Metastatic Sites Of Lung Cancer Research Articles

Analysis of risk factors and gene mutation characteristics of different metastatic sites of lung cancer.

Risk factors vary in terms of the pattern of lung cancer metastasis and specific metastatic organs. In this study, we retrospectively analyzed the clinical risk factors of tumor metastasis in lung cancer patients and used second‐generation gene sequencing to characterize relevant gene mutations. The risk factors of different metastatic sites of real‐world lung cancer were explored to find the differentially expressed genes and risk factors in different metastatic organs, which laid a foundation for further study on the metastasis patterns and mechanisms of lung cancer. The clinical risk factors of tumor metastasis in 137 lung cancer patients who attended our department from May 2017 to March 2019 were retrospectively analyzed and grouped based on bone metastasis, brain metastasis, other distant metastasis, and no metastasis. Single‐ or multi‐factor logistic regression analysis was performed to analyze the effect of neutrophil/lymphocyte ratio/platelet/lymphocyte ratio/lymphocyte to monocyte ratio on platelets (PLTs) and bone metastasis by combining PLT values, age, pathology type, gender, and smoking history. Based on the presence or absence of bone metastasis, distal metastasis, and PLT values of lung cancer, 39 tissue specimens of primary lung cancer were taken for 773 gene grouping and gene mutation characterization. The tumor mutation load, gene copy number instability, microsatellite instability, and tumor heterogeneity among different groups were analyzed. Age and PLT level were independent risk factors for bone metastasis and distal metastasis, but not for brain metastasis. The RB1 gene was mutated during bone metastasis, and tumor heterogeneity was less in the elevated PLT group. PLT values were an independent risk factor for distant metastases from lung cancer other than the brain. Age has a significant effect on bone metastasis formation. RB1 gene mutation was significantly associated with bone metastasis.

Analysis of bevacizumab treatments and metastatic sites of lung cancer

IntroductionLiver metastasis has not been sufficiently evaluated in lung cancer so far. We retrospectively analyzed the distant metastasis of Non-squamous non-small cell lung cancer (NSQ-NSCLC), including liver metastasis, and association between prognosis and therapeutic effect of bevacizumab treatment. Patients and MethodsClinical data were collected from 1954 patients with lung cancer admitted in our hospital between 1st April 2011 and 31 March 2019. Information is extracted from the electronic medical record. Main collection data was the age, gender, smoking history, performance status, histology and driver mutation, distant metastasis site. Efficacy data of treatment including treatment duration and survival time were obtained from medical record, image data and local registry. ResultsTotal 366 patients receiving any chemotherapy with NSQ-NSCLC were eligible for this study. Most frequent extrathoracic metastasis is bone (N = 59) followed by brain (37), liver (18), adrenal gland (23), and OS analysis showed liver metastasis was worse prognosis compared to brain and bone metastasis (median OS: 11.6, 18.9, 15.0, respectively). Bevacizumab treatment was tend to have favorable efficacy in patients with each metastatic sites, especially, induced significant longer OS for patients with liver metastasis. Conclusion;Though this study was retrospective study for small sized metastatic patients, the study suggested that liver metastasis was refractory, and that bevacizumab treatment might improve the worse prognosis.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of paraesophageal lung tumors - diagnostic yield and added value.

There are few data on the use of endoscopic ultrasound (EUS) for the biopsy of suspected malignant lesions of thelung. The main objective of this study was to evaluate the performance of transesophageal EUS fine needle aspiration (EUSFNA)for the diagnosis of paraesophageal lung tumors and also for the confirmation of metastatic sites of lung cancer duringthe same procedure. We performed a retrospective study in a tertiary care unit including 19 patientswith paraesophageal lung tumors referred to our department for a lung biopsy. Transesophageal EUS-FNA was performedusing a linear echoendoscope and 22G needles. In all 19 patients with suspected lung tumors the confirmation of themalignant disease was achieved. Pathological examination revealed 16 cases of non-small cell lung cancers, 2 small cell lungcancers and one case of lung metastases. Diagnostic yield of lung EUS-FNA was 1, with no post-procedural complications. In7 cases, we performed also biopsies of suspected metastasis and all biopsies revealed the same histopathological type as theprimary tumor. Our study supports the use of this minimally invasive technique for paraesophageally locatedlung tumors and demonstrates that EUS-FNA is safe and has an excellent diagnostic yield.

EP1.14-03 Driver Genes as Predictive Indicators of Brain Metastasis in Patients with Advanced NSCLC: EGFR and ALK as Well as RET Gene Mutations

Brain metastasis is a cause of disease progression and death in lung cancer patients, and is also one of the most common metastatic sites of lung cancer. Non-small lung cancer (NSCLC) accounts for about 80% of all lung cancer patients, and adenocarcinoma has become the main subtype of NSCLC in recent years. A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small lung cancer (NSCLC). The clinicopathological data of 552 patients who received driver genes detection for lung cancer in the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from January 2015 to June 2017 were collected; NGS was used for gene detection. The driving genes for detection were EGFR, ALK, KRAS, ROS-1, BRAF, ERBB2, RET and c-MET, which were eight lung cancer driving genes recommended in NCCN guidelines. All the tests were carried out in the Center of Molecular Pathology in the Affiliated Tumor Hospital of Zhengzhou University. Of the 552 patients with advanced NSCLC, 153 (27.7%) had brain metastases. Univariate analysis showed that age (P = 0.008), gender (P = 0.016), smoking history (P = 0.010), lymph node metastasis (P = 0.003), and three driver genes: positive EGFR mutation (P = 0.001), positive ALK gene fusion (P = 0.021) and positive RET gene fusion (P = 0.003) were factors influencing the incidence of brain metastasis. Logistic multivariate regression analysis revealed that only positive EGFR mutation (P = 0.012), positive ALK gene fusion (P = 0.015), positive RET gene fusion (P = 0.003), pathological type (P = 0.009), lymph node N2–3 metastasis (P = 0.000) and a younger age (P = 0.000) were independent risk factors for brain metastasis. In addition, a ROC curve was plotted with the above factors with AUC=0.705 (P=0.000). EGFR mutation, ALK gene fusion and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes.

Incidence, prognostic factors, and a nomogram of lung cancer with bone metastasis at initial diagnosis: a population-based study.

Bone is one of the common metastatic sites of lung cancer, and its prognosis is not optimistic. We performed a study to evaluate the incidence, survival, and prognostic factors of lung cancer with bone metastasis (LCBM) at initial diagnosis, and to develop a nomogram to predict its outcomes. We conducted a retrospective study choosing 13,541 patients with LCBM from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. An X-tile analysis provided the optimal age cutoff point. The incidence, overall survival, and prognosis of bone metastasis were evaluated according to the patient information, characteristics of the tumor, and therapy. We also used multivariable Cox regression to estimate mortality hazard ratios (HRs) among patients with LCBM, while a visual nomogram was established to judge the prognosis. The incidence of disease increased with age, but survival rates show the opposite trend. The median survival time was about 4 months. In addition, although the differences for patient race is not significant (P=0.445), White patients are prone to have bone metastases from lung cancer according to the incidence analysis. The difference for laterality is also not significant (P=0.534), while the factors of age, gender, the total number of sites, histological types, grade, tumor size, and treatment are significantly related to the outcome of patients with LCBM. Furthermore, our nomogram could predict the probability of surviving to the median survival time of the population with a c-index of 0.72. Age, characteristics of the tumor, and therapy should be considered for prediction of prognosis for patients with lung cancer bone metastasis. Putatively, the younger patients and the patients with chemotherapy and surgery may indicate improved survival.

Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer

Bone is one of the prone metastatic sites of lung cancer. Osteoclast plays an important role in bone resorption and the growth of bone metastases of lung cancer. In order to treat bone metastases of lung cancer, we reported a docetaxel (DTX)-loaded nanoparticle, DTX@AHP, which could target dually at osteoclasts and bone metastatic tumor cells. The in vitro drug release from DTX@AHP exhibited pH and redox responsive characteristics. DTX@AHP displayed high binding affinity with bone matrix. In addition, DTX@AHP significantly inhibited the differentiation of RAW264.7 into osteoclast and effectively inhibited the proliferation of osteoclasts and tumor cells in in-vitro 3D bone metastases model of lung cancer. DTX@AHP could accumulate in bone metastases sites in vivo. Consequently, DTX@AHP not only markedly inhibited the growth of bone metastases of lung cancer but also reduced osteolysis in tumor-bearing mice. DTX@AHP exhibited great potential in the treatment of bone metastases of lung cancer.

An Unusual Case of Cardiac and Thyroid Metastasis From Lung Cancer

SESSION TITLE: Non-Small Cell Lung Cancer SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Lung cancer is the leading cause of cancer related death worldwide. It is metastatic in a significant percentage of patients at diagnosis. Common sites of metastasis include adrenals, brain, bone and liver. Uncommon sites include intestine, skin, heart and thyroid. We present a rare case of lung cancer with metastasis to heart and thyroid. CASE PRESENTATION: A 67 year old female presented with cough and hemoptysis for 3 weeks. Computerized tomography (CT) scan of the chest showed right sided lung mass with mediastinal lymphadenopathy. Positron emission tomography (PET-CT) scan showed increased uptake in these lesions, with no other activity outside the chest. Endobronchial ultrasound and biopsy confirmed the diagnosis of squamous cell lung cancer-stage IIIB (T2bN3M0), and she was started on chemotherapy. PET-CT done 2 months after treatment showed improvement in size of lung lesion and mediastinal lymph nodes, but new lesions were identified in the thoracic spine and ribs. Palliative radiotherapy was started in additional to chemotherapy. A PET-CT repeated after 3 months showed progression of disease with enlarging spine lesions and new lesion in the right lobe of thyroid. Thyroid lesion was biopsied and the histological findings were similar to the prior lung biopsy sample. Patient started having hemoptysis again and presented to emergency room. CT chest revealed multiple metastatic lesions in liver, large pericardial effusion and a mass involving the left ventricular lateral wall measuring up to 4.3 cm. Echocardiogram confirmed large pericardial effusion and a large extra-cardiac mass attached to the lateral wall of left ventricle. Given her prognosis and poor response to treatment, she opted for hospice care. DISCUSSION: More than one thirds of patients with lung cancer have spread at the time of diagnosis. Common sites of metastasis from lung cancer include adrenals, brain, bone and liver. Rarely lung cancer can metastasize to intestines, skin, heart and thyroid. Very few cases of cardiac metastasis from lung cancer are reported. Most cases are diagnosed on autopsy. About two thirds of all cardiac metastases involve the pericardium, one third the epicardium or myocardium and rarely the endocardium. Of all the cardiac metastasis, it is adenocarcinoma in 26%, squamous cell carcinoma in 23.4%, undifferentiated in 21.2%, and bronchoalveolar carcinoma in 17.4% of cases(1). Thyroid metastasis from primary lung cancer is an even rarer thing. Common cancers which metastasize to thyroid include colon and kidneys. On extensive literature review, we could find very few cases of lung metastases to thyroid. Our patient had unfortunately two unusual metastatic sites of lung cancer. CONCLUSIONS: Lung cancer can rarely metastasize to locations like heart and thyroid, and we report the only case in literature with combined cardiac and thyroid metastasis. Reference #1: Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol 2007;60:27-34. DISCLOSURE: The following authors have nothing to disclose: Jay Patel, Shejuti Guha, Vishesh Paul No Product/Research Disclosure Information

Immune Checkpoint Protein Expression at Multiple Metastatic Sites of Lung Cancer

Immune Checkpoint Protein Expression at Multiple Metastatic Sites of Lung Cancer

Nebulizable colloidal nanoparticles co-encapsulating a COX-2 inhibitor and a herbal compound for treatment of lung cancer

A challenging disease such as lung cancer requires the combination of different modalities to achieve beneficial therapeutic outcomes. In this work, PLGA nanoparticles were chosen as colloidal carrier for two drugs with reported anti-lung cancer activity: naringin and celecoxib. PLGA nanoparticles were prepared and characterized for their particle size, zeta potential, entrapment efficiency, in vitro release, stability, morphology, cytotoxicity, as well as aerosolization and nebulization behaviors. Their biodistribution pattern upon pulmonary aerosolization, and safety on healthy lung tissues were determined as well. Results showed that the described system displayed a particle size <260nm with unimodal distribution, entrapment efficiency for celecoxib and naringin reaching 96% and 62% respectively and a controlled release profile for the two drugs. The selected formula displayed favorable nebulization properties with high drug deposition percentages in lower impinger and impactor stages. It also exhibited higher cytotoxic activity on A549 lung cancer cell lines compared to the free drugs combination, while displaying considerable safety on healthy lung tissues. Biodistribution studies delineated the lung deposition potential of the nanoparticles accompanied with high distribution to the bones, brain and liver which are common metastatic sites of lung cancer, proving their promising nature in the treatment of lung cancer.

Unchanged frequency of loss of heterozygosity and size of the deleted region at 8p21-23 during metastasis of lung cancer.

The genetic mechanisms involved in lung cancer development and progression are beginning to be understood. Many studies have documented frequent loss of heterozygosity (LOH) at specific chromosomal regions in cancer cells; this implies that tumor suppressor genes (TSG) are usually present in those regions. Recently, it has been reported that LOH or chromosomal deletions at chromosome 8p21-23 represent early events frequently occurring in lung cancer. In addition, the size of these chromosome 8 deletions, as well as their frequency, was also reported to increase during lung cancer progression. To determine the spectrum and frequency of alterations of chromosome 8p21-23 in human lung cancer and whether these increase with progression of the tumors, we performed LOH analysis of chromosome 8p and 3p in the genomic DNA from cells from primary and metastatic sites of lung cancer, as well as from normal lung. We studied 35 subjects with primary lung cancer including 30 tumors with distant metastasis. Detection of allelic deletion utilized a PCR-based approach of microsatellite polymorphism analysis, which was performed using the microsatellite markers D8S1130, D8S1106, D8S511, D8S1827, D8S549, D8S261, LPL, D8S258, D8S136, NEFL, D3S1295, D3S1313, D3S1234, D3S1300, D3S1351, D3S1339, and D3S1340. The overall allelic deletion rates were 10 of 28 (35.7%) at 8p and 13 of 33 (39.4%) at 3p. The allelic deletions in the primary cancer and its metastatic sites were in each case identical in both frequency and size of the deleted regions. In our analysis, 8p21-23 deletions were not always associated with 3p deletions in primary lung cancer. These results therefore suggest that allelic deletion at chromosome 8p21-23 is an early and frequent event in the carcinogenesis and development of lung cancer, independent of chromosome 3p deletion. However, a continuing increase in the frequency of LOH at 8p21-23 and in the size of the deleted region rarely occurs during the process of metastasis.

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Tumor stem cell assay for detecting metastases of human lung cancer.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.