2741 - Effect of Proton vs. Photon Radiation Therapy on Bone Density and Insufficiency Fractures in Gynecologic Patients

Purpose/Objective(s): Pelvic external beam radiation therapy (EBRT) is standard adjuvant treatment for locally advanced uterine and cervical cancer. Pelvic EBRT increases the risk of pelvic insufficiency fractures (PIFs), ranging from 0% to 50% in studies. There is little data investigating the role of proton vs photon radiation therapy (RT) in risk of PIFs. We sought to compare the change in pelvic bone density and risk of PIFs in gynecologic cancer patients treated with proton vs photon pelvic RT.

Materials/Methods: This study was IRB approved. Patients with stage IIIC uterine and cervical cancer status post hysterectomy, lymphadenopathy, and pelvic RT were eligible. Proton and photon patients were case-matched based on EBRT and brachytherapy dose. Patient, tumor, and treatment characteristics were extracted from medical records. Change in pelvic bone density was assessed by measuring the Hounsfield Unit (HU) of the S1 vertebral body pre- and post-RT on computed tomography (CT) at time of simulation and after completion of all RT. Adverse event of interest included PIFs and was assessed using the Common Terminology Criteria for Adverse Events version 5.0.

Results: Forty-two patients were identified, half received proton pencil-beam scanning (PBS) RT and half received photon RT (PRT) to the pelvis to 45 Gy followed by a 15 Gy brachytherapy boost to the vaginal cuff. 86% had uterine cancer and 14% had cervical cancer. Median age at diagnosis was 59.8 years (IQR: 55.5-72.0 years) and 61.3 years (IQR: 55.2-68.9 years) in the PBS and PRT groups, respectively. Median follow-up time from completion of RT was 6.8 years (IQR: 1.6-8.3 years) and 5.7 years (IQR: 3.2-11.7 years) in the PBS and PRT groups, respectively. Median time to obtain post-RT CT was 11.6 months (IQR: 10.2-12.9 months) and 12.5 months (IQR: 8.2-14.8 months) in the PBS and PRT groups, respectively. Median pre- and post-RT mean HU at S1 was 213.8 (IQR: 196.3-219.4) and 182.9 (IQR: 156.1-197.4) in the PBS group, respectively, and 211.45 (IQR: 180.12-263.82) and 178.1 (IQR: 145.3-228.2) in the PRT group, respectively. Median percent change in pre- and post-RT HU was 14.8% (IQR: 3.1-25.4%) in the PBS group and 19.7% (IQR: 6.1-24.9%) in the PRT group (p = 0.8). PIFs occurred in 1 patient (4.8%) in the PBS group and 6 (28.6%) in the PRT group. Median time to fracture was 12.9 months in the PBS group and 17.0 months (IQR: 10.6-10.5 months) in the PRT group. One patient had abnormal DEXA scan pre-RT in the PBS group and did not develop PIF; two patients had abnormal DEXA scans pre-RT in the PRT group and 1 developed PIF.

Conclusion: The change in bone density pre- vs post-RT, measured by HU, was not significantly different between proton and photon RT. However, photon RT patients experienced a larger number of PIFs and at a later time from completion of RT. Further investigation with a larger cohort of case-matched proton and photon RT patients is warranted to better understand the increased risk of PIFs in patients undergoing proton vs photon pelvic RT.