Stereotactic body radiation therapy using the CyberKnife(®) system for patients with liver metastases

Abstract

The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with liver metastases. Between August 2006 and July 2011, patients with 1-4 liver metastases were enrolled and treated with SBRT using the CyberKnife(®) system at Tianjin Medical University Cancer Institute and Hospital. The metastases were from different primary tumors, with a maximum tumor diameter of less than 6 cm. The primary endpoint was local control. Secondary endpoints were overall survival, progression-free survival, distant progression-free survival, and adverse events. Fifty-seven patients with 80 lesions were treated with SBRT. The 1-year and 2-year local control rates were 94.4% and 89.7%, respectively. The difference in local control between patients who received adjuvant treatment before SBRT and those who did not reached statistical significance (P=0.049). The median overall survival for the entire cohort was 37.5 months. According to the primary tumor sites, the median overall survival was not reached. The 2-year overall survival rate was 72.2% in the favorable group (primary tumors originating from the colon, breast, or stomach, as well as sarcomas); however, in the unfavorable group (primary tumors originating from the pancreas, lung, ovary, gallbladder, uterus, hepatocellular carcinoma, as well as olfactory neuroblastoma), the median overall survival and 2-year overall survival rates were 37.5 months and 55.9%, respectively (P=0.0001). Grade 1-2 fatigue, nausea, and vomiting were the most common adverse events, and no grade 3 and higher adverse events were observed. With excellent local control in the absence of severe toxicity, SBRT provides an alternative for patients with 1-4 liver metastases who cannot undergo surgery or other treatments.

Keywords: liver metastasis; local control; stereotactic body radiotherapy.

Figure 1

Representative planning CT and isodose distributions with SBRT for patients with 1–3 LM. Notes: Each representative patient had axial, sagittal, and coronal images taken, and red and purple lines indicate GTV and PTV, respectively. (A) A 38-year-old woman treated for a solitary LM from breast carcinoma. SBRT was performed using three fractions of 12 Gy prescribed to the 78% isodose line. (B) A 54-year-old man treated for two LM from rectal carcinoma. SBRT was performed using five fractions of 9 Gy to the 77% isodose line. (C) An 18-year-old man treated for three LM from pancreatic carcinoma. SBRT was performed in three fractions of 12 Gy to the 77% isodose line. Abbreviations: LM, liver metastasis; CT, computer tomography; GTV, gross tumor volume; PTV, planning target volume; Gy, Gray; SBRT, stereotactic body radiation therapy.

Figure 2

Analysis of initial planning CT and PET/CT as well as follow-up MRI images for a representative patient (a 23-year-old woman treated for a solitary LM from breast carcinoma). Notes: SBRT was delivered in three fractions of 14 Gy to the 81% isodose line. (A) Initial planning CT and PET/CT images showing a 3.2 cm lesion. (B–G) T1-weighted and T2-weighted MRI images showing a complete response, with decreased attenuation in the surrounding region 6 months after completion of SBRT. The red arrows indicate changes in the liver metastasis after treatment. Abbreviations: CT, computer tomography; PET/CT, positron emission tomography/computer tomography; MRI, magnetic resonance imaging; LM, liver metastasis; Gy, Gray; PTV, planning target volume; SBRT, stereotactic body radiation therapy.

Figure 3

Actuarial local control, PFS, and DPFS of patients with LM. Notes: (A) Overall local control, (B) local control depending on tumor-based or patient-based analyses, (C) local control depending on primary tumor, (D) local control depending on LM site, (E) local control depending on time between first LM and SBRT, (F) local control depending on prior systematic treatment or lack thereof, (G) local control depending on BED, and (H) PFS and DPFS of patients with LM. Abbreviations: PFS, progression-free survival; DPFS, distant progression-free survival; LM, liver metastases; BED, biologically equivalent dose; IT, interval time; SBRT, stereotactic body radiation therapy; Gy, Gray; Cum, cumulative.

Figure 4

Actuarial overall survival in patients with LM. Notes: (A) OS in general, (B) OS depending on patient age, (C) OS depending on patient gender, (D) OS depending on primary tumor, (E) OS depending on number of LM, (F) OS depending on extrahepatic metastasis or lack thereof, (G) OS depending on time between first LM and SBRT, and (H) OS depending on prior systematic treatment or no such history. Abbreviations: OS, overall survival; LM, liver metastasis; IT, interval time; SBRT, stereotactic body radiation therapy; Cum, cumulative; Y, year.