Survival Rate For Lung Cancer Research Articles

Automatic Detection of Lung Nodules Using 3D Deep Convolutional Neural Networks

Lung cancer is the leading cause of cancer deaths worldwide. Accurate early diagnosis is critical in increasing the 5-year survival rate of lung cancer, so the efficient and accurate detection of lung nodules, the potential precursors to lung cancer, is paramount. In this paper, a computer-aided lung nodule detection system using 3D deep convolutional neural networks (CNNs) is developed. The first multi-scale 11-layer 3D fully convolutional neural network (FCN) is used for screening all lung nodule candidates. Considering relative small sizes of lung nodules and limited memory, the input of the FCN consists of 3D image patches rather than of whole images. The candidates are further classified in the second CNN to get the final result. The proposed method achieves high performance in the LUNA16 challenge and demonstrates the effectiveness of using 3D deep CNNs for lung nodule detection.

Transmembrane-4 L-six family member-1 (TM4SF1) promotes non-small cell lung cancer proliferation, invasion and chemo-resistance through regulating the DDR1/Akt/ERK-mTOR axis

BackgroundTumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer. Transmembrane-4 L-six family member-1 (TM4SF1), an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of TM4SF1 in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity.MethodsTM4SF1 was silenced by small interfering RNA transfection.TM4SF1 expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied.ResultsTM4SF1 was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of TM4SF1 is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of TM4SF1 substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of TM4SF1 induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that TM4SF1 is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis.ConclusionsThese findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.

Early non-invasive detection of stage Ia lung cancer using circulating tumor DNA methylation haplotypes (ctmDNA) in plasma.

e13159 Background: Lung cancer is one of the most common forms of cancer and is responsible for approximately 1.8 million deaths per year worldwide. The current 5-year survival rate for lung cancer is only 18%; however, this improves to 56% if the cancer is detected early. While low-dose CT scans have shown promise as an early detection method, only 16% of lung cancer is currently detected at an early stage. We therefore set out to develop a non-invasive blood-based screening assay to identify lung cancer at an early stage using ctmDNA (circulating tumor methylated DNA haplotypes). Methods: Blood samples were prospectively collected from two partner hospitals from 325 healthy individuals and 116 individuals diagnosed with lung nodules by low-dose CT scan in EDTA or Streck BCT tubes and immediately separated into plasma. Patients with lung nodules that appeared cancerous then underwent surgical resection, and cancer diagnosis was confirmed via pathology. Patients were matched between healthy and cancer groups by age, sex, and smoking status. Plasma samples were processed using the Singlera Genomics LUNA assay, a targeted bisulfite sequencing method which identifies methylation haplotype patterns related to early-stage lung cancer. 241 samples were used to train a classification model based on pathology results, and 200 samples were used as a test set to validate the model. Results: In the independent test set, the LUNA assay was able to show a sensitivity of 91.9% to detect early-stage lung cancer with a specificity of 93.3% in healthy patients. Even patients with stage Ia lung cancer were readily detected by the LUNA assay (sensitivity of 91.7%). Conclusions: We have shown that ctmDNA can be utilized to non-invasively screen for early-stage lung cancer with high sensitivity and specificity, paving the way for a blood-based lung cancer early screening assay.

Trends in immunotherapy use and survival impact in stage IV non-small cell lung cancer.

e20715 Background: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. 5-year survival rate for metastatic non-small cell lung cancer (NSCLC) is estimated at 4%. For patients who lack a driver mutation, platinum based chemotherapy had been the cornerstone treatment, but the addition of immunotherapy has altered the treatment landscape for many advanced NSCLC patients. Immunotherapy, with or without chemotherapy, has been demonstrated in many clinical trials to extend survival in both the first-line setting as well as subsequent lines of therapy. While the clinical trial data over the past several years has been robust, less is known about how these agents have fared in routine clinical practice. To understand this better, we utilized the National Cancer Data Base (NCDB) to examine the survival of patients who received immunotherapy for stage IV NSCLC. Methods: We queried the NCDB from 2004-2015 for patients with stage IV NSCLC treated with chemotherapy and at least 3 months of follow-up. Multivariable logistic regression was used to determine predictors of immunotherapy use. Multivariable cox regression was used to determine predictors of overall survival. A propensity score was calculated and used to mitigate indication bias. Results: Of 203,069 eligible patients, 5,877 received immunotherapy. The median age was 65 years (40-90). The median follow up was 10.6 months (3-154). Patients were more likely to receive immunotherapy if they were younger, had a lower comorbidity score, received treatment at an academic facility, had adenocarcinoma histology, private insurance, Caucasian race, and a more recent treatment year. The use of immunotherapy rose steadily across the dataset years, rising from 1% to 12%. Predictors of survival were younger age, lower comorbidity score, lower grade tumor, treatment at an academic facility, higher education, higher income, private insurance, metropolitan location, immunotherapy use, adenocarcinoma histology, and more recent year of treatment. On propensity-matched Kaplan-Meier analysis patients treated with immunotherapy in addition to chemotherapy had improved survival, 13.7 months compared to 11.8 months, p < 0.0001. Conclusions: This analysis demonstrates improved overall survival in stage IV NSCLC patients who received immunotherapy. There are inherent limitations of retrospective analyses of data from large databases, however the survival improvement noted in this study is concordant with the more robust prospective clinical research published to date.

LDH isoenzymes to hospital patients with exacerbation of chronic obstructive pulmonary disease (COPD)

Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.

Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer

BackgroundLung cancer is the leading cause of cancer death in China and around the world. Early detection is key to improving the survival rate of non-small cell lung cancer (NSCLC). Alteration in glycosylation has been observed in cancers, and glycans can be a source for the development of new biomarkers for NSCLC.MethodsIn this glycan biomarker discovery study, we measured serum N- and O-glycan profiles in NSCLC patients with different stages and healthy controls by performing lectin microarray analysis. The alterations of serum glycopatterns were compared between NSCLC patients and controls, and the stage-related changes in serum glycosylation were evaluated.ResultsThere were 18 lectins (e.g., AAL, Jacalin, GSL-I and DBA) to give significantly alterations of serum glycopatterns in lung adenocarcinoma compared with control group. Meanwhile, 16 lectins (e.g., Jacalin, HHL, and PHA-E+L) exhibited significantly alterations of serum glycopatterns in squamous cell carcinoma (SCC) compared with control group. Importantly, most of the lectins showing altered signals exhibited significantly increased or decreased NFIs in patients with early stage adenocarcinoma and SCC.ConclusionsThe serum glycan profiles were significantly different between NSCLC and healthy control, and most of the glycosylation changes had occurred at early stage. Further evaluation is needed to examine the diagnostic value of the glycan markers identified in this study.

Use of Antihypertensive Medications and Survival Rates for Breast, Colorectal, Lung, or Stomach Cancer.

Using time-dependent Cox regression models, we examined associations of common antihypertensive medications with overall cancer survival (OS) and disease-specific survival (DSS), with comprehensive adjustment for potential confounding factors. Participants were from the Shanghai Women's Health Study (1996-2000) and Shanghai Men's Health Study (2002-2006) in Shanghai, China. Included were 2,891 incident breast, colorectal, lung, and stomach cancer cases. Medication use was extracted from electronic medical records. With a median 3.4-year follow-up after diagnosis (interquartile range, 1.0-6.3), we found better outcomes among users of angiotensin II receptor blockers with colorectal cancer (OS: adjusted hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.44, 0.86; DSS: adjusted HR = 0.61, 95% CI: 0.43, 0.87) and stomach cancer (OS: adjusted HR = 0.62, 95% CI: 0.41, 0.94; DSS: adjusted HR = 0.63, 95% CI: 0.41, 0.98) and among users of β-adrenergic receptor blockers with colorectal cancer (OS: adjusted HR = 0.50, 95% CI: 0.35, 0.72; DSS: adjusted HR = 0.50, 95% CI: 0.34, 0.73). Better survival was also found for calcium channel blockers (DSS: adjusted HR = 0.67, 95% CI: 0.47, 0.97) and diuretics (OS: adjusted HR = 0.66, 95% CI: 0.45, 0.96; DSS: adjusted HR = 0.57, 95% CI: 0.38, 0.85) with stomach cancer. Our findings suggest angiotensin II receptor blockers, β-adrenergic receptor blockers, and calcium channel blockers might be associated with improved survival outcomes of gastrointestinal cancers.

Diagnóstico precoz del cáncer de pulmón: utilidad de la tomografía computarizada de baja dosis de radiación

IntroductionThe prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis. Material and methodsWe performed low-dose CT (LDCT) in asymptomatic individuals ≥50years old, smokers or former smokers of ≥10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5years. ResultsWe studied 4,951 individuals (65.4% males) with an average age of 56.89±5.26years; 550 presented nodules. Of the 3,891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49LC), 25 (52.08%) in stageI. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients). ConclusionLDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC.

Serum miR-210-3p as a Potential Noninvasive Biomarker of Lung Adenocarcinoma: A Preliminary Study.

Background: Development of noninvasive biomarkers could potentially contribute to extending the 5-year overall survival rate of nonsmall cell lung cancer (NSCLC) patients. Circulating microRNAs (miRNAs), due to their high stability, have the potential to become valuable cancer biomarkers. Methods: Using reverse transcription-quantitative polymerase chain reaction and testing three methods for data normalization, the expression levels of six miRNAs were evaluated in serum samples obtained from 50 NSCLC patients. Subsequently, the clinical significance of the tested miRNAs was determined. Results: Significant downregulation of miR-21-5p, miR-30a-5p, and miR-126-3p and upregulation of miR-210-3p and miR-486-5p in serum samples of NSCLC patients were identified in comparison to healthy controls. miR-205-5p appeared to be undetectable in all tested samples. Furthermore, miR-210-3p was differentially expressed between two subtypes of NSCLC. Receiver operating characteristic analysis for miR-210-3p revealed the area under the curve of 0.842 (95% confidence interval, 0.72-0.96; p = 0.0003) and demonstrated that miR-210-3p displayed considerable accuracy in discriminating between lung adenocarcinoma (AC) patients and healthy controls. Conclusions: Findings from this preliminary study indicate that five of six tested miRNAs were deregulated in the serum of NSCLC patients. Moreover, miR-210-3p appears to be a promising biomarker for diagnosis of lung AC.

144P - Clinical and treatment features associated with improved 5-year survival rate in ALK-positive lung cancer treated with ALK-TKIs

144P - Clinical and treatment features associated with improved 5-year survival rate in ALK-positive lung cancer treated with ALK-TKIs

Early diagnosis of lung cancer: is rapid access CT scanning the answer?

Lung cancer remains the most common cause of cancer mortality in Britain. The 10-year survival rate from the disease is in the order of 5%, because the majority of patients present with advanced disease. Five-year survival rates for lung cancer in the UK from 2000–2014 are only 13%, lagging far behind most other EU nations. These findings, which were published in the Lancet in January 2018, have also been widely reported in many national newspapers.1 Currently, the US, Canada, and a number of European countries have implemented screening programmes for lung cancer with low-dose computed tomography (CT). Early diagnosis by low-dose CT (LDCT) screening has been shown to lead to a reduction in lung cancer mortality by 20% in the National Lung Screening Trial (NLST), a large randomised clinical trial from the US.2 The final results from the Dutch-Belgian NELSON trial, the only other clinical study powered to detect a reduction in mortality, are still awaited.3 The Accelerate, Coordinate, Evaluate (ACE) Programme was funded by Cancer Research UK and Macmillan Cancer Support, and took place between 2014 and 2017. The final ACE report was published in April 2017.4 Although not funding local screening programmes as such, the ACE programme was an important early diagnostic cancer initiative focused on evaluating a wide variety of innovations designed to either streamline diagnostic pathways or identify individuals at an increased risk of cancer.5 One strand of ACE was the lung cancer cluster, which aimed to explore the most …

MiR-183-5p is required for non-small cell lung cancer progression by repressing PTEN

Lung cancer is the leading cause in all cancer deaths. A low survival rate and high recurrence rate of lung cancer make the endeavor to identify new, more effective therapies a primary goal. MicroRNAs (miRNAs) are regarded as regulators of tumorigenesis and it is known that miR-183-5p is significantly upregulated in non-small cell lung cancer (NSCLC), suggesting it has an oncogenic function in lung cancer. In this study, we found that miR-183-5p could promote lung carcinogenesis by directly targeting phosphatase tensin (PTEN). Further experiments indicated that miR-183-5p could suppress p53 and activate AKT signaling through phosphorylation. Moreover, our data indicated that miR-183-5p promoted tumor metastasis and tumor growth in vivo. Collectively, these results showed that miR-183-5p is required for NSCLC development through the suppressing PTEN, and might be a promising target in the diagnosis and treatment of lung cancer in the future.

Systemic immune-inflammation index is a promising noninvasive marker to predict survival of lung cancer: A meta-analysis.

Background:The prognostic value of pretreatment systemic immune-inflammation index (SII) in lung cancer has yet to be fully established.Methods:Relevant articles were obtained by performing a systematic search. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the relationship between SII index and overall survival (OS) in lung cancer; the OS was calculated from the time of cancer diagnosis to the date of death due to any cause or to the last date of follow-up.Results:In total, 2786 patients with lung cancer from 7 studies were included in this meta-analysis. The median thresholds to define high SII was 640 (range 395.4–1600) in the analyzed studies. The pooled HR for OS was 1.77 (95% CI: 1.54–2.00, P < .001), suggesting that the patients with a high SII score had a worse OS. In addition, results from subgroup meta-analysis showed the significant prognostic significance of SII in lung cancer. Especially, the predictive value of SII was significant in the multivariable model for NSCLC (HR: 1.97, 95% CI: 1.69–2.25, P < .001; 5 studies, 1746 patients), and SCLC (HR: 1.38, 95% CI: 1.02–1.85, P < .001; 1 study, 919 patients).Conclusion:Our data suggest that high SII index indicates poor survival rate in lung cancer. Further researches are warranted to verify the significance of SII index in clinical practice.

Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades.

PurposeThis study used the Surveillance, Epidemiology, and End Results (SEER) data to investigate the changes in incidence, treatment, and survival of lung cancer from 1973 to 2015.Patients and methodsThe clinical and epidemiological data of patients with lung cancer were obtained from the SEER database. Joinpoint regression models were used to estimate the rate changes in lung cancer related to incidence, treatment, and survival.ResultsFrom 1973 to 2015, the average incidence of lung cancer was 59.0/100,000 person-years. The incidence increased initially, reached a peak in 1992, and then gradually decreased. A higher incidence rate was observed in males than in females and in black patients than in other racial groups. Since 1985, adenocarcinoma became the most prevalent histopathological type. The surgical rate for lung cancer was about 25%, and treatment with chemotherapy showed an increasing trend, while the radiotherapy rate was in downward trend. The surgical rate for non-small-cell lung cancer (NSCLC) was higher than that for small cell lung cancer (SCLC), while chemotherapy for SCLC far exceeded that for NSCLC. Treatment with chemotherapy and radiotherapy for advanced stage had higher rate than early stage. The 5-year relative survival rate of lung cancer increased with time, but <21%.ConclusionIn the past four decades, the lung cancer incidence increased initially and then gradually decreased. Surgical rate experienced a fluctuant reduction, while the chemotherapy rate was in upward trend. The 5-year relative survival rate increased with years, but was still low.

EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil.

In Brazil, cancer is the second most common cause of death. Most patients in resource-limited countries are diagnosed in advanced stages. Current guidelines advocate for EGFR mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of EGFR testing and the changes in patterns of testing overtime. This was an observational, retrospective study. We obtained deidentified data from a commercial database, which included 11,684 patients with non-small cell lung cancer treated between 2011 and 2016 in both public and private settings. We analyzed the frequency of EGFR mutation testing over time. We also directly studied 3,664 tumor samples, which were analyzed between 2011 and 2013. These samples were tested for EGFR mutations through an access program to tyrosine kinase inhibitors in Brazil. Overall, 38% of patients were tested for EGFR mutations; 76% of them were seen in the private sector, and 24% were seen in the public center. The frequency of testing for EGFR mutations increased significantly over time: 13% (287/2,228 patients) in 2011, 34% (738/2,142) in 2012, 39% (822/2,092) in 2013, 44% (866/1,972) in 2014, 53% (1,165/2,184) in 2015, and 42% (1,359/3,226) in 2016. EGFR mutations were detected in 25.5% of analyzed samples (857/3,364). Deletions in Exon 19 were the most frequent mutations, detected in 54% of patients (463/857). Our findings suggest that the frequency of EGFR mutation in this cohort was lower than that found in Asia but higher than in North American and Western European populations. The most commonly found mutations were in Exon 19 and Exon 21. Our study shows that fewer than half of patients are being tested and that the disparity is greater in the public sector. These data not only indicate the shortage of testing but also show that the rates of positivity in those tested seem to be higher than in other cohorts for which data have been published. This study further supports the idea that awareness and access to testing should be improved in order to improve survival rates in lung cancer in Brazil.

Integrative Analysis of CD133 mRNA in Human Cancers Based on Data Mining.

CD133 is a wildly used cancer stem cell marker. The purpose of this study was to explore the significance of CD133 mRNA in human cancers mainly based on The Cancer Genome Atlas (TCGA) database. Bioinformatic analyses were done by using public repositories, including BioGPS, SAGE Genie tools, Oncomine analysis, Regulome Explorer, COSMIC analysis, and Kaplan-Meier Plotter. The main findings in this study were: 1) High CD133 mRNA was correlated with a benign survival rate of gastric cancer and lung cancer; 2) Transmembrane protein 125 (TMEM125) in bladder urothelial carcinoma and intercellular adhesion molecule 2 (ICAM2) in ovarian serous cystadenocarcinoma were closely related to CD133 expression; 3) The location and the topological structure of CD133 protein were not determined by its transcript variant in cancer cells; 4) CD38 and CD200 may be used as novel surface markers for solid cancers. However, the mechanism of these findings is not completely clear, further studies have to be performed in the future.

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80–85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC.Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein–protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset.Results: A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha (TOP2A), a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 (IL-6) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest P-value. Besides, five hub genes with high degree of connectivity were selected, including TOP2A, CCNB1, CCNA2, UBE2C, and KIF20A, and they were all correlated with worse OS in NSCLC. Conclusion: The results showed that TOP2A, CCNB1, CCNA2, UBE2C, KIF20A, and IL-6 may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.

Prevention of Brain Metastases.

The incidence of brain metastases is projected to rise because survival rates of lung cancer, breast cancer, and melanoma continue to improve (1). The brain is being identified as a sanctuary site for harboring metastases despite excellent control of extracranial disease. This is thought to occur because the drug therapies that control extracranial disease have limited central nervous system (CNS) penetration. The development of brain metastases is a devastating diagnosis affecting both quality of life (QOL) and survival. Symptoms after diagnosis can include headache, nausea, vomiting, seizure, neurocognitive decline, and focal neurologic deficit. Some of these symptoms can be irreversible even after successful treatment of intracranial disease. Treatment of brain metastases often necessitates surgery and radiation. There have been some reports of systemic therapies offering an intracranial response however long-term data is lacking. These treatments for CNS metastases can also lead to neurocognitive sequelae impacting quality of life. Therefore, preventing disease from spreading to the brain is a topic that has generated much interest in oncology. Prophylactic cranial Irradiation (PCI) has been used in leukemia, small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). While showing effectiveness in preventing intracranial disease development, its carries with it side effects of neurocognitive decline that can affect QOL. There are Clinical trials exploring novel delivery of PCI and concurrent neuroprotective drug therapy to try to mitigate these neurocognitive sequelae. These will be important trials to complete, as PCI has shown promise in controlling disease and prolonging survival in select patient populations. There are also drug therapies that have shown efficacy in preventing CNS metastases development. This review will explore the current therapies available to prevent CNS metastases.

Trend analysis of major cancer statistics according to sex and severity levels in Korea.

Existing epidemiologic reports or studies of cancer statistics in Korea lack sufficient data on cancer severity distributions and observed survival rates. This study analyzed trends in major cancer statistics according to sex and severity levels in Korea from 2006 to 2013. We included eight cancers (hepatocellular carcinoma, and thyroid, colorectal, gastric, lung, prostate, breast, and cervical cancer), using Korea Central Cancer Registry data. Severity level was classified by Surveillance, Epidemiology, and End Results (SEER) stage as follows: localized, regional, distant, or unknown. Numbers of incident cancer cases from 2006 to 2013 were described by sex and SEER stage. We estimated up to 8-year observed survival rates of major cancers by sex and SEER stage, and provided prevalence rates by sex and SEER stage in 2011, 2012, and 2013. Although increases in new cancer cases are slowing and the total number of incident cancer cases in 2013 decreased for the first time since 2006, the number of prevalent cancer cases was 663,530 in 2013, an increase of 13.3% compared to 2011. Among the five cancers affecting both sexes, sex-related differences in 5-year observed survival rates for lung cancer were greatest in the localized stage (men, 31.9%; women, 48.1%), regional stage (men, 20.0%; women, 31.3%), and unknown stage (men, 24.3%; women, 37.5%). The sum of the proportions of localized and regional stages for thyroid and breast cancer was over 90% in 2013, while the sum of the proportions of localized and regional stages for lung cancer was only 56.7% in 2013. Differences in observed survival rates between men and women were prominent in lung cancer for all SEER stages. The reported epidemiologic data from this study can be used to obtain a more valid measure of cancer burden using a summary measure of population health.

Membrane expression of thymidine kinase 1 and potential clinical relevance in lung, breast, and colorectal malignancies

BackgroundLung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance.MethodsWe assessed TK1 surface localization by flow cytometry and confocal microscopy in lung (NCI-H460, A549), breast (MDA-MB-231, MCF7), and colorectal (HT-29, SW620) cancer cell lines. We also isolated cell surface proteins from HT-29 cells and performed a western blot confirming the presence of TK1 on cell membrane protein fractions. To evaluate TK1’s clinical relevance, we compared TK1 expression levels in normal and malignant tissue through flow cytometry and immunohistochemistry. We also analyzed RNA-Seq data from The Cancer Genome Atlas (TCGA) to assess differential expression of the TK1 gene in lung, breast, and colorectal cancer patients.ResultsWe found significant expression of TK1 on the surface of NCI-H460, A549, MDA-MB-231, MCF7, and HT-29 cell lines and a strong association between TK1’s localization with the membrane through confocal microscopy and Western blot. We found negligible TK1 surface expression in normal healthy tissue and significantly higher TK1 expression in malignant tissues. Patient data from TCGA revealed that the TK1 gene expression is upregulated in cancer patients compared to normal healthy patients.ConclusionsOur results show that TK1 localizes on the surface of lung, breast, and colorectal cell lines and is upregulated in malignant tissues and patients compared to healthy tissues and patients. We conclude that TK1 is a potential clinical biomarker for the treatment of lung, breast, and colorectal cancer.