A multidisciplinary approach to therapy for unresectable malignant thymoma

Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. Objective: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. Design: Prospective cohort study. Setting: Tertiary care cancer center. Participants: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. Intervention: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. Measurements: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. Results: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r = -0.88). Conclusions: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.