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Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority = 0.380, P for superiority = 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov , registration number: NCT0064660. • TOSCA trial compared 3 or 6 months of adjuvant chemotherapy. • We here provided the updated results of OS at 7 years of median follow up. • The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). • At the last follow-up analysis, the absolute OS difference between arms was <1%. • The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. [ABSTRACT FROM AUTHOR]

Abstract Purpose Because the role of the primary tumour location in the adjuvant setting has not been clearly established in colon cancer, we analysed the clinical outcome according to the primary tumour location from three Italian trials assessing adjuvant therapy in colon cancer. Patients and methods Overall survival (OS) and disease-free survival (DFS) were assessed globally and in each trial, according to right-sided, transverse and left-sided primary colon cancer. Analysis was planned to provide overall and stage-specific results. Results Individual data of 5239 patients were included in this analysis. The right-sided tumours were 1540 (29%), tumours originating in the transverse were 815 (16%) and left-sided tumours were 2884 (55%). At the multivariate analysis, DFS findings from the comparison of the right-sided versus left-sided tumours (hazard ratio [HR] = 1.00; 95% confidence interval [CI] = 0.89–1.14) were not statistically associated with clinical outcomes in the overall population. On the contrary, OS findings, from the comparison of the right-sided versus left-sided tumours, were significantly associated with outcomes (HR = 1.20; 95% CI = 1.04–1.39). In stage II patients, there was no difference in terms of DFS and OS among the three different tumour locations, whereas in stage III patients, the left-sided tumours showed an improved prognosis in terms of OS (HR: 1.36 95% CI = 1.14–1.62, p < 0.001). Conclusion This is the largest analysis demonstrating a prognostic effect of the tumour location on patients with colon cancer receiving adjuvant chemotherapy. Nevertheless, the effect is limited to OS in stage III colon cancer. In stage II tumours, the primary location has a lesser impact. The transverse tumours should be prognostically considered in between the right-sided and left-sided tumours. Highlights • The primary tumour location has a prognostic effect even on patients with colon cancer receiving an adjuvant chemotherapy. • The effect is limited to overall survival in stage III colon cancer. • The transversum tumours should be prognostically considered between right-sided and left-sided tumours. [ABSTRACT FROM AUTHOR]

Background: Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. Patients and methods: TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. Results: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). [ABSTRACT FROM AUTHOR]

Background Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with HCC and CP class B. Patients and methods A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. [Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19–21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.] Results Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar. Conclusion Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Success of targeted therapy requires expression of the protein. Tumor tissue source can include diagnostic biopsy, surgical samples from initial or follow-up surgeries, fluids e.g. pleural or ascites and circulating tumor cells (CTC). The goal of using CTCs was 1. To determine whether CTC can be used as a "liquid" tumor biopsy and enable gene sequence information at the single cell level and 2. To determine the heterogeneity represented in the circulation compared to that seen in solid tumor by examining single cells (or a small cluster of cells) for the presence of a specific mutation which was detected in tissue tumor source. METHODS: We performed sequencing for mutational analysis on tissue(s) from patients with inflammatory breast cancer (IBC). Tumor sources varied from mastectomy tissue, metastatic site(s) e.g. liver or skin from chest wall disease, pleural fluid and CTC isolated into pure single cell populations (or groups of cells) using Silicon Biosystems DEPArray. Ampli1™ WGA kit was used for CTC amplification. Of the 22 patients sequenced, mastectomy primary tumor was examined in 3, metastatic site skin chest wall disease in 15, other metastatic site in 4, pleural fluid in 2 and CTC collected to investigate p53 mutations in 8. RESULTS: To date 22 patients have had mutational data performed, 14/22 had mutations in p53, 4/22 in RB1, 2/22 in each PI3K and ERBB2, 1/22 in each of BRAC1, BRAC2, ATM, KRAS, Notch 1, MEN1 and ESR1. Numerous amplifications were noted including AKT1, RPTOR, MLC1, MYC, CCND1 and ERBB2. For one patient's chest wall biopsy compared to two single CTCs and a cluster of 10 CTCs the same TP53C229fs*10 mutation was detected revealing the same 2bp deletion. No 2bp deletion was found in single white blood cells. Whereas, another patient which showed a TP53 S215G mutation in her skin biopsy of chest wall disease, only amplifications of AURKA, CCND1, IGF1R, MDM2 and SRC in pleural tumor cells were detected and no mutations in three single CTC, two single pleural tumor cells and in single white blood cells were seen. Primary tumor tissue is being sort for both of these patients. Mutational data reviewed to date suggest that IBC is not one disease but a multiplicity of diseases, revealing a variety of target(s). Aberrations are not consistent across tissue source. CONCLUSIONS: Successful treatment outcomes using standard of care chemotherapy combined with target therapies will require not one, but a panel, of tissue sources for sequencing to guide the selection of appropriate targeted therapies. [ABSTRACT FROM AUTHOR]