perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2019-64-2-47-51perinatology-855Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSОстеосаркома – на пути к персонализированной терапии. Часть I: стандартная химиотерапия в настоящее времяOsteosarcoma – on the way to personalized therapy. Part I: standard chemotherapy in the presenthttps://orcid.org/0000-0002-8398-7001РыковМ. Ю.RykovM. Yu.

Рыков Максим Юрьевич – к.м.н., зам. директора НИИ детской онкологии и гематологии НМИЦ онкологии им. академика Н.Н. Блохина;

115478 Москва, Каширское ш., д. 24 ;

доцент кафедры онкологии лечебного факультета Первого Московского государственного медицинского университета им. И.М. Сеченова;

гл. внештатный детский специалист-онколог Минздрава России по Центральному федеральному округу.

SPIN-код: 7652-0122

Moscow

wordex2006@rambler.ruhttps://orcid.org/0000-0003-2310-3259СенжаповаЭ. Р.SenzhapovaE. R.

Сенжапова Эльмира Рифатовна – к.м.н., науч. сотр. отделения опухолейопорно-двигательного аппарата.

115478 Москва, Каширское ш., д. 24

Moscow

ФБГУ «Национальный медицинский исследовательский центр онкологии им. академика Н.Н. Блохина» Минздрава России; ФГАОУ ВО «Первый московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияBlokhin National Medical Research Center of Oncology; Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФБГУ «Национальный медицинский исследовательский центр онкологии им. академика Н.Н. Блохина» Минздрава РоссииРоссияBlokhin National Medical Research Center of OncologyRussian Federation2019140520196424751Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20192019Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/855

Саркомы костей составляют 7% в структуре злокачественных новообразований у детей, из них 35–50% – остеосаркомы. Значительное число пациентов выявляются на распространенных стадиях заболеваний, что диктует необходимость поиска новых подходов к лечению. При этом оптимальная терапевтическая стратегия неизвестна, результаты лечения детей остаются неудовлетворительными. В части I данной статьи описаны схемы лечения, применяемые в настоящее время. В части II будут представлены достижения в области персонализированной терапии. Таким образом, изменения в подходах к лечению иллюстрируют вектор развития принципов терапии столь сложных заболеваний, которые еще несколько лет назад являлись для большинства пациентов фатальными.

Bone sarcomas account for 7% of malignant tumors in children, and osteosarcomas make up 35–50% of them. Many patients are diagnosed at spread stages of the disease, which dictates the need to search for new approaches to treatment. At the same time, the optimal therapeutic strategy is unknown, the results of treatment of such children remain unsatisfactory. Part I of this article describes currently used treatment regimens. Part II presents achievements in the field of personalized therapy. Thus, changes in treatment approaches illustrate the vector of development of the treatment principles of such complex diseases, being fatal for most patients a few years ago.

детская онкологияостеосаркомаперсонализированная терапияхимиотерапияpediatric oncologyosteosarcomapersonalized therapychemotherapyReferencesIsakoff M.S., Bielack S.S., Meltzer P., Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Сlin Oncol 2015; 33(27): 3029–3035. DOI: 10.1200/JCO.2014.59.4895.Isakoff M.S., Bielack S.S., Meltzer P., Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Сlin Oncol 2015; 33(27): 3029–3035. DOI: 10.1200/JCO.2014.59.4895.Пунанов Ю.А., Андреева Т.В., Гафтон Г.И., Гудзь Ю.В., Сафонова С.А., Набоков В.В., Новик В.И. Результаты комбинированного лечения детей и подростков с остеосаркомой. Онкопедиатрия 2014; 1(2): 49–53.Punanov Yu.A., Andreeva T.V., Gafton G.I., Gudz Y.V., Safonova S.A., Nabokov V.V., Novik V.I. The Results of Combined Therapy in Children and Adolescents with Osteosarcoma. Onkopediatriya (Onkopediatria) 2014; 1(2): 49–53. (in Russ)Doyle L.A. Sarcoma classification: An update based on the 2013 World health organization classification of tumors of soft tissue and bone. Cancer 2014; 120(12): 1763–1774. DOI: 10.1002/cncr.28657Doyle L.A. Sarcoma classification: An update based on the 2013 World health organization classification of tumors of soft tissue and bone. Cancer 2014; 120(12): 1763–1774. DOI: 10.1002/cncr.28657Fletcher C.D.M., Bridge J.A., Hogendoorn J.A., Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. WHO, 2013; 427.Fletcher C.D.M., Bridge J.A., Hogendoorn J.A., Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. WHO, 2013; 427.Ritter J., Bielack S.S. Osteosarcoma. Ann Oncol 2010; 21: 320–325. DOI: 10.1093/annonc/mdq276.Ritter J., Bielack S.S. Osteosarcoma. Ann Oncol 2010; 21: 320–325. DOI: 10.1093/annonc/mdq276.Avella M., Bacci G., McDonald D.J., Di Scioscio M., Picci P., Campanacci M. Adjuvant chemotherapy with six drugs (Adriamycin, methotrexate, cisplatinum, bleomycin, cyclophosphamide and dactinomycin) for non-metastatic high grade osteosarcoma of the extremities. Results of 32 patients and comparison to 127 patients concomitantly treated with the same drugs in a neoadjuvant form. Chemioterapia 1988; 7(2): 133–137.Avella M., Bacci G., McDonald D.J., Di Scioscio M., Picci P., Campanacci M. Adjuvant chemotherapy with six drugs (Adriamycin, methotrexate, cisplatinum, bleomycin, cyclophosphamide and dactinomycin) for non-metastatic high grade osteosarcoma of the extremities. Results of 32 patients and comparison to 127 patients concomitantly treated with the same drugs in a neoadjuvant form. Chemioterapia 1988; 7(2): 133–137.Fuchs N., Bielack S.S., Epler D., Biding P., Delling G., Korholz D. Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 1998; 9: 893–899.Fuchs N., Bielack S.S., Epler D., Biding P., Delling G., Korholz D. Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 1998; 9: 893–899.Ngan R.K.C. Chemotherapy for non-metastatic high-grade osteosarcoma of extremity – is neoadjuvant better than adjuvant? Hong Kong J Radiol 2003; 6: 7–14.Ngan R.K.C. Chemotherapy for non-metastatic high-grade osteosarcoma of extremity – is neoadjuvant better than adjuvant? Hong Kong J Radiol 2003; 6: 7–14.Pratt C.B., Meyer W.H., Rao B.N., Parham D.M., Fleming I.D. Osteosarcoma studies at St. Jude Children’s research hospital from 1968 through 1990. J Cancer Treatment Res 1993; 62: 323–326.Pratt C.B., Meyer W.H., Rao B.N., Parham D.M., Fleming I.D. Osteosarcoma studies at St. Jude Children’s research hospital from 1968 through 1990. J Cancer Treatment Res 1993; 62: 323–326.Saeter G., Alvegard T.A., Elomaa I., Stenwig A.E., Holmstrom T., Solheim O.P. Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effect of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study. J Clin Oncol 1991; 9(10): 1766–1775. DOI: 10.1200/JCO.1991.9.10.1766Saeter G., Alvegard T.A., Elomaa I., Stenwig A.E., Holmstrom T., Solheim O.P. Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effect of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study. J Clin Oncol 1991; 9(10): 1766–1775. DOI: 10.1200/JCO.1991.9.10.1766Souhami R.L., Craft A.W., der Eijken J.W.V., Nooij M., Spooner D., Bramwell V.H. et al. Randomised trial of two regimens of chemotherapy inoperable osteosarcoma: a study of the European Osteosarcoma Intergroup. The Lancet 1997; 350: 911–917. DOI: 10.1016/S0140-6736(97)02307-6Souhami R.L., Craft A.W., der Eijken J.W.V., Nooij M., Spooner D., Bramwell V.H. et al. Randomised trial of two regimens of chemotherapy inoperable osteosarcoma: a study of the European Osteosarcoma Intergroup. The Lancet 1997; 350: 911–917. DOI: 10.1016/S0140-6736(97)02307-6Bacci G., Ferrari S., Bertoni F., Ruggieri P., Picci P., Longhi A. et al. Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report. J Clin Oncol 2000; 18(24): 4016–4027. DOI: 10.1200/JCO.2000.18.24.4016Bacci G., Ferrari S., Bertoni F., Ruggieri P., Picci P., Longhi A. et al. Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report. J Clin Oncol 2000; 18(24): 4016–4027. DOI: 10.1200/JCO.2000.18.24.4016Ferrari S., Ruqqieri P., Cefalo G., Tamburini A., Rodolfo C., Fagioli F. et al. Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: An Italian Sarcoma Group Trial ISG/OS-1. J Clin Oncol 2012; 30(17): 2112–2118. DOI: 10.1200/JCO.2011.38.4420Ferrari S., Ruqqieri P., Cefalo G., Tamburini A., Rodolfo C., Fagioli F. et al. Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: An Italian Sarcoma Group Trial ISG/OS-1. J Clin Oncol 2012; 30(17): 2112–2118. DOI: 10.1200/JCO.2011.38.4420Ferrari S., Smeland S., Mercuri M., Bertoni F., longhi A., Ruggieri P. et al. Neoadjuvant Chemotherapy With High-Dose Ifosfamide, High-Dose Methotrexate, Cisplatin, and Doxorubicin for Patients With Localized Osteosarcoma of the Extremity: A Joint Study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol 2005; 23(34): 8845–8852. DOI: 10.1200/JCO.2004.00.5785Ferrari S., Smeland S., Mercuri M., Bertoni F., longhi A., Ruggieri P. et al. Neoadjuvant Chemotherapy With High-Dose Ifosfamide, High-Dose Methotrexate, Cisplatin, and Doxorubicin for Patients With Localized Osteosarcoma of the Extremity: A Joint Study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol 2005; 23(34): 8845–8852. DOI: 10.1200/JCO.2004.00.5785Hegyi M., Semsei A.F., Jakab Z., Antal I., Kiss J., Szendroi M. et al. Good Prognosis of Localized Osteosarcoma in Young Patients Treated With Limb-Salvage Surgery and Chemotherapy. Pediatric Blood Cancer 2011; 57: 415–422. DOI: 10.1002/pbc.23172Hegyi M., Semsei A.F., Jakab Z., Antal I., Kiss J., Szendroi M. et al. Good Prognosis of Localized Osteosarcoma in Young Patients Treated With Limb-Salvage Surgery and Chemotherapy. Pediatric Blood Cancer 2011; 57: 415–422. DOI: 10.1002/pbc.23172Smeland S., Bruland O.S., Hjorth L., Brosjo O., Bjerkehagen B., Osterlundh G. et al. Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma. Acta Orthopaedica 2011; 82(2): 211–216. DOI: 10.3109/17453674.2011.566141Smeland S., Bruland O.S., Hjorth L., Brosjo O., Bjerkehagen B., Osterlundh G. et al. Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma. Acta Orthopaedica 2011; 82(2): 211–216. DOI: 10.3109/17453674.2011.566141Iwamoto Y., Tanaka K., Isu K., Kawai A., Tatezaki S., Ishii T. et al. Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J. J Orthoped Sci 2009; 14: 397–404. DOI: 10.1007/s00776-009-1347-6Iwamoto Y., Tanaka K., Isu K., Kawai A., Tatezaki S., Ishii T. et al. Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J. J Orthoped Sci 2009; 14: 397–404. DOI: 10.1007/s00776-009-1347-6Petrilli S., de Camargo B., Filho V.O., Bruniera P., Brunetto A.L., Jesus-Garcia R. et al. Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival. J Clin Oncol 2006; 24(7): 1161–1168. DOI: 10.1200/JCO.2005.03.5352Petrilli S., de Camargo B., Filho V.O., Bruniera P., Brunetto A.L., Jesus-Garcia R. et al. Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival. J Clin Oncol 2006; 24(7): 1161–1168. DOI: 10.1200/JCO.2005.03.5352Goorin A.M., Shwartzentruber D.J., Devidas M., Gebhardt M.C., Ayala A.G., Harris M.B. Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 2003; 21: 1574–1580. DOI: 10.1200/JCO.2003.08.165Goorin A.M., Shwartzentruber D.J., Devidas M., Gebhardt M.C., Ayala A.G., Harris M.B. Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 2003; 21: 1574–1580. DOI: 10.1200/JCO.2003.08.165Le Deley M.C., Guinebretiere J.M., Gentet V.C. SFOP OS94: A randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients. Eur J Cancer 2007; 43: 752–761. DOI: 10.1016/j.ejca.2006.10.023Le Deley M.C., Guinebretiere J.M., Gentet V.C. SFOP OS94: A randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients. Eur J Cancer 2007; 43: 752–761. DOI: 10.1016/j.ejca.2006.10.023Hinds P.S., Gattuso J.S., Billups C.A., West N.K.; Wu J.; Rivera C. et al. Aggressive treatment of non-metastatic osteosarcoma improves health-related quality of life in children and adolescents. Eur J Cancer 2009; 45: 2007–2014. DOI: 10.1016/j.ejca.2009.04.020Hinds P.S., Gattuso J.S., Billups C.A., West N.K.; Wu J.; Rivera C. et al. Aggressive treatment of non-metastatic osteosarcoma improves health-related quality of life in children and adolescents. Eur J Cancer 2009; 45: 2007–2014. DOI: 10.1016/j.ejca.2009.04.020Daw N.C., Neel M.D., Rao B.N., Billups C.A., Wu J., Jenkins J. et al. Frontline Treatment of Localized Osteosarcoma Without Methotrexate: results of the St. Jude Children’s research hospital OS99 trial. Cancer 2011; 117(12): 2770–2778. DOI: 10.1002/cncr.25715Daw N.C., Neel M.D., Rao B.N., Billups C.A., Wu J., Jenkins J. et al. Frontline Treatment of Localized Osteosarcoma Without Methotrexate: results of the St. Jude Children’s research hospital OS99 trial. Cancer 2011; 117(12): 2770–2778. DOI: 10.1002/cncr.25715Meyers P.A., Schwartz C.L., Krailo M.D., Healey J.H., Bernstein M.L., Betcher D. et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol 2008; 28(9): 633–638. DOI: 10.1200/JCO.2008.14.0095Meyers P.A., Schwartz C.L., Krailo M.D., Healey J.H., Bernstein M.L., Betcher D. et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol 2008; 28(9): 633–638. DOI: 10.1200/JCO.2008.14.0095Meyers P. A., Healeya J.H., Chou A.J., Wexler L.H., Merola P.L., Morris C.D. et al. Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer 2011; 117(8): 1736–1744. DOI: 10.1002/cncr.25744Meyers P. A., Healeya J.H., Chou A.J., Wexler L.H., Merola P.L., Morris C.D. et al. Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer 2011; 117(8): 1736–1744. DOI: 10.1002/cncr.25744Isakoff M.S., Barkauskas D.A., Ebb D. Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children’s Oncology Group. Clin Orthop Relat Res 2012; 470: 2007–2013. DOI: 10.1007/s11999-012-2284-9Isakoff M.S., Barkauskas D.A., Ebb D. Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children’s Oncology Group. Clin Orthop Relat Res 2012; 470: 2007–2013. DOI: 10.1007/s11999-012-2284-9Boye K., Del Prever A.B., Eiksson E., Saeter G., Tienghi A., Lindholm P. et al. High-Dose Chemotherapy with Stem Cell Rescue in the Primary Treatment of Metastatic and Pelvic Osteosarcoma: Final Results of the ISG/SSG II Study. Pediatr Blood Cancer 2014; 61(5): 840–845. DOI: 10.1002/pbc.24868Boye K., Del Prever A.B., Eiksson E., Saeter G., Tienghi A., Lindholm P. et al. High-Dose Chemotherapy with Stem Cell Rescue in the Primary Treatment of Metastatic and Pelvic Osteosarcoma: Final Results of the ISG/SSG II Study. Pediatr Blood Cancer 2014; 61(5): 840–845. DOI: 10.1002/pbc.24868Smeland S., Whelan J.S., Bielack S.S., Marina N.M., Jovic G., Butterfass-Bahloul T. et al. Event-free survival and overall survival in 2,253 patients with osteosarcoma registered to EURAMOS-1. J Clin Oncol 2015; 33(suppl): abstr 10512.Smeland S., Whelan J.S., Bielack S.S., Marina N.M., Jovic G., Butterfass-Bahloul T. et al. Event-free survival and overall survival in 2,253 patients with osteosarcoma registered to EURAMOS-1. J Clin Oncol 2015; 33(suppl): abstr 10512.Whelan J.S., Bielack S.S., Marina N., Smeland S., Jovic G., Hook J.M. et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol 2015; 26: 407–414. DOI: 10.1093/annonc/mdu526Whelan J.S., Bielack S.S., Marina N., Smeland S., Jovic G., Hook J.M. et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol 2015; 26: 407–414. DOI: 10.1093/annonc/mdu526Daw N.C., Billups C.A., Rodriques-Galindo C. Metastatic Osteosarcoma. Results of Two Consecutive Therapeutic Trials at St. Jude Children’s Research Hospital. Cancer 2006; 106: 403–412. DOI: 10.1002/cncr.21626Daw N.C., Billups C.A., Rodriques-Galindo C. Metastatic Osteosarcoma. Results of Two Consecutive Therapeutic Trials at St. Jude Children’s Research Hospital. Cancer 2006; 106: 403–412. DOI: 10.1002/cncr.21626Ferrari S., Meazza C., Palmerini E., Tamburini A., Fagi li F., Cozza R. et al. Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian sarcoma group (ISG/OS-oss). Tumori 2014; 100: 612–618. DOI: 10.1700/1778.19262Ferrari S., Meazza C., Palmerini E., Tamburini A., Fagi li F., Cozza R. et al. Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian sarcoma group (ISG/OS-oss). Tumori 2014; 100: 612–618. DOI: 10.1700/1778.19262Goorin A.M., Harris M.B., Bernstein M., Ferguson W., Devidas M., Siegal G. et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. J Clin Oncol 2002; 2: 426–433. DOI: 10.1200/JCO.2002.20.2.426.Goorin A.M., Harris M.B., Bernstein M., Ferguson W., Devidas M., Siegal G. et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. J Clin Oncol 2002; 2: 426–433. DOI: 10.1200/JCO.2002.20.2.426.Marina N.M., Smeland S., Bielack S.S., Bernstein M., Jovic G., Krail M. et al. Comparison of MAPIE versus MAP in patients with poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS1): an open-label, international, randomized controlled trial. Lancet Oncology 2016; 17 (10): 1396–1408. DOI: 10.1016/S1470-2045(16)30214-5.Marina N.M., Smeland S., Bielack S.S., Bernstein M., Jovic G., Krail M. et al. Comparison of MAPIE versus MAP in patients with poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS1): an open-label, international, randomized controlled trial. Lancet Oncology 2016; 17 (10): 1396–1408. DOI: 10.1016/S1470-2045(16)30214-5.

The authors declare that there are no conflicts of interest present.