ABSTRACT: Molecular markers in colon cancer are needed for a more accurate classification and personalized treatment. We determined the effects on clinical outcome of the BRAF mutation, microsatellite instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.
Stage II colon carcinoma patients (n = 106) treated with surgery only and 258 stage III patients all adjuvantly treated with 5-fluorouracil chemotherapy were included. KRAS mutations in codons 12 and 13, V600E BRAF mutation and MSI status were determined.
Older patients (P < 0.001), right-sided (P = 0.018), better differentiated (P = 0.003) and MSI tumors (P < 0.001) were significantly more frequent in stage II than stage III. In both groups, there was a positive association between mutated BRAF and MSI (P = 0.001) and BRAF mutation and right-sided tumors (P = 0.001). Mutations in BRAF and KRAS were mutually exclusive. In a multivariate survival analysis with pooled stage II and stage III data, BRAF mutation was an independent prognostic factor for overall survival (OS) and cancer-specific survival [hazards ratio (HR) = 0.45, 95% confidence interval (CI) 0.25-0.8 for OS and HR = 0.47, 95% CI 0.22-0.99]. KRAS mutation conferred a poorer disease-free survival (HR = 0.6, 95% CI 0.38-0.97).
The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.
Annals of Oncology 12/2010; 21(12):2396-402. · 6.43 Impact Factor
ABSTRACT: The aim was to investigate whether a set of measures directed at increasing lymph node (LN) detection among colon cancer patients led to clinically relevant changes in LN detection rate.
Data of all patients with curative colon cancer (pT(any) N(any) M0) diagnosed in 1999-2007 whose resection specimens were evaluated by the Institute for Pathology and Medical Microbiology in Eindhoven (n=1501) were included. Feedback to specialists, increased fixation time, and ex-vivo injection of the specimen with Patent blue V dye were used to increase LN detection rate. Trends in the proportion of patients with insufficient LNs examined were investigated; moreover, the Patent blue-stained patients (n=86) were compared with a group of unstained patients (n=84). Based on the decrease in the proportion of high-risk node-negative patients, a calculation of chemotherapy-related costs saved was made.
The proportion of patients with <12 LNs examined decreased from 87% in 1999 to 48% in 2007 (p(trend)<0.0001). In the stained group this was 37%, versus 56% for the unstained group (p=0.010). In 1999, 79% of stage II patients were high-risk compared to 55% in 2007, which translates to a saving of almost 1,000,000 euro based on 92 stage II patients diagnosed in 2007.
A diverse set of measures increased the number of examined lymph nodes among patients with colon cancer. Large savings can be made due to the reduced proportion of high-risk node-negative patients who would otherwise have received adjuvant chemotherapy.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 08/2009; 36(2):135-40. · 2.56 Impact Factor
ABSTRACT: The present phase II study aimed to assess the feasibility and efficacy of a new paclitaxel-based neoadjuvant chemoradiation regimen followed by surgery in patients with stage II-III esophageal cancer.
From January 2002 to November 2004, 50 patients with a potentially resectable stage II-III esophageal cancer received chemotherapy with paclitaxel, carboplatin, and 5-FU in combination with radiotherapy 45 Gy in 25 fractions. Surgery followed 6-8 weeks after completion of neoadjuvant treatment.
Patient characteristics: male/female: 44/6, median age 60 years (34-75), median WHO 1 (0-2), adenocarcinoma (n = 42), squamous cell carcinoma (n = 8). Toxicity was mild, and 84 % of the patients completed the whole regimen. Forty-seven patients underwent surgery with a curative intention (transhiatal n = 44, transthoracic n = 3). Pathologic complete tumor regression was achieved in 18 of 47 operated patients (38%). R0 resection was achieved in 45 of 47 operated patients (96%). There were four postoperative deaths (8.5). Postoperative complications were comparable with other studies. After a median follow-up of 41.5 months (21-59) estimated 3- and 5-year survival on an intention-to-treat basis was 56 and 48%. Estimated 3-year survival in responders was 61%, in nonresponders 33%.
This novel neoadjuvant chemoradiation regimen for treatment of patients with stage II-III esophageal cancer is feasible. Results are encouraging with a high pathologic complete tumor regression and R0 resection rate and an acceptable morbidity and mortality. Preliminary survival data are very promising.
Annals of Surgical Oncology 02/2008; 15(1):88-95. · 4.17 Impact Factor