Long Term Risk of Pelvic Insufficiency Fractures and Lower Extremity Edema After Definitive Chemoradiation for Squamous Cell Carcinoma of the Anal Canal.

Abstract

PURPOSE/OBJECTIVE(S)\nDefinitive chemoradiation is the standard of care of treatment of squamous cell carcinomas (SCC) of the anal canal. While this treatment is effective, definitive chemoradiation is associated with significant acute and late toxicities. In this study, we seek to evaluate the incidence and identify risk factors of radiotherapy (RT) induced pelvic insufficiency fractures and lower extremity (LE) edema.\n\n\nMATERIALS/METHODS\nWe performed a single-institution retrospective analysis of 185 patients treated with chemoradiation for anal SCC between 2007-2019. Median age was 61 (range: 15-92); 9.8% were metastatic and 34.1% were men. All patients received concurrent chemotherapy, including 160 patients treated with concurrent 5-fluorouracil /MMC, 12 treated with 5-fluorouracil /Cisplatin, 9 patients treated with 5FU alone, 2 treated with FOLFOX alone, and 2 treated with Carboplatin/Paclitaxel. Median dose to the pelvis was 54 Gy. RT modalities included IMRT/VMAT (N\u202f=\u202f157), pencil beam proton beam (N\u202f=\u202f17), 3D-CRT (N\u202f=\u202f6), and multi-modalities (N\u202f=\u202f5). Patient medical charts and imaging were reviewed for patient/treatment characteristics, and to determine incidence of development of post-RT related insufficiency fractures and LE. Pelvic insufficiency fractures were all confirmed radiographically with CT or MRI pelvis. Patients with baseline LE edema were excluded from the analysis of post-RT related LE edema. Cox univariate analysis was performed to identify predictors of pelvic fracture.\n\n\nRESULTS\nMedian follow-up was 59 months. Among 185 patients, 11 (6%) patients developed pelvic insufficiency fractures at a median time of 11 months (range: 2.7-60) since completion of RT treatment (range: 2-60). Treatment for pelvic insufficiency fractures included narcotics (n\u202f=\u202f3), and no patient required sacroplasty. All but 1 of the patients who developed pelvic insufficiency fractures were women. However, gender (P\u202f=\u202f0.12) and menopausal status (P\u202f=\u202f0.87) were not significant on univariate analysis. On univariate analysis, only treatment with IMRT/VMAT (HR 2.33, P\u202f=\u202f0.02) predicted for higher risk of development of pelvic insufficiency fracture. Among patients without baseline LE edema, 5.95% of patients developed LE or pelvic edema after completion of RT at a median of 3 months post-treatment (range: 0-42). Of these, 7 patients developed LE edema, 1 developed vulvar edema, and 1 patient developed scrotal edema. All patients had grade 1+ edema.\n\n\nCONCLUSION\nRT related pelvic insufficiency fractures and LE edema are rare after chemoradiation to the pelvis, and often are incidental findings appreciated radiographically. IMRT/VMAT may be associated with higher risk of pelvic insufficiency fractures.