THYMIC CARCINOMA- TREATMENT

Thymic carcinomas have a greater propensity to capsular invasion and metastases than thymomas. Patients more often present with advanced disease and have a 5-year survival rate of 30% to 50%.[1] Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. As with thymoma, in most published series, carefully selected patients with clearly resectable, well-defined disease, have received complete surgical extirpation. For clinically borderline or frankly unresectable lesions, induction chemotherapy, thoracic radiation therapy, or both, have been used.

In most published studies, surgery has been followed by adjuvant radiation therapy. A prescriptive dose range has yet to be identified; most studies use 40 Gy to 70 Gy with standard fractionation scheme (1.8 Gy–2.0 Gy/fraction).

In the largest series reported to date, data was obtained from 1,320 Japanese patients.[2] The Masaoka clinical stage was found to correlate well with prognosis of thymoma and thymic carcinoma. Patients with thymic carinoma were treated with radiation therapy or chemotherapy. For patients with thymic carcinoma, the 5-year survival rates were 67% for patients treated with total resection, 30% for patients treated with subtotal resection, and 24% for patients whose disease was inoperable. Adjuvant therapy including radiation or chemotherapy did not appear to improve the prognosis in patients with thymic carcinoma.[2]

A multi-institutional retrospective outcome analysis of 186 patients with thymic carcinoma has been reported.[2] This study failed to detect a long-term survival benefit in patients treated with subtotal resection nor any statistically significant survival augmentation from the addition of adjuvant radiation to surgical resection. The authors stipulated that no definitive conclusions could be made regarding the role of adjuvant radiation therapy in thymic carcinoma as a result of sample size limitations.

The 5-year survival rates for patients with totally resected thymic carcinoma were 81.5% for patients treated with chemotherapy; 46.6% for patients treated with radiation chemotherapy; 73.6% for patients treated with radiation therapy alone; and, 72.2% for patients who received no adjuvant treatment.[2]

The results from this study call into question conventional thinking regarding the efficacy of an aggressive multimodality approach including debulking, radiation therapy, and cisplatin-based chemotherapy.[3-5] While other studies support the addition of adjuvant radiation and chemotherapy, optimum treatment regimens are undetermined.

Chemotherapy is also utilized in the management of patients with inoperable thymic carcinoma. Most regimens used are similar to those used to treat thymoma and include cisplatin.[6-10]

Objective responses and improved outcomes compared to historical data have been reported from small uncontrolled studies. Combinations of doxorubicin, cyclophosphamide, and vincristine and cisplatin have also shown favorable responses in studies.[6-8] Etoposide, ifosfamide, and cisplatin (VIP) was utilized in a prospective North American Intergroup trial.[9] There was a 25% (2 of 8 patients) partial response rate. The 1-year and 2-year survival rates were 75% and 50%, respectively.

Standard treatment options for patients with operable disease include the following:

1.     En bloc surgical resection.

2.     Postoperative radiation therapy may be considered whether or not the surgical resection has been complete, and especially for stage III and stage IVA patients.

Standard treatment options for patients with inoperable disease (stage III and stage IV with vena caval obstruction, pleural involvement, pericardial implants, etc.) include the following:

1.     Radiation therapy.

2.     Chemotherapy with or without surgery and/or radiation therapy.

3.     Chemoradiation therapy.

4.     Chemotherapy.

Treatment options under clinical evaluation:

Areas of active clinical evaluation for patients with thymic carcinoma include the following:

·         New drug regimens.

·         Variation of drug doses in current regimens.

·         New radiation therapy schedules.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withthymic carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1.     Eng TY, Fuller CD, Jagirdar J, et al.: Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 59 (3): 654-64, 2004. [PUBMED Abstract]

2.     Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]

3.     Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002. [PUBMED Abstract]

4.     Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003. [PUBMED Abstract]

5.     Lucchi M, Mussi A, Ambrogi M, et al.: Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol 27 (7): 636-40, 2001. [PUBMED Abstract]

6.     Koizumi T, Takabayashi Y, Yamagishi S, et al.: Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 25 (3): 266-8, 2002. [PUBMED Abstract]

7.     Weide LG, Ulbright TM, Loehrer PJ Sr, et al.: Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer 71 (4): 1219-23, 1993. [PUBMED Abstract]

8.     Carlson RW, Dorfman RF, Sikic BI: Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Cancer 66 (10): 2092-4, 1990. [PUBMED Abstract]

9.     Loehrer PJ Sr, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001. [PUBMED Abstract]

10.                       Igawa S, Murakami H, Takahashi T, et al.: Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic carcinoma. Lung Cancer 67 (2): 194-7, 2010. [PUBMED Abstract]