A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer.
BACKGROUND
Clinical trials have indicated a benefit of adjuvant chemotherapy for patients with stage IB, II, or IIIA--but not stage IA--non-small-cell lung cancer (NSCLC). This classification scheme is probably an imprecise predictor of the prognosis of an individual patient. Indeed, approximately 25 percent of patients with stage IA disease have a recurrence after surgery, suggesting the need to identify patients in this subgroup for more effective therapy.


METHODS
We identified gene-expression profiles that predicted the risk of recurrence in a cohort of 89 patients with early-stage NSCLC (the lung metagene model). We evaluated the predictor in two independent groups of 25 patients from the American College of Surgeons Oncology Group (ACOSOG) Z0030 study and 84 patients from the Cancer and Leukemia Group B (CALGB) 9761 study.


RESULTS
The lung metagene model predicted recurrence for individual patients significantly better than did clinical prognostic factors and was consistent across all early stages of NSCLC. Applied to the cohorts from the ACOSOG Z0030 trial and the CALGB 9761 trial, the lung metagene model had an overall predictive accuracy of 72 percent and 79 percent, respectively. The predictor also identified a subgroup of patients with stage IA disease who were at high risk for recurrence and who might be best treated by adjuvant chemotherapy.


CONCLUSIONS
The lung metagene model provides a potential mechanism to refine the estimation of a patient's risk of disease recurrence and, in principle, to alter decisions regarding the use of adjuvant chemotherapy in early-stage NSCLC.
Potti
Anil
A
Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
Mukherjee
Sayan
S
Petersen
Rebecca
R
Dressman
Holly K
HK
Bild
Andrea
A
Koontz
Jason
J
Kratzke
Robert
R
Watson
Mark A
MA
Kelley
Michael
M
Ginsburg
Geoffrey S
GS
West
Mike
M
Harpole
David H
DH
Nevins
Joseph R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D005810:Multigene Family; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D012306:Risk; D016019:Survival Analysis
D012334:RNA, Neoplasm