Bone Mineral Density Changes Within and Outside of RT Fields Used to Treat Cervical Cancer

Abstract

Pelvic insufficiency fractures and decreased bone mineral density (BMD) can occur in women treated with radiotherapy (RT) for gynecologic cancers. The purpose of this study was to compare the magnitude of BMD changes inside and outside of the radiation field in patients treated with radiation +/- chemotherapy for cervical cancer.In an IRB-approved prospective study, women (N = 78) with cervical cancer were assessed with serial tomographic scans and dual-energy x-ray absorptiometry (DXA) scans to evaluate the incidence of pelvic fractures (previously reported) and post-treatment BMD changes. Patients were treated with definitive RT or chemoradiation (CRT) at a single institution between 09/2008 and 07/2015. DXA scans were obtained at baseline (before CRT), 3 months, 1 year, and 2 years after completion of therapy. Serial BMD values at L1, L2, L3 and L4 were extracted from DXA reports. Patients with a pre-treatment history of pelvic fractures, bone metastases, or pelvic RT were excluded. The current analysis focused on a subset of 78 patients whose RT fields had upper borders below L1 and above L4, permitting a comparison of BMD changes in the field (L4) with those in a vertebral body outside the field (L1). Linear mixed models (LMM) were performed to examine the impact of radiotherapy on BMD change over time, and were adjusted for covariates (age, menopausal status, BMI, number of chemotherapy cycles).The median age of 78 patients was 45.5 years (range 23-88); all received RT and 76/78 (97.5%) received concurrent CRT. Treatment was associated with a significant decline in BMD in all 4 lumbar vertebral bodies over time, P < 0.05 with nadir at 3 months (L4) and 1 year (L1). By pairwise comparisons at 3 months and 2 years after treatment, BMD in L4 (inside RT field, P = 0.037) significantly improved while BMD in L1 (outside RT field) did not significantly change. After controlling for covariates noted above, there was no significant difference in BMD between 3 months and 2 years. Levels of C-terminal telopeptide of type I collagen (P = 0.018), bone alkaline phosphatase (P < 0.001), and number of chemotherapy cycles (P = 0.031) were significant predictors of L1 BMD loss. A trend of higher BMD at all time points was found for patients who were premenopausal versus postmenopausal at study entry. At 1- and 2-years of follow-up, trends towards BMD at levels higher than baseline were seen for patients who received hormone replacement therapy (HRT) after RT.Significant BMD loss following radiation treatment in all lumbar vertebrae (both in and out of field) was observed. On multivariate analysis, in-field vertebral bodies experienced no additional significant BMD decline earlier than those out-of-field, suggesting multifactorial contributors to bone density loss. HRT may improve BMD recovery and emphasizes the need for HRT after radiotherapy in appropriate premenopausal women.J. Wu: None. D.S. Lakomy: None. B. Fellman: None. M.P. Salcedo: IGCS-International Gynecologic Cancer Society, Brazilian Federation of Gynecology and Obstetricians (FEBRASGO)/BRAZIL (Federação Brasileira de Ginecologia e Obstetricia, FEBRASGO). A. Sood: Consultant; Kiyatec, Astra Zeneca. Stock; BioPath. sponsored research; M-Trap. A. Jhingran: American Board of Radiology. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. R.B. Iyer: None. C. Jimenez: None. L. Colbert: None. K. Schmeler: None. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca.