Multimodality treatment of thymic tumors.

Combined modality therapy is gaining acceptance for treating stage 3 and 4A thymic tumors. Also, specific subsets of stage 2 tumors deserve particular attention. Single-center experiences demonstrate that there are some advantages in selected groups of patients. The overall relatively low complete response rate, however, imposes the search for better systemic therapy to optimize results. In fact, although thymic tumors are responsive to different cytotoxic regimens, none has been demonstrated to be the ideal one. New therapies and strategies should be designed and tested in large-scale multicenter prospective trials. Among the others, epidermal growth factor receptor inhibitors have shown some clinical response, because EGFR is overexpressed in thymoma. c-KIT is overexpressed in thymic carcinoma. Although in a recent study a clinical response to imatinib has been reported, results of a prospective study in patients who have thymic carcinoma are pending. Clinical responses have been reported also to other tyrosine kinase inhibitors, such as dasatinib. Other reports have stressed the presence of an up-regulation of COX-2 with a potential separate therapeutic pathway. Other markers, such as the expression of thymidine synthase and dihydropyrimidine dehydrogenase, which predict sensitivity to 5-fluoruracil-based chemotherapy, were not correlated with the clinicopathological characteristics in a series of thymomas. These new therapies should be incorporated in a standardized approach that goes from a careful assessment of histology, staging, and lymph node status, and a constructive and nonempiric cooperation between the oncologist, radiotherapist, pathologist, and thoracic surgeon.