World J Oncol
World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Review

Volume 7, Number 5-6, December 2016, pages 95-97


The Place and the Role of Radiation Therapy in the Treatment of Thymic Carcinoma

Memtsa Pinelopi-Theopistia, d, Papadopoulou Aikaterinib, Kyriakogiannaki Ariadnic, Iliopoulou Chrysoulaa, Pantelis Panagiotisa, Charalambidou Marthaa

aDepartment of Radiation Oncology, Cancer Hospital “Theageneio”, Thessaloniki, Greece
bDepartment of Radiation Oncology, AHEPA Hospital, Aristotle University, Thessaloniki, Greece
cDepartment of Radiation Oncology, Alexandra Hospital, Athens, Greece
dCorresponding Author: Memtsa Pinelopi-Theopisti, Department of Radiation Oncology, AHEPA Hospital, Aristotle University, Psarron 26, 54453, Thessaloniki, Greece

Manuscript accepted for publication December 07, 2016
Short title: Radiation Therapy for Thymic Carcinoma
doi: https://doi.org/10.14740/wjon972e

Abstract▴Top 

Thymic carcinomas arise from the epithelial cells of the thymus gland and are the most common tumors of the anterior mediastinum despite their overall rarity. Because of their rarity, their treatment remains a challenging topic. Although historically they have been treated surgically, radiation therapy (RT) has an important role either as a definitive or as a postoperative treatment. In this article, we present a review of the current therapies for the thymic carcinomas and try to identify the exact place of the RT in the optimal management of these patients.

Keywords: Thymic carcinoma; Radiation therapy

Introduction▴Top 

Thymic malignancies are the most common primary neoplasms of the anterior mediastinum; however, they are a relatively rare disease. They usually occur in patients aged 40 - 60 years with a male to female ratio of 1:1. Thymic carcinomas arise from the epithelial cells of the thymus gland and are classified into six subtypes from the Masaoka clinical staging system [1] and the World Health Organization (WHO) [2]. They grow in close proximity to critical structures like heart, lungs and great vessels; hence, it is very difficult to treat without causing great morbidity to patients.

Up to 40% of thymoma patients present no symptoms. Common signs and symptoms are caused by local invasion of the disease or paraneoplastic syndrome, especially myasthenia gravis. Other commonly observed signs in thymic carcinomas include chest pain, dyspnea, dysphagia, cough and superior vena cava obstruction [3].

Treatment of thymoma depends on the respectability of the disease and surgery is the mainstay of therapy [4]. Completeness of resection is prognostically significant. Radiotherapy (RT) has long been established as an important component in the therapy of this disease, although its outstanding benefit versus toxicity in the postoperative setting remains debatable [5]. The evolution of the RT from 3D conformal treatment to four-dimensional (4D) treatment, intensity modulated radiation therapy (IMRT) and proton use has led to less toxicity and better control of the tumor [6].

Adjuvant RT▴Top 

Postoperative RT (PORT) should be considered for various indications. There are no phase III studies investigating adjuvant treatment but adjuvant RT is recommended following incomplete excision of stage II and III tumors [7]. Radiation for R1 or R2 thymic malignancies should be started within 3 months of surgical resection. Doses between 40 and 64 Gy are most appropriate for microscopically positive margins, whereas doses of 54 Gy or higher should be used for gross disease. Patients with positive margins should be considered for concurrent RT and chemotherapy [8].

In completely resected (R0) thymic malignancies, RT should be considered more strongly as the risk of recurrence increases. Some of the indications are aggressive tumor histologies or Masaoka stage II and III disease [9]. The minimum acceptable dose for postoperative R0 disease is 50 Gy with standard fractionation 1.8 - 2 Gy/day.

Radiation to elective nodal region is not recommended, while the extend of the malignancy before the surgery should be used as a guide for the delineation of the target volumes [5].

Neo-Adjuvant RT▴Top 

When the disease appears to be unresectable at diagnosis, neo-adjuvant chemotherapy and RT can increase the likelihood of resection for patients who are otherwise eligible for surgery. RT in this context can be difficult to deliver without exceeding dose constraints and it should include the gross area of involvement with an appropriate margin [10]. The dose for neo-adjuvant RT should be 45 Gy in 1.8 Gy daily fractions.

Definite RT▴Top 

Definite RT is preferred for patients who are not candidates for surgery because of the extent of disease during the diagnosis or because they are unfit for surgery due to medical conditions [11]. The control of the disease is more achievable with the combination of RT and chemotherapy. The radiation dose should be 60 - 66 Gy to encompass the gross disease plus a margin for microscopic regions at risk.

Target Volume Delineation and RT Techniques▴Top 

The multidisciplinary team plays an essential role in the delivery of RT so as to assure the maximum benefit and the less toxicity for the patient. Discussion with the surgeon and the pathologist is very important to define sites at risk of local recurrence [12]. The delineation of the gross tumor volume (GTV) is defined if there is residual macroscopic disease. GTV is expanded isotropically by 10 mm to form the clinical target volume (CTV) so as to encompass the microscopic disease. If chemotherapy has been given, the CTV should encompass all initial sites of disease and possible sites of microscopic invasion which may include the mediastinum and pericardium. The CTV is then expanded by 5 mm to form the PTV so as to include the systematic and random errors and the organ motion [13].

Because of the central location of these malignancies, the use of 3D CRT, IMRT or, if available, proton beam therapy, is strongly recommended. Adaptive re-planning should also be considered, because of the important change in the size and shape of these tumors during the several weeks of the course of radiation treatment. This includes obtaining an additional CT halfway through treatment and re-evaluating the tumor coverage; hence, we can significantly minimize the radiation dose to normal tissues [14].

Inverse planned IMRT may enable the delivery of higher doses of radiation, increase the probability of disease control and limit the dose to the surrounding esophagus, spinal cord, heart and lung [15].

Discussion▴Top 

Because of the rarity of the disease, there is a lack of studies which evaluate whether the inclusion of RT affects disease control and survival in thymic malignancies.

Currently, the role of adjuvant RT in the treatment of thymic malignancies largely depends on the stage of the disease and the extent of surgical resection. Patients with stage I or stage II, R0 or with favorable histology (WHO class A, B, B1) seem to have no benefit with the addition of RT [16].

In contrast, patients with stage III and IV disease and other unfavorable factors seem to benefit in terms of survival, local control or recurrence upon the addition of RT after surgical resection [17].

More data are necessary to establish a definite algorithm for treatment and radiation- dose relationship as well as the incidence of toxicity from treatment. It is important to follow patients carefully so as to monitor for signs of recurrence and late toxicity from RT.

In conclusion, a great deal of concern should be given in the development of multicenter, randomized studies/trials which will provide the scientific community with evidence-based treatment algorithms for thymic malignancies.


References▴Top 
  1. Masaoka A. Staging system of thymoma. J Thorac Oncol. 2010;5(10 Suppl 4):S304-312.
    doi pubmed
  2. Engels EA. Epidemiology of thymoma and associated malignancies. J Thorac Oncol. 2010;5(10 Suppl 4):S260-265.
    doi pubmed
  3. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003;105(4):546-551.
    doi pubmed
  4. Okereke IC, Kesler KA, Morad MH, Mi D, Rieger KM, Birdas TJ, Badve S, et al. Prognostic indicators after surgery for thymoma. Ann Thorac Surg. 2010;89(4):1071-1077; discussion 1077-1079.
    doi pubmed
  5. Ogawa K, Uno T, Toita T, Onishi H, Yoshida H, Kakinohana Y, Adachi G, et al. Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer. 2002;94(5):1405-1413.
    doi pubmed
  6. Gomez D, Komaki R. Technical advances of radiation therapy for thymic malignancies. J Thorac Oncol. 2010;5(10 Suppl 4):S336-343.
    doi pubmed
  7. Curran WJ, Jr., Kornstein MJ, Brooks JJ, Turrisi AT, 3rd. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol. 1988;6(11):1722-1727.
    pubmed
  8. Berman AT, Litzky L, Livolsi V, Singhal S, Kucharczuk JC, Cooper JD, Friedberg JR, et al. Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer. 2011;117(15):3502-3508.
    doi pubmed
  9. Fan C, Feng Q, Chen Y, Zhai Y, Zhou Z, Chen D, Xiao Z, et al. Postoperative radiotherapy for completely resected Masaoka stage III thymoma: a retrospective study of 65 cases from a single institution. Radiat Oncol. 2013;8:199.
    doi pubmed
  10. Fernandes AT, Shinohara ET, Guo M, Mitra N, Wilson LD, Rengan R, Metz JM. The role of radiation therapy in malignant thymoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Oncol. 2010;5(9):1454-1460.
    doi pubmed
  11. Shin DM, Walsh GL, Komaki R, Putnam JB, Nesbitt J, Ro JY, Shin HJ, et al. A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med. 1998;129(2):100-104.
    doi pubmed
  12. Feigen M, Lee ST, Lawford C, Churcher K, Zupan E, Scott AM, Hamilton C. Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and (18) F-FDG PET/CT scan correlation. J Med Imaging Radiat Oncol. 2011;55(3):320-332.
    doi pubmed
  13. Pollack A, Komaki R, Cox JD, Ro JY, Oswald MJ, Shin DM, Putnam JB, Jr. Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Phys. 1992;23(5):1037-1043.
    doi
  14. Britton KR, Starkschall G, Liu H, Chang JY, Bilton S, Ezhil M, John-Baptiste S, et al. Consequences of anatomic changes and respiratory motion on radiation dose distributions in conformal radiotherapy for locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2009;73(1):94-102.
    doi pubmed
  15. Huang EX, Hope AJ, Lindsay PE, Trovo M, El Naqa I, Deasy JO, Bradley JD. Heart irradiation as a risk factor for radiation pneumonitis. Acta Oncol. 2011;50(1):51-60.
    doi pubmed
  16. Mangi AA, Wright CD, Allan JS, Wain JC, Donahue DM, Grillo HC, Mathisen DJ. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg. 2002;74(4):1033-1037.
    doi
  17. Mangi AA, Wain JC, Donahue DM, Grillo HC, Mathisen DJ, Wright CD. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg. 2005;79(6):1834-1839.
    doi pubmed


This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


World Journal of Oncology is published by Elmer Press Inc.

 

Browse  Journals  

     

Journal of clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 

 

 

 

World Journal of Oncology, bimonthly, ISSN 1920-4531 (print), 1920-454X (online), published by Elmer Press Inc.            
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.wjon.org   editorial contact: editor@wjon.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.