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Влияние коррекции нутритивной недостаточности на эффективность неоадъювантной химиотерапии у больных местно-распространенным раком желудка
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Brish NA, Semiglazova TYu, Karachun AM, Shevkunov LN, Ulyanchenko YaA, Artemyeva AS, Golovanova TS, Tkachenko EV, Alexeeva YuV, Sharashenidze SM, Strakh LV, Protsenko SA, Teletaeva GM, Filatova LV, Kasparov BS, Semiglazov VV, Belyaev AM. Influence of correction of nutritive deficiency on the effectiveness of neoadjuvant chemotherapy in patients with locally advanced gastric cancer. Journal of Modern Oncology. 2021; 23 (3): 519–524. DOI: 10.26442/18151434.2021.3.201075
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Материалы и методы. Из 200 больных МРРЖ, средний возраст 57,2 года (46,1–68,3): 100 больных получали НАХТ на фоне нутритивной поддержки (НП) с 2018 по 2020 г.; 100 больных – НАХТ без НП с 2013 по 2018 г. (исторический контроль). Нутритивный статус оценивался при помощи антропометрии, опросников (NRS-2002, MUST, GLIM), динамометрии, анализов крови, биоимпедансометрии. Оценивались осложнения по NCI CTCAE v5.0; частота объективных ответов по RECIST 1.1; патоморфологический регресс по классификации Японской ассоциации по изучению рака желудка (2017 г.); 2-летняя бессобытийная выживаемость.
Результаты. Частота НН до начала лечения в группе НАХТ+НП составила 54%; в группе НАХТ – 47%. После завершения НАХТ в группе НАХТ+НП частота НН составила 1%, в группе НАХТ без НП – 62%. У больных с НН частичный регресс зарегистрирован в группе НАХТ+НП (n=54) у 51,9% больных, в группе НАХТ (n=47) – у 27,6% (p<0,05). Частота развития осложнений в группе НАХТ+НП ниже, чем в группе НАХТ. Двухлетняя бессобытийная выживаемость у больных без НН в группе НАХТ+НП составила 100% против 68,5% в группе НАХТ (р<0,001); у больных с НН – 72,5% против 60,6% соответственно (р<0,05).
Заключение. Комплексная диагностика нутритивного статуса и проведение НП позволяют улучшить результаты НАХТ больных МРРЖ. НН является неблагоприятным прогностическим фактором эффективности НАХТ больных МРРЖ.
Ключевые слова: местно-распространенный рак желудка, нутритивный статус, нутритивная недостаточность, неоадъювантная химиотерапия
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Aim. To increase the effectiveness of neoadjuvant chemotherapy in patients with locally advanced gastric cancer by correcting nutritional deficiency.
Materials and methods. Of 200 patients with locally advanced gastric cancer (mean age 57.2 years (46.1–68.3), 100 patients received neoadjuvant chemotherapy with nutritional support from 2018 to 2020. One hundred patients received neoadjuvant chemotherapy without nutritional support from 2013 to 2018 (historical control). The incidence of nutritional deficiency before treatment in the “neoadjuvant chemotherapy + nutritional support” group was 54%, and in the “neoadjuvant chemotherapy only” group it was 47%. Nutritional status was assessed using anthropometry, questionnaires (NRS-2002, MUST, GLIM), dynamometry, blood tests, bioimpedance. Complications according to NCI CTCAE v5.0; оbjective response rate according to RECIST 1.1; pathomorphological regression according to the JGCA classification (2017); 2-year event-free survival were assessed.
Results. The frequency of nutritional deficiency before the start of treatment in the “neoadjuvant chemotherapy + nutritional support” group was 54%, in the “neoadjuvant chemotherapy only” group – 47%. After the completion of neoadjuvant chemotherapy in the group “neoadjuvant chemotherapy + nutritional support” the frequency of nutritional deficiency was 1%, in the group “neoadjuvant chemotherapy only” without nutritional support – 62%. In patients with nutritional deficiency in the “neoadjuvant chemotherapy + nutritional support” group, partial regression was registered in 51.9% of cases, in the “neoadjuvant chemotherapy only ”group it was 27.6% (p<0.05). There were no differences in the frequency of pathological response. 2-year event-free survival in patients without nutritional deficiency in the group “neoadjuvant chemotherapy + nutritional support” was 100%, in the “neoadjuvant chemotherapy only” group it was 68.5% (p<0.001); in patients with nutritional deficiency – 72,5 and 60.6% respectively (p<0.05).
Conclusion. Nutritional deficiency is an important predictive and prognostic marker of the efficacy of neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Comprehensive diagnosis of nutritional status and nutritional support can improve the results of neoadjuvant chemotherapy in patients with locally advanced gastric cancer.
Keywords: locally advanced gastric cancer, nutritional status, nutritional deficiency, neoadjuvant chemotherapy
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3. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11‑20.
4. Ychou М, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715-21. DOI:10.1200/JCO.2010.33.0597
5. Al-Batran SE, Homann N, Schmalenberg H, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. J Clin Oncol. 2017;35(15):4004.
6. Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210-8. DOI:10.1200/JCO.2009.26.6114
7. Mirkin KA, Luke FE, Gangi A, et al. Sarcopenia related to neoadjuvant chemotherapy and perioperative outcomes in resected gastric cancer: a multi-institutional analysis. J Gastrointest Oncol. 2017;8(3):589-95. DOI:10.21037/jgo.2017.03.02
8. Palmela C, Velho S, Agostinho L, et al. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer. J Gastric Cancer. 2017;17(1):74-87. DOI:10.5230/jgc.2017.17.e8
9. Kawamura T, Makuuchi R, Tokunaga M, et al. Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia. Ann Surg Oncol. 2018;25(6):1625‑32. DOI:10.1245/s10434-018-6452-3
10. Prado CM, Baracos VE, McCargar LJ, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007;13:3264‑8. DOI:10.1158/1078-0432.CCR-06-3067
11. Huang DD, Zhou CJ, Wang SL, et al. Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer. Surgery. 2017;161:680-93. DOI:10.1016/j.surg.2016.08.030
12. Chen FF, Zhang FY, Zhou XY, et al. Role of frailty and nutritional status in predicting complications following total gastrectomy with D2 lymphadenectomy in patients with gastric cancer: a prospective study. Langenbecks Arch Surg. 2016;401:813-22.
DOI:10.1007/s00423-016-1490-4
13. Zhuang CL, Huang DD, Pang WY, et al. Sarcopenia is an independent predictor of severe postoperative complications and long-term survival after radical gastrectomy for gastric cancer: analysis from a large-scale cohort. Medicine (Baltimore). 2016;95:e3164. DOI:10.1097/MD.0000000000003164
14. Wang SL, Zhuang CL, Huang DD, et al. Sarcopenia adversely impacts postoperative clinical outcomes following gastrectomy in patients with gastric cancer: a prospective study. Ann Surg Oncol. 2016;23:556-64. DOI:10.1245/s10434-015-4887-3
15. Fukuda Y, Yamamoto K, Hirao M, et al. Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy. Gastric Cancer. 2016;19:986-93. DOI:10.1007/s10120-015-0546-4
16. Tamandl D, Paireder M, Asari R, et al. Markers of sarcopenia quantified by computedtomography predict adverse long-term outcome in patients withresected oesophageal or gastro-oesophageal junction cancer. Eur Radiol. 2016;26(5):1359-67. DOI:10.1007/s00330-015-3963-1
17. Okumura S, Kaido T, Hamaguchi Y, et al. Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies. Surgery. 2016;159(3):821-33. DOI:10.1016/j.surg.2015.08.047
18. Levolger S, van Vledder MG, Muslem R, et al. Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma. J Surg Oncol. 2015;112(2):208-13. DOI:10.1002/jso.23976
19. Huang DD, Chen XX, Chen XY, et al. Sarcopenia predicts 1-year mortality in elderly patients undergoing curative gastrectomy for gastric cancer: a prospective study. J Cancer Res Clin Oncol. 2016;142:2347-56. DOI:10.1007/s00432-016-2230-4
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1. Rosania R, Chiapponi C, Malfertheiner P, Venerito M. Nutrition in Patients with Gastric Cancer: An Update. Gastrointest Tumors. 2016;2(4):178-87. DOI:10.1159/000445188
2. Weimann A, Braga M, Carli F, et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017;36(3):623-50. DOI:10.1016/j.clnu.2017.02.013
3. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11‑20.
4. Ychou М, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715-21. DOI:10.1200/JCO.2010.33.0597
5. Al-Batran SE, Homann N, Schmalenberg H, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. J Clin Oncol. 2017;35(15):4004.
6. Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210-8. DOI:10.1200/JCO.2009.26.6114
7. Mirkin KA, Luke FE, Gangi A, et al. Sarcopenia related to neoadjuvant chemotherapy and perioperative outcomes in resected gastric cancer: a multi-institutional analysis. J Gastrointest Oncol. 2017;8(3):589-95. DOI:10.21037/jgo.2017.03.02
8. Palmela C, Velho S, Agostinho L, et al. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer. J Gastric Cancer. 2017;17(1):74-87. DOI:10.5230/jgc.2017.17.e8
9. Kawamura T, Makuuchi R, Tokunaga M, et al. Long-Term Outcomes of Gastric Cancer Patients with Preoperative Sarcopenia. Ann Surg Oncol. 2018;25(6):1625‑32. DOI:10.1245/s10434-018-6452-3
10. Prado CM, Baracos VE, McCargar LJ, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007;13:3264‑8. DOI:10.1158/1078-0432.CCR-06-3067
11. Huang DD, Zhou CJ, Wang SL, et al. Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer. Surgery. 2017;161:680-93. DOI:10.1016/j.surg.2016.08.030
12. Chen FF, Zhang FY, Zhou XY, et al. Role of frailty and nutritional status in predicting complications following total gastrectomy with D2 lymphadenectomy in patients with gastric cancer: a prospective study. Langenbecks Arch Surg. 2016;401:813-22.
DOI:10.1007/s00423-016-1490-4
13. Zhuang CL, Huang DD, Pang WY, et al. Sarcopenia is an independent predictor of severe postoperative complications and long-term survival after radical gastrectomy for gastric cancer: analysis from a large-scale cohort. Medicine (Baltimore). 2016;95:e3164. DOI:10.1097/MD.0000000000003164
14. Wang SL, Zhuang CL, Huang DD, et al. Sarcopenia adversely impacts postoperative clinical outcomes following gastrectomy in patients with gastric cancer: a prospective study. Ann Surg Oncol. 2016;23:556-64. DOI:10.1245/s10434-015-4887-3
15. Fukuda Y, Yamamoto K, Hirao M, et al. Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy. Gastric Cancer. 2016;19:986-93. DOI:10.1007/s10120-015-0546-4
16. Tamandl D, Paireder M, Asari R, et al. Markers of sarcopenia quantified by computedtomography predict adverse long-term outcome in patients withresected oesophageal or gastro-oesophageal junction cancer. Eur Radiol. 2016;26(5):1359-67. DOI:10.1007/s00330-015-3963-1
17. Okumura S, Kaido T, Hamaguchi Y, et al. Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies. Surgery. 2016;159(3):821-33. DOI:10.1016/j.surg.2015.08.047
18. Levolger S, van Vledder MG, Muslem R, et al. Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma. J Surg Oncol. 2015;112(2):208-13. DOI:10.1002/jso.23976
19. Huang DD, Chen XX, Chen XY, et al. Sarcopenia predicts 1-year mortality in elderly patients undergoing curative gastrectomy for gastric cancer: a prospective study. J Cancer Res Clin Oncol. 2016;142:2347-56. DOI:10.1007/s00432-016-2230-4
Б.С. Каспаров1, В.В. Семиглазов1,3, А.М. Беляев1,2
1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Россия;
3 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Санкт-Петербург, Россия
*elenatkachen@yandex.ru
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Nadezhda A. Brish1, Tatiana Yu. Semiglazova*1,2, Aleksei M. Karachun1, Lev N. Shevkunov1, Yana A. Ulyanchenko1, Anna S. Artemyeva1, Tatiana S. Golovanova1, Elena V. Tkachenko1, Yuliia V. Alexeeva1, Sofiko M. Sharashenidze1, Liubov V. Strakh3, Svetlana A. Protsenko1, Gulfiia M. Teletaeva1, Larisa V. Filatova1,2, Boris S. Kasparov1,
Vladislav V. Semiglazov1,3, Aleksei M. Belyaev1,2
1 Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia;
2 Mechnikov North-Western State Medical University, Saint Petersburg, Russia;
3 Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia
*elenatkachen@yandex.ru