International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationInsufficiency Fractures After Pelvic Radiation Therapy for Uterine Cervical Cancer: An Analysis of Subjects in a Prospective Multi-institutional Trial, and Cooperative Study of the Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG)
Introduction
Insufficiency fractures (IF) are a type of stress fracture, occurring after normal or physiologic stress on bone with decreased mineralization and elastic resistance (1). Insufficiency fractures of the pelvic bones are thought to be associated with postmenopausal or corticosteroid-induced osteoporosis 1, 2. Pelvic radiation therapy (RT) also can affect the development of pelvic IF, although the precise pathogenesis is as yet unclear 1, 2. Although some investigators 3, 4, 5 have reported that pelvic IF are an uncommon adverse event in irradiated patients with gynecologic cancer, others 6, 7, 8, 9, 10 have reported that radiation-induced pelvic IF were frequently observed in women after RT. It seems that the precise incidence of IF is unclear. The findings on conventional radiographs are usually subtle 2, 10 and may be misleading. The fractures usually show increased uptake on radionuclide bone scans. A pattern of increased uptake in the body of the sacrum and in one or both sacrum alae 1, 2, 11 is indicative of a fracture, but increased uptake may also be present in metastases and sacroiliac joint osteoarthritis (12). The importance of understanding a pelvic IF lies in the potential for its misdiagnosis as bony metastases. Computed tomography (CT) is capable of displaying fracture lines and/or sclerotic changes associated with IF 8, 9, 11, whereas magnetic resonance imaging (MRI) is highly sensitive for revealing the reactive bone marrow changes associated with IF 9, 13.
Not only for unresectable locally advanced stages, RT has played an important role in the treatment of early-stage cervical cancer. Originally, to determine the efficacy of definitive RT using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study (JAROG0401/JROSG04-2) (14). Two-year pelvic disease progression-free rate was the primary endpoint, and late complication including IF was one of the secondary endpoints in the study (14). At first, IF was evaluated by only symptomatic features. However, we noticed that some follow-up imaging features after RT had shown IF of pelvic bones in several asymptomatic patients. Therefore, we planned this additional study to assess pelvic IF by adding a minute imaging evaluation prospectively, without changing the schedule and methods of the follow-up CT and MRI in the protocol.
The purpose of this study was to investigate the incidence of radiation-induced pelvic IF using CT and MRI and to investigate the risk factors and radiation doses associated with IF, as well as the distribution of IF sites among patients with this complication. In our study, patients were treated with the constant RT method described in the protocol and followed with CT and MRI regularly. To our knowledge, this is the first multi-institutional prospective analysis on IF.
Section snippets
Patient eligibility criteria
The women enrolled in these analyses were a group of patients with cervical carcinoma who were treated with a protocol JAROG0401/JROSG04-2) (14). Eligible patients had histologically proven squamous cell carcinoma of the intact uterine cervix with International Federation of Gynecologic Oncology and Obstetrics (FIGO) stage Ib1/IIa/IIb disease and were aged 20-80 years. A complete physical examination, pelvic examination performed without anesthesia, and chest X-ray were required to determine
Patients
Between September 2004 and July 2007, 60 patients were enrolled from 13 institutions. One patient was considered ineligible, leaving 59 patients in the final patient cohort.
The median age was 73 years (range, 37-84 years). The eligible patients had squamous cell carcinoma of the uterine cervix, and the FIGO stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. No patients had pelvic/paraortic lymphadenopathy. The median follow-up was 24 months.
Incidents and clinical characteristics of IF
A total of 21 patients were diagnosed with IF
Discussion
Insufficiency fractures occur most often in elderly women with postmenopausal osteoporosis (2). Other predisposing factors include rheumatoid arthritis, corticosteroid therapy, heparin use, diabetes mellitus, low body weight, current smoking, and RT (15). Fu et al (16) reported that the incidence of IF increased when the dose was above the threshold of 45 Gy. However, there have been no tolerance dose data for IF. In conventional pelvic RT, the irradiated dose of the pelvic bone is usually
Acknowledgment
The authors thank Ms. Y Asazawa and Ms. K Ayabe for their helpful assistance.
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2020, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Patient characteristics associated with an increased risk of developing fractures include age, weight, BMI, menopausal status, use of hormone replacement therapy, birth history, and smoking status. Older age was identified as a risk factor for PIFs in 12 studies.10-20,26 Multiple studies10,12,18,20 found that patients who developed PIFs had a higher mean (or median) age than patients who did not develop fractures.
Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients
2020, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :It was found that more recent publications (P = .0074) and series that include patients treated with IMRT technique (P = .0299) were significantly associated with fewer PIF events (Supplementary Material E5, appendix available online at https://doi.org/10.1016/j.ijrobp.2019.09.012). The total number of PIFs (each patient could have more than 1) was provided by 14 studies,4,5,7,14,17,20-29 with a total of 704 PIFs in 409 patients who developed any PIF (mean, 1.72 PIFs per patient). Of these studies, the location of the fracture was presented in 11 reports, comprising 610 fractures (mean, 1.65 PIFs per patient).
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This study was supported by Ministry of Health, Labor and Welfare (Japan) Grant-in-Aid for Cancer Research No. 16-12.
Conflict of interest: none.