Современная лучевая терапия в мультимодальном лечении больных первичной медиастинальной (тимической) В-крупноклеточной лимфомой (результаты лечения 131 больного в ФГБУ «НМИЦ онкологии им. Н.Н.Блохина» Минздрава России)

Трофимова О.П., Заводнова И.З., Тумян Г.С. и др. Современная лучевая терапия в мультимодальном лечении больных первичной медиастинальной (тимической) В-крупноклеточной лимфомы (результаты лечения 131 больного в ФГБУ «НМИЦ онкологии им. Н.Н.Блохина» Минздрава России). Современная Онкология. 2018; 20 (4): 5–15. DOI: 10.26442/18151434.2018.4.180142

________________________________________________

Trofimova O.P., Zavodnova I.Z., Tumyan G.S. et al. Modern radiation therapy in part of treatment primary mediastinal (thymic) B-large cell lymphoma (results of 131 patients treated at N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation). Journal of Modern Oncology. 2018; 20 (4): 5–15. DOI: 10.26442/18151434.2018.4.180142

Читать PDF

Аннотация

Введение. На протяжении многих десятилетий ХХ в. лучевая терапия играла ведущую роль в лечении больных с лимфопролиферативными заболеваниями, являющимися высокочувствительными к ионизирующему излучению новообразованиями. Но в связи с эффективным развитием химиотерапии, открытием и бурным внедрением в практику таргетных препаратов роль лучевого лечения при различных видах лимфом становится менее определенной во многих клинических ситуациях. Первичная медиастинальная (тимическая) В-крупноклеточная лимфома (ПМВКЛ) относится к первичным экстранодальным опухолям и происходит из В-клеток мозгового слоя вилочковой железы. Болезнь имеет специфические морфоиммунологическую и генетическую характеристики, которые позволяют идентифицировать ее от остальных схожих по проявлениям лимфопролиферативных заболеваний. Стандартом лечения ПМВКЛ является иммунохимиотерапия с последующим облучением остаточной опухоли в средостении. К настоящему времени преимуществ одного лекарственного режима перед другим в рамках контролируемых исследований не показано.
Цель. Изучение современных подходов к химиолучевому лечению больных ПМВКЛ с попыткой их «индивидуализации» в зависимости от различных прогностических факторов.
Методы. В работе проведен тщательный анализ результатов терапии 131 больного ПМВКЛ, которые проходили лечение в ФГБУ «НМИЦ онкологии им. Н.Н.Блохина» с 2005 по 2017 г. Более 1/2 (58%) – женщины, медиана возраста составила 30 лет. На разных исторических этапах лечение ПМВКЛ осуществлялось по разным режимам химиотерапии: MACOP-B+R – 55 (42%), R-CHOP – 40 (30,5%), R-DA-EPOCH – 36 (27,5%). Лучевую терапию получили 99 пациентов.
Результаты. Эффективность лечения во всей группе больных ПМВКЛ оказалась высокой: ремиссии достигнуты у 87% больных, 3-летняя выживаемость без прогрессирования составила 78%, общая выживаемость – 88%. При медиане наблюдения 37 мес у 17 (13%) из 131 больного в сроки до 13 мес от начала противоопухолевого лечения был рецидив или прогрессирование заболевания. Терапия этой группы больных оказалась малоэффективной: 12-месячная общая выживаемость не превышала 37%. В группе 99 пациентов с проведенной иммунохимиолучевой терапией были достигнуты высокие показатели 3-летней общей выживаемости и выживаемости без прогрессирования (при медиане наблюдения 37 мес) – 91 и 88% соответственно. Показано, что интенсивные режимы иммунохимиотерапии (R-MACOP-B, R-DAEPOCH) не различаются по эффективности и имеют статистически значимые преимущества перед стандартной схемой R-CHOP. Позитронно-эмиссионная томография (ПЭТ) является важным прогностическим инструментом при лечении больных ПМВКЛ: 3-летняя выживаемость без прогрессирования в ПЭТ-негативной группе составила 92% по сравнению с 26% в ПЭТ-позитивной группе. Проанализирована частота лучевых повреждений легких при проведении конвенциональной и 3D-конформной лучевой терапии.
Заключение. Определен алгоритм оптимального лечения больных ПМВКЛ с учетом клинических факторов, программы лекарственного лечения, степени регрессии опухоли и ее метаболической активности, объема и метода облучения.

Ключевые слова: первичная медиастинальная В-крупноклеточная лимфома, лечение, прогностические факторы, лучевая терапия.

________________________________________________

Background. For many decades of the twentieth century, radiation therapy has played a leading role in the treatment of patients with lymphoproliferative diseases, which are highly susceptible to ionizing radiation by neoplasms. But due to the effective development of chemotherapy, the discovery and rapid introduction of targeted drugs into practice, the role of radiation treatment in various types of lymphomas becomes less defined in many clinical situations. Primary mediastinal (thymic) B-cell lymphoma (PMBCL) belongs to the primary extranodal tumors and originate from a thymic medullary B cell. The disease has specific morphoimmunological and genetic characteristics that allows it to be identified from the others similar in manifestations lymphoproliferative diseases. The standard of treatment for PMBCL is immunochemotherapy with subsequent irradiation of a residual tumor in the mediastinum. Currently, the benefits of one chemotherapy regimen over the other ones have not been shown in controlled studies.
Aim. To study the modern approaches to the chemoradiotherapy in PMBCL patients with an attempt to "individualize" them depending on various prognostic factors.
Methods. The study conducted a thorough analysis of the treatment results of 131 patients with PMBCL who were treated in the N.N.Blokhin National Medical Research Center of Oncology from 2005 to 2017. More than half of the patients were women (58%), the median age was 30 years. At different historical periods, the treatment of PMBCL was applied according to different chemotherapy regimens: MACOP-B+R – 55 (42%), R-CHOP – 40 (30.5%), R-DA-EPOCH – 36 (27.5%); 99 patients received radiation therapy.
Results. The efficacy of treatment in the whole group of PMBCL patients was high: remission was achieved in 87% of patients, 3-year progression-free survival was 78%, and overall survival was 88%. With a median follow-up of 37 months, 17 (13%) of 131 patients had a relapse or progression of the disease within 13 months from the start of treatment; no late relapses were detected. Treatment of this group was ineffective: the 12-month overall survival did not exceed 37%. In the group of 99 patients with immunochemoradiotherapy, high rates of 3-year overall survival and progression-free survival (with a median of 37 months) were achieved – 91% and 88%, respectively. It has been shown that intensive immunochemotherapy regimens (R-MACOP-B, R-EPOCH) do not differ in efficacy and have statistically significant advantages over the standard R-CHOP regimen. Positron emission tomography (PET) is an important prognostic tool in the treatment of patients with PMBCL: 3-year progression-free survival in the PET-negative group was 92% compared with 26% in the PET-positive group. The frequency of radiation damage to the lungs during conventional and 3D conformal radiation therapy was analyzed.
Conclusion. The algorithm of optimal treatment for PMBCL patients was determined based on clinical factors, the drug treatment program, the degree of regression of the tumor and its metabolic activity, volume and method of irradiation.

Key words: primary mediastinal B-cell lymphoma, treatment, prognostic factors, radiotherapy.

Полный текст

Материалы доступны только для специалистов сферы здравоохранения.
Чтобы посмотреть материал полностью Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Сотников В.М. Лучевая терапия в современных программах лечения неходжкинских лимфом. Автореф. дис. … д-ра мед. наук. М., 1996. / Sotnikov V.M. Luchevaia terapiia v sovremennykh programmakh lecheniia nekhodzhkinskikh limfom. Avtoref. dis. … d-ra med. nauk. M., 1996. [in Russian]
2. Виноградова Ю.Н. Значение лучевой терапии при химиолучевом лечении больных неходжкинскими лимфомами. Автореф. дис. … д-ра мед. наук. СПб., 2015. / Vinogradova Iu.N. Znachenie luchevoi terapii pri khimioluchevom lechenii bol'nykh nekhodzhkinskimi limfomami. Avtoref. dis. … d-ra med. nauk. SPb., 2015. [in Russian]
3. Трофимова О.П., Ткачев С.И., Юрьева Т.В. Прошлое и настоящее лучевой терапии в онкологии. Клин. онкогематология. 2013; 6 (4): 355–64. / Trofimova O.P., Tkachev S.I., Iur'eva T.V. Proshloe i nastoiashchee luchevoi terapii v onkologii. Klin. onkogematologiia. 2013; 6 (4): 355–64. [in Russian]
4. Moller P, Lammler B, Herrmann B et al. The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression. Immunology 1986; 59 (3): 411–7. DOI: 10.1007/bf00705408
5. Bishop PC, Wilson WH, Pearson D et al. CNS involvement in primary mediastinal large B-cell lymphoma. J Clin Oncol 1999; 17 (8): 2479–85.
6. Levitt LJ, Aisenberg AC, Harris NL et al. Primary non-Hodgkin’s lymphoma of the mediastinum. Cancer 1982; 50 (11): 2486–92. DOI: 10.1002/1097-0142 (19821201)50: 11<2486: AID-CNCR2820501138>3.0.CO; 2-G
7. Поддубная И.В. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В.Поддубной, В.Г.Савченко 2016; с. 155–61. / Poddubnaia I.V. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu limfoproliferativnykh zabolevanii. Pod red. I.V.Poddubnoi, V.G.Savchenko 2016; s. 155–61. [in Russian]
8. Hamlin PA, Portlock CS, Straus DJ et al. Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999. Br J Haematol 2005; 130 (5): 691–9. DOI: 10.1111/j.1365-2141.2005.05661.x
9. Rosenwald A, Wright G, Leroy K et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003; 198 (6): 851–62. DOI: 10.1084/jem.20031074
10. Jacobson JO, Aisenberg AC, Lamarre L et al. Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer 1988; 62 (9): 1893–8. DOI: 10.1002/1097-0142 (19881101)62: 9<1893: AID-CNCR2820620904>3.0.CO; 2-X
11. Zinzani PL, Martelli M, Magagnoli M et al. Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients. Blood 1999; 94 (10): 3289–93.
12. Todeschini G, Ambrosetti A, Meneghini V et al. Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. J Clin Oncol 1990; 8 (5): 804–8.
13. Bertini M, Orsucci L, Vitolo U et al. Stage II large B-cell lymphoma with sclerosis treated with MACOP-B. Ann Oncol 1991; 2 (10): 733–7.
14. Moskowitz CH, Schöder H, Teruya-Feldstein J et al. Risk-Adapted Dose-Dense Immunochemotherapy Determined by Interim FDG-PET in Advanced-Stage Diffuse Large B-Cell Lymphoma. J Clin Oncol 2010; 28 (11): 1896–903. DOI: 10.1200/JCO.2009.26.5942
15. Savage KJ, Al-rajhi N, Voss N et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 2006; 17 (1): 123–30.
16. Dunleavy K, Pittaluga S, Maeda LS et al. Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma. New Engl J Med 2013; 368 (15): 1408–16. DOI: 10.1056/NEJMoa1214561
17. Zinzani PL, Martelli M, Bertini M et al. Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. International Extranodal Lymphoma Study Group (IELSG). Haematologica 2002; 87 (12): 1258–64.
18. Todeschini G, Secchi S, Morra E et al. Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer 2004; 90: 372–6. DOI: 10.1038/ sj.bjc.6601460
19. Wang J, Liu X, Ma F et al. Role of radiotherapy in the treatment of primary mediastinal large B-cell lymphoma. Oncol Letters 2015; 10 (5): 2925–30. DOI: 10.3892/ol.2015.3700
20. Broccoli A, Casadei B, Stefoni V et al. The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients. BMC Cancer 2017; 1 (17): 1–8. DOI: 10.1186/s12885-017-3269-6
21. Smith D. Oncology 1998; 55: 284–8.
22. Martelli M, Ceriani L, Zucca E et al. [18F]Fluorodeoxyglucose Positron Emission Tomography Predicts Survival After Chemoimmunotherapy for Primary Mediastinal Large B-Cell Lymphoma: Results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol 2014; 32 (17): 1769–75. DOI: 10.1200/JCO.2013.51.7524
23. Pinnix CC, Dabaja B, Ahmed MA. Single-Institution Experience in the Treatment of Primary Mediastinal B Cell Lymphoma Treated With Immunochemotherapy in the Setting of Response Assessment by 18Fluorodeoxyglucose Positron Emission Tomography. Int J Radiation Oncol Biol Phys. Series: Radiation and the Modern Management of Lymphoma 2015; 92 (1): 113–21. DOI: 10.1016/j.ijrobp.2015.02.006
24. Асланиди И.П, Мухортова О.В., Катунина Т.А. и др. Современные аспекты применения позитронно-эмиссионной томографии при лимфомах. Клин. онкогематология. 2015; 8 (1): 13–25. / Aslanidi I.P, Mukhortova O.V., Katunina T.A. i dr. Sovremennye aspekty primeneniia pozitronno-emissionnoi tomografii pri limfomakh. Klin. onkogematologiia. 2015; 8 (1): 13–25. [in Russian]
25. Kuruvilla J, Pintilie M, Tsang R et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leukemia Lymphoma 2008; 49 (7): 1329–36. DOI: 10.1080/10428190802108870
26. The international non-hodgkin lymphoma prognostic factors project. NEJM 1993; 329: 987–94.
27. Moormeier JA, Williams SF, Golomb HM. The staging of non-Hodgkin's lymphomas. Semin Oncol 1990; 17: 43–50.
28. Common Toxicity Criteria of National Cancer Institute, 2005.
29. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31 (5): 1341–6.
30. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda: International Commission on Radiation Units and Measurements – 1999.
31. Emami B, Lyman J, Brown A et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. Series: Three-Dimensional Photon Treatment Planning Report of the Collaborative Working Group on the Evaluation of Treatment Planning for External Photon Beam Radiotherapy 1991; 21 (1): 109–22. DOI: 10.1016/ 0360-3016 (91)90171-Y
32. Marks LB, Yorke ED, Jackson A et al. Use of Normal Tissue Complication Probability Models in the Clinic. Int J Radiat Oncol Biol Phys. Series: Quantitative Analyses of Normal Tissue Effects in the Clinic 2010; 76 (3). Suppl.: S10–S19. DOI: 10.1016/j.ijrobp.2009.07.1754

________________________________________________

1. Sotnikov V.M. Luchevaia terapiia v sovremennykh programmakh lecheniia nekhodzhkinskikh limfom. Avtoref. dis. … d-ra med. nauk. M., 1996. [in Russian]
2. Vinogradova Iu.N. Znachenie luchevoi terapii pri khimioluchevom lechenii bol'nykh nekhodzhkinskimi limfomami. Avtoref. dis. … d-ra med. nauk. SPb., 2015. [in Russian]
3. Trofimova O.P., Tkachev S.I., Iur'eva T.V. Proshloe i nastoiashchee luchevoi terapii v onkologii. Klin. onkogematologiia. 2013; 6 (4): 355–64. [in Russian]
4. Moller P, Lammler B, Herrmann B et al. The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression. Immunology 1986; 59 (3): 411–7. DOI: 10.1007/bf00705408
5. Bishop PC, Wilson WH, Pearson D et al. CNS involvement in primary mediastinal large B-cell lymphoma. J Clin Oncol 1999; 17 (8): 2479–85.
6. Levitt LJ, Aisenberg AC, Harris NL et al. Primary non-Hodgkin’s lymphoma of the mediastinum. Cancer 1982; 50 (11): 2486–92. DOI: 10.1002/1097-0142 (19821201)50: 11<2486: AID-CNCR2820501138>3.0.CO; 2-G
7. Poddubnaia I.V. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniiu limfoproliferativnykh zabolevanii. Pod red. I.V.Poddubnoi, V.G.Savchenko 2016; s. 155–61. [in Russian]
8. Hamlin PA, Portlock CS, Straus DJ et al. Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999. Br J Haematol 2005; 130 (5): 691–9. DOI: 10.1111/j.1365-2141.2005.05661.x
9. Rosenwald A, Wright G, Leroy K et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003; 198 (6): 851–62. DOI: 10.1084/jem.20031074
10. Jacobson JO, Aisenberg AC, Lamarre L et al. Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer 1988; 62 (9): 1893–8. DOI: 10.1002/1097-0142 (19881101)62: 9<1893: AID-CNCR2820620904>3.0.CO; 2-X
11. Zinzani PL, Martelli M, Magagnoli M et al. Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients. Blood 1999; 94 (10): 3289–93.
12. Todeschini G, Ambrosetti A, Meneghini V et al. Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. J Clin Oncol 1990; 8 (5): 804–8.
13. Bertini M, Orsucci L, Vitolo U et al. Stage II large B-cell lymphoma with sclerosis treated with MACOP-B. Ann Oncol 1991; 2 (10): 733–7.
14. Moskowitz CH, Schöder H, Teruya-Feldstein J et al. Risk-Adapted Dose-Dense Immunochemotherapy Determined by Interim FDG-PET in Advanced-Stage Diffuse Large B-Cell Lymphoma. J Clin Oncol 2010; 28 (11): 1896–903. DOI: 10.1200/JCO.2009.26.5942
15. Savage KJ, Al-rajhi N, Voss N et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol 2006; 17 (1): 123–30.
16. Dunleavy K, Pittaluga S, Maeda LS et al. Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma. New Engl J Med 2013; 368 (15): 1408–16. DOI: 10.1056/NEJMoa1214561
17. Zinzani PL, Martelli M, Bertini M et al. Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. International Extranodal Lymphoma Study Group (IELSG). Haematologica 2002; 87 (12): 1258–64.
18. Todeschini G, Secchi S, Morra E et al. Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer 2004; 90: 372–6. DOI: 10.1038/ sj.bjc.6601460
19. Wang J, Liu X, Ma F et al. Role of radiotherapy in the treatment of primary mediastinal large B-cell lymphoma. Oncol Letters 2015; 10 (5): 2925–30. DOI: 10.3892/ol.2015.3700
20. Broccoli A, Casadei B, Stefoni V et al. The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients. BMC Cancer 2017; 1 (17): 1–8. DOI: 10.1186/s12885-017-3269-6
21. Smith D. Oncology 1998; 55: 284–8.
22. Martelli M, Ceriani L, Zucca E et al. [18F]Fluorodeoxyglucose Positron Emission Tomography Predicts Survival After Chemoimmunotherapy for Primary Mediastinal Large B-Cell Lymphoma: Results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol 2014; 32 (17): 1769–75. DOI: 10.1200/JCO.2013.51.7524
23. Pinnix CC, Dabaja B, Ahmed MA. Single-Institution Experience in the Treatment of Primary Mediastinal B Cell Lymphoma Treated With Immunochemotherapy in the Setting of Response Assessment by 18Fluorodeoxyglucose Positron Emission Tomography. Int J Radiation Oncol Biol Phys. Series: Radiation and the Modern Management of Lymphoma 2015; 92 (1): 113–21. DOI: 10.1016/j.ijrobp.2015.02.006
24. Aslanidi I.P, Mukhortova O.V., Katunina T.A. i dr. Sovremennye aspekty primeneniia pozitronno-emissionnoi tomografii pri limfomakh. Klin. onkogematologiia. 2015; 8 (1): 13–25. [in Russian]
25. Kuruvilla J, Pintilie M, Tsang R et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leukemia Lymphoma 2008; 49 (7): 1329–36. DOI: 10.1080/10428190802108870
26. The international non-hodgkin lymphoma prognostic factors project. NEJM 1993; 329: 987–94.
27. Moormeier JA, Williams SF, Golomb HM. The staging of non-Hodgkin's lymphomas. Semin Oncol 1990; 17: 43–50.
28. Common Toxicity Criteria of National Cancer Institute, 2005.
29. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31 (5): 1341–6.
30. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda: International Commission on Radiation Units and Measurements – 1999.
31. Emami B, Lyman J, Brown A et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. Series: Three-Dimensional Photon Treatment Planning Report of the Collaborative Working Group on the Evaluation of Treatment Planning for External Photon Beam Radiotherapy 1991; 21 (1): 109–22. DOI: 10.1016/ 0360-3016 (91)90171-Y
32. Marks LB, Yorke ED, Jackson A et al. Use of Normal Tissue Complication Probability Models in the Clinic. Int J Radiat Oncol Biol Phys. Series: Quantitative Analyses of Normal Tissue Effects in the Clinic 2010; 76 (3). Suppl.: S10–S19. DOI: 10.1016/j.ijrobp.2009.07.1754

Авторы

О.П.Трофимова*1,2, И.З.Заводнова1, Г.С.Тумян1,2, Ю.И.Прямикова1, Н.В.Волкова1, О.С.Зайченко1, А.В.Назаренко1

1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23;
2 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1
*dr.Trofimova@mail.ru

________________________________________________

O.P.Trofimova*1,2, I.Z.Zavodnova1, G.S.Tumyan1,2, Yu.I.Pryamikova1, N.V.Volkova1, O.S.Zaichenko1, A.V.Nazarenko1

1 N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
2 Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Nametkina, d. 16
*dr.Trofimova@mail.ru

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.