Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer

Background First line chemotherapy is effective in 75 to 80% of patients with metastatic colorectal cancer (mCRC). We studied whether microRNA (miR) expression profiles can predict treatment outcome for first line fluoropyrimidine containing systemic therapy in patients with mCRC. Methods MiR expression levels were determined by next generation sequencing from snap frozen tumor samples of 88 patients with mCRC. Predictive miRs were selected with penalized logistic regression and posterior forward selection. The prediction co-efficients of the miRs were re-estimated and validated by real-time quantitative PCR in an independent cohort of 81 patients with mCRC. Results Expression levels of miR-17-5p, miR-20a-5p, miR-30a-5p, miR-92a-3p, miR-92b-3p and miR-98-5p in combination with age, tumor differentiation, adjuvant therapy and type of systemic treatment, were predictive for clinical benefit in the training cohort with an AUC of 0.78. In the validation cohort the addition of the six miR signature to the four clinicopathological factors demonstrated a significant increased AUC for predicting treatment response versus those with stable disease (SD) from 0.79 to 0.90. The increase for predicting treatment response versus progressive disease (PD) and for patients with SD versus those with PD was not significant. in the validation cohort. MiR-17-5p, miR-20a-5p and miR-92a-3p were significantly upregulated in patients with treatment response in both the training and validation cohorts. Conclusion A six miR exp

Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient

The use of perfusion CT for the evaluation of therapy combining AZD2171 with gefitinib in cancer patients

The purpose of this study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (CTP) in evaluating the hemodynamic response of tumors in the chest and abdomen treated with a combination of AZD2171 and gefitinib. Thirteen patients were examined just before and every 4-6 weeks after starting therapy. Following intravenous injection of a contrast agent, dynamic image acquisition was obtained at the level of a selected tumor location. To calculate perfusion, the maximum-slope method was used. Pre-treatment average perfusion for extra-hepatic masses was 84 ml/min/100 g, for liver masses arterial perfusion was 25 ml/min/100 g, and a portal perfusion of 30 ml/min/100 g was found. After the administration of AZD2171 and gefitinib, in extra-hepatic masses an initial decrease in perfusion of 18% was followed by a plateau and in liver masses an initial decrease of 39% within the lesions and of 36% within a rim region surrounding the lesions was followed by a tendency to recovery of hepatic artery flow. In conclusion, CTP is feasible in showing changes of perfusion induced by anti-angiogenic therapy