Lung cancer is the leading cause of cancer death in the world. Four recent randomized phase III trials have demonstrated a survival advantage for stage IB to IMA patients treated with adjuvant chemotherapy [cisplatin/vinorelbine (NCI-C JBR-10); carboplatin/paclitaxel (CALGB 9633)]. Due to improved screening, patients with pathologic stage IA (T1NO) are the fastest growing segment of lung cancer patients with an estimated 70% 5-year survival. Therefore, a standard randomized trial would likely require more than 1000 patients to accumulate enough deaths for significant power. In addition, the likely benefit may be small compared to the risk encountered by stage IA patients (70% do not need treatment). If a molecular-based tumor model could be created which stratified patients for risk of cancer recurrence, adjuvant therapy could increase the survival in the high risk group, while limiting exposure to potentially harmful treatments in the low risk patients'. Patients suspected with T1NO non-small cell lung cancer who have undergone a complete surgical resection will be registered to the study. Their risk of cancer recurrence will be predicted by the lung cancer genomic model. Patients who have correct pathological stage and usable genomic data will be assigned to one of the three treatment cohorts based on their genomic-predicted risk of cancer death. In particular, patients with a less than 33% risk of cancer recurrence within 5 years will be identified as """"""""low risk"""""""" and assigned to observation (LRO); the rest of patients who have a greater than 33% risk of cancer recurrence within 5 years will are identified as """"""""high risk"""""""" and will be randomized with equal probability to receive either adjuvant chemotherapy [HRC: cisplatin/ vinorelbine (NCI-C JBR-10) or carboplatin/paclitaxel (CALGB 9633)] or observation (HRO).
The specific aims of this proposal are to prospectively validate the survival superiority of LRO to HRO as predicted by the genomic-based risk model, and to determine the efficacy of adjuvant chemotherapy in the high risk population, i.e. a survival benefit for patients on HRC against those on HRO. The endpoint for both objectives will be overall survival (OS), defined as the time from randomization to death of all causes. Secondary objectives of this proposal are to compare progression free survival of patients on three treatment cohorts, to compare prediction accuracy of the risk of quick death (die within 5 years) based on the clinical prediction model and the genomic model, to characterize the toxicity related to the adjuvant chemotherapy that HRC patients actually received. ? ? ?
