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Continue NCCN Clinical Practice Guidelines in Oncology™ Thymic Malignancies V.2.2010 www.nccn.org Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® NCCN Thymic Malignancies Panel Members † Medical Oncology ¶ Surgery/Surgical oncology § Radiation oncology/ Pathology ‡ Hematology/Hematology oncology Radiotherapy *Writing Committee Member � Continue NCCN Guidelines Panel Disclosures *David S. Ettinger, MD/Chair † The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Wallace Akerley, MD Huntsman Cancer Institute at the University of Utah Gerold Bepler, MD, PhD H. Lee Moffitt Cancer Center & Research Institute Matthew G. Blum, MD Andrew Chang, MD University of Michigan Comprehensive Cancer Center Richard T. Cheney, MD Lucian R. Chirieac, MD Dana-Farber/Brigham and Women's Cancer Center † † ¶ Robert H. Lurie Comprehensive Cancer Center of Northwestern University ¶ Roswell Park Cancer Institute Thomas A. D’Amico, MD ¶ Duke Comprehensive Cancer Center Todd L. Demmy, MD ¶ Roswell Park Cancer Institute Apar Kishor P. Ganti, MD † UNMC Eppley Cancer Center at The Nebraska Medical Center Ramaswamy Govindan, MD † Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine Frederic W. Grannis, Jr., MD ¶ City of Hope Comprehensive Cancer Center � � Raymond U. Osarogiagbon, MD St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute Gregory A. Otterson, MD † Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University Jyoti D. Patel, MD ‡ Robert H. Lurie Comprehensive Cancer Center of Northwestern University Katherine M. Pisters, MD ¶ † The University of Texas M. D. Anderson Cancer Center Karen Reckamp, MD, MS † City of Hope Comprehensive Cancer Center † Memorial Sloan-Kettering Cancer Center The University of Texas M. D. Anderson Cancer Center † ¶ Dana-Farber/Brigham and Women's Cancer Center ¶ Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Stephen C. Yang, MD ¶ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Gregory J. Riely, MD, PhD Eric Rohren, MD, PhD George R. Simon, MD Fox Chase Cancer Center Scott J. Swanson, MD Douglas E. Wood, MD † ф Thierry Jahan, MD † Mohammad Jahanzeb, MD St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute David H. Johnson, MD Vanderbilt-Ingram Cancer Center Anne Kessinger, MD UNMC Eppley Cancer Center at The Nebraska Medical Center Ritsuko Komaki, MD The University of Texas M. D. Anderson Cancer Center Feng-Ming Kong, MD, PhD University of Michigan Comprehensive Cancer Center Mark G. Kris, MD † UCSF Helen Diller Family Comprehensive Cancer Center † † † § § Memorial Sloan-Kettering Cancer Center Lee M. Krug, MD † Memorial Sloan-Kettering Cancer Center Quynh-Thu Le, MD § Stanford Comprehensive Cancer Center Inga T. Lennes, MD † Massachusetts General Hospital Cancer Center Renato Martins, MD † Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Janis O’Malley, MD University of Alabama at Birmingham Comprehensive Cancer Center ф * Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Table of Contents NCCN Thymic Malignancies Panel Members Summary of Guidelines Updates Initial Evaluation (THYM-1) Initial Management (THYM-2) Resectable Disease (THYM-3) Advanced Disease (THYM-4) Principles of Surgical Resection (THYM-A) Principles of Radiation Therapy (THYM-B) Principles of Chemotherapy (THYM-C) Guidelines Index Print the Thymic Malignancies Guideline These 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 these 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 makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2010. Clinical Trials: Categories of Evidence and Consensus: NCCN All recommendations are Category 2A unless otherwise specified. See The believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NCCN NCCN Categories of Evidence and Consensus Click here to find a clinical trial at an NCCN Center For help using these documents, please click here Staging Discussion References Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Summary of the Guidelines updates UPDATES Summary of the changes in the 1.2010 version of the Thymic Malignancies Guidelines from the 2.2009 version include: ”MRI of the chest, as clinically indicated” was added to the workup section. Thyroid levels and PFTs were clarified “as clinically indicated.” R0 resection; ostoperative RT was clarified “for high-risk patients” with a category 2B designation. “Resection of isolated oligometastases” was removed as an initial treatment option for localized tumors. ”Re-evaluate for surgery” was added after chemotherapy. The outcomes of “resectable” and “unresectable” were added after the re-evaluation for surgery. For resectable disease, the option listed is “surgical resection” with a clarifying statement “of primary tumor and isolated metastases.” A subsequent treatment option of “consider postoperative RT” was also added. The following bullets are new to the Principles of Surgical Resection page: Phrenic nerve was added to bullet 5. Principles of Radiation Therapy revised to include General Principles, recommendations for Radiation Dose and Radiation Volume, and Radiation Techniques. Reference in footnote “2” updated. Carboplatin/paclitaxel regimen modified and reference added, “Lemma GL, Loehrer PJ, Lee JW, et al. A phase II study of carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: E1C99. J Clin Oncol 2008;26:abstr 8018.” � � � � � � � � patients with thymoma, or thymic carcinoma with capsular invasion: Consider p Surgical biopsy should be avoided if a resectable thymoma is strongly suspected based on clinical and radiologic features (category 2B). Biopsy of a possible thymoma should avoid a transpleural approach (category 2B). During thymectomy, the pleural surfaces should be examined for pleural metastases. In some cases, resection of pleural metastases to achieve complete gross resection may be appropriate. Minimally invasive procedures are not routinely recommended due to lack of long-term data. � � � � � � � � THYM-1 THYM-4 THYM-A THYM-B THYM-C THYM-3 The 2.2010 version of the Thymic Malignancies guidelines represents the addition of the Discussion section correspondent to the changes in the algorithm. Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-1 Mediastinal Mass � � � � � � � CT chest with contrast Serum beta-HCG, AFP, if appropriate CBC, platelets FDG-PET and radiolabeled octreotide scan optional TSH, T3, T4 levels, as clinically indicated Pulmonary function tests (PFTs), as clinically indicated MRI chest, as clinically indicated INITIAL EVALUATION Thymic malignancy likely Thymic malignancy unlikely See Initial Management (THYM-2) See disease specific guidelines (NCCN Table of Contents) Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-2 INITIAL MANAGEMENT Thymic malignancy likely: All patients should be managed by a multidisciplinary team with experience in the management of thymoma Surgically resectable Locally advanced, not resectable Surgical resection (total thymectomy and complete excision of tumor) a Tissue diagnosis with core needle biopsy or open biopsy (Biopsy should not violate the pleural space) See Postoperative Management (THYM-3) See Treatment (THYM-4) a .See Principles of Surgical Resection for Thymic Malignancies (THYM-A) Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-3 POSTOPERATIVE MANAGEMENTRESECTABLE DISEASEa Pathology evaluation R0 resection R1 resection R2 resection Thymoma, no capsular invasion Thymoma or thymic carcinoma, capsular invasion present Thymoma Thymic carcinoma Thymoma or thymic carcinoma Surveillance for recurrence with annual chest CT Consider postoperative RT in high-risk patients (category 2B) b Postoperative RTb Postoperative + Chemotherapy RTb c RT ± chemotherapyb c Surveillance for recurrence with annual chest CT a . b c . . See Principles of Surgical Resection for Thymic Malignancies (THYM-A) See Principles of Radiation Therapy for Thymic Malignancies (THYM-B) See Principles of Chemotherapy for Thymic Malignancies (THYM-C) Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-4 ADVANCED DISEASE Thymoma or thymic carcinoma Localized tumor Evidence of distant metastases Chemotherapyc Chemotherapyc Surgical resection of primary tumor and isolated metastases TREATMENT Re-evaluate for surgery RT ± chemotherapy b c Resectablea Unresectable Consider postoperative RTb a . b c . . See Principles of Surgical Resection for Thymic Malignancies (THYM-A) See Principles of Radiation Therapy for Thymic Malignancies (THYM-B) See Principles of Chemotherapy for Thymic Malignancies (THYM-C) Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-A PRINCIPLES OF SURGICAL RESECTION FOR THYMIC MALIGNANCIES � � � � � � � Surgical biopsy should be avoided if a resectable thymoma is strongly suspected based on clinical and radiologic features (category 2B). Biopsy of a possible thymoma should avoid a transpleural approach (category 2B). Prior to surgery, patients should be evaluated for signs and symptoms of myasthenia gravis and they should be medically controlled prior to undergoing surgical resection. Goal of surgery is complete excision of the lesion with total thymectomy and complete resection of contiguous and noncontiguous disease. Complete resection may require the resection of adjacent structures including pericardium, phrenic nerve, pleura, lung, and even major vascular structures. During thymectomy, the pleural surfaces should be examined for pleural metastases. In some cases, resection of pleural metastases to achieve complete gross resection may be appropriate. Minimally invasive procedures are not routinely recommended due to lack of long-term data. Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. THYM-B 1 OF 2 PRINCIPLES OF RADIATION THERAPY FOR THYMIC MALIGNANCIES (1 of 2) General principles Radiation Dose � � � � � � � � Prior to surgery, all patients should be evaluated by radiation oncologists, surgeons, medical oncologists, diagnostic imaging specialists, and pulmonologists for evaluation of resectability of the tumor and operability of the patients. RT should be given for patients with unresectable (after failure of induction chemotherapy) or incompletely resected invasive thymoma or thymic carcinoma. Prior to RT, any cardiac, pulmonary, and/or neurological toxicities related to the paraneoplastic syndrome, surgery, or induction chemotherapy need to be documented as baseline. Radiation oncologists need to communicate with the surgeon to review the operative findings and to help determine the target volume at risk, and also with the pathologist regarding the detailed pathology report regarding extra-capsular extension and histology. Acronyms and abbreviations of RT are the same as listed in the Principles of RT for non-small cell lung cancer. The dose and fractionation schemes of RT depend on the indication of the radiation and the completeness of surgical resection in postoperative cases. A dose of 60-70 Gy should be given to patients with unresectable disease. For adjuvant treatment, the radiation dose consists of 45-50 Gy for clear/close margins and 54 Gy for microscopically positive resection margins. A total dose of 60 Gy and above should be given to patients with gross residual disease (similar to patients with unresectable disease), when conventional fractionation (1.8 to 2.0 Gy per daily fraction) is applied.1 See NCCN Non-Small Cell Lung Cancer Guidelines 1Mornex F, Resbeut M, Richaud P, et al. Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. Int J Radiat Oncol Biol Phys 1995;32:651-9. See Radiation Volume and Radiation Techniques THYM-B 2 of 2 Version 2.2010, 02/23/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2010 Guidelines Index Thymic Table of Contents Staging, Discussion, ReferencesThymic MalignanciesNCCN ® Radiation Volume Radiation Techniques � � � � � � � � � The gross tumor volume (GTV) should include any grossly visible tumor. Surgical clips indicative of gross residual tumor should be included for postoperative cases. The clinical tumor volume (CTV) for postoperative RT should encompass the entire thymus (for partial resection cases) and any potential sites with residual disease. The CTV should be reviewed with the thoracic surgeon. Extensive elective nodal irradiation (entire mediastinum and bilateral supraclavicular nodal regions) is not recommended, as thymomas do not commonly metastasize to regional lymph nodes. The planning target volume (PTV) should consider the target motion and daily set-up error. The PTV margin should be based on the individual patient's motion, simulation techniques used (with and without inclusion motion), and reproducibility of daily set-up of each clinic. CT-based planning is highly recommended. CT scans should be taken in the treatment position with arms raised above head (treatment position). Simulations of target motion are encouraged whenever possible. CT scans can be performed at the end of natural inhale, exhale, and under free breathing, when more sophisticated techniques like 4D CT, gated CT, or active breathing control (ABC) are not available. Target motion should be managed using the Principles of RT for non-small cell lung cancer. . Intravenous contrast is beneficial in the unresectable setting. Radiation beam arrangements should be selected based on the shape of PTV aiming to confine the prescribed high dose to the target and minimize dose to adjacent critical structures. Anterior-posterior and posterior-anterior (AP/PA) ports weighting more anteriorly, or wedge pair technique may be considered. These techniques, although commonly used during the traditional 2D era, can generate excessive dose to normal tissue RT should be given by 3D conformal technique to reduce surrounding normal tissue damage (e.g., heart, lungs, esophagus, and spinal cord). Intensity-modulated RT (IMRT) may further improve the dose distribution and decrease dose to the normal tissue as indicated. If IMRT is applied, the NCT/ASTRO IMRT guidelines should be followed strictly. In addition to following the normal tissue constraints recommendation using the Principles of RT for non-small cell lung cancer, special attention should be paid to minimize the dose volumes to all the normal structures. Since these patient