Altered metastatic behavior of small cell carcinoma of the lung after chemotherapy and radiation

Heterogeneity of malignant neoplasms is a recognized phenomenon now, but the implications of this with respect to the responsiveness of carcinomas to different modes of therapy are not known. To examine this question, we reviewed the clinical and pathologic features of 85 autopsied patients with small cell carcinoma of the lung. Patients who were treated with chemotherapy plus radiation survived significantly longer than all other patients (P <0.005), but there were no significant differences in the mean number of metastatic sites or overall tumor burden at autopsy. Patients who were treated with chemotherapy only had significantly more frequent (P <0.05) and more extensive (P <0.005) metastases to the leptomeninges, more frequent metastases to other sites within the lungs (P <0.05),and less frequent metastases to the adrenal glands (P <0.01) and pancreas (P <0.05). The patients who were treated with radiation only had more extensive metastases to the adrenal glands (P <0.005), and more frequent metastases to the pancreas (P <0.001), colon (P <0.01), and cerebral white matter (P <0.05). The patients who were treated with both chemotherapy and radiation had more frequent and more extensive metastases to the gastrointestinal tract (P <0.05) and serosal surfaces (P <0.01), but not to any site within the central nervous system (CNS). The latter suggests that prophylactic treatment of the CNS may not be necessary to prolong survival when patients are treated with both chemotherapy and radiation. The results also suggest that although chemotherapy and radiation may prolong survival in patients with small cell carcinoma of the lung, these forms of treatment change the biologic behavior of the tumors by eliminating certain clones that are distinguishable by their matastatic patterns.