NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Neuroendocrine Tumors Version 1.2015 NCCN.org Continue Version 1.2015, 11/11/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. Printed by Alexandre Ferreira on 10/25/2015 6:11:33 AM. For personal use only. Not approved for distribution. Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved. NCCN Guidelines Version 1.2015 Panel Members NCCN Guidelines Index Neuroendocrine TOC Neuroendocrine Tumors Discussion * Matthew H. Kulke, MD/Chair † * Whitney S. Goldner, MD ð Venu G. Pillarisetty, MD ¶ Dana-Farber/Brigham and Women’s Fred & Pamela Buffett Cancer Center Fred Hutchinson Cancer Research Cancer Center at The Nebraska Medical Center Center/Seattle Cancer Care Alliance Manisha H. Shah, MD/ Vice Chair † Thorvardur R. Halfdanarson, MD Þ † * Leonard Saltz, MD † Þ The Ohio State University Comprehensive Mayo Clinic Memorial Sloan Kettering Cancer Center Cancer Center - James Cancer Hospital Cancer Center and Solove Research Institute Julie Ann Sosa, MD ¶ ð Martin J. Heslin, MD ¶ Duke Cancer Institute Al B. Benson, III, MD † University of Alabama at Birmingham Robert H. Lurie Comprehensive Cancer Comprehensive Cancer Center Jonathan R. Strosberg, MD † Center of Northwestern University Moffitt Cancer Center Fouad Kandeel, MD, PhD ð * Emily Bergsland, MD † City of Hope Comprehensive Cancer Center UCSF Helen Diller Family Jean-Nicolas Vauthey, MD ¶ Comprehensive Cancer Center * Pamela L. Kunz, MD † The University of Texas Stanford Cancer Institute MD Anderson Cancer Center Jordan D. Berlin, MD † Vanderbilt-Ingram Cancer Center Boris W. Kuvshinoff, II, MD, MBA ¶ Christopher Wolfgang, MD, PhD The Sidney Kimmel Comprehensive Lawrence S. Blaszkowsky, MD † Roswell Park Cancer Institute Cancer Center at Johns Hopkins Massachusetts General Hospital Cancer Center Christopher Lieu, MD † University of Colorado Cancer Center James C. Yao, MD † * Lyska Emerson, MD ≠ The University of Texas Huntsman Cancer Institute Jeffrey F. Moley, MD ¶ MD Anderson Cancer Center at the University of Utah Siteman Cancer Center at Barnes- Jewish Hospital and Washington Paul F. Engstrom, MD † NCCN University School of Medicine Fox Chase Cancer Center Jennifer Burns Deborah Freedman-Cass, PhD * Paul Fanta, MD Gitonga Munene, MD Fayna Ferkle, PharmD UC San Diego Moores Cancer Center St. Jude Children`s Research Hospital/ The University of Tennessee Thomas Giordano, MD, PhD ≠ Health Science Center ¶ Surgery/Surgical oncology University of Michigan † Medical oncology Comprehensive Cancer Center ð Endocrinology ≠ Pathology Þ Internal medicine * Writing Committee Member NCCN Guidelines Panel Disclosures Continue Version 1.2015, 11/11/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. Printed by Alexandre Ferreira on 10/25/2015 6:11:33 AM. For personal use only. Not approved for distribution. Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved. NCCN Guidelines Version 1.2015 Table of Contents NCCN Guidelines Index Neuroendocrine TOC Neuroendocrine Tumors Discussion NCCN Neuroendocrine Tumors Panel Members Clinical Trials: NCCN believes that Summary of the Guidelines Updates the best management for any cancer patient is in a clinical trial. Neuroendocrine Tumors, Clinical Presentations and Diagnosis (NE-1) Participation in clinical trials is especially encouraged. Neuroendocrine Tumors of the Gastrointestinal Tract, Lung and Thymus (Carcinoid Tumors) (CARC-1) To find clinical trials online at NCCN Neuroendocrine Tumors of the Pancreas (PanNET-1) Member Institutions, click here: nccn.org/clinical_trials/physician.html. Neuroendocrine Tumors of Unknown Primary (NUP-1) NCCN Categories of Evidence and Adrenal Gland Tumors (AGT-1) Consensus: All recommendations are category 2A unless otherwise Pheochromocytoma/Paraganglioma (PHEO-1) specified. See NCCN Categories of Evidence Poorly Differentiated (High Grade)/Large or Small Cell (HGNET-1) and Consensus. Multiple Endocrine Neoplasia, Type 1 (MEN1-1) Multiple Endocrine Neoplasia, Type 2 (MEN2-1) Principles of Pathology for Diagnosis and Reporting of Neuroendocrine Tumors (NE-A) Principles of Biochemical Testing (NE-B) Surgical Principles for Management of Neuroendocrine Tumors (NE-C) Principles of Systemic Anti-Tumor Therapy (NE-D) Staging (ST-1) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2014. Version 1.2015, 11/11/14 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. Printed by Alexandre Ferreira on 10/25/2015 6:11:33 AM. For personal use only. Not approved for distribution. Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved. NCCN Guidelines Version 1.2015 Updates NCCN Guidelines Index Neuroendocrine TOC Neuroendocrine Tumors Discussion Updates in Version 1.2015 of the NCCN Guidelines for Neuroendocrine Tumors from Version 2.2014 include: Global CARC-5 • “Carcinoid tumors” was changed to “Neuroendocrine tumors of the • Evaluation, bronchopulmonary and thymus: Under as appropriate: gastrointestinal tract, lung and thymus (carcinoid tumors).” “ACTH/cortisol” was replaced by “Biochemical workup for • Details regarding biochemical evaluations are now listed in the Principles of Cushing’s syndrome if clinically indicated (See NE-B).” Biochemical Testing (NE-B). Specific biochemical tests were removed from the • Thymus, locoregional disease:Treatment options after algorithm where appropriate and replaced with: “Biochemical evaluation as “incomplete resection” were revised: “RT +/- and/or clinically indicated (see NE-B).” chemotherapy (category 3 for adition of chemotherapy).” • The following footnotes were removed: CARC-6 “Lanreotide is approved for symptom control in Europe. Lanreotide has a similar • Under locoregional unresectable disease and/or distant mechanism of action as octreotide and may be preferable in patients who have metastases: 2nd bullet was revised: “Consider 24-hour urine difficulty tolerating an IM versus SC injection.” 5-HIAA, if not already done.” “Prior to evaluating ACTH, confirm hypercortisolemia using one of the following: • For asymptomatic low tumor burden, clinically significant tumor Overnight 1 mg dexamethasone suppression test with 8 am plasma cortisol; burden, and carcinoid syndrome, lanreotide was added as a Repeated (2–3) midnight salivary cortisols; 24-hour urine free cortisol.” treatment option: “Octreotide or lanreotide.” “For tumor control, the PROMID study (J Clin Oncol 2009;27:4656-4663) used • Following clinically significant progressive disease: octreotide LAR 30 mg IM every 4 weeks.” The first option was revised: “Octreotideor lanreotide, if not • The following footnote was moved from the algorithm to the Principles of Systemic already receiving.” Anti-Tumor Therapy (NE-D): “For symptom control, octreotide 150–250 mcg SC The following option was added: “Consider interferon alfa-2b TID or octreotide LAR 20–30 mg IM every 4 weeks. Dose and frequency may be (category 3). further increased for symptom control as needed. Therapeutic levels of octreotide • Footnotes: would not be expected to be reached for 10–14 d after LAR injection. Short-acting Footnote “b” was added: “See Principles of Biochemical Testing octreotide can be added to octreotide LAR for rapid relief of symptoms or for (NE-B).” breakthrough symptoms.” The following footnote was removed: “Anticancer agents such Neuroendocrine Tumors of the Gastorintestinal Tract, Lung and Thymus as capecitabine, dacarbazine, 5-FU, interferon, oxaliplatin, (Carcinoid Tumors) and temozolomide can be used in patients with progressive CARC-4 metastases for whom there are no other treatment options. See • Hypergastrinemic patients, Tumor ≤2 cm: Discussion for details.” The treatment for Zollinger-Ellison patients was revised to include lanreotide: Neuroendocrine Tumors of the Pancreas “Octreotide or lanreotide for Zollinger-Ellison patients.” The “category 2B” PanNET-1 recommendation was removed. • The following footnote was removed: “Risks and benefits of Surveillance recommendations were revised: surgical resection should be carefully weighed in patients with ◊ Removed separate surveillance recommendations for those treated with small lesions.” observation. • Footnote “h” was revised: “Observation can be considered in ◊ Markers were removed: “H&P and markers.” select cases: tumors <1 cm, incidently