Stage I and Stage II Thymoma
Excellent long-term survival can be obtained following complete surgical excision for a pathologic stage I thymoma. There appears to be no benefit to adjuvant radiation therapy following complete resection of encapsulated noninvasive tumors.[1,2] For patients with stage II thymomas with pathologically demonstrated capsular invasion, adjuvant radiation therapy following complete surgical excision has been considered a standard of care despite the lack of prospective clinical trials.[3,4]
Most studies use 40 Gy to 70 Gy with standard fractionation scheme (1.8–2.0 Gy/fraction). Some, but not all, retrospective clinical studies show improved local control and survival with the addition of postoperative radiation therapy (PORT).[5-8][Level of evidence: 3iiiDiv] More recent retrospective studies have found no outcome difference in patients treated with or without PORT following complete resection of the thymic tumor.[8-12]
In the largest series reported to date, data was obtained from 1,320 Japanese patients. The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with stage I thymoma were treated with surgery only, and patients with stage II thymoma underwent surgery and additional radiation therapy. Prophylactic mediastinal radiation therapy did not appear to prevent local recurrences effectively in patients with totally resected stage II thymoma.
The role and risks of adjuvant radiation therapy for patients with completely resected stage II thymomas need further study. To avoid the potential morbidity and costs associated with thoracic radiation, PORT may be reserved for stage II patients where adjacent organs are within a few millimeters or involve of the surgical margin as determined by both pathological and intraoperative findings.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I thymoma and stage II thymoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Operable or Potentially Operable Stage III and Stage IVA Thymoma
Stage III thymoma may be difficult to identify prior to surgery as subtle invasion to the adjacent organs may only be identified at the time of mediastinal exploration. Such patients often receive aggressive surgical resection including wide surgical margins with consideration of adjuvant radiation therapy. Invasion of local organs can be apparent on pretreatment computed tomographic imaging. Such patients may be offered combined modality treatment with chemotherapy followed by surgery and/or radiation therapy.[13-20] The optimal strategy for induction therapy, which minimizes operative morbidity and mortality and optimizes resectability rates and ultimately survival, currently remains unknown.
Two large series have reported outcomes. In the first study, data was obtained from 1,320 Japanese patients. The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with stage III thymoma underwent surgery and additional radiation therapy. Patients with stage IV thymoma were treated with radiation therapy or chemotherapy. For patients with stage III or stage IV thymoma, the 5-year survival rates were 93% for patients treated with total resection, 64% for patients treated with subtotal resection, and 36% for patients whose disease was inoperable. Prophylactic mediastinal radiation therapy did not appear to prevent local recurrences effectively in patients with totally resected stage III thymoma. Adjuvant therapy including radiation or chemotherapy did not appear to improve the prognosis in patients with totally resected stage III or stage IV thymoma.
In the second study, 1,334 patients diagnosed and treated between 1973 and 2005 were identified in a SEER database. At a relatively short median follow-up of 65 months, radiation therapy did not appear to increase the risk of cardiac mortality or secondary malignancy. Routine use of PORT did not appear to improve long-term survival.
Most invasive thymomas have been found to be relatively sensitive to cisplatin-based combination chemotherapy regimens. The combinations that follow have reported objective response rates from 79% to 100% with subsequent resectability rates ranging between 36% and 69%:[13-19,21]
- The combination of cisplatin, doxorubicin, and cyclophosphamide (PAC) with or without prednisone.
- The combination of cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC).
- The combination of cisplatin, etoposide, and epirubicin.
Long-term survival rates following induction chemotherapy and surgery with or without radiation therapy and consolidation chemotherapy have ranged from 50% at 4 years, 77% at 7 years and, respectively, 86% and 76% for stage III and IV patients at 10 years in different published series.[14,16,17,22]
However, similar results have been reported with preoperative radiation therapy without chemotherapy, particularly if great vessels are involved (5-year overall survival rate of 77% and 10-year OS rate of 59%).[23,24]
An intergroup trial conducted in the United States reported a predicted 5-year OS rate of 52% in 26 patients receiving the PAC chemotherapy regimen followed by radiation therapy without surgery.
The role of surgical debulking for patients with either stage III or stage IVA disease is controversial. Phase II data suggests that prolonged survival can be accomplished with chemotherapy and radiation therapy alone in many patients presenting with locally advanced or even metastatic thymoma. Therefore, the value of surgery may be questioned if complete, or at the very least, near complete extirpation cannot be accomplished.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III thymoma and stage IV thymoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Standard treatment options for patients with operable disease include the following:
- En bloc surgical resection.
- PORT may be considered, especially for patients with close or involved surgical margins and for stage III and stage IVA patients.
- Induction chemotherapy followed by surgery with or without radiation.
Standard treatment options for patients with inoperable disease (stage III and stage IV with vena caval obstruction, pleural involvement, pericardial implants, etc.) include the following:
- Induction chemotherapy followed by surgery or radiation.
- Induction chemotherapy followed by surgery and radiation.
- Radiation therapy.
Treatment options under clinical evaluation:
Areas of active clinical evaluation for patients with thymoma include the following:
- New drug regimens.
- Variation of drug doses in current regimens.
- New radiation therapy schedules and techniques.
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