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Pelvic Insufficiency Fracture after Pelvic Irradiation in Uterine Cervix Cancer
Gynecologic Oncology 86, 264 –268 (2002) doi:10.1006/gyno.2002.6756
Pelvic Insufficiency Fracture after Pelvic Irradiation in Uterine Cervix Cancer Seung Jae Huh, M.D., 1 BoKyoung Kim, M.D., Min Kyu Kang, M.D., Jeong Eun Lee, M.D., Do Hoon Lim, M.D., Won Park, M.D., Seong Soo Shin, M.D., and Young Chan Ahn, M.D. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Gu, Seoul 135-710, Korea Received October 25, 2001
Objectives. Pelvic insufficiency fractures (IF) are well known but uncommon and are frequently misinterpreted sequelae. The clinical features were investigated. Methods. Four hundred sixty-three patients, who were treated between 1994 and 2000 for uterine cervix cancer, were clinically examined. All patients had been treated with 10 or 15 MV photons, with 50.4 –55.8 Gy in 28 fractions with adjuvant intent (n ⴝ 235) in addition to high-dose-rate brachytherapy 24 Gy in 6 fractions for curative treatment (n ⴝ 228). The median follow-up was 38 months. Results. Eight patients (8/463, 1.7%) developed pelvic IF 7–19 months (median, 12 months) after the treatment. Among these, seven patients (7/228, 3.1%) were treated with curative intent and one (1/235, 0.4%) was treated with adjuvant intent. All patients were postmenopausal and complained of moderate to severe pelvic pain, which resolved after 1–11 months with conservative therapy in all patients. Two of these patients also had radiation proctitis. Conclusion. In women who present with pelvic pain after radiotherapy for cervical cancer, bony destruction and fractures may be indicative of a late radiation effect rather than osseous metastasis. IF are more common in the curative treatment group than in the postoperative adjuvant group. © 2002 Elsevier Science (USA) Key Words: pelvic insufficiency fracture; pelvic irradiation; uterine cervix cancer.
INTRODUCTION Osseous complications are considered rare after pelvic irradiation in the megavoltage era. The advent of megavoltage equipment has helped reduce the incidence; however, it remains an important late complication [1–5]. Insufficiency fractures (IF) have been described in several situations with no history of prior trauma: (i) the postmenopausal state, (ii) subsequent to treatment with high-dose corticosteroids, and (iii) radiation exposure. IF differ from fatigue fractures, which are caused by the application of abnormal muscular stress to a bone that has normal elastic resistance [6]. Although the inci1
To whom correspondence and reprint requests should be addressed. Fax: ⫹82-2-3410-2619. E-mail: [email protected]. 0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.
264
dence of pelvic IF in patients being treated for cervical cancer and endometrial carcinoma with radiation is unknown, several recent studies now report an incidence of symptomatic pelvic fractures of 3– 6% [1– 4, 7]. Radiotherapy is usually used as a sole treatment modality or as a combined treatment with surgery or chemotherapy. Contrary to what was previously believed, radiation-induced pelvic bone complications are a much more common sequelae. When actively sought in asymptomatic patients, an incidence of 34% has been reported [8]. After pelvic irradiation in cervix cancer, patients with IF complain of pelvic pain associated with radiological findings such as hot uptakes on bone scan or pelvic bone fractures by plain radiography or CT scan. The importance of understanding pelvic IF lies in the potential for misdiagnosis as bony metastasis. In this investigation, we present eight cases of IF occurring in patients being treated with radiotherapy for carcinoma of the cervix and further discuss the possible risk factors. MATERIALS AND METHODS From September 1994 to December 2000, 463 patients were given pelvic radiotherapy for uterine cervix cancer at the Samsung Medical Center, Seoul, Korea. Among these, 228 patients with intact uteri were treated with curative intent, while 235 patients were treated with postoperative adjuvant radiotherapy. The median follow-up was 38 months. Eight patients with no history of trauma or bone pathology among the total 463 patients (8/463, 1.7%) developed pelvic IF 7–19 months (median, 12 months) following treatment. Among these 8 patients, 7 (7/228, 3.1%) had been treated with curative intent. In these patients, the entire pelvis was treated with external irradiation, using 10- or 15-MV photons from a linear accelerator, with a four-field pelvic box in 4 patients and with a parallel opposing AP/PA field technique in 3. The external radiation dose ranged from 50.4 to 55.8 Gy in 1.8-Gy fractions for 5 days each week. Intracavitary brachytherapy with a high-dose-rate brachytherapy (microSelectron-HDR) of 24 Gy
265
PELVIC INSUFFICIENCY FRACTURE AFTER PELVIC IRRADIATION
TABLE 1 Clinical Characteristics of Patients with Pelvic IF Patient No.
Age (years)
Stage
Surgery
ChemoTx
EBRT dose (Gy)
BT
Site
1 2 3 4 5
74 55 60 66 79
IB IIB IIA IIB IIB
⫺ ⫺ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺
50.4 50.4 50.4 55.8 55.8
⫹ ⫹ ⫹ ⫹ ⫹
6
59
IIA
⫹
⫺
50.4
⫺
7 8
67 60
II B IIIB
⫺ ⫺
⫺ ⫺
55.8 55.8
⫹ ⫹
Sacrum Sacrum Sacrum Sacrum Sacrum Pubis Sacrum, L4 spine Sacrum Sacrum
Onset (months)
Other complications
11 7 19 12 16
Radiation proctitis
19 16 12
Radiation proctitis
Note. EBRT, external beam radiation therapy; BT, brachytherapy.
in six fractions was conducted twice each week in all 7 patients in tandem and with colpostats. Among the 235 patients with postoperative radiation therapy following radical hysterectomy, 1 (1/235, 0.4%) developed pelvic IF 19 months following treatment. She received pelvic irradiation with 10-MV photons, a total dose of 50.4 Gy in 1.8-Gy fractions. Table 1 provides a clinical description of these patients. All of the patients were postmenopausal women at the time of the diagnosis, and the ages ranged from 59 to 79 years. The initial stages were IB in one patient, IIA in two, IIB in two, and IIIB in three. The histological diagnoses were squamous cell carcinoma in six, adenocarcinoma in one, and adenosquamous cell cancer in one. Patient 4 received neoadjuvant chemotherapy. None of the patients had any history of treatment with corticosteroids.
RESULTS Pelvic fractures were diagnosed when patients were diseasefree. Pain in the pelvic area was the initial symptom in all the patients with no history of trauma. The symptoms resolved after 1–11 months with rest and anti-inflammatory medication in all the patients. Bone scans showed pathological increased uptake in all patients, and subsequent radiographic studies were performed. Upon initial examination, all bone scans revealed increased uptake in the sacrum and/or sacroiliac joint. Among the eight patients, high uptake in the sacrum was symmetric, and the typical H-sign was observed in three (Fig. 1). In two patients, IF occurred in the lower lumbar spine or in the pubis, in addition to the sacrum. Correlating CT scans demonstrated small fractures and bony destruction (Fig. 2). No patient was biopsied in our series to confirm the etiology of pathological uptake observed on bone scan due to a high risk of osteonecrosis. Two patients also had chronic radiation proctitis.
DISCUSSION IF can occur as a result of normal physiological stress on bones with deficient elastic resistance. These fractures occur in areas of stress, such as the mandible, the neck of the femur, the pelvic bones, and the knee joint. They are painful, especially with motion, but may be asymptomatic and may not be diagnosed unless specific studies are performed [1– 4, 9]. Furthermore, insufficiency fractures can be misdiagnosed as bony metastasis. Radiation osteonecrosis can affect any irradiated bone probably due to injury of the microvasculature of a mature bone. This injury results in microcirculation occlusion and, consequently, injury to the periostic vasculature. Osteoblastic function is also compromised, and, ultimately, the patient suffers an increased risk of spontaneous fracture or IF [6]. In addition to radiation, other factors may modify bone physiology and cause IF. IF have mostly been reported in postmenopausal women who are at risk for estrogen-deficiency dependent osteoporosis [10, 11]. In this series, all patients were postmenopausal. The advent of megavoltage radiation with a reduced absorbed dose in the bone has been expected to eliminate radiation osteonecrosis. However, bone complication still remains an important late sequela. Several recent papers report the incidence of symptomatic pelvic fractures to be 3– 6% [1–5]. The estimated incidence in this series is 1.7% of all symptomatic patients treated for carcinoma of the cervix. According to Erickson et al. [4], radiation-induced pelvic bone complications are a much more common sequelae of pelvic irradiation than previously believed. In their study, Erickson et al. reported an incidence of 5.9% and concluded that the radiationinduced pelvic bone complications, including IF, are an underestimated sequela of pelvic irradiation. IF involving the pelvis is often overlooked, and increasingly it is being recognized as a major cause of low-back, buttock, and groin pain in elderly women. Abe et al. [8] report an incidence of 34% when fractures are actively sought in asymptomatic patients. The
266
HUH ET AL.
FIG. 1.
Bone scan showing the H-shaped sacral fracture and hot uptake on left pubic ramus.
authors concluded that IF appear more commonly in symptomatic patients than asymptomatic patients, and clinical manifestations usually occurred approximately 1 year after completion of radiotherapy. The time to develop an IF from radiotherapy is between 1 and 190 months [1–5]. In our study, onset of symptoms ranged from 7 to 19 months after completion of radiotherapy. Pelvic pain was the initial symptom and spontaneously resolved after several months, a progression similar to published reports. The current knowledge on the tolerance of pelvic bones to irradiation is insufficient. The tolerance dose of radiation depends on age, the size of the radiation field, the size of each fraction, and the total dose administered. The tolerance dose for elderly pelvic bones is less than that of young adult. Chemotherapeutic agents, adriamycin, vincristine, and cis-platinum alone may induce osteonecrosis, and used in combination with irradiation, the risk is even greater [2]. The National Cancer Institute (United States) issued a clinical alert in 1999 with regard to positive advantages found with cisplatin-based concurrent chemoirradiation in five randomized prospective trials for cervical cancer [12]. However, increased use of combined radiation and chemotherapy may predispose to IF in cervical cancer [2]. The TD 5/5 (tolerance dose of the probability of 5% complication within 5 years) and the TD 50/5 (the probability of 50% complication within 5 years) for the fem-
oral head have been estimated to be 52 and 65 Gy, respectively [13]. However, the tolerance dose for the pelvic bones, the TD 5/5 and TD 50/5 complication rate of radio-osteonecrosis and IF, has not been reported. In this series, IF were more common in the group treated with both external beam and brachytherapy (7 of 228, 3.1%) than in the external beam alone group (1 of 235, 0.4%). IF in the pelvis are often missed or overlooked in the elderly, who have nonspecific pelvic pain or lower back pain. In other patients, IF are often misdiagnosed as metastatic disease. Hence, clinical suspicion is necessary for accurate diagnosis. Diagnostic criteria of IF include the radiological presence of fracture lines, with or without sclerotic reaction, and the absence of osteolysis or progression of metastases. It is essential to rule out metastatic disease in order to prevent inappropriate treatment. Bone scan, CT scan, and MRI can all sufficiently reveal radiological findings of IF. Bone scan shows increased radionuclide uptake in one or more foci on the sacroiliac joint or the sacrum in most cases of IF. Foci were sometimes distributed bilaterally and symmetrically in both sacroiliac joints, with a characteristic H or butterfly appearance [11, 14]. Less commonly, increased radionuclide uptake was observed in the pubic bone. CT scan using a bone window setting is also an appropriate method of establishing the differential diagnosis for bone metastasis. IF have not been associated with osteolytic
PELVIC INSUFFICIENCY FRACTURE AFTER PELVIC IRRADIATION
267
FIG. 2. (A) Plain pelvic radiograph 16 months postradiotherapy shows fracture, sclerosis, and fragmentation of the left pubic bone. (B) CT scan of the pelvis showing fracture line and surrounding callus formation on left superior pubic ramus.
lesions or soft tissue growth, which are common in metastatic disease [15]. Pubic fracture near the symphysis may be accompanied by soft tissue growth, sometimes showing a pseudoma-
lignant appearance [5]. Sacral sclerosis or a fracture line may be observed on the sacrum or the pubic bone. In general, pubic fractures are combined with preexisting sacral fractures [15].
268
HUH ET AL.
MRI is also a useful method for evaluating bone marrow changes after irradiation. Bone biopsy as a diagnostic tool is not recommended due to the high risk of osteonecrosis and low diagnostic yield [10, 11, 16]. Histologic findings of those identified were hemorrhage, fibrosis, necrotic bone fragments, and trabecular bone and cartilage growth. Consequently, IF may be misdiagnosed with inadequate material, osteomyelitis, and tumors such as enchondroma, osteosarcoma, or chondrosarcoma [5]. The significance of IF is that they can be misdiagnosed as bone metastases, and consequently, inappropriate treatment may be given to the patients. For prevention of these misdiagnoses, clinical suspicion is vital, and patients with pelvic irradiation due to pelvic cancer must be carefully assessed when pain arises. In preparation for pelvic irradiation, particularly in elderly patients, the pelvic bones are one of the dose-limiting organs, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the initiation of the radiation treatment. It is important to reduce the volume of the pelvic bony structure that is included in the radiation portal in order to reduce chronic morbidity by using the multifield treatment plan and 3-dimensional conformal radiotherapy technique. REFERENCES 1. Bliss P, Parsons CA, Blake PR. Incidence and possible etiological factors in the development of pelvic insufficiency fractures following radical radiotherapy. Br J Radiol 1996;69:548 –54. 2. Jenkins PJ, Sebag Montefiore DJ, Arnott SJ. Hip complications following chemoradiotherapy. Clin Oncol 1995;7:123–26. 3. Peh WC, Khong PL, Sham JS, Ho WY, Yeung HW. Sacral and pubic insufficiency fractures after irradiation of gynaecological malignancies. Clin Oncol 1995;7:117–22.
4. Erickson BA, Murray KJ, Erickson SJ, Carrera GF. Radiation-induced pelvic bone complications: an underestimated sequelae of pelvic irradiation. Int J Radiat Oncol Biol Phys 2000;48(S):126. 5. Moreno A, Clemente J, Crespo C, Martinez A, Navarro M, Fernandez L, Minguell J, Vazquez G, Andreu FJ. Pelvic insufficiency fractures in patients with pelvic irradiation. Int J Radiat Oncol Biol Phys 1999;44: 61– 6. 6. Fajaro LF, Berthrong M, Anderson RE, Musculoskeletal system. In: Fajaro LF, Berthrong M, Anderson RE, editors. Radiation pathology. 1st ed. Oxford: Oxford Univ. Press, 2001:371–73. 7. Konski A, Sowers M. Pelvic fractures following irradiation for endometrial carcinoma. Int J Radiat Oncol Biol Phys 1996;35:361–7. 8. Abe H, Nakamura M, Takahashi S, Maruoka S, Ogawa Y, Sakamoto K. Radiation-induced insufficiency fractures of the pelvis: evaluation with 99mTc-methylene diphosphonate scintigraphy. Am J Roentgenol 1992; 158:599 – 602. 9. Blomlie V, Rofstad EK, Talle K, Sundfor K, Winderen M, Lien HH. Incidence of radiation-induced insufficiency fractures of the female pelvis: evaluation with MR imaging. Am J Roentgenol 1996;167:1205–10. 10. Casey D, Mirra J, Staple TW. Parasymphyseal insufficiency fractures of the os pubis. Am J Roentgenol 1984;142:581– 6. 11. De Smet AA, Neft JR. Pubic and sacral insufficiency fractures after irradiation: clinical course and radiologic findings. Am J Roentgenol 1985;145:601– 6. 12. NCI Clinical Announcement: Concurrent Chemoirradiation for Cervical Cancer. February 1999. 13. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109 –22. 14. Schneider R, Yaconove J, Ghelman B. Unsuspected sacral insufficiency fractures: detection by radionuclide bone scanning. Am J Roentgenol 1985;144:337– 41. 15. Cooper KL, Beabout JW, Swee RG. Insufficiency fractures of the sacrum. Radiology 1985;156:15–20. 16. Hall FM, Goldberg RP, Kadson EJ, Glick H. Post-traumatic osteolysis of pubic bone simulating a malignant lesion. J Bone Joint Surg Am 1984; 66:121– 6.
Pelvic Insufficiency Fracture after Pelvic Irradiation in Uterine Cervix Cancer Seung Jae Huh, M.D., 1 BoKyoung Kim, M.D., Min Kyu Kang, M.D., Jeong Eun Lee, M.D., Do Hoon Lim, M.D., Won Park, M.D., Seong Soo Shin, M.D., and Young Chan Ahn, M.D. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Gu, Seoul 135-710, Korea Received October 25, 2001
Objectives. Pelvic insufficiency fractures (IF) are well known but uncommon and are frequently misinterpreted sequelae. The clinical features were investigated. Methods. Four hundred sixty-three patients, who were treated between 1994 and 2000 for uterine cervix cancer, were clinically examined. All patients had been treated with 10 or 15 MV photons, with 50.4 –55.8 Gy in 28 fractions with adjuvant intent (n ⴝ 235) in addition to high-dose-rate brachytherapy 24 Gy in 6 fractions for curative treatment (n ⴝ 228). The median follow-up was 38 months. Results. Eight patients (8/463, 1.7%) developed pelvic IF 7–19 months (median, 12 months) after the treatment. Among these, seven patients (7/228, 3.1%) were treated with curative intent and one (1/235, 0.4%) was treated with adjuvant intent. All patients were postmenopausal and complained of moderate to severe pelvic pain, which resolved after 1–11 months with conservative therapy in all patients. Two of these patients also had radiation proctitis. Conclusion. In women who present with pelvic pain after radiotherapy for cervical cancer, bony destruction and fractures may be indicative of a late radiation effect rather than osseous metastasis. IF are more common in the curative treatment group than in the postoperative adjuvant group. © 2002 Elsevier Science (USA) Key Words: pelvic insufficiency fracture; pelvic irradiation; uterine cervix cancer.
INTRODUCTION Osseous complications are considered rare after pelvic irradiation in the megavoltage era. The advent of megavoltage equipment has helped reduce the incidence; however, it remains an important late complication [1–5]. Insufficiency fractures (IF) have been described in several situations with no history of prior trauma: (i) the postmenopausal state, (ii) subsequent to treatment with high-dose corticosteroids, and (iii) radiation exposure. IF differ from fatigue fractures, which are caused by the application of abnormal muscular stress to a bone that has normal elastic resistance [6]. Although the inci1
To whom correspondence and reprint requests should be addressed. Fax: ⫹82-2-3410-2619. E-mail: [email protected]. 0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.
264
dence of pelvic IF in patients being treated for cervical cancer and endometrial carcinoma with radiation is unknown, several recent studies now report an incidence of symptomatic pelvic fractures of 3– 6% [1– 4, 7]. Radiotherapy is usually used as a sole treatment modality or as a combined treatment with surgery or chemotherapy. Contrary to what was previously believed, radiation-induced pelvic bone complications are a much more common sequelae. When actively sought in asymptomatic patients, an incidence of 34% has been reported [8]. After pelvic irradiation in cervix cancer, patients with IF complain of pelvic pain associated with radiological findings such as hot uptakes on bone scan or pelvic bone fractures by plain radiography or CT scan. The importance of understanding pelvic IF lies in the potential for misdiagnosis as bony metastasis. In this investigation, we present eight cases of IF occurring in patients being treated with radiotherapy for carcinoma of the cervix and further discuss the possible risk factors. MATERIALS AND METHODS From September 1994 to December 2000, 463 patients were given pelvic radiotherapy for uterine cervix cancer at the Samsung Medical Center, Seoul, Korea. Among these, 228 patients with intact uteri were treated with curative intent, while 235 patients were treated with postoperative adjuvant radiotherapy. The median follow-up was 38 months. Eight patients with no history of trauma or bone pathology among the total 463 patients (8/463, 1.7%) developed pelvic IF 7–19 months (median, 12 months) following treatment. Among these 8 patients, 7 (7/228, 3.1%) had been treated with curative intent. In these patients, the entire pelvis was treated with external irradiation, using 10- or 15-MV photons from a linear accelerator, with a four-field pelvic box in 4 patients and with a parallel opposing AP/PA field technique in 3. The external radiation dose ranged from 50.4 to 55.8 Gy in 1.8-Gy fractions for 5 days each week. Intracavitary brachytherapy with a high-dose-rate brachytherapy (microSelectron-HDR) of 24 Gy
265
PELVIC INSUFFICIENCY FRACTURE AFTER PELVIC IRRADIATION
TABLE 1 Clinical Characteristics of Patients with Pelvic IF Patient No.
Age (years)
Stage
Surgery
ChemoTx
EBRT dose (Gy)
BT
Site
1 2 3 4 5
74 55 60 66 79
IB IIB IIA IIB IIB
⫺ ⫺ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺
50.4 50.4 50.4 55.8 55.8
⫹ ⫹ ⫹ ⫹ ⫹
6
59
IIA
⫹
⫺
50.4
⫺
7 8
67 60
II B IIIB
⫺ ⫺
⫺ ⫺
55.8 55.8
⫹ ⫹
Sacrum Sacrum Sacrum Sacrum Sacrum Pubis Sacrum, L4 spine Sacrum Sacrum
Onset (months)
Other complications
11 7 19 12 16
Radiation proctitis
19 16 12
Radiation proctitis
Note. EBRT, external beam radiation therapy; BT, brachytherapy.
in six fractions was conducted twice each week in all 7 patients in tandem and with colpostats. Among the 235 patients with postoperative radiation therapy following radical hysterectomy, 1 (1/235, 0.4%) developed pelvic IF 19 months following treatment. She received pelvic irradiation with 10-MV photons, a total dose of 50.4 Gy in 1.8-Gy fractions. Table 1 provides a clinical description of these patients. All of the patients were postmenopausal women at the time of the diagnosis, and the ages ranged from 59 to 79 years. The initial stages were IB in one patient, IIA in two, IIB in two, and IIIB in three. The histological diagnoses were squamous cell carcinoma in six, adenocarcinoma in one, and adenosquamous cell cancer in one. Patient 4 received neoadjuvant chemotherapy. None of the patients had any history of treatment with corticosteroids.
RESULTS Pelvic fractures were diagnosed when patients were diseasefree. Pain in the pelvic area was the initial symptom in all the patients with no history of trauma. The symptoms resolved after 1–11 months with rest and anti-inflammatory medication in all the patients. Bone scans showed pathological increased uptake in all patients, and subsequent radiographic studies were performed. Upon initial examination, all bone scans revealed increased uptake in the sacrum and/or sacroiliac joint. Among the eight patients, high uptake in the sacrum was symmetric, and the typical H-sign was observed in three (Fig. 1). In two patients, IF occurred in the lower lumbar spine or in the pubis, in addition to the sacrum. Correlating CT scans demonstrated small fractures and bony destruction (Fig. 2). No patient was biopsied in our series to confirm the etiology of pathological uptake observed on bone scan due to a high risk of osteonecrosis. Two patients also had chronic radiation proctitis.
DISCUSSION IF can occur as a result of normal physiological stress on bones with deficient elastic resistance. These fractures occur in areas of stress, such as the mandible, the neck of the femur, the pelvic bones, and the knee joint. They are painful, especially with motion, but may be asymptomatic and may not be diagnosed unless specific studies are performed [1– 4, 9]. Furthermore, insufficiency fractures can be misdiagnosed as bony metastasis. Radiation osteonecrosis can affect any irradiated bone probably due to injury of the microvasculature of a mature bone. This injury results in microcirculation occlusion and, consequently, injury to the periostic vasculature. Osteoblastic function is also compromised, and, ultimately, the patient suffers an increased risk of spontaneous fracture or IF [6]. In addition to radiation, other factors may modify bone physiology and cause IF. IF have mostly been reported in postmenopausal women who are at risk for estrogen-deficiency dependent osteoporosis [10, 11]. In this series, all patients were postmenopausal. The advent of megavoltage radiation with a reduced absorbed dose in the bone has been expected to eliminate radiation osteonecrosis. However, bone complication still remains an important late sequela. Several recent papers report the incidence of symptomatic pelvic fractures to be 3– 6% [1–5]. The estimated incidence in this series is 1.7% of all symptomatic patients treated for carcinoma of the cervix. According to Erickson et al. [4], radiation-induced pelvic bone complications are a much more common sequelae of pelvic irradiation than previously believed. In their study, Erickson et al. reported an incidence of 5.9% and concluded that the radiationinduced pelvic bone complications, including IF, are an underestimated sequela of pelvic irradiation. IF involving the pelvis is often overlooked, and increasingly it is being recognized as a major cause of low-back, buttock, and groin pain in elderly women. Abe et al. [8] report an incidence of 34% when fractures are actively sought in asymptomatic patients. The
266
HUH ET AL.
FIG. 1.
Bone scan showing the H-shaped sacral fracture and hot uptake on left pubic ramus.
authors concluded that IF appear more commonly in symptomatic patients than asymptomatic patients, and clinical manifestations usually occurred approximately 1 year after completion of radiotherapy. The time to develop an IF from radiotherapy is between 1 and 190 months [1–5]. In our study, onset of symptoms ranged from 7 to 19 months after completion of radiotherapy. Pelvic pain was the initial symptom and spontaneously resolved after several months, a progression similar to published reports. The current knowledge on the tolerance of pelvic bones to irradiation is insufficient. The tolerance dose of radiation depends on age, the size of the radiation field, the size of each fraction, and the total dose administered. The tolerance dose for elderly pelvic bones is less than that of young adult. Chemotherapeutic agents, adriamycin, vincristine, and cis-platinum alone may induce osteonecrosis, and used in combination with irradiation, the risk is even greater [2]. The National Cancer Institute (United States) issued a clinical alert in 1999 with regard to positive advantages found with cisplatin-based concurrent chemoirradiation in five randomized prospective trials for cervical cancer [12]. However, increased use of combined radiation and chemotherapy may predispose to IF in cervical cancer [2]. The TD 5/5 (tolerance dose of the probability of 5% complication within 5 years) and the TD 50/5 (the probability of 50% complication within 5 years) for the fem-
oral head have been estimated to be 52 and 65 Gy, respectively [13]. However, the tolerance dose for the pelvic bones, the TD 5/5 and TD 50/5 complication rate of radio-osteonecrosis and IF, has not been reported. In this series, IF were more common in the group treated with both external beam and brachytherapy (7 of 228, 3.1%) than in the external beam alone group (1 of 235, 0.4%). IF in the pelvis are often missed or overlooked in the elderly, who have nonspecific pelvic pain or lower back pain. In other patients, IF are often misdiagnosed as metastatic disease. Hence, clinical suspicion is necessary for accurate diagnosis. Diagnostic criteria of IF include the radiological presence of fracture lines, with or without sclerotic reaction, and the absence of osteolysis or progression of metastases. It is essential to rule out metastatic disease in order to prevent inappropriate treatment. Bone scan, CT scan, and MRI can all sufficiently reveal radiological findings of IF. Bone scan shows increased radionuclide uptake in one or more foci on the sacroiliac joint or the sacrum in most cases of IF. Foci were sometimes distributed bilaterally and symmetrically in both sacroiliac joints, with a characteristic H or butterfly appearance [11, 14]. Less commonly, increased radionuclide uptake was observed in the pubic bone. CT scan using a bone window setting is also an appropriate method of establishing the differential diagnosis for bone metastasis. IF have not been associated with osteolytic
PELVIC INSUFFICIENCY FRACTURE AFTER PELVIC IRRADIATION
267
FIG. 2. (A) Plain pelvic radiograph 16 months postradiotherapy shows fracture, sclerosis, and fragmentation of the left pubic bone. (B) CT scan of the pelvis showing fracture line and surrounding callus formation on left superior pubic ramus.
lesions or soft tissue growth, which are common in metastatic disease [15]. Pubic fracture near the symphysis may be accompanied by soft tissue growth, sometimes showing a pseudoma-
lignant appearance [5]. Sacral sclerosis or a fracture line may be observed on the sacrum or the pubic bone. In general, pubic fractures are combined with preexisting sacral fractures [15].
268
HUH ET AL.
MRI is also a useful method for evaluating bone marrow changes after irradiation. Bone biopsy as a diagnostic tool is not recommended due to the high risk of osteonecrosis and low diagnostic yield [10, 11, 16]. Histologic findings of those identified were hemorrhage, fibrosis, necrotic bone fragments, and trabecular bone and cartilage growth. Consequently, IF may be misdiagnosed with inadequate material, osteomyelitis, and tumors such as enchondroma, osteosarcoma, or chondrosarcoma [5]. The significance of IF is that they can be misdiagnosed as bone metastases, and consequently, inappropriate treatment may be given to the patients. For prevention of these misdiagnoses, clinical suspicion is vital, and patients with pelvic irradiation due to pelvic cancer must be carefully assessed when pain arises. In preparation for pelvic irradiation, particularly in elderly patients, the pelvic bones are one of the dose-limiting organs, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the initiation of the radiation treatment. It is important to reduce the volume of the pelvic bony structure that is included in the radiation portal in order to reduce chronic morbidity by using the multifield treatment plan and 3-dimensional conformal radiotherapy technique. REFERENCES 1. Bliss P, Parsons CA, Blake PR. Incidence and possible etiological factors in the development of pelvic insufficiency fractures following radical radiotherapy. Br J Radiol 1996;69:548 –54. 2. Jenkins PJ, Sebag Montefiore DJ, Arnott SJ. Hip complications following chemoradiotherapy. Clin Oncol 1995;7:123–26. 3. Peh WC, Khong PL, Sham JS, Ho WY, Yeung HW. Sacral and pubic insufficiency fractures after irradiation of gynaecological malignancies. Clin Oncol 1995;7:117–22.
4. Erickson BA, Murray KJ, Erickson SJ, Carrera GF. Radiation-induced pelvic bone complications: an underestimated sequelae of pelvic irradiation. Int J Radiat Oncol Biol Phys 2000;48(S):126. 5. Moreno A, Clemente J, Crespo C, Martinez A, Navarro M, Fernandez L, Minguell J, Vazquez G, Andreu FJ. Pelvic insufficiency fractures in patients with pelvic irradiation. Int J Radiat Oncol Biol Phys 1999;44: 61– 6. 6. Fajaro LF, Berthrong M, Anderson RE, Musculoskeletal system. In: Fajaro LF, Berthrong M, Anderson RE, editors. Radiation pathology. 1st ed. Oxford: Oxford Univ. Press, 2001:371–73. 7. Konski A, Sowers M. Pelvic fractures following irradiation for endometrial carcinoma. Int J Radiat Oncol Biol Phys 1996;35:361–7. 8. Abe H, Nakamura M, Takahashi S, Maruoka S, Ogawa Y, Sakamoto K. Radiation-induced insufficiency fractures of the pelvis: evaluation with 99mTc-methylene diphosphonate scintigraphy. Am J Roentgenol 1992; 158:599 – 602. 9. Blomlie V, Rofstad EK, Talle K, Sundfor K, Winderen M, Lien HH. Incidence of radiation-induced insufficiency fractures of the female pelvis: evaluation with MR imaging. Am J Roentgenol 1996;167:1205–10. 10. Casey D, Mirra J, Staple TW. Parasymphyseal insufficiency fractures of the os pubis. Am J Roentgenol 1984;142:581– 6. 11. De Smet AA, Neft JR. Pubic and sacral insufficiency fractures after irradiation: clinical course and radiologic findings. Am J Roentgenol 1985;145:601– 6. 12. NCI Clinical Announcement: Concurrent Chemoirradiation for Cervical Cancer. February 1999. 13. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109 –22. 14. Schneider R, Yaconove J, Ghelman B. Unsuspected sacral insufficiency fractures: detection by radionuclide bone scanning. Am J Roentgenol 1985;144:337– 41. 15. Cooper KL, Beabout JW, Swee RG. Insufficiency fractures of the sacrum. Radiology 1985;156:15–20. 16. Hall FM, Goldberg RP, Kadson EJ, Glick H. Post-traumatic osteolysis of pubic bone simulating a malignant lesion. J Bone Joint Surg Am 1984; 66:121– 6.