NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Thymomas and Thymic Carcinomas Version 2.2019 — March 11, 2019 NCCN.org Continue Version 2.2019, 03/11/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Thymomas and Thymic Carcinomas Discussion *David S. Ettinger, MD/Chair † Ramaswamy Govindan, MD † Sandip P. Patel, MD ‡ † Þ The Sidney Kimmel Comprehensive Siteman Cancer Center at Barnes- UC San Diego Moores Cancer Center Cancer Center at Johns Hopkins Jewish Hospital and Washingtn University School of Medicine Karen Reckamp, MD, MS † ‡ *Douglas E. Wood, MD/Vice Chair ¶ City of Hope National Medical Center Fred Hutchinson Cancer Research Matthew A. Gubens, MD, MS † Center/Seattle Cancer Care Alliance UCSF Helen Diller Family Gregory J. Riely, MD, PhD † Þ Comprehensive Cancer Center Memorial Sloan Kettering Cancer Center Dara L. Aisner, MD, PhD ≠ University of Colorado Cancer Center Mark Hennon, MD ¶ Steven E. Schild, MD § Roswell Park Cancer Institute Mayo Clinic Cancer Center Wallace Akerley, MD † Huntsman Cancer Institute Leora Horn, MD, MSc † Theresa A. Shapiro, MD, PhD Þ at the University of Utah Vanderbilt-Ingram Cancer Center The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Jessica Bauman, MD ‡ † Rudy P. Lackner, MD ¶ Fox Chase Cancer Center Fred & Pamela Buffett Cancer Center James Stevenson, MD † Case Comprehensive Cancer Center/ Ankit Bharat, MD ¶ Michael Lanuti, MD ¶ University Hospitals Seidman Cancer Center Robert H. Lurie Comprehensive Cancer Massachusetts General Hospital Cancer Center and Cleveland Clinic Taussig Cancer Institute Center of Northwestern University Ticiana A. Leal, MD † Scott J. Swanson, MD ¶ Debora Bruno, MD † University of Wisconsin Carbone Cancer Center Dana-Farber/Brigham and Women’s Case Comprehensive Cancer Center/ Cancer Center Rogerio Lilenbaum, MD † University Hospitals Seidman Cancer Center Yale Cancer Center/Smilow Cancer Hospital Kurt Tauer, MD † and Cleveland Clinic Taussig Cancer Institute St. Jude Children’s Research Hospital/ Joe Y. Chang, MD, PhD § Jules Lin, MD ¶ University of Tennessee Health Science Center The University of Texas University of Michigan Rogel Cancer Center Stephen C. Yang, MD ¶ MD Anderson Cancer Center The Sidney Kimmel Comprehensive Lucian R. Chirieac, MD ≠ Billy W. Loo, Jr., MD, PhD § Cancer Center at Johns Hopkins Dana-Farber/Brigham and Women’s Stanford Cancer Institute Cancer Center Renato Martins, MD, MPH † Thomas A. D’Amico, MD ¶ Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance NCCN Duke Cancer Institute Kristina Gregory, RN, MSN, OCN Gregory A. Otterson, MD † Lydia Hammond, MBA Thomas J. Dilling, MD, MS § Miranda Hughes, PhD Moffitt Cancer Center The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Michael Dobelbower, MD, PhD § ф Diagnostic/Interventional § Radiation oncology/ University of Alabama at Birmingham radiology Radiotherapy Comprehensive Cancer Center ‡ Hematology/Hematology ¶ Surgery/Surgical oncology oncology NCCN Guidelines Panel Disclosures Continue Þ Internal medicine * Discussion Section † Medical oncology Writing Committee ≠ Pathology Version 2.2019, 03/11/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Thymomas and Thymic Carcinomas Discussion NCCN Thymomas and Thymic Carcinomas Panel Members Clinical Trials: NCCN believes that Summary of Guidelines Updates the best management for any patient with cancer is in a clinical trial. Initial Evaluation (THYM-1) Participation in clinical trials is especially encouraged. Initial Management (THYM-2) To find clinical trials online at NCCN Postoperative Treatment and Management (THYM-3) Member Institutions, click here: Locally Advanced, Advanced, or Recurrent Disease (THYM-4) nccn.org/clinical_trials/clinicians.aspx. NCCN Categories of Evidence and Principles of Surgical Resection (THYM-A) Consensus: All recommendations Principles of Radiation Therapy (THYM-B) are category 2A unless otherwise Principles of Systemic Therapy for Thymic Malignancies (THYM-C) indicated. World Health Organization Histologic Classification (THYM-D) See NCCN Categories of Evidence and Consensus. 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. ©2019. Version 2.2019, 03/11/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Thymomas and Thymic Carcinomas Discussion Updates in Version 2.2019 of the NCCN Guidelines for Thymomas and Thymic Carcinomas from Version 1.2019 include: MS-1 • The discussion section was updated to reflect the changes in the algorithm. Updates in Version 1.2019 of the NCCN Guidelines for Thymomas and Thymic Carcinomas from Version 2.2018 include: General: References have been updated throughout the guidelines, as appropriate. THYM-1 • Initial Evaluation Fourth bullet was modified: PET/CT scan (whole-body or skull base to mid-thigh), as clinically indicated (Also applies to bullet 2 on THYM-4) THYM-3 • Footnote i was added: MRI is an appropriate alternative to CT in certain clinical situations. (Also added to THYM-4) THYM-4 • Treatment Pathway for patients with locally advanced disease was revised. THYM-C (1 of 2) • Title was changed: Principles of Chemotherapy Systemic Therapy for Thymic Malignancies • Second-Line Systemic Therapy Regimen was modified: Gemcitabine± capecitabine Regimen was added: Pembrolizumab (thymic carcinomas only) ◊ Footnote † was added: Pembrolizumab is not recommended for patients with thymoma. In patients with thymic carcinoma, there is a concern for a higher rate of immune-related adverse events than seen in most other malignancies treated with PD-1/PD-L1 inhibitor therapy. For example, grade 3–4 myocarditis has been reported in 5%–9% of patients receiving pembrolizumab. Version 2.2019, 03/11/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. UPDATES NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Thymomas and Thymic Carcinomas Discussion INITIAL EVALUATION a b See Initial Management • Chest CT with contrast Thymic tumor likely (THYM-2) • Serum beta-HCG, AFP, if appropriate • CBC, platelets Mediastinal • PET/CT scan (whole-body or skull base mass to mid-thigh), as clinically indicated • Pulmonary function tests, as clinically indicated • Chest MRI with contrast, as clinically See disease-specific indicateda Thymic tumor unlikely Consider tissue biopsy guidelines as appropriate (NCCN Table of Contents) aWhen assessing a mediastinal mass, detection of thymic malignancy versus thymic cyst can be better discriminated with chest MRI compared to chest CT, potentially avoiding an unneccessary thymectomy. bWell-defined anterior mediastinal mass in the thymic bed, tumor markers negative, absence of other adenopathy, and absence of continuity with the thyroid. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. Version 2.2019, 03/11/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. THYM-1 NCCN Guidelines Index NCCN Guidelines Version 2.2019 Table of Contents Thymomas and Thymic Carcinomas Discussion INITIAL MANAGEMENT d Surgically Surgical resection (total See Postoperative resectablec thymectomy and complete Management (THYM-3) All patients should be excision of tumor) managed by a multidisciplinary team Thymic tumor likelyb with experience in the management of thymoma Tissue diagnosis with core and thymic carcinoma Locally advanced, See Treatment needle biopsy or open biopsy unresectablec (THYM-4) (Avoid transpleural approach) bWell-defined anterior mediastinal mass in the thymic bed, tumor markers negative, absence of other adenopathy, and absence of continuity with the thyroid. cDetermination of resectability should be made by a board-certified thoracic surgeon, with