NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Thymomas and Thymic

Carcinomas
Version 1.2022 — December 22, 2021

[Link]

Continue

Version 1.2022, 12/22/21 © 2021 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.
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

*David S. Ettinger, MD/Chair † Scott Gettinger, MD † Þ Jose M. Pacheco, MD †

The Sidney Kimmel Comprehensive Yale Cancer Center/Smilow Cancer Hospital University of Colorado Cancer Center
Cancer Center at Johns Hopkins Travis E. Grotz, MD ¶ Sandip P. Patel, MD ‡ † Þ
*Douglas E. Wood, MD/Vice Chair ¶ Mayo Clinic Cancer Center UC San Diego Moores Cancer Center
Fred Hutchinson Cancer Research Center/ Matthew A. Gubens, MD, MS † Jonathan Riess, MD ‡
Seattle Cancer Care Alliance UCSF Helen Diller Family UC Davis Comprehensive Cancer Center
Gregory J. Riely, MD, PhD/Lead † Þ Comprehensive Cancer Center Steven E. Schild, MD §
Memorial Sloan Kettering Cancer Center Aparna Hegde, MD † Mayo Clinic Cancer Center
Dara L. Aisner, MD, PhD ≠ O'Neal Comprehensive Cancer Center at UAB Theresa A. Shapiro, MD, PhD ¥
University of Colorado Cancer Center Rudy P. Lackner, MD ¶ The Sidney Kimmel Comprehensive
Wallace Akerley, MD † Fred & Pamela Buffett Cancer Center Cancer Center at Johns Hopkins
Huntsman Cancer Institute Michael Lanuti, MD ¶ Aditi P. Singh, MD †
at the University of Utah Massachusetts General Hospital Cancer Center Abramson Cancer Center at the
Jessica R. Bauman, MD ‡ † Jules Lin, MD ¶ University of Pennsylvania
Fox Chase Cancer Center University of Michigan Rogel Cancer Center James Stevenson, MD †
Ankit Bharat, MD ¶ Billy W. Loo, Jr., MD, PhD §
Case Comprehensive Cancer Center/
Robert H. Lurie Comprehensive Cancer Center University Hospitals Seidman Cancer Center
Stanford Cancer Institute
of Northwestern University and Cleveland Clinic Taussig Cancer Institute
Christine M. Lovly, MD, PhD †
Debora S. Bruno, MD, MS † Vanderbilt-Ingram Cancer Center Alda Tam, MD ф
Case Comprehensive Cancer Center/ The University of Texas
University Hospitals Seidman Cancer Center Renato G. Martins, MD, MPH † MD Anderson Cancer Center
and Cleveland Clinic Taussig Cancer Institute Fred Hutchinson Cancer Research Center/
Seattle Cancer Care Alliance Tawee Tanvetyanon, MD, MPH †
Joe Y. Chang, MD, PhD § Moffitt Cancer Center
The University of Texas Erminia Massarelli, MD, PhD †
MD Anderson Cancer Center City of Hope National Medical Center Jane Yanagawa, MD ¶
UCLA Jonsson Comprehensive Cancer Center
Lucian R. Chirieac, MD ≠ Daniel Morgensztern, MD †
Dana-Farber/Brigham and Women’s Siteman Cancer Center at Barnes-Jewish Hospital Stephen C. Yang, MD ¶
Cancer Center and Washington University School of Medicine The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
Thomas A. D’Amico, MD ¶ Thomas Ng, MD ¶
Duke Cancer Institute The University of Tennessee Edwin Yau, MD, PhD †
Health Science Center Roswell Park Comprehensive Cancer Center
Malcolm DeCamp, MD ¶
University of Wisconsin Carbone Cancer Center Gregory A. Otterson, MD † NCCN
The Ohio State University Comprehensive Kristina Gregory, RN, MSN, OCN
Thomas J. Dilling, MD, MS § Cancer Center - James Cancer Hospital
Moffitt Cancer Center Miranda Hughes, PhD
and Solove Research Institute
Jonathan Dowell, MD † ‡ Hematology/Hematology oncology § Radiation oncology/
UT Southwestern Simmons Comprehensive Þ Internal medicine Radiotherapy
Cancer Center Continue † Medical oncology
≠ Pathology
¶ Surgery/Surgical oncology
ф Interventional oncology
¥ Patient advocacy * Discussion Writing Committee
NCCN Guidelines Panel Disclosures
Version 1.2022, 12/22/21 © 2021 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.
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

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)
Find an NCCN Member Institution:
Postoperative Treatment and Management (THYM-3) [Link]
Locally Advanced, Advanced, or Recurrent Disease (THYM-4) institutions.

Principles of Surgical Resection (THYM-A) NCCN Categories of Evidence and

Consensus: All recommendations
Principles of Radiation Therapy (THYM-B) are category 2A unless otherwise
Principles of Systemic Therapy (THYM-C) indicated.
World Health Organization Histologic Classification (THYM-D) See NCCN Categories of Evidence
and Consensus.
Staging (ST-1)
NCCN Categories of Preference:
All recommendations are considered
appropriate.
See NCCN Categories of Preference.

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. ©2021.

Version 1.2022, 12/22/21 © 2021 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.
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

Updates in Version 1.2022 of the NCCN Guidelines for Thymomas and Thymic Carcinomas from Version 1.2021 include:
THYM-1
• Footnote a modified: When assessing a mediastinal mass, detection of thymic malignancy versus thymic cyst or thymic hyperplasia can be
better discriminated with chest MRI compared to chest CT, potentially avoiding an unnecessary thymectomy.
THYM-2
• Footnote c modified: Determination of resectability should be made by a thoracic surgeon, with primary focus on thoracic oncology and in
multidisciplinary consultation with medical oncology as needed. Resectability is defined as complete (R0) resection. (also applies to THYM-
4)
THYM-B 2 of 3
• Radiation Techniques
Bullet 3 modified: Compared to IMRT, proton therapy has been shown to improve the dosimetry allowing better sparing of the normal
organs (lungs, heart, and esophagus) with favorable local control and toxicity, and is appropriate for certain patients.
THYM-C 2 of 3
• Thymic Carcinoma; Other Recommended
The following regimen was removed: Octreotide (including LAR) ± prednisone
THYM-D
• Reference updated: Marx A, Detterback F, Marom EM, et al. Tumours of the thymus. In: WHO Classification of Tumours Editorial Board.
Thoracic tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2021 [2021 9 12]. (WHO classification of tumours
series, 5th ed.; vol. 5). Available from: [Link]
THYM-D 2 of 2
• Thymoma Carcinoma Subtypes updated.

Version 1.2022, 12/22/21 © 2021 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
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

INITIAL EVALUATION

• Chest CT with contrasta See Initial Management

Thymic tumor likelyb (THYM-2)
• Serum beta-HCG, AFP, if appropriate
• CBC, platelets
• FDG PET/CT scan (whole-body or
Mediastinal skull base to mid-thigh), as clinically
mass indicated
• Pulmonary function tests, as clinically
indicated See disease-specific
• Chest MRI with contrast, as clinically guidelines as appropriate
Thymic tumor unlikely Consider tissue biopsy
indicateda (NCCN Guidelines for
Treatment by Cancer Type)

a When assessing a mediastinal mass, detection of thymic malignancy versus thymic cyst or thymic hyperplasia can be better discriminated with chest MRI compared to
chest CT, potentially avoiding an unnecessary thymectomy.
b Well-defined anterior mediastinal mass in the thymic bed, tumor markers negative, absence of other adenopathy, and absence of continuity with the thyroid. Marom
EM, et al. J Thorac Oncol 2011;6:S1717-S1723.

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 1.2022, 12/22/21 © 2021 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
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

INITIAL MANAGEMENT

Surgically Surgical resectiond (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 thymomas Tissue diagnosis with core
and thymic carcinomas needle biopsy.d Open biopsy, See Treatment
Locally advanced,
if core biopsy is not feasible
unresectablec (THYM-4)
or not diagnostic (avoid
transpleural approach)

b Well-defined anterior mediastinal mass in the thymic bed, tumor markers negative, absence of other adenopathy, and absence of continuity with the thyroid. Marom
EM, et al. J Thorac Oncol 2011;6:S1717-S1723.
c Determination of resectability should be made by a thoracic surgeon, with primary focus on thoracic oncology and in multidisciplinary consultation with medical
oncology as needed. Resectability is defined as complete (R0) resection.
d See Principles of Surgical Resection (THYM-A).

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 1.2022, 12/22/21 © 2021 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-2
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

POSTOPERATIVE TREATMENT POSTOPERATIVE MANAGEMENT

Thymoma, no Surveillance for recurrence with

capsular invasion or chest CTi with contrast every Recurrent
thymic carcinoma, 6–12 mo for 2 y, then annuallyj disease,
Masaoka-Koga for 5 y for thymic carcinoma and see THYM-4
stage I 10 y for thymoma
R0 resectione
Thymoma or thymic
carcinoma, capsular Consider
invasion present Postoperative RTf
Masaoka-Koga
stages II–IV
Thymoma Postoperative RTf
Pathology
evaluation R1 resectione Surveillance for recurrence with
Thymic Postoperative RTf chest CTi with contrast every 6 Recurrent
carcinoma ± chemotherapyg,h mo for 2 y, then annuallyj for 5 y disease,
for thymic carcinoma and 10 y for see THYM-4
thymoma

Definitive RTf ±
Thymoma chemotherapyg,h
R2 resectione
Thymic Definitive RTf +
carcinoma chemotherapyg,h

e R0 = no residual tumor, R1 = microscopic residual tumor, R2 = macroscopic residual tumor.

f See Principles of Radiation Therapy (THYM-B).
g See Principles of Systemic Therapy for Thymomas and Thymic Carcinomas (THYM-C).
h There is a diversity of opinion on treatment approach. Ruffini E, et al. Eur J Cardiothorac Surg 2019;55:601-609.
i MRI is an appropriate alternative to CT in certain clinical situations.
j The duration for surveillance has not been established.

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 1.2022, 12/22/21 © 2021 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-3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

LOCALLY ADVANCED, TREATMENT

ADVANCED, OR
RECURRENT DISEASE

Surveillance for
Unresectablec Concurrent chemoradiationf,g recurrence with
Surgical
chest CTi with
resectiond
Consider contrast every
of primary
Resectablec,d postoperative 6 mo for 2 y,
Locally tumor and
RTf then annuallyj
advanced isolated
• Chest CTi for 5 y for thymic
metastases
with contrast carcinoma and
• FDG PET/CT 10 y for thymoma
Potentially (whole-body
Thymoma or Chemotherapyg
resectablec,d or skull base
thymic carcinoma: to mid-thigh)
All patients should Solitary as clinically
be managed by a metastasis indicated
multidisciplinary or
team with ipsilateral RTf ±
Unresectablec
experience in the pleural chemotherapyg
management of metastasis
thymomas and Consider chemotherapyg
thymic carcinomas Surgeryd or
RTf

Evidence of
extrathoracic Chemotherapyg
metastases

c Determination of resectability should be made by a thoracic surgeon, with primary focus on thoracic oncology and in multidisciplinary consultation with medical
oncology as needed. Resectability is defined as complete (R0) resection.
d See Principles of Surgical Resection (THYM-A).
f See Principles of Radiation Therapy (THYM-B).
g See Principles of Systemic Therapy for Thymomas and Thymic Carcinomas (THYM-C).
i MRI is an appropriate alternative to CT in certain clinical situations.
j The duration for surveillance has not been established.

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 1.2022, 12/22/21 © 2021 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-4
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF SURGICAL RESECTION

• Surgical resection should be performed on carefully evaluated patients by thoracic surgeons with experience in managing thymomas
and thymic carcinomas. Locally advanced (unresectable) and resectable stage ≥ II cases should be discussed and evaluated by a
multidisciplinary team.
• Surgical biopsy should be avoided if a resectable thymoma is strongly suspected based on clinical and radiologic features because of the
substantial potential of tumor seeding when the tumor capsule is violated.
• Biopsy of a possible thymoma should avoid a transpleural approach because of the substantial risk of converting a stage I thymoma to a
stage IV thymoma by spreading tumor within the pleural space.
• Prior to surgery, patients should be evaluated for signs and symptoms of myasthenia gravis and 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 the pericardium, phrenic nerve, pleura, lung, and even major
vascular structures. Bilateral phrenic nerve resection should be avoided due to severe respiratory morbidity.
• Surgical clips should be placed at the time of resection to areas of close margins, residual disease, or tumor adhesion to unresected normal
structures to help guide accurate radiation therapy when indicated.
• During thymectomy, the pleural surfaces should be examined for pleural metastases. If feasible, resection of pleural metastases to achieve
complete gross resection is appropriate.
• Minimally invasive procedures are not routinely recommended due to the lack of long-term data. However, minimally invasive procedures
may be considered for clinical stage I–II if all oncologic goals can be met as in standard procedures, and if performed in specialized centers
by surgeons with experience in these techniques.1-6

1 Pennathur A, Qureshi I, Schubert MJ, et al. Comparison of surgical techniques for early stage thymoma: feasibility of minimally invasive thymectomy and comparison
with open resection. J Thorac Cardiovasc Surg 2011;141:694-701.
2 Ye B, Tantai JC, Ge XX, et al. Surgical techniques for early-stage thymoma: video-assisted thorascopic thymectomy versus transsternal thymectomy. J Thorac
Cardiovasc Surg 2014;147:1599-1603.
3 Sakamaki Y, Oda T, Kanazawa G, et al. Intermediate-term oncologic outcomes after video-assisted thorascopic thymectomy for early-stage thymoma. J Thorac
Cardiovasc Surg 2014;148:1230-1237.
4 Manoly I, Whistance RN, Sreekumar R, et al. Early and mid-term outcomes of trans-sternal and video-assisted thoracoscopic surgery for thymoma. Eur J Cardiothorac
Surg 2014;45:e187-193.
5 Liu TJ, Lin MW, Hsieh MS, et al. Video-assisted thoracoscopic surgical thymectomy to treat early thymoma: a comparison with the conventional transsternal approach.
Ann Surg Oncol 2014;322-328.
6 Friedant AJ, Handorf EA, Su S, Scott WJ. Minimally invasive versus open thymectomy for thymic malignancies: systematic review and meta-analysis. J Thorac Oncol
2016;11:30-38.

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 1.2022, 12/22/21 © 2021 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-A
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF RADIATION THERAPY1,2

General Principles
• Recommendations regarding RT should be made by radiation oncologists with experience in managing thymomas and thymic carcinomas.
• Definitive RT should be given for patients with unresectable disease (if disease progresses on induction chemotherapy), incompletely
resected invasive thymoma or thymic carcinoma, or as adjuvant therapy after chemotherapy and surgery for patients with locally advanced
disease.
• Radiation oncologists need to communicate with the surgeon to review the operative findings and to help determine the target volume
at risk. They also need to communicate with the pathologist regarding the detailed pathology on histology, disease extent such as
extracapsular extension, and surgical margins.
• The review of preoperative imaging and co-registration of preoperative imaging into the planning system are helpful in defining treatment
volumes.
• Acronyms and abbreviations for RT are the same as listed in the Principles of Radiation Therapy for the NCCN Guidelines for Non-Small Cell
Lung Cancer.

Radiation Dose
• 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 to 70 Gy should be given to patients with unresectable disease.
• For adjuvant treatment, the radiation dose consists of 45 to 50 Gy for clear/close margins and 54 Gy for microscopically positive resection
margins. A total dose of 60–70 Gy should be given to patients with gross residual disease (similar to patients with unresectable disease),3,4
when conventional fractionation (1.8–2.0 Gy per daily fraction) is applied.
• Depending on the treatment objectives in the palliative setting, typical palliative doses (eg, 8 Gy in a single fraction, 20 Gy in 5 fractions, 30
Gy in 10 fractions) up to definitive doses for more durable local control and highly conformal techniques for limited volume metastases may
be appropriate, given the relatively long natural history of even metastatic thymoma.

Radiation Volume
• The gross tumor volume should include any grossly visible tumor. Surgical clips indicative of gross residual tumor should be included for
postoperative adjuvant RT.
• The clinical target volume (CTV) for postoperative RT should encompass the entire thymus (for partial resection cases), surgical clips, and
any potential sites with residual disease. The CTV should be reviewed with the thoracic surgeon.
• Extensive elective nodal irradiation (ENI) (entire mediastinum and bilateral supraclavicular nodal regions) is not recommended, as thymomas
do not commonly metastasize to regional lymph nodes.5
• The planning target volume (PTV) should consider the target motion and daily setup 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 setup of each clinic.
See Radiation Techniques (THYM-B 2 of 3)
References on THYM-B (3 of 3)

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.
THYM-B
Version 1.2022, 12/22/21 © 2021 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.
® ® ®
1 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF RADIATION THERAPY

Radiation Techniques
• Target motion should be managed using the Principles of Radiation Therapy in the NCCN Guidelines for Non-Small Cell Lung Cancer.
Intravenous contrast is beneficial in the unresectable setting.
• In addition to following the normal tissue constraints recommendation using the Principles of Radiation Therapy in the NCCN Guidelines for
Non-Small Cell Lung Cancer, more conservative limits are recommended to minimize the dose volumes to all the normal structures. Since
these patients are younger and mostly long-term survivors, the mean total dose to the heart should be as low as reasonably achievable to
potentially maximize survival.
• A minimum technological standard for RT is CT-planned 3-D conformal radiation therapy (3D-CRT). More advanced technologies are
appropriate when needed to deliver curative RT safely. These technologies include (but are not limited to) 4D-CT and/or PET/CT simulation,
IMRT/VMAT, IGRT, motion management, and proton therapy. In particular, IMRT is preferred over 3D-CRT. Compared to IMRT, proton therapy
has been shown to improve the dosimetry allowing better sparing of the normal organs (lungs, heart, and esophagus)6 with favorable local
control and toxicity, and is appropriate.7

See General Principles, Radiation Dose, and Radiation Volume (THYM-B 1 of 3)

References on THYM-B (3 of 3)

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.
THYM-B
Version 1.2022, 12/22/21 © 2021 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.
® ® ®
2 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF RADIATION THERAPY

REFERENCES
1 Gomez D, Komaki R, Yu J, et al. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol 2011;6:S1743-1748.
2 Gomez D, Komaki R. Technical advances of radiation therapy for thymic malignancies. J Thorac Oncol 2010;5:S336-343.
3 Mornex 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;32:651-659.
4 Myojin M, Choi NC, Wright CD, et al. Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat
Oncol Biol Phys 2000;46:927-933.
5 Ruffini E, Mancuso M, Oliaro A, et al. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 1997;113:55-63.
6 Parikh RR, Rhome R, Hug E, et al. Adjuvant proton beam therapy in the management of thymoma: a dosimetric comparison and acute toxicities. Clin Lung Cancer
2016;17:362-366.
7 Vogel J, Berman AT, Pechet TT, et al. Prospective study of proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma: early
response and toxicity assessment. Radiother Oncol 2016;118:504-509.

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.
THYM-B
Version 1.2022, 12/22/21 © 2021 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.
® ® ®
3 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF SYSTEMIC THERAPY

FIRST-LINE COMBINATION CHEMOTHERAPY REGIMENSa
THYMOMA THYMIC CARCINOMA
Preferred (Other Recommended for Thymic Carcinoma) Preferred (Other Recommended for Thymoma)
• CAP1 • Carboplatin/paclitaxel6,7
Cisplatin 50 mg/m2 IV day 1 Carboplatin AUC 6
Doxorubicin 50 mg/m2 IV day 1 Paclitaxel 200 mg/m2
Cyclophosphamide 500 mg/m2 IV day 1 Administered every 3 weeks
Administered every 3 weeks

Other Recommended for Thymic Carcinoma and Thymoma

• CAP with prednisone2
Cyclophosphamide 500 mg/m2 IV on day 1;
Doxorubicin, 20 mg/m2/day IV continuous infusion on days 1–3;
Cisplatin 30 mg/m2 days 1–3;
Prednisone 100 mg/day days 1–5;
Administered every 3 weeks

• ADOC3
Doxorubicin 40 mg/m2 IV day 1;
Cisplatin 50 mg/m2 IV day 1;
Vincristine 0.6 mg/m2 IV day 3;
Cyclophosphamide 700 mg/m2 IV day 4
Administered every 3 weeks

• PE4
Cisplatin 60 mg/m2 IV day 1; Etoposide 120 mg/m2/day IV days 1–3;
Administered every 3 weeks
Subsequent Therapy THYM-2 of 3
• Etoposide/ifosfamide/cisplatin5
References THYM-C 3 of 3
Etoposide 75 mg/m2 on days 1–4; Ifosfamide 1.2 g/m2 on days 1–4; Cisplatin 20 mg/m2 on days 1–4
Administered every 3 weeks
a If patients cannot tolerate first-line combination regimens, consider second-line systemic therapy options.

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.
THYM-C
Version 1.2022, 12/22/21 © 2021 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.
® ® ® 1 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF SYSTEMIC THERAPY

SECOND-LINE SYSTEMIC THERAPY

(in alphabetical order)

THYMOMA THYMIC CARCINOMA

Other Recommended Other Recommended
• Etoposide4,8,9 • Everolimus10
• Everolimus10 • 5-FU and leucovorin11
• 5-FU and leucovorin11 • Gemcitabine ± capecitabine12,13
• Gemcitabine ± capecitabine12,13 • Lenvatinibc,18
• Ifosfamide14 • Paclitaxel17
• Octreotideb (including LAR) +/- prednisone15 • Pembrolizumabd,19,20
• Paclitaxel16 • Pemetrexed16
• Pemetrexed17 • Sunitinib21

Useful in Certain Circumstances

• Etoposide4,8,9
• Ifosfamide14

b Nuclear medicine scan to assess for octreotide-avid disease.

c There is a high risk for side effects and frequent dose reductions may be needed.
References THYM-C 3 of 3
d Pembrolizumab is not recommended for patients with thymoma. In patients with thymic carcinoma, there is 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.

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.
THYM-C
Version 1.2022, 12/22/21 © 2021 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.
® ® ® 2 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

PRINCIPLES OF SYSTEMIC THERAPY FOR THYMIC MALIGNANCIES — REFERENCES

1 Loehrer PJ Sr, Kim K, Aisner SC, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The
Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 1994;12:1164-1168.
2 Kim ES, Putnam JB, Komaki R, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and
consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 2004;44:369-379.
3 Fornasiero A, Daniele O, Ghiotto C, et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer 1991;68:30-33.
4 Giaccone G, Ardizzoni A, Kirkpatrick A, et al. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the
European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 1996;14:814-820.
5 Loehrer PJ Sr, Jiroutek M, Aisner S, et al. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an
intergroup trial. Cancer 2001;91:2010-2015.
6 Lemma GL, Lee JW, Aisner SC, et al. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 2011;29:2060-2065.
7 Hirai F, Yamanaka T, Taguchi K, et al A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L. Ann Oncol 2015;26:363-8.
8 Bluthgen MV, Boutros C, Fayard F, et al. Activity and safety of oral etoposide in pretreated patients with metastatic or recurrent thymic epithelial tumors (TET): A single-
institution experience. Lung Cancer 2016;99:111-116.
9 Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin
Oncol 1990;8:1613-1617.
10 Zucali PA, De Pas TM, Palmieri G, et al. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based
chemotherapy. J Clin Oncol 2018;36:342-349.
11 Thomas CR, Wright CD, Loehrer PJ. Thymoma: state of the art. J Clin Oncol 1999;17:2280-2289.
12 Palmieri G, Merola G, Federico P, et al. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic
epithelial tumors (TETs). Ann Oncol 2010;21:1168-1172.
13 Palmieri G, Buonerba C, Ottaviano M, et al. Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a phase II trial. Future Oncol 2014;10:2141-
2147.
14 Highley MS, Underhill CR, Parnis FX, et al. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol 1999;17:2737-2744.
15 Loehrer PJ Sr, Wang W, Johnson DH, et al. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative
Oncology Group Phase II Trial. J Clin Oncol 2004;22:293-299.
16 Umemura S, Segawa Y, Fujiwara K, et al. A case of recurrent metastatic thymoma showing a marked response to paclitaxel monotherapy. Jpn J Clin Oncol
2002;32:262-265.
17 Gbolahan OB, Porter RF, Salter JT, et al. A phase II study of pemetrexed in patients with recurrent thymoma and thymic carcinoma. J Thorac Oncol 2018;13:1940-
1948.
18 Sato J, Satouchi M, Itoh S, et al. Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol 2020;
21:843-850.
19 Giaccone G, Kim C, Thompson J, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol 2018;19:347-355.
20 Cho J, Kim HS, Ku BM, et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: An open-label phase II trial. J Clin Oncol 2019;37:2162-
2170.
21 Thomas A, Rajan A, Berman A, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol
2015;16:177-186.

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.
THYM-C
Version 1.2022, 12/22/21 © 2021 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.
® ® ® 3 OF 3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

WORLD HEALTH ORGANIZATION HISTOLOGIC CLASSIFICATION1

Thymoma subtype Obligatory criteria Optional criteria

Type A Occurrence of bland, spindle shaped epithelial cells (at least focally); paucitya Polygonal epithelial cells CD20+
or absence of immature (TdT+) T cells throughout the tumor epithelial cells
Atypical type A Criteria of type A thymoma; in addition: comedo-type tumor necrosis; Polygonal epithelial cells CD20+
variant increased mitotic count (>4/2mm2); nuclear crowding epithelial cells
Type AB Occurrence of bland, spindle shaped epithelial cells (at least focally); Polygonal epithelial cells CD20+
abundancea of immature (TdT+) T cells focally or throughout tumor epithelial cells
Type B1 Thymus-like architecture and cytology: abundance of immature T cells, areas Hassall’s corpuscles; perivascular
of medullary differentiation (medullary islands); paucity of polygonal or spaces
dendritic epithelia cells without clustering (i.e.<3 contiguous epithelial cells)
Type B2 Increased numbers of single or clustered polygonal or dendritic epithelial cells Medullary islands; Hassall’s
intermingled with abundant immature T cells corpuscles; perivascular spaces
Type B3 Sheets of polygonal slightly to moderately atypical epithelial cells; absent or Hassall’s corpuscles; perivascular
rare intercellular bridges; paucity or absence of intermingled TdT+ T cells spaces
MNTb Nodules of bland spindle or oval epithelial cells surrounded by an epithelial Lymphoid follicles; monoclonal B cells
cell-free lymphoid stroma and/or plasma cells (rare)
Metaplastic Biphasic tumor composed of solid areas of epithelial cells in a background of Pleomorphism of epithelial cells; actin,
thymoma bland-looking spindle cells; absence of immature T cells keratin, or EMA-positive spindle cells
Rare othersc

a Paucity versus abundance: any area of crowded immature T cells or moderate numbers of immature T cells in >10% of the investigated tumor are indicative of “abundance.”
b MNT, micronodular thymoma with lymphoid stroma.
c Microscopic thymoma; sclerosing thymoma, lipofibroadenoma.

1 Marx A, Detterback F, Marom EM, et al. Tumours of the thymus. In: WHO Classification of Tumours Editorial Board. Thoracic tumours [Internet]. Lyon (France):
International Agency for Research on Cancer; 2021 [2021 9 12]. (WHO classification of tumours series, 5th ed.; vol. 5).
Available from: [Link]

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.
THYM-D
Version 1.2022, 12/22/21 © 2021 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.
® ® ® 1 OF 2
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

WORLD HEALTH ORGANIZATION HISTOLOGIC CLASSIFICATION1

Thymic Carcinoma Subtypes
• Squamous carcinomas
Squamous cell carcinoma, NOS
Basaloid carcinoma
Lymphoepithelial carcinoma
• Adenocarcinomas
Adenocarcinoma, NOS
Low grade papillary adenocarcinoma
Thymic carcinoma with adenoid cystic carcinoma-like features
Adenocarcinoma, enteric-type
• Adenosquamous carcinoma
• NUT carcinomas
• Salivary gland-like carcinomas
Mucoepidermoid carcinoma
Clear cell carcinoma
Sarcomatoid carcinoma
Carcinosarcoma
• Carcinoma, undifferentiated, NOS
• Thymic Carcinoma, NOS

1 Marx A, Detterback F, Marom EM, et al. Tumours of the thymus. In: WHO Classification of Tumours Editorial Board. Thoracic tumours [Internet]. Lyon (France):
International Agency for Research on Cancer; 2021 [2021 9 12]. (WHO classification of tumours series, 5th ed.; vol. 5).
Available from: [Link]

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.
THYM-D
Version 1.2022, 12/22/21 © 2021 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.
® ® ® 2 OF 2
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

Staging
Table 1. Modified Masaoka clinical staging of thymoma1-3

Masaoka Stage Diagnostic Criteria

Stage I Macroscopically and microscopically completely encapsulated
Stage II (A) Microscopic transcapsular invasion
(B) Macroscopic invasion into surrounding fatty tissue or grossly
adherent to but not through mediastinal pleura or pericardium
Stage III Macroscopic invasion into neighboring organs (ie, pericardium, great
vessels, lung)
(A) Without invasion of great vessels
(B) With invasion of great vessels
Stage IV (A) Pleural or pericardial dissemination
(B) Lymphogenous or hematogenous metastasis

1 Reprinted from Wright CD. Management of thymomas. Crit Rev Oncol Hematol 2008;65:109-120, with permission from Elsevier.
2 Note that the Masaoka staging system is also used to stage thymic carcinomas.
3 Detterbeck FC, Nicholson AG, Kondo K, et al. The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol
2011;6:S1710-S1716.

Version 1.2022, 12/22/21 © 2021 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.
ST-1
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

Staging
Table 2. Definitions for TNM*,** AJCC Prognostic Groups
Primary Tumor (T) Stage I T1a,b N0 M0
TX Primary tumor cannot be assessed Stage II T2 N0 M0
T0 No evidence of primary tumor Stage IIIA T3 N0 M0
T1 Tumor encapsulated or extending into the mediastinal fat; may involve the mediastinal Stage IIIB T4 N0 M0
pleura
Stage IVA Any T N1 M0
T1a Tumor with no mediastinal pleura involvement
Any T N0-N1 M1a
T1b Tumor with direct invasion of mediastinal pleura
T2 Tumor with direct invasion of the pericardium (either partial or full thickness)
Stage IVB Any T N2 M0-M1a
T3 Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior Any T Any N M1b
vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins
T4 Tumor with invasion into any of the following: aorta (ascending, arch, or descending)
arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in anterior (perithymic) lymph nodes
N2 Metastasis in deep intrathoracic or cervical lymph nodes
Distant Metastasis (M)
M0 No pleural, pericardial, or distant metastasis
M1 Pleural, pericardial, or distant metastasis
M1a Separate pleural or pericardial nodule(s)
M1b Pulmonary intraparenchymal nodule or distant organ metastasis

*Involvement must be microscopically confirmed in pathological staging, if possible.

**T categories are defined by “levels” of invasion; they reflect the highest degree of invasion regardless of how many other (lower-level) structures are invaded. T1, level 1
structures: thymus, anterior mediastinal fat, mediastinal pleura; T2, level 2 structures: pericardium; T3, level 3 structures: lung, brachiocephalic vein, superior vena cava,
phrenic nerve, chest wall, hilar pulmonary vessels; T4, level 4 structures: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium,
trachea, esophagus.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition
(2017) published by Springer International Publishing.

Version 1.2022, 12/22/21 © 2021 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.
ST-2
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022 NCCN Guidelines Index

Table of Contents
Thymomas and Thymic Carcinomas Discussion

NCCN Categories of Evidence and Consensus

Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.

NCCN Categories of Preference

Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate,
Preferred intervention affordability.
Other recommended Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data;
intervention or significantly less affordable for similar outcomes.
Useful in certain
Other interventions that may be used for selected patient populations (defined with recommendation).
circumstances
All recommendations are considered appropriate.

Version 1.2022, 12/22/21 © 2021 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.
CAT-1
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

Discussion This discussion is being updated to correspond with the

newly updated algorithm. Last updated 03/11/19

Table of Contents

Overview .............................................................................................................................................................................................................. MS-2

Literature Search Criteria and Guidelines Update Methodology............................................................................................................................. MS-2

Mediastinal Masses .............................................................................................................................................................................................. MS-2

Thymic Masses .................................................................................................................................................................................................... MS-3

Diagnosis .......................................................................................................................................................................................................... MS-3

Staging ............................................................................................................................................................................................................. MS-4

Treatment ......................................................................................................................................................................................................... MS-4

Thymomas ........................................................................................................................................................................................................... MS-4

Thymic Carcinomas .............................................................................................................................................................................................. MS-7

Summary.............................................................................................................................................................................................................. MS-9

References......................................................................................................................................................................................................... MS-10

Version 1.2022 © 2021 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.
MS-1
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

Overview Literature Search Criteria and Guidelines Update

Thymic epithelial tumors originate in the thymus and include thymomas
Methodology
and thymic carcinomas.1,2 Thymomas are a common primary tumor in An electronic search of the PubMed database was performed to obtain
the anterior mediastinum, although they are rare (1.5 cases/million).3-6 key literature in Thymomas and Thymic Carcinomas using the
Thymic carcinomas are very rare. Although thymomas can spread following search terms: Thymomas; Thymic Carcinomas. The PubMed
locally, they are much less invasive than thymic carcinomas.4 Patients database was chosen, because it is the most widely used resource for
with thymic carcinomas often present with metastases.7 Patients with medical literature and indexes peer-reviewed biomedical literature. The
thymomas have 5-year survival rates of approximately 90%.8-10 search results were narrowed by selecting studies in humans published
However, 5-year survival rates for thymic carcinomas are approximately in English. Results were confined to the following article types: Clinical
55%.11-13 Trial, Phase 1; Clinical Trial, Phase 2; Clinical Trial, Phase 3; Clinical
Trial, Phase 4; Guideline; Meta-Analysis; Randomized Controlled Trial;
These NCCN Clinical Practice Guidelines in Oncology (NCCN Systematic Reviews; and Validation Studies.
Guidelines®) focus on thymomas and thymic carcinomas and outline the
evaluation, treatment, and management of these mediastinal tumors; The data from key PubMed articles selected by the NCCN Panel for
these NCCN Guidelines® were first published in 2007 and have been review during the NCCN Guidelines update meeting, as well as articles
subsequently updated every year. The Summary of the Guidelines from additional sources deemed as relevant to these Guidelines and
Updates section in the algorithm briefly describes the new changes for discussed by the NCCN Panel, have been included in this version of the
2019, which are described in greater detail in this revised Discussion Discussion section (eg, e-publications ahead of print, meeting
text; new references have been added. Additional supplementary abstracts). If high-level evidence is lacking, recommendations are
material in the NCCN Guidelines for Thymomas and Thymic based on the panel’s review of lower-level evidence and expert opinion.
Carcinomas includes the Principles of Surgical Resection, Principles of The complete details of the development and update of the NCCN
Radiation Therapy, Principles of Systemic Therapy for Thymic Guidelines are available at [Link].
Malignancies, and the World Health Organization Histologic
Classification. These NCCN Guidelines for Thymomas and Thymic Mediastinal Masses
Carcinomas were developed and are updated by panel members who Masses in the anterior mediastinum can be neoplasms (eg, thymomas,
are also on the NCCN Guidelines for Non-Small Cell Lung Cancer lymphomas, thymic carcinomas, thymic carcinoids, thymolipomas, germ
Panel. All recommendations are category 2A unless otherwise cell tumors, lung metastases) or non-neoplastic conditions (eg,
indicated. Category 2A recommendations are based on lower-level intrathoracic goiter, thymic cysts, lymphangiomas, aortic
evidence (eg, phase 2 trials, case reports), and there is uniform NCCN aneurysms).5,14-17 Many mediastinal masses are benign, especially
consensus that the intervention is appropriate (ie, ≥85% of panel those occurring in asymptomatic patients; however, symptomatic
members agree). patients often have malignant mediastinal lesions. All patients with a
mediastinal mass should be evaluated to determine the type of mass

Version 1.2022 © 2021 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.
MS-2
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

and the extent of disease before treatment (see Initial Evaluation in the the algorithm).15,27-35 On CT, a thymoma is usually a well-defined round
algorithm). It is essential to differentiate between thymic malignancies or oval mass in the thymus without lymph node enlargement.33,36,37 In
and other conditions (eg, lung metastases, lymphoma, goiter, germ cell patients who cannot tolerate iodinated contrast, chest MRI is
tumors) before treatment, because management differs for these indicated.33 Combined PET/CT may be useful for determining whether
conditions.1,18,19 Most masses in the mediastinum are metastases from extrathoracic metastases are present.38,39 PET/CT provides better
a primary lung cancer (eg, non-small cell lung cancer). However, about correlation with anatomic structures than PET alone. For the 2019
50% of primary cancers in the anterior mediastinum are thymomas.20 update (Version 1), the NCCN Panel clarified that PET/CT scans are
whole body or skull base to mid-thigh, as clinically indicated.
Patients with thymomas often have an indolent presentation, whereas Alpha-fetoprotein (AFP) levels and beta–human chorionic gonadotropin
those with lymphoma or germ cell tumors have a rapid onset of (beta-hCG) levels may be measured to rule out germ cell tumors (see
symptoms.19 Lymphomas typically manifest as generalized disease but Initial Evaluation in the algorithm). Thymic epithelial tumors are likely if
can also be primary anterior mediastinal lesions (ie, nodular sclerosing the following are present: 1) a well-defined mediastinal mass in the
Hodgkin’s disease, non-Hodgkin’s lymphomas [diffuse large B-cell thymic bed that is not continuous with the thyroid gland; 2) tumor
lymphoma and acute lymphoblastic lymphoma]); patients typically have markers for AFP or beta-hCG are negative; and 3) no other adenopathy
lymphadenopathy (see the NCCN Guidelines for Hodgkin Lymphoma is present.1,2,40
and the NCCN Guidelines for Non-Hodgkin’s Lymphomas, available at
[Link]).17,21 Thymic carcinoids are rare neuroendocrine tumors Thymic Masses
that can be associated with multiple endocrine neoplasia type 1 (MEN1) Diagnosis
syndrome (see the NCCN Guidelines for Neuroendocrine Tumors,
The WHO histologic classification system can be used to distinguish
available at [Link]).22,23 Extragonadal germ cell tumors are
between thymomas, thymic carcinomas, and thymic carcinoids (see
rare tumors that may also occur in the mediastinum.24,25
the algorithm).2,41 The WHO classification is also used to differentiate
Low-dose CT is recommended for detecting lung cancer in individuals among different histologic types of thymomas (ie, A, AB, B1, B2, B3);
at high risk (see the NCCN Guidelines for Lung Cancer Screening, however, it is difficult to classify thymomas.42 The WHO histologic
available at [Link]).26 There are no data to suggest that classification system was revised in 2015.1,2 Thymic carcinomas are
screening with low-dose CT improves survival for patients with type C in the WHO classification, although they are very different from
thymomas and thymic carcinomas; therefore, low-dose CT screening is thymomas and are not advanced thymomas (see Thymic Carcinomas
not recommended for detecting thymomas and thymic carcinomas.26 in this Discussion).2,43 However, the histologic subtype is less
However, mediastinal masses (eg, lung metastases, thymomas, thymic important for management than stage of disease and the extent of
carcinomas) may be detected in individuals undergoing chest imaging. resection (ie, R0, R1, R2) (see Postoperative Treatment and
Management in the algorithm).12,44-48 For stage III to IV thymomas,
Recommended tests for assessing mediastinal masses include chest 5-year survival rates have been reported to be 90% in patients with
CT with contrast and blood chemistry studies (see Initial Evaluation in

Version 1.2022 © 2021 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.
MS-3
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

total resection.8,12 For thymic carcinomas, 5-year survival rates are thymectomy, the pleural surfaces should be examined for metastases.
lower, even in those with total resection.11,49 To achieve a complete gross resection, removal of pleural metastases
may be appropriate in some patients.71-73 Core needle or open biopsy is
Staging recommended for locally advanced, unresectable thymic masses. The
Although several staging systems exist, the Masaoka staging system cancer protocol for thymic tumors from the College of American
has been the most widely accepted system for management and Pathologists may be useful for assessing specimens.74
determination of prognosis for both thymomas and thymic carcinomas
(see Table 1 in the algorithm).10,12,50-56 A new staging system for Minimally invasive procedures are not routinely recommended, because
thymomas and thymic carcinomas is based on a combined effort by the only a few long-term studies are available regarding recurrence and
International Thymic Malignancy Interest Group (ITMIG) and survival.75-77 However, minimally invasive procedures may be
International Association for the Study of Lung Cancer (IASLC); this considered if recommended oncologic goals can be met (as previously
staging system was used as the basis for the new AJCC TNM system described) and if performed in specialized centers with surgeons with
for thymic malignancies (8th edition).40,57-62 Clinicians may find it useful expertise in these techniques.77-81 A systematic review of 1061 patients
to use both the Masaoka and the AJCC TNM staging systems.2,58 The with thymomas reported that 5-year overall survival after video-assisted
new staging system for thymic malignancies from the AJCC (8th thoracoscopic surgery (VATS: 83%–100% vs. open: 79%–98%) and
edition) became effective on January 1, 2018 (see Table 2 in the 10-year recurrence-free survival (VATS: 89%–100% vs. open: 80%–
algorithm).1,63 Patients with stage I to III thymomas have a 5-year 93%) were similar in patients undergoing VATS compared to open
survival rate of approximately 85% versus 65% for those with stage IV thymectomy, although outcomes may be skewed due to selection
disease.10,64,65 In approximately 50% of patients, mortality is not related bias.75 A retrospective review in 2835 patients assessed VATS
to thymoma.51 Mortality is related to myasthenia gravis in approximately thymectomy compared with sternotomy in patients with thymomas.82
20% of patients. The 5-year overall survival rate was 97.9% in the VATS group. The
overall survival rates were not significantly different when comparing the
Treatment VATs group versus the sternotomy group (P = .74). A meta-analysis
The optimal plan of care for patients with thymic malignancies should be also showed that VATS was safe and patients had similar overall
developed before treatment, after evaluation by radiation oncologists, survival when compared with those receiving open thymectomy.83
thoracic surgeons, medical oncologists, and diagnostic imaging
Thymomas
specialists.66,67 It is critical to determine whether the mass can be
surgically resected; a board-certified thoracic surgeon with a primary Thymomas typically occur in adults 40 to 70 years of age; they are rare
focus on thoracic oncology should make this decision. Total in children and adolescents.19,84 The etiology of thymomas is unknown;
thymectomy and complete surgical excision of the tumor are alcohol, tobacco smoking, and ionizing radiation do not appear to be
recommended whenever possible for most resectable tumors (see risk factors for thymomas.3 The incidence of thymomas is higher in
Principles of Surgical Resection in the algorithm).10,12,19,68-70 During African Americans as well as Asians and Pacific Islanders, which

Version 1.2022 © 2021 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.
MS-4
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

suggests there may be a genetic component.3,85 Although some Adjuvant therapy is not recommended for completely resected (R0)
patients are asymptomatic, others present with chest pain, cough, or stage I thymomas.69,100,101 For incompletely resected thymomas,
dyspnea. Patients with thymomas often have autoimmune diseases. postoperative RT is recommended (see Postoperative Treatment and
Approximately 30% to 50% of patients with thymomas have myasthenia Management in the algorithm).66,69,102,103 Note that extensive elective
gravis.86 Symptoms suggestive of myasthenia gravis include drooping nodal radiation is not recommended, because thymomas do not
eyelids, double vision, drooling, difficulty climbing stairs, hoarseness, typically metastasize to regional lymph nodes.10,104 CT-based treatment
and/or dyspnea. Before any surgical procedure, all patients suspected planning is highly recommended before RT (see Principles of Radiation
of having thymomas (even those without symptoms) should have their Therapy in the algorithm).105 RT should be given by the 3D conformal
serum antiacetylcholine receptor antibody levels measured to determine technique to reduce damage to surrounding normal tissue (eg, heart,
whether they have myasthenia gravis to avoid respiratory failure during lungs, esophagus, spinal cord).66
surgery.64,87 If patients have myasthenia gravis, they should receive
treatment by a neurologist with experience in myasthenia gravis before Use of intensity-modulated RT (IMRT) may decrease the dose to the
undergoing surgical resection.88-91 normal tissues.105,106 If IMRT is used, guidelines from the NCI Advanced
Technology Center (ATC) and ASTRO/ACR should be followed.107-111
Although thymomas can be locally invasive (eg, pleura, lung), they The ICRU-83 (International Commission on Radiation Units and
uncommonly spread to regional lymph nodes or extrathoracic Measurements Report 83) recommendations are also a useful
sites.10,64,92,93 Surgery (ie, total thymectomy and complete excision of resource.110,112 Although the normal tissue constraints
tumor) is recommended for all resectable thymomas for patients who recommendations for lung cancer may be used (see the Principles of
can tolerate the surgery.20,94,95 For resected stage I and II thymomas, Radiation Therapy in the NCCN Guidelines for Non-Small Cell Lung
the 10-year survival rate is excellent (approximately 90% and 70%, Cancer, available at [Link]), more conservative limits are
respectively).19,96 Completeness of resection is the most important recommended to minimize the dose volumes to all the normal
predictor of outcome.8 Surgical biopsy is not necessary if a resectable structures.113,114 Because these patients are younger and usually
thymoma is strongly suspected based on clinical and radiologic features long-term survivors, the mean dose to the heart should be as low as
(eg, patients have myasthenia gravis and a characteristic mass on reasonably achievable. Note that the normal tissue dose-volume
CT).19 A transpleural approach should be avoided during biopsy of a constraints for the lung, heart, spinal cord, esophagus, and brachial
possible thymoma to prevent tumor seeding.89,97 Small biopsy sampling plexus for conventionally fractionated chemoradiation were revised for
(fine-needle or core needle biopsy) does not always indicate whether the 2019 update (Version 1) (see the Principles of Radiation Therapy in
invasion is present.98 ITMIG and CAP have established procedures for the NCCN Guidelines for Non-Small Cell Lung Cancer).
reporting the surgical and pathologic findings from resection
specimens.74,99 A definitive dose of 60 to 70 Gy is recommended for patients with
unresectable disease. For adjuvant treatment, a dose of 45 to 50 Gy is
recommended for clear or close margins; a dose of 54 Gy is

Version 1.2022 © 2021 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.
MS-5
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

recommended for microscopically positive resection margins (see fractionation is appropriate for larger metastases. In the palliative
Principles of Radiation Therapy in the algorithm).105,106,115 However, a setting, typical palliative doses may be used—8 Gy in a single fraction,
total dose of 60 to 70 Gy (1.8–2 Gy/fraction per day) is recommended 20 Gy in 5 fractions, or 30 Gy in 10 fractions—depending on the
for patients with gross residual disease after surgery.116,117 In patients treatment objectives. However, RT dosing can extend up to definitive
with thymomas who have capsular invasion after an R0 resection, doses for more durable local control. Highly conformal techniques may
postoperative RT can be considered (see Postoperative Treatment and be appropriate for limited volume metastases, given the relatively long
Management in the algorithm).101,105,118-120 Patients with stage III (with natural history of even metastatic thymoma.66 For metastatic disease,
macroscopic invasion into neighboring organs) thymoma have higher systemic therapy is recommended (see Principles of Systemic Therapy
risks of recurrent disease and, as such, postoperative radiation is for Thymic Malignancies in the algorithm).7,101,133,135-147 Six different
recommended.121-124 Data suggest that patients with stage II thymoma combination chemotherapy regimens are recommended in the NCCN
may not benefit from postoperative radiation.69,100,101,119,125 Postoperative Guidelines. The NCCN Panel voted that the preferred regimen for
chemotherapy is also not beneficial in this setting.126,127 thymoma is cisplatin/doxorubicin/cyclophosphamide (CAP), because it
seems to yield the best outcomes.69,148-150 Response rates are
Induction therapy followed by surgery may be useful for potentially approximately 44% with CAP for thymomas.7 However,
resectable thymic malignancies.49,128-133 A recent cohort study reported non-anthracycline regimens (eg, cisplatin/etoposide [with or without
that 5-year overall survival was similar for those receiving induction ifosfamide], carboplatin/paclitaxel) may be useful for patients who
chemotherapy followed by surgery versus surgery alone (77.4% vs. cannot tolerate the more aggressive regimens.150,151
76.7%, P = .596).128 For locally advanced thymomas, induction
chemotherapy is recommended followed by an evaluation for surgery; After primary treatment for resectable thymomas, panel members agree
postoperative RT can be considered after surgical resection of the that surveillance for recurrence should include chest CT every 6 months
primary tumor and isolated metastases (see Postoperative Treatment for 2 years, then annually for 10 years for thymoma.33 MRI may be used
and Management in the algorithm).133,134 For those with solitary for surveillance for certain clinical situations, including: 1) if patients
metastasis or ipsilateral pleural metastases, options include: 1) cannot tolerate contrast; and 2) to decrease radiation if patients are
induction chemotherapy followed by surgery for resectable patients; or young and will be screened for many years. Given the risk of later
2) surgery alone.128,129 After induction chemotherapy, imaging is recurrence for thymoma, surveillance should continue for at least 10
recommended (eg, chest CT, MRI, PET/CT) as clinically indicated to years. However, the duration, frequency, and type of imaging for
determine whether resection is feasible. For patients with unresectable surveillance for patients with thymomas have not been established in
disease in both of these settings, RT with [or without] chemotherapy is published studies. Patients with thymoma also have an increased risk
recommended. It is difficult to specify RT dosing regimens for metastatic for second malignancies, although no particular screening studies are
disease given the very broad range of metastatic scenarios that are recommended.3,152,153
possible. Stereotactic body radiation therapy (SBRT) may be
appropriate for limited focal metastases, whereas conventional

Version 1.2022 © 2021 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.
MS-6
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

Second-line systemic therapy for thymomas includes pemetrexed, thymic carcinomas vary depending on stage (stages 1–2: 91%; stages
everolimus, paclitaxel, octreotide (long-acting release [LAR]) with or 3–4: 31%) and resectability (including completeness of resection).11
without prednisone, gemcitabine with or without capecitabine, These tumors can be distinguished from thymomas because of their
5-fluorouracil (5-FU), etoposide, and ifosfamide.136,137,150,154-162 However, malignant histologic features and their different immunohistochemical
none of these agents has been assessed in randomized phase 3 trials, and genetic features.2,16,43 They are predominantly squamous cell
because there are not enough patients with thymic malignancies to do carcinomas and undifferentiated carcinomas. However, thymic
large trials. For thymomas, response rates for subsequent systemic carcinomas should be differentiated from primary lung malignancies that
therapy (ie, second-line and beyond) range from 15% to 39%.7 Panel metastasize to the thymus and have a similar histologic
members feel that pemetrexed and paclitaxel are more efficacious as appearance.165,170 Thymic carcinomas often cause pericardial and
second-line therapy for thymomas than the other recommended agents pleural effusions. The Masaoka staging system and the AJCC TNM
(see the NCCN Guidelines with Evidence Blocks™ for Thymomas and staging system can also be used to stage thymic carcinomas (see
Thymic Carcinomas, available at [Link]).7 A study of Tables 1 and 2 in the algorithm).50,171,172
pemetrexed in patients with thymoma (n = 16) reported 2 complete
responses and 5 partial responses.163 For the 2019 update (Version 1), It is important to note that thymic carcinomas are associated with a
the NCCN Panel clarified that capecitabine may be added to different clinical course from thymomas.43,135,173 Unlike thymomas,
gemcitabine based on clinical trial data.154,161 In 22 patients with paraneoplastic syndromes, including myasthenia gravis, are very rare in
thymomas receiving gemcitabine/capecitabine, there were 3 complete patients with thymic carcinoma.115 If myasthenia gravis is diagnosed,
responses and 5 partial responses. Octreotide may be useful in patients then the diagnosis of thymic carcinoma should be reassessed; the
with thymoma who have a positive octreotide scan or symptoms of patient may actually have thymoma.11 In contrast to thymomas (which
carcinoid syndrome. Pembrolizumab is not recommended in patients mainly occur in adults), thymic carcinomas occur over a wide age range
with thymomas because of concerns about immune-related events. Of including adolescents when assessed in a single-institution Western
patients with thymoma receiving pembrolizumab, 71% (5/7) had grade population; they predominantly occur in Caucasian individuals.11
3 or higher immune-related adverse events including myocarditis.164
Similar to thymomas, patients with completely resected thymic
Sunitinib is not recommended in patients with thymomas, because they
carcinomas have longer survival than those who are either incompletely
do not have c-Kit mutations.165 Surgery is an option for patients with
resected or are unresectable.47,49,174 Patients who have an R0 resection
recurrent locally advanced disease, solitary metastases, or ipsilateral
have a 5-year survival of about 60%.11 Thus, management depends on
metastases.166
the extent of resection. Patients with thymic carcinoma have higher
Thymic Carcinomas risks of recurrent disease; therefore, postoperative radiation is
recommended to maximize local control.11 After resection of thymic
Thymic carcinomas are rare aggressive tumors that often metastasize
carcinomas, postoperative management includes RT with (or without)
to regional lymph nodes and extrathoracic sites; thus, they have a
chemotherapy, depending on the completeness of resection (see
worse prognosis than thymomas.5,9,12,13,17,47,48,167-169 Survival rates for

Version 1.2022 © 2021 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.
MS-7
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

Postoperative Treatment and Management in the Postoperative Treatment and Management in the algorithm).11 Patients
algorithm).11,47,48,105,125,175,176 A study suggests that adjuvant therapy may with unresectable disease can then receive RT with [or without]
not be necessary for early-stage thymic carcinomas.177 For chemotherapy. For those with solitary metastasis or ipsilateral pleural
unresectable or metastatic thymic carcinomas, chemotherapy with (or metastases, options include induction chemotherapy or surgery. After
without) RT is recommended (see Principles of Systemic Therapy for primary treatment for resectable disease, panel members agree that
Thymic Malignancies and Principles of Radiation Therapy in the surveillance for recurrence should include chest CT every 6 months for
algorithm).149 2 years, then annually for 5 years for thymic carcinoma.33 However, the
duration, frequency, or type of imaging for surveillance for thymic
A definitive dose of 60 to 70 Gy is recommended for patients with carcinomas has not been established in published studies.
unresectable thymic carcinomas. For adjuvant treatment, a dose of 45
to 50 Gy is recommended for clear or close margins; a dose of 54 Gy is For thymic carcinomas, there are little data regarding second-line
recommended for microscopically positive resection margins (see systemic therapy.136 Second-line systemic therapy for thymic
Principles of Radiation Therapy in the algorithm).105,106,115 However, a carcinomas includes sunitinib, pemetrexed, everolimus, paclitaxel,
total dose of 60 to 70 Gy (1.8–2 Gy/fraction per day) is recommended octreotide (LAR) with or without prednisone, gemcitabine with or without
for patients with gross residual disease after surgery.116,117 In patients capecitabine, 5-FU, etoposide, ifosfamide, and pembrolizumab (see
with thymic carcinomas who have capsular invasion after an R0 Principles of Systemic Therapy for Thymic Malignancies in the
resection, postoperative RT can be considered (see Postoperative algorithm).7,136,137,163 For thymic carcinomas, response rates for
Treatment and Management in the algorithm).101,105,118-120 Adjuvant subsequent systemic therapy range from 4% to 21%.7 However, panel
therapy is not recommended for completely resected (R0) stage I members voted that these second-line agents are not very efficacious
thymic carcinomas.69,100,101 for thymic carcinomas (see the NCCN Guidelines with Evidence
Blocks™ for Thymomas and Thymic Carcinomas, available at
Unfortunately, thymic carcinomas respond poorly to chemotherapy. [Link]). Sunitinib is recommended for patients with c-Kit
The NCCN Panel voted that carboplatin/paclitaxel is preferred for mutations; however, these mutations are rare in thymic carcinomas
first-line therapy, because it has the highest response rate in patients (<10%).85,137,157,188-194 Patients with thymomas do not have c-Kit
with thymic carcinomas in clinical trials (overall response rate, 22%– mutations.165 S-1 (an oral fluorouracil) appears to be active in patients
36%).146,151,178-187 Data suggest that the CAP and with thymic carcinomas.195,196
cisplatin/doxorubicin/vincristine/ cyclophosphamide (ADOC) regimens
are also effective for thymic carcinomas, but these regimens are more Pembrolizumab is active (response rate, 22.5% [95% CI, 10.8%–
toxic than carboplatin/paclitaxel.7,185 Induction chemotherapy is 38.5%]) as second-line therapy in patients with thymic carcinomas but
recommended followed by an evaluation for surgery for locally is associated with a high rate of severe immune-related adverse
advanced disease; postoperative RT can be considered after surgical events (15%).197 For example, grade 3 to 4 myocarditis has been
resection of the primary tumor and isolated metastases (see reported in 5% to 9% of patients with thymic carcinomas receiving

Version 1.2022 © 2021 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.
MS-8
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

pembrolizumab, which is a higher adverse rate than seen in patients

with other malignancies who receive pembrolizumab.164,197 For the
2019 update (Version 1), the NCCN Panel now recommends
pembrolizumab (category 2A) as second-line systemic therapy for
patients with thymic carcinomas based on the clinical data.164,197 For
the 2019 update (Version 1), the NCCN Panel clarified that capecitabine
may be added to gemcitabine based on clinical trial data.154,161 There
were 3 partial responses in 8 patients with thymic carcinomas receiving
gemcitabine/capecitabine.

Summary
These NCCN Guidelines focus on thymomas and thymic carcinomas
and outline the evaluation, treatment, and management of these
mediastinal tumors. The Summary of the Guidelines Updates section in
the algorithm briefly describes the new changes for 2019, which are
described in greater detail in this revised Discussion text; references
have been added. For the 2019 update (Version 1), panel members
voted to add pembrolizumab (category 2A) as second-line therapy for
patients with thymic carcinomas with the caveat that pembrolizumab is
associated with a high rate of severe immune-related adverse events
(15%), including myocarditis.164,197 The NCCN Panel does not
recommend pembrolizumab in patients with thymomas because of
concerns about immune-related events.164

Version 1.2022 © 2021 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.
MS-9
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

References 2016;49:1144-1149. Available at:

[Link]
1. Marx A, Chan JK, Coindre JM, et al. The 2015 World Health
Organization classification of tumors of the thymus: continuity and 9. Huang J, Rizk NP, Travis WD, et al. Comparison of patterns of
changes. J Thorac Oncol 2015;10:1383-1395. Available at: relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg
[Link] 2009;138:26-31. Available at:
[Link]
2. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of
Tumours of the Lung, Pleura, Thymus and Heart. Fourth edition. WHO 10. Masaoka A. Staging system of thymoma. J Thorac Oncol
Classification of Tumours. Volume 7. Vol. 7: World Health Organization; 2010;5:S304-312. Available at:
2015. [Link]
3. Engels EA. Epidemiology of thymoma and associated malignancies. 11. Litvak AM, Woo K, Hayes S, et al. Clinical characteristics and
J Thorac Oncol 2010;5:S260-265. Available at: outcomes for patients with thymic carcinoma: evaluation of Masaoka
[Link] staging. J Thorac Oncol 2014;9:1810-1815. Available at:
[Link]
4. Proceedings of the First International Conference on Thymic
Malignancies. August 20-21, 2009. Bethesda, Maryland, USA. J Thorac 12. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical
Oncol 2010;5:S259-370. Available at: study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878-884;
[Link] discussion 884-875. Available at:
[Link]
5. Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal
tumors. Part 1: tumors of the anterior mediastinum. Chest 13. Eng TY, Fuller CD, Jagirdar J, et al. Thymic carcinoma: state of the
1997;112:511-522. Available at: art review. Int J Radiat Oncol Biol Phys 2004;59:654-664. Available at:
[Link] [Link]
6. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: 14. den Bakker MA, Marx A, Mukai K, Strobel P. Mesenchymal tumours
demographic patterns in incidence and associations with subsequent of the mediastinum--part I. Virchows Arch 2015;467:487-500. Available
malignancies. Int J Cancer 2003;105:546-551. Available at: at: [Link]
[Link]
15. Araki T, Nishino M, Gao W, et al. Anterior mediastinal masses in the
7. Merveilleux du Vignaux C, Dansin E, Mhanna L, et al. Systemic Framingham Heart Study: prevalence and CT image characteristics.
therapy in advanced thymic epithelial tumors: insights from the Eur J Radiol Open 2015;2:26-31. Available at:
RYTHMIC prospective cohort. J Thorac Oncol 2018;13:1762-1770. [Link]
Available at: [Link]
16. Marchevsky A, Marx A, Strobel P, et al. Policies and reporting
8. Zhao Y, Shi J, Fan L, et al. Surgical treatment of thymoma: an guidelines for small biopsy specimens of mediastinal masses. J Thorac
11-year experience with 761 patients. Eur J Cardiothorac Surg Oncol 2011;6:S1724-1729. Available at:
[Link]

Version 1.2022 © 2021 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.
MS-10
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

17. Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary clinical prognostic variables, and differential diagnostic considerations.
mediastinal tumors: part II. Tumors of the middle and posterior Adv Anat Pathol 2007;14:69-92. Available at:
mediastinum. Chest 1997;112:1344-1357. Available at: [Link]
[Link]
26. Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer
18. Rashid OM, Cassano AD, Takabe K. Thymic neoplasm: a rare mortality with low-dose computed tomographic screening. N Engl J Med
disease with a complex clinical presentation. J Thorac Dis 2011;365:395-409. Available at:
2013;5:173-183. Available at: [Link]
[Link]
27. Yokoi K, Kondo K, Fujimoto K, et al. JLCS medical practice
19. Detterbeck FC, Parsons AM. Management of stage I and II guidelines for thymic tumors: summary of recommendations. Jpn J Clin
thymoma. Thorac Surg Clin 2011;21:59-67, vi-vii. Available at: Oncol 2017;47:1119-1122. Available at:
[Link] [Link]

20. Detterbeck FC, Zeeshan A. Thymoma: current diagnosis and 28. Carter BW, Benveniste MF, Madan R, et al. ITMIG classification of
treatment. Chin Med J (Engl) 2013;126:2186-2191. Available at: mediastinal compartments and multidisciplinary approach to mediastinal
[Link] masses. Radiographics 2017;37:413-436. Available at:
[Link]
21. Barth TFE, Leithäuser F, Joos S, et al. Mediastinal (thymic) large
B-cell lymphoma: where do we stand? Lancet Oncol 2002;3:229-234. 29. Priola AM, Priola SM. Imaging of thymus in myasthenia gravis: from
Available at: [Link] thymic hyperplasia to thymic tumor. Clin Radiol 2014;69:e230-245.
Available at: [Link]
22. Ferolla P, Falchetti A, Filosso P, et al. Thymic neuroendocrine
carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: 30. Tomiyama N, Honda O, Tsubamoto M, et al. Anterior mediastinal
the Italian series. J Clin Endocrinol Metab 2005;90:2603-2609. tumors: diagnostic accuracy of CT and MRI. Eur J Radiol
Available at: [Link] 2009;69:280-288. Available at:
[Link]
23. Teh BT. Thymic carcinoids in multiple endocrine neoplasia type 1. J
Intern Med 1998;243:501-504. Available at: 31. Benveniste MF, Rosado-de-Christenson ML, Sabloff BS, et al. Role
[Link] of imaging in the diagnosis, staging, and treatment of thymoma.
Radiographics 2011;31:1847-1861; discussion 1861-1843. Available at:
24. Moran CA, Suster S. Primary germ cell tumors of the mediastinum: [Link]
I. Analysis of 322 cases with special emphasis on teratomatous lesions
and a proposal for histopathologic classification and clinical staging. 32. Marom EM. Advances in thymoma imaging. J Thorac Imaging
Cancer 1997;80:681-690. Available at: 2013;28:69-80; quiz 81-63. Available at:
[Link] [Link]

25. McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal 33. Marom EM. Imaging thymoma. J Thorac Oncol 2010;5:S296-303.
germ cell tumors: a review with emphasis on pathologic features, Available at: [Link]

Version 1.2022 © 2021 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.
MS-11
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

34. Rosado-de-Christenson ML, Strollo DC, Marom EM. Imaging of 41. Kondo K, Yoshizawa K, Tsuyuguchi M, et al. WHO histologic
thymic epithelial neoplasms. Hematol Oncol Clin North Am classification is a prognostic indicator in thymoma. Ann Thorac Surg
2008;22:409-431. Available at: 2004;77:1183-1188. Available at:
[Link] [Link]

35. Sadohara J, Fujimoto K, Muller NL, et al. Thymic epithelial tumors: 42. Moran CA, Weissferdt A, Kalhor N, et al. Thymomas I: a
comparison of CT and MR imaging findings of low-risk thymomas, clinicopathologic correlation of 250 cases with emphasis on the World
high-risk thymomas, and thymic carcinomas. Eur J Radiol Health Organization schema. Am J Clin Pathol 2012;137:444-450.
2006;60:70-79. Available at: Available at: [Link]
[Link]
43. Marx A, Rieker R, Toker A, et al. Thymic carcinoma: is it a separate
36. Quint LE, Reddy RM, Lin J, et al. Imaging in thoracic oncology: case entity? From molecular to clinical evidence. Thorac Surg Clin
studies from Multidisciplinary Thoracic Tumor Board: (part 2 of 2 part 2011;21:25-31 v-vi. Available at:
series). Cancer Imaging 2013;13:440-447. Available at: [Link]
[Link]
44. Ruffini E, Detterbeck F, Van Raemdonck D, et al. Tumours of the
37. Marom EM, Rosado-de-Christenson ML, Bruzzi JF, et al. Standard thymus: a cohort study of prognostic factors from the European Society
report terms for chest computed tomography reports of anterior of Thoracic Surgeons database. Eur J Cardiothorac Surg
mediastinal masses suspicious for thymoma. J Thorac Oncol 2014;46:361-368. Available at:
2011;6:S1717-1723. Available at: [Link]
[Link]
45. Margaritora S, Cesario A, Cusumano G, et al. Thirty-five-year
38. Treglia G, Sadeghi R, Giovanella L, et al. Is (18)F-FDG PET useful follow-up analysis of clinical and pathologic outcomes of thymoma
in predicting the WHO grade of malignancy in thymic epithelial tumors? surgery. Ann Thorac Surg 2010;89:245-252; discussion 252. Available
A meta-analysis. Lung Cancer 2014;86:5-13. Available at: at: [Link]
[Link]
46. Regnard JF, Magdeleinat P, Dromer C, et al. Prognostic factors and
39. Sung YM, Lee KS, Kim BT, et al. 18F-FDG PET/CT of thymic long-term results after thymoma resection: a series of 307 patients. J
epithelial tumors: usefulness for distinguishing and staging tumor Thorac Cardiovasc Surg 1996;112:376-384. Available at:
subgroups. J Nucl Med 2006;47:1628-1634. Available at: [Link]
[Link]
47. Yano M, Sasaki H, Yokoyama T, et al. Thymic carcinoma: 30 cases
40. Marx A, Strobel P, Badve SS, et al. ITMIG consensus statement on at a single institution. J Thorac Oncol 2008;3:265-269. Available at:
the use of the WHO histological classification of thymoma and thymic [Link]
carcinoma: refined definitions, histological criteria, and reporting. J
Thorac Oncol 2014;9:596-611. Available at: 48. Ogawa K, Toita T, Uno T, et al. Treatment and prognosis of thymic
[Link] carcinoma: a retrospective analysis of 40 cases. Cancer
2002;94:3115-3119. Available at:
[Link]

Version 1.2022 © 2021 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.
MS-12
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

49. Okereke IC, Kesler KA, Freeman RK, et al. Thymic carcinoma: 57. Carter BW, Benveniste MF, Madan R, et al. IASLC/ITMIG staging
outcomes after surgical resection. Ann Thorac Surg system and lymph node map for thymic epithelial neoplasms.
2012;93:1668-1672; discussion 1672-1663. Available at: Radiographics 2017;37:758-776. Available at:
[Link] [Link]

50. Detterbeck FC, Nicholson AG, Kondo K, et al. The Masaoka-Koga 58. Meurgey A, Girard N, Merveilleux du Vignaux C, et al. Assessment
stage classification for thymic malignancies: clarification and definition of the ITMIG statement on the WHO histological classification and of the
of terms. J Thorac Oncol 2011;6:S1710-1716. Available at: eighth TNM staging of thymic epithelial tumors of a series of 188 thymic
[Link] epithelial tumors. J Thorac Oncol 2017;12:1571-1581. Available at:
[Link]
51. Huang J, Detterbeck FC, Wang Z, Loehrer PJ, Sr. Standard
outcome measures for thymic malignancies. J Thorac Oncol 59. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG
2011;6:S1691-1697. Available at: Thymic Epithelial Tumors Staging Project: proposal for an
[Link] evidence-based stage classification system for the forthcoming (8th)
edition of the TNM classification of malignant tumors. J Thorac Oncol
52. Moran CA, Walsh G, Suster S, Kaiser L. Thymomas II: a 2014;9:S65-72. Available at:
clinicopathologic correlation of 250 cases with a proposed staging [Link]
system with emphasis on pathologic assessment. Am J Clin Pathol
2012;137:451-461. Available at: 60. Roden AC, Yi ES, Jenkins SM, et al. Reproducibility of 3 histologic
[Link] classifications and 3 staging systems for thymic epithelial neoplasms
and its effect on prognosis. Am J Surg Pathol 2015;39:427-441.
53. Kondo K. Tumor-node metastasis staging system for thymic Available at: [Link]
epithelial tumors. J Thorac Oncol 2010;5:S352-356. Available at:
[Link] 61. Fukui T, Fukumoto K, Okasaka T, et al. Clinical evaluation of a new
tumour-node-metastasis staging system for thymic malignancies
54. Lee HS, Kim ST, Lee J, et al. A single institutional experience of proposed by the International Association for the Study of Lung Cancer
thymic epithelial tumours over 11 years: clinical features and outcome Staging and Prognostic Factors Committee and the International
and implications for future management. Br J Cancer 2007;97:22-28. Thymic Malignancy Interest Group. Eur J Cardiothorac Surg
Available at: [Link] 2016;49:574-579. Available at:
[Link]
55. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of
thymomas with special reference to their clinical stages. Cancer 62. Bhora FY, Chen DJ, Detterbeck FC, et al. The ITMIG/IASLC Thymic
1981;48:2485-2492. Available at: Epithelial Tumors Staging Project: a proposed lymph node map for
[Link] thymic epithelial tumors in the forthcoming 8th edition of the TNM
classification of malignant tumors. J Thorac Oncol 2014;9:S88-96.
56. Wright CD. Management of thymomas. Crit Rev Oncol Hematol Available at: [Link]
2008;65:109-120. Available at:
[Link] 63. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging
Manual, 8th edition: Springer International Publishing; 2017:1-1032.

Version 1.2022 © 2021 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.
MS-13
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

64. Lewis JE, Wick MR, Scheithauer BW, et al. Thymoma. A 72. Wright CD. Extended resections for thymic malignancies. J Thorac
clinicopathologic review. Cancer 1987;60:2727-2743. Available at: Oncol 2010;5:S344-347. Available at:
[Link] [Link]

65. Park HS, Shin DM, Lee JS, et al. Thymoma. A retrospective study of 73. Huang J, Rizk NP, Travis WD, et al. Feasibility of multimodality
87 cases. Cancer 1994;73:2491-2498. Available at: therapy including extended resections in stage IVA thymoma. J Thorac
[Link] Cardiovasc Surg 2007;134:1477-1483; discussion 1483-1474. Available
at: [Link]
66. Basse C, Thureau S, Bota S, et al. Multidisciplinary tumor board
decision making for postoperative radiotherapy in thymic epithelial 74. Dacic S, Beasley MB, Berman M, et al. Protocol for the examination
tumors: insights from the RYTHMIC prospective cohort. J Thorac Oncol of specimens from patients with thymic tumors: College of American
2017;12:1715-1722. Available at: Pathologists; 2017. Available at: [Link]/cancerprotocols.
[Link]
75. Xie A, Tjahjono R, Phan K, Yan TD. Video-assisted thoracoscopic
67. Ruffini E, Van Raemdonck D, Detterbeck F, et al. Management of surgery versus open thymectomy for thymoma: a systematic review.
thymic tumors: a survey of current practice among members of the Ann Cardiothorac Surg 2015;4:495-508. Available at:
European Society of Thoracic Surgeons. J Thorac Oncol [Link]
2011;6:614-623. Available at:
[Link] 76. Chao YK, Liu YH, Hsieh MJ, et al. Long-term outcomes after
thoracoscopic resection of stage I and II thymoma: a
68. Fiorelli A, Natale G, Freda C, Santini M. Is thymomectomy propensity-matched study. Ann Surg Oncol 2015;22:1371-1376.
equivalent to complete thymectomy in non-myasthenic patients with Available at: [Link]
early-stage thymoma? Interact Cardiovasc Thorac Surg
2019;28:399-403. Available at: 77. Liu TJ, Lin MW, Hsieh MS, et al. Video-assisted thoracoscopic
[Link] surgical thymectomy to treat early thymoma: a comparison with the
conventional transsternal approach. Ann Surg Oncol 2014;21:322-328.
69. Kondo K. Optimal therapy for thymoma. J Med Invest Available at: [Link]
2008;55:17-28. Available at:
[Link] 78. Pennathur A, Qureshi I, Schuchert MJ, et al. Comparison of surgical
techniques for early-stage thymoma: feasibility of minimally invasive
70. Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg thymectomy and comparison with open resection. J Thorac Cardiovasc
2004;77:1860-1869. Available at: Surg 2011;141:694-701. Available at:
[Link] [Link]

71. Wright CD. Stage IVA thymoma: patterns of spread and surgical 79. Ye B, Tantai JC, Ge XX, et al. Surgical techniques for early-stage
management. Thorac Surg Clin 2011;21:93-97, vii. Available at: thymoma: video-assisted thoracoscopic thymectomy versus transsternal
[Link] thymectomy. J Thorac Cardiovasc Surg 2014;147:1599-1603. Available
at: [Link]

Version 1.2022 © 2021 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.
MS-14
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

80. Sakamaki Y, Oda T, Kanazawa G, et al. Intermediate-term 88. Gilhus NE, Owe JF, Hoff JM, et al. Myasthenia gravis: a review of
oncologic outcomes after video-assisted thoracoscopic thymectomy for available treatment approaches. Autoimmune Dis 2011;2011:847393.
early-stage thymoma. J Thorac Cardiovasc Surg 2014;148:1230-1237 Available at: [Link]
e1231. Available at: [Link]
89. Mehran R, Ghosh R, Maziak D, et al. Surgical treatment of
81. Manoly I, Whistance RN, Sreekumar R, et al. Early and mid-term thymoma. Can J Surg 2002;45:25-30. Available at:
outcomes of trans-sternal and video-assisted thoracoscopic surgery for [Link]
thymoma. Eur J Cardiothorac Surg 2014;45:e187-193. Available at:
[Link] 90. Autoantibodies to acetylcholine receptors in myasthenia gravis. N
Engl J Med 1983;308:402-403. Available at:
82. Agatsuma H, Yoshida K, Yoshino I, et al. Video-assisted thoracic [Link]
surgery thymectomy versus sternotomy thymectomy in patients with
thymoma. Ann Thorac Surg 2017;104:1047-1053. Available at: 91. Howard FM, Lennon VA, Finley J, et al. Clinical correlations of
[Link] antibodies that bind, block, or modulate human acetylcholine receptors
in myasthenia gravis. Ann N Y Acad Sci 1987;505:526-538. Available
83. Yang Y, Dong J, Huang Y. Thoracoscopic thymectomy versus open at: [Link]
thymectomy for the treatment of thymoma: A meta-analysis. Eur J Surg
Oncol 2016;42:1720-1728. Available at: 92. Benveniste MF, Korst RJ, Rajan A, et al. A practical guide from the
[Link] International Thymic Malignancy Interest Group (ITMIG) regarding the
radiographic assessment of treatment response of thymic epithelial
84. Yamada Y, Yoshino I, Nakajima J, et al. Surgical outcomes of tumors using modified RECIST criteria. J Thorac Oncol
patients with stage III thymoma in the Japanese nationwide database. 2014;9:S119-124. Available at:
Ann Thorac Surg 2015;100:961-967. Available at: [Link]
[Link]
93. Hwang Y, Park IK, Park S, et al. Lymph node dissection in thymic
85. Kelly RJ, Petrini I, Rajan A, et al. Thymic malignancies: from clinical malignancies: implication of the ITMIG lymph node map, TNM stage
management to targeted therapies. J Clin Oncol 2011;29:4820-4827. classification, and recommendations. J Thorac Oncol 2016;11:108-114.
Available at: [Link] Available at: [Link]

86. Bernard C, Frih H, Pasquet F, et al. Thymoma associated with 94. Bretti S, Berruti A, Loddo C, et al. Multimodal management of
autoimmune diseases: 85 cases and literature review. Autoimmun Rev stages III-IVa malignant thymoma. Lung Cancer 2004;44:69-77.
2016;15:82-92. Available at: Available at: [Link]
[Link]
95. Ried M, Potzger T, Sziklavari Z, et al. Extended surgical resections
87. Cata JP, Lasala JD, Williams W, Mena GE. Myasthenia gravis and of advanced thymoma Masaoka stages III and IVa facilitate outcome.
thymoma surgery: a clinical update for the cardiothoracic Thorac Cardiovasc Surg 2014;62:161-168. Available at:
anesthesiologist. J Cardiothorac Vasc Anesth 2018. Available at: [Link]
[Link]

Version 1.2022 © 2021 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.
MS-15
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

96. Detterbeck F, Youssef S, Ruffini E, Okumura M. A review of 104. Ruffini E, Mancuso M, Oliaro A, et al. Recurrence of thymoma:
prognostic factors in thymic malignancies. J Thorac Oncol analysis of clinicopathologic features, treatment, and outcome. J Thorac
2011;6:S1698-1704. Available at: Cardiovasc Surg 1997;113:55-63. Available at:
[Link] [Link]

97. Murakawa T, Nakajima J, Kohno T, et al. Results from surgical 105. Gomez D, Komaki R, Yu J, et al. Radiation therapy definitions and
treatment for thymoma. 43 years of experience. Jpn J Thorac reporting guidelines for thymic malignancies. J Thorac Oncol
Cardiovasc Surg 2000;48:89-95. Available at: 2011;6:S1743-1748. Available at:
[Link] [Link]

98. Wakely PE, Jr. Fine needle aspiration in the diagnosis of thymic 106. Gomez D, Komaki R. Technical advances of radiation therapy for
epithelial neoplasms. Hematol Oncol Clin North Am 2008;22:433-442. thymic malignancies. J Thorac Oncol 2010;5:S336-343. Available at:
Available at: [Link] [Link]

99. Detterbeck FC, Moran C, Huang J, et al. Which way is up? Policies 107. ATC Guidelines for the Use of IMRT (including Intra-Thoracic
and procedures for surgeons and pathologists regarding resection Treatments). May 31, 2006. Available at:
specimens of thymic malignancy. J Thorac Oncol 2011;6:S1730-1738. [Link]
Available at: [Link]
108. Hartford AC, Palisca MG, Eichler TJ, et al. American Society for
100. Utsumi T, Shiono H, Kadota Y, et al. Postoperative radiation Therapeutic Radiology and Oncology (ASTRO) and American College
therapy after complete resection of thymoma has little impact on of Radiology (ACR) Practice Guidelines for Intensity-Modulated
survival. Cancer 2009;115:5413-5420. Available at: Radiation Therapy (IMRT). Int J Radiat Oncol Biol Phys 2009;73:9-14.
[Link] Available at: [Link]

101. Korst RJ, Kansler AL, Christos PJ, Mandal S. Adjuvant 109. Moran JM, Dempsey M, Eisbruch A, et al. Safety considerations
radiotherapy for thymic epithelial tumors: a systematic review and for IMRT: executive summary. Med Phys 2011;38:5067-5072. Available
meta-analysis. Ann Thorac Surg 2009;87:1641-1647. Available at: at: [Link]
[Link]
110. Gregoire V, Mackie TR. State of the art on dose prescription,
102. Hamaji M, Shah RM, Ali SO, et al. A meta-analysis of reporting and recording in Intensity-Modulated Radiation Therapy (ICRU
postoperative radiotherapy for thymic carcinoma. Ann Thorac Surg report No. 83). Cancer Radiother 2011;15:555-559. Available at:
2017;103:1668-1675. Available at: [Link]
[Link]
111. Holmes T, Das R, Low D, et al. American Society of Radiation
103. Forquer JA, Rong N, Fakiris AJ, et al. Postoperative radiotherapy Oncology recommendations for documenting intensity-modulated
after surgical resection of thymoma: differing roles in localized and radiation therapy treatments. Int J Radiat Oncol Biol Phys
regional disease. Int J Radiat Oncol Biol Phys 2010;76:440-445. 2009;74:1311-1318. Available at:
Available at: [Link] [Link]

Version 1.2022 © 2021 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.
MS-16
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

112. ICRU Report 83: Prescribing, Recording, and Reporting Intensity 120. Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy
Modulated Photon Beam Therapy (IMRT). Journal of the ICRU 2010;10. for stage II thymoma. Ann Thorac Surg 2002;74:1033-1037. Available
Available at: [Link] at: [Link]

113. Kong FM, Pan C, Eisbruch A, Ten Haken RK. Physical models and 121. Lim YJ, Kim HJ, Wu HG. Role of postoperative radiotherapy in
simpler dosimetric descriptors of radiation late toxicity. Semin Radiat nonlocalized thymoma: propensity-matched analysis of Surveillance,
Oncol 2007;17:108-120. Available at: Epidemiology, and End Results database. J Thorac Oncol
[Link] 2015;10:1357-1363. Available at:
[Link]
114. Milano MT, Constine LS, Okunieff P. Normal tissue tolerance dose
metrics for radiation therapy of major organs. Semin Radiat Oncol 122. Perri F, Pisconti S, Conson M, et al. Adjuvant treatment in patients
2007;17:131-140. Available at: at high risk of recurrence of thymoma: efficacy and safety of a
[Link] three-dimensional conformal radiation therapy regimen. Onco Targets
Ther 2015;8:1345-1349. Available at:
115. Ruffini E, Venuta F. Management of thymic tumors: a European [Link]
perspective. J Thorac Dis 2014;6 Suppl 2:S228-237. Available at:
[Link] 123. Sugie C, Shibamoto Y, Ikeya-Hashizume C, et al. Invasive
thymoma: postoperative mediastinal irradiation, and low-dose entire
116. Myojin M, Choi NC, Wright CD, et al. Stage III thymoma: pattern of hemithorax irradiation in patients with pleural dissemination. J Thorac
failure after surgery and postoperative radiotherapy and its implication Oncol 2008;3:75-81. Available at:
for future study. Int J Radiat Oncol Biol Phys 2000;46:927-933. [Link]
Available at: [Link]
124. Ogawa K, Uno T, Toita T, et al. Postoperative radiotherapy for
117. Mornex F, Resbeut M, Richaud P, et al. Radiotherapy and patients with completely resected thymoma: a multi-institutional,
chemotherapy for invasive thymomas: a multicentric retrospective retrospective review of 103 patients. Cancer 2002;94:1405-1413.
review of 90 cases. The FNCLCC trialists. Federation Nationale des Available at: [Link]
Centres de Lutte Contre le Cancer. Int J Radiat Oncol Biol Phys
1995;32:651-659. Available at: 125. Omasa M, Date H, Sozu T, et al. Postoperative radiotherapy is
[Link] effective for thymic carcinoma but not for thymoma in stage II and III
thymic epithelial tumors: the Japanese Association for Research on the
118. Singhal S, Shrager JB, Rosenthal DI, et al. Comparison of stages Thymus Database Study. Cancer 2015;121:1008-1016. Available at:
I-II thymoma treated by complete resection with or without adjuvant [Link]
radiation. Ann Thorac Surg 2003;76:1635-1641; discussion 1641-1632.
Available at: [Link] 126. Attaran S, McCormack D, Pilling J, Harrison-Phipps K. Which
stages of thymoma benefit from adjuvant chemotherapy
119. Rena O, Papalia E, Oliaro A, et al. Does adjuvant radiation therapy post-thymectomy? Interact Cardiovasc Thorac Surg 2012;15:273-275.
improve disease-free survival in completely resected Masaoka stage II Available at: [Link]
thymoma? Eur J Cardiothorac Surg 2007;31:109-113. Available at:
[Link]

Version 1.2022 © 2021 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.
MS-17
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

127. Cowen D, Richaud P, Mornex F, et al. Thymoma: results of a 134. Hassan M, Seoud DE. Multimodality treatments in locally
multicentric retrospective series of 149 non-metastatic irradiated advanced stage thymomas. Hematol Oncol Stem Cell Ther
patients and review of the literature. FNCLCC trialists. Federation 2009;2:340-344. Available at:
Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol [Link]
1995;34:9-16. Available at:
[Link] 135. Kelly RJ. Systemic treatment of advanced thymic malignancies.
Am Soc Clin Oncol Educ Book 2014:e367-373. Available at:
128. Park S, Park IK, Kim YT, et al. Comparison of neoadjuvant [Link]
chemotherapy followed by surgery to upfront surgery for thymic
malignancy. Ann Thorac Surg 2019;107:355-362. Available at: 136. Girard N, Lal R, Wakelee H, et al. Chemotherapy definitions and
[Link] policies for thymic malignancies. J Thorac Oncol 2011;6:S1749-1755.
Available at: [Link]
129. Ruffini E, Guerrera F, Brunelli A, et al. Report from the European
Society of Thoracic Surgeons prospective thymic database 2017: a 137. Girard N. Chemotherapy and targeted agents for thymic
powerful resource for a collaborative global effort to manage thymic malignancies. Expert Rev Anticancer Ther 2012;12:685-695. Available
tumours. Eur J Cardiothorac Surg 2019. Available at: at: [Link]
[Link]
138. Loehrer PJ, Sr., Chen M, Kim K, et al. Cisplatin, doxorubicin, and
130. Kanzaki R, Kanou T, Ose N, et al. Long-term outcomes of cyclophosphamide plus thoracic radiation therapy for limited-stage
advanced thymoma in patients undergoing preoperative chemotherapy unresectable thymoma: an intergroup trial. J Clin Oncol
or chemoradiotherapy followed by surgery: a 20-year experience. 1997;15:3093-3099. Available at:
Interact Cardiovasc Thorac Surg 2019;28:360-367. Available at: [Link]
[Link]
139. Loehrer PJ, Kim K, Aisner SC, et al. Cisplatin plus doxorubicin plus
131. Riely GJ, Huang J. Induction therapy for locally advanced cyclophosphamide in metastatic or recurrent thymoma: final results of
thymoma. J Thorac Oncol 2010;5:S323-326. Available at: an intergroup trial. The Eastern Cooperative Oncology Group,
[Link] Southwest Oncology Group, and Southeastern Cancer Study Group. J
Clin Oncol 1994;12:1164-1168. Available at:
132. Wright CD, Choi NC, Wain JC, et al. Induction chemoradiotherapy [Link]
followed by resection for locally advanced Masaoka stage III and IVA
thymic tumors. Ann Thorac Surg 2008;85:385-389. Available at: 140. Giaccone G, Ardizzoni A, Kirkpatrick A, et al. Cisplatin and
[Link] etoposide combination chemotherapy for locally advanced or metastatic
thymoma. A phase II study of the European Organization for Research
133. Kim ES, Putnam JB, Komaki R, et al. Phase II study of a and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol
multidisciplinary approach with induction chemotherapy, followed by 1996;14:814-820. Available at:
surgical resection, radiation therapy, and consolidation chemotherapy [Link]
for unresectable malignant thymomas: final report. Lung Cancer
2004;44:369-379. Available at: 141. Shin DM, Walsh GL, Komaki R, et al. A multidisciplinary approach
[Link] to therapy for unresectable malignant thymoma. Ann Intern Med

Version 1.2022 © 2021 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.
MS-18
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

1998;129:100-104. Available at: 149. Rajan A, Giaccone G. Chemotherapy for thymic tumors: induction,
[Link] consolidation, palliation. Thorac Surg Clin 2011;21:107-114, viii.
Available at: [Link]
142. Fornasiero A, Daniele O, Ghiotto C, et al. Chemotherapy for
invasive thymoma. A 13-year experience. Cancer 1991;68:30-33. 150. Schmitt J, Loehrer PJ, Sr. The role of chemotherapy in advanced
Available at: [Link] thymoma. J Thorac Oncol 2010;5:S357-360. Available at:
[Link]
143. Loehrer PJ, Jiroutek M, Aisner S, et al. Combined etoposide,
ifosfamide, and cisplatin in the treatment of patients with advanced 151. Lemma GL, Lee JW, Aisner SC, et al. Phase II study of carboplatin
thymoma and thymic carcinoma: an intergroup trial. Cancer and paclitaxel in advanced thymoma and thymic carcinoma. J Clin
2001;91:2010-2015. Available at: Oncol 2011;29:2060-2065. Available at:
[Link] [Link]

144. Lucchi M, Melfi F, Dini P, et al. Neoadjuvant chemotherapy for 152. Kumar V, Garg M, Goyal A, et al. Changing pattern of secondary
stage III and IVA thymomas: a single-institution experience with a long cancers among patients with malignant thymoma in the USA. Future
follow-up. J Thorac Oncol 2006;1:308-313. Available at: Oncol 2018;14:1943-1951. Available at:
[Link] [Link]

145. Yokoi K, Matsuguma H, Nakahara R, et al. Multidisciplinary 153. Pan CC, Chen PC, Wang LS, et al. Thymoma is associated with
treatment for advanced invasive thymoma with cisplatin, doxorubicin, an increased risk of second malignancy. Cancer 2001;92:2406-2411.
and methylprednisolone. J Thorac Oncol 2007;2:73-78. Available at: Available at: [Link]
[Link]
154. Palmieri G, Buonerba C, Ottaviano M, et al. Capecitabine plus
146. Lemma GL, Loehrer PJ, Sr., Lee JW, et al. A phase II study of gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial.
carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: Future Oncol 2014;10:2141-2147. Available at:
E1C99 [abstract]. J Clin Oncol 2008;26(Suppl 15):Abstract 8018. [Link]
Available at:
[Link] 155. Bluthgen MV, Boutros C, Fayard F, et al. Activity and safety of oral
etoposide in pretreated patients with metastatic or recurrent thymic
147. Venuta F, Rendina EA, Longo F, et al. Long-term outcome after epithelial tumors (TET): A single-institution experience. Lung Cancer
multimodality treatment for stage III thymic tumors. Ann Thorac Surg 2016;99:111-116. Available at:
2003;76:1866-1872; discussion 1872. Available at: [Link]
[Link]
156. Zucali PA, De Pas T, Palmieri G, et al. Phase II study of
148. Okuma Y, Saito M, Hosomi Y, et al. Key components of everolimus in patients with thymoma and thymic carcinoma previously
chemotherapy for thymic malignancies: a systematic review and pooled treated with cisplatin based chemotherapy. J Clin Oncol
analysis for anthracycline-, carboplatin- or cisplatin-based 2018;36:342-349. Available at:
chemotherapy. J Cancer Res Clin Oncol 2015;141:323-331. Available [Link]
at: [Link]

Version 1.2022 © 2021 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.
MS-19
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

157. Thomas A, Rajan A, Berman A, et al. Sunitinib in patients with trial. J Clin Oncol 2018:JCO2017773184. Available at:
chemotherapy-refractory thymoma and thymic carcinoma: an open-label [Link]
phase 2 trial. Lancet Oncol 2015;16:177-186. Available at:
[Link] 165. Strobel P, Hohenberger P, Marx A. Thymoma and thymic
carcinoma: molecular pathology and targeted therapy. J Thorac Oncol
158. Liang Y, Padda SK, Riess JW, et al. Pemetrexed in patients with 2010;5:S286-290. Available at:
thymic malignancies previously treated with chemotherapy. Lung [Link]
Cancer 2015;87:34-38. Available at:
[Link] 166. Dai J, Song N, Yang Y, Jiang G. Is it valuable and safe to perform
reoperation for recurrent thymoma? Interact Cardiovasc Thorac Surg
159. Longo F, De Filippis L, Zivi A, et al. Efficacy and tolerability of 2015;21:526-531. Available at:
long-acting octreotide in the treatment of thymic tumors: results of a [Link]
pilot trial. Am J Clin Oncol 2012;35:105-109. Available at:
[Link] 167. Gharwan H, Kim C, Thomas A, et al. Thymic epithelial tumors and
metastasis to the brain: a case series and systematic review. Transl
160. Loehrer PJ, Sr., Wang W, Johnson DH, et al. Octreotide alone or Lung Cancer Res 2017;6:588-599. Available at:
with prednisone in patients with advanced thymoma and thymic [Link]
carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J
Clin Oncol 2004;22:293-299. Available at: 168. Wu JX, Chen HQ, Shao LD, et al. Long-term follow-up and
[Link] prognostic factors for advanced thymic carcinoma. Medicine (Baltimore)
2014;93:e324. Available at:
161. Palmieri G, Merola G, Federico P, et al. Preliminary results of [Link]
phase II study of capecitabine and gemcitabine (CAP-GEM) in patients
with metastatic pretreated thymic epithelial tumors (TETs). Ann Oncol 169. Suster S, Rosai J. Thymic carcinoma. A clinicopathologic study of
2010;21:1168-1172. Available at: 60 cases. Cancer 1991;67:1025-1032. Available at:
[Link] [Link]

162. Highley MS, Underhill CR, Parnis FX, et al. Treatment of invasive 170. Moran CA, Suster S. Thymic carcinoma: current concepts and
thymoma with single-agent ifosfamide. J Clin Oncol 1999;17:2737-2744. histologic features. Hematol Oncol Clin North Am 2008;22:393-407.
Available at: [Link] Available at: [Link]

163. Gbolahan OB, Porter RF, Salter JT, et al. A phase II study of 171. Hosaka Y, Tsuchida M, Toyabe S, et al. Masaoka stage and
pemetrexed in patients with recurrent thymoma and thymic carcinoma. J histologic grade predict prognosis in patients with thymic carcinoma.
Thorac Oncol 2018;13:1940-1948. Available at: Ann Thorac Surg 2010;89:912-917. Available at:
[Link] [Link]

164. Cho J, Kim HS, Ku BM, et al. Pembrolizumab for patients with 172. Blumberg D, Burt ME, Bains MS, et al. Thymic carcinoma: current
refractory or relapsed thymic epithelial tumor: An open-label phase II staging does not predict prognosis. J Thorac Cardiovasc Surg

Version 1.2022 © 2021 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.
MS-20
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

1998;115:303-308; discussion 308-309. Available at: 180. Maruyama R, Suemitsu R, Okamoto T, et al. Persistent and
[Link] aggressive treatment for thymic carcinoma. Results of a single-institute
experience with 25 patients. Oncology 2006;70:325-329. Available at:
173. Okuma Y, Hosomi Y, Watanabe K, et al. Clinicopathological [Link]
analysis of thymic malignancies with a consistent retrospective
database in a single institution: from Tokyo Metropolitan Cancer Center. 181. Weide LG, Ulbright TM, Loehrer PJ, Williams SD. Thymic
BMC Cancer 2014;14:349. Available at: carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer
[Link] 1993;71:1219-1223. Available at:
[Link]
174. Ruffini E, Detterbeck F, Van Raemdonck D, et al. Thymic
carcinoma: a cohort study of patients from the European society of 182. Lucchi M, Mussi A, Ambrogi M, et al. Thymic carcinoma: a report
thoracic surgeons database. J Thorac Oncol 2014;9:541-548. Available of 13 cases. Eur J Surg Oncol 2001;27:636-640. Available at:
at: [Link] [Link]

175. Ahmad U, Yao X, Detterbeck F, et al. Thymic carcinoma outcomes 183. Yoh K, Goto K, Ishii G-i, et al. Weekly chemotherapy with cisplatin,
and prognosis: results of an international analysis. J Thorac Cardiovasc vincristine, doxorubicin, and etoposide is an effective treatment for
Surg 2015;149:95-100, 101 e101-102. Available at: advanced thymic carcinoma. Cancer 2003;98:926-931. Available at:
[Link] [Link]

176. Mao Y, Wu S. Treatment and survival analyses of completely 184. Igawa S, Murakami H, Takahashi T, et al. Efficacy of
resected thymic carcinoma patients. Onco Targets Ther chemotherapy with carboplatin and paclitaxel for unresectable thymic
2015;8:2503-2507. Available at: carcinoma. Lung Cancer 2010;67:194-197. Available at:
[Link] [Link]

177. Sakai M, Onuki T, Inagaki M, et al. Early-stage thymic carcinoma: 185. Koizumi T, Takabayashi Y, Yamagishi S, et al. Chemotherapy for
is adjuvant therapy required? J Thorac Dis 2013;5:161-164. Available advanced thymic carcinoma: clinical response to cisplatin, doxorubicin,
at: [Link] vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin
Oncol 2002;25:266-268. Available at:
178. Hirai F, Yamanaka T, Taguchi K, et al. A multicenter phase II study [Link]
of carboplatin and paclitaxel for advanced thymic carcinoma:
WJOG4207L. Ann Oncol 2015;26:363-368. Available at: 186. Kanda S, Koizumi T, Komatsu Y, et al. Second-line chemotherapy
[Link] of platinum compound plus CPT-11 following ADOC chemotherapy in
advanced thymic carcinoma: analysis of seven cases. Anticancer Res
179. Furugen M, Sekine I, Tsuta K, et al. Combination chemotherapy 2007;27:3005-3008. Available at:
with carboplatin and paclitaxel for advanced thymic cancer. Jpn J Clin [Link]
Oncol 2011;41:1013-1016. Available at:
[Link] 187. Komatsu Y, Koizumi T, Tanabe T, et al. Salvage chemotherapy
with carboplatin and paclitaxel for cisplatin-resistant thymic

Version 1.2022 © 2021 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.
MS-21
Printed by Huan Yao on 3/31/2022 10:06:00 PM. For personal use only. Not approved for distribution. Copyright © 2022 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 1.2022

Thymomas and Thymic Carcinomas

carcinoma--three cases. Anticancer Res 2006;26:4851-4855. Available 195. Okuma Y, Shimokawa T, Takagi Y, et al. S-1 is an active
at: [Link] anticancer agent for advanced thymic carcinoma. Lung Cancer
2010;70:357-363. Available at:
188. Remon J, Girard N, Mazieres J, et al. Sunitinib in patients with [Link]
advanced thymic malignancies: Cohort from the French RYTHMIC
network. Lung Cancer 2016;97:99-104. Available at: 196. Koizumi T, Agatsuma T, Komatsu Y, Kubo K. Successful S-1
[Link] monotherapy for chemorefractory thymic carcinoma. Anticancer Res
2011;31:299-301. Available at:
189. Remon J, Girard N, Mazieres J, et al. Erratum to "Sunitinib in [Link]
patients with advanced thymic malignancies: cohort from the French
RYTHMIC network" [Lung Cancer, 97 (July 2016), 99-104]. Lung 197. Giaccone G, Kim C, Thompson J, et al. Pembrolizumab in patients
Cancer 2016;101:146. Available at: with thymic carcinoma: a single-arm, single-centre, phase 2 study.
[Link] Lancet Oncol 2018. Available at:
[Link]
190. Palmieri G, Marino M, Buonerba C, et al. Imatinib mesylate in
thymic epithelial malignancies. Cancer Chemother Pharmacol
2012;69:309-315. Available at:
[Link]

191. Strobel P, Bargou R, Wolff A, et al. Sunitinib in metastatic thymic

carcinomas: laboratory findings and initial clinical experience. Br J
Cancer 2010;103:196-200. Available at:
[Link]

192. Bisagni G, Rossi G, Cavazza A, et al. Long lasting response to the

multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated
metastatic thymic carcinoma. J Thorac Oncol 2009;4:773-775. Available
at: [Link]

193. Strobel P, Hartmann M, Jakob A, et al. Thymic carcinoma with

overexpression of mutated KIT and the response to imatinib. N Engl J
Med 2004;350:2625-2626. Available at:
[Link]

194. Girard N. Targeted therapies for thymic malignancies. Thorac Surg

Clin 2011;21:115-123, viii. Available at:
[Link]

Version 1.2022 © 2021 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.
MS-22