Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7671-7671
Author(s):  
G. Srivastava ◽  
V. Rana ◽  
S. Taylor ◽  
M. Debnam ◽  
Y. Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cerebrovascular Accidents ◽  
Metastatic Nsclc ◽  
Nsclc Patients

7671 Background: Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). This is a low suspected risk, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Methods: Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. 2143 patients with metastatic NSCLC registering from Jan 1998 to Sept 2005 were followed till March 2006. 776 patients with and 1367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. Results: The incidence of ICH seemed to be higher in those with brain metastasis compared to those without. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and were not anticoagulated. Most of the brain metastasis-associated ICH's were asymptomatic, detected during radiologic surveillance. The rates of symptomatic ICH, or cerebrovascular accidents were similar and not significantly different between the two groups. The following table depicts the rates of CVA and/or ICH in metastatic NSCLC patients. Conclusions: In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared to those without, but was very low in both groups nonetheless without a statistically significant difference. These data suggest minimal risk of clinically significant ICH for NSCLC brain metastasis patients and justifies for them clinical trials of AAT. No significant financial relationships to disclose. [Table: see text]

scholarly journals Analysis of outcomes and brain metastases (BM) of molecular selected non-small cell lung cancer (NSCLC) patients included in clinical trials

2016 ◽  
Vol 27 ◽  
pp. vi440
Author(s):  
S. Cedres ◽  
N. Pardo Aranda ◽  
A. Martinez de Castro ◽  
A. Navarro Mendivil ◽  
A. Martinez Marti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

A comparative analysis of survival in patients with non-small cell lung cancer with brain metastases receiving intracranial radiation with and without immunotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9025-9025
Author(s):  
Sunita Patruni ◽  
Ahmed Khattab ◽  
Stephen Abel ◽  
Shaakir Hasan ◽  
Saleha Rizwan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Independent Predictor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Intracranial Metastasis ◽  
Metastatic Nsclc ◽  
Nsclc Patients

9025 Background: Many patients diagnosed with advanced non-small cell lung cancer (NSCLC) will develop intracranial metastasis, contributing significantly to morbidity and mortality. Immunotherapy (IMT) has emerged as the standard of care in select cases of metastatic NSCLC, though data investigating the survival impact of IMT and radiation (XRT) in these patients is limited. To characterize the survival impact of intracranial XRT and IMT in NSCLC patients with brain metastasis, we analyzed the National Cancer Database (NCDB). Methods: We queried the NCDB for patients with metastatic NSCLC having brain metastasis receiving intracranial XRT ± IMT. Univariable and multivariable analyses identified characteristics predictive of overall survival. Cox proportional hazard ratios with propensity matching mitigated indication bias between the two arms. Results: 13,998 NSCLC patients who received IMT (n = 545) or did not receive IMT (n = 13,545) were eligible for analysis. Univariable analysis demonstrated a median overall survival of 13.1 months (95% CI: 11.8-15.0) vs. 9.7 months (95% CI: 9.5-9.9) (p < 0.0001) and 3-year overall survival of 17% vs. 12% [p < 0.0001; HR: 0.77 (0.71-0.84)] in patients receiving and not receiving IMT respectively. Patients with N3 disease and those diagnosed between 2012 and 2014 were more likely to have received IMT. Receipt of IMT remained an independent predictor of increased survival on propensity score matched multivariable comparison (p = 0.0002). Conclusions: Receipt of IMT was an independent predictor of increased overall survival in patients with NSCLC having intracranial metastasis. Randomized, prospective studies are needed to further validate these findings. [Table: see text]

scholarly journals Brain metastases (BM) development in molecular selected non-small cell lung cancer (NSCLC) patients included in clinical trials

2017 ◽  
Vol 28 ◽  
pp. ii39
Author(s):  
S. Cedres ◽  
N. Pardo ◽  
A. Navarro-Mendivil ◽  
A. Martinez ◽  
A. Martinez de Castro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals Comparative survival in patients with brain metastases from non-small-cell lung cancer treated before and after implementation of radiosurgery

2017 ◽  
Vol 24 (2) ◽  
pp. 146 ◽  
Author(s):  
J.N. Greenspoon ◽  
P.M. Ellis ◽  
G. Pond ◽  
S. Caetano ◽  
J. Broomfield ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Introduction Survival after a diagnosis of brain metastasis in non-small-cell lung cancer (nsclc) is generally poor. We previously reported a median survival of approximately 4 months in a cohort of patients treated with whole-brain radiotherapy (wbrt). Since that time, we implemented a program of stereotactic radiosurgery (srs). In the present study, we examined survival and prognostic factors in a consecutive cohort of patients after the introduction of the srs program.Methods Data from a retrospective review of 167 nsclc patients with brain metastasis referred to a tertiary cancer centre during 2010–2012 were compared with data from a prior cohort of 91 patients treated during 2005–2007(“pre-srs cohort”).Results Median overall survival from the date of diagnosis of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs cohort, p = 0.74) was not significantly different in the cohorts. The result was similar when the no-treatment group was excluded from the srs cohort. Within the srs cohort only, significant differences is overall survival were observed between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with improved survival being observed on univariate and multivariate analysis for patients receiving srs compared with patients receiving wbrt alone (p < 0.001).Conclusions No improvement in survival was observed for nsclc patients with brain metastases after the implementation of srs. Selected patients (younger age, female sex, good performance status, fewer brain metastases) treated with srs appeared to demonstrate improved survival. However, those observations might also reflect better patient selection for srs or a greater tendency to offer those patients systemic therapy in addition to srs.

scholarly journals The structure of blood–tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ling-yun Ye ◽  
Li-xiang Sun ◽  
Xiu-hua Zhong ◽  
Xue-song Chen ◽  
Song Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Blood Vessels ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chemotherapeutic Drugs ◽  
Small Cell Lung ◽  
Metastatic Lesions

Abstract Background Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood–brain barrier (BBB) is frequently impaired, forming blood–tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. Methods Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. Conclusions Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

scholarly journals Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy

2020 ◽  
Vol 12 ◽  
pp. 175883592093688
Author(s):  
Fan Zhang ◽  
Di Huang ◽  
Lei Zhao ◽  
Tao Li ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Platinum Based Chemotherapy ◽  
Paclitaxel Group ◽  
Nsclc Patients

Background: Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Methods: The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed. Results: Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [ p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status ( p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group ( p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) ( p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group. Conclusion: PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

Development of brain metastases in stage III/IV non-small cell lung cancer patients treated with or without erlotinib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19011-e19011 ◽  
Author(s):  
Jing Liu ◽  
Li Kong ◽  
Xue Meng ◽  
Jinbo Yue ◽  
Xindong Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Control Group ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
And Control

e19011 Background: Non-small cell lung cancer (NSCLC) has a risk of death from brain metastases (BM) that exceeds potential mortality from extracranial disease progression. Erlotinib has been proved to be effective for NSCLC patients. We hold a study to evaluate value of erlotinib in preventing BM in stage III/IV NSCLC patients. Methods: Pathologically confirmed NSCLC stage III/IV patients were included and divided into erlotinib group and control group according to whether erlotinib administration (at least one month) in 1- or 2-line therapy or not. Stage IV patients with BM were excluded. Patients with any EGFR-TKI treatment were excluded from control group. Times of erlotinib administration to BM and to death or last follow-up were recorded for erlotinib group. Times of corresponding 1- or 2-line chemotherapy to BM and to death or last follow-up were recorded for control group correspondingly. Time to BM, 1- and 2-year incidence of BM were end points. Results: 140 patients were included (68 in erlotinib group and 72 in control group) and all clinical characteristics between two groups were balanced. At a median follow-up of 20.0 months, the median time to BM for all patients was 28.0 months (95% CI, 23.795-32.205 months). 1- and 2-year incidence of BM were 17.8% (95% CI, 10.744-24.856%) and 38.8% (95% CI, 27.236-50.364%) respectively. The median time to BM were 42.0 months (95% CI, 15.567-68.433 months) and 19.0 months (95% CI, 11.305-26.695 months) (P=0.028) for erlotinib group and control group. Erilotinib group has a lower BM incidence than control group (1-year: 14.4%, 95% CI: 4.992%-23.808%, vs 21.1%, 95% CI: 10.712%-31.488%, P=0.384; 2-year: 26.2%, 95% CI: 18.712%-33.688%, vs 50.2%, 95% CI: 34.128%-66.272%, P=0.005). Multivariate analysis shows interval to BM were longer for erlotinib group (HR, 2.531; 95% CI, 1.272-5.051; P=0.008) and stage III disease (HR, 2.093; 95% CI, 1.035-4.231; P=0.040). Conclusions: Erlotinib administration improves time to BM and 2-year incidence of BM of stage III/IV NSCLC patients. Erlotinib administration and stage III disease predicts lower incidence of BM in all patients.

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