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

Henry Stevenson, MD; Adi F. Gazdar, MD; Ruby Phelps, AAS; R. Ilona Linnoila, MD; Daniel C. Ihde, MD; Bimal Ghosh, MD; Thomas Walsh, MD; Edward L. Woods, MD; Herbert Oie, PhD; Teresa O'Connor, MPH; Robert Makuch, PhD; Barnett S. Kramer, MD; and James L. Mulshine, MD
[+] Article, Author, and Disclosure Information

Grant Support: By the G. Harold and Leila Y. Mathers Charitable Trust.

Requests for Reprints: James L. Mulshine, MD, Biotherapy Section, NCI-Navy Medical Oncology Branch, National Naval Medical Center, Building 8, Room 5101, Bethesda, MD 20814.

Current Author Addresses: Drs. Stevenson, Gazdar, Linnoila, Ihde, Ghosh, Walsh, Oie, Kramer, Mulshine, and Ms. Phelps: The NCI-Navy Medical Oncology Branch, National Cancer Institute, National Naval Medical Center, and Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

Dr. Makuch and Ms. O'Connor: Department of Epidemiology and Public Health, Yale University, New Haven, CT 06510.

Ann Intern Med. 1990;113(10):764-770. doi:10.7326/0003-4819-113-10-764
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Objective: To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung 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 HIB 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.





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