Cell kinetic studies in patients with small cell carcinoma of the lung.

Abstract

Small cell carcinoma of the lung is a type of lung cancer characterized by abrupt onset of clinical manifestations, running a short course with early signs of dissemination, and often responding favorably to chemotherapy. A delineation of its growth characteristics by determination of thymidine labeling index (LI), duration of intermitotic cycle (Tc) of proliferating tumor cells, and of its cell cycle phases (G1, S1 G2, M) and proliferative fraction (growth fraction, GF) was undertaken. The studies employed the technique of intratumoral thymidine injection; aspirates or biopsy samples of injected subcutaneous nodules, lymph nodes, and bone marrow replaced by tumor were then processed autoradiographically. The LI was obtained in 12 patients; the median LI was 16.7% (range 7.2–23.8%). Chemotherapy achieved prolonged remission in 3 patients with the highest LI prior to treatment. In 1 patient the duration of DNA synthesis period (Ts) by the labeled mitoses curve method was estimated to be 18.8 hours. Repeated pulses into nodules at intervals less than 12 hours showed a linear rise to 55–44% LI within 48 hours in 2 other patients. These results suggest that whereas cell cycle times may be similar to those of other human solid tumors, the growth fraction is usually higher in small cell carcinoma of the lung than in other common human malignancies. This parameter may be an important determinant in responsiveness to chemotherapy. Similar studies in other human malignancies, coupled with such clinical correlations are necessary to confirm this concept.