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Thymoma Treatment & Management

  • Author: Kendrix J Evans, MD, MS; Chief Editor: John Geibel, MD, DSc, MSc, MA  more...
 
Updated: Dec 16, 2015
 

Medical Therapy

Chemotherapy

A few reports in the literature suggest that thymomas are chemosensitive tumors.[7] Potential candidates for chemotherapy include approximately one third of the patients with an invasive thymoma that later metastasizes and all patients with stage IV disease.

Fornasiero et al reported successful cases and some long-term survivors following the administration of a regimen of cisplatin/vincristine/doxorubicin/cyclophosphamide for incompletely resected invasive thymomas or cases with unresectable disease.[8] In 32 patients, a 47% complete and 90% overall response rate was noted with a median survival time of 15 months.

A trial conducted by the European Organisation for Research and Treatment of Cancer reported that among 16 patients with recurrent or metastatic thymomas, five complete remissions and four partial remissions were observed. Median survival time in this study was 4.3 years.

Corticosteroids

Case reports have documented the administration of oral glucocorticoids resulting in regression of an invasive thymoma. In one case, the patient showed complete regression to the thymoma and associated symptoms and has remained without radiologic recurrence after 12 months.[9]

Multidisciplinary approach

A multidisciplinary approach to therapy for unresectable thymomas has been advocated.[10] In a trial conducted by the M.D. Anderson Cancer Center, 12 patients received a treatment regimen consisting of induction chemotherapy (ie, three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (ie, three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone).[11]

Of the 12 patients, three (25%) had a complete response, eight (67%) a partial response, and one (8%) a minor response.[11] One patient refused surgery, nine (82%) had complete resections, and two (18%) who had been receiving radiation therapy and consolidation chemotherapy had incomplete resections. All 12 patients (100%) were alive at 7 years, and 10 (73%) were disease-free at 7 years. The authors suggested that aggressive multimodal treatment is effective and may be curative in locally advanced, unresectable, malignant thymomas.

Octreotide (0.5 mg SC q8hr) alone or with prednisone (0.6 mg/kg/day) was evaluated in 38 patients with advanced thymomas that expressed somatostatin receptors.[12] Of the 38, four (10.5%) had a partial response with octreotide alone. Of the 21 patients who received octreotide plus prednisone, two had complete responses and four had partial responses. Octrotide plus prednisone yielded better progression-free survival than octreotide alone. Octreotide therapy may be a valuable treatment option when chemotherapy is ineffective.

See Thymoma Treatment Protocols for more information.

Future options

Studies have investigated the molecular changes in thymomas. In one study, 10 out of 12 thymomas exhibited epidermal growth factor receptor (EGFR) expression. This information would be useful in selecting patients that may benefit from EGFR inhibitors as part of their treatment regimen. Other areas of investigation include apoptosis-related markers, such as p63, a member of the p53 family. This marker is expressed in virtually all thymomas. Further research pertaining to the biology of thymomas will allow more adequate approaches to treatment.

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Surgical Therapy

In most cases of thymoma, initial management is surgical.[7] Surgical excision provides the histologic characteristics of the tumor and provides staging information that helps determine the need for adjuvant therapy. Small and encapsulated thymomas are excised for diagnosis and treatment. In the past, obtaining a preoperative biopsy of large invasive thymomas was shunned for fear of local implantation of tumor cells. Currently, biopsies are performed for these atypical tumors to discover the histology of the tumor and to ascertain its invasive potential.

A single-institution retrospective study was conducted of five patients with stage IVA thymoma treated with pleuropneumonectomy.[13] The median survival was 86 months, and the Kaplan-Meier survival was 75% at 5 years and 50% at 10 years. There was no operative mortality in this study. It has been suggested that in select patients, this approach after a complete resection and neoadjuvant chemotherapy may be promising.[13]

The prognosis for a thymoma patient is based on the tumor's gross characteristics at operation, not its histologic appearance. Benign tumors are noninvasive and encapsulated. Conversely, malignant tumors are defined by local invasion into the thymic capsule or surrounding tissue. As noted (see Staging), the Masaoka system is the most commonly accepted staging system for thymomas.

Although controversy exists regarding the use of postoperative radiation for invasive thymomas, the preponderance of evidence indicates that all thymomas, except completely encapsulated stage I tumors, benefit from adjuvant radiation therapy.[2]

Preparation for surgery

Preoperative adjuvant radiation therapy has been used to increase the possibility of complete resection when computed tomography (CT) suggests that a tumor is very large or invasive. Although doses of 30-45 Gy have been used in this approach, complete responses rarely have been reported. One caveat to this therapy is that the patient is placed at increased risk for radiation pneumonitis because of the large size of ports required to cover the field.

Patients with a preoperative diagnosis of myasthenia gravis (MG) and a thymoma should optimize their medical condition before surgery by using cholinesterase inhibitors and plasmapheresis if indicated.

Procedural details

Although the preferred approach is a median sternotomy to provide adequate exposure of the mediastinal structures and allowing complete removal of the thymus, the cervical approach also is adequate.

If the tumor is small and appears readily accessible, perform a total thymectomy with contiguous removal of mediastinal fat. If the tumor is invasive, perform a total thymectomy in addition to en-bloc removal of involved pericardium, pleura, lung, phrenic nerve, innominate vein, or superior vena cava. Resect one phrenic nerve; however, if both phrenic nerves are involved, do not resect either one, and debulk the area. Clip areas of close margins or residual disease to assist the radiation oncologist in treatment planning.

Controversy persists with regard to whether biopsy or subtotal excision is superior for treating unresectable tumors. Some studies have supported subtotal excision, whereas others have shown no difference between the two modalities. A generally accepted rule is that patients with invasive or residual disease should receive adjuvant therapy.

Future options

With the advent of video-assisted minimally invasive surgery, many of the traditional thoracic procedures have been abandoned. Cases of video-assisted thoracoscopic surgery (VATS) have been described; however, few long-term results are available.

Roviaro et al performed video thoracoscopy on six patients with thymomas; however, they did not describe the extent of resection, the size of the tumor, or the tumor stage, and long-term follow-up data are unavailable.[14] Kaiser advocated the use of transcervical dissection in conjunction with video thoracoscopy, allowing better exposure.[15]

Mack presented a series of photographs of thymus glands removed by means of thoracoscopy.[16] These photographs confirmed that the thymus gland can be resected completely by experienced surgeons. Long-term follow-up data are required to determine the true efficacy of this procedure compared with traditional thymectomy.

In a study of 140 patients with stage I and II thymoma, Chao et al compared perioperative and oncologic outcomes after VATS resection for stage I and II thymoma with those obtained after median sternotomy.[17] No operative deaths occurred, and there were no statistically significant differences in 5-year survival between the two study groups. VATS was associated with better perioperative outcomes (eg, less intraoperative blood loss, greater frequency of extubation in the operating room after surgery, and a shorter length of stay).

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Postoperative Care

Adjuvant radiation therapy[7] in completely or incompletely resected stage III or IV thymomas is considered a standard of care. The use of postoperative radiation therapy in stage II thymomas, however, has been more questionable.

Thymomas are indolent tumors that may take at least 10 years to recur; therefore, short-term follow-up will not depict relapses accurately. Furthermore, the gross appearance of tumor invasiveness is subjective, depending on the opinion of the surgeon. In one report from the Massachusetts General Hospital, five (22%) of 23 patients with stage II disease developed recurrences, leading to a proposed recommendation that postoperative radiation be instituted in all patients with stage II thymoma.[18]

In a study conducted by Curran et al that included 21 patients with stage II and III disease who did not undergo postoperative (total resection) radiation therapy, eight patients had recurrences in the mediastinum.[19] The five patients who received adjuvant radiation did not have recurrences.

A series from Memorial Sloan-Kettering Cancer Center, however, showed that adjuvant radiation therapy did not improve survival or decrease recurrence in stage II and III disease.[3] To reduce the incidence of local relapse, perform postoperative adjuvant radiation therapy in patients without completely encapsulated stage I tumors.

In a retrospective review of 241 patients with thymoma who received radiation therapy after total thymectomy, partial resection, debulking, or biopsy, Wu et al reported 10-year survival rates of 87% for stage I thymoma, 78.7% for stage II, 57.4% for stage III disease, and 24.3% for stage IV.[20] They concluded that surgery and postoperative radiotherapy should be standard for stage II or III but that further research was needed to establish whether this is true for stage I. They also found that the following tended to have a more favorable prognosis:

  • Female patients
  • Patients with early-stage thymoma
  • Patients who underwent surgical extirpation of the neoplasm
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Complications

Complications (eg, radiation pericarditis, radiation pneumonitis, pulmonary fibrosis) have been reported after postoperative radiation therapy. Deaths from these complications have been reported; accordingly, clinicians must carefully consider the risk-to-benefit ratio of adjuvant radiation therapy.

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Long-Term Monitoring

Relapse after primary therapy for a thymoma may occur after 10-20 years. Therefore, long-term follow-up probably should continue to be performed throughout the patient's life.

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Contributor Information and Disclosures
Author

Kendrix J Evans, MD, MS Resident Physician, Department of General Surgery, University of Utah School of Medicine

Kendrix J Evans, MD, MS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Medical Student Association/Foundation, Association of Military Surgeons of the US, Christian Medical and Dental Associations

Disclosure: Nothing to disclose.

Coauthor(s)

A Letch Kline, MD Chief, Academic Affliations, Gulf Coast Veterans Health Care System; Clinical Assistant Professor, Department of Surgery, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine

A Letch Kline, MD is a member of the following medical societies: American College of Chest Physicians, American College of Surgeons, Southeastern Surgical Congress

Disclosure: Nothing to disclose.

Quintessa Miller, MD 

Quintessa Miller, MD is a member of the following medical societies: American College of Surgeons, National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John Geibel, MD, DSc, MSc, MA Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Received royalty from AMGEN for consulting; Received ownership interest from Ardelyx for consulting.

Additional Contributors

Juan B Ochoa, MD Assistant Professor, Department of Surgery, University of Pittsburgh School of Medicine; Medical and Scientific Director, HCN, Nestle Healthcare Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

References
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Anatomy of thymus, with emphasis on blood supply and relation to recurrent laryngeal and phrenic nerves.
Lateral view of thymus. Thymic arteries are derived from adjacent internal mammary arteries; inferior thymic vein empties into innominate vein. Thymus gland's surrounding vascular and neural structures may be invaded during spread of thymoma.
CT scan clearly illustrates mass in right anterolateral mediastinum.
Table 1. Survival of Thymoma by Stage: Memorial Sloan-Kettering Experience
Stage 5-Year Survival 10-Year Survival
I 90% 80%
II 90% 80%
III 60% 30%
IV Less than 25% N/A
Table 2. World Health Organization (WHO) Pathologic Classification and Associated Prognostic Categories
Type Histologic Description Disease-Free Survival at 10 years,* %
A Medullary thymoma 100
AB Mixed thymoma 100
B1 Predominantly cortical thymoma 83
B2 Cortical thymoma 83
B3 Well-differentiated thymic carcinoma 35
C Thymic carcinoma 28
*Series of 100 thymomas resected in Japan between 1973 and 2001 using WHO classification.[6]
Table 3. Masaoka Staging System of Thymomas and Corresponding Therapy
Stage Definition Treatment
I Encapsulated tumor with no gross or microscopic invasion Complete surgical excision
II Macroscopic invasion into the mediastinal fat or pleura or microscopic invasion into the capsule Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence
III Invasion of the pericardium, great vessels, or lung Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence
IVA Pleural or pericardial metastatic spread Surgical debulking, radiotherapy, and chemotherapy
IVB Pleural or pericardial metastatic spread Surgical debulking, radiotherapy, and chemotherapy
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