Tumor Cell Lines Established in Vitro: An Independent Prognostic Factor for Survival in Non-Small-Cell Lung Cancer

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Abstract
Objective: To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lunger cancer. Design: Cohort study. Setting: Single-institution tertiary care center. Patients. One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. Intervention: tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. Measurements and Main Results: Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%. Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P < 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P < 0.0001 for curable group; P < 0.01 for palliative group). Conclusion: In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.