<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Bone and soft tissue sarcomas, tumors of the skin</journal-id><journal-title-group><journal-title xml:lang="en">Bone and soft tissue sarcomas, tumors of the skin</journal-title><trans-title-group xml:lang="ru"><trans-title>Саркомы костей, мягких тканей и опухоли кожи</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2219-4614</issn><issn publication-format="electronic">2782-3687</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">730</article-id><article-id pub-id-type="doi">10.17650/2219-4614-2025-17-1-32-39</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>BONE SARCOMAS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>САРКОМЫ КОСТЕЙ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Experience of using neoadjuvant three-component chemotherapy (cisplatin, doxorubicin, methotrexate) in young adults with osteosarcoma</article-title><trans-title-group xml:lang="ru"><trans-title>Опыт применения неоадъювантной трехкомпонентной химиотерапии (цисплатин, доксорубицин, метотрексат) у молодых взрослых с остеосаркомой</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6971-3266</contrib-id><name-alternatives><name xml:lang="en"><surname>Konev</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Конев</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Andrey Andreevich Konev</p><p><italic>24 Kashirskoe Shosse, Moscow 115522</italic></p></bio><bio xml:lang="ru"><p>Андрей Андреевич Конев</p><p><italic>115522 Москва, Каширское шоссе, 24</italic></p></bio><email>aakkpn@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5548-3295</contrib-id><name-alternatives><name xml:lang="en"><surname>Tararykova</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Тарарыкова</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>24 Kashirskoe Shosse, Moscow 115522</italic></p></bio><bio xml:lang="ru"><p><italic>115522 Москва, Каширское шоссе, 24</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1396-3434</contrib-id><name-alternatives><name xml:lang="en"><surname>Bokhyan</surname><given-names>B. Yu.</given-names></name><name xml:lang="ru"><surname>Бохян</surname><given-names>Б. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>24 Kashirskoe Shosse, Moscow 115522</italic></p></bio><bio xml:lang="ru"><p><italic>115522 Москва, Каширское шоссе, 24</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2038-3729</contrib-id><name-alternatives><name xml:lang="en"><surname>Valiev</surname><given-names>A. K.</given-names></name><name xml:lang="ru"><surname>Валиев</surname><given-names>А. К.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>24 Kashirskoe Shosse, Moscow 115522</italic></p></bio><bio xml:lang="ru"><p><italic>115522 Москва, Каширское шоссе, 24</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-04-17" publication-format="electronic"><day>17</day><month>04</month><year>2025</year></pub-date><volume>17</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>32</fpage><lpage>39</lpage><history><date date-type="received" iso-8601-date="2025-04-16"><day>16</day><month>04</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-04-16"><day>16</day><month>04</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Konev A.A., Tararykova A.A., Bokhyan B.Y., Valiev A.K.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Конев А.А., Тарарыкова А.А., Бохян Б.Ю., Валиев А.К.</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Konev A.A., Tararykova A.A., Bokhyan B.Y., Valiev A.K.</copyright-holder><copyright-holder xml:lang="ru">Конев А.А., Тарарыкова А.А., Бохян Б.Ю., Валиев А.К.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://sarbon.abvpress.ru/jour/article/view/730">https://sarbon.abvpress.ru/jour/article/view/730</self-uri><abstract xml:lang="en"><p><bold>Introduction</bold>. Modern treatment of osteosarcoma requires multicomponent therapy including pre-surgery chemotherapy. The benefits of such therapy are <italic>in vivo</italic> evaluation of chemotherapy drug activity and creation of conditions for more effective surgical intervention.</p><p><bold>Aim</bold>. To analyze the effectiveness of three-component chemotherapy based on a combination of doxorubicin, cisplatin and methotrexate in young adults with osteosarcoma.</p><p><bold>Materials and methods</bold>. Between 2022 and 2024, 22 patients between the ages of 18 and 42 years (mean age 30 years) with malignant tumors of the bones received treatment at the N.N. Blokhin National Medical Research Center of Oncology. Before the start of chemotherapy, all patients underwent morphological and clinical imaging examinations. The patients received 2 courses of neoadjuvant chemotherapy (doxorubicin + cisplatin + methotrexate) with subsequent surgical treatment stage.</p><p><bold>Results</bold>. Sixteen patients fully completed neoadjuvant polychemotherapy and local control stage, 12 of them received 2 courses of MAP (doxorubicin + cisplatin + methotrexate) chemotherapy. Complete response was not observed. Stable disease was registered in 1 (8.3 %) patient, partial response in 8 (66.6 %) patients. Tumor control was achieved in 74.9 % of patients. In 3 cases, disease progression was observed. Surgical treatment was performed in 10 (83.3 %) cases, among them 9 (75 %) interventions were organ-sparing. One patient refused surgical treatment and received radical external beam radiotherapy. In 1 (8.3 %) case grade IV therapeutic pathomorphosis was observed, in 3 (25 %) – grade III, in 3 (25 %) – grade II, in 3 (25 %) – grade I, in 2 (16.7 %) cases it was not registerable (disease progression was observed).</p><p><bold>Conclusion</bold>. During our study we achieved high level of tumor control (74.9 % of cases) but grade III–IV therapeutic pathomorphosis was achieved only in 33.3 % cases. According to our data, peak methotrexate concentration does not affect therapy effectiveness. In the future, it is necessary to include more patients in the study group, analyze recurrence-free and overall survival and compare MAP chemotherapy with standard regimen chemotherapy (cisplatin+ doxorubicin).</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение</bold>. Современное лечение остеосаркомы требует многокомпонентной терапии с включением предоперационной химиотерапии. Преимущества такой терапии заключаются в возможности оценки <italic>in vivo</italic> активности химиотерапевтических препаратов и создания условий для более абластичного хирургического вмешательства.</p><p><bold>Цель исследования</bold> – проанализировать эффективность трехкомпонентной химиотерапии на основе комбинации доксорубицина, цисплатина и метотрексата у молодых взрослых с остеосаркомой. Материалы и методы. С 2022 по 2024 г. в Национальном медицинском исследовательском центре онкологии им. Н.Н. Блохина получили лечение 22 пациента от 18 до 42 лет (средний возраст – 30 лет) со злокачественными новообразованиями костей. Перед началом химиотерапии всем больным проведены морфологические и клиникорентгенологические исследования. Пациенты получили 2 курса неоадъювантной химиотерапии (доксорубицин + цисплатин + метотрексат) с последующим хирургическим этапом лечения.</p><p><bold>Результаты</bold>. Полностью завершили неоадъювантную полихимиотерапию и этап локального контроля 16 пациентов, 12 из которых получили 2 курса химиотерапии по схеме МАР (доксорубицин + цисплатин + метотрексат). Полных ремиссий зарегистрировано не было. Стабилизация заболевания отмечена у 1 (8,3 %) пациента, частичный ответ – у 8 (66,6 %). Контроль за опухолью достигнут у 74,9 % пациентов. В 3 случаях выявлено прогрессирование заболевания. Хирургическое лечение выполнено в 10 (83,3 %) случаях, из них органосохраняющее – в 9 (75 %). Один пациент отказался от хирургического вмешательства, и ему был проведен радикальный курс дистанционной лучевой терапии. В 1 (8,3 %) случае отмечен лечебный патоморфоз IV степени, в 3 (25 %) – III степени, в 3 (25 %) – II степени, в 3 (25 %) – I степени, в 2 (16,7 %) он не определялся (отмечено прогрессирование заболевания).</p><p><bold>Заключение</bold>. В ходе нашего исследования мы получили высокий уровень контроля над ростом опухоли (74,9 % случаев), но лечебный патоморфоз III–IV степени был достигнут лишь в 33,3 % случаев. Согласно полученным данным пиковая концентрация метотрексата не влияет на эффективность терапии. В перспективе целесообразно включить в исследуемую группу большее число пациентов, проанализировать безрецидивную и общую выживаемость, а также сравнить эффективность химиотерапии по схеме MAP с результатами химиотерапии в стандартном режиме (цисплатин + доксорубицин).</p></trans-abstract><kwd-group xml:lang="en"><kwd>osteosarcoma</kwd><kwd>methotrexate</kwd><kwd>chemotherapy</kwd><kwd>bone tumors</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>остеосаркома</kwd><kwd>метотрексат</kwd><kwd>химиотерапия</kwd><kwd>опухоли костей</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The study was supported by RNF grant (grant No. 23-65-00003).</funding-statement><funding-statement xml:lang="ru">Исследование выполнено при поддержке гранта РНФ (грант № 23-65-00003).</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">1. Raymond A.K., Jaffe N. Osteosarcoma multidisciplinary approach to the management from the pathologist’s perspective. Cancer Treat Res 2009;152:63–84. DOI: 10.1007/978-1-4419-0284-9_4</mixed-citation><mixed-citation xml:lang="ru">Raymond A.K., Jaffe N. Osteosarcoma multidisciplinary approach to the management from the pathologist’s perspective. Cancer Treat Res 2009;152:63–84. DOI: 10.1007/978-1-4419-0284-9_4</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">2. Mirabello L., Troisi R.J., Savage S.A. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 2009;125(1):229–34. DOI: 10.1002/ijc.24320.</mixed-citation><mixed-citation xml:lang="ru">Mirabello L., Troisi R.J., Savage S.A. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 2009;125(1):229–34. DOI: 10.1002/ijc.24320.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">3. Abate M.E., Longhi A., Galletti S. et al. Non-metastatic osteosarcoma of the extremities in children aged 5 years or younger. Pediatr Blood Cancer 2010;55(4):652–4. DOI: 10.1002/pbc.22567</mixed-citation><mixed-citation xml:lang="ru">Abate M.E., Longhi A., Galletti S. et al. Non-metastatic osteosarcoma of the extremities in children aged 5 years or younger. Pediatr Blood Cancer 2010;55(4):652–4. DOI: 10.1002/pbc.22567</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">4. Kager L., Zoubek A., Potschger U. et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2003;21(10):2011–8. DOI: 10.1200/JCO.2003.08.132</mixed-citation><mixed-citation xml:lang="ru">Kager L., Zoubek A., Potschger U. et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2003;21(10):2011–8. DOI: 10.1200/JCO.2003.08.132</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">5. Pakos E.E., Nearchou A.D., Grimer R.J. et al. Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 2009;45(13):2367–75. DOI: 10.1016/j.ejca.2009.03.005</mixed-citation><mixed-citation xml:lang="ru">Pakos E.E., Nearchou A.D., Grimer R.J. et al. Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 2009;45(13):2367–75. DOI: 10.1016/j.ejca.2009.03.005</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">6. Cho W.H., Song W.S., Jeon D.G. et al. Differential presentations, clinical courses, and survivals of osteosarcomas of the proximal humerus over other extremity locations. Ann Surg Oncol 2010;17(3):702–8. DOI: 10.1245/s10434-009-0825-6</mixed-citation><mixed-citation xml:lang="ru">Cho W.H., Song W.S., Jeon D.G. et al. Differential presentations, clinical courses, and survivals of osteosarcomas of the proximal humerus over other extremity locations. Ann Surg Oncol 2010;17(3):702–8. DOI: 10.1245/s10434-009-0825-6</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">7. Kaste S.C., Liu T., Billups C.A. et al. Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity. Pediatr Blood Cancer 2004;43(7):723–8. DOI: 10.1002/pbc.20077</mixed-citation><mixed-citation xml:lang="ru">Kaste S.C., Liu T., Billups C.A. et al. Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity. Pediatr Blood Cancer 2004;43(7):723–8. DOI: 10.1002/pbc.20077</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">8. Sutow W.W. Combination chemotherapy with Adriamycin (NSC-123127) in primary treatment of osteosarcoma (Part III). Cancer Chemother Rep 1975;6:315–7.</mixed-citation><mixed-citation xml:lang="ru">Sutow W.W. Combination chemotherapy with Adriamycin (NSC-123127) in primary treatment of osteosarcoma (Part III). Cancer Chemother Rep 1975;6:315–7.</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">9. Sutow W.W., Gehan E.A., Dyment P.C. et al Multi-drug adjuvant chemotherapy in osteosarcoma: interim report of the Southwest Oncology Group Studies. Cancer Treat Rep 1978;62(2):265–9.</mixed-citation><mixed-citation xml:lang="ru">Sutow W.W., Gehan E.A., Dyment P.C. et al Multi-drug adjuvant chemotherapy in osteosarcoma: interim report of the Southwest Oncology Group Studies. Cancer Treat Rep 1978;62(2):265–9.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">10. Cortez E.P., Holland J.F., Wang J.J. et al. Doxorubicin in disseminated osteosarcoma. JAMA 1972;221(10):1132–7. DOI: 10.1001/jama.221.10.1132</mixed-citation><mixed-citation xml:lang="ru">Cortez E.P., Holland J.F., Wang J.J. et al. Doxorubicin in disseminated osteosarcoma. JAMA 1972;221(10):1132–7. DOI: 10.1001/jama.221.10.1132</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">11. Bonnaonna G., Monifardi S., Douglass R.C. et al Phase I and preliminary phase II evaluation of Adriamycin (NSC-123127). Cancer Res 1970;30(10):2572–82.</mixed-citation><mixed-citation xml:lang="ru">Bonnaonna G., Monifardi S., Douglass R.C. et al Phase I and preliminary phase II evaluation of Adriamycin (NSC-123127). Cancer Res 1970;30(10):2572–82.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">12. Cortez E.P., Holland J.F., Wang J.J. et al. Chemotherapy of adjuvant osteosarcoma. In: Proceedings of the 24th symposium of the Colston Research Society, April, 1972. London: Butterworths, 1972.</mixed-citation><mixed-citation xml:lang="ru">Cortez E.P., Holland J.F., Wang J.J. et al. Chemotherapy of adjuvant osteosarcoma. In: Proceedings of the 24th symposium of the Colston Research Society, April, 1972. London: Butterworths, 1972.</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">13. Middleman E., Luce L., Frei E. Clinical trials with Adriamycin. Cancer 1971;28(4):844–50. DOI: 10.1002/1097-0142(1971)28:43.0.co;2-9</mixed-citation><mixed-citation xml:lang="ru">Middleman E., Luce L., Frei E. Clinical trials with Adriamycin. Cancer 1971;28(4):844–50. DOI: 10.1002/1097-0142(1971)28:43.0.co;2-9</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">14. Smith M.A., Ungerleider R.S., Horowitz M.E. et al. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Nat Cancer Inst 1991;83(20):1460–70. DOI: 10.1093/jnci/83.20.1460</mixed-citation><mixed-citation xml:lang="ru">Smith M.A., Ungerleider R.S., Horowitz M.E. et al. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Nat Cancer Inst 1991;83(20):1460–70. DOI: 10.1093/jnci/83.20.1460</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">15. Nitschke R., Starling K.A., Vats T. et al. Cis-diamminedichloroplatinum II (NSC119875) In: Childhood malignancies. A Southwest Oncology Group study. Med Pediatr Oncol 1978;4(2):127–32. DOI: 10.1002/mpo.2950040208</mixed-citation><mixed-citation xml:lang="ru">Nitschke R., Starling K.A., Vats T. et al. Cis-diamminedichloroplatinum II (NSC119875) In: Childhood malignancies. A Southwest Oncology Group study. Med Pediatr Oncol 1978;4(2):127–32. DOI: 10.1002/mpo.2950040208</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">16. Ochs J.J., Freeman A.I., Douglass H.O. Jr et al. Cis-diamminedichloroplatinum (II) in advanced osteogenic sarcoma. Cancer Treat Rep 1978;62(2):239–45.</mixed-citation><mixed-citation xml:lang="ru">Ochs J.J., Freeman A.I., Douglass H.O. Jr et al. Cis-diamminedichloroplatinum (II) in advanced osteogenic sarcoma. Cancer Treat Rep 1978;62(2):239–45.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">17. Pratt C.B., Champion J.E., Senzer N. et al. Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin – doxorubicin. Cancer 1985;56(8):1930–3. DOI: 10.1002/1097-0142(19851015)56:83.0.co;2-u</mixed-citation><mixed-citation xml:lang="ru">Pratt C.B., Champion J.E., Senzer N. et al. Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin – doxorubicin. Cancer 1985;56(8):1930–3. DOI: 10.1002/1097-0142(19851015)56:83.0.co;2-u</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">18. Jaffe N., Knapp J., Chuang V.P. et al. Osteosarcoma intra-arterial treatment of the primary tumor with cis-diamminedichloroplatinum-II (CDP). Angiographic, pathologic and pharmacologic studies. Cancer 1983;51(3):402–7. DOI: 10.1002/1097-0142(19830201)51:33.0.co;2-p</mixed-citation><mixed-citation xml:lang="ru">Jaffe N., Knapp J., Chuang V.P. et al. Osteosarcoma intra-arterial treatment of the primary tumor with cis-diamminedichloroplatinum-II (CDP). Angiographic, pathologic and pharmacologic studies. Cancer 1983;51(3):402–7. DOI: 10.1002/1097-0142(19830201)51:33.0.co;2-p</mixed-citation></citation-alternatives></ref><ref id="B19"><label>19.</label><citation-alternatives><mixed-citation xml:lang="en">19. Jaffe N., Raymond A.K., Ayala A. et al. Effect of cumulative courses of intra-arterial cis- diamminedichloroplatinum II on the primary tumor in osteosarcoma. Cancer 1989;63(1):63–8. DOI: 10.1002/1097-0142(19890101)63:13.0.co;2-o</mixed-citation><mixed-citation xml:lang="ru">Jaffe N., Raymond A.K., Ayala A. et al. Effect of cumulative courses of intra-arterial cis- diamminedichloroplatinum II on the primary tumor in osteosarcoma. Cancer 1989;63(1):63–8. DOI: 10.1002/1097-0142(19890101)63:13.0.co;2-o</mixed-citation></citation-alternatives></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">20. Petrilli A.S., de Camargo B., Filho V.O. 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):1161–8. DOI: 10.1200/JCO.2005.03.5352</mixed-citation><mixed-citation xml:lang="ru">Petrilli A.S., de Camargo B., Filho V.O. 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):1161–8. DOI: 10.1200/JCO.2005.03.5352</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">21. Jaffe N. Recent advances in the chemotherapy of osteogenic sarcoma. Cancer 1972;30(6):1627–31. DOI: 10.1002/1097-0142(197212)30:63.0.co;2-h</mixed-citation><mixed-citation xml:lang="ru">Jaffe N. Recent advances in the chemotherapy of osteogenic sarcoma. Cancer 1972;30(6):1627–31. DOI: 10.1002/1097-0142(197212)30:63.0.co;2-h</mixed-citation></citation-alternatives></ref><ref id="B22"><label>22.</label><citation-alternatives><mixed-citation xml:lang="en">22.Skipper H.E., Schabel F.M., Wilcox W.S. Experimental evaluation of potential anticancer agents. XIV Further study of certain basic concepts underlying chemotherapy of leukemia. Cancer Chemother Rep 1964;35:1–28.</mixed-citation><mixed-citation xml:lang="ru">Skipper H.E., Schabel F.M., Wilcox W.S. Experimental evaluation of potential anticancer agents. XIV Further study of certain basic concepts underlying chemotherapy of leukemia. Cancer Chemother Rep 1964;35:1–28.</mixed-citation></citation-alternatives></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">23. Laster W.R. Jr, Mayo J.G., Simpson-Herrin L. et al. Success and failure in the treatment of solid tumors. II. Kinetic parameters and “cell cure” of moderately advanced carcinoma. Cancer Chemother Rep 1969;53(3):169–88.</mixed-citation><mixed-citation xml:lang="ru">Laster W.R. Jr, Mayo J.G., Simpson-Herrin L. et al. Success and failure in the treatment of solid tumors. II. Kinetic parameters and “cell cure” of moderately advanced carcinoma. Cancer Chemother Rep 1969;53(3):169–88.</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><citation-alternatives><mixed-citation xml:lang="en">24. Schabel F.M. Jr. Concepts for systemic treatment of micro-metastases. Cancer 1975;35(1):15–24. DOI: 10.1002/1097-0142(197501)35:13.0.co;2-w</mixed-citation><mixed-citation xml:lang="ru">Schabel F.M. Jr. Concepts for systemic treatment of micro-metastases. Cancer 1975;35(1):15–24. DOI: 10.1002/1097-0142(197501)35:13.0.co;2-w</mixed-citation></citation-alternatives></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">25. Jaffe N. Progress report on high-dose methotrexate (NSC-740) with citrovorum rescue in the treatment of metastatic bone tumor. Cancer Chemother Rep 1974;58(2):275–80.</mixed-citation><mixed-citation xml:lang="ru">Jaffe N. Progress report on high-dose methotrexate (NSC-740) with citrovorum rescue in the treatment of metastatic bone tumor. Cancer Chemother Rep 1974;58(2):275–80.</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><citation-alternatives><mixed-citation xml:lang="en">26. Jaffe N., Traggis D. Toxicity of high-dose methotrexate (NSC-740) and citrovorum factor (NSC-3590) in osteogenic sarcoma. Cancer Chemother Rep 1975;6(1):31–6. DOI: 10.1002/1097-0142(197701)39:13.0.co;2-t</mixed-citation><mixed-citation xml:lang="ru">Jaffe N., Traggis D. Toxicity of high-dose methotrexate (NSC-740) and citrovorum factor (NSC-3590) in osteogenic sarcoma. Cancer Chemother Rep 1975;6(1):31–6. DOI: 10.1002/1097-0142(197701)39:13.0.co;2-t</mixed-citation></citation-alternatives></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">27. Jaffe N., Traggis D., Cassady J.R. et al. Multidisciplinary treatment for macrometastatic osteogenic sarcoma. Br Med J 1976;2(6043):1039–41. DOI: 10.1136/bmj.2.6043.1039</mixed-citation><mixed-citation xml:lang="ru">Jaffe N., Traggis D., Cassady J.R. et al. Multidisciplinary treatment for macrometastatic osteogenic sarcoma. Br Med J 1976;2(6043):1039–41. DOI: 10.1136/bmj.2.6043.1039</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><citation-alternatives><mixed-citation xml:lang="en">28. Frei E. III, Jaffe N., Tattersall M.H.N. et al. New approaches to cancer chemotherapy with methotrexate. N Engl J Med 1975;292(16):846–51. DOI: 10.1056/NEJM197504172921607</mixed-citation><mixed-citation xml:lang="ru">Frei E. III, Jaffe N., Tattersall M.H.N. et al. New approaches to cancer chemotherapy with methotrexate. N Engl J Med 1975;292(16):846–51. DOI: 10.1056/NEJM197504172921607</mixed-citation></citation-alternatives></ref><ref id="B29"><label>29.</label><citation-alternatives><mixed-citation xml:lang="en">29. Pratt C., Shanks E., Hustu O. et al. Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity. Cancer 1977;39(1):51–7. DOI: 10.1002/1097-0142(197701)39:13.0.co;2-t</mixed-citation><mixed-citation xml:lang="ru">Pratt C., Shanks E., Hustu O. et al. Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity. Cancer 1977;39(1):51–7. DOI: 10.1002/1097-0142(197701)39:13.0.co;2-t</mixed-citation></citation-alternatives></ref><ref id="B30"><label>30.</label><citation-alternatives><mixed-citation xml:lang="en">30. Rosen G., Tefft M., Martinez A. et al. Combination chemotherapy and radiation therapy in the treatment of metastatic osteosarcoma. Cancer 1975;35(3):622–30. DOI: 10.1002/1097-0142(197503)35: 33.0.co;2-c</mixed-citation><mixed-citation xml:lang="ru">Rosen G., Tefft M., Martinez A. et al. Combination chemotherapy and radiation therapy in the treatment of metastatic osteosarcoma. Cancer 1975;35(3):622–30. DOI: 10.1002/1097-0142(197503)35: 33.0.co;2-c</mixed-citation></citation-alternatives></ref><ref id="B31"><label>31.</label><citation-alternatives><mixed-citation xml:lang="en">31.Meyers P.A., Schwartz C.L., Krailo M. et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate J Clin Oncol 2005;23(9):2004–11. DOI: 10.1200/JCO.2005.06.031</mixed-citation><mixed-citation xml:lang="ru">Meyers P.A., Schwartz C.L., Krailo M. et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate J Clin Oncol 2005;23(9):2004–11. DOI: 10.1200/JCO.2005.06.031</mixed-citation></citation-alternatives></ref><ref id="B32"><label>32.</label><citation-alternatives><mixed-citation xml:lang="en">32.Meyers P.A., Schwartz C.L., Krailo M.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;26(4):633–8. DOI: 10.1200/JCO.2008.14.0095</mixed-citation><mixed-citation xml:lang="ru">Meyers P.A., Schwartz C.L., Krailo M.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;26(4):633–8. DOI: 10.1200/JCO.2008.14.0095</mixed-citation></citation-alternatives></ref><ref id="B33"><label>33.</label><citation-alternatives><mixed-citation xml:lang="en">33.Whelan J.S., Bielack S.S., Marina N. et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol 2015;26(2):407–14. DOI: 10.1093/annonc/mdu526</mixed-citation><mixed-citation xml:lang="ru">Whelan J.S., Bielack S.S., Marina N. et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol 2015;26(2):407–14. DOI: 10.1093/annonc/mdu526</mixed-citation></citation-alternatives></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">34. Smeland S., Muller C., Alvegard T.A. et al. Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders. Eur J Cancer 2003;39(4):488–94. DOI: 10.1016/s0959-8049(02)00747-5</mixed-citation><mixed-citation xml:lang="ru">Smeland S., Muller C., Alvegard T.A. et al. Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders. Eur J Cancer 2003;39(4):488–94. DOI: 10.1016/s0959-8049(02)00747-5</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><citation-alternatives><mixed-citation xml:lang="en">35.Ferrari S., Ruggieri P., Cefalo G. 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):2112–8. DOI: 10.1200/JCO.2011.38.4420</mixed-citation><mixed-citation xml:lang="ru">Ferrari S., Ruggieri P., Cefalo G. 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):2112–8. DOI: 10.1200/JCO.2011.38.4420</mixed-citation></citation-alternatives></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">36.Fuchs N., Bielack S.S., Epler D. et al. Long-term results of the cooperative 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(8):893–9. DOI: 10.1023/a:1008391103132</mixed-citation><mixed-citation xml:lang="ru">Fuchs N., Bielack S.S., Epler D. et al. Long-term results of the cooperative 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(8):893–9. DOI: 10.1023/a:1008391103132</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><citation-alternatives><mixed-citation xml:lang="en">37. Bielack S.S., Kempf-Bielack B., Delling G. et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20(3):776–90. DOI: 10.1200/JCO.2002.20.3.776</mixed-citation><mixed-citation xml:lang="ru">Bielack S.S., Kempf-Bielack B., Delling G. et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20(3):776–90. DOI: 10.1200/JCO.2002.20.3.776</mixed-citation></citation-alternatives></ref><ref id="B38"><label>38.</label><citation-alternatives><mixed-citation xml:lang="en">38. Janeway K.A., Barkauskas D.A., Krailo M.D. et al. Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children’s Oncology Group. Cancer 2012;118(18):4597–605. DOI: 10.1002/cncr.27414</mixed-citation><mixed-citation xml:lang="ru">Janeway K.A., Barkauskas D.A., Krailo M.D. et al. Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children’s Oncology Group. Cancer 2012;118(18):4597–605. DOI: 10.1002/cncr.27414</mixed-citation></citation-alternatives></ref><ref id="B39"><label>39.</label><citation-alternatives><mixed-citation xml:lang="en">39. Whelan J.S., Jinks R.C., McTiernan A. et al. Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials. Ann Oncol 2012;23(6):1607–16. DOI: 10.1093/annonc/mdr491</mixed-citation><mixed-citation xml:lang="ru">Whelan J.S., Jinks R.C., McTiernan A. et al. Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials. Ann Oncol 2012;23(6):1607–16. DOI: 10.1093/annonc/mdr491</mixed-citation></citation-alternatives></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">40. Angelini A., Mavrogenis A.F., Trovarelli G. et al. Telangiectatic osteosarcoma: a review of 87 cases. J Cancer Res Clin Oncol 2016;142(10):2197–207. DOI: 10.1007/s00432-016-2210-8</mixed-citation><mixed-citation xml:lang="ru">Angelini A., Mavrogenis A.F., Trovarelli G. et al. Telangiectatic osteosarcoma: a review of 87 cases. J Cancer Res Clin Oncol 2016;142(10):2197–207. DOI: 10.1007/s00432-016-2210-8</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">41. Bacci G., Picci P., Ferrari S. et al. Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients. Eur J Cancer 1994;30A(5):620–6. DOI: 10.1016/0959-8049(94)90532-0</mixed-citation><mixed-citation xml:lang="ru">Bacci G., Picci P., Ferrari S. et al. Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients. Eur J Cancer 1994;30A(5):620–6. DOI: 10.1016/0959-8049(94)90532-0</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><citation-alternatives><mixed-citation xml:lang="en">42.Marina N.M., Smeland S., Bielack S.S. et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol 2016;17(10):1396–408. DOI: 10.1016/S1470-2045(16)30214-5</mixed-citation><mixed-citation xml:lang="ru">Marina N.M., Smeland S., Bielack S.S. et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol 2016;17(10):1396–408. DOI: 10.1016/S1470-2045(16)30214-5</mixed-citation></citation-alternatives></ref><ref id="B43"><label>43.</label><citation-alternatives><mixed-citation xml:lang="en">43. Bielack S., Jurgens H., Jundt G. et al. Osteosarcoma: the COSS experience. Cancer Treat Res 2009;152:289–308. DOI: 10.1007/978-1-4419-0284-9_15</mixed-citation><mixed-citation xml:lang="ru">Bielack S., Jurgens H., Jundt G. et al. Osteosarcoma: the COSS experience. Cancer Treat Res 2009;152:289–308. DOI: 10.1007/978-1-4419-0284-9_15</mixed-citation></citation-alternatives></ref><ref id="B44"><label>44.</label><citation-alternatives><mixed-citation xml:lang="en">44. Boye K., Del Prever A.B., Eriksson M. 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):840–5. DOI: 10.1002/pbc.24868</mixed-citation><mixed-citation xml:lang="ru">Boye K., Del Prever A.B., Eriksson M. 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):840–5. DOI: 10.1002/pbc.24868</mixed-citation></citation-alternatives></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">45. Bacci G., Longhi A., Versari M. et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 2006;106(5):1154–61. DOI: 10.1002/cncr.21724</mixed-citation><mixed-citation xml:lang="ru">Bacci G., Longhi A., Versari M. et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 2006;106(5):1154–61. DOI: 10.1002/cncr.21724</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><citation-alternatives><mixed-citation xml:lang="en">46. Hauben E.I., Weeden S., Pringle J. et al. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 2002;38(9):1218–25. DOI: 10.1016/s0959-8049(02)00037-0</mixed-citation><mixed-citation xml:lang="ru">Hauben E.I., Weeden S., Pringle J. et al. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 2002;38(9):1218–25. DOI: 10.1016/s0959-8049(02)00037-0</mixed-citation></citation-alternatives></ref><ref id="B47"><label>47.</label><citation-alternatives><mixed-citation xml:lang="en">47. Bacci G., Picci P., Ruggieri P. et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. The Istituto Rizzoli Experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin. Cancer 1990;65(11):2539. DOI: 10.1002/1097-0142(19900601)65:113.0.co;2-m</mixed-citation><mixed-citation xml:lang="ru">Bacci G., Picci P., Ruggieri P. et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. The Istituto Rizzoli Experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin. Cancer 1990;65(11):2539. DOI: 10.1002/1097-0142(19900601)65:113.0.co;2-m</mixed-citation></citation-alternatives></ref><ref id="B48"><label>48.</label><citation-alternatives><mixed-citation xml:lang="en">48. Graf N., Winkler K., Betlemovic M. et al. Methotrexate pharmacokinetics and prognosis in osteosarcoma. J Clin Oncol 1994;12(7):1443. DOI: 10.1200/JCO.1994.12.7.1443</mixed-citation><mixed-citation xml:lang="ru">Graf N., Winkler K., Betlemovic M. et al. Methotrexate pharmacokinetics and prognosis in osteosarcoma. J Clin Oncol 1994;12(7):1443. DOI: 10.1200/JCO.1994.12.7.1443</mixed-citation></citation-alternatives></ref><ref id="B49"><label>49.</label><citation-alternatives><mixed-citation xml:lang="en">49. Bacci G., Ferrari S., Delepine N. et al. Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin. J Clin Oncol 1998;16(2):658. DOI: 10.1200/JCO.1998.16.2.658</mixed-citation><mixed-citation xml:lang="ru">Bacci G., Ferrari S., Delepine N. et al. Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin. J Clin Oncol 1998;16(2):658. DOI: 10.1200/JCO.1998.16.2.658</mixed-citation></citation-alternatives></ref><ref id="B50"><label>50.</label><citation-alternatives><mixed-citation xml:lang="en">50. Li .Z., Ma X., Wang Z. et al. A meta-analysis of theefficacy and safety of first-line chemotherapeutic agents for osteosarcoma. Adv Clin Exp Med 2024;33(5):445–54. DOI: 10.17219/acem/170098</mixed-citation><mixed-citation xml:lang="ru">Li .Z., Ma X., Wang Z. et al. A meta-analysis of theefficacy and safety of first-line chemotherapeutic agents for osteosarcoma. Adv Clin Exp Med 2024;33(5):445–54. DOI: 10.17219/acem/170098</mixed-citation></citation-alternatives></ref><ref id="B51"><label>51.</label><citation-alternatives><mixed-citation xml:lang="en">51. Bramwell V.H., Burgers M., Sneath R. et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol 1992;10(10):1579–91. DOI: 10.1200/JCO.1992.10.10.1579</mixed-citation><mixed-citation xml:lang="ru">Bramwell V.H., Burgers M., Sneath R. et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol 1992;10(10):1579–91. DOI: 10.1200/JCO.1992.10.10.1579</mixed-citation></citation-alternatives></ref><ref id="B52"><label>52.</label><citation-alternatives><mixed-citation xml:lang="en">52. Bielack S.S., Smeland S., Whelan J.S. et al. Methotrexate, doxorubicin, and cisplatin (MAP) plus maintenance pegylated interferon alfa-2b versus MAP alone in patients with resectable highgrade osteosarcoma and good histologic response to preoperative MAP: First results of the EURAMOS-1 good response randomized controlled trial. J Clin Oncol 2015;33(20):2279–87. DOI: 10.1200/JCO.2014.60.0734</mixed-citation><mixed-citation xml:lang="ru">Bielack S.S., Smeland S., Whelan J.S. et al. Methotrexate, doxorubicin, and cisplatin (MAP) plus maintenance pegylated interferon alfa-2b versus MAP alone in patients with resectable highgrade osteosarcoma and good histologic response to preoperative MAP: First results of the EURAMOS-1 good response randomized controlled trial. J Clin Oncol 2015;33(20):2279–87. DOI: 10.1200/JCO.2014.60.0734</mixed-citation></citation-alternatives></ref><ref id="B53"><label>53.</label><citation-alternatives><mixed-citation xml:lang="en">53. Senerchia A.A., Macedo C.R., Ferman S. et al. Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: a report from the Latin American Group of Osteosarcoma Treatment. Cancer 2017;123(6):1003–10. DOI: 10.1002/cncr.30411</mixed-citation><mixed-citation xml:lang="ru">Senerchia A.A., Macedo C.R., Ferman S. et al. Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: a report from the Latin American Group of Osteosarcoma Treatment. Cancer 2017;123(6):1003–10. DOI: 10.1002/cncr.30411</mixed-citation></citation-alternatives></ref></ref-list></back></article>
