Primary Mediastinal Nonseminomatous Germ Cell Research Articles

Is High-Dose Chemotherapy After Primary Chemotherapy a Therapeutic Option for Patients With Primary Mediastinal Nonseminomatous Germ Cell Tumor?

Patients with primary mediastinal nonseminomatous germ cell tumors have a poor prognosis, with a 5-year overall survival of nearly 50%. We investigated the feasibility and activity of early high-dose chemotherapy (HDCT) in these patients. After conventional induction chemotherapy, patients underwent a single shot of HDCT consisting of carboplatin, etoposide, and cyclophosphamide, followed by peripheral blood progenitor cell support. Twenty-one patients were considered for treatment with HDCT. Median age was 29 years (range, 19-55 years). Eight (38%) patients had lung metastases. After primary chemotherapy, 7 patients achieved complete remission, 4 achieved partial remission with negative marker, 1 achieved partial remission with positive marker, 2 had stable disease, and 7 progressive disease. Twelve patients were not treated with HDCT due to progressive disease and poor physical conditions. No HDCT-related deaths or irreversible organ toxicities were observed. Residual surgery after HDCT was performed in 4 patients and resulted in 3 pathologic complete remissions. With a median follow-up of 52 months (range, 15-71 months) in 9 patients treated with HDCT, 8 have been continuously free of disease. Of 12 patients who did not receive HDCT, 0 was alive at 2 years from diagnosis. A single course of HDCT after induction chemotherapy appeared to be inapplicable in most of our patients, mainly due to early progressive disease. These data should be considered in the analysis of retrospective series and in the design of new prospective trials with HDCT in these patients. Earlier HDCT administration followed by residual surgery should be considered for further investigation.

Salvage chemotherapy with high dose carboplatin + etoposide (HDCE) and peripheral blood stem cell transplant (PBSCT) in patients with germ cell tumors (GCT)

4549 Background: We began studies with HDCE for patients (pts.) with recurrent GCTs 20 years ago. During the past decade, better supportive care and use of PBSCT allowed outpatient therapy and more rapid hematopoietic recovery between the 2 courses of HDCE. Methods: Retrospective review of 184 consecutive pts. treated with HDCE at Indiana University from 2–96 to 12–04. Late relapse (> 2 years from prior therapy) and primary mediastinal non-seminomatous germ cell tumor pts. were not offered HDCE. Cytoreduction with 0–2 courses of vinblastine + ifosfamide + cisplatin preceded HDCE. C dosage was 700 mg/M2 × 3 and E 750 mg/M2 × 3. A second course was given after hematologic recovery. Results: Toxicity was as previously described (JCO 18:3346, 2000). There were 3 drug- related mortalities. An additional 3 patients developed AML (2 fatal), and 1 glioma following CNS XRT for metastases. 11 pts. did not receive second course (8 due to progression or HDCE mortality). Median time to second course HDCE was 28 days (range 20 to 42). 116 of 184 pts. are alive and continuously (cont) NED (63%) with median followup 42 months (range 11 to 118). 113 (97%) of these are 12+ months NED. 5 additional pts. are currently NED with further therapy. Results are tabulated below. Conclusions: HDCE has a high cure rate with acceptable toxicity as salvage therapy for GCT pts. [Table: see text] [Table: see text]

Short- and Long-Term Outcomes After Large Pulmonary Resection for Germ Cell Tumors After Bleomycin-Combination Chemotherapy

Abstract Background Treatment of nonseminomatous germ cell tumors frequently requires bleomycin-combination chemotherapy followed by resection of residual disease. Bleomycin administration however raises concerns with respect to postoperative respiratory complications, particularly for patients undergoing large pulmonary resections. We undertook an institutional review to determine the outcome of large pulmonary resections after bleomycin-combination chemotherapy. Methods Between 1981 and 2001, 530 patients presented to our institution for resection of residual intrathoracic disease for either metastatic testicular or primary mediastinal nonseminomatous germ cell tumors. We subsequently reviewed 32 of these patients who required pneumonectomy (n = 19; right=9, left=10) or bilobectomy (n = 13) after bleomycin-combination chemotherapy. Results There were four operative deaths (13%). All postoperative deaths occurred in patients undergoing right-sided resections (pneumonectomy, n=2; bilobectomy, n=2) as a consequence of pulmonary complications. Operative survivors had a pulmonary morbidity of 18%. Fourteen of 20 long-term survivors were found to have a satisfactory performance status at follow-up. Conclusions Otherwise young and healthy male nonseminomatous germ cell tumors patients requiring large pulmonary resections after bleomycin-combination chemotherapy appear to be at higher than anticipated risk for pulmonary-related morbidity and mortality. However long-term survivors report an acceptable functional status.

Short- and Long-Term Outcomes after Large Pulmonary Resection for Germ Cell Tumors After Bleomycin-Combination Chemotherapy

Background Treatment of nonseminomatous germ cell tumors frequently requires bleomycin-combination chemotherapy followed by resection of residual disease. Bleomycin administration however raises concerns with respect to postoperative respiratory complications, particularly for patients undergoing large pulmonary resections. We undertook an institutional review to determine the outcome of large pulmonary resections after bleomycin-combination chemotherapy. Methods Between 1981 and 2001, 530 patients presented to our institution for resection of residual intrathoracic disease for either metastatic testicular or primary mediastinal nonseminomatous germ cell tumors. We subsequently reviewed 32 of these patients who required pneumonectomy (n = 19; right = 9, left = 10) or bilobectomy (n = 13) after bleomycin-combination chemotherapy. Results There were four operative deaths (13%). All postoperative deaths occurred in patients undergoing right-sided resections (pneumonectomy, n = 2; bilobectomy, n = 2) as a consequence of pulmonary complications. Operative survivors had a pulmonary morbidity of 18%. Fourteen of 20 long-term survivors were found to have a satisfactory performance status at follow-up. Conclusions Otherwise young and healthy male nonseminomatous germ cell tumors patients requiring large pulmonary resections after bleomycin-combination chemotherapy appear to be at higher than anticipated risk for pulmonary-related morbidity and mortality. However long-term survivors report an acceptable functional status.

Familial primary mediastinal nonseminomatous germ-cell tumors

In this article, we describe the case of 4 brothers, 2 of which had primary mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had benign mediastinal disease. We discuss the relationship between these diseases of the mediastinum and the thymic microenvironment. Additionally, we suggest that a genetic predisposition for germ-cell tumors (GCT) may be involved since the parents were relatives.

Outcome of patients with residual germ cell or non-germ cell malignancy after resection of primary mediastinal nonseminomatous germ cell cancer.

To identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer. Forty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed. At diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively. The presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.

850 Refractory germ-cell tumors (GCTs): salvage high-dose chemotherapy (HDCT) combining 2 mobilization regimen followed by 3 HDCT with blood stem cell transplantation (the taxif regimen — Getug group)

Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m2 × 3 plus etoposide 750 mg/m2 × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy.

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.

Primary mediastinal nonseminomatous germ cell tumors: The influence of postchemotherapy pathology on long-term survival after surgery

Objectives: The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery. Methods: Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy. Results: There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8). Conclusions: Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease. (J Thorac Cardiovasc Surg 1999;118:692-701)

Primary mediastinal nonseminomatous germ cell tumour in an adult female

Primary mediastinal nonseminomatous germ cell tumour in an adult female

Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy.

Primary mediastinal nonseminomatous germ cell tumors (NSGCT) are uncommon neoplasms and clinically and biologically distinct from other germ cell tumors (GCT). We describe the clinical and biologic features of these patients and evaluate the results of treatment during the cisplatin era. Between 1976 and 1993, 38 patients with mediastinal NSGCT received cisplatin-based chemotherapy as part of their primary treatment. Twenty-nine of them were initially treated at the Institut Gustave-Roussy (IGR), VillejuiF, France, and nine were referred for salvage treatment. Of the 29 patients initially treated at IGR, 11 (39%) had metastasis. A complete response (CR) to therapy was obtained in 19 of 29 patients (66%) after chemotherapy and surgery. Ten patients (34.5%) have remained free of disease with a median follow-up of 89 months. All patients who did not achieve a CR died of disease. The 2-year overall survival rate for the IGR patients is 45% and the 2-year disease-free survival is 37%. Only the presence of extrapulmonary metastasis was of prognostic significance in the univariate analysis (P = .0095). None of the 20 patients who required salvage therapy is currently disease-free. Five patients developed and subsequently died of a hematologic malignancy at an interval range of 1 to 47 months from treatment of mediastinal NSGCT. Cytogenetic analysis of leukemic cells found an isochromosome of the short arm of chromosome 12 (12p) in two cases. The incidence of leukemia was 21% in patients who attained a CR. Primary mediastinal NSGCT is a clinical and biologic entity that should be distinguished from other GCT. About 40% of these patients can envisage long-term survival with modern therapy that includes cisplatin-based chemotherapy followed by surgical resection of residual masses. New strategies are required for patients who do not attain a CR. Predictive factors and improvement in therapy are required for mediastinal NSGCT-associated leukemia.

Mediastinal non-seminomatous germ cell tumours (MNSGCT) treated with cisplatin-based combination chemotherapy

Primary mediastinal non-seminomatous germ cell tumours (MNSGCT) constitute a rare malignancy. This study was performed to review our experience with cisplatin-based chemotherapy in patients with MNSGCT. Patients with MNSGCT treated with cisplatin-based combination chemotherapy between 1978-1995 in three university hospitals in Spain were retrospectively studied. There were 25 males and two females with a median age of 26 years (range 4-71). Fifteen patients had disease confined to the mediastinum and 12 had metastatic disease. All patients were treated with cisplatin chemotherapy regimens (PVB: 7, BEP: 6, and other regimens 12) and considered for residual mass surgery (RMS) when indicated. Eleven patients (40.7%) were rendered disease-free with initial treatment: four with chemotherapy alone, one with surgery plus adjuvant chemotherapy and six with chemotherapy plus RMS. Three of these patients relapsed at two, six and seven months. The remaining 16 had unfavourable responses (five partial response, three no change, seven progressive disease and one toxic death). Eleven patients received salvage treatment but none of them achieved a durable response. After a median follow-up of 77 months (range 1-168), 10 patients remain alive. Actuarial survival at five years is 31.7%. No patients in this series developed a haematological malignancy. Chromosomal analysis showed that 2 out of 10 patients (20%) had a 47XXY karyotype. Only patients who achieved disease-free status are likely to be cured. Therefore, new up-front strategies are needed for the treatment of MNSGCT.

A Case of Recurred Primary Mediastinal Nonseminomatous Germ Cell Tumor Associated with Klinefelters Syndrome

Primary mediastinal nonseminomatous germ cell tumor associated with Klinefelter's syndrome is a rare disorder. We experienced a case of recurred primary mediastinal nonseminomatous germ cell tumor developed in a 24-year-old patient with Klinefelter's syndrome. The patient had been treated with surgery and combination chemotherapy under the diagnosis of primary mediastinal nonseminomatous germ cell tumor before. A round mass was found on the right lower lung field in the chest X-ray during follow up. The patient was diagnosed as recurred primary nonseminomatous genu cell tumor and Klinefelter's syndrome through tumor markers, peripheral blood karyotyping, and other tests including hormonal assay and was treated with combination chemotherapy and surgery again. When the patient is diagnosed as primary mediastinal nonseminomatous germ cell tumor, Klinefelter's syndrome and hematologic malignancies should be considered to be associated diseases and vice versa.

Fatal primary mediastinal non-seminomatous germ cell tumour initially diagnosed as malignant mesothelioma

A patient with a missed diagnosis of a primary mediastinal germ cell tumour is reported. The initial diagnosis of malignant mesothelioma was not compatible with the clinical course. The true diagnosis was reached after the patient had completed a course of palliative irradiation following the development of superior vena cava obstruction. He succumbed to a massive haemoptysis before chemotherapy could begin.

Primary mediastinal nonseminomatous germ cell tumors. A modern single institution experience

Between 1976 and 1988, 31 patients with mediastinal nonseminomatous germ cell tumors (MNGCT) received initial cisplatin-based chemotherapy of uniform intensity. Eighteen of these patients (58%) obtained disease-free status; 11 with chemotherapy alone and seven with adjunctive surgery. Eleven have remained continuously free of disease. Two have had recurrence of teratoma and are disease-free after resection of teratoma at 12+ and 68+ months. Three patients developed recurrence of germ cell tumor. Three patients developed a hematologic malignancy. Of the 18 patients who obtained disease-free status, 15 remain alive and disease-free. Overall, 13 of the 31 patients and 24 other patients received salvage chemotherapy at Indiana University, Indianapolis, Indiana. Of these 37 patients, six obtained a disease-free status and four (11%) remain alive at 13+, 56+, 78+, and 122+ months, respectively. This series represents the largest series of patients with MNGCT ever reported. Analysis of these data and results from other recent series suggest that approximately 50% of patients with MNGCT will be cured with modern, intense cisplatin-based chemotherapy coupled with adjunctive surgery if needed.

Primary mediastinal nonseminomatous germ cell tumors: Results of a multimodality approach

Before cisplatin-based chemotherapy, long-term survival after resection of primary mediastinal nonseminomatous germ cell tumors was unusual. We reviewed the case histories of 48 patients who underwent multimodality treatment for mediastinal nonseminomatous germ cell tumor between 1976 and 1988. Twenty-eight patients received initial therapy at Indiana University and 20 were referred after having had unsuccessful initial therapy elsewhere. In 44 patients (92%) the levels of either one or both serum tumor markers were elevated at the time of diagnosis. Five patients had choriocarcinoma, three embryonal carcinoma, 12 yolk sac carcinoma, four teratocarcinoma, 22 mixed cell type, and two had an unclassified type. Twenty-two of the 28 patients in our initial therapy group had a complete response to treatment, as defined by normal serum tumor markers and absence of residual tumor. In this group, 16 patients had resection of residual disease after chemotherapy, four had total or near total resection before chemotherapy, and only two had chemotherapy alone. Seventeen patients are surviving after this treatment with a median survival of 64 months and a 57% 5-year Kaplan-Meier survival rate. Only two of the 20 patients who were referred for salvage chemotherapy had a complete response. Both required resection of residual disease after salvage chemotherapy. Only one patient survived after this treatment. There was no significant treatment morbidity or mortality. A multimodality approach to primary mediastinal nonseminomatous germ cell tumor with intensive cisplatin-based chemotherapy, emphasis on normalizing serum tumor markers, and aggressive resection of residual disease now offers survival to a significant number of patients.