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Lawrence Einhorn



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    MTE 23 - Mediastinal Tumors including Thymic Tumors, Lymphoma, Germ Cell Tumors: Biopsy, Diagnosis and Treatment (Sign Up Required) (ID 572)

    • Event: WCLC 2017
    • Type: Meet the Expert
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      MTE 23.02 - Mediastinal Germ Cell Tumor (ID 7809)

      07:00 - 08:00  |  Presenting Author(s): Lawrence Einhorn

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      Abstract:
      Extragonadal germ cell tumors (EGCTs) are among the most perplexing and embryologically intriguing entities in clinical oncology. They represent only 2-5% of adult germ cell malignancies. Their histology is identical to germ cell tumors (GCTs) derived from primary gonadal sites. However, their biology, especially primary mediastinal non-seminomatous GCT (PMNSGCT), is substantially different. PMNSGCT represents a clinically and biologically distinct subset of EGCT. It carries a poor prognosis with 40-50% overall survival after platinum-based chemotherapy and surgery (1-3). The cure rate is even worse if there is metastatic disease of the lung, liver, or supraclavicular lymph nodes with only 25% overall survival. In contrast, mediastinal seminomas have a good prognosis with 88-90% overall survival (4,5). Survival outcome for PMNSGCT is dependent on successful chemotherapy and expert thoracic surgery to remove residual disease when feasible. Patients presenting with anterior mediastinal tumor do not have a testis primary and there is no need to evaluate with testis ultrasound. The significant elevation in tumor markers including human chorionic gonadotrophin (hCG) > 1,000 U/1 and/or any elevation in alphafetoprotein (AFP) confirms the diagnosis of NSGCT and no biopsy is needed. The patient should be treated with 4 courses of platinum-based triple chemotherapy. We recommend using etoposide (VP-16), ifosfamide and cisplatin (VIP x 4) as the standard chemotherapy for PMNSGCT followed by surgical resection (2). Patients with normal tumor markers or mild elevation in hCG require a biopsy to establish the diagnosis of pure seminoma vs. NSGCT vs. other etiology such as thymic malignancy or lymphoma. Between 1980 and 2013, 221 patients with PMNSGCT who underwent postchemotherapy surgery at Indiana University were retrospectively reviewed. Our initial experience was entirely with BEP x 4. Because of our clinical observation of unacceptable pulmonary toxicity, we subsequently substituted ifosfamide for bleomycin. One hundred sixty-six patients received BEP and 55 received VIP. There were 11perioperative deaths when bleomycin was part of the preoperative chemotherapy (6.6%). By contrast, we saw no perioperative deaths on the VIP arm. Furthermore, 30 patients (18.1%) had prolonged ventilator use for greater than 48 hours. Only 2 patients (3.6%) had this complication on the VIP arm (6). A phase III intergroup study of 181 patients with poor-risk germ cell tumors, including patients with PMNSGCT, demonstrated equivalent survival in patients with VIP compared to BEP. Given the high rate of postoperative pulmonary failure and mortality after BEP, we feel these results strongly support our present policy of preferring to use VIP chemotherapy in patients with PMNSGCT before major thoracic surgical procedure. Surgical resection of residual disease after chemotherapy is an integral part of the management of patients with PMNSGCT. Surgical resection after chemotherapy serves to assess response, remove chemotherapy-resistant disease and direct additional chemotherapy. Viable teratoma or germ cell cancer is present in 30-47% of patients who undergo resection post-chemotherapy (7,8). Chest CT scan every 4 months for 2 years, then every 6 months for years 3-5 is recommended if teratoma or malignant transformation of teratoma is present in the surgical specimen. However, if there is persistent germ cell cancer in the surgical specimen, then patients should receive 2 post-operative courses of etoposide and cisplatin (EP). Surgical treatment for relapsed PMNSGCT in the presence of rising tumor markers after chemotherapy is controversial. Our preferred treatment option is surgery, if feasible, especially if carried out by experienced thoracic surgical oncologists. We recently reported our results with surgery alone in 35 patients with relapsed PMNSGCTs with rising serum AFP (32 patients) or hCG (3 patients). Seven (20%) of 35 patients remained continuously disease-free, with median followup of 64 months (range, 25-220 months) (10). If surgery is not feasible, then high dose chemotherapy in an experienced center is a reasonable approach. Mature teratoma is the most common GCT in the mediastinum. Patients present with large circumscribed anterior mediastinal mass with normal serum hCG and AFP. The treatment of mature teratoma is surgical resection and there is no role for chemotherapy unless elevated tumor markers are present. Mediastinal pure seminomas comprise 30-40% of malignant mediastinal GCT. Mediastinal seminoma carries an excellent prognosis and should be treated with good-risk chemotherapy regimen (3 cycles of bleomycin, etoposide, and platinum or 4 cycles of EP) with no surgical resection needed. References: International Germ Cell Consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997; 15:594-603. Kesler KA, Rieger KM, Hammoud ZT, et al.: A 25-year single institution experience with surgery for primary mediastinal non-seminomatous germ cell tumors. Ann Thorac Surg 2008; 85:371-378. Rivera C, Arame A, Jougon J, et al.: Prognostic factors in patients with primary mediastinal germ cell tumors, a surgical multicenter retrospective study. Interact Cardiovasc Thorac Surg 2010; 11:585-589. Bokemeyer C, Nichols CR, Droz JP, et al.: Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 2002; 20:1864-1873. Hartmann JT, Nichols CR, Droz JP, et al.: Prognostic variables for response and outcome in patients with extragonadal germ cell tumors. Ann Oncol 2002; 13:1017-1028. Ranganath P, Kesler KA and Einhorn LH: Perioperative morbidity and mortality associated with bleomycin in primary mediastinal non-seminomatous germ cell tumor. J Clin Oncol 2016; 34:4445-4448. 2016. Vuky J, Bains M, Bacik J, et al.: Role of postchemotherapy adjunctive surgery in the management of patients with non-seminoma arising from the mediastinum. J Clin Oncol 2001; 19:682-688. Kesler KA, Rieger KM, Ganjoo KN, et al.: Primary mediastinal non-seminomatous germ cell tumors; the influence of postchemotherapy pathology on long-term survival after surgery. J Thorac Cardiovasc Surg 1999; 118:692-700. Hinton S, Catalano PJ, Einhorn LH, et al.: Cisplatin, etoposide , and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors. Final analysis of an intergroup trial. Cancer 2003; 97:1869-1875. Radaideh SM, Cook VC, Kesler KA, Einhorn LH: Outcome following resection for patients with primary mediastinal non-seminomatous germ cell tumors and rising serum tumor markers postchemotherapy. Ann Oncol 2010; 21:804-807.

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