To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan-Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.
We investigated the clinical efficacy of stereotactic ablative radiotherapy (SABR) in patients with oligometastatic hepatocellular carcinoma (HCC). The inclusion criteria were patients receiving definitive treatment for HCC with 1–5 metastatic lesions, <3 metastases in a single organ and receiving radiotherapy with fraction doses ≥6 Gy. A total of 100 patients with 121 metastatic lesions were reviewed. The most common site of metastasis was the bones (40%), followed by the lungs (38%). Systemic therapy was administered to 71% of patients. With a median follow-up of 13 months, the median overall survival (OS) was 16 months. The 2-year OS rate was 40%. The prognostic factors in univariate analysis were performance status, Child–Pugh class, primary HCC status, and time interval of metastasis. Performance status and Child–Pugh class remained in multivariate analysis. OS differed significantly depending on the number of prognostic factors: 46 months in patients with both factors (Group 1), 13 months with one factor (Group 2), and 6 months with no risk factor (Group 3) (p < 0.001). Nine patients experienced grade 1 radiation pneumonitis. Given its efficacy and safety, SABR deserves active consideration in the treatment of oligometastatic HCC.
The “oxygen effect” improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.