Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients

Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4–7.3%) at 3 months, and 11.3% (IC95 9.4–13.2%) at 12 months. The incidence of any VTE was 7.6% (IC95 6.0–9.3%) at 3 months, and 15.3% (IC95 13.1–17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis

Heterozygosity of SNP513 in intron 9 of the human calretinin gene (CALB2) is a risk factor for colon cancer

BACKGROUND: The Ca2+-binding protein calretinin (CR), while absent in normal colonocytes, is expressed in the majority of poorly differentiated colon carcinomas, and is hypothesized that mutations in the distal part (from exon 7 to 10) of the CR gene (CALB2) could be responsible for the aberrant CR expression. MATERIALS AND METHODS: Using PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, four single nucleotide polymorphisms (SNPs) were identified in CALB2 intron 9. RESULTS: A significant positive association between the genotype at SNP513 and colon cancer was found: more C/T heterozygotes were found in patients with colon tumors (60%) compared to healthy controls (35%) or patients with lung tumors (38%). Our results indicate that C/T heterozygosity at position 513 is linked to CR expression in colon tumors and colon cancer cell lines, suggesting a link with increased carcinogenesis. CONCLUSION: The SNP513 in human CALB2 may thus be a predictive marker for colon tumors

Response to Osimertinib in a Patient with Non-Small Cell Lung Cancer and Two Uncommon *EGFR* Mutations

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (*EGFR*) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several *EGFR* genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare *EGFR* mutations and showing sustained response to osimertinib

Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation

PURPOSE: To review the evidence implicating the deregulation of cyclin D1 in the pathogenesis of non-small cell lung cancer (NSCLC), and to discuss the opportunities for targeted clinical intervention. METHODS: Data published until June 2006 are summarized, and previously unpublished results from our own research are included. RESULTS: In normal cells, cyclin D1 complexes with and activates cyclin-dependent kinases (CDK) and acts as a transcriptional regulator. The protein is frequently overexpressed in a wide range of cancers, sometimes coincident with CCND1 (cyclin D1) gene amplification (5-20% of tumours). A low level of somatic mutations have been seen in certain tumours. CCND1 is amplified in NSCLC and cyclin D1 is frequently overexpressed in tumours and pre-invasive bronchial lesions, generally from one parental allele. Mutation analyses revealed a frequent CCND1 gene polymorphism (A870G) that modulates alternative splicing and allows expression of an alternative cyclin D1 transcript (transcript cyclin D1b). The encoded cyclin D1b protein lacks a specific phosphorylation site required for nuclear export. Genotype has been correlated with the risk and/or severity of disease or drug response across a range of malignancies, including lung cancer. Together, these findings suggest a strong pathological role for cyclin D1 deregulation in bronchial neoplasia. CONCLUSION: Current data indicate that cyclin D1 overexpression is not a consequence of, but rather a pivotal element in the process of malignant transformation in the lung and other tissues. This understanding may open new avenues for lung cancer diagnosis, treatment and prevention

The stem cell gene "inhibitor of differentiation 1" (ID1) is frequently expressed in non-small cell lung cancer

Inhibitor of differentiation 1 (ID1) plays a role in cellular differentiation, proliferation, angiogenesis and tumor invasion. As shown recently, ID1 is positively regulated by the tyrosine kinase SRC in lung carcinoma cell lines and with that appears as a potential new therapeutic target in non-small cell carcinoma (NSCLC). To substantiate this hypothesis we examined ID1, SRC and matrix metalloproteinase-9 (MMP-9) immunohistochemically in human NSCLC specimens

A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?

We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G>A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation