The Development of Rib Fractures after Stereotactic Body Radiation Therapy to the Liver

Abstract

Chest wall toxicity – pain and/or fracture – is well described complication of thoracic stereotactic body radiation therapy (SBRT). While well described for lung SBRT, limited data exists on the frequency and predictors for chest wall toxicity with SBRT to the liver for primary or metastatic lesions. We aimed to characterize the incidence and predictors of rib fractures in these patients. With IRB approval, we retrospectively reviewed the records of patients treated at a single NCI designated cancer center with SBRT to the liver from 2014-2019. Inclusion criteria included: (1) Age of ≥18 years; (2) SBRT defined as the delivery of at least 5 Gy per fraction in ≤ 5 fractions; (3) at least one follow-up scan that included imaging of the chest wall and liver ≥ 3 months. Using the linear quadratic model, a/b ratios of 10 Gy and 3 Gy were used to evaluate the impact of dose as a continuous variable. Univariate logistic regression was used to characterize predictors for the development of rib fractures, where the null hypothesis was rejected for p<0.05. All statistical analyses were conducted in R Studio Version 1.1.383. Three hundred eighty-one courses of liver SBRT were queried from 2014-2019. Of these, 319 SBRT treatments delivered to 283 patients (204 male and 79 female) met inclusion criteria. The median age was 65 years (range: 22-91 years). The median follow-up was 9.3 months (range: 3-50 months). With respect to primary site, 81% were primary liver tumors and 19% metastases. SBRT doses ranged from 60 Gy in 5 fractions to 30 Gy in 5 fractions. The most commonly used doses were: 40 Gy in 5 fractions (29%), 45 Gy in 5 fractions (23%), 50 Gy in 5 fractions (18%), 35 Gy in 5 fractions (9%), 48 Gy in 3 fractions (8%), and 30 Gy in 5 fractions (5%). A total of 17 patients (6%) experienced rib fractures at least 3 months after completing liver SBRT. Of these patients, three (17.6%) and one (6%) underwent two and three liver SBRT courses, respectively. On logistic regression, female gender (odds ratio [OR]: 3.7; 95% confidence interval [CI]: 1.41-10.02; p = 0.008), increasing BED3 Gy (OR: 1.01; 1.00-1.01; p = 0.05), and BED10 Gy (OR: 1.02; 95% CI: 1.00-1.04; p = 0.047) were associated with the development of rib fractures. Undergoing more than one course of SBRT to the liver (OR: 1.32; 95% CI: 0.41-3.63; p = 0.61) and administration of 3 fractions versus 5 fractions (OR: 1.98; 95% CI: 0.44-6.57; p = 0.31) were not associated with the development of rib fractures. The incidence of rib fractures after undergoing liver SBRT remains low at approximately 5%. Female gender and increasing BED appear to increase this risk. Future investigation will aim further characterize dosimetric parameters to better define this risk.