Stage IVA Thymoma Research Articles

Feasibility of multimodality therapy including extended resections in stage IVA thymoma

Extended resections for advanced-stage thymomas are not commonly performed because of the potential morbidity in the face of unclear survival or palliative benefit. We reviewed our experience with multimodality treatment for Masaoka stage IVA thymomas for feasibility and outcomes. We conducted a retrospective review of a single-institution surgical database. Data included patient demographics, preoperative staging and treatment, perioperative events, pathologic findings, and postoperative outcomes. During the period from 1996 to 2006, 18 patients who had Masaoka stage IVA thymoma underwent surgical resection. All patients received preoperative chemotherapy. Four patients with extensive pleural involvement underwent concomitant extrapleural pneumonectomy and postoperative hemithoracic radiation. Complete resection was achieved in 12 (67%) patients. There was no operative mortality. With a median follow-up of 32.2 months (range 1.4-129.9 months), 3-year, 5-year, and 10-year survivals were 91%, 78%, and 65%, respectively, and median survival has not yet been reached. Multimodality therapy including extended surgical resection can be performed in select patients with stage IVA thymoma with low morbidity and mortality and can result in excellent long-term survival.

Pleuropneumonectomy for the Treatment of Masaoka Stage IVA Thymoma

The treatment of locally advanced Masaoka stage IVA thymoma is not standardized and is problematic. A single-institution retrospective study was made of 5 patients with World Health Organization B3 thymomas who underwent pleuropneumonectomy for locally advanced thymoma. Two patients had recurrent thymoma and 3 presented de novo with stage IVA disease. Patients had a variety of induction and adjuvant treatments. There was no operative mortality, and only 1 patient had a major complication. Several patients had relatively prolonged disease-free survival. The median survival was 86 months, and the Kaplan-Meier survival was 75% (95% confidence interval: 53% to 97%) at 5 years and 50% (95% confidence interval: 25% to 75%) at 10 years. Pleuropneumonectomy can be performed safely in patients with advanced thymomas and may improve survival. Highly selected patients might be cured with this approach if a complete resection is performed. While the optimal multimodality strategy for these patients is unknown, induction chemotherapy followed by resection then chemoradiotherapy seems promising.

A phase II trial of pemetrexed in patients with recurrent thymoma or thymic carcinoma

7079 Background: Few prospective trials have been conducted in patients with advance thymic malignancies. Pemetrexed a multi-targeted antifolate with a broad range of clinical activity, but previously untested in thymic malignancies. As a result, a phase II trial was initiated to evaluate the clinical activity of pemetrexed in previously treated patients with thymoma (THY) and thymic carcinoma (TC). Methods: From February, 2005 to November, 2005, twenty-seven previously treated patients with unresectable stage IVA (n = 16) or stage IVB (n =11) disease were treated with pemetrexed at a dosage of 500 mg/m2 every three weeks for a maximum of 6 cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Profile of patients include: median age = 52 years (range 26–84); M: F = 13:14; PS 0/1= 17/10; median number of prior therapies = 2 (range 1–6); 21 had prior radiation therapy; and histology (THY = 16, TC = 11). Results: The median number of cycles administered was 5 (range 1–6). Eleven patients had grade 3 toxicities including: dyspnea, infections, fatigue, abnormal chemistries and neutropenia. No Grade 4 toxicities were noted. Accrual was completed in November, 2005 with four patients still on therapy. In 23 fully evaluable patients, two complete and two partial responses (RECIST) were noted. All four responding patients had had stage IVA thymoma. Five patients progressed on therapy and two patients discontinued therapy for intolerance to chemotherapy (constipation, dyspnea) and 1 patient for progressive Morvan’s Syndrome. The median time to progression for all patients was 45 weeks (THY = 45.4 weeks vs. TC = 5.1 weeks). With three deaths thus far, the median overall survival has not been reached. Conclusions: Pemetrexed is an active agent in a heavily pretreated population of patients with recurrent thymoma. Patients with recurrent thymic carcinoma appear to have a much more aggressive clinical course than thymoma. [Table: see text]

World Health Organization histologic classification: An independent prognostic factor in resected thymomas

The histologic classification of thymoma remained controversial since 1999, when the World Health Organization (WHO) Consensus Committee published a histologic typing system for tumours of thymus. Clinical features, postoperative relapsing rates, and survival of patients with thymoma were evaluated with reference to the WHO histologic classification, based on a series of 178 patients, submitted to surgery between 1988 and 2000. There were 21 type A, 49 type AB, 45 type B1, 50 type B2 and 13 type B3 tumours. The invasiveness of tumours was 23.8%, 51%, 73.3%, 82% and 100% for types A, AB, B1, B2 and B3 tumours, respectively. The frequency of invasion of the great vessels increased according to the tumour type in the order A (0%), AB (4%), B1 (6.6%), B2 (22%), and B3 (23%). The 10-year disease-free survival was 95%, 90%, 85%, 71% and 40% for types A, AB, B1, B2 and B3, respectively. According to the Masaoka staging system, the disease-free survival rates were 94%, 88% and 66% for stages I, II and III, respectively, at 10 years. No stage IVA thymomas reached 10 years follow-up. Overall survival at 10 years were 88% and 25% when complete and incomplete resection were considered. By multivariate analysis, Masaoka staging system, WHO histologic classification and complete resection were significant independent prognostic factors, whereas age- and sex-associated myasthenia gravis were not. The present study demonstrated the World Health Organization histologic classification a good prognostic factor, such as completeness of surgical resection and Masaoka staging system.

Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread

Background. Thymoma and thymic carcinoma with pleural spread have a high rate of locoregional recurrence and poor prognosis. Maximal debulking coupled with aggressive local treatment could offer a chance for cure. This study evaluates the early and midterm results of operation and hyperthermic pleural perfusion with cisplatinum for thymic malignancies. Methods. Fifteen patients (11 men), 20 to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst) underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All had pleural spread proven before or intraoperatively. Six of the thymoma cases were recurrent. Current operation included resection without pleurectomy (9 patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1 patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural temperature reached 40.3°C to 43°C. The total dose of cisplatinum was 150 mg or more in 14 patients. Results. Complete resection (R0) was achieved in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative mortality, no hemodynamic or respiratory disturbances during perfusion, and no hematologic, neurologic, or renal complications. Complications consisted of significant bleeding (2 patients), fever (2), and air leak (1 patient). Two patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with no evidence of disease at 54 months. Two patients with thymoma died after 7 and 36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive without local recurrence more than 60 months after operation and hyperthermic pleural perfusion. Conclusions. Operation and thermochemotherpy is feasible and safe in patients with thymic tumors. This method seems to offer excellent local control for patients with stage IV-a thymic malignancies. Midterm results suggest that operation plus hyperthermic pleural perfusion may lengthen survival in stage IV-a thymoma.