Possibilities of treating patients with generalized neuroendocrine tumors

Maistrenko N.A.; Romashchenko P.N.; Orlova R.V.; Lysanyuk M.V.

doi:https://doi.org/10.17116/onkolog20187216-25

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Abstract:

Objective — to clarify the rational treatment policy for patients with generalized neuroendocrine tumors of the gastrointestinal tract and pancreas, which can increase the duration of life and improve its better quality in patients. Subject and methods. The results of examination and treatment were studied in 63 patients with generalized neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. Combination treatment was performed in 32 (50.8%) patients; 31 (49.2%) patients received drug therapy as a sole treatment option. Results. Combination versus drug therapy was ascertained to increase survival for patients with Grades 1—2 NETs by 2 times (from 29.9 to 60 months) and for those with grade 3 neuroendocrine carcinoma (NEC) by 2.9-fold (from 10.1 to 28.5 months). There were adverse prognostic factors of the disease: 1) primary pancreatic tumor; 2) type III liver metastasis; 3) Grade 3 NEC; 4) drug therapy as the only treatment option (p<0.05). Conclusion. Patients with generalized NETs should be treated in specialized medical centers that have a chance of applying a multidisciplinary approach that makes it possible to significantly increase the duration of life and to improve its quality of life.

Keywords:

neuroendocrine tumor

neuroendocrine carcinoma

combination treatment

Authors:

Maistrenko N.A.

S.M. Kirov Military Medical Academy, Saint Petersburg, Russia

Romashchenko P.N.

S.M. Kirov Military Medical Academy, Saint Petersburg, Russia

Orlova R.V.

Saint-Petersburg State University, Saint-Petersburg, Russia

Lysanyuk M.V.

S.M. Kirov Military Medical Academy, Saint Petersburg, Russia

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References:

Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Adalla EK, Fleming JB, Vauthey J-N, Rashid A, Evans DB. One hundred years after «carcinoid»: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063-3072. https://doi.org/10.1200/JCO.2007.15.4377
Öberg K, Knigge U, Kwekkeboom D, Perren A. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(7):124-130.
Partelli S, Bartsch DK, Capdevila J, Chen J, Knigge U, Niederle B, Nieveen van Dijkum JM, Pape U-F, Pascher A, Ramage J, Reed N, Ruszniewski P, Scoazec J-Y, Toumpanakis C, Kiamanesh R, Falconi M. ENETS consensus guidelines for standard of care in neuroendocrine tumours: surgery for small intestinal and pancreatic neuroendocrine tumours. Neuroendocrinology. 2017;105(3):255-265. https://doi.org/10.1159/000464292
Pavel M, O’Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, Krenning E, Knigge U, Salazar R, Pape U-F, Öberg K. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103(2):172-185. https://doi.org/10.1159/000443167
Maistrenko NA, Romashchenko PN, Lysanyuk MV. Diagnosis and surgical treatment of neuroendocrine tumors of the pancreas and the gastrointestinal tract. Annaly khirurgicheskoi gepatologii. 2016;21(1):13-20. (In Russ.)
Vinik AI, Woltering EA, Warner RR, Caplin M, O’Dorisio TM, Wiseman GA, Coppola D, Go VL. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713-734. https://doi.org/10.1097/MPA.0b013e3181ebaffd
Klimstra DS. Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin Oncol. 2013;40(1):23-36. https://doi.org/10.1053/j.seminoncol.2012.11.001
Frilling A, Li J, Malamutmann E, Schmid KW, Bockisch A, Broelsch CE. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease. Br J Surg. 2009;96(2):175-184. https://doi.org/10.1002/bjs.6468
Sandvik OM, Soreide K, Gudlaugsson E, Kvaloy JT, Soreide JA. Epidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteria. Br J Surg. 2016;103(3):226-232. https://doi.org/10.1002/bjs.10034
Kaprin AD, Starinskii VV, Petrova GV, eds. Malignant neoplasms in Russia in 2015 (morbidity and mortality). Zlokachestvennye novoobrazovaniya v Rossii v 2015 (zabolevaemost’ i smertnost’). Moscow: MNIOI im. P.A. Gertsena — filial FGBU NMIRTs Minzdrava Rossii; 2017. (In Russ.)
Fairweather M, Swanson R, Wang J, Brais LK, Dutton T, Kulke MH, Clancy TE. Management of neuroendocrine tumor liver metastases: long-term outcomes and prognostic factors from a large prospective database. Ann Surg Oncol. 2017;24(8):2319-2325. https://doi.org/10.1245/s10434-017-5839-x
Watzka FM, Fottner C, Miederer M, Schad A, Weber MM, Otto G, Lang H, Musholt TJ. Surgical therapy of neuroendocrine neoplasm with hepatic metastasis: patient selection and prognosis. Langenbecks Arch Surg. 2015;400(3):349-358. https://doi.org/10.1007/s00423-015-1277-z
Maxwell JE, Sherman SK, O’Dorisio TM, Bellizzi AM, Howe JR. Liver-directed surgery of neuroendocrine metastases: What is the optimal strategy? Surgery. 2016;159(1):320-333. https://doi.org/10.1016/j.surg.2015.05.040
Farley HA, Pommier RF. Treatment of neuroendocrine liver metastases. Surg Oncol Clin N Am. 2016;25(1):217-225. https://doi.org/10.1016/j.soc.2015.08.010
Krausch M, Raffel A, Anlauf M, Schott M, Lehwald N, Krieg A, Topp SA, Cupisti K, Knoefel WT. «Cherry Picking», a multiple non-anatomic liver resection technique, as a promising option for diffuse liver metastases in patients with neuroendocrine tumours. World J Surg. 2014;38(2):392-401. https://doi.org/10.1007/s00268-013-2267-3
Saxena A, Chua TC, Perera M, Chu F, Morris DL. Surgical resection of hepatic metastases from neuroendocrine neoplasms: а systematic review. Surg Oncol. 2012;21(3):131-141. https://doi.org/10.1016/j.suronc.2012.05.001
Bertani E, Fazio N, Radice D, Zardini C, Spinoglio G, Chiappa A, Ribero D, Biffi R, Partelli S, Falconi M. Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation. Eur J Surg Oncol. 2017;43(2):372-379. https://doi.org/10.1016/j.ejso.2016.09.011
Romashchenko PN, Maistrenko NA, Orlova RV, Lysаnyuk MV. Prediction of treatment outcomes gastroenteropancreatic neuroendocrine tumors. Meditsinskii akademicheskii zhurnal. 2017;17(1):54-66. (In Russ.)
Orgera G, Krokidis M, Cappucci M, Gourtsoyianni S, Tipaldi MA, Hatzidakis A, Rebonato A, Rossi M. Current status of interventional radiology in the management of gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs). Cardiovasc Intervent Radiol. 2015;38(1):13-24. https://doi.org/10.1007/s00270-014-1005-z
McDermott S, Gervais DA. Radiofrequency ablation of liver tumors. Semin Intervent Radiol. 2013;30(1):49-55. https://doi.org/10.1055/s-0033-1333653
Taner T, Atwell TD, Zhang L, Oberg TN, Harmsen WS, Slettedahl SW, Kendrick ML, Nagorney DM, Que FG. Adjunctive radiofrequency ablation of metastatic neuroendocrine cancer to the liver complements surgical resection. HPB (Oxford). 2013;15(3):190-195. https://doi.org/10.1111/j.1477-2574.2012.00528.x
Norlen O, Stalberg P, Zedenius J, Hellman P. Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumours. Br J Surg. 2013;100(11):1505-1514. https://doi.org/10.1002/bjs.9262
Mohan H, Nicholson P, Winter C, O’Shea D, O’Toole D, Geoghegan J, Maguire D, Hoti E, Traynor O, Cantwell CP. Radiofrequency ablation for neuroendocrine liver metastases: a systematic review. J Vasc Interv Radiol. 2015;26(7):935-942. https://doi.org/10.1016/j.jvir.2014.12.009
Del Prete M, Fiore F, Modica R, Marotta V, Marciello F, Ramundo V, Di Sarno A, Carratù A, de Luca di Roseto C, Tafuto S, Tatangelo F, Baldelli R, Colao A, Faggiano A. Hepatic arterial embolization in patients with neuroendocrine tumors. J Exp Clin Cancer Res. 2014;33:43. https://doi.org/10.1186/1756-9966-33-43
Chen JX, Rose S, White SB, El-Haddad G, Fidelman N, Yarmohammadi H, Hwang W, Sze DY, Kothary N, Stashek K, Wileyto EP, Salem R, Metz DC, Soulen MC. Embolotherapy for neuroendocrine tumor liver metastases: prognostic factors for hepatic progression-free survival and overall survival. Cardiovasc Intervent Radiol. 2017;40(1):69-80. https://doi.org/10.1007/s00270-016-1478-z
Pericleous M, Caplin ME, Tsochatzis E, Yu D, Morgan-Rowe L, Toumpanakis С. Hepatic artery embolization in advanced neuroendocrine tumors: Efficacy and long-term outcomes. Asia Pac J Clin Oncol. 2016;12(1):61-69. https://doi.org/10.1111/ajco.12438
Gaba RC, Mendoza-Elias N, Morrison JD, Valeshabad AK, Lipnik AJ. Decision making for selection of transarterial locoregional therapy of metastatic neuroendocrine tumors. Semin Intervent Radiol. 2017;34(2):101-108. https://doi.org/10.1055/s-0037-1602590
Berardi R, Morgese F, Torniai M, Savini A, Partelli S, Rinaldi S, Caramanti M, Ferrini C, Falconi M, Cascinu S. Medical treatment for gastro-entero-pancreatic neuroendocrine tumours. World J Gastrointest Oncol. 2016;8(4):389-401. https://doi.org/10.4251/wjgo.v8.i4.389
Lee A, Chana DL, Wong MH, Lic BT, Lumbaa S, Clarkea SJ, Samrad J, Pavlakisa N. Systematic review of the role of targeted therapy in metastatic neuroendocrine tumors. Neuroendocrinology. 2017;104(3):209-222. https://doi.org/10.1159/000446115
Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, Dueland S, Hofsli E, Guren MG, Ohrling K, Birkemeyer E, Thiis-Evensen E, Biagini M, Gronbaek H, Soveri LM, Olsen IH, Federspiel B, Assmus J, Janson ET, Knigge U. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study. Ann Oncol. 2013;24(1):152-160. https://doi.org/10.1093/annonc/mds276
Cavalcoli F, Rausa E, Conte D, Nicolini AF, Massironi S. Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies? World J Gastroenterol. 2017;23(15):2640-2650. https://doi.org/10.3748/wjg.v23.i15.2640
Lepage C, Ciccolallo L, De Angelis R, Bouvier AM, Faivre J, Gatta G. European disparities in malignant digestive endocrine tumours survival. Int J Cancer. 2010;126(12):2928-2934. https://doi.org/10.1002/ijc.24698
Panzuto F, Merola E, Rinzivillo M, Partelli S, Campana D, Iannicelli E, Pilozzi E, Mercantini P, Rossi M, Capurso G, Scarpa A, Cascinu S, Tomassetti P, Falconi M, Delle Fave G. Advanced digestive neuroendocrine tumors: metastatic pattern is an independent factor affecting clinical outcome. Pancreas. 2014;43(2):212-218. https://doi.org/10.1097/MPA.0000000000000032
Haugvik SP, Janson ET, Österlund P, Langer SW, Falk RS, Labori KJ, Vestermark LW, Grønbæk H, Gladhaug IP, Sorbye H. Surgical treatment as a principle for patients with high-grade pancreatic neuroendocrine carcinoma: A Nordic Multicenter Comparative Study. Ann Surg Oncol. 2016;23(5):1721-1728. https://doi.org/10.1245/s10434-015-5013-2