ABSTRACT
OBJECTIVE: To profile and correlate KRAS mutations with outcome in stage III colon cancer (CC) patients who underwent adjuvant chemotherapy following curative resection surgery. PATIENTS AND METHODS: In this retrospective study, eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with fluoropyrimidine monotherapy (FP) or with oxaliplatin-based regimens (O-FP). Disease-free survival (DFS) and overall survival (OS) were analyzed and computed using the Kaplan-Meier method and the log-rank test. RESULTS: The study population included 148 patients (n=65 FP and n=83 O-FP). We identified KRAS mutations in 41/148 (27%) patients, of which 18 (44%) received FP and 23 (56%) O-FP. Five-year DFS and OS were significantly higher in patients with KRAS wild-type vs. mutant [DFS: 78 vs. 56%, HR: 0.47 (95% CI: 0.25; 0.87), p=0.01; OS: 73 vs. 68%, HR: 0.44 (95% CI: 0.21; 0.88), p=0.01]. In patients treated with FP, the 5-year DFS and OS was significantly improved in the KRAS wild-type vs. mutant group, respectively [DFS: 80 vs. 43%, HR: 2.88 (95% CI: 0.67; 3.76), p=0.014; OS: 85 vs. 68%, HR: 0.27 (95% CI: 0.10; 0.73), p=0.005]. Conversely, 5-year DFS and OS were not statistically different for patients with KRAS wild-type vs. mutations treated with O-FP, respectively [DFS: 78 vs. 65%, HR: 1.59 (95% CI: 0.67; 3.76), p=0.281; OS: 80 vs. 75%, HR: 0.73 (95% CI: 0.55; 2.12), p=0.57)]. CONCLUSIONS: Our results suggest that curatively resected stage III CC patients exhibiting wild-type KRAS status might benefit from FP alone. Conversely, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/therapy , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endonucleases/genetics , Endonucleases/metabolism , Female , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Proto-Oncogene Proteins p21(ras)/metabolism , Retrospective StudiesABSTRACT
The prevalence of goiter among schoolchildren and the daily urinary iodine excretion in the general population were evaluated in 4 municipalities in the endemic goiter area in Northeastern Sicily in two different surveys. The first, carried out in 1977-1978, covered 2,493 (91%) schoolchildren; the second, in 1987-1988, covered 2,167 (92%) schoolchildren. A dramatic decrease in goiter prevalence was apparent in each community as follows: in Castell'Umberto (3,904 inhabitants, altitude 641/750 m above sea level) goiter prevalence (G) decreased from 79.7% to 44.2% with a percent reduction (%r) of 44.5 and an increase in 24-h urinary iodine excretion (UIE) from 22.3 +/- 16.4 micrograms/24 h (n = 30) to 48.7 +/- 43.4 (n = 50). A similar trend was apparent in Tortorici (10,194 inhabitants, 475/700 m) where G decreased from 62.2 to 26.5% (% r 57.4) with a UIE increase from 28.4 +/- 29.6 (n = 35) to 47.6 +/- 59.3 (n = 40); in Sinagra (3,387 inhabitants, 300 m) where G decreased from 61.6 to 32.7% (% r 46.9) and UIE increased from 26.0 +/- 21.1 (n = 25) to 66.6 +/- 69.6 (n = 102) and in Sant'Angelo di Brolo (5,732 inhabitants, 380 m) where G decreased from 48.7 to 27.5% (% r 43.5) and UIE increased from 26.3 +/- 16.7 (n = 30) to 47.7 +/- 73.8 (n = 34). These events are clearly related and certainly dependent on the changed alimentary habits in the area due to the improved distribution of frozen food and industrially prepared dairy products, eventually enriched by iodine.(ABSTRACT TRUNCATED AT 250 WORDS)
