scholarly journals Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study

Blood ◽  
2015 ◽  
Vol 126 (4) ◽  
pp. 494-499 ◽  
Author(s):  
Jessica Donato ◽  
Federico Campigotto ◽  
Erik J. Uhlmann ◽  
Erika Coletti ◽  
Donna Neuberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Brain Metastasis ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Intracranial Hemorrhage ◽  
Matched Cohort ◽  
Metastatic Brain Tumors ◽  
Matched Cohort Study ◽  
Therapeutic Anticoagulation ◽  
Key Points

Key Points Significant intracranial hemorrhage occurs in 20% to 50% of patients with metastatic brain tumors. Therapeutic anticoagulation in patients with brain metastasis did not increase the risk for intracranial hemorrhage.

Intracranial Hemorrhage in Patients with Primary Brain Tumors Treated with Therapeutic Enoxaparin: A Matched Cohort Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 142-142 ◽  
Author(s):  
Charlene Mantia ◽  
Erik Uhlmann ◽  
Maneka Puligandla ◽  
Donna S. Neuberg ◽  
Griffin M. Weber ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thromboembolism ◽  
Brain Tumors ◽  
Intracranial Hemorrhage ◽  
Cumulative Incidence ◽  
Competing Risk ◽  
Matched Cohort ◽  
Intracranial Hemorrhages ◽  
Primary Brain Tumors ◽  
Therapeutic Anticoagulation

Abstract BACKGROUND Venous thromboembolism occurs in approximately 15-30% of individuals with primary brain tumors (e.g. glioblastoma, astrocytoma, and oligodendroglioma). Spontaneous intracranial hemorrhage (ICH) is also a frequent complication of primary brain tumors thus complicating the decision to administer therapeutic anticoagulation. Therapeutic anticoagulation does not appear to increase the risk of intracranial hemorrhage among patients with solid tumor brain metastases but whether anticoagulation is safe to administer to patients with primary brain tumors is less clear. The aim of this study was to determine the rate of intracranial hemorrhage associated with therapeutic enoxaparin for treatment of venous thromboembolism in patients with primary brain tumors compared to those patients with brain tumors not exposed to therapeutic anticoagulation. METHODS A 1:1 matched, cohort study was performed using a large hospital-based online medical record database (CQ2) linking ICD-9 codes with prescription medication records, cases were initially identified based on coding for primary brain tumors, venous thromboembolism, and prescription of enoxaparin. Matched controls were identified using a "round-robin" algorithm that ranked controls according to a scoring formula based on successful match for year of diagnosis, age, and gender. A blinded review of radiographic imaging was performed and intracranial hemorrhages were categorized as trace, measurable, and significant. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and "significant" intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic (defined as focal neurologic deficit, headache, nausea, or change in cognitive function), or required surgical intervention. Time-to-event statistical analysis was performed using a competing risk analysis to account for death from any cause as an absorbing competing risk. Statistical comparison of event rates between cases and controls was performed using Fine and Gray competing risk regression. RESULTS A total of 100 patients with primary brain tumors were included in the study. The most common diagnosis was glioblastoma (85%), followed by anaplastic oligodendroglioma (8%), and anaplastic astrocytoma (7%). The two cohorts were well matched for age (60 years old), gender (65% male), and types of treatment received (99% radiation, 34% stereotactic radiosurgery, and 71% surgical resection). There was no statistical difference in the rate of measurable intracranial hemorrhage for the group of patients who received therapeutic enoxaparin at any point following the diagnosis of glioma compared to those who did not receive anticoagulation (subdistribution ratio hazard ratio 1.09, 95% CI 0.53-2.22). The 1-year cumulative incidence of measurable hemorrhage among those who were treated with enoxaparin was 23.6% compared with 20.0% in the control group (Gray's test P=0.48). The 1-year cumulative incidence of significant hemorrhage was 13.1% in those receiving enoxaparin compared with 6.0% in controls (sHR 1.45, 95% CI .47-4.65, P=0.68). The median survival was similar for the enoxaparin (1.56 years) and controls (1.63 years, Log rank P=0.81). CONCLUSION Intracranial hemorrhage is common in patients with primary brain tumors. In this matched cohort analysis utilizing a blinded radiologic review, the administration of therapeutic low molecular weight heparin did not significantly increase the risk of intracranial hemorrhage in the setting of glioma and venous thromboembolism. In patients with primary brain tumors, the diagnosis of venous thromboembolism treated with therapeutic enoxaparin did not impact overall survival. Disclosures Zwicker: Quercegen Pharma: Research Funding.

Unique histopathologic features of brain metastases from hepatocellular carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 169-169
Author(s):  
Yu Yun Shao ◽  
Min-Shu Hsieh ◽  
Chung-Yi Huang ◽  
Li-Chun Lu ◽  
Chih-Hung Hsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Brain Metastasis ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Lung Metastasis ◽  
Positive Staining ◽  
Metastatic Brain Tumors ◽  
Tumor Tissues ◽  
Metastatic Lung ◽  
Histopathologic Features

169 Background: In the era of anti-angiogenic therapy as treatment for advanced hepatocellular carcinoma (HCC), the incidence and importance of brain metastases are increasing. We aimed to study their histopathologic features. Methods: We searched for all patients who were diagnosed to have HCC with brain metastasis from 1999 to 2010 at National Taiwan University Hospital, Taipei, Taiwan. Patients who had HCC with lung metastasis were also included for comparison. Patients with available tissues of both primary and metastatic tumors were enrolled in this study. Tumor slides from paired primary and metastatic HCCs were stained by H and E, and immunohistochemically stained for CK7, p53, Ki67, vimentin, Hes1, and c-Met. The expressions of CK7, p53, and vimentin were graded according to percentages of positive staining, but those of Hes1 and c-Met were recorded as an H score, which was defined as intensity (0, 1, 2, or 3) × percentages of positive staining. Results: A total of 14 patients had available tumor tissues of both primary and metastatic brain tumors. Another 21 patients had tumor tissues of both primary and metastatic lung tumors. The metastatic brain tumors, comparing to the metastatic lung tumors, had significantly more bizarre dilated vessels (86% vs. 14%, p < 0.001), hyaline globules (50% vs. 5%, p = 0.003), higher Hes1 H scores (mean, 245 vs. 131, p = 0.001), and lower c-Met H scores (mean, 15.4 vs. 38.1, p = 0.046). Tumor necrosis also tended to be more common among metastatic brain tumors (93% vs. 62%, p = 0.056). On the contrary, the above differences were not identified between the primary tumors which later developed brain metastasis and those which later developed lung metastasis. When disease progressed from primary liver to brain metastasis, mitosis counts (p = 0.034) and bizarre dilated vessels (p = 0.020) significantly increased, and necrosis (p = 0.059) tended to be more common. Conclusions: Metastatic brain tumors from HCC had unique histopathologic features compared to primary liver tumors or lung metastases. The increased Hes1 expression and decreased c-Met expression in HCC brain metastasis should be further explored. (This study was supported by the grant of NSC101-2314-B-002 -141, 100CAP1020-2 & NTUH.101-N1965.)

Radiographic features of metastatic brain tumors from non-small cell lung cancer with ALK rearrangement.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20533-e20533
Author(s):  
Li Chu ◽  
Ruimin Li ◽  
Xi Yang ◽  
Fan Xia ◽  
Zhengfei Zhu
Keyword(s):  
Brain Metastasis ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Brain Edema ◽  
Metastatic Brain Tumors ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Peritumoral Brain Edema ◽  
Nsclc Patients ◽  
The Military

e20533 Background: Approximately 5% of Non-Small Cell Lung Cancer (NSCLCs) have ALK rearrangement, in which brain metastases are common. The radiographic features of metastatic brain tumors have not been previously studied. Finding the features of brain metastasis could help establishing the treatment pattern for the ALK-rearranged NSCLC patients. Methods: All NSCLC patients with ALK rearrangement (132 patients) were detected from March 2008 through December 2016. The metastatic brain tumors (34 patients) detected from July 2014 through December 2016 were divided into metachronous brain metastasis (MBM) and synchronous brain metastasis (SBM) groups according to the diagnosis time. All patients were followed up using brain magnetic resonance imaging (MRI). The number of brain tumors, size of the largest brain tumors, and size of peritumoral brain edema were compared between the two groups. Results: Thirty-four patients were observed.The number of brain tumors in ALK-rearranged NSCLC patients is 4.6 with 41.07mm Peritumoral Brain Edema Size (PBES). Only one patient has the military brain metastases. All patients were divided into two groups: metachronous (15 patients) and synchronous (19 patients). The two groups had rare active and former smoker. The SBM group had more female patients. The SBM group had larger number of brain tumors (6.1 VS 2.8), but there was no significant difference ( P= 0.0672). The MBM group had smaller brain tumors (14.2mm vs 20.9mm, P= 0.0798) with smaller PBES (25.7mm vs 53.2mm, P= 0.0018) and Peritumoral Brain Edema Index (PBEI) (0.9 vs 1.9, P= 0.0201) than the SBM group. Conclusions: Only one patient in SBM group has the military brain metastases. The SBM group has larger brain tumors with larger peritumoral brain edema and PBEI. The MBM patients have smaller ones. Our studies show that ALK-rearranged NSCLC patients have a small number brain tumors and relatively large PBES.

Risk of Intracranial Hemorrhage Associated with Enoxaparin Administration in Patients with Brain Metastasis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 348-348
Author(s):  
Jessica Donato ◽  
Federico Campigotto ◽  
Erika Coletti ◽  
Donna Neuberg ◽  
Griffin Weber ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Intracranial Hemorrhage ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Intracranial Hemorrhages ◽  
Therapeutic Anticoagulation

Abstract BACKGROUND Approximately 20% of patients with brain metastases develop VTE, but limited evidence is available regarding whether anticoagulation can be administered safely in such patients. Most large prospective trials on the use of anticoagulation have excluded patients with brain metastases. Spontaneous hemorrhage into brain metastases is common in pathologic specimens (3-10%), with rates considerably higher for certain tumor types such as renal cell carcinoma and melanoma. Whether therapeutic anticoagulation increases the risk of intracranial hemorrhage is unclear. The aim of this study is to determine the rate of intracranial hemorrhage associated with therapeutic enoxaparin for treatment of venous thromboembolism in patients with brain metastases compared to those patients with brain metastases not exposed to therapeutic anticoagulation. METHODS A 1:1 matched, cohort study was performed at Beth Israel Deaconess Medical Center. Using a large hospital-based online medical record database (CQ2) linking ICD-9 codes with prescription medication records, cases were initially identified based on coding for brain metastasis, venous thromboembolism, and prescription of enoxaparin. Matched controls were identified using a “round-robin” algorithm that ranked controls according to a scoring formula based on successful match for tumor diagnosis, year of diagnosis of brain metastasis, age, and gender. All records were reviewed for eligibility based on inclusion criteria (adult with metastatic solid malignancy with imaging proven parenchymal CNS metastasis) and exclusion criteria (i.e. primary brain tumors, leptomeningeal disease only, non-solid malignancies or therapeutic anticoagulation in the control arm). A “confirmed” intracranial hemorrhage was defined as unequivocal radiographic evidence while less conclusive imaging reports were classified as “possible” intracranial hemorrhage. Time-to-event statistical analysis was performed using a competing risk analysis to account for death as a competing risk. Statistical comparison of event rates between cases and controls was performed using Fine and Gray competing risk regression. RESULTS A total of 193 patients with confirmed brain metastases were included in the study. The predominant cancer subgroup was non-small cell lung cancer (N=96, 49.7%), followed by breast cancer (11.7%), melanoma (8.3%), renal cell carcinoma (7.8%), other (7.8%), colorectal cancer (4.1%), and small cell lung cancer (2.6%). There was no statistical difference in the rate of confirmed intracranial hemorrhage for the group of patients who received therapeutic enoxaparin at any point following the diagnosis of brain metastasis compared to those who did not receive anticoagulation (hazard ratio 0.96, 95% CI 0.56-1.69). The 12-month cumulative incidence of confirmed hemorrhage among those who were treated with enoxaparin was 24.9% compared with 25.6% in the control group (Gray’s test P=0.88). There was no difference in survival between the two groups (Log Rank P=0.29). The risk of confirmed intracranial hemorrhage according to malignancy subgroups did not differ. The 12-month cumulative incidence of all intracranial hemorrhages (confirmed and possible) was 46.2% among those treated with enoxaparin versus 34.9% (P=0.11) in the control arm. Among the subgroup with non-small cell lung cancer there was a significant increase in risk of all intracranial hemorrhages (confirmed and possible) in those receiving enoxaparin (hazard ratio 1.94, 95% CI 1.06-3.38, P=0.033). CONCLUSIONS Intracranial hemorrhage is common in patients with brain metastases. However, the administration of enoxaparin to patients with brain metastases does not increase the risk of confirmed intracranial hemorrhage nor influence overall survival. The clinical significance of an increased rate of total intracranial hemorrhages (possible and confirmed) associated with enoxaparin administration in patients with metastatic non-small cell lung cancer is uncertain. These data represent the largest clinical study to date assessing the risk of intracranial hemorrhage in patients with brain metastases treated with therapeutic anticoagulation and support the safety of enoxaparin to treat venous thromboembolism in patients with brain metastases. Disclosures Zwicker: Sanofi: Research Funding.

Metastatic Brain Tumors: To Treat or Not to Treat, and with What?

2020 ◽  
Vol 16 (3) ◽  
pp. 168-181
Author(s):  
Patricia Tai ◽  
Kurian Joseph ◽  
Avi Assouline ◽  
Osama Souied ◽  
Nelson Leong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Performance Status ◽  
Primary Lung Cancer ◽  
Small Cell ◽  
Metastatic Brain Tumors ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

A long time ago, metastatic brain tumors were often not treated and patients were only given palliative care. In the past decade, researchers selected those with single or 1-3 metastases for more aggressive treatments like surgical resection, and/or stereotactic radiosurgery (SRS), since the addition of whole brain radiotherapy (WBRT) did not increase overall survival for the vast majority of patients. Different studies demonstrated significantly less cognitive deterioration in 0-52% patients after SRS versus 85-94% after WBRT at 6 months. WBRT is the treatment of choice for leptomeningeal metastases. WBRT can lower the risk for further brain metastases, particularly in tumors of fast brain metastasis velocity, i.e. quickly relapsing, often seen in melanoma or small cell lung carcinoma. Important relevant literature is quoted to clarify the clinical controversies at point of care in this review. Synchronous primary lung cancer and brain metastasis represent a special situation whereby the oncologist should exercise discretion for curative treatments, with reported 5-year survival rates of 7.6%-34.6%. Recent research suggests that those patients with Karnofsky performance status less than 70, not capable of caring for themselves, are less likely to derive benefit from aggressive treatments. Among patients with brain metastases from non-small cell lung cancer (NSCLC), the QUARTZ trial (Quality of Life after Radiotherapy for Brain Metastases) helps the oncologist to decide when not to treat, depending on the performance status and other factors.

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