Natalia B. Kouzminova

Effect of KRAS Mutational Status in Advanced Colorectal Cancer on the Outcomes of Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: A Systematic Review and Meta-analysis

BACKGROUND Emerging data suggest that somatic KRAS mutation in advanced colorectal cancer is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy. PATIENTS AND METHODS A comprehensive search through March 2010 identified randomized controlled trials in metastatic colorectal cancer that evaluated chemotherapy regimens or best supportive care, with and without anti-EGFR therapy. Outcomes included progression-free survival (PFS), median overall survival (OS), and predictive test performance. RESULTS In pooled data from 8 trials with 5325 patients, the addition of anti-EGFR to standard chemotherapy resulted in improved PFS (HR 0.66 [95% CI, 0.53-0.82]) in patients with wild-type KRAS in the tumor tissue, but not in patients with KRAS mutation (HR 1.07 [95% CI, 0.91-1.27]). Anti-EGFR treatment in the wild-type group did not significantly improve median OS. As a predictive biomarker, KRAS mutation had a positive likelihood ratio of 2.0 (95% CI, 1.45-2.76) in predicting nonresponse to anti-EGFR treatment. CONCLUSION In patients with advanced colorectal cancer, the addition of anti-EGFR treatment to standard chemotherapy improves PFS for those with wild-type, but not mutant KRAS status. KRAS gene mutation testing provides a fair biomarker in predicting non-response to anti-EGFR treatment.

Impact of initial surgical margins and residual cancer upon re-excision on outcome of patients with localized breast cancer

BACKGROUND A significant proportion of patients undergoing breast conservation therapy require additional operations to obtain clear margins. The aim of this study was to assess the impact of initial margins and residual carcinoma found on second surgery on the outcomes of breast cancer patients. METHODS In this retrospective study, Cox proportional-hazard regression analysis was performed to evaluate data from 437 patients with stage I to IIIA breast cancer who underwent initial breast-conserving surgery between 1994 and 2004. RESULTS The distant recurrence rate was higher among patients with initial positive margins than among those with initial negative margins (15.5% vs 4.9%; hazard ratio, 3.6; 95% confidence interval 1.5-8.7; P = .003). For patients who had underwent second surgery, the finding of a residual invasive carcinoma was associated with increased risk for distant recurrence (22.8% vs 6.6%; hazard ratio, 3.5; 95% confidence interval, 1.8-7.4; P = .0001). CONCLUSION Invasive residual carcinoma found during subsequent surgery after initial compromised margins is an important prognostic marker for distant recurrence.

Su1039 Ethnic Differences in Early-Onset Colorectal Cancer

BACKGROUND: The incidence of colorectal cancer (CRC) in persons under the age of 50 is rising, and people of Hispanic ethnicity comprise a growing proportion of cases. Previous studies have shown that Hispanics present at younger ages and at later stages, and have poorer survival than non-Hispanic whites. However, little is known about differences in methods of presentation, tumor location, and family history of these patients. METHODS: All CRC patients under the age of 50 diagnosed from 1990 onwards were ascertained through our hospitals tumor registry. We reviewed endoscopy and surgery reports, clinic notes, laboratory results, radiology reports, pathology reports, and inpatient discharge summaries to determine key demographic and clinical features of these patients. RESULTS:We identified 139 patients, of whom 58 (41.3%) were Hispanic and 81 (58.3%) were non-Hispanic. Hispanics had a lower mean age at diagnosis (39 years vs. 42 years, p=0.01), and had a trend towards higher BMI (26.7 vs. 25.1 kg/m2, p= NS), with 49% being overweight. For both groups, the most common symptoms were abdominal pain (59%) and bleeding (38%). Weight loss was a more common presenting symptom among Hispanics (19% vs. 7%, p = 0.04). Most patients in both groups presented at late stage, with 72% having Stage III/IV disease. Among Stage IV patients, 44% had multiple sites of metastasis. Thirty eight percent of cancers were diagnosed at surgery, with the remainder being found via diagnostic colonoscopy or flexible sigmoidoscopy. None of the tumors were found by screening, even among patients with elevated risk. Rectal cancer comprised 20-30 % of tumors in both groups, and Hispanic patients had more cancers in the sigmoid or descending colon (49% vs. 31%, p =0.04). Although the majority of cases were sporadic rather than familial, Hispanics were more likely than non-Hispanics to have a family history of CRC (19% vs. 5%, p =0.009). CONCLUSIONS: Hispanics appear to be at high risk for early-onset CRC, possibly due to a higher prevalence of obesity. The majority of patients present at later stages. Presenting symptoms are non-specific, although a fair number of Hispanic CRC patients had involuntary weight loss prior to diagnosis. Although most cases of early-onset CRC are sporadic, a higher proportion of Hispanic patients reported a family history of colon cancer, suggesting that a thorough family history and possibly early screening colonoscopy is indicated in this population. Presenting Symptoms by Ethnicity