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肝细胞癌恶性骨病的自然史:一项多中心骨转移调查的最终结果

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

作者信息

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

机构信息

Medical Oncology Unit - University Campus Bio-Medico, Rome, Italy.

Medical Oncology Unit, Cardarelli Hospital, Naples, Italy.

出版信息

PLoS One. 2014 Aug 29;9(8):e105268. doi: 10.1371/journal.pone.0105268. eCollection 2014.

Abstract

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.

摘要

背景

在晚期肝细胞癌(HCC)患者中,骨转移并不常见。因此,关于HCC患者骨转移自然史的研究较少。

患者与方法

对211例已故且有骨转移证据的HCC患者的临床病理、生存情况、骨相关事件(SREs)及骨靶向治疗数据进行统计学分析。

结果

中位年龄为70岁;172例患者为男性(81.5%)。中位总生存期为19个月。骨转移发生的中位时间为13个月(HCC诊断时为22.2%);64.9%的患者有多处骨转移。脊柱是最常见的骨转移部位(59.7%)。这些病变大多为溶骨性(82.4%);其中88.5%接受了唑来膦酸治疗。多因素分析显示,只有Child评分与骨转移诊断时间较短显著相关(p = 0.001,HR = 1.819)。骨转移后的中位生存期为7个月。多因素分析显示,HCC病因(p = 0.005)、东部肿瘤协作组(ECOG)体能状态(p = 0.002)和双膦酸盐治疗(p = 0.024)与骨病发生后的生存期较短相关。骨转移部位而非骨病变数量与首次骨相关事件(SRE)后的生存期(p = 0.021)和总生存期(p = 0.001)相关。

结论

本研究显著增进了对HCC患者骨骼疾病自然史的理解。迫切需要对这些患者进行早期且恰当的管理,以避免其生活质量随后恶化。

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