Differential Expression of Decorin in Metastasising Colorectal Carcinoma Is Regulated by miR-200c and Long Non-Coding RNAs

Decorin (DCN) is one of the matricellular proteins that participate in normal cells’ function as well as in cancerogenesis. While its expression in primary tumours is well known, there is limited data about its expression in metastases. Furthermore, the post-transcriptional regulation of DCN is still questionable, although it is well accepted that it is an important mechanism of developing metastatic cancer. The aim of our study was to analyse the expression of DCN and its potential regulatory ncRNAs in metastatic colorectal carcinoma (CRC). Nineteen patients with metastatic CRC were included. Using qPCR, we analysed the expression of DCN, miR-200c and five lncRNAs (LUCAT1, MALAT1, lncTCF7, XIST, and ZFAS1) in lymph node and liver metastases in comparison to the invasive front and central part of a primary tumour. Our results showed insignificant upregulation of DCN and significant upregulation for miR-200c, MALAT1, lncTCF7 and ZFAS1 in metastases compared to the primary tumour. miR-200c showed a positive correlation with DCN, and the aforementioned lncRNAs exhibited a significant positive correlation with miR-200c expression in metastatic CRC. Our results suggest that DCN as well as miR-200c, MALAT1, lncTCF7 and ZFAS1 contribute to the development of metastases in CRC and that regulation of DCN expression in CRC by ncRNAs is accomplished in an indirect manner.

Yttrium-90 Internal Radiation Therapy as Part of the Multimodality Treatment of Metastatic Colorectal Carcinoma

About 70% of patients with metastatic colorectal carcinoma (mCRC) have liver metastases. Hepatic failure accounts for most mCRC-related deaths. Therefore, controlling liver metastases may improve outcomes. A data overview of liver-directed treatment using yttrium-90 selective internal radiation therapy (SIRT) is provided as part of a multimodality treatment. SIRT in mCRC is discussed, and the prognostic factors for patient selection are defined. Pooled analyses of three recent trials incorporating SIRT plus chemotherapy revealed subsets of patients with mCRC who might benefit from SIRT. A multidisciplinary treatment for most mCRC patients is proposed to achieve long-term survival in this cohort of patients.

KRAS, NRAS and BRAF mutational status and first line treatment patterns in Slovenian population with metastatic colorectal carcinoma: Five year results.

e15546 Background: A phase IV non-interventional study was performed from 2013 till 2018 including 650 patients with primary aim to assess KRAS, NRAS and BRAF mutational status in Slovenian population with metastatic colorectal carcinoma (mCRC) suitable for first-line treatment. The evaluation of decisions for first-line treatment regarding the biomarkers status and assessing the possible impact of the time period of the biomarker status analysis report on the treatment decision were also incorporated in the analysis. The molecular analyses for KRAS and NRAS gene mutations were performed on exons 2, 3 and 4, and for BRAF gene mutations on exon 15. The first line systemic treatment options for RAS (KRAS/NRAS) wild type (wt) and mutated type (mt) mCRC subjects were as follows: chemotherapy - Fluoropyrimidine based systemic therapy combined with oxaliplatin and/or irinotecan with/without VEGF inhibitor bevacizumab and for RAS wt subjects, with/without EGFR inhibitors, cetuximab or panitumumab. Methods: To indicate the degree of certainty of KRAS, NRAS and BRAF status frequency as being wild type or mutant type 95% confidence interval was calculated. Results: The KRAS/NRAS/BRAF mutation rates were as follows - The distribution of subjects with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively. Eighty nine percent of the subjects had NRAS wild type tumours and 86.1% had BRAF wild type tumours. The most frequently used treatment regardless the biomarkers status and in accordance with the treatment guidelines was bevacizumab based combination therapy (53.1%). The EGFR inhibitor (cetuximab or panitumumab) based combination therapy was used in one third of mCRC subjects (30.9%), all with mCRC RAS wt. The time period from the initial presentation of the patient until the biomarker status analysis report was two weeks. Conclusions: With this study, we have proven that the distribution of the mutations in exons 2-4 of KRAS and NRAS genes and exon 15 in the BRAF gene in the Slovenian population with metastatic colorectal cancer matches historical data. Based on this, we conclude that the treatment decision in Slovenian population with metastatic colorectal carcinoma should be in the accordance with international treatment guidelines and on evidence based medicine. The molecular analysis performed at the Institute of Oncology Ljubljana was providing necessary biomarkers status report in an acceptable time that didn’t affect the treatment decision or delay the needed cancer treatment.

A rare presentation of panitumumab-involved interstitial lung disease: Spontaneous pneumomediastinum

Introduction Developments in targeted molecular therapies have considerably improved patient survival in cancer. Panitumumab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). It is used to treat metastatic colorectal carcinoma. Although panitumumab is well tolerated in most patients, pulmonary toxicity, especially interstitial lung disease (ILD), is a life-threatening condition. The presentation of panitumumab-induced ILD with spontaneous pneumomediastinum and subcutaneous emphysema is rarely reported. Case report We describe a 61-year-old male with metastatic colorectal carcinoma treated with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) and panitumumab. He presented to our hospital with a complaint of severe dyspnea. On the evaluation of dyspnea, the patient was diagnosed with ILD. Management and outcome After exclusion of other common causes of pneumomediastinum and subcutaneous emphysema, panitumumab was attributed as a cause of ILD. Oxygen therapy via high flow nasal cannula and intravenous methylprednisolone regimen was started. After two weeks, the patient became asymptomatic with the radiologic amelioration. Discussion Panitumumab-induced ILD is associated with a poor prognosis and might occur randomly in one year after the drug administration. The possibility of the disease should be considered on every admission. Early recognition, discontinuation of causative medication, and immediate glucocorticoid therapy are essential to reduce mortality.