The most accurate answer is the third option. The other options are mostly utilized in the setting of WD NETs. Due to rarity of PNECs, studies evaluating their medical management are limited. Patients with PNEC are at extremely high risk of metastatic disease and are not expected to achieve disease control with surgery alone; current NCCN guideline recommends the regimen of platinum-based chemotherapy (i.e. cisplatin/ carboplatin) and etoposide. This recommendation is extrapolated from treatment algorithms for small cell lung cancer. Adjuvant chemotherapy with or without radiation (cisplatin, etoposide, and radiation generally favored) should be considered for all resectable PNECs. Chemotherapy is associated with improved survival, even in patients with early-stage disease. Following recurrence, due to concerns for cumulative toxicity (e.g. nephrotoxicity) from previous cisplatin administration, carboplatin is often substituted for cisplatin.
- Alese OB, Jiang R, Shaib W, Wu C, Akce M, Behera M, El-Rayes BF. High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study. Oncologist. 2018 Nov 27. pii: theoncologist.2018-0382. [Epub ahead of print]
- Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, Vakiani E, LaRosa S, Jang KT, Frankel WL, Liu X, Zhang L, Giordano TJ, Bellizzi AM, Chen JH, Shi C, Allen P, Reidy DL, Wolfgang CL, Saka B, Rezaee N, Deshpande V, Klimstra DS. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014 Apr;38(4):437-47.
- Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, Krasinskas AM, Jang KT, Frankel WL, Balci S, Sigel C, Klimstra DS. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015 May;39(5):683-90.
- Carrera S, Sancho A, Azkona E, Azkuna J, Lopez-Vivanco G. Hereditary pancreatic cancer: related syndromes and clinical perspective. Hered Cancer Clin Pract. 2017 Jun 28;15:9.
- Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33.
- Qiao XW, Qiu L, Chen YJ, Meng CT, Sun Z, Bai CM, Zhao DC, Zhang TP, Zhao YP,Song YL, Wang YH, Chen J, Lu CM. Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas. BMC Endocr Disord. 2014 Aug 7;14:64.
- Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1,NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009 Apr;33(4):626-32.
- Tang LH, Basturk O, Sue JJ Klimstra DS. A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas. Am J Surg Pathol. 2016 Sep;40(9):1192-202.
- Winter JM, Narang AK, Mansfield AS, Herman JM, Cameron JL, Laheru D, Eckhauser FE, Olson MT, Hruban RH, Miller RC, Andersen DK. Resectable pancreatic small cell carcinoma. Rare Tumors. 2011 Mar 30;3(1):e5.
- Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, de Wilde RF, Maitra A, Hicks J, Demarzo AM, Shi C, Sharma R, Laheru D, Edil BH, Wolfgang CL, Schulick RD, Hruban RH, Tang LH, Klimstra DS, Iacobuzio-Donahue CA. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol. 2012 Feb;36(2):173-84.
- Zell JA, Rhee JM, Ziogas A, Lipkin SM, Anton-Culver H. Race, socioeconomic status, treatment, and survival time among pancreatic cancer cases in California. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):546-52.
- Zhu J, Strosberg JR, DropkinE, and Strickler JH. Treatment of High-Grade Metastatic Pancreatic Neuroendocrine Carcinoma with FOLFIRINOX. Oncologist. 2018 Nov 27. [Epub ahead of print] J Gastrointest Canc (2015) 46:166–169