Nonsurgical management of malignant thymoma

Abstract

Thymoma is a rare tumor entity. Surgery remains the mainstay of treatment, but radiation and chemotherapy also have been applied widely in both the adjuvant and the palliative setting. The objective of this study was to review briefly the clinical trials available in the current literature utilizing nonsurgical oncologic treatment (radiotherapy and chemotherapy) either in patients with advanced (i.e., locally inoperable) or metastatic thymoma or as an adjunct to surgery. A computerized (MEDLINE) and a manual search was performed to identify articles published on this topic between 1965-1998. Only articles with an English abstract were reviewed for inclusion; information abstracted included histologic proof of diagnosis, number of patients, dose and modality of treatment, assessment of response, response rate, survival duration, and side effects. Seventy-one trials were identified subsequently. These included 51 chemotherapy studies in a total of 410 patients (including 19 single agent trials and 32 combination chemotherapy trials) and 20 radiotherapy studies. In the adjuvant setting, radiation appeared to result in a higher survival rate compared with historic controls as well as excellent local control in patients with advanced stage of disease, whereas no apparent benefit was observed in patients with Masaoka et al. classified Stage I disease. The large majority of chemotherapeutic studies were case reports or Phase II trials of advanced disease, whereas no prospectively randomized trials were performed. Response rates were relatively heterogeneous and ranged between 24% and 100%, not including the results published in single case reports, and response rates >50% have been found consistently with the application of polychemotherapy. In the absence of randomized trials, multimodality approaches using induction chemotherapy followed by resection and consecutive radiation have produced highly promising results in terms of resectability and long term survival, even in patients with advanced disease. To the authors' knowledge, there is no standard approach to advanced thymoma apart from surgery (i.e., total resection whenever possible). Despite reports of long term disease control, symptomatic palliation, and encouraging survival data, the majority of studies involved only a small number of patients and were performed in a Phase II approach. Large scale, randomized trials to elucidate the potential of multimodality approaches clearly are needed, and patients with thymoma should be included in such studies.