Abstract
Background: Platelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied. Methods: Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count <150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). Results: Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3-13.8] vs. 5.5 [3.8-7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001). Conclusions: Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.
| Original language | English |
|---|---|
| Journal | Liver Cancer |
| Volume | 8 |
| Issue number | 3 |
| Pages (from-to) | 203-217 |
| Number of pages | 15 |
| ISSN | 2235-1795 |
| DOIs | |
| Publication status | Published - 2019 |
Funding
B.S. received travel support from Gilead; M.M.K. received speaker and consulting fees from Shire, Roche, and BMS; S.P. has nothing to declare, F.H. and S.B. received travel support from Bayer; N.R.-U. received travel support or honoraria from Roche and Bayer HealthCare; M.P.R. received grant support and honoraria from Bayer HealthCare and BMS, and served as a consultant for Bayer HealthCare, BMS, Lilly, ONXEO, and Eisai; T.R. received travel support from Gilead, Roche, MSD, and Gore, grant support from Gilead, Abbvie, Philips, Boehringer Ingelheim, Phenex Pharmaceuticals, and Gore, and served as a consultant for MSD, Gilead, Abbvie, and Boehringer Ingelheim; C.M. has nothing to declare; M.T. received grants from MSD, honoraria for consulting from AbbVie, Gilead, Janssen, and MSD, payments for lectures from Gilead, MSD, and Roche, as well as travel support from Gilead; A.V. received speaker and consulting fees from Bayer, Lilly, Roche, BMS and MSD; W.S. received speaker and consulting fees and research grants from Bayer Schering Pharma; M.P. is advisory board member of Bayer, BMS, and Eisai, and received travel support from Bayer and speaking fees from Bayer and BMS. He is also an investigator for Bayer, BMS, and Lilly.
