The role of LDH serum levels in predicting global outcome in HCC patients treated with sorafenib: implications for clinical management

Abstract

BackgroundIn many tumour types serumlactate dehydrogenase (LDH) levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. As we previously reported LDH is an important predictive factor in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Sorafenib represents the therapeutic stronghold in advanced HCC patients. As a tyrosine kinase inhibitor (TKI) mainly directed against the angiogenetic pathway, the correlation of sorafenib administration with markers of hypoxia could be an important tool in patients management. Aim of our analysis was to evaluate the role of LDH pre-treatment levels and its variation during treatment in HCC patients receiving sorafenib.Methods78 patients were available for our analysis. For all patients LDH values were collected within one month before the start of treatment and after the end of therapy. For study purposes we divided our patients into two groups, according to LDH pre-treatment levels, cut-off levels was determined with ROC curve analysis. Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased vs decreased).ResultsPatients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values under the cut-off median progression free survival (PFS) was 6.7 months, whereas it was 1.9 months in patients above the cut-off (p = 0.0002). Accordingly median overall survival (OS) was 13.2 months and 4.9 months (p = 0.0006). In patients with decreased LDH values after treatment median PFS was 6.8 months, and median OS was 21.0 months, whereas PFS was 2.9 months and OS 8.6 months in patients with increased LDH levels (PFS: p = 0.0087; OS: p = 0.0035).ConclusionsIn our experience, LDH seemed able to predict clinical outcome in terms of PFS and OS for HCC patients treated with sorafenib. Given the correlation between LDH levels and tumour angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for other emerging therapeutic agents or strategies targeting different molecular pathways.

1009 Serum lactate dehydrogenase and survival following cancer diagnosis

“…Similar associations with survival have been established in chronic myeloid and lymphocytic leukaemias (Weinberg et al, 2007;Goldaniga et al, 2008) and small cell lung cancer (SCLC) (You et al, 2008;Danner et al, 2010). In recent clinical trials, elevated serum LDH has been shown as an independent predictor of overall survival in advanced or metastatic cancer of the breast (Brown et al, 2012), prostate (Scher et al, 2009;Gravis et al, 2014), colorectum (Bar et al, 2014), oesophagus (Polee et al, 2003), pancreas (Tas et al, 2001), ovary (Schneider et al, 1998), nasopharynx (Jin et al, 2013), gastric adenocarcinoma (Sougioultzis et al, 2011), hepatocellular carcinoma (HCC) (Faloppi et al, 2014), renal cell carcinoma (Armstrong et al, 2012) and melanoma (Balch et al, 2004;Weide et al, 2012). The inverse association with overall survival in solid tumours were shown in a recent meta-analysis, with HR for overall death of 1.7 (95% CI: 1.62-1.79) (Petrelli et al, 2015).…”

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

“…A recent study has indicated that LDHA is up-regulated in HCC cells and promotes tumor growth and metastasis[38]. A series of clinical studies assessed the serum levels of LDH in HCC patients who were treated with hepatic resection[39,40], transarterial chemoembolization[41,42] and sorafenib[43,44] and found a similar conclusion that LDH may be an easily obtained biomarker for prognosis prediction and treatment selection for HCC patients.…”

Lactate dehydrogenase 5: An old friend and a new hope in the war on cancer

“…Studies on hepatocellular carcinoma (HCC) have proved that pretreatment serum LDH levels might help to predict clinical outcome for HCC patients undergoing transarterial-chemoembolization (TACE) [45]. Additionally, it was found that serum LDH might be a useful marker for predicting global clinical outcomes in HCC patients treated with a tyrosine kinase inhibitor (sorafenib) [46]. The determination of serum LDH levels appeared to be a helpful clinical tool also in the diagnosis of prostate cancer and in the control of androgenic treatment [47].…”