Therapy of Thymoma

SURGERY

Since there are no reliable histologic criteria for the malignant nature of thymomas, all such tumors should be considered potentially malignant. Total thymectomy (rather than thymomectomy) is the procedure of choice, even for stage I encapsulated tumors.. It is also the procedure indicated for patients with myasthenia gravis, with or without thymoma. The usual approach is by medial sternotomy, although additional thoracic or cervical incisions may be necessary, and some surgeons advocate maximal thymectomy with exploration of all the possible areas where ectopic thymic tissue might be found.. There is a need for the surgeon to carefully explore the mediastinum for evidence of local invasion, the most reliable indication of malignancy and the most important prognostic factor. The tumor capsule should not be breached. Systematic microscopic examination is necessary to search for capsular invasion and to distinguish it from simple adhesions. Following total thymectomy, the recurrence rate is usually low (about 2%) for stage I encapsulated thymomas.. Recently, video thoracoscopic approaches have been performed for well-encapsulated small thymomas, but the long-term results are unknown.

In patients with thymoma and MG, remission of MG occurs in about 10 to 30% following thymectomy, often after a delay of up to 2 years or more, as compared to a remission rate of about 40 to 80% in patients with MG without a thymoma. An additional fraction of patients show improvement of MG. Early thymectomy (within 1 year) after onset of MG is associated with a higher percentage of more benign and less invasive thymomas. Recurrence, and even first occurrence, of MG after apparent total thymectomy has been observed and could be related to tumor regrowth or persistent ectopic thymic tissue. In the past, MG was a poor prognostic sign in patients with thymoma. Most recent surgical series, however, do not show a significant difference in survival for patients with thymoma, with or without MG.. Such a change is attributed to better surgical and anesthesia techniques, which have largely prevented postoperative deaths from MG.

Local invasion is seen in about 30 to 40% of thymomas at surgery, but the slow-growing nature of the tumor and the rarity of metastases justify attempts at radical surgery. Identification of the phrenic, recurrent and vagus nerves is of major importance.. Extended resections to include one lung, one phrenic nerve, pericardium, or even resection and repair of great vessels such as the innominate vein or superior vena cava have been performed. They should be undertaken only if they lead to complete tumor resection. Radiotherapy is indicated in case of invasive thymoma (see below). With modern techniques of peri- and postsurgical care, surgical mortality is low (0 to 5%), even in patients with myasthenia gravis..

In four large series with a total of 744 patients, the 5- and 10-year survival rates were 75 to 85% and 63 to 80%, respectively, for patients with noninvasive thymomas. Survival figures for patients with invasive thymomas were 50 to 67% at 5 years and 30 to 53% at 10 years. Whereas invasiveness is the major prognostic factor in patients with thymoma, most series also report a better prognosis for spindle-cell thymomas and those with a higher lymphocyte–epithelial cell ratio. Local recurrences and/or metastases (often intrathoracic) may also be amenable to surgical resection.

RADIOTHERAPY

Thymomas are radiosensitive, and the efficacy of radiotherapy (RT) has been emphasized in many reports. Following surgical biopsy, or partial excision, survival of more than 10 years after RT has been seen.. The argument that it is the lymphocytic component rather than the epithelial one which is sensitive to RT is not shared by most authors.

The role of RT is best discussed according to stage. For stage I disease following total surgical resection, postoperative RT is not indicated in view of the very low relapse rates. For stage II and III disease, the use of postoperative RT is recommended even after total surgical resection. In a review of the literature added to their own experience, Curran and colleagues reported a 28% intrathoracic relapse rate after complete surgical resection without RT, as opposed to 5% when postoperative RT was given. The latter figure may be an underestimate, however, since others have reported no such differences in favor of RT after complete surgical resection.

The irradiated volume should include the mediastinum with adjacent areas, and probably the supraclavicular areas which are possible sites of relapse. The total dose is usually about 45 Gy, with appropriate protection of the spinal cord, although doses of 50 Gy and higher have been used.. Radiation pneumonitis, as well as mediastinitis, pericarditis, coronary artery fibrosis, and hypothyroidism are potential complications.

RT is also given to patients with residual disease following incomplete surgical resection or biopsy only for stage III disease. In 20 such cases, Curran and colleagues observed four mediastinal recurrences and five others outside the mediastinum, whereas no local relapse was seen when radiotherapy was given after total surgical resection for stage II or III.. Tumor debulking by surgery prior to radiotherapy in patients with stage III or IV disease does not appear beneficial. The 5-year survival for such patients was 45% overall, including 61% for stage III and 23% for stage IV after radiotherapy. Collaboration between the surgeon and the radiotherapist is essential to delineate areas of tumor involvement by radiopaque clips and to plan the treatment.

CHEMOTHERAPY

Thymomas are also relatively chemosensitive. As experience with chemotherapy is increasing, good response rates and sometimes dramatic tumor regressions have been observed.

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