following the consistent results of multiple phase III studies which demonstrated that, despite improved CNS control, the addition of WBRT to SRS does not improve overall survival (OS) and is associated with a reduction in cognitive function. Thus, it may be reasonable to consider the benchmark necessary to favor a paradigm of SRS alone over strategies incorporating WBRT as the demonstration of comparable OS in the context of decreased treatment-related side effects. However, patients with small-cell lung cancer (SCLC) brain metastases were excluded from the landmark trials that established SRS alone for limited brain metastases, largely due to concerns for short-interval CNS progression in SCLC as well the historic role of prophylactic cranial irradiation (PCI) in SCLC in the absence of known brain metastases. As a result, WBRT has remained the standard for SCLC for limited and even solitary brain lesions. With shifting SCLC care patterns including increased MRI surveillance, decreased PCI delivery, and emerging systemic agents, interest in first-line SRS for SCLC is likely to continue to increase over time. Herein we will review the emerging data for first-line SRS in the management of SCLC brain metastases and the potential for its increasing role in the setting of a greater utilization of MRI surveillance and improving systemic therapies.

Abstract 5254: Combined in vitro TTFields and paclitaxel reduce proliferation and clonogenicity in non-small cell lung cancer (NSCLC) cells from a patient previously treated with standard-of-care

Abstract TTFields therapy in conjunction with chemotherapy has been FDA approved as a first line treatment regimen for patients with unresectable malignant pleural mesothelioma. Clinical trials are underway to test the efficacy of TTFields in patients with progressive NSCLC or NSCLC brain metastases following standard-of-care or radiosurgery, respectively. Our study utilized tumor cells extracted from a NSCLC metastatic brain tumor from a patient previously treated with standard-of-care chemoradiation prior to progression to brain metastasis. These patient-derived NSCLC cells were subjected to TTFields application with and without paclitaxel to determine if the combination of TTFields with paclitaxel would be more effective than either treatment alone. Written informed consent was obtained from the patient, who was 60 years-old and female. She received concurrent carboplatin/paclitaxel and radiotherapy to the upper lobe of her left lung prior to discovery and resection of a solitary brain lesion. Cells isolated from the metastatic brain tumor were cultured for 3 passages prior to plating on coverslips (4 × 104 each) in DMEM/F12 media with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 kHz. Paclitaxel was added to the media to a final concentration of 5 nM. Cells were treated for 14 days. At the end of the treatment period, some coverslips of cells were lysed and assayed for lactate dehydrogenase (LDH) to represent cell number (n=5) and another set of coverslips of cells were harvested and replated in triplicate for the clonogenic assay (n=3). Groups were compared with one-way ANOVA. Data shown in table are mean ± SD. For the LDH assay, ANOVA p&amp;lt;0.0001. For the clonogenic assay, ANOVA p=0.0003. Overall, the combination of TTFields with paclitaxel produced additive reductions in cell proliferation (75%) and reduced the clonogenic potential (95%) compared to untreated controls. The additive effects of TTFields and paclitaxel suggest that they target different cell populations within a heterogeneous tumor, and that lung cancer patients previously treated with standard-of-care may benefit from TTFields therapy. Proliferation and clonogenic assay results from combined TTFields and paclitaxelAssayControlPaclitaxel (5 nM)TTFieldsTTFields ± Paclitaxel (5 nM)Proliferation (LDH assay)1.83±0.090.81±0.041.34±0.150.46±0.21Clonogenicity (cell counts)26641±46258697±161717399±59981598±598 Citation Format: Sharon K. Michelhaugh, Sandeep Mittal. Combined in vitro TTFields and paclitaxel reduce proliferation and clonogenicity in non-small cell lung cancer (NSCLC) cells from a patient previously treated with standard-of-care [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5254.

Multimodality management of brain metastasis from colorectal cancer.

204 Background: More than 50% of colorectal cancer (CRC) patients will develop metastatic disease. Brain metastasis (BM) from colorectal cancer is uncommon (0.6-1.36%). This study aims to investigate the patient characteristics, treatment modalities and prognostic factors in this rare population. Methods: 104 patients with brain metastasis disease from CRC were identified from over 30,000 colorectal cancer patients at the Mayo Clinic Rochester between 1/1994 and 6/2019. A retrospective review was conducted by using data from electronic medical records (EMR). Statistical analysis utilized the Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: Among the 104 patients, 62 were male (59.6%) and 42 were female (40.4%). Median age at CRC diagnosis was 58.4 and at BM diagnosis was 61. Thirty-three patients had right-sided colon cancers, 27 patients had left-sided colon cancers and 39 patients had rectal cancer. Median time from CRC diagnosis to BM was 30.7 months. The majority of patients (58.7%) presented with a solitary brain lesion. Eighty-six patients (82.7%) had extracranial metastatic disease at BM diagnosis. Median survival was 7.0 months (95% CI 2.6-16.9) from BM diagnosis. Age &lt;70, solitary BM, surgery, radiation, and chemotherapy were associated with statistically significant improved survival on univariate and multivariate analysis. Multi-modality treatment including surgical brain lesion resection, postoperative stereotactic radiation (SRS) with/without whole brain radiation (WBRT), and chemotherapy significantly improved median overall survival (Table). Conclusions: Although BM from CRC carries poor prognosis, multi-modality treatment (surgery, radiation and systemic chemotherapy) for patients with limited BM improves clinical outcome. [Table: see text]

Diagnostic Value of CT of Chest, Abdomen, and Pelvis in Patients With Solitary and Multiple Brain Lesions.

OBJECTIVE. A common goal in patients with newly discovered brain lesions is to determine if the lesions are primary malignant brain neoplasms, metastases, or benign entities. Such patients often undergo CT of the chest, abdomen, and pelvis (CT CAP) to identify a primary neoplasm that may have metastasized to the brain. The aim of this study is to determine the frequency of finding a primary cancer on CT CAP. MATERIALS AND METHODS. A large academic hospital imaging database was searched for cases of new intracranial lesions with subsequent CT CAP performed for metastatic workup. The frequency of primary neoplasms diagnosed in the chest versus abdominal and pelvic portions of CT scans was determined in patients with newly identified intraaxial and extraaxial brain lesions. Lesion characteristics were recorded including size, number, and the presence of enhancement and hemorrhage. Ancillary signs of an abdominopelvic neoplasm were also recorded. RESULTS. A total of 227 of 287 (79%) cases of newly discovered intracranial lesions were malignant (primary or metastatic) and 60 (21%) were benign. Of the 227 malignant cases, 136 (60%) were primary brain neoplasms and 91 (40%) were brain metastases, and 68 of the 91 (75%) lung primary. Chest CT (CTC) identified a primary neoplasm in 65 of 287 (23%) cases; 63 of those 65 (96%) neoplasms arose in the lungs. CT of the abdomen and pelvis (CTAP) identified a primary neoplasm in only 3 of 287 (1%) cases. In 26 cases in which the intracranial lesions did not enhance, only one was metastatic. CONCLUSION. In patients with newly discovered brain lesions, CTC is warranted, but CTAP is unlikely to be useful in patients without ancillary signs of abdominopelvic neoplasm.

Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging

The incidence of second primary tumors in adults is increasing due to betterment in the diagnosis and management of first primary tumors. In literature so far, second primary brain tumors are not reported. Glioblastoma has a poor prognosis despite all recent advances in its molecular genetics and treatment. We report two cases of glioblastoma presenting as second primary tumor of the brain. The first patient was a 70-year-old female with seizures who was treated for carcinoma cervix 6 years back. The second patient was a 75-year-old male patient, a known case of colonic carcinoma treated a year back, and he presented with seizure. Both the patients were operated, and biopsy turned out glioblastoma. A solitary brain lesion in the known first primary patient may be a glial tumor which needs proper evaluation since its management differs from metastasis.

EXTH-31. COMBINATION OF TUMOR TREATING FIELDS (TTFIELDS) AND PACLITAXEL PRODUCES ADDITIVE REDUCTIONS IN PROLIFERATION AND CLONOGENICITY IN PATIENT-DERIVED METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) CELLS

Abstract Clinical trials are underway to test the efficacy of TTFields in patients with progressive NSCLC or NSCLC brain metastases following standard-of-care or radiosurgery, respectively. Our study utilized patient-derived cells isolated from NSCLC brain metastases from a patient previously treated with standard-of-care chemo-radiation prior to progression to brain metastasis. These patient-derived cells underwent TTFields application in vitro with and without paclitaxel to determine if the response to the combination of TTFields with paclitaxel would be different from either treatment alone. Use of patient tissues was approved by the Institutional Review Board. Written informed consent was obtained from the patient, who was 60 years-old and female. She received concurrent carboplatin/paclitaxel and radiotherapy to the upper lobe of her left lung prior to discovery and resection of a solitary brain lesion. Cells isolated from the metastatic brain tumor were cultured for 3 passages prior to plating on coverslips (4×104 each) in DMEM/F12 media with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 kHz. Paclitaxel was added to the media to a final concentration of 5 nM. After 14 days, cell lysates were assayed for lactase dehydrogenase (LDH) to represent cell number (n=5) or were harvested and replated in triplicate for the clonogenic assay (n=3). Groups were compared with one-way ANOVA. Mean ± SD of LDH for the control, TTFields-alone, paclitaxel-alone, and the combination were 1.83 ± 0.09, 1.34 ± 0.15, 0.81 ± 0.04, and 0.46 ± 0.21, respectively (ANOVA p&lt; 0.0001). Clonogenic assay counts for the same groups were 26641 ± 4625, 17399 ± 5998, 8697 ± 1617, and 1598 ± 598 (ANOVA p= 0.0003). The additive effects of TTFields and paclitaxel suggest that they target different cell populations within a heterogeneous tumor, and that patients previously treated with standard-of-care may benefit from TTFields therapy.

352P - Clinical profile and outcome of HER2 positive breast cancer patients with brain metastases treated with HER2 targeted therapy: Real-world experience

BackgroundBrain metastases (BM) is a commonly encountered clinical scenario in patients with HER2 positive breast cancer (BC). We report here the clinical profile and outcome of patients with HER2 positive breast cancer with brain metastasis (BCBM) who were treated with HER2 targeted therapy at a single institution. MethodsClinical and outcome data of patients with HER2 positive BCBM treated with HER2 targeted agents were retrospectively collected. Efficacy variables were progression-free survival (PFS, time from diagnosis of BM to first progression or death due to any cause, whichever was earlier) and overall survival (OS). ResultsBetween 2013 and 2017, 102 HER2 positive BCBM patients with median age 52 (IQR 45-57) years were treated with HER2 targeted therapy. Of these, 40 (39.2%) had ER positive disease, 98 (96.1%) were symptomatic at diagnosis of BM, 69 (67.6%) had received ≥2 lines of chemotherapy before BM, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions and 43 (49.4%) had > 5 lesions. After BM diagnosis, whole brain radiotherapy (WBRT) was administered in 93 (91.2%) patients, stereotactic radiosurgery (SRS) in 4 (4.0%), WBRT and SRS in 4 (4%), and 9 (8.9%) patients underwent surgical resection of BM. The first HER2 targeted therapy after BM diagnosis was lapatinib in 70 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in 3 (2.9%), trastuzumab emtansine in 4 (3.9%) and intrathecal trastuzumab in 5 (4.9%), patients. After diagnosis of BM, 17 (16.7%) patients received ≥3 lines of therapy. At a median follow-up of 13.5 months, there were 91 PFS events and 80 deaths. The median PFS after BM was 8 [95% confidence interval (CI), 6.2-9.8] months and median OS was 14 (95%CI, 10.8-17.2) months with a 2-year OS of 25% (95% CI, 16.7-34.4%). Median PFS in patients who received lapatinib-capecitabine regimen (n=62) was 9.0 (95%CI, 7.3-10.7) months. ConclusionsThe median OS in patients with HER2 positive BCBM, treated with HER2 targeted therapy, is good and exceeds that reported in metastatic triple negative breast cancer. The difference between median PFS and OS suggests that continued treatment after first or subsequent progression may be therapeutically beneficial in some patients. Legal entity responsible for the studySudeep Gupta. FundingHas not received any funding. DisclosureJ. Bajpai: Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Samsung Bioepis; Research grant / Funding (institution): Sun Pharma. S. Gupta: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Johnson & Johnson; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Celltrion; Advisory / Consultancy, Research grant / Funding (institution): Oncosten; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Intas; Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Biocon; Advisory / Consultancy: Dr. Reddy’s Laboratories; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Core Diagnostics. All other authors have declared no conflicts of interest.

MR Imaging of Meningioangiomatosis in a Pediatric Population

Meningioangiomatosis (MA) is a rare intracranial hamartomatous lesion. We retrospectively reviewed the MRIs in 6 pediatric patients with a histopathologic diagnosis of MA. Patients with MA demonstrated a solitary lesion in the frontotemporal regions, with FLAIR hyperintensity and leptomeningeal enhancement. A solitary brain lesion in the frontotemporal lobes associated with leptomeningeal enhancement and T2/FLAIR hyperintensity should include the possibility of MA in a pediatric patient who presents with seizures or headaches.

SURG-04. SIMULTANEOUS CRANIOTOMIES FOR MULTIPLE BRAIN METASTASES

BACKGROUND: It is well known that for patients with solitary metastatic disease in the brain, aggressive surgical treatment can prolong survival. However, there is a paucity of literature focusing on simultaneous resection of multiple metastatic brain tumors. METHODS: We analyzed 13 patients and 26 tumors between 2005–2019 who had simultaneous resection of at least 2 metastatic brain tumors via either one or two craniotomies. We independently analyzed those patients with simultaneous resection of metastatic disease in both the supra- and infratentorial compartments. RESULTS: Overall, 26 tumors were resected in a simultaneous fashion. There were 7 females (53.8%) and 6 males (46.2%) total. 5/13 (38.5%) patients had previously known brain metastases in which all 5 had previous adjuvant radiation. All 13 patients had 2 metastatic lesions resected during one operation. Gross total resection rate reached 88.5% with a median post-operative stay of 3 days. Complications presented in only 3 out of 13 cases (grade 2 and 3 according to CTCAE). Primary sites of metastatic disease were lung, breast, skin and renal. 12/13 (92.3%) had two distinct craniotomies and 23/26 (88.5%) tumors had gross total resection of both lesions. There were 11 frontal (42.3%), 7 parietal (26.9%), 2 temporal (7.7%), 1 occipital (3.8%) and 5 cerebellar (19.2%) tumors. There were three patients with both supra- and intratentorial tumors with simultaneous resection. All three patients had two craniotomies and two separate incisions. 1 of the 3 had pre-operative SRS. Overall, average local progression since surgery to at least one resected tumor bed was 88.3 days. CONCLUSIONS: Our results suggest that patients with multiple metastatic brain lesions have comparable outcomes and similar rates of surgical risk to those with solitary brain lesions. In patients with simultaneous supra- and infratentorial brain metastatic disease and indications for decompression, safe resection is feasible.

The Utility of Whole Body Imaging in the Evaluation of Solitary Brain Tumors

Solitary brain tumors can propose a diagnostic dilemma owing to the difficulty in differentiating between primary brain tumors and metastatic disease. The similar radiologic appearance on routine magnetic resonance imaging will necessitate the need for additional noninvasive testing. We sought to determine the clinical utility of preoperative whole body screening with computed tomography (CT) to detect metastatic disease in patients with solitary brain tumors. A prospectively maintained surgical database for a large quaternary care academic institution was retrospectively reviewed for all patients undergoing craniotomy for a new diagnosis of enhancing solitary brain lesion from January 2011 to January 2016. Patients were excluded if the imaging findings had demonstrated multiple brain tumors, they had a known diagnosis of malignancy, or they had undergone previous craniotomy. The demographic and radiographic information and clinical and histopathologic data were collected and tallied. A total of 218 patients with solitary brain tumors met the inclusion criteria and were included in the present study. Histopathologic analysis confirmed primary central nervous system tumors in 152 patients (74.4%) and metastatic disease in 66 (25.6%). Preoperative screening with whole body CT had a sensitivity of 0.92 and specificity of 0.95 for detecting systemic metastases in the patients. Preoperative whole body CT correctly identified systemic malignancy in 88% of the patients ultimately diagnosed with metastasis (positive predictive value, 88%). Of those with negative whole body imaging findings, 97% had a diagnosis of a primary central nervous system neoplasm (negative predictive value, 97%). Preoperative whole body CT had a positive predictive value of 88% and negative predictive value of 97% in the present study and was both sensitive (92%) and specific (95%) for the detection of extracranial tumors. The identification of extracranial tumors on whole body CT screening might alter management.

Demyelinating lesions behaving like aggressive tumours on advanced MRI techniques

Tumefactive demyelinating lesions are a rare disorder in which inflammatory demyelination manifests as solitary or multiple focal brain lesions (greater than 2 cm in size), which can be mistaken for glioma, lymphoma, metastasis and in some cases even brain abscess. The symptomatology of tumefactive demyelinating lesions depends on the white matter area involved and includes quickly progressing neurological deterioration of motor, sensory and visual function, praxis, language and mood impairment, as well as seizures. Recognising the key imaging features in a patient with a prior history of demyelination may expedite appropriate management. Preoperative diagnosis or at least the consideration of a demyelinating process is important to avoid unnecessary surgery. We report three patients with demyelinating lesions who presented with findings suggestive of demyelination on conventional magnetic resonance imaging studies. However, in all patients the lesions showed high perfusion and in two high permeability, which are findings generally seen with high-grade neoplasias. In rare instances, tumefactive demyelinating lesions may show increased perfusion and high permeability, imaging findings more commonly seen in high-grade gliomas. We suggest that if white matter lesions on conventional magnetic resonance imaging are compatible with tumefactive demyelinating lesions, atypical findings of high perfusion/permeability should not dissuade the radiologist from suggesting the presence of tumefactive demyelinating lesions rather than high-grade gliomas.