Gastrointestinal ve Pankreatik Nöroendokrin Tümörler
Özet
Nöroendokrin tümörler (NET’ler), gastrointestinal sistem, pankreas ve akciğerler ve diğer endokrin organlardaki nöroendokrin hücrelerden gelişebilen, peptit ve aminler salgılayarak çeşitli klinik semptomlara yol açabilen tümörlerdir. Son yıllarda insidansı artan NET'ler, daha çok 50 yaş sonrasında ve en sık gastrointestinal sistemde görülmektedir. Tanıda histopatolojik incelemeler ve görüntüleme yöntemleri (BT, MRI, 68Ga-PET) kullanılırken, somatostatin reseptör ekspresyonu tanı ve tedavide önemli bir rol oynamaktadır. Tedavi seçenekleri arasında cerrahi (özellikle erken evrelerde), somatostatin analogları, lokal ablasyon yöntemleri, hedefe yönelik tedaviler ve seçilmiş vakalarda kemoterapi yer alır. Rezeke edilmiş NET’ler için takip stratejileri, hastaların klinik durumlarına ve tümör türlerine göre farklılık gösterir. Çalışmalar, rezeke edilen NET'lerde uzun vadeli nüks oranlarının yaklaşık %50 olduğunu gösterirken takibin önemli olduğunu vurgulanmıştır. İyi diferansiye NET'lerin yavaş büyüyen doğası nedeniyle, nüksler yıllar sonra ortaya çıkabilir ve takip sıklığı, tümörün derecesine göre değişir. Önerilen takip protokollerinde, çeşitli görüntüleme yöntemleri (BT, MR, daha nadir olarak 68Ga-PET gibi) ve biyokimyasal testlerin kullanımı yer alır. Ayrıca, bazı özel durumlarda (örneğin, <1 cm rektal veya <2 cm apendiks tümörleri), rutin takip gerekli değildir. Takip sırasında biyolojik belirteçlerin (Kromogranin A, nöron spesifik enolaz, 5-HIAA gibi) rolü sınırlıdır, ancak hastalığın seyrini izlemek için önemli olabilir. Takip süresi genellikle 10 yıl kadar uzayabilir ve klinik olarak endike olduğu sürece devam etmelidir. Bu bölümde; gastrointestinal ve pankreatik nöroendokrin tümörlerde takip önerileri tartışılarak güncel kılavuzlardaki öneriler bölüm sonunda özetlenecektir.
Neuroendocrine tumours (NETs) are tumours that may develop from neuroendocrine cells in the gastrointestinal tract, pancreas, lungs and other endocrine organs, secreting peptides and amines and causing various clinical symptoms. NETs, whose incidence has increased in recent years, are mostly seen after the age of 50 years and most commonly in the gastrointestinal system. Histopathological examinations and imaging methods (CT, MRI, 68Ga-PET) are used in the diagnosis, while somatostatin receptor expression plays an important role in diagnosis and treatment. Treatment options include surgery (especially in early stages), somatostatin analogues, local ablation methods, targeted therapies and chemotherapy in selected cases. Follow-up strategies for resected NETs differ according to the clinical status of patients and tumour types. Studies have shown that the long-term recurrence rate of resected NETs is approximately 50%, emphasising the importance of follow-up. Due to the slow-growing nature of well-differentiated NETs, recurrences may occur years later and the frequency of follow-up varies according to the grade of the tumour. Recommended follow-up protocols include the use of various imaging modalities (such as CT, MRI, less commonly 68Ga-PET) and biochemical tests. In addition, in some special cases (e.g. <1 cm rectal or <2 cm appendiceal tumours), routine follow-up is not necessary. The role of biological markers (such as Chromogranin A, neuron specific enolase, 5-HIAA) during follow-up is limited, but may be important for monitoring the course of the disease. The follow-up period can usually be as long as 10 years and should be continued as long as clinically indicated. In this chapter, recommendations for follow-up in gastrointestinal and pancreatic neuroendocrine tumours will be discussed and recommendations in current guidelines will be summarised at the end of the chapter.
Referanslar
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Journal of clinical oncology. 2008;26(18):3063-72.
Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA oncology. 2017;3(10):1335-42.
Institute NC. SEER cancer statistics review 1975-2004. Complete and limited-duration cancer prevalence estimates. [Available from: http://seer.cancer.gov/csr/1975_2004/results_merged/topic_prevalence.pdf.
Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gönen M, et al. Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. The American journal of surgical pathology. 2010;34(3):300-13.
Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707-12.
Keskin O, Yalcin S. A review of the use of somatostatin analogs in oncology. OncoTargets and therapy. 2013:471-83.
Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. Journal of nuclear medicine. 2007;48(4):508-18.
Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schäfer M, et al. Comparison of 68 Ga-DOTATOC PET and 111 In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. European journal of nuclear medicine and molecular imaging. 2007;34:1617-26.
Partelli S, Maurizi A, Tamburrino D, Baldoni A, Polenta V, Crippa S, et al. GEP–NETS UPDATE: A review on surgery of gastro-entero-pancreatic neuroendocrine tumors. European journal of endocrinology. 2014;171(4):R153-R62.
Öberg KE, Reubi JC, Kwekkeboom DJ, Krenning EP. Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology. 2010;139(3):742-53. e1.
Rinke A, Müller H-H, Schade-Brittinger C, Klose K-J, Barth P, Wied M, et al. 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. Journal of Clinical oncology. 2009;27(28):4656-63.
Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. New England Journal of Medicine. 2014;371(3):224-33.
Coppa J, Pulvirenti A, Schiavo M, Romito R, Collini P, Di Bartolomeo M, et al., editors. Resection versus transplantation for liver metastases from neuroendocrine tumors. Transplantation Proceedings; 2001: Orlando, FL: Grune & Stratton, 1969-.
Elvin A, Skogseid B, Hellman P. Radiofrequency ablation of neuroendocrine liver metastases. Abdominal imaging. 2005;30:427-34.
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364(6):514-23.
Raymond E, Dahan L, Raoul J-L, Bang Y-J, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364(6):501-13.
Le Roux C, Lombard-Bohas C, Delmas C, Dominguez-Tinajero S, Ruszniewski P, Samalin E, et al. Relapse factors for ileal neuroendocrine tumours after curative surgery: a retrospective French multicentre study. Digestive and Liver Disease. 2011;43(10):828-33.
Dieckhoff P, Runkel H, Daniel H, Wiese D, Koenig A, Fendrich V, et al. Well-differentiated neuroendocrine neoplasia: relapse-free survival and predictors of recurrence after curative intended resections. Digestion. 2014;90(2):89-97.
Halfdanarson TR, Strosberg JR, Tang L, Bellizzi AM, Bergsland EK, O'Dorisio TM, et al. The North American neuroendocrine tumor society consensus guidelines for surveillance and medical management of pancreatic neuroendocrine tumors. Pancreas. 2020;49(7):863-81.
NCCN Clinical Practice Guidelines in Oncology Version 2.2024 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf.
Pavel M, Öberg K, Falconi M, Krenning E, Sundin A, Perren A, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020;31(7):844-60.
Coşkun H, Bostancı Ö, Dilege M, Mihmanlı M, Yılmaz B, Akgün İ, et al. Carcinoid tumors of appendix: treatment and outcome. Turkish Journal of Trauma and Emergency Surgery. 2006;12(2):150-4.
Murray SE, Lloyd RV, Sippel RS, Chen H, Oltmann SC. Postoperative surveillance of small appendiceal carcinoid tumors. The American Journal of Surgery. 2014;207(3):342-5.
Shapiro R, Eldar S, Sadot E, Papa MZ, Zippel DB. Appendiceal carcinoid at a large tertiary center: pathologic findings and long-term follow-up evaluation. The American journal of surgery. 2011;201(6):805-8.
Boninsegna L, Panzuto F, Partelli S, Capelli P, Delle Fave G, Bettini R, et al. Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. European Journal of Cancer. 2012;48(11):1608-15.
Casadei R, Ricci C, Pezzilli R, Campana D, Tomassetti P, Calculli L, et al. Are there prognostic factors related to recurrence in pancreatic endocrine tumors? Pancreatology. 2010;10(1):33-8.
Kim S-J, Kim JW, Oh D-Y, Han S-W, Lee S-H, Kim D-W, et al. Clinical course of neuroendocrine tumors with different origins (the pancreas, gastrointestinal tract, and lung). American Journal of Clinical Oncology. 2012;35(6):549-56.
Cives M, Anaya DA, Soares H, Coppola D, Strosberg J. Analysis of postoperative recurrence in stage I–III midgut neuroendocrine tumors. JNCI: Journal of the National Cancer Institute. 2018;110(3):282-9.
Di Giacinto P, Rota F, Rizza L, Campana D, Isidori A, Lania A, et al. Chromogranin A: from laboratory to clinical aspects of patients with neuroendocrine tumors. International Journal of Endocrinology. 2018;2018(1):8126087.
Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. Journal of clinical oncology. 2010;28(1):69-76.
Massironi S, Rossi RE, Casazza G, Conte D, Ciafardini C, Galeazzi M, et al. Chromogranin A in diagnosing and monitoring patients with gastroenteropancreatic neuroendocrine neoplasms: a large series from a single institution. Neuroendocrinology. 2015;100(2-3):240-9.
Rossi RE, Ciafardini C, Sciola V, Conte D, Massironi S. Chromogranin A in the follow-up of gastroenteropancreatic neuroendocrine neoplasms: is it really game over? A systematic review and meta-analysis. Pancreas. 2018;47(10):1249-55.
Ter-Minassian M, Chan JA, Hooshmand SM, Brais LK, Daskalova A, Heafield R, et al. Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocrine-related cancer. 2013;20(2):187-96.
Bodei L, Kidd MS, Singh A, Van Der Zwan WA, Severi S, Drozdov IA, et al. PRRT genomic signature in blood for prediction of 177 Lu-octreotate efficacy. European journal of nuclear medicine and molecular imaging. 2018;45:1155-69.
Bodei L, Kidd MS, Singh A, van der Zwan WA, Severi S, Drozdov IA, et al. PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest. European journal of nuclear medicine and molecular imaging. 2020;47:895-906.
Van Treijen MJ, Korse CM, Van Leeuwaarde RS, Saveur LJ, Vriens MR, Verbeek WH, et al. Blood transcript profiling for the detection of neuroendocrine tumors: results of a large independent validation study. Frontiers in endocrinology. 2018;9:740.
Joish VN, Shah S, Tierce JC, Patel D, McKee C, Lapuerta P, et al. Serotonin levels and 1-year mortality in patients with neuroendocrine tumors: a systematic review and meta-analysis. Future oncology. 2019;15(12):1397-406.
