oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2019-18-5-80-85oncotomsk-1193Research ArticleОПЫТ РАБОТЫ ОНКОЛОГИЧЕСКИХ УЧРЕЖДЕНИЙONCOLOGY PRACTICEОСОБЕННОСТИ ЛЕЧЕНИЯ ПАЦИЕНТОВ С НЕЙРОЭНДОКРИННОЙ ОПУХОЛЬЮ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ В ЗАВИСИМОСТИ ОТ ДИФФЕРЕНЦИРОВКИTREATMENT OF PATIENTS WITH PANCREATIC NEUROENDOCRINE TUMOURS DEPENDING ON THE DIFFERENTIATION GRADEИсянгуловаА. З.IsyangulovaA. Z.

Исянгулова Алина Зульфатовна, врач-онколог

г. Казань, 420029, ул. Сибирский тракт, 29

SPIN-код: 2245-6327

Alina Z. Isyangulova, MD, oncologist

29, Sibirski tract, 420029-Kazan

a.isyangulova@rambler.ruХасановР. Ш.KhasanovR. Sh.

Хасанов Рустем Шамильевич, доктор медицинских наук, член-корреспондент РАН, профессор, главный онколог ПФО и РТ, директор

г. Казань, 420012, ул. Бутлерова, 36

SPIN-код: 9198-5989

Rustem Sh. Khasanov, MD, Professor, Corresponding Member of Russian Academy of Sciences, Honored Physician of RF and TR, Director

36, Butlerov Street, 420012-Kazan

ЕникеевР. Ф.EnikeevR. F.

Еникеев Рафаэль Фаридович, кандидат медицинских наук, врач-онколог

г. Казань, 420029, ул. Сибирский тракт, 29

SPIN-код: 8333-4247

Rafael F. Enikeev, MD, PhD

29, Sibirski tract, 420029-Kazan

ГордиевМ. Г.GordievM. G.

Гордиев Марат Гордиевич

г. Санкт-Петербург, 194100, ул. Литовская, 17А

SPIN-код: 8388-3566

Marat G. Gordiev

17A, Litovskaya Street, 194100-St. Petersburg

ГАУЗ «Республиканский клинический онкологический диспансер» Министерства здравоохранения Республики ТатарстанРоссияTatarstan Cancer CenterRussian FederationКазанская государственная медицинская академия – филиал ФГБОУ ДПО образования» Министерства здравоохранения Российской ФедерацииРоссияKazan State Medical Academy – Branch of Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian FederationRussian FederationООО «Национальный БиоСервис»РоссияNational BioServiceRussian Federation2019011120191858085Copyright © Исянгулова А.З., Хасанов Р.Ш., Еникеев Р.Ф., Гордиев М.Г., 20192019Исянгулова А.З., Хасанов Р.Ш., Еникеев Р.Ф., Гордиев М.Г.Isyangulova A.Z., Khasanov R.S., Enikeev R.F., Gordiev M.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1193

В последние десятилетия наблюдается рост заболеваемости нейроэндокринными опухолями, в связи с чем возрос интерес к методам лечения данной патологии.

Целью исследования явился анализ результатов лечения пациентов с нейроэндокринными опухолями поджелудочной железы (НЭПЖ) в зависимости от гистологической дифференцировки опухоли.

Материал и методы

Материал и методы. Проведен ретроспективный анализ историй болезни 1077 пациентов с новообразованиями поджелудочной железы, у 50 из них была диагностирована нейроэндокринная опухоль. Проанализированы результаты лечения с учетом дифференцировки опухоли, стадии процесса, объема оперативного лечения и лекарственной терапии.

Результаты

Результаты. Самой гистологически частой формой нейроэндокринной опухоли поджелудочной железы является G1, при которой получены лучшие показатели 1и 3-летней выживаемости вне зависимости от стадии процесса. Факторами, влияющими на прогноз течения опухолевого процесса нейроэндокринных опухолей поджелудочной железы, являются радикальное хирургическое лечение, уровень экспрессии Ki67, степень дифференцировки G1–3, стадия опухолевого процесса на момент постановки диагноза.

The incidence of neuroendocrine tumors has significantly increased over the last years.

The purpose of the study was to analyze treatment outcomes in patients with pancreatic endocrine tumors (PETs) with regard to histopathologic diagnosis.

Material and Methods

Material and Methods. The clinical records of 1077 patients with pancreatic tumors were retrospectively analyzed. Fifty patients were diagnosed with PET. Treatment outcomes were assessed with regard to tumor differentiation grade, tumor stage, extent of surgery and drug therapy.

Results

Results. The most common histological grade was G1. Patients with G1 tumors had the best 1-and 3-year survival rates regardless of tumor stage. Factors influencing prognosis in patients with PETs were: radical surgery, Ki67 expression level, histological grade (G1–3), tumor stage at diagnosis.

нейроэндокринные опухоли поджелудочной железыкарциноидстепень дифференцировкистадия процессатаргетная терапиясоматостатинpancreatic neuroendocrine tumorscarcinoid tumorsdifferentiation gradetumor stagetargeted therapysomatostatinReferencesStrosberg J.R., Coppola D., Klimstra D.S., Phan A.T., Kulke M.H., Wiseman G.A., Kvols L.K.; North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010 Aug; 39(6): 799–800. doi: 10.1097/MPA.0b013e3181ebb56f.Strosberg J.R., Coppola D., Klimstra D.S., Phan A.T., Kulke M.H., Wiseman G.A., Kvols L.K.; North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010 Aug; 39(6): 799–800. doi: 10.1097/MPA.0b013e3181ebb56f.Yao J.C., Hassan M., Phan A., Dagohoy C., Leary C., Mares J.E., Abdalla E.K., Fleming J.B., Vauthey J.N., Rashid A., Evans D.B. One hundred years after «carcinoid»: epidemiology of and prognostiс factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20; 26(18): 3063–72. doi: 10.1200/JCO.2007.15.4377.Yao J.C., Hassan M., Phan A., Dagohoy C., Leary C., Mares J.E., Abdalla E.K., Fleming J.B., Vauthey J.N., Rashid A., Evans D.B. One hundred years after «carcinoid»: epidemiology of and prognostiс factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20; 26(18): 3063–72. doi: 10.1200/JCO.2007.15.4377.Горбунова В.А. Нейроэндокринные опухоли. Общие принципы диагностики и лечения. М., 2015, 456.Gorbunova V.A. Neuroendocrine tumors. General principles of diagnostics and treatment. Moscow, 2015, 456. (in Russian).Ramage J.K., Davies A.H., Ardill J., Bax N., Caplin M., Grossman A., Hawkins R., McNicol A.M., Reed N., Sutton R., Thakker R., Aylwin S., Breen D., Britton K., Buchanan K., Corrie P., Gillams A., Lewington V., McCance D., Meeran K., Watkinson A.; UKNETwork for Neuroendocrine Tumours. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005 Jun; 54 Suppl 4: iv1–16. doi: 10.1136/gut.2004.053314.Ramage J.K., Davies A.H., Ardill J., Bax N., Caplin M., Grossman A., Hawkins R., McNicol A.M., Reed N., Sutton R., Thakker R., Aylwin S., Breen D., Britton K., Buchanan K., Corrie P., Gillams A., Lewington V., McCance D., Meeran K., Watkinson A.; UKNETwork for Neuroendocrine Tumours. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005 Jun; 54 Suppl 4: iv1–16. doi: 10.1136/gut.2004.053314.Halfdanarson T.R., Rabe K.G., Rubin J., Petersen G.M. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008 Oct; 19(10): 1727–33. doi: 10.1093/annonc/mdn351.Halfdanarson T.R., Rabe K.G., Rubin J., Petersen G.M. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008 Oct; 19(10): 1727–33. doi: 10.1093/annonc/mdn351.Kim M.K. Neuroendocrine Tumors: A Multidisciplinary Approach. Gastroenterology. 2017; 152(4): 910. doi: https://doi.org/10.1053/j.gastro.2017.01.023.Kim M.K. Neuroendocrine Tumors: A Multidisciplinary Approach. Gastroenterology. 2017; 152(4): 910. doi: https://doi.org/10.1053/j.gastro.2017.01.023.Klimstra D., Arnold R., Capella C. Neuroendocrine neoplasms of the pancreas. WHO Classification of Tumors of the Digestive System. 4th Ed. Lyon: IARC. 2010; 12: 322.Klimstra D., Arnold R., Capella C. Neuroendocrine neoplasms of the pancreas. WHO Classification of Tumors of the Digestive System. 4th Ed. Lyon: IARC. 2010; 12: 322.Oberg K. Neuroendocrine gastrointestinal tumors A condensed overview of diagnosis and treatment. Ann Oncol. 1999; 10(2): S3–S8. doi: 10.1093/annonc/10.suppl_2.s3.Oberg K. Neuroendocrine gastrointestinal tumors A condensed overview of diagnosis and treatment. Ann Oncol. 1999; 10(2): S3–S8. doi: 10.1093/annonc/10.suppl_2.s3.Симоненко В.Б., Дудин П.А., Маканин М.А. Нейроэндокринные опухоли. М., 2010, 237.Simonenko V.B., Dudin P.A., Makanin M.A. Neuroendocrine tumors. Moscow; 2010, 237. (in Russian).Shkarban V., Nichitaylo M., Scums A. Surgical treatment of malignant nonfunctioning neuroendocrine tumors of the pancreas. Ann Oncol. 2013 June; 24(4): 85. doi: 10.1093/annonc/mdt203.170.Shkarban V., Nichitaylo M., Scums A. Surgical treatment of malignant nonfunctioning neuroendocrine tumors of the pancreas. Ann Oncol. 2013 June; 24(4): 85. doi: 10.1093/annonc/mdt203.170.Öberg K.U., Knigge D., Kwekkeboom A., Perrenon behalf of the ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2012; 23(7): 24–30. doi: 10.1093/annonc/mds295.Öberg K.U., Knigge D., Kwekkeboom A., Perrenon behalf of the ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2012; 23(7): 24–30. doi: 10.1093/annonc/mds295.Halfdanarson T.R., Rabe K.G., Rubin J., Petersen G.M. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008; 19(10): 1727–33. doi: 10.1093/annonc/mdn351.Halfdanarson T.R., Rabe K.G., Rubin J., Petersen G.M. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008; 19(10): 1727–33. doi: 10.1093/annonc/mdn351.Moertel C.G., Kvols L.K., O’Connell M.J., Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin: evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991; 68: 227–232. doi: 10.1002/1097-0142(19910715)68:2<227::aid-cncr2820680202>3.0.co;2-i.Moertel C.G., Kvols L.K., O’Connell M.J., Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin: evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991; 68: 227–232. doi: 10.1002/1097-0142(19910715)68:2<227::aid-cncr2820680202>3.0.co;2-i.Vilar E., Salazar R., Pérez-García J., Cortes J., Oberg K., Tabernero J. Chemotherapy and role of the proliferation marker ki-67 in digestive neuroendocrine tumors. Endocr Relat Cancer. 2007; 14: 221–232. doi: 10.1677/ERC-06-0074.Vilar E., Salazar R., Pérez-García J., Cortes J., Oberg K., Tabernero J. Chemotherapy and role of the proliferation marker ki-67 in digestive neuroendocrine tumors. Endocr Relat Cancer. 2007; 14: 221–232. doi: 10.1677/ERC-06-0074.Childs A., Kirkwood A., Edeline J., Luong T.V., Watkins J., Lamarca A., Alrifai D., Nsiah-Sarbeng P., Gillmore R., Mayer A., Thirlwell C., Sarker D., Valle J.W., Meyer T. Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours. Endocr Relat Cancer. 2016; 563–570. doi: 10.1530/ERC-16-0099.Childs A., Kirkwood A., Edeline J., Luong T.V., Watkins J., Lamarca A., Alrifai D., Nsiah-Sarbeng P., Gillmore R., Mayer A., Thirlwell C., Sarker D., Valle J.W., Meyer T. Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours. Endocr Relat Cancer. 2016; 563–570. doi: 10.1530/ERC-16-0099.Rinke A., Müller H.H., Schade-Brittinger C., Klose K.J., Barth P., Wied M., Mayer C., Aminossadati B., Pape U.F., Bläker M., Harder J., Arnold C., Gress T., Arnold R.; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1; 27(28): 4656–63. doi: 10.1200/JCO.2009.22.8510.Rinke A., Müller H.H., Schade-Brittinger C., Klose K.J., Barth P., Wied M., Mayer C., Aminossadati B., Pape U.F., Bläker M., Harder J., Arnold C., Gress T., Arnold R.; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1; 27(28): 4656–63. doi: 10.1200/JCO.2009.22.8510.Caplin M.E., Pavel M., Ruszniewski P. Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors. N Engl J Med. 2014 Oct 16; 371(16): 1556–7. doi: 10.1056/NEJMc1409757.Caplin M.E., Pavel M., Ruszniewski P. Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors. N Engl J Med. 2014 Oct 16; 371(16): 1556–7. doi: 10.1056/NEJMc1409757.Yao J.C., Shah M.H., Ito T. A randomized, double-blind, placebocontrolled, multicenter phase III trial of everolimus in patients with advanced pancreatic neuroendocrine tumors (PNET) (RADIANT-3). 35th ESMO Congress; 2010 Oct 8–12; Milan. LBA9.Yao J.C., Shah M.H., Ito T. A randomized, double-blind, placebocontrolled, multicenter phase III trial of everolimus in patients with advanced pancreatic neuroendocrine tumors (PNET) (RADIANT-3). 35th ESMO Congress; 2010 Oct 8–12; Milan. LBA9.Симоненко В.Б., Дулин П.А., Маканин М.А. Возможности таргетной терапии нейроэндокринных опухолей. Клиническая медицина. 2014; 92(8): 5–14.Simonenko V.B., Dulin P.A., Makanin M.A. Possibilities for targeted therapy of neuroendocrine tumours. Clinical Medicine. 2014; 92(8): 5–14. (in Russian).Wimmel A., Wiedenmann B., Rosewicz S. Autocrine growth inhibition by transforming growth factor beta-1 (TGFbeta-1) in human neuroendocrine tumour cells. Gut. 2003 Sep; 52(9): 1308–16. doi: 10.1136/gut.52.9.1308.Wimmel A., Wiedenmann B., Rosewicz S. Autocrine growth inhibition by transforming growth factor beta-1 (TGFbeta-1) in human neuroendocrine tumour cells. Gut. 2003 Sep; 52(9): 1308–16. doi: 10.1136/gut.52.9.1308.von Marschall Z., Scholz A., Cramer T., Schafer G., Schirner M., Oberg K., Wiedenmann B., Hocker M., Rosewicz S. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst. 2003 Mar 19; 95(6): 437–48. doi: 10.1093/jnci/95.6.437.von Marschall Z., Scholz A., Cramer T., Schafer G., Schirner M., Oberg K., Wiedenmann B., Hocker M., Rosewicz S. Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst. 2003 Mar 19; 95(6): 437–48. doi: 10.1093/jnci/95.6.437.Chaudhry A., Papanicolaou V., Oberg K., Heldin C.H., Funa K. Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res.1992; 52: 1006–1012.Chaudhry A., Papanicolaou V., Oberg K., Heldin C.H., Funa K. Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res.1992; 52: 1006–1012.Wulbrand U., Remmert G., Zofel P., Wied M., Arnold R., Fehmann H.C. mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours. Eur J Clin Invest. 2000; 30: 729–739.Wulbrand U., Remmert G., Zofel P., Wied M., Arnold R., Fehmann H.C. mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours. Eur J Clin Invest. 2000; 30: 729–739.von Wichert G., Jehle P.M., Hoeflich A., Koschnick S., Dralle H., Wolf E., Wiedenmann B., Boehm B.O., Adler G., Seufferlein T. Insulinlike growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res. 2000; 60: 4573–4581.von Wichert G., Jehle P.M., Hoeflich A., Koschnick S., Dralle H., Wolf E., Wiedenmann B., Boehm B.O., Adler G., Seufferlein T. Insulinlike growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res. 2000; 60: 4573–4581.Nilsson O., Wangberg B., Theodorsson E., Skottner A., Ahlman H. Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? Int J Cancer. 1992; 51: 195203. doi: 10.1002/ijc.2910510206.Nilsson O., Wangberg B., Theodorsson E., Skottner A., Ahlman H. Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? Int J Cancer. 1992; 51: 195203. doi: 10.1002/ijc.2910510206.Zhang H., Yee D. The therapeutic potential of agents targeting the type I insulin-like growth factor receptor. Expert Opin Investig Drugs. 2004 Dec; 13(12): 1569–77. doi: 10.1517/13543784.13.12.1569.Zhang H., Yee D. The therapeutic potential of agents targeting the type I insulin-like growth factor receptor. Expert Opin Investig Drugs. 2004 Dec; 13(12): 1569–77. doi: 10.1517/13543784.13.12.1569.Kulke M.H., Lenz H.J., Meropol N.J., Posey J., Ryan D.P., Picus J., Bergsland E., Stuart K., Tye L., Huang X., Li J.Z., Baum C.M., Fuchs C.S. Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors. J Clin Oncol. 2008 Jul 10; 26(20): 3403–10. doi: 10.1200/JCO.2007.15.9020.Kulke M.H., Lenz H.J., Meropol N.J., Posey J., Ryan D.P., Picus J., Bergsland E., Stuart K., Tye L., Huang X., Li J.Z., Baum C.M., Fuchs C.S. Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors. J Clin Oncol. 2008 Jul 10; 26(20): 3403–10. doi: 10.1200/JCO.2007.15.9020.Raymond E., Dahan L., Raoul J.L., Bang Y.J., Borbath I., LombardBohas C., Valle J., Metrakos P., Smith D., Vinik A., Chen J.S., Hörsch D., Hammel P., Wiedenmann B., Van Cutsem E., Patyna S., Lu D.R., Blanckmeister C., Chao R., Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10; 364(6): 501–13. doi: 10.1056/NEJMoa1003825.Raymond E., Dahan L., Raoul J.L., Bang Y.J., Borbath I., LombardBohas C., Valle J., Metrakos P., Smith D., Vinik A., Chen J.S., Hörsch D., Hammel P., Wiedenmann B., Van Cutsem E., Patyna S., Lu D.R., Blanckmeister C., Chao R., Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10; 364(6): 501–13. doi: 10.1056/NEJMoa1003825.Lloyd R.V., Osamura R.Y., Kloppel G., Rosai J. WHO classification of tumours of endocrine organs. 4th edn. Lyon. IARC Press. 2017.Lloyd R.V., Osamura R.Y., Kloppel G., Rosai J. WHO classification of tumours of endocrine organs. 4th edn. Lyon. IARC Press. 2017.Делекторская В.В. Нейроэндокринные новообразования поджелудочной железы: новые аспекты морфологической классификации (Всемирная организация здравоохранения, 2017). Успехи молекулярной онкологии. 2017; 4(3): 104–108.Delektorskaya V.V. Pancreatic neuroendocrine tumors: new aspects of morphological classification (World Health Organization, 2017). Advances in molecular oncology. 2017; 4(3): 104–108. (in Russian).Modlin I.M., Gustafsson B.I., Moss S.F., Pavel M., Tsolakis A.V., Kidd M. Chromogranin A – biological function and clinical utility in neuroendocrine tumor disease. Ann Surg Oncol. 2010 Sep; 17(9): 2427–43. doi: 10.1245/s10434-010-1006-3.Modlin I.M., Gustafsson B.I., Moss S.F., Pavel M., Tsolakis A.V., Kidd M. Chromogranin A – biological function and clinical utility in neuroendocrine tumor disease. Ann Surg Oncol. 2010 Sep; 17(9): 2427–43. doi: 10.1245/s10434-010-1006-3.Моисеенко В.М. Злокачественные опухоли: практические рекомендации по лекарственному лечению злокачественных опухолей (RUSSCO). М., 2017, 656.Moiseenko V.М. Malignant tumors: practical recommendations for the treatment of malignant tumors (RUSSO). Moscow; 2017, 656. (in Russian).

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