Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends.

Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with a mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples, is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made, thanks to continuous extensive research in this field, however, no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can easily be tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

An open label phase II study evaluating first-line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients with tumors showing high EGFR gene copy number.

BACKGROUND: First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. PATIENTS AND METHODS: A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells. FINDINGS: Between December 2007 and April 2011, tumor samples from 149 subjects were screened for EGFR gene copy number by fluorescence in-situ hybridization (FISH), Out of 49 patients with positive EGFR FISH test, 45 were treated with erlotinib. Median PFS in the intent-to-treat population was 3.3 months (95%CI: 1.8-3.9 months), and median overall survival was 7.9 months (95% CI: 5.1-12.6 months). Toxicity profile of erlotinib was consistent with its known safety profile. The trial was stopped prematurely at 63% of originally planned sample size due to accumulating evidence that EGFR gene copy number should not be used to select NSCLC patients to first-line therapy with EGFR TKI. Data on erlotinib efficacy according to EGFR, KRAS and BRAF mutations are additionally presented. INTERPRETATION: This trial argues against using high gene copy number for selection of NSCLC patients to first-line therapy with EGFR TKIs. The study adds to the discussion on efficacy of other targeted agents in patients with target gene amplified tumors.

Concurrent chemotherapy and short course radiotherapy in patients with stage IIIA to IIIB non-small cell lung cancer not eligible for radical treatment: results of a randomized phase II study.

INTRODUCTION: The optimal treatment for patients with stage IIIA to IIIB non-small cell lung cancer (NSCLC) not eligible for surgery and definitive chemoradiotherapy is unknown. The aim of this study was to evaluate concurrent chemotherapy and palliative radiotherapy. METHODS: Patients with stage IIIA to IIIB NSCLC with tumor >8 cm and/or forced expiratory volume < or =40%, performance status 0 to 2, and tumor-related chest symptoms were randomly assigned to arm A: radiotherapy alone (30 Gy/10 fractions) or arm B: chemoradiotherapy (two cycles of cisplatin and vinorelbine followed by radiotherapy together with third cycle). Primary end point was response rate, the power of the study was 90%, and the significance level was p = 0.1. RESULTS: A total of 99 patients were eligible for response, overall survival, and progression-free survival evaluation. Median age was 66 years (45-78 years). Response rate was 27% versus 53%, p = 0.08; median overall survival was 9.0 versus 12.9 months, p = 0.0342; and median progression-free survival was 4.7 versus 7.3 months, p = 0.046, in arm A versus arm B, respectively. There were no deaths during treatment in arm A and six deaths in arm B; no hematological G3 to G4 toxicities in arm A and 14 toxicities in arm B. Symptom control was high and similar in both arms. CONCLUSIONS: Upfront chemotherapy combined with palliative radiotherapy (30 Gy) is a promising treatment option in the subpopulation of patients with stage IIIA to IIIB NSCLC not amenable for definitive chemoradiotherapy and deserves further investigation.