Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis

Abstract

The respective pretreatment prognostic impacts of the following markers were evaluated in 125 patients with small cell lung cancer (SCLC): lactic dehydrogenase (LDH), serum thymidine kinase (S-TK), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and tissue polypeptide antigen (TPA). More traditional clinical and serologic markers were also evaluated. Univariate analysis showed that all of the biochemical markers mentioned above, the Karnofsky index (KI) and the patient's sex were related to both the stage of disease (limited/extensive disease: LD/ED) and to survival. The strongest marker for the clinical stage was S-TK, whereas TPA showed the strongest relationship with survival. Multivariate analyses produced a model consisting of S-TK, CEA, NSE, and the patient's sex for determining the clinical stage. To compare the prognostic capacity of easily determined biochemical and simple clinical variables to the more resource-demanding variable of the clinical stage, three multivariate analyses in relation to survival were performed: (1) biochemical markers and simple clinical variables; (2) LD/ED and simple clinical variables; and (3) all available variables. The model obtained from the first analysis included TPA, KI, age, and the patient's sex; the model from the second analyses included LD/ED, patient's age, and KI; and the model from the third analysis, TPA, KI, age, sex, and LD/ED. Indices based on these three multivariate models were calculated for each patient and the prognostic capacity of these indices was compared. Pretreatment serum marker levels also had the capacity to predict both the grade and the duration of the response to therapy.

Serum thymidine kinase 1 reflects the progression of pre-malignant and malignant tumors during therapy

“…It is of considerable interest in clinical settings because its level is highly dependent on cell growth. TK1 is a sensitive and specific marker for prognosis (16,18,19), for the monitoring of the outcome of cancer therapy (25)(26)(27)(28), and for the screening of healthy individuals for the risk of malignant disease (unpublished data).…”

“…Thymidine kinase activity has been used as a proliferation marker since 1980 in serum and cytosol fractions of tissues. It is almost undetectable in normal serum (14)(15)(16), but increases to varying degrees in malignant tumors, depending on their type, stage (16), whether they are fast or slow growing (17), and whether they are treated or untreated (18). In a clinical study of 1,692 breast cancer patients (19), TK1 activity in the cytosol was correlated to a shorter survival time and poor outcome using endocrine treatment (tamoxifen) (20).…”

Serum neuron specific enolase (NSE) is a determinant of response duration in small cell lung cancer (SCLC)

“…NSE was not included in these studies, but a close correlation between LDH and NSE has been shown (J0rgensen et al, 1988). In numerous investigations (Carney et al, 1982;Akoun et al, 1985;Cooper et al, 1987;J0rgensen et al, 1989;Gronowitz et al, 1990) a close correlation between disease extent and NSE was found. The lack of influence of NSE on probability for CR vs that of a PR may partly be caused by the extremely difficult distinction between the responses.…”

“…The concentration of NSE correlates with the extent of disease, but independent of this relationship NSE in itself contributes to the prognosis of the patients (J0rgensen et al, 1988), albeit the prognostic impact of NSE has not been significant in all investigations (Carney et al, 1982;Akoun et al, 1985;Gronowitz et al, 1990). …”

Clinical evaluation of serum tumour marker CA 242 in non-small cell lung cancer

“…pooling SCLC and NSCLC). This perturbs the interpretation of the results because it is now demonstrated that CEA level has a prognostic influence on patients with SCLC (Gronowitz et al, 1990). Moreover, only univariate analyses of survival have been done and, inasmuch as CEA is related to disease extent, its value as an independent prognostic variable is questionable.…”