Prognostic significance of DNA content in Stage I adenocarcinoma of the lung

Purpose: Up to 30% of lung cancers (Stage I) with the most favorable outcome recur within 5 years after surgery. This study reviews the pattern of failure after surgical resection in early lung cancers and determines whether flow cytometric DNA variables were prognostic indicators for survival, disease-free survival (DFS), or distant metastasis-free survival (DMFS). Methods and Materials: Pathologic specimens from 45 patients at The University of Texas M.D. Anderson Cancer Center who underwent surgical resection and mediastinal nodal dissection for Stage I (AJCC) adenocarcinomas of the lung were analyzed by flow cytometry for DNA content. Survival was calculated by the method of Desu and Lee. Chi-square and cross tabulation were used in the analysis. Results: The mean age of the patients was 62 years, and 52.3% were male. All patients were clinical Stage I (T1-2 NO), Karnofsky performance status ≤70, and had a weight loss <10 lbs. Median overall survival (OS) and DFS were 50 months and 33 months, respectively. OS, DFS, and DMFS at 1, 3 and 5 years were 73%, 57%, and 35%; 63%, 53%, and 45%; and 67%, 56%, and 48%, respectively. Analysis of all 45 patients revealed 86% of patients developing brain metastasis had an abnormal DNA content ≤30%, whereas 4% of patients with brain metastasis had abnormal DNA content <30% (p = 0.01). This correlation maintained significance when only pT 1/4 lesions were analyzed. There was a significant statistical correlation between abnormal DNA and 5-year OS, with 74% OS for those with abnormal DNA < 30% vs. 42% for ≤ 30% (p = 0.036). The 5-year DFS for pT 1/4 patients was significantly correlated with abnormal DNA content: 53% for patients with abnormal DNA < 30% vs. 17% for patients with abnormal DNA ≤ 30%, respectively (p = 0.03). Of those with %S fraction (%S) < 2, 13% failed locally compared to 41% of those with %S ≤ 2. There was a highly significant correlation between DNA index (DNAI) and aneuploid %S: 68% of patients with a DNAI ≤ 1.7 had ≤ 2.6 aneuploid %S, whereas only 13% of patients with DNAI ≤ 1.7 had aneuploid %S < 2.6. (p < 0.001). Grouping the percent of abnormal DNA and overall %S according to low vs. mixed vs. high values correlated with DFS (p = 0.02). Conclusions: This study confirms significant correlation between a high DNA index and a higher frequency of brain metastasis, as well as worse OS. Although DNA content variables were not predictive of recurrence at other sites, brain metastasis represents the worst outcome from distant metastasis. Further studies are needed, as well as prospective trials, for evaluating adjuvant therapy in patients with adverse DNA variables following complete surgical resection for early disease. If high-risk patients could be identified after resection, adjuvant therapy (chemotherapy or elective brain irradiation) could be administered.