ABSTRACT
Circulating tumor cells (CTCs) may provide a liquid biopsy approach to disease monitoring in small cell lung cancer (SCLC), a particularly aggressive tumor subtype. Yet, the prognostic role of CTCs during and after treatment in relation to baseline remains ill-defined. Here, we assessed the value of longitudinal CTC analysis and the potential of low-molecular-weight heparin (LMWH) to reduce CTC abundance in SCLC patients from a randomized trial (RASTEN). Blood samples were collected at baseline, before chemotherapy Cycle 3, and at 2-month follow-up from 42 patients in total, and CTCs were quantified using the FDA-approved CellSearch system. We found a gradual decline in CTC count during and after treatment, independently of the addition of LMWH to standard therapy. Detectable CTCs at baseline correlated significantly to reduced survival compared to undetectable CTCs (unadjusted hazard ratio (HR) of 2.75 (95% CI 1.05-7.20; p = 0.040)). Furthermore, a persistent CTC count at 2-month follow-up was associated with a HR of 4.22 (95% CI 1.20-14.91; p = 0.025). Our findings indicate that persistently detectable CTCs during and after completion of therapy offer further prognostic information in addition to baseline CTC, suggesting a role for CTC in the individualized management of SCLC.
ABSTRACT
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.
