Biomarkers of lung damage with possible predictiveness of ARDS within CS in super high-risk patients with germ cell tumors.

Abstract

411 Background: Germ cell tumors (GCTs) represent a highly curable disease; however, a small proportion of patients with super-high-risk characteristics (choriocarcinoma, massive lung metastases, choriogonadotropin > 50 000 mIU/ml) can develop choriocarcinoma syndrome (CS) and consecutive acute respiratory distress syndrome (ARDS) shortly after the chemotherapy start with high mortality rate. This study aimed to evaluate biomarkers of lung damage as predictive biomarkers for ARDS development within CS in poor-risk GCTs patients. Methods: This study included 23 poor-risk GCTs treated from November 2000 to May 2018 in National Cancer Institute in Slovakia for whom plasma samples before chemotherapy initiation were available. Plasma levels of lung damage biomarkers (surfactant protein (D-SPD), receptor of advanced glycation end-products (sRAGE), and club cell secretory protein – (CC16)) were evaluated by ELISA assays. Results: Five (22%) of 23 patients developed CS, and all of them died shortly after the chemotherapy start. with median of 7 days (4 - 35 days). Four of them developed ARDS within CS, while one patient died due to massive abdominal hemorrhage. Pre-treatment levels of s-RAGE and SPD but not CC-16 were significantly associated with CS development ( P = 0.03 and P = 0.04). Level of sRAGE and SPD correlated significantly with dyspnea, weight loss, extent of metastatic lung involvement and need of mechanical ventilation after chemotherapy start, as well as with PFS and OS, while CC-16 did not correlate with any of these factors. Conclusions: In this study we identified new predictive biomarkers for CS development in poor-risk GCTs. Abovementioned factors might help to improve the risk stratification of these patients with GCTs as well as discover new treatment approaches preventing ARDS development within CS which may result in enhanced treatment outcome.