Abstract
Simple SummaryCardiovascular disease is common in patients with small cell lung cancer, partly reflecting its high correlation with smoking. Cardiovascular comorbidities may limit patient tolerance to cytotoxic drugs, thereby influencing the choice and intensity of treatment and, ultimately, patient survival. In light of the challenges relating to assessing cardiovascular status clinically in newly diagnosed lung cancer, objective biomarkers of cardiovascular vulnerability are warranted. Here, we show that circulating levels of ST2, an established biomarker in heart failure, and adrenomedullin, a vasodilator peptide known to reflect several aspects of cardiovascular status, strongly correlate with survival in small cell lung cancer. Our data, which are based on a large, randomized trial cohort, suggest the potential use of cardiovascular biomarkers in guiding clinicians in making individualized treatment decisions.Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.
Highlights
Lung cancer is the worldwide leading cause of death from cancer [1]
MR-proADM, MR-proANP, copeptin, and ST2 were determined at baseline in treatmentnaïve Small cell lung cancer (SCLC) patients to exclude potential interaction effects of prior cytotoxic therapy
Of the first 292 consecutively enrolled patients in the RASTEN trial, 40 patients were excluded from the biochemical analysis due to poor sample quality (N = 11), unavailable sample (N = 15) or inclusion criteria not being fulfilled (N = 14) (Supplementary Figure S1)
Summary
Lung cancer is the worldwide leading cause of death from cancer [1]. Small cell lung cancer (SCLC), an aggressive subtype accounting for ~15% of all lung cancer cases [2], is associated with a poor prognosis, with 5-year survival rates of ~5% [3,4]. The presence of one or more comorbidity was reported in 76% of SCLC patients in 2011–2012, compared to 55% in 1995–1998 [5], with cardiovascular (CV) and pulmonary disease being among the most prevalent. In this large cohort (N = 4142), CV disease (CVD) was observed in 36% and 24% in male and female patients, respectively [5]. This is consistent with other studies, reporting CVD in 42%–48% of SCLC patients [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
