Natural history of malignant bone disease in hepatocellular carcinoma: Final results of a multicenter bone metastasis survey

Daniele Santini, Francesco Pantano, Ferdinando Riccardi, Giovan Giuseppe Di Costanzo, Raffaele Addeo, Francesco Maria Guida, Mariella Spalato Ceruso, Sandro Barni, Paola Bertocchi, Sara Marinelli, Paolo Marchetti, Antonio Russo, Mario Scartozzi, Luca Faloppi, Matteo Santoni, Stefano Cascinu, Evaristo Maiello, Franco Silvestris, Marco Tucci, Toni IbrahimGianluca Masi, Antonio Gnoni, Alessandro Comandone, Nicola Fazio, Alessandro Conti, Ilaria Imarisio, Salvatore Pisconti, Elisa Giommoni, Saverio Cinieri, Vincenzo Catalano, Vincenzo Ostilio Palmieri, Giovanni Infante, Michele Aieta, Antonio Trogu, Cosmo Damiano Gadaleta, Anna Elisabetta Brunetti, Vito Lorusso, Nicola Silvestris

Research output: Contribution to journalArticlepeer-review


Background: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. Patients and Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. Results: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). Conclusions: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

Original languageEnglish
Article numbere105268
JournalPLoS One
Issue number8
Publication statusPublished - Aug 29 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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