Trimodality treatment in Stage III nonsmall cell lung carcinoma: prrognostic impact of K-ras mutations after neoadjuvant therapy.
BACKGROUND
In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated.


METHODS
Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis.


RESULTS
K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005).


CONCLUSIONS
These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches.
Broermann
Petra
P
Department of Medicine/Hematologic and Oncology and Respiratory Medicine, University of Muenster, Albert-Schweitzer-Strasse 33, 48129 Muenster, Germany. broerma@uni-muenster.de
Junker
Klaus
K
Brandt
Burkhard H
BH
Heinecke
Achim
A
Freitag
Lutz
L
Klinke
Folker
F
Berdel
Wolfgang E
WE
Thomas
Michael
M
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D016019:Survival Analysis
D004273:DNA, Neoplasm