Evaluation of invasion patterns and their correlation with integrin alphavbeta expression in brain metastases of solid cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2059-2059
Author(s):  
Anna Sophie Berghoff ◽  
Orsolya Rajky ◽  
Frank Winkler ◽  
Michael Weller ◽  
Christoph Zielinski ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Brain Parenchyma ◽  
T Test ◽  
Integrin Expression ◽  
Tumor Type ◽  
Diffuse Infiltration ◽  
Invasion Pattern ◽  
Invasion Patterns

2059 Background: Understanding the pathobiology of brain metastases (BM) could guide the establishment of new targeted therapies. Methods: We collected 57 autopsy specimens of BM (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 1 kidney cancer, 2 colorectal cancer, 13 other) and histologically evaluated the patterns of invasion into the surrounding brain parenchyma. Expression of the following integrins was evaluated using immunohistochemistry: with novel antibodies for αv subunit, αvβ3, αvβ5, αvβ6 and αvβ8 integrin. Results: We observed three main invasion patterns: well-demarcated (29/57, 51%), vascular co-option (10/57, 18%) and diffuse infiltration (18/57, 32%). There was no association of invasion pattern with primary tumor type, although vascular co-option was most common in melanomas (4/10, 40%). αv subunit expression was lowest in the vascular co-option group (p = 0.05, t-test). αvβ6 levels were higher in the well-demarcated group than in the vascular co-option group (p = 0.025; t-test) and were higher in lung cancer BM than in melanoma BM (0.01, t-test). αvβ3 and αvβ5 were frequently expressed in tumoral (αvβ3: 30/57, 53%; αvβ5: 55/57, 97%) and peritumoral (αvβ3: 29/57, 51%, αvβ5: 54/57 (95%) vascular structures and 27/57 (47%) specimens showed avb5 and 6/57 (11%) αvβ3 expression on tumor cells. Prior radio- or chemotherapy did not correlate with invasion pattern or integrin expression. Conclusions: We delineate three distinct invasion patterns of BM into the brain parenchyma: well-demarcated growth, vascular co-option and diffuse infiltration. Integrin expression is frequent on tumor and vascular cells in BM and associated with distinct invasion patterns. Anti-integrin therapy could be a valid treatment option in patients with BM.

scholarly journals Impact of Immunotherapy on the Survival of Patients With Cancer and Brain Metastases

2020 ◽  
Vol 18 (7) ◽  
pp. 832-840
Author(s):  
Saber Amin ◽  
Michael Baine ◽  
Jane Meza ◽  
Chi Lin
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Small Cell ◽  
Tumor Type ◽  
National Cancer Database ◽  
Small Cell Lung ◽  
The Impact

Background: Immunotherapy has shown excellent efficacy in various cancers. However, there is a lack of knowledge regarding the significant role of immunotherapy in patients with brain metastases (BMs). The objective of this study was to investigate, using the National Cancer Database, the impact of immunotherapy on the overall survival (OS) of patients with BMs who did not receive definitive surgery of the primary tumor. Patients and Methods: Patients diagnosed with the primary cancer of non–small cell lung cancer, small cell lung cancer, other types of lung cancer, breast cancer, melanoma, colorectal cancer, or renal cancer who had BMs at the time of diagnosis were identified from the National Cancer Database. We assessed OS using a Cox proportional hazards model adjusted for age at diagnosis, sex, race, education level, income level, residential area, treatment facility type, insurance status, Charlson-Deyo comorbidity status, year of diagnosis, primary tumor type, and receipt of chemotherapy, radiation therapy (RT), and/or immunotherapy, because these factors were significantly associated with OS in the univariable analysis. Results: Of 94,215 patients who were analyzed, 3,097 (3.29%) received immunotherapy. In the multivariable analysis, immunotherapy was associated with significantly improved OS (hazard ratio [HR], 0.694; 95% CI, 0.664–0.726; P<.0001) compared with no immunotherapy. Treatment using chemotherapy plus immunotherapy was significantly associated with improved OS (HR, 0.643; 95% CI, 0.560–0.738; P<.0001) compared with chemotherapy without immunotherapy. RT plus immunotherapy was also associated with significantly improved OS (HR, 0.389; 95% CI, 0.352–0.429; P<.0001) compared with RT alone. Furthermore, chemoradiation (CRT) plus immunotherapy was associated with significantly improved OS (HR, 0.793; 95% CI, 0.752–0.836; P<.0001) compared with CRT alone. Conclusions: In this comprehensive analysis, the addition of immunotherapy to chemotherapy, RT, and CRT was associated with significantly improved OS in patients with BMs. The study warrants future clinical trials of immunotherapy in patients with BMs, who have historically been excluded from these trials.

scholarly journals A Rare Case of Diffuse Subependymal Periventricular Metastases from Small Cell Lung Carcinoma

2020 ◽  
Vol 13 (3) ◽  
pp. 1304-1310
Author(s):  
Cong Thao Trinh ◽  
Thanh Tam Thi Nguyen ◽  
Hoang Anh Thi Van ◽  
Van Trung Hoang
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Brain Parenchyma ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Small cell lung cancer, whose essence is neuroendocrine tumors, makes up proximately 14–20% of all lung cancer circumstances. Compared to non-small cell lung cancer, its clinical manifestation seems more positive and has a tendency to disseminate earlier in the process of its natural past. About 10% of patients present with brain metastases at the time of provisional diagnosis and sometimes all along the course of their disease, there will be 40–50% of developed brain metastases in addition. Although metastases in the brain parenchyma are often found in patients with advanced lung cancer, periventricular metastases are rare. We report one case of diffuse subependymal periventricular metastases from small cell carcinoma of the lung.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Type ◽  
Primary Cancer ◽  
Extracranial Metastases ◽  
The Brain

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Molecular profiling using the 92-gene assay for tumor classification of brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13583-e13583
Author(s):  
Andrew Jacob Brenner ◽  
Raul Collazo ◽  
Catherine A. Schnabel ◽  
F Anthony Greco
Keyword(s):  
Brain Metastases ◽  
Targeted Therapies ◽  
Primary Tumor ◽  
Tumor Type ◽  
Federal Drug Administration ◽  
Gene Assay ◽  
Clinical Series ◽  
The Us ◽  
Tumor Types

e13583 Background: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types/subtypes for patients with uncertain diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. Methods: An IRB-approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. Results: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested ( < 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA) (Table). Conclusions: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival. [Table: see text]

Aggressive Treatment of Primary Tumor in Patients With Non–Small-Cell Lung Cancer and Exclusively Brain Metastases

2013 ◽  
Vol 14 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Cynthia Villarreal-Garza ◽  
Dolores de la Mata ◽  
Diego G. Zavala ◽  
Eleazar O. Macedo-Perez ◽  
Oscar Arrieta
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Small Cell ◽  
Aggressive Treatment ◽  
Small Cell Lung

scholarly journals Genetic Heterogeneity Between Paired Primary and Brain Metastases in Lung Adenocarcinoma

2020 ◽  
Vol 14 ◽  
pp. 117955492094733
Author(s):  
Li Li ◽  
Zhulin Liu ◽  
Rui Han ◽  
Lin Li ◽  
Mengyao Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Adenocarcinoma ◽  
Gene Mutation ◽  
Genetic Heterogeneity ◽  
Primary Tumor ◽  
Copy Number ◽  
Primary Tumors ◽  
Paired Samples ◽  
Primary Lung Adenocarcinoma

Purpose: About one-third of nonsmall cell lung cancer (NSCLC) patients develop brain metastases (BM). However, there is an unmet need for early diagnosis and treatment of BM. The precise mechanism for BM is still unknown. However, the genetic heterogeneity between primary tumor and paired BM indicates that sampling from the primary tumor may not be able to fully represent the mutational status in metastases. In this study, the genetic heterogeneity of primary lung adenocarcinoma and paired BM was analyzed. Patients and methods: A total of 11 paired samples of primary tumors and BM from lung cancer patients were included, in which 7 paired samples of patients were finally analyzed. Samples were sequenced by whole-exome sequencing (WES) to investigate the common and unique mutations in the primary tumors and BM, and the similarities and differences in copy number variation (CNV). Results: The consistency of gene mutation between primary lung adenocarcinoma and paired BM was 33% to 86%. FAM129C and ADAMTSs specifically mutated in BM, along with NKX2-1 high amplification and SAMD2/4 copy number deletion. Conclusion: The consistency of gene mutation between primary lung adenocarcinoma and corresponding BM is relatively high, while the individual differences were significant. FAM129C and ADAMTSs mutations and high amplification of NKX2-1 may be related to BM of lung cancer. The loss of copy number of SAMD2/4 may be a potential therapeutic target for BM from lung adenocarcinoma.

scholarly journals Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Hu ◽  
Zhi-Yong Xu ◽  
Qian Zhu ◽  
Xi Liu ◽  
Si-Cong Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Advanced Lung Cancer ◽  
Tumor Type ◽  
Significant Difference

BackgroundBrain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.MethodsElectronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.ResultsFourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52–0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71–0.80; P &lt;0.001; and PFS-HR, 0.68; 95% CI, 0.56–0.82, P &lt;0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78–1.18; P = 0.72) and 0.97 (95% CI, 0.79–1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.ConclusionWe demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

RICTOR amplification as a novel therapeutic target for lung cancer brain metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3597-3597
Author(s):  
Haiying Cheng ◽  
Ni Fan ◽  
Ethan Sokol ◽  
Feng Wang ◽  
Yiyu Zou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Lung Cancer Cells ◽  
Parental Line ◽  
Metastatic Sites ◽  
The Brain

3597 Background: Approximately 20% to 50% of patients with advanced lung cancer develop brain metastases, which are associated with debilitating neurologic impairment and a dismal prognosis. There have been very limited studies investigating the genomics of brain metastases in lung cancer. Methods: We comprehensively investigated the frequency of PI3K/AKT/RICTOR/mTOR pathway aberrations in primary and metastatic sites using an extensive database of 11845 cases of lung adenocarcinoma by NGS (FoundationOne). The potential roles of RICTOR amplification in the development of brain metastases were studied both in vitro and in vivo in orthotopic mouse models. Results: Compared to the primary tumor, PI3K/AKT/mTOR gene alterations were more frequent in metastatic sites, with particular enrichment noted in brain metastases. RICTOR amplification alone accounted for the observed higher frequency both in brain metastases (brain vs. primary: 9.73% vs 3.50%, P = 2.6E-14; brain vs. other mets: 9.73% vs. 7.3%, P = 0.03) and other metastatic sites (other mets vs. primary: 7.3% vs.3.5%, P = 10E-15), whereas the frequency of PTEN, AKT1, PK3CA or mTOR genetic alterations was not different in the primary tumor, brain and other metastatic sites. In vitro, inducible RICTOR knockdown in H23 lung cancer cells (parental line with RICTOR amplification) was associated with reduced cell migration and invasion, whereas upregulation of RICTOR in HCC827 lung cancer cells (parental line with normal RICTOR copy numbers) was associated with an increase of both processes. These results were confirmed with pharmacological inhibition using mTOR1/2 inhibitors with known CNS penetration. In vivo, both inducible ablation of RICTOR and the mTOR1/2 inhibitor TAK228 (Sapanisertinib) significantly inhibited lung cancer H23-R4-Luc tumor growth in the brain, including a number of near complete responses. Mechanistic studies suggest that RICTOR may regulate the brain metastasis process through AKT and CXCL12 chemokine-CXCR4 axis. Conclusions: RICTOR amplification is the first identified actionable target that is markedly enriched in brain metastases. Our study provides a strong rationale for the development of RICTOR-targeted therapeutic strategies for the treatment and/or prevention of these major causes of lung cancer morbidity and mortality.

Racial and Gender Disparities and the Role of Primary Tumor Type on Inpatient Outcomes Following Craniotomy for Brain Metastases

2012 ◽  
Vol 19 (8) ◽  
pp. 2657-2663 ◽  
Author(s):  
Miriam Nuño ◽  
Debraj Mukherjee ◽  
Adam Elramsisy ◽  
Kristin Nosova ◽  
Shivanand P. Lad ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Primary Tumor ◽  
Gender Disparities ◽  
Tumor Type ◽  
Inpatient Outcomes ◽  
And Gender ◽  
Primary Tumor Type

Surgical treatment of brain metastases from lung cancer

1983 ◽  
Vol 58 (5) ◽  
pp. 666-671 ◽  
Author(s):  
Narayan Sundaresan ◽  
Joseph H. Galicich ◽  
Edward J. Beattie
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Survival Time ◽  
Survival Data ◽  
Primary Tumor ◽  
Systemic Disease ◽  
Initial Symptom ◽  
Postoperative Radiation Therapy ◽  
Content Type

✓ Thirty-five patients underwent surgical resection of brain metastases from non-oat-cell lung cancer between 1978 and 1981. Twenty-nine patients received postoperative radiation therapy to the brain. Twenty-three patients were male and 12 were female. Intracranial metastases occurred as the initial symptom of malignancy in 14 patients, and at varying periods following treatment of the primary tumor in 21 patients. The primary tumor and involved nodes were treated by definitive surgery in 18 patients, palliative resection and interstitial radiation in 10 patients, and by radiation therapy or chemotherapy alone in seven patients. The overall median survival time was 14 months. Favorable prognostic variables included: 1) absence of local or systemic disease at time of craniotomy (median 23 months survival time); 2) aggressive treatment of the primary tumor (median 18 months survival time); and 3) metachronous onset of brain metastases (median 15 months survival time). These survival data represent a considerable improvement over the historical 6 months median period of survival in such patients.

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