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Mediastinal Seminoma: Treatment
Updated: Oct 31, 2008
Treatment
Medical Therapy
The current therapy for seminomas depends on presenting features at the time of diagnosis and staging. Treatment usually involves a combination of surgery, radiotherapy, and systemic chemotherapy.2
Radiation
In the past, primary treatment with radiation often yielded survival rates of 50-60%. The standard radiotherapy protocols call for 40-50 Gy delivered by external beam radiation to the mediastinum and supraclavicular regions. The neck region is included in the field of radiation because of the tendency of seminomas to initially spread to the cervical lymph nodes. Some oncologists also incorporate the axilla in the radiation field when the cervical nodes are enlarged. The radiation therapy is administered at a daily dose of 45-60 Gy over a period of 6 weeks. A failure of radiation therapy is believed to be due to the development of distant metastases rather than local recurrences. Combination treatment with radiation and surgery is not logical because both are aimed at achieving local control only. Because these tumors are bulky at presentation, the radiation may not encompass the entire tumor.
Complications
The complications of radiation are well known and predictable. Rapidly dividing cells are affected most significantly; these include cells of the dermis and the GI tract. Patients may present with nausea, vomiting, general malaise, poor wound healing, eczema, and ulcerations. The most frequent adverse effect is esophagitis, which occurs in most patients following radiation to the chest. This complication usually occurs 2 weeks after the start of radiation and subsides 1-2 weeks after completion.
All patients may have radiographic evidence of radiation-induced pneumonitis, but less than 5% of patients may be clinically symptomatic. Life-threatening pneumonitis occurs in less than 1% of patients.
Late complications may include bone deformities, cataracts, sterility, lung fibrosis, chromosomal damage, and, perhaps, an increased risk of cancer. Although rare, the risks of radiation-induced myocarditis and pericarditis are directly related to the amount of cardiac tissue near the field of treatment.
Chemotherapy
In the last decade, significant improvements in survival have been achieved with multimodal chemotherapy regimens involving bleomycin, cisplatin, and etoposide. Cisplatin-based chemotherapy has induced complete responses in a small number of patients with seminomas.3 Chemotherapy is administered in 4-6 cycles, and intermittent pulmonary function tests are performed in all patients because of the toxicity of bleomycin to the lungs. At present, cisplatin forms the basis of most combination chemotherapeutic regimens that are active against seminomas.
Other agents used for chemotherapy are vinblastine, cyclophosphamide, and dactinomycin. The response rates are difficult to compare with most other study results because many of the studies on these 3 agents were not randomized. In addition, the patient populations have been heterogeneous, and the chemotherapeutic regimens have been different.
Chemotherapy clearly exerts a biologic effect in patients with advanced disease. Whenever possible during clinical trials, patients should be treated with either newer agents or a combination of agents. At this time, chemotherapy is sufficiently justified for use in patients with advanced disease, provided its limitations and toxicity are understood.
Cisplatin
Cisplatin is an important agent in the treatment of seminomas and is generally administered in combination with other agents in divided doses over 3-5 days. Cisplatin is recognized as an excellent agent because of its superior activity and its only modest myelosuppression. It generally acts in synergy with other chemotherapeutic agents. For this reason, it forms the basis of most combination regimens. In addition, cisplatin can be administered with thoracic radiation without undue toxicity.
Various platinum analogs, such as carboplatin and iproplatin, are now available. These agents induce greater response but may be more myelosuppressive than cisplatin.
Vinca alkaloids
Both vincristine and vinblastine have been used to treat seminomas. These agents act as mitosis inhibitors by binding to microtubules and causing arrest in the metaphase. Although these alkaloids share a similar structure, they have a wide spectrum of clinical activity and toxicity. They are almost always used in combination with other chemotherapeutic agents.
Etoposide
Etoposide, an epipodophyllotoxin, has only mild activity as a single agent but because of its synergy with other agents is always used in combination regimens. This agent shows phase-specific activity for cells in the dividing phase. The correct dosing is still being debated, but most authorities recommend long-term administration for weeks.
Ifosfamide
Ifosfamide is a non–cell-specific alkylating agent that is replacing cyclophosphamide in many studies. It can be used in higher doses than cyclophosphamide, although hemorrhagic cystitis is still a major adverse effect. It can also cause renal and hepatic dysfunction. Ifosfamide is generally administered intravenously.
Bleomycin
Bleomycin belongs to the antibiotic classification of chemotherapeutic drugs. It is derived from Streptomyces and causes breaks in the DNA molecule. Bleomycin is used in combination therapy and is usually administered parenterally. Although it has a number of adverse effects, the most well known is pulmonary fibrosis.
Complications of chemotherapy
Most chemotherapeutic agents are associated with adverse effects, and some have specific organ toxicity. Most produce nausea, vomiting, and flulike syndromes.
Cisplatin can cause renal dysfunction, and renal parameters must be constantly monitored. Cisplatin is also associated with ototoxicity, neurotoxicity, anaphylaxis, a Raynaud-type phenomenon, and local vesication.
Ifosfamide can cause myelosuppression, renal and hepatic dysfunction, hemorrhagic cystitis, alopecia, and confusion.
Etoposide can also cause myelosuppression and has been associated with bronchospasm, hypotension, and ileus.
Bleomycin can cause fever and pulmonary fibrosis.
Combination Therapy with Radiation and Chemotherapy
Recent clinical trials have demonstrated excellent results when multimodality chemotherapy is combined with radiation for large, localized mediastinal seminomas or extensive residual disease. In these cases, the patient is administered chemotherapy consisting of cisplatin, bleomycin, and etoposide. After the patient has recovered (4-6 wk), radiation is administered at a dose of 40-60 Gy for 4-6 weeks. A CT scan is then obtained to assess the response of the tumor to treatment. If only a small mass remains, it is excised.
Follow-up care
After radiation and/or chemotherapy, CT scans are delayed for 6 weeks to allow maximum reduction of the mass. Regular blood workups are obtained to assess the effects of chemotherapy on the bone marrow, kidneys, and liver. Residual disease as seen on radiographs following treatment is a medical dilemma. If CT scans reveal a residual mediastinal mass, surgery is offered; however, some patients still have viable seminomas or teratomas after excision.
If a small mediastinal mass remains after nonsurgical therapy, it must be excised; however, this treatment is not a universal protocol. Some oncologists instead prefer to monitor these masses with serial CT scans, a course that carries a risk of recurrent disease.
Surgical Therapy
Strict airway maintenance is required whenever patients with large anterior mediastinal tumors are sedated because these tumors can compress the trachea and make intubation difficult. A rigid bronchoscopy cart must always be available during this procedure. All anesthesia must be reversed before extubating the patient. Some patients may require longer intubation and may be extubated slowly, after the administration of steroids and bronchodilators. An arterial line, a Foley catheter, and a dose of preoperative antibiotic are required.
Preoperative Details
Generally, most patients with seminomas are young, healthy males who have minimal comorbid disorders. The preoperative workup for patients with mediastinal tumors involves CT scanning, pulmonary function tests, and nutritional status assessment. Because the mass in the mediastinum has the tendency to compress the airways, knowing the extent of airway compromise before the operation is extremely important. Bronchoscopy must be performed if bronchomalacia is possible. If the airway is compromised, anesthesia must be induced with the patient in a semi-Fowler position and a long endotracheal tube that can bypass the obstructed site must be used.
If the mass has produced symptoms of superior vena cava compression, MRI can be ordered. MRI does not require contrast and can help identify the site and extent of obstruction. In all patients with superior vena cava obstruction, lower extremity intravenous access must be available. Some surgeons also recommend that standby cardiopulmonary bypass be available when patients have tracheal compromise or superior vena cava syndrome.
Intraoperative Details
Depending on the mass location, excision via a thoracotomy can be performed; however, the typical and preferred incision for anterior mediastinal tumors is the median sternotomy. The sternum is divided from the suprasternal notch to the xiphoid, and all bleeding from the sternum is stopped. Once hemostasis has been achieved, the tumor is palpated in the anterior mediastinum prior to any resection. Structures such as the superior vena cava, pericardium, innominate vein, pleura, and phrenic nerves are identified.
Because seminomas are sensitive to radiation, unnecessary resection of vital structures must be avoided. When the entire mass is not resectable, adjuvant radiation is required. Once the mass (or appropriate portions thereof) is resected, complete hemostasis is obtained and mediastinal drainage tubes are inserted. Surgical clips are placed in the area where the mass was excised to allow for the radiation field to be mapped later. If the pleural space was inadvertently entered, chest drainage tubes are also placed. The sternum is closed with wires, and the patient is awakened from anesthesia.
Postoperative Details
The typical patient with an anterior mediastinal mass is observed in the ICU for a few hours and, if hemodynamically stable with minimal chest drainage, is transferred to a monitored floor. Postoperative chest radiographs are obtained in every patient to view the placement of the drainage tubes and endotracheal tube (if present) and to assess for pneumothorax.
Intravenous fluids are kept to a minimum, and adequate pain control is maintained. Most drainage tubes are removed on the second postoperative day, and the patient is encouraged to ambulate. Daily chest radiographs are not required after the mediastinal drains have been removed, but they are obtained after the chest tubes are removed in order to evaluate for the presence of pleural fluid or pneumothorax. The average hospital stay after a routine median sternotomy exploration is approximately 2-4 days.
Complications
Because surgery is usually performed for small tumors, complication rates are much lower. The usual complications following a median sternotomy include incision pain, atelectasis, injury to the phrenic nerve and/or vascular structures, and postoperative bleeding.
A common complication is airway compression from the mediastinal mass. During anesthesia, intubation may prove to be very difficult. Additionally, some patients may not be able to be weaned off the respirator because the prolonged compression of the airways may have caused tracheobronchomalacia. These patients may remain intubated for prolonged periods and may even require stenting of the airways. When aggressive surgical resection is undertaken for a seminoma, injury to the phrenic nerve(s) can result in diaphragm paralysis; however, in young, healthy patients, the complication rates are negligible, and most patients have an uneventful recovery.
More on Mediastinal Seminoma |
| Overview: Mediastinal Seminoma |
| Workup: Mediastinal Seminoma |
 Treatment: Mediastinal Seminoma |
| Follow-up: Mediastinal Seminoma |
| References |
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References
Weidner N. Germ-cell tumors of the mediastinum. Semin Diagn Pathol. Feb 1999;16(1):42-50. [Medline].
Flechon A, Biron P, Philip I, et al. [High dose chemotherapy with autologous stem cell support in the treatment of germ cell tumors: experience of the centre Leon-Berard between 1982 and 1996]. Bull Cancer. Apr 1999;86(4):391-9. [Medline].
Gholam D, Fizazi K, Terrier-Lacombe MJ, et al. Advanced seminoma--treatment results and prognostic factors for survival after first-line, cisplatin-based chemotherapy and for patients with recurrent disease: a single-institution experience in 145 patients. Cancer. Aug 15 2003;98(4):745-52. [Medline].
Thomas GM. Over 20 Years of Progress in Radiation Oncology: Seminoma. Semin Radiat Oncol. Apr 1997;7(2):135-45. [Medline].
Algaba Arrea F. [Morphologic keys for the interpretation of the biology of testicular germ tumors]. Arch Esp Urol. Jul-Aug 2000;53(6):407-21. [Medline].
Amato RJ, Millikan R, Daliani D, et al. Cyclophosphamide and carboplatin and selective consolidation in advanced seminoma. Clin Cancer Res. Jan 2000;6(1):72-7. [Medline].
Fang FM, Ko SF, Hwang CH, Wang CJ. Healing of superior vena cava defect in mediastinal seminoma with invasion. Ann Thorac Surg. Aug 2000;70(2):667-9. [Medline].
Ganjoo KN, Chan RJ, Sharma M, Einhorn LH. Positron emission tomography scans in the evaluation of postchemotherapy residual masses in patients with seminoma. J Clin Oncol. Nov 1999;17(11):3457-60. [Medline].
Hainsworth JD. Diagnosis, staging, and clinical characteristics of the patient with mediastinal germ cell carcinoma. Chest Surg Clin N Am. Nov 2002;12(4):665-72. [Medline].
Horvath L, Bayfield M, Clifford A, et al. Unusual presentations of germ cell tumors. Case 1. Recurrent laryngeal nerve palsy in mediastinal seminoma. J Clin Oncol. Feb 1 2001;19(3):909-11. [Medline].
Komatsubara S, Itoi T, Watanabe M, et al. [Treatment of metastatic seminoma by chemotherapy, an experience]. Nippon Hinyokika Gakkai Zasshi. Oct-Nov 2000;91(10-11):666-72. [Medline].
Lemarie E. [Malignant germinal tumours of the mediastinum: diagnosis and treatment]. Rev Pneumol Clin. Nov 2004;60(5 Pt 2):3S79-85. [Medline].
Moran CA. Germ cell tumors of the mediastinum. Pathol Res Pract. 1999;195(8):583-7. [Medline].
Okada M, Sugimoto T, Yamamoto H. [Surgical strategy for invasive pulmonary and mediastinal tumors requiring superior vena cava reconstruction]. Kyobu Geka. Jan 1999;52(1):14-8. [Medline].
Oyoshi T, Nakayama M, Hirano H, et al. Intracranial dural metastasis of mediastinal seminoma--case report. Neurol Med Chir (Tokyo). Aug 2000;40(8):423-6. [Medline].
Pectasides D, Aravantinos G, Visvikis A, et al. Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience. Oncology. Jul 1999;57(1):1-9. [Medline].
Rick O, Beyer J, Kingreen D, et al. High-dose chemotherapy in germ cell tumours: a large single centre experience. Eur J Cancer. Nov 1998;34(12):1883-8. [Medline].
Silverman JF, Olson PR, Dabbs DJ, Landreneau R. Fine-needle aspiration cytology of a mediastinal seminoma associated with multilocular thymic cyst. Diagn Cytopathol. Apr 1999;20(4):224-8. [Medline].
Takeda S, Miyoshi S, Omori K, et al. Surgical rescue for life-threatening hypoxemia caused by a mediastinal tumor. Ann Thorac Surg. Dec 1999;68(6):2324-6. [Medline].
Further Reading
Keywords
mediastinal seminoma, germ cell, germ cell tumor, germ-cell tumor, germ cell mass, germ-cell mass, malignant germ cells of the mediastinum, seminoma, radiation, mediastinum, gonads, mediastinal mass, cisplatin-based chemotherapy, respiratory compromise, intrathoracic mass, anterior mediastinal mass, extragonadal malignancy, totipotential cells, spermatogenesis, median sternotomy, median sternotomy exploration, teratoma, radiation, chemotherapy, cisplatin, vinca alkaloids, etoposide, ifosfamide, bleomycin, combination chemotherapy, induction chemotherapy, mediastinum cancer, mediastinal cancer, malignant seminoma, benign seminoma
