日本整形外科学会骨・軟部腫瘍委員会編：整形外科・病理悪性骨腫瘍取扱い規約、第3版、金原出版、2000.
Krishnan Unni, et al.:Dahlin’s Bone tumors. 6th ed, Lippincott Williams & Wilkins, 2009.
日本整形外科学会診療ガイドライン委員会、軟部腫瘍診療ガイドライン策定委員会編：軟部腫瘍診療ガイドライン2020（改訂第3版）、南江堂、2020.
岩本幸英: 整形外科のための外来で見逃さない骨・軟部腫瘍ABC. メジカルビュー社, 2005.
神中整形外科学 第22版. 杉岡洋一監修 , 岩本幸英編, 南山堂, 2004.
日本整形外科学会診療ガイドライン委員会、原発性悪性骨腫瘍診療ガイドライン策定委員会編：原発性悪性骨腫瘍診療ガイドライン2022、南江堂、2022.
Yukihide Iwamoto, Kazuhiro Tanaka, Kazuo Isu, Akira Kawai, Shin-ichiro Tatezaki, Takeshi Ishii, Kazuyoshi Kushida, Yasuo Beppu, Masamichi Usui, Akio Tateishi, Kiyoo Furuse, Takeshi Minamizaki, Noriyoshi Kawaguchi, Shinya Yamawaki
Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J.
J Orthop Sci. 2009 Jul;14(4):397-404. doi: 10.1007/s00776-009-1347-6. Epub 2009 Aug 7.
Abstract/Text
BACKGROUND: Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out.
METHODS: To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible.
RESULTS: The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy.
CONCLUSIONS: We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.
Holcombe E Grier, Mark D Krailo, Nancy J Tarbell, Michael P Link, Christopher J H Fryer, Douglas J Pritchard, Mark C Gebhardt, Paul S Dickman, Elizabeth J Perlman, Paul A Meyers, Sarah S Donaldson, Sheila Moore, Aaron R Rausen, Teresa J Vietti, James S Miser
Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone.
N Engl J Med. 2003 Feb 20;348(8):694-701. doi: 10.1056/NEJMoa020890.
Abstract/Text
BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease.
METHODS: Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide.
RESULTS: A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01).
CONCLUSIONS: The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.
Copyright 2003 Massachusetts Medical Society
Richard B Womer, Daniel C West, Mark D Krailo, Paul S Dickman, Bruce R Pawel, Holcombe E Grier, Karen Marcus, Scott Sailer, John H Healey, John P Dormans, Aaron R Weiss
Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children's Oncology Group.
J Clin Oncol. 2012 Nov 20;30(33):4148-54. doi: 10.1200/JCO.2011.41.5703. Epub 2012 Oct 22.
Abstract/Text
PURPOSE: Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome.
PATIENTS AND METHODS: This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750×10(6)/L and a platelet count greater than 75×10(9)/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734).
RESULTS: Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P=.048). The toxicity of the regimens was similar.
CONCLUSION: For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
日本整形外科学会骨・軟部腫瘍委員会編：整形外科・病理悪性軟部腫瘍取扱い規約、第3版、金原出版、2002.
岩本幸英編: 骨・軟部腫瘍外科の要点と盲点. 文光堂, 2005.
日本整形外科学会骨・軟部腫瘍委員会編：整形外科・病理悪性骨腫瘍取扱い規約、第3版、金原出版、2002.
Nabeel Pervaiz, Nigel Colterjohn, Forough Farrokhyar, Richard Tozer, Alvaro Figueredo, Michelle Ghert
A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma.
Cancer. 2008 Aug 1;113(3):573-81. doi: 10.1002/cncr.23592.
Abstract/Text
BACKGROUND: The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival.
METHODS: A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model.
RESULTS: Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy.
CONCLUSIONS: This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.
(c) 2008 American Cancer Society
Kazuhiro Tanaka, Junki Mizusawa, Norifumi Naka, Akira Kawai, Hirohisa Katagiri, Toru Hiruma, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Munenori Watanuki, Yukihiro Yoshida, Takeshi Okamoto, Satoshi Abe, Kunihiro Asanuma, Ryohei Yokoyama, Hiroaki Hiraga, Tsukasa Yonemoto, Takeshi Morii, Keisuke Ae, Akihito Nagano, Hideki Yoshikawa, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto
Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304.
BMC Cancer. 2019 Sep 6;19(1):890. doi: 10.1186/s12885-019-6114-2. Epub 2019 Sep 6.
Abstract/Text
BACKGROUND: Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304.
METHODS: Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model.
RESULTS: A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size.
CONCLUSIONS: Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up.
TRIAL REGISTRATION: This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.
