The mutations of the EGFR and K-ras genes in resected stage I lung adenocarcinoma and their clinical significance

AimsThere is no internationally accepted grading system for lung adenocarcinoma despite the new WHO classification. The architectural grade, the Kadota grade and the Sica score were evaluated and compared with overall (OS) and disease-free survival (DFS).MethodsComprehensive histological subtyping was used in a series of resected stage I lung adenocarcinoma to identify subtypes of adenocarcinomas, the architectural grade, the Kadota grade, the Sica grade, the mitotic count, nuclear atypia, the presence of lymphovascular, vascular and airway propagation, necrosis, and micropapillary or solid growth pattern in any percentage. Statistical models fitted included Kaplan-Meier estimates and Cox proportional hazard regression models.Results261 stage I adenocarcinomas were included. The 5-year survivals of different subtypes were as follows: lepidic (n=40, OS: 92.5%; DFS 91.6%), acinar (n=54, OS: 81.8%; DFS: 68.6%), papillary (n=49, OS: 73.6%; DFS: 61.0%), solid (n=95, OS: 64.7%; DFS: 57.8%) and micropapillary (n=23, OS: 34.8%; DFS: 33.5%). Concerning the architectural grade, there were significant differences between OS and DFS of low and intermediate (pOS=0.005, pDFS<0.001), low and high (pOS<0.001, pDFS<0.001) and intermediate and high grades (pOS=0.002, pDFS<0.001). Low-grade and intermediate grade tumours did not differ in survival according to Kadota grade and Sica grade. In the multivariable model, architectural grade was found to be an independent prognostic marker. In another model, architectural pattern proved to be superior to architectural grade.ConclusionsOf the three grading systems compared, the architectural grade makes the best distinction between the outcome of low-grade, intermediate-grade and high-grade stage I adenocarcinomas.

Download Full-text

Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7523 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7523-7523

Author(s):

Y. Y. Janjigian ◽

B. J. Park ◽

M. G. Kris ◽

V. A. Miller ◽

G. J. Riely ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Disease Free Survival ◽

Stage I ◽

Egfr Mutations ◽

Free Survival ◽

Resected Stage ◽

Lung Adenocarcinomas ◽

Disease Free ◽

Exon 19

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]

Download Full-text