Stage at presentation is the most powerful prognostic factor in non-small cell carcinoma of the lung (NSCLC). Stage I NSCLC is associated with a higher probability of long-term survival than any of the higher stages. Standard treatment consists of surgical resection alone, although up to 50% of clinical stage I and 3O-4O% of pathological stage I patients recur and die following resection. An extensive body of published literature exists describing prognostic features in stage I NSCLC, and, in fact, 20 separate prognostic variables have been reported as contributing to a determination of disease outcome. These include 8 clinico-pathologic variables, 2 flow cytometric parameters, and 8 biologic factors, including abnormal oncogene expression or activation, and altered expression of blood group antigens of the surface of tumor cells. However, because no single study has evaluated all or even most of the potentially important prognostic variables in a single patient population, it is not possible at the present time to reach definitive conclusions regarding which of the multitude of prognostic factors are dominant, which are of secondary importance, and which are unimportant in providing independent prognostic information regarding outcome. The primary objective of this application is to carry out a retrospective study in a population of approximately 250 resected stage I NSCLC patient at the Brigham and Women's Hospital for whom there exists an extensive clinical database, adequate followup, and sufficient tumor tissue available for determination of the presence or absence of 15 prognostic variables that have been previously described as affecting outcome in NSCLC. The goal is to identify which of these 15 prognostic factors are dominant, which are secondary, and which are not independent predictors of outcome, and to then utilize this information to develop a risk stratification model in resected stage NSCLC. Within the context of the model developed, stage I patients would be categorized as """"""""high risk"""""""" or """"""""low risk"""""""" for recurrence following complete surgical resection. The ultimate goal of this project (though not included within this project) is to subsequently utilize the risk stratification model as the basis for a prospective randomized controlled study, which will likely be carried out by the CALGB, in which """"""""high risk"""""""" patients will be randomized to receive surgical resection alone or resection followed by adjuvant chemotherapy, and """"""""low risk"""""""" patients will receive surgical resection alone. Such a trial could definitively determine if outcome can be predicted by a battery of prognostic variables, and simultaneously ascertain if adjuvant chemotherapy can favorably alter the prognosis of those judged to be at high risk of recurrence.
| Kwiatkowski, D J; Harpole Jr, D H; Godleski, J et al. (1998) Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications. J Clin Oncol 16:2468-77 |
