Complete resection of a well-encapsulated, non-invasive thymoma is usually curative, with a risk of local recurrence of less than 2%. In patients with myasthenia gravis, operative mortality can now be minimised with close attention to respiratory support when planning surgical treatment. There is no role for radiotherapy unless a non-invasive thymoma is incompletely resected.
Surgery
En bloc surgical resection of the tumour with intact capsule is standard. The surgeon must carefully assess the tumour during the operation in an attempt to identify any invasive qualities, and should mark areas that are suspicious for invasion in an effort to guide the pathologist's microscopic description and the radiation oncologist's adjuvant therapy.
Radiotherapy
The value of adjuvant radiation therapy in invasive thymomas is well documented and should be included in the treatment regimen regardless of the completeness of tumour resection. In a review of 115 completely resected invasive thymomas (Curran et al. 1988), a recurrence rate of 5% was documented when adjuvant radiation therapy was employed; this increased to 28% without adjuvant radiotherapy.
Chemotherapy
Adjuvant chemotherapy has not been reported in stage II thymoma. Radiotherapy is the treatment of choice when the area at risk of recurrence can be encompasses within a reasonable radiotherapy volume. In cases where the surgeon identifies pleural invasion (Stage IIB) such that the pleural space is judged to be at risk of drop metastases, the area at risk extends outside a reasonable radiotherapy volume. In such cases, adjuvant chemotherapy may be a consideration particularly in young or fit patients. Complex cases are ideal for multi-disciplinary review at lung conference.
Surgery
When invasion of neighbouring organs is identified intra-operatively, aggressive resection including lung, pleura, phrenic nerve, pericardium, and great vessels is occasionally necessary. Adjuvant thoracic irradiation may be guided if areas at high risk of recurrence are marked with surgical clips. The role of subtotal resection or debulking procedures in advanced, unresectable stage III disease is uncertain.
When invasion of adjacent organs is identified before surgery, preoperative downstaging with chemotherapy or chemoradiation should be considered. After pre-operative therapy, definitive local surgery should be performed 4 to 6 weeks after the final cycle of chemotherapy.
Chemotherapy
During the past decade, thymoma has clearly been identified as a chemosensitive tumour. The optimal regimen and precise role of chemotherapy continues to be uncertain because the low incidence of thymomas limits feasibility of large clinical trials.
Cisplatin containing combination chemotherapy regimens appear to be the most active. The PAC regimen consisting of cisplatin, doxorubicin, and cyclophosphamide (Loehrer et al. 1994) and etoposide plus cisplatin (Giaccone et al. 1996) are capable of inducing responses in the majority of patients with advanced disease with some complete responses. Neoadjuvant chemotherapy with PAC before resection of locally advanced cases is associated with a high response rate but the majority of patients had histologically viable tumour in the resection specimen and received post-operative radiotherapy (Rea et al. 1993). Theoretically, risk of tumour dissemination outside the mediastinum at the time of surgery should be diminished if a higher proportion of patients were downstaged to pT0. A higher pT0 rate should be possible when combined chemoradiation is given before surgery. Preoperative thoracic irradiation given concurrently with cisplatin plus etoposide has been widely used in the combined modality therapy of stage III NSCLC (Albain et al. 1995) with acceptable risk of toxicity and promising results. A similar model of treatment may be suitable for stage III thymoma when initial complete resection appears unlikely.
Radiotherapy
Adjuvant radiotherapy after resection is standard in cases where the risk for recurrence is judged to reside within a reasonable radiotherapy volume.
Thoracic irradiation delivered concurrently with cisplatin plus etoposide should be delivered in the same fashion described for Stage III NSCLC (at Lung page, click on 6.Management).
Chemotherapy
Etoposide plus cisplatin or the PAC regimen induce responses in more than half of advanced cases with median survival of 3-4 years and 5-year survival of 20-30%. Concurrent chemoradiation should not be considered for patients with disease not encompassable within a reasonable radiotherapy volume.
Surgery and Radiotherapy
Surgery may be considered in Stage IVA thymomas that respond well to initial chemotherapy. Such cases are appropriate for lung conference.
Thoracic irradiation as a consolidative therapy after good chemotherapy response of stage IV thymomas should be considered on a case by case basis. Recurrent thymoma that is resistant to chemotherapy may be appropriate for palliative radiotherapy.
References:
McKenna WG, Bonomi P, Barnes MM, et al. Malignancies of the thymus. In:Roth JA, Ruckdeschel JC, Weisenburger TH: Thoracic Oncology. Philadelphia, Pa, WB Saunders Co 1989, pp 466-477.
Shamji F, Pearson FG, Todd TRJ, Ginsberg RJ, Ilves R, Cooper JD. Results of surgical treatment of thymoma. J Thorac Cardiovasc Surg 1984;87:43.
Curran WJ, Kornstein MJ, Brooks JJ, et al. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 1988;6:1722-1727.
Pollack A, Komaki R, Cox JD, et al. Thymoma: treatment and prognosis. Int J Radiol Oncol Biol Phys 1992;23:1037
Loehrer PJ, Kim K, Aisner SC, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. J Clin Oncol 1994;12:1164-1168
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 Lung Cancer Cooperative Group. J Clin Oncol 1996;14:814-820.
Rea F, Sartori F, Loy M, et al. Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 1993;106:543-549.
Albain K, Rusch V, Crowley J, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol 1995;13:1880-92.
For patients with invasive thymoma in complete remission after definitive treatment, follow-up should include clinical examination and chest radiographs every four months for two years, every six months until five years and annually thereafter. The rationale of this follow-up is that recurrent thymomas can occasionally achieve long lasting second remissions with salvage therapy. Thymoma patients treated palliatively should have follow-up based on symptomatology and treatment modality used. The BCCA doctor in charge should explicitly clarify the physician in charge of palliative patient follow-up.
