Pelvic Fractures and Changes in Bone Mineral Density Following Radiotherapy for Cervical, Endometrial and Vaginal Cancer: A Prospective Study of 239 Women

Background: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers, however, the long-term effects and survivorship implications need further evaluation. The purpose of our study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) following pelvic RT. Methods: We prospectively evaluated 239 women undergoing RT for cervical, endometrial or vaginal cancer between 2008 and 2015. BMD scans and biomarkers of bone turnover were obtained at baseline and three months, one year and two years following RT. Imaging studies were assessed for pelvic fracture for up to 5 years. Patients with osteopenia, osteoporosis or a pelvic fracture at any point were referred to the endocrinology service for evaluation and treatment. Findings: Median age at diagnosis was 51 years; 132 patients (56%) were menopausal. Primary diagnoses were cervical (64%), endometrial (30%) and vaginal (6%) cancer. Sixteen patients (7·8% 95% CI: 4·5–12·4%) developed a pelvic fracture with actuarial rates of 3·6%, 12·7% and 15·7% at one, two, and three years respectively. Fractures were associated with older age (p=0·007), lower BMI (p = 0·035), menopausal status (p = 0·049), higher baseline BAP level (p<0·001) and osteoporosis at baseline (p<0·001). The proportion of patients with osteopenia/osteoporosis increased from 50% at baseline to 58%, 59%, and 70% at three months, one year, and two years, respectively. Vitamin D deficiency was diagnosed and treated at baseline in 43% of patients. Interpretation: A high proportion of women had significant decreases in BMD following pelvic RT, with 7·8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered in these high-risk women. Trial Registration: The study was registered with clinicaltrials.gov (NCT00800644). Funding Statement: National Institutes of Health through MD Anderson's Cancer Center Support Grant CA016672, MD Anderson Cancer Center Institutional Research Grant and Dunaway Family Fund. Declaration of Interests: All the authors declare that they have no conflicts of interest related to this study. Dr. Anil K. Sood has declared consulting relationships (Merck and Kivatec), research funding (M-Trap) and to be a shareholder of BioPath. None of his conflicts are related to this study. Ethics Approval Statement: Institutional Review Board approval was obtained and all patients provided informed consent. This manuscript has been prepared accordingly the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.