Thymoma Treatment & Management
- Author: Kendrix J Evans, MD, MS; Chief Editor: John Geibel, MD, DSc, MSc, MA more...
A few reports in the literature suggest that thymomas are chemosensitive tumors. 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. 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.
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.
A multidisciplinary approach to therapy for unresectable thymomas has been advocated. 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).
Of the 12 patients, three (25%) had a complete response, eight (67%) a partial response, and one (8%) a minor response. 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. 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.
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.
In most cases of thymoma, initial management is surgical. 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. 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.
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.
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.
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.
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. Kaiser advocated the use of transcervical dissection in conjunction with video thoracoscopy, allowing better exposure.
Mack presented a series of photographs of thymus glands removed by means of thoracoscopy. 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. 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).
Adjuvant radiation therapy 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.
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. 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. 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. 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:
Patients with early-stage thymoma
Patients who underwent surgical extirpation of the neoplasm
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.
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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|Stage||5-Year Survival||10-Year Survival|
|IV||Less than 25%||N/A|
|Type||Histologic Description||Disease-Free Survival at 10 years,* %|
|B1||Predominantly cortical thymoma||83|
|B3||Well-differentiated thymic carcinoma||35|
|*Series of 100 thymomas resected in Japan between 1973 and 2001 using WHO classification.|
|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|