How Chronologic Age Modifies the Effect of Lung Cancer on Short-term Survival Following Hospitalization

Lung cancer has been one of the leading causes of death in the United States, with the five-year survival of non-small cell lung cancer (NSCLC) reported to be 19% and of small-cell lung cancer to be only 6%. Once reaching the advanced stages of lung cancer (Stage III and Stage IV), patients’ short-term survival rate declines rapidly. Many studies have investigated the individual effect of chronologic age and lung cancer on patients’ short-term survival outcomes. Nonetheless, very few studies have investigated how chronologic age could modify the effect of lung cancer on short-term survival. There are also established studies that investigated the association of advanced-stage cancers and survival outcomes in different age groups, yet they did not look at lung cancer specifically. Therefore, the objective of this study was to evaluate whether the effect of lung cancer on short-term survival was modified by chronologic age, measured on both multiplicative and additive scales. This study was a secondary analysis using data from the SUPPORT study by Knaus, et al. in 1995, with the original purpose of developing and validating a prognostic model predicting individual’s survival probability. The study population included 9105 patients from five tertiary care centers who were diagnosed during the first 24 hours after study entry and classified into one of the nine disease groups: nontraumatic coma, multiple organ system failure and malignancy, acute respiratory failure, multiple organ system failure and sepsis, acute exacerbation of severe chronic obstructive pulmonary disease, acute exacerbation of severe congestive heart failure, chronic liver disease, colon cancer with liver metastasis, and non-small cell carcinoma of the lung (NSCLC) (Knaus et al, 1995). All patients were predicted to have overall 6-month survival rates of 50% according to a literature review (Knaus et al, 1995). In this study, patients were classified according to their lung cancer diagnoses and age groups. In stratified analyses, lung cancer was associated with an 110%, 58% and 35% increase in short-term death among the youngest, middle and oldest age groups, respectively, compared with patients without lung cancer. The stratum-specific estimates were significantly different from each other. The second analysis comparing the observed and expected joint effects of age and lung cancer indicated that there was effect modification of lung cancer across strata of age on both additive and multiplicative scales, and the interaction between two factors tended to be antagonistic. More specifically, for the multiplicative scale interaction, the p-values for the cross-product terms between age tertiles and lung cancer diagnoses were highly significant (p<0.0001). The ratio of the RRs were 0.59 (95% CI: 0.49, 0.62). The Relative Excess Risk due to Interaction (RERI) was -0.73 (95% CI: -0.62, -0.80), and the p-value for the RERI was 0.0014. That is, despite advanced-stage NSCLC being associated with an elevated risk of short-term death, this risk became less apparent in the older population. These results should influence policy by assuring that age is used appropriately in lung cancer treatment guidelines and medical decision making.

Keywords:  Department of Health Research & Policy
Lung cancer
effect modification
short-term survival
Stanford University
Department of Health Research &amp; Policy
Thesis
Advisor: King Abby
Popat Rita