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Title: Insufficiency 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)

Abstract

Purpose: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study. Materials and Methods: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images. Results: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria formore » Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test). Conclusions: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [5];  [10];  [11];  [12];  [13];  [14];  [15];  [16];  [17];
  1. Department of Heavy Particle Therapy and Radiation Oncology, Saga University, Saga (Japan)
  2. Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Okinawa (Japan)
  3. Radiation Oncology Department, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo (Japan)
  4. Gunma University Heavy Ion Medical Center, Maebashi (Japan)
  5. Department of Radiation Oncology, Saitama Medical University, International Medical Center, Saitama (Japan)
  6. Department of Radiology, School of Medicine, Kitasato University, Sagamihara (Japan)
  7. Department of Radiology, Saitama Cancer Center, Saitama (Japan)
  8. Department of Radiation Oncology, Aichi Cancer Center, Nagoya (Japan)
  9. Department of Radiology, National Shikoku Cancer Center, Matsuyama (Japan)
  10. Department of Radiation Oncology, Graduate School of Medical Science, Hiroshima University, Hiroshima (Japan)
  11. Department of Radiation Oncology, Shiga Medical Center for Adults, Moriyama (Japan)
  12. Department of Radiation Oncology, Osaka Medical Center for Cancer, Osaka (Japan)
  13. Proton Medical Research Center and Tsukuba University, Tuskuba (Japan)
  14. Department of Medical Physics and Engineering, Graduate School of Medicine, Osaka University, Suita (Japan)
  15. Department of Radiology, Showa University School of Medicine, Tokyo (Japan)
  16. Department of Radiation Oncology, Gunma University, Graduate School of Medicine, Maebashi (Japan)
  17. Department of Radiation Oncology and Image-applied Therapy, Kyoto University, Graduate School of Medicine, Kyoto (Japan)
Publication Date:
OSTI Identifier:
22149521
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 84; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANALGESICS; BRACHYTHERAPY; CHEMOTHERAPY; DIAGNOSIS; DOSE RATES; FRACTURES; GYNECOLOGY; HEALTH HAZARDS; IMAGES; NARCOTICS; NEOPLASMS; NMR IMAGING; PAIN; PATIENTS; SKELETON

Citation Formats

Tokumaru, Sunao, E-mail: tokumaru@cc.saga-u.ac.jp, Toita, Takafumi, Oguchi, Masahiko, Ohno, Tatsuya, Kato, Shingo, Niibe, Yuzuru, Kazumoto, Tomoko, Kodaira, Takeshi, Kataoka, Masaaki, Shikama, Naoto, Kenjo, Masahiro, Yamauchi, Chikako, Suzuki, Osamu, Sakurai, Hideyuki, Teshima, Teruki, Kagami, Yoshikazu, Nakano, Takashi, Hiraoka, Masahiro, and and others. Insufficiency 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). United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2012.03.042.
Tokumaru, Sunao, E-mail: tokumaru@cc.saga-u.ac.jp, Toita, Takafumi, Oguchi, Masahiko, Ohno, Tatsuya, Kato, Shingo, Niibe, Yuzuru, Kazumoto, Tomoko, Kodaira, Takeshi, Kataoka, Masaaki, Shikama, Naoto, Kenjo, Masahiro, Yamauchi, Chikako, Suzuki, Osamu, Sakurai, Hideyuki, Teshima, Teruki, Kagami, Yoshikazu, Nakano, Takashi, Hiraoka, Masahiro, & and others. Insufficiency 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). United States. doi:10.1016/J.IJROBP.2012.03.042.
Tokumaru, Sunao, E-mail: tokumaru@cc.saga-u.ac.jp, Toita, Takafumi, Oguchi, Masahiko, Ohno, Tatsuya, Kato, Shingo, Niibe, Yuzuru, Kazumoto, Tomoko, Kodaira, Takeshi, Kataoka, Masaaki, Shikama, Naoto, Kenjo, Masahiro, Yamauchi, Chikako, Suzuki, Osamu, Sakurai, Hideyuki, Teshima, Teruki, Kagami, Yoshikazu, Nakano, Takashi, Hiraoka, Masahiro, and and others. 2012. "Insufficiency 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)". United States. doi:10.1016/J.IJROBP.2012.03.042.
@article{osti_22149521,
title = {Insufficiency 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)},
author = {Tokumaru, Sunao, E-mail: tokumaru@cc.saga-u.ac.jp and Toita, Takafumi and Oguchi, Masahiko and Ohno, Tatsuya and Kato, Shingo and Niibe, Yuzuru and Kazumoto, Tomoko and Kodaira, Takeshi and Kataoka, Masaaki and Shikama, Naoto and Kenjo, Masahiro and Yamauchi, Chikako and Suzuki, Osamu and Sakurai, Hideyuki and Teshima, Teruki and Kagami, Yoshikazu and Nakano, Takashi and Hiraoka, Masahiro and and others},
abstractNote = {Purpose: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study. Materials and Methods: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images. Results: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test). Conclusions: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy.},
doi = {10.1016/J.IJROBP.2012.03.042},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 84,
place = {United States},
year = 2012,
month =
}
  • Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). Methods and Materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. Results: Between July 2004 and November 2008, 169 patients from 15 institutionsmore » were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. Conclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.« less
  • Purpose: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study. Patients and Methods: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanesemore » hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7-2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25-60 Gy). Results: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% (p = 0.018). Three-year overall survival rates of the total dose {>=}51 Gy and that of {<=}50 Gy were 58.0% and 42.8%, respectively (p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity. Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.« less
  • Purpose: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). Methods and Materials: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition. Follow-up magnetic resonance imaging was performed routinely at 3 and 12 months after the end of treatment or basedmore » on clinical indication. PIF was defined as a fracture line with or without sclerotic changes in the pelvic bones. D{sub 50%} and V{sub 55Gy} were calculated for the os sacrum and jointly for the os ileum and pubis. Patient- and treatment-related factors including dose were analyzed for correlation with PIF. Results: The median follow-up period was 25 months. The median age was 50 years. In 20 patients (20%), a median of 2 PIFs (range, 1-3 PIFs) were diagnosed; half were asymptomatic. The majority of the fractures were located in the sacrum (77%). Age was a significant risk factor (P<.001), and the incidence of PIF was 4% and 37% in patients aged ≤50 years and patients aged >50 years, respectively. Sacrum D{sub 50%} was a significant risk factor in patients aged >50 years (P=.04), whereas V{sub 55Gy} of the sacrum and V{sub 55Gy} of the pelvic bones were insignificant (P=.33 and P=.18, respectively). A dose-effect curve for sacrum D{sub 50%} in patients aged >50 years showed that reduction of sacrum D{sub 50%} from 40 Gy{sub EQD2} to 35 Gy{sub EQD2} reduces PIF risk from 45% to 22%. Conclusions: PIF is common after treatment of LACC and is mainly seen in patients aged >50 years. Our data indicate that PIFs are not related to lymph node boosts but rather to dose and volume associated with irradiation of the elective pelvic target. Reducing the prescribed elective dose from 50 to 45 Gy may reduce the risk of PIF considerably.« less
  • In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. Inmore » both groups the external pelvis irradiation was followed by intracavity brachytherapy in the uterus and vagina. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reations, and survival. (JMT)« less
  • In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. Inmore » both groups the external pelvis irradiation was followed by intracavity brachytherapy in the uterus and vagina. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reations, and survival. (JMT)« less