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BACKGROUND: MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE: To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS: miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS: MiR-21 high expression ( p = 0.034) and miR-335 low expression ( p = 0.0061) were significantly associated with MSI-H. A positive trend (p = 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066-6.605, p = 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749-7.815, p = 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p = 0.03). CONCLUSIONS: Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.

Aim VITAL, a phase II single‐arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5‐fluorouracil (5‐FU), mitomycin‐C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). Methods Adult, treatment‐naïve SCCAC patients (Stage T2‐T4, any N, M0) and ECOG‐PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5‐FU (1000 mg/m2/d, days 1‐4 and 29‐32), MMC (10 mg/m2, days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10‐15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3‐years (expected 3‐year DFS rate: 73.7 ± 12%). Results Fifty‐eight patients (31 women; median age: 59 years; ECOG‐PS 0‐1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1‐T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow‐up was 45 months. The 3‐year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3‐year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3‐4 toxicities were experienced by 53 (91%) patients. Most common grade 3‐4 treatment‐related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy‐free survival and complete response rate was observed in human papilloma virus positive patients. Conclusions Panitumumab addition to MMC‐5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes. RT plus MMC‐5FU remains the standard of care for localized SCCAC patients., VITAL, a phase II single‐arm study, was aimed to evaluate efficacy and safety of panitumumab addition to 5‐fluorouracil (5‐FU), mitomycin‐C (MMC) and radiotherapy in patients with localized squamous cell carcinoma of the anal canal (SCCAC). The study concluded that panitumumab addition to MMC‐5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes.