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診療ガイドライン
8 章
Ewing 肉腫ファミリー腫瘍
Ewing 肉腫ファミリー腫瘍(Ewing’s sarcoma of family tumors:ESFT)は,
1) Mankin HJ, Mankin CJ, Simon MA. The hazard of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am 1996; 78: 656-63.(エビデンスレベルⅣa)
2) Ambros IM, Ambros PF, Strehl S, et al. MIC2 is a specific marker for Ewing’s sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ew-ing’s sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration. Cancer 1991; 67: 1886-93.(エビデンスレベルⅣa)
3) Navarro S, Cavazzana AO, Llomobart-Bosch A, et al. Comparison of Ewing’s sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructual analysis of two primitive neuroectodermal neoplasms. Arch Pathol Lab Med 1994; 118: 608-15.(エビデンスレベルⅣa)
4) Shanfelt RL, Edelman J, Willis JE, et al. Immunohistochemical analysis of neural markers in peripheral primitive neuroectodermal tumors(pPNET)without light microscopic evidence of neural differentiation. Appl Immunohistochem 1997; 5: 78-86.(エビデンスレベルⅣa)
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表 1 ESFT における染色体異常とキメラ遺伝子および出現頻度
染色体転座 キメラ遺伝子 EWS における割合(%)
t(11;12)(q24;q12) EWS-FLI1 85
t(21;22)(q22;q12) EWS-ERG 10
t(7;22)(q22;q12) EWS-ETV1 rare
t(17;22)(q12;q12) EWS-E1AF rare
t(2;22)(q33;q12) EWS-FEV rare
304
5) Dellatre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors. Nature 1992; 359: 162-5.(エビデンスレベルⅠ)
6) Delattre O, Zucman J, Melot T, et al. The Ewing family of tumors ─ a subgroup of small round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994; 331: 294-9.(エビデンスレベルⅠ)
European Intergroup Cooperative Ewing’s Sarcoma Study(EICESS),Medical Re-search Council(MRC)/United kingdom Children’s Cancer Study Group(UKCCSG),Cooperative Ewing’s Sarcoma Study (CESS) Group の治療研究1)では,登録された975 例の予後に関して後方視的に検討した。データベースはイギリスでは 1977 年,ドイツでは 1981 年から登録されている。予後因子としては,転移が強い予後因子となり
1) Cotterill SJ, Ahrens S, Paulussen HF, et al. Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group. J Clin Oncol 2000; 18: 3108-14.(エビデンスレベルⅣa)
2) Bacci G, Ferrari S, Bertoni F, et al. Prognostic factors in nonmetastatic Ewing’s sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedi-co Rizzoli. J Clin Oncol 2000; 18: 4-11.(エビデンスレベルⅣa)
3) Picci P, Rougraff BT, Bacci G, et al. Prognostic significance of histopathologic response toch-emotherapy in nonmetastatic Ewing’s sarcoma of the extremities. J Clin Oncol 1993; 11: 1763-9.(エビデンスレベルⅣa)
4) Picci P, Böhling T, Bacci G, et al. Chemotherapy-induced tumor necrosis as prognostic fac-tor in localized Ewing’s sarcoma of the extremities. J Clin Oncol 1997; 15: 1553-9.
5) Wunder JS, Paulian G, Huvos AG, et al. The histological response to chemotherapy as a pre-dictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone and joint Surg Am 1998; 80: 1020-33.(エビデンスレベルⅣa)
6) Bacci G, Balladelli A, Forni C, et al. Ewing’s sarcoma family tumours. Differences in clinico-pathological characteristics at presentation between localised and metastatics tumours. J Bone and joint Surg Br 2007; 89: 1229-33.(エビデンスレベルⅣa)
7) Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard che-motherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003; 348: 694-701.(エビデンスレベルⅡ)
1) Sutow WW, Sullivan MP. Cyclophosphamide therapy in children with Ewing’s sarcoma. Cancer Chemother Rep 1962; 23: 55-60.(エビデンスレベルⅣa)
2) Phillips RF, Higinbotham NL. The curability of treatment of Ewing’s sarcma with concur-rent radiotherapy and chemotherapy. J Pediatr 1967; 73: 249-251.(エビデンスレベルⅣa)
3) Sutow WW. Vincristine(NSC-67574)therapy for malignant solid tumors in children(ex-cept Wilm’s tumor). Cancer Chemother Rep 1968; 52: 485-7.(エビデンスレベルⅣa)
4) Oldham RK, Pomeroy TC. Treatment of Ewing’s sarcoma with adriamycin(NSC-123127).Cancer Chemother Rep 1972; 56: 635-9.(エビデンスレベルⅣa)
5) Van Dyk JJ, Falkson HC, Van der Merwe AM, et al. Unexpected toxicity in patients treated with iphosphamide. Cancer Res 1972; 32: 921-4.(エビデンスレベルⅣa)
6) Nesbit ME Jr, Gehan EA, Burgert EO Jr, et al. Multimodal therapy for the management of primary, nonmetastatic Ewing’s sarcma of bone: a long-term follow-up of the First Inter-group study. J Clin Oncol 1990; 8: 1664-74.(エビデンスレベルⅡ)
7) Burgert EO Jr, Nesbit ME, Garnsey LA, et al. Multimodal therapy for the management of nonpelvic, localized Ewing’s sarcoma of bone: Intergroup study IESS-II. J Clin Oncol 1990; 8: 1514-24.(エビデンスレベルⅡ)
8) Smith MA, Ungerleider RS, Horowitz ME,et al. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Natl Cancer Inst 1991; 83: 1460-70.(エビデンスレベルⅣa)
9) Rosen G, Wollner N, Tan C,et al. Procedings: Disease-free survival in children with Ewing’s sarcoma treated with radiation therapy and adjuvant four-drug sequential chemotherapy. Cancer 1974; 33: 384-93.(エビデンスレベルⅣa)
10) Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987; 5: 1191-8.(エビデンスレベルⅣa)
11) Kamalakar P, Freeman AI, Higby DJ, et al. Clinical response and toxicity with cis-dichloro-diammineplatinum(Ⅱ)in children.Cancer Treat Rep 1977; 61: 835-9.(エビデンスレベルⅣb)
12) Baum ES, Gaynon P, Greenberg L, et al. Phase Ⅱ trial cispltin in refractory childhood can-cer: Children Cancer Study Group Report. Cancer Treat Rep 1981; 65: 815-22.(エビデンスレベルⅣb)
13) Pratt CB, Hayes A, Green AA, et al. Pharmacokinetic evaluation of cisplatin in children with malignant solid tumors: a phase Ⅱ study. Cancer Treat Rep 1981; 65: 1021-6.(エビデンスレベルⅣb)
1) Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard che-motherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003; 348: 694-701.(エビデンスレベルⅡ)
2) Paulussen M, Ahrens S, Dunst J, et al. Localized Ewing tumor of bone: final results of the cooperative Ewing’s sarcoma study CESS 86. J Clin Oncol 2001; 19: 1818-29.(エビデンスレベルⅡ)
3) Craft A, Cotterill S, Malcolm A, et al. Ifosfamide-containig chemotherapy in Ewing’s sarco-ma: The second United Kingdom Children’s Cancer Study Group and the Medical Research Council Ewing’s Tumor Study. J Clin Oncol 1998; 16: 3628-33.(エビデンスレベルⅢ)
4) Paulussen M, Craft AW, Lewis I, et al. Results of the EICESS-92 Study: two randomized tri-als of Ewing’s sarcoma treatment--cyclophosphamide compared with ifosfamide in stan-dard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol 2008; 26: 4385-93.(エビデンスレベルⅡ)
PubMed で“Ewing sarcoma” AND “local therapy”を検索し重要と思われる文献を参考にした。また,NCI-PDQⓇ(http://www.cancer.gov/cancertopics/type/ewing/)を参考にした。
1) Paulussen M, Ahrens S, Dunst J, et al. Localized Ewing tumor of bone: final results of the cooperative Ewing’s Sarcoma Study CESS 86. J Clin Oncol 2001; 19: 1818-29.(エビデンスレベルⅣ)
2) Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard che-motherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of Bone. N Engl J Med 2003; 348: 694-701. (エビデンスレベルⅡ)
3) Schuck A, Ahrens S, Paulussen M, et al. Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys 2003; 55: 168-77. (エビデンスレベルⅣ)
PubMed で“Ewing sarcoma” AND “surgical therapy”を検索し重要と思われる文献を参考にした。また,NCI-PDQⓇ(http://www.cancer.gov/cancertopics/type/ewing/)を参考にした。
1) Paulussen M, Ahrens S, Dunst J, et al. Localized Ewing tumor of bone: final results of the cooperative Ewing’s Sarcoma Study CESS 86. J Clin Oncol 2001; 19: 1818-29.(エビデンスレベルⅣ)
2) Schuck A, Ahrens S, Paulussen M, et al. Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys 2003; 55: 168-77. (エビデンスレベルⅣ)
1) Ozaki T, Hillmann A, Hoffmann C, et al. Significanse of surgical margin on the prognosis of patients with Ewing’s sarcoma. A report from the Cooperative Ewing’s Sarcoma Study. Cancer 1996; 78: 892-900.(エビデンスレベルⅢ)
2) Bacci G, Longhi A, Briccoli A, et al. The role of surgical margins in treatment of Ewing’s sarcoma family tumors: experience of a single institution with 512 patients treated with ad-juvant and neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys 2006; 65: 766-72.(エビデンスレベルⅢ)
3) Schuck A, Ahrens S, Paulussen M, et al. Local therapy in localized Ewing tumors: result Of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys 2003; 55: 168-77.(エビデンスレベルⅢ)
4) Arai Y, Kun LE, Brooks MT, et al. Ewing’s sarcoma: local tumor control and patterns of fail-ure following limited-volume radiation therapy. Int J Radiat Oncol Biol Phys 1991; 21: 1501-8.(エビデンスレベルⅣa)
1) Schuck A, Hoffman J, Rübe C, et al. Radiotherapy in Ewing’s sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86, and EICESS 92 tumor. Int J Radiat Oncol Biol Phys 1998; 42: 1001-6.(エビデンスレベルⅣa)
2) Shamberger RC, LaQuaglia MP, Gebhardt MC, et al. Ewing sarcoma/primitive neuroecto-dermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy. Ann Surg 2003; 238: 563-8.(エビデンスレベルⅣa)
3) Shamberger RC, Laquaglia MP, Krailo MD, et al. Ewing sarcoma of the rib: results of an in-tergroup study with analysis of outcome by timing of resection. J Thorac Cardiovasc Surg 2000; 119: 1154-61.(エビデンスレベルⅣa)
1) Schuck A, Ahrens S, von Schorlemer I, et al. Radiotherapy in Ewing tumors of the verte-brae: treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials. Int J Radiat Oncol Biol Phys 2005; 63: 1562-7.(エビデンスレベルⅢ)
2) Bacci G, Boriani S, Balladelli A, et al. Treatment of nonmetastatic Ewing’s sarcoma family of tumors of the spine and sacrum: the experience from a single institution. Eur Spine J 2009; 18: 1091-5. (エビデンスレベルⅣa)
3) Indelicato DJ, Keole SR, Shahlaee AH, et al. Spinal and paraspinal Ewing tumors. Int J Radi-at Oncol Biol Phys 2010; 76: 1463-71. (エビデンスレベルⅣa)
1) Picci P, Böhling T, Bacci G, et al. Chemotherapy-induced tumor necrosis as a prognostic factoer in localized Ewing’ s sarcoma of the extremities. J Clin oncol 1997; 15: 1553-9.(エビデンスレベルⅣa)
2) Wunder JS, Paulian G, Huvos AG, et al. The histological response to chemotherapy as a pre-dictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone Joint Surg Am 1998; 80: 1020-33. (エビデンスレベルⅢ)
3) Bacci G, Ferrari S, Bertoni F, et al. Prognosic Factors in nonmetastatic Ewing’s sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Instiuto Ortopedi-co Rizzoli. J Clin Oncol 2000; 18: 4-11.(エビデンスレベルⅢ)
4) Sluga M, Windhager R, Lang S, et al. The role of surgery and resection margins in the treatment of Ewing’s Sarcoma. Clin Orthop Relat Res 2001; (392): 394-9.(エビデンスレベルⅣb)
1) Schleiermacher G, Peter M, Oberlin O, et al. Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells inlocalized Ewing tumor. J Clin Oncol 2003; 21: 85-91. (エビデンスレベルⅢ)
2) Fagnou C, Michon J, Peter M, et al. Presence of tumor cells in bone marrow but not in blood is associated with adverse prognosis in patients with Ewing’s tumor. Société Fran-çaise d’Oncologie Pédiatrique. J Clin Oncol 1998; 16: 1707-11.(エビデンスレベルⅣa)
3) Avigad S, Cohen IJ, Zilberstein J, et al. The predictive potential of molecular detection in the nonmetastatic Ewing family of tumors. Cancer 2004; 100: 1053-8.(エビデンスレベルⅣa)
4) Yaniv I, Cohen IJ, Stein J, et al. Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse. Pediatr Blood Cancer 2004; 42: 404-9.(エビデンスレベルⅣa)
5) Vermeulen V, Ballet S, Oberlin O, et al. Incidence and prognostic value of tumor cells de-tected by RT-PCR in peripheral blood stem cell collections from patients with Ewing tu-mor. Br J Cancer 2006; 95: 1326-33.(エビデンスレベルⅣa)
1) Miser JS, Krailo MD, Tarbell NJ, et al. Treatment of metastatic Ewing’s sarcoma or primi-tive neuroectdermal tumor of bone: evaluation of combination ifosfamide and etoposide-a Children’s Cancer Group and Pediatric Oncology Group study. J Clin Oncol 2004; 22: 2873-6.(エビデンスレベルⅡ)
2) Paulussen M, Ahrens S, Burdach S, et al. Primary metastatic(stage Ⅳ)Ewing tumor: sur-vival analysis of 171 patients from the EICESS studies. Ann Oncol 1998; 9: 275-81.(エビデンスレベルⅢ)
3) Grier HE, Krailo M, Tarbell N, et al. Addition of ifosfamide and etoposide to standard che-motherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003; 348: 694-701.(エビデンスレベルⅡ)
4) Kushner BH, Meyers PA, Gerald WL, et al. Very high-dose short term chemotherapy for poor-risk peripheral primitive neuroectdermal tumors, including Ewing’s sarcoma, in chil-dren and young adult. J Clin Oncol 1995; 13: 2796-804.(エビデンスレベルⅣa)
5) Paulussen M, Craft AW, Lewis I, et al. Results of the EICESS-92 Study: two randomized tri-als of Ewing’s sarcoma treatment ─ cyclophosphamide compared with ifosfamide in stan-dard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol 2008; 26: 4385-93.(エビデンスレベルⅡ)
6) Miser JS, Goldsby RE, Chen Z, et al. Treatment of metastatic Ewing sarcoma/primitive neu-roectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy-a report from the Children’s Oncology Group. Pediatr Blood Cancer 2007; 49: 894-900.(エビデンスレベルⅢ)
1) Stewart DA, Gyonyor E, Paterson AH, et al. High-dose melphalan+/−total body irradia-tion and autologous hematopoietic stem cell rescue for adult patients with Ewing’s sarcoma or peripheral neuroectodermal tumor. Bone Marrow Transplant 1996; 18: 315-8.(エビデンスレベルⅣa)
2) Burdach S, Meyer-Bahlburg A, Laws HJ, et al. High dose therapy for patients with primary multifocal and early relapsed Ewing’s tumors: results of two consecutive regimens assessing the role of total-body irradiation. J Clin Oncol 2003; 21: 3072-8.(エビデンスレベルⅡ)
3) Meyers PA, Krailo MD, Ladanyi M, et al. High-dose melphalan, etoposide, total-body irradi-ation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing’s sarcoma does not improve prognosis. J Clin Oncol 2001; 19: 2812-20.(エビデンスレベルⅣa)
4) Oberlin O, Rey A, Desfachelles AS, et al. Impact of high-dose busulfan plus melphalan as consolidation in metastatic Ewing tumors: a study by the Société Française des Cancers de l’Enfant. J Clin Oncol 2006; 24: 3997-4002.(エビデンスレベルⅢ)
5) Gardner SL, Carreras J, Boudreau C, et al. Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma. Bone Marrow Transplant 2008; 41: 867-72.(エビデンスレベルⅢ)
6) Rosenthal J, Bolotin E, Shakhnovits M, et al. High-dose therapy with hematopoietic stem cell rescue in patients with poor prognosis Ewing family tumors. Bone Marrow Transplant 2008; 42: 311-8.(エビデンスレベルⅣa)
1) Paulussen M, Ahrens S, Burdach S, et al. Primary metastatic(stage IV)Ewing tumor: sur-vival analysis of 171 patients from the EICESS studies. Ann Oncol 1998; 9: 275-81.(エビデンスレベルⅢ)
2) Spunt SL, McCarville MB, Kun LE, et al. Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis. J Pediatr Hematol Oncol 2001; 23: 93-8.(エビデンスレベルⅣa)
3) Bölling T, Schuck A, Paulussen M, et al. Whole lung irradiation in patients with exclusively pulmonary metastases of Ewing tumors. Toxicity analysis and treatment results of the El-CESS-92 trial. Strahlenther Onkol 2008; 184: 193-7.(エビデンスレベルⅢ)
は,診断時から 2年以降の再発例の予後は比較的良好であるのに対して,2年以内の再発の予後は非常に不良であると報告している。再発部位では,局所の単独再発の場合は,放射線治療と化学療法を行えば予後は良好だが,再発が複数部位の場合は不良である。肺の単独再発例は,肺照射を行うほうが化学療法単独より 5年無病生存率は有意に高い3)ことより,肺照射は治療法の選択の一つとして考えられる。新規薬剤に関しては,トポイソメラーゼ I 阻害剤であるイリノテカン(CPT-11)や
1) Barker LM , Pendergrass TW, Sanders JE, et al. Survival after recurrence of Ewing’s sarco-ma family of tumors. J Clin Oncol 2005; 23: 4354-62.(エビデンスレベルⅢ)
2) Shankar AG, Ashley S, Craft AW, et al. Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma. Med Pediatr Oncol 2003; 40: 141-7.(エビデンスレベル Ⅳa)
3) Rodriguez-Galindo C, Billups CA, Kun LE, et al. Survival after Recurrence of Ewing tumors: the St Jude Children’s Research Hospital experience, 1979-1999. Cancer 2002; 94: 561-9.(エビデンスレベルⅢ)
4) Bacci G, Ferrari S, Longhi A, et al. Therapy and survival after recurrence of Ewing’s tu-mors: the Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemo-therapy from 1979 to 1997. Ann Oncol 2003; 14: 1654-9.(エビデンスレベルⅣa)
5) Kung FH, Desai SJ, Dickerman JD, et al. Ifosfamide/carboplatin/etoposide(ICE)for recur-rent malignant solid tumor of childhood: a Pediatric Oncology Group Phase Ⅰ / Ⅱ study. J pediatr Hematol Oncol 1995; 17; 265-9.(エビデンスレベルⅤ)
6) Van Winkle P, Angiolillo A, Krailo M, et al. Ifosfamide, carboplatin, and etoposide(ICE)re-induction chemotherapy in large cohort of children and adolescents with recurrent/refrac-tory sarcoma: The children’s Cancer Group(CCG)experience. Pediatr Blood Cancer 2005; 44: 338-47.(エビデンスレベルⅣa)
7) Wagner LM, McAllister N, Goldsby RE et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing Sarcoma. Pediatr Blood Cancer 2007; 48: 132-9.(エビデンスレベルⅣb)
8) Hunold A, Weddeling N, Paulussen M et al. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer 2006; 47: 795-800.(エビデンスレベルⅣb)
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331
8
Ew
ing
肉腫ファミリー腫瘍
Ewing 肉腫ファミリー腫瘍(ESFT)に対する治療は,アルキル化剤やトポイソメラーゼ II 阻害剤を含む多剤併用化学療法に放射線治療を併用することにより予後の改善が図られてきた。一方,これら抗がん剤および放射線治療による治療関連性の二次がんの報告も散見される。実際,これらの影響による二次がん発症率,発症要因に関して検討した。
1) Paulussen M, Ahrens S, M. Lehnert M, et al. Second malignancies after ewing tumor treat-ment in 690 patients from a cooperative German/Austrian/Dutch study. Ann Oncol 2001; 12: 1619-30.(エビデンスレベルⅢ)
2) Dunst J, Ahrens S, Paulussen M, et al. Second malignancies after treatment for Ewing’s sar-coma: a report of the CESS-studies. Int J Radiat Oncol Biol Phys 1998; 42: 379-84.(エビデンスレベルⅢ)
3) Bacci G, Longhi A, Barbieri E,et al. Second malignancy in 597 patients with ewing sarcoma of bone treated at a single institution with adjuvant and neoadjuvant chemotherapy be-tween 1972 and 1999. J Pediatr Hematol Oncol 2005; 27: 517-20.(エビデンスレベルⅢ)
4) Navid F, Billups C, Liu T, et al. Second cancers in patients with the Ewing sarcoma family of tumors. Eur J Cancer 2008; 44: 983-91.(エビデンスレベルⅣa)
5) Kuttesch JF Jr, Wexler LH, Marcus RB, et al. Second malignancies after Ewing’s sarcoma: radiation dose-dependency of secondary sarcomas. J Clin Oncol 1996; 14: 2818-25.(エビデンスレベルⅢ)
6) Le Deley MC, Leblanc T, Shamsaldin A, et al. Risk of Secondary leukemia after a solid tu-mor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Sociótó Française d’Oncologie Pédiatrique. J Clin Oncol 2003; 21: 1074-81.(エビデンスレベルⅢ)
7) Bhatia S, Krailo MD, Chen Z, et al. Therapy-related myelodysplasia and acute myeloid leu-kemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children’s Oncology Group. Blood 2007; 109: 46-51.(エビデンスレベルⅢ)