Serial Bone Density Changes in Women Undergoing Pelvic (Chemo) Radiation: Results From the PARCER Trial.

PURPOSE: Pelvic irradiation leads to substantial dose to the pelvic girdle. However, bone density loss as a function of radiation therapy dose and time has not been investigated. This study was undertaken to evaluate such a dose-response relationship.

METHODS AND MATERIALS: Women undergoing pelvic radiation therapy for cervix cancer within a phase 3 trial were included. The study necessitated 2 computed tomography imaging sets acquired at least 12 months apart in patients with no evidence of relapse. All images were transferred to the treatment planning system to determine radiation dose and Hounsfield unit (HU). Across the entire lumbopelvic region (lumbar 1-5 [L1-5] vertebrae, pubic symphysis, femur, acetabulum, greater trochanter, and anterior-superior iliac spine) multiple regions were defined to measure radiation therapy dose and HU. Bone health was categorized as normal if >130 HU, osteopenic at 110 to 130 HU, and osteoporotic <110 HU at baseline and follow-up. Univariate analysis was performed to test the effect of various factors on HU. Further interaction among radiation therapy dose, time, and HU was assessed using a linear mixed model.

RESULTS

Overall, 132 of 300 patients were eligible. The median age was 49 (42-56) years. With a prescription dose of 50 Gy, the L1 and L2 vertebrae received a median dose of 1.2 and 4 Gy, respectively, and L3-5 received 10 to 50 Gy. At 24 months, median HU loss at L4-5 was 45 HU (interquartile range, 34-77 HU). Out of the 132 patients, at baseline 96% had normal bone health. However, at the last follow-up, 3% of patients had normal bone health, 12% developed osteopenia, and 85% developed osteoporosis (P < .001). There were no patient- or treatment-related factors predicted for HU loss on univariate analysis. HU loss >60 to 70 was observed at >45 Gy at L5 vertebra (60-70 HU, P < .02) and >15 Gy at L4 vertebra (33 HU; P = .04).

CONCLUSIONS

Dose-response relationship is observed between radiation dose and bone mineral density loss. Prospective studies are needed to corroborate these observations and design future interventions.