Ann Thorac Surg 2005;79:1844
© 2005 The Society of Thoracic Surgeons
Original article: General thoracic
Invited commentary
Giuliano Maggi, MD,
Enrico Ruffini, MD
Department of Thoracic Surgery, University of Torino, 3, Via Genova, Torino, 10126 Italy
(E-mail: giuliano.maggi{at}unito.it).
Thymomas are rare mediastinal tumors that are encapsulated in approximately half the cases and invasive to the surrounding mediastinal structures in the remaining half. Thymomas are both chemo and radiosensitive neoplasms, which makes the possibility of a multimodal approach rather promising. Multimodality treatment in solid thoracic organ neoplasms has become the standard of care in locally advanced nonsmall cell lung cancer, Pancoast’s tumors, and recently in malignant pleural mesothelioma. The basic concept is attractive, ie, that chemotherapy is used as an induction therapy to downstage the tumor, which is possibly associated with radiotherapy to enhance the cytoreductive effect; surgery is used to remove all visible disease; postoperative radiotherapy is used to achieve maximal local control of the disease, which is eventually followed by consolidation chemotherapy to eradicate the microscopic disease responsible for late treatment failures. In recent years, several studies, although limited to case reports or phase II trials, indicate that the use of induction chemotherapy for invasive thymomas (in addition to postoperative radiotherapy and possibly postoperative consolidation chemotherapy) optimizes surgical resectability and may contribute to an excellent control of residual disease and improved long-term survival.
The article by Lucchi and co-workers [1] represents a large series of patients, although distributed during a long time period of time (1976 to 2003). A total of 56 patients were treated, including 14 thymic carcinomas (25%), 36 of whom received induction chemotherapy. The response rate to chemotherapy was 66%, and the rate of complete resections was 77%. Five-year and 10-year survival rates in the group of patients receiving induction treatment were 78% and 65%, respectively. In a survival analysis, induction therapy offered a significant survival advantage in both stage III and stage IV thymomas. Surprisingly, radical resection was not a prognostic factor in the group of patients receiving induction treatment; this resulted more from the small number of cases in their series than from the alternative suggested hypothesis that tumor clearance may be equally obtained by a multimodality treatment. Despite some otherwise unavoidable methodological biases, including the fact that the two groups (ie, primary surgery and induction chemotherapy plus surgery) are consecutive and not concurrent, and that the series included some old cases in whom radiologic techniques were insufficient to correctly stage the disease, the results of the study are of interest. Some questions still arise necessitating future attention. First, thymomas are low-grade tumors with the exception of thymic carcinomas that may recur locally or at distant sites as long as 10 years from primary complete resection; treatment of recurrences may offer good long-term survival, but even in these cases, a multimodality therapy may be advocated and investigated accordingly. Second, symptoms associated with paraneoplastic syndromes (other than myasthenia gravis), including lupus erythematosus, hypogammaglobulinemia, or pure red cell aplasia may worsen during follow-up of operated thymomas; the role of these fluctuating syndromes after surgical resection still needs to be elucidated. By contrast, myasthenia gravis is no longer considered an adverse prognostic factor, and the improved medical therapy allows a better disease control and an earlier diagnosis in case of associated thymoma.
In conclusion, the efficacy of a multimodal approach in locally advanced thymomas is multifactorial, and conclusions from a limited series of patients treated over a long period of time should be cautiously interpreted, besides the statement that chemotherapy may be offered as the first treatment in patients with a radiologic evidence of locally advanced disease. A long follow-up is needed to support any conclusion about survival advantages from novel treatments. Recent experimental and clinical studies have introduced new fields of interest in the biology of this tumor; the role of new chemotherapy regimens, somatostatin analogues, and prednisone have recently been investigated and found to be potentially useful treatments. Therefore, it may be speculated in the not-too-long future a scenario in which novel molecularly targeted agents can be used and specifically directed in a patient-based therapy for each patient before surgery. Until then, we cannot help welcoming clinical studies such as this one on this exciting topic.
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References
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- Lucchi M, Ambrogi MC, Duranti L, et al. Advanced stage thymomas and thymic carcinomasresults of multimodality treatments. Ann Thorac Surg 2005;79:1840-1844.[Abstract/Free Full Text]
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