Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma

Oncotarget. 2016 Jul 26;7(30):48586-48599. doi: 10.18632/oncotarget.9374.

Abstract

We evaluated radiotherapy using helical tomotherapy (HT) combined with sorafenib for treatment of pulmonary metastases from hepatocellular carcinoma (HCC). We also analyzed potential prognostic factors and further validated the combination treatment. The objective response rate in the total cohort of 45 patients treated with HT (with or without sorafenib) was 66.7% (complete response, n = 1; partial response, n = 29), with no adverse events > grade 2 in severity. Median progression-free survival (PFS) and overall survival (OS) were 7.50 ± 0.53 and 26.40 ± 2.66 months, respectively. The addition of sorafenib was associated with increased PFS (11.80 ± 1.55 vs 5.80 ± 0.52 months, p = 0.006) and increased OS (29.60 ± 5.23 vs 21.90 ± 5.17 months, p = 0.007). After multivariate adjustment, the risk of disease progression associated with combination treatment was significantly lower (p = 0.022) compared with HT only, and survival was significantly longer (p = 0.014). Further validation confirmed the benefit of combination treatment. Prognostic factors were number of pulmonary metastases for PFS (19.00 ± 7.15 months for ≤3 lesions vs 5.80 ± 0.26 months for >3 lesions, p < 0.001) and intrahepatic tumor status for OS (28.50 ± 2.76 months for well-controlled tumors vs 15.60 ± 6.38 months for uncontrolled tumors, p = 0.011). In conclusion, radiotherapy with HT for pulmonary metastases is feasible without major complications, and its combination with sorafenib may be a promising approach in a subgroup of patients.

Keywords: helical tomotherapy; hepatocellular carcinoma; prognosis; pulmonary metastases; radiotherapy.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cohort Studies
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Disease-Free Survival
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Lung Neoplasms / blood
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Sorafenib
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Sorafenib