surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2020-10-3-249-253surgonco-513Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSПерспективы химиотерапии гастроинтестинальных стромальных опухолей толстой кишкиProspects of Chemotherapy for Gastrointestential Stromal Colon TumoursМухамедияровА. Р.MukhamediyarovA. R.

онкологическое отделение,

Республика Башкортостан, Уфа

Oncology Department,

Ufa

https://orcid.org/0000-0001-5370-7796БашироваЛ. И.BashirovaL. I.

кафедра фармакологии с курсом клинической фармакологии, 

Республика Башкортостан, Уфа

Department of Pharmacology with a course of Clinical Pharmacology, 

Ufa

lindadeireko.lb@gmail.comМаксютоваА. И.MaksyutovaA. I.

врач-ординатор,

Москва

Resident,

Moscow

ГаттароваА. Т.GattarovaA. T.

врач-ординатор,

Москва

Resident,

Moscow

Республиканская клиническая больница им. Г.Г. КуватоваРоссияKuvatov Republican Clinical HospitalRussian FederationБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian FederationГосударственный научный центр Российской Федерации — Федеральный медицинский биофизический центр имени А.И. БурназянаРоссияBurnazyan Federal Medical Biophysical CentreRussian Federation202030112020103249253Copyright © Мухамедияров А.Р., Баширова Л.И., Максютова А.И., Гаттарова А.Т., 20202020Мухамедияров А.Р., Баширова Л.И., Максютова А.И., Гаттарова А.Т.Mukhamediyarov A.R., Bashirova L.I., Maksyutova A.I., Gattarova A.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/513

Гастроинтестинальные стромальные опухоли  — наиболее распространенная первичная мезенхимальная опухоль желудочно-кишечного тракта. По данным статистики, ежегодная заболеваемость в России составляет 13 больных на 1 млн жителей, что в среднем составляет около 2000 больных в год, в США регистрируется от 3000 до 4000 больных в год. В статье представлены общие и частные вопросы заболеваемости и смертности от гастроинтестинальных стромальных опухолей, причины частой неэффективности хирургической и таргетной терапии, предложены варианты комбинированого лечения пациентов с гастроинтестинальными стромальными опухолями. С развитием иммуногистохимического анализа лечение данных опухолей эволюционировало вместе с терапией, направленной против специфичных KIT/PDGFRA протоонкогенов. Использование низкомолекулярных ингибиторов киназы совершило революцию в  терапии. Однако по-прежнему только полное хирургическое удаление гастроинтестинальных стромальных опухолей толстой кишки позволяет увеличить общую безрецидивную выживаемость. В оперативном лечении можно выделить три основных подхода: начальный этап лечения, если опухоль резектабельна и имеет небольшие размеры; хирургическое лечение после неоадъювантной терапии; симптоматическое лечение, так называемая debulking surgery. Адъювантная таргетная терапия иматинибом позволяет добиться высокого общего объективного ответа. Применение химиотерапии иматинибом обуславливает в большинстве случаев эффективность и радикальность хирургического лечения. В целом проблема лечения гастроинтестинальных стромальных опухолей толстой кишки далека от своего окончательного решения и требует тщательного изучения и объективной оценки всех технических и тактических подходов в свете отдаленных результатов.

Gastrointetinal stromal tumours are the most common primary mesenchymal tumours of the gastrointestinal tract. According to statistical data, the annual incidence of this pathology in Russia comprises 13 patients per 1 million inhabitants, i.e. about 2,000 patients per year on average. In the United States, 3,000–4,000 cases are registered every year. This article discusses general and specific issues associated with morbidity and mortality from gastrointestinal stromal tumours, as well as reasons for the low efficacy of surgical and targeted therapies. Methods for combined treatment of patients with gastrointestinal stromal tumours are proposed. The treatment of such pathologies has evolved with the development of immunohystochemical analytical procedures and therapies against KIT/PDGFRA-specific protooncogenes, as well as the emergence of low-molecular kinase inhibitors. However, the probability of non-recurrence survival can only be increased by complete surgical removal of gastrointestinal stromal colon tumours. In the surgical treatment, three main approaches are defined: the initial stage of treatment, provided that the tumour is resectable and has a small size; surgical treatment after neoadjuvant therapy; symptomatic treatment, so-called ‘debulking surgery’. Adjuvant targeted therapy with Imatinib provides for a high objective response. The use of Imatinib chemotherapy determines the efficacy and radicality of surgical treatment in most cases. In general, the question of treating gastrointestinal stromal colon tumours is still relevant, requiring further research and objective evaluation of all technical and tactical approaches in the context of distant results.

гастроинтестинальные стромальные опухолижелудочно-кишечные болезниадъювантная химиотерапияиматинибпротоонкогена белки c‑kitgastrointestinal stromal tumoursgastrointestinal diseasesadjuvant chemotherapyImatinibproto-oncogene proteins c-kitReferencesНикулин М.П., Стилиди И.С. Эпидемиология гастроинтестинальных стромальных опухолей. Регистр в России: первый опыт. Современная онкология. 2009;11(2):50–3.Nikulin M.P., Stilidi I.S. Epidemiology of gastrointestinal stromal tumors. Register in Russia: first experience. Journal of Modern Oncology. 2009;11(2):50–3 (In Russ.).Joensuu H., Eriksson M., Sundby Hall K., Hartmann J.T., Pink D., Schütte J., et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012;307(12):1265–72. DOI: 10.1001/jama.2012.347Joensuu H., Eriksson M., Sundby Hall K., Hartmann J.T., Pink D., Schütte J., et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012;307(12):1265–72. DOI: 10.1001/jama.2012.347Schöffel N., Groneberg D.A., Kaul T., Laatsch D., Thielemann H. Gastrointestinal stromal tumors (GIST) — literature review. MMW Fortschr Med. 2016;158(3):60–2. DOI: 10.1007/s15006-016-7824-xSchöffel N., Groneberg D.A., Kaul T., Laatsch D., Thielemann H. Gastrointestinal stromal tumors (GIST) — literature review. MMW Fortschr Med. 2016;158(3):60–2. DOI: 10.1007/s15006-016-7824-xLópez-Tomassetti Fernández E.M., Hernández Hernández J.R., Nuñez Jorge V. Perforated gastrointestinal stromal tumor in Meckel’s diverticulum treated laparoscopically. Asian J Endosc Surg. 2013;6(2):126–9. DOI: 10.1111/ases.12016López-Tomassetti Fernández E.M., Hernández Hernández J.R., Nuñez Jorge V. Perforated gastrointestinal stromal tumor in Meckel’s diverticulum treated laparoscopically. Asian J Endosc Surg. 2013;6(2):126–9. DOI: 10.1111/ases.12016Prablek M., Srinivasan V.M., Srivatsan A., Holdener S., Oneissi M., Heck K.A., et al. Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature. BMC Cancer. 2019;19(1):1119. DOI: 10.1186/s12885-019-6316-7Prablek M., Srinivasan V.M., Srivatsan A., Holdener S., Oneissi M., Heck K.A., et al. Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature. BMC Cancer. 2019;19(1):1119. DOI: 10.1186/s12885-019-6316-7Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019;35(6):555–9. DOI: 10.1097/MOG.0000000000000584Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019;35(6):555–9. DOI: 10.1097/MOG.0000000000000584Demetri G.D., Titton R.L., Ryan D.P., Fletcher C.D. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 32-2004. A 68-year-old man with a large retroperitoneal mass. N Engl J Med. 2004;351(17):1779–87. DOI: 10.1056/NEJMcpc049024Demetri G.D., Titton R.L., Ryan D.P., Fletcher C.D. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 32-2004. A 68-year-old man with a large retroperitoneal mass. N Engl J Med. 2004;351(17):1779–87. DOI: 10.1056/NEJMcpc049024Liu L., Zhu Y., Wang D., Yang C., Zhang Q.I., Li X., et al. Coexisting and possible primary extra-gastrointestinal stromal tumors of the pancreas and liver: A single case report. Oncol Lett. 2016;11(5):3303–7. DOI: 10.3892/ol.2016.4420Liu L., Zhu Y., Wang D., Yang C., Zhang Q.I., Li X., et al. Coexisting and possible primary extra-gastrointestinal stromal tumors of the pancreas and liver: A single case report. Oncol Lett. 2016;11(5):3303–7. DOI: 10.3892/ol.2016.4420Waidhauser J., Bornemann A., Trepel M., Märkl B. Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia. World J Gastroenterol. 2019;25(30):4261–77. DOI: 10.3748/wjg.v25.i30.4261Waidhauser J., Bornemann A., Trepel M., Märkl B. Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia. World J Gastroenterol. 2019;25(30):4261–77. DOI: 10.3748/wjg.v25.i30.4261Kawanowa K., Sakuma Y., Sakurai S., Hishima T., Iwasaki Y., Saito K., et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Human Pathol. 2006;37(12):1527–35. DOI: 10.1016/j.humpath.2006.07.002Kawanowa K., Sakuma Y., Sakurai S., Hishima T., Iwasaki Y., Saito K., et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Human Pathol. 2006;37(12):1527–35. DOI: 10.1016/j.humpath.2006.07.002Tan C.B., Zhi W., Shahzad G., Mustacchia P. Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol. 2012;2012:595968. DOI: 10.5402/2012/595968Tan C.B., Zhi W., Shahzad G., Mustacchia P. Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol. 2012;2012:595968. DOI: 10.5402/2012/595968Ip C.K.M., Ng P.K.S., Jeong K.J., Shao S.H., Ju Z., Leonard P.G., et al. Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies. Nat Commun. 2018;9(1):4583. DOI: 10.1038/s41467-018-06949-wIp C.K.M., Ng P.K.S., Jeong K.J., Shao S.H., Ju Z., Leonard P.G., et al. Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies. Nat Commun. 2018;9(1):4583. DOI: 10.1038/s41467-018-06949-wСафонов А.С., Забелин М.В. Формирование колостомы из мини-доступа и колоректальное стентирование при острой толстокишечной непроходимости опухолевого генеза. Здравоохранение, образование и безопасность. 2017;(3):42–8.Safonov A.S., Zabelin M.V. Making colostomy from short-scar incision and colorectal stenting in acute colonic obstruction of tumoral genesis. Healthcare, education and security. 2017;(3):42–8 (In Russ.).Khoshnood A. Gastrointestinal stromal tumor — A review of clinical studies. J Oncol Pharm Pract. 2019;25(6):1473–85. DOI: 10.1177/1078155219846955Khoshnood A. Gastrointestinal stromal tumor — A review of clinical studies. J Oncol Pharm Pract. 2019;25(6):1473–85. DOI: 10.1177/1078155219846955Нагаева В.В., Кокорева Е.Г., Елисеев Е.В. Тканеспецифические антитела и продолжительность заболевания: диагностическое и прогностическое значение. Здравоохранение, образование и безопасность. 2015;(2):17–9.Nagaeva V.V., Kokoreva E.G., Eliseev E.V. Tissue-specific antibodies and duration of the disease: diagnostic and prognostic value. Healthcare, education and security. 2015;(2):17–9 (In Russ.).Guo W., Yang Z., Wei Y., Qin X., Li C., Huang R., et al. Radical excision versus local resection for primary rectal gastrointestinal stromal tumors. Cohort Study. Int J Surg. 2020;77:190–7. DOI: 10.1016/j.ijsu.2020.03.068Guo W., Yang Z., Wei Y., Qin X., Li C., Huang R., et al. Radical excision versus local resection for primary rectal gastrointestinal stromal tumors. Cohort Study. Int J Surg. 2020;77:190–7. DOI: 10.1016/j.ijsu.2020.03.068Yang Z., Feng X., Zhang P., Chen T., Qiu H., Zhou Z., et al. Clinicopathological features and prognosis of 276 cases of primary small (≤2 cm) gastric gastrointestinal stromal tumors: a multicenter data review. Surg Endosc. 2019;33(9):2982–90. DOI: 10.1007/s00464-018-6564-7Yang Z., Feng X., Zhang P., Chen T., Qiu H., Zhou Z., et al. Clinicopathological features and prognosis of 276 cases of primary small (≤2 cm) gastric gastrointestinal stromal tumors: a multicenter data review. Surg Endosc. 2019;33(9):2982–90. DOI: 10.1007/s00464-018-6564-7Patel D.J., Lutfi W., Sweigert P., Eguia E., Abood G., Knab L., et al. Adjuvant systemic therapy for intermediate and large gastric gastrointestinal stromal tumors (GISTs): Is there a survival benefit following margin negative surgical resection? Am J Surg. 2020;219(3):436–9. DOI: 10.1016/j.amjsurg.2019.10.014Patel D.J., Lutfi W., Sweigert P., Eguia E., Abood G., Knab L., et al. Adjuvant systemic therapy for intermediate and large gastric gastrointestinal stromal tumors (GISTs): Is there a survival benefit following margin negative surgical resection? Am J Surg. 2020;219(3):436–9. DOI: 10.1016/j.amjsurg.2019.10.014Wolfe C.R., Reyna V.F., Widmer C.L., Cedillos-Whynott E.M., BrustRenck P.G., Weil A.M., et al. Understanding genetic breast cancer risk: processing loci of the BRCA gist intelligent tutoring system. Learn Individ Differ. 2016;49:178–89. DOI: 10.1016/j.lindif.2016.06.009Wolfe C.R., Reyna V.F., Widmer C.L., Cedillos-Whynott E.M., BrustRenck P.G., Weil A.M., et al. Understanding genetic breast cancer risk: processing loci of the BRCA gist intelligent tutoring system. Learn Individ Differ. 2016;49:178–89. DOI: 10.1016/j.lindif.2016.06.009Vetto J.T. Role of imatinib in the management of early, operable, and advanced GI stromal tumors (GISTs). Onco Targets Ther. 2009;2:151– 9. DOI: 10.2147/ott.s4740Vetto J.T. Role of imatinib in the management of early, operable, and advanced GI stromal tumors (GISTs). Onco Targets Ther. 2009;2:151– 9. DOI: 10.2147/ott.s4740Li G.Z., Raut C.P. Targeted therapy and personalized medicine in gastrointestinal stromal tumors: drug resistance, mechanisms, and treatment strategies. Onco Targets Ther. 2019;12:5123–33. DOI: 10.2147/OTT.S180763Li G.Z., Raut C.P. Targeted therapy and personalized medicine in gastrointestinal stromal tumors: drug resistance, mechanisms, and treatment strategies. Onco Targets Ther. 2019;12:5123–33. DOI: 10.2147/OTT.S180763Boichuk S., Galembikova A., Dunaev P., Valeeva E., Shagimardanova E., Gusev O., et al. Novel receptor tyrosine kinase switch promotes gastrointestinal stromal tumor drug resistance. Molecules. 2017;22(12):2152. DOI: 10.3390/molecules22122152Boichuk S., Galembikova A., Dunaev P., Valeeva E., Shagimardanova E., Gusev O., et al. Novel receptor tyrosine kinase switch promotes gastrointestinal stromal tumor drug resistance. Molecules. 2017;22(12):2152. DOI: 10.3390/molecules22122152Laurent M., Brahmi M., Dufresne A., Meeus P., Karanian M., RayCoquard I., et al. Adjuvant therapy with imatinib in gastrointestinal stromal tumors (GISTs)-review and perspectives. Transl Gastroenterol Hepatol. 2019;4:24. DOI: 10.21037/tgh.2019.03.07Laurent M., Brahmi M., Dufresne A., Meeus P., Karanian M., RayCoquard I., et al. Adjuvant therapy with imatinib in gastrointestinal stromal tumors (GISTs)-review and perspectives. Transl Gastroenterol Hepatol. 2019;4:24. DOI: 10.21037/tgh.2019.03.07Колесник Е.А., Лесной И.И., Махмудов Д.Э., Лукашенко А.В., Приймак В.В., Жуков Ю.А. и др. Результаты применения мультимодальной программы Fast track surgery в хирургическом лечении больных раком ободочной кишки. Евразийский онкологический журнал. 2015;(2):85–97.Kolesnik E.1, Lisnoy I.1, Mahmudov D.1, Lukashenko A.1, Priymak V.1, Zhukov Y. Results of a multimodal program Fast track surgery implementation in surgical treatment of patients with colon cancer. Eurasian journal of oncology. 2015;(2):85–97 (In Russ.).Yamaoka T., Kusumoto S., Ando K., Ohba M., Ohmori T. Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci. 2018;19(11):3491. DOI: 10.3390/ijms19113491Yamaoka T., Kusumoto S., Ando K., Ohba M., Ohmori T. Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci. 2018;19(11):3491. DOI: 10.3390/ijms19113491Taylor M., Coleman R.L., Sood A.K. The role of angiogenesis in cancer. In: Tsimberidou A.-M., Kurzrock R., Anderson K.C. (editors). Target therapy in translational cancer research. Wiley-Blackwell; 2015:64–71. DOI: 10.1002/9781118468678Taylor M., Coleman R.L., Sood A.K. The role of angiogenesis in cancer. In: Tsimberidou A.-M., Kurzrock R., Anderson K.C. (editors). Target therapy in translational cancer research. Wiley-Blackwell; 2015:64–71. DOI: 10.1002/9781118468678 27 Rajabi M., Mousa S.A. The role of angiogenesis in cancer treatment. Biomedicines. 2017;5(2):34. DOI: 10.3390/biomedicines5020034Rajabi M., Mousa S.A. The role of angiogenesis in cancer treatment. Biomedicines. 2017;5(2):34. DOI: 10.3390/biomedicines5020034International Agency for Research on Cancer. World cancer report 2014. In: Stewart B.W., Wild C.P. (editors). World Cancer Report. Lyon: International Agency for Research on Cancer; 2015.International Agency for Research on Cancer. World cancer report 2014. In: Stewart B.W., Wild C.P. (editors). World Cancer Report. Lyon: International Agency for Research on Cancer; 2015.Zabelin M.V., Seryakov A.P., Safonov A.S. Colonic GIST: what do we know today? Coloproctology. 2015;(S1):67a–8 (In Russ.). 30 Joensuu H., Vehtari A., Riihimäki J., Nishida T., Steigen S.E., Brabec P., et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265–74. DOI: 10.1016/S1470-2045(11)70299-6Забелин М.В., Серяков А.П., Сафонов А.С. GIST толстой кишки: что нам известно на сегодняшний день? Колопроктология. 2015;(S1):67a–8.Забелин М.В., Серяков А.П., Сафонов А.С. GIST толстой кишки: что нам известно на сегодняшний день? Колопроктология. 2015;(S1):67a–8.Joensuu H., Vehtari A., Riihimäki J., Nishida T., Steigen S.E., Brabec P., et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265–74. DOI: 10.1016/S1470-2045(11)70299-6Joensuu H., Vehtari A., Riihimäki J., Nishida T., Steigen S.E., Brabec P., et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265–74. DOI: 10.1016/S1470-2045(11)70299-6

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