Myocardial infarction and other major vascular events during chemotherapy for testicular cancer.

BACKGROUND: Chronic vascular morbidity resulting from chemotherapy for testicular germ-cell cancer (TGCC) is recognized. Cardiovascular events (CVEs) occurring early during chemotherapy are less understood. We evaluated the incidence and clinical features of CVEs associated with chemotherapy of TGCC. PATIENTS AND METHODS: A questionnaire was sent to 355 institutions in Germany to explore for early CVEs occurring during 1996-2008. To assess the relative incidence of CVEs, the number of events was put into relation to the total number of patients treated during the time span (n = 8233, calculated from national database). The response rate was 79%. RESULTS: Twenty cases with myocardial infarction (MI), 3 with cerebral stroke, and 2 with arterial thrombosis were recorded. The estimated incidence of MI and of all CVEs during chemotherapy is 0.24% [95% confidence intervals (CIs) 0.137% to 0.349%] and 0.30% (95% CI 0.188% to 0.423%), respectively. This estimate represents a minimum figure because the calculation is on the basis of simplifications. Six MI patients had no risk factors. Coronary angiography was indicative of thromboembolic rather than atherosclerotic origin of MI. CONCLUSIONS: There is a small but definite risk of major early CVE associated with chemotherapy of TGCC. Physicians caring for TGCC patients must be aware of this hazard.

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

BACKGROUND: 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. METHODS: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS: 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). CONCLUSION: 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.

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.

PURPOSE: Despite generally high cure rates in patients with metastatic testicular germ cell tumors, patients with incomplete response to cisplatin-based first-line therapy or with relapsed disease after high-dose salvage chemotherapy have a very poor prognosis. This phase II study evaluates the use of gemcitabine in patients with intensively pretreated or cisplatin-refractory testicular germ cell cancers. PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled; 31 patients were fully assessable. All patients had metastatic nonseminomatous germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%) had received high-dose chemotherapy with autologous stem-cell transplantation, and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients (54%) were considered refractory or absolutely refractory to chemotherapy. RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine, 11 patients (35%) displayed no change, and 14 patients (45%) had disease progression. The median time to treatment failure was 4 months (range, 2 to 9+ months), and the median survival was 6 months (range, 2 to 23 months). Patients received a median of six gemcitabine applications. Ten patients (32%) required dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients (22%). One case of severe sepsis was observed. CONCLUSION: Gemcitabine displays antitumor activity in intensively pretreated and refractory germ cell tumors. Responses were observed in approximately 20% of patients, including three of 22 patients after previous high-dose chemotherapy and one of four patients with mediastinal tumors. Gemcitabine may be a reasonable palliative option for intensively pretreated patients and should be further investigated to define its role in the risk-adapted treatment strategies for germ cell tumors.

Validity of predictions of residual retroperitoneal mass histology in nonseminomatous testicular cancer.

PURPOSE: To validate predictions of the histology (necrosis, mature teratoma, or cancer) of residual retroperitoneal masses in patients treated with chemotherapy for metastatic nonseminomatous testicular germ cell tumor. PATIENTS AND METHODS: We studied 172 testicular cancer patients who underwent resection while tumor markers were normal. Predictive characteristics for the residual histology were registered, including the presence of teratoma elements in the primary tumor, the prechemotherapy level of tumor markers (alpha-fetaprotein [AFP], human chorionic gonadotropin [HCG], lactate dehydrogenase [LDH]), the size of the residual mass, and the percentage of shrinkage in mass diameter. We calculated the predicted probability of necrosis and the ratio of cancer and mature teratoma with previously published logistic regression formulas. RESULTS: The distribution of the residual histology was necrosis in 77 (45%), mature teratoma in 72 (42%), and cancer in 23 (13%). Necrosis could be well distinguished from other tissue, with an area under the receiver operating characteristic (ROC) curve of 82%. No tumor was found in 15 patients with a predicted probability of necrosis over 90%. The predicted probabilities corresponded reliably with the observed probabilities (goodness-of-fit tests, P > .20), although a somewhat higher probability of necrosis was observed in patients treated with chemotherapy containing etoposide. Conversely, cancer could not reliably be predicted or adequately discriminated from mature teratoma. CONCLUSION: The predicted probabilities of necrosis have adequate reliability and discriminative power. These predictions may validly support the decision-making process regarding the need and extent of retroperitoneal lymph node dissection.

Second-line chemotherapy in patients with relapsed extragonadal nonseminomatous germ cell tumors: results of an international multicenter analysis.

PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment. RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P =.003), sensitivity to cisplatin (P =.003), elevated beta-HCG at relapse (P: =.04), and normal LDH at diagnosis (P =.01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis. CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.

Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group.

PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a diaminocyclohaxane platinum derivative with incomplete cross-resistance to cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer. PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease after high-dose chemotherapy (HDCT) plus autologous stem-cell support were treated with single-agent oxaliplatin 60 mg/m(2) on days 1, 8, and 15 repeated every 4 weeks (group 1; n = 16) or oxaliplatin 130 mg/m(2) given on days 1 and 15 of a 4-week cycle (group 2; n = 16). Patients were pretreated with a median of seven (range, three to 13) cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide-based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to cisplatin therapy. RESULTS: Overall, four patients achieved a partial remission (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved disease stabilization. All responses were observed in cisplatin-refractory patients, including three who had not responded to previous HDCT. Patients received a median two cycles of oxaliplatin with a median cumulative dose of 350 mg/m(2). Hematologic toxicity was generally mild, with five patients developing grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of nausea/vomiting. One patient developed grade 3 neurotoxicity. CONCLUSION: Considering the particularly unfavorable prognostic characteristics of this patient population compared with patients from previous trials for new drugs in germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and a 19% response rate in the group treated with oxaliplatin 130 mg/m(2) seems to be of interest. Oxaliplatin may be a palliative treatment option for this patient population, and evaluation in combination regimens is warranted.

Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Does serum tumor marker half-life complement pretreatment risk stratification in metastatic nonseminomatous germ cell tumors?

The goal of this study was to determine whether the serum tumor marker half-life (MHL) of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) during initial chemotherapy can complement pretreatment risk stratification in metastatic nonseminomatous germ cell tumors. One hundred forty-seven patients were assessable for MHL during the first two cycles of platinum-based chemotherapy. MHL calculation was based on two consecutive values using Kohn's apparent half-life formula (MHL =ln 1/2/G, where G was the gradient of the marker slope) or on three (or more) values using simple linear regression. MHL was regarded as prolonged if it was more than 3.5 days for HCG or more than 7 days for AFP. The median MHL for HCG was 2.8 days (range, 0.7-16.7) and for AFP was 6.2 days (range, 2. 6-65.4). Thirty-five of 108 patients (32%) had a prolonged MHL for HCG, 41 of 114 (36%) had a prolonged MHL for AFP, and in 59 of 147 patients (40%), either or both MHLs were prolonged. If patients with both MHLs normal were compared against patients with either or both MHLs prolonged, highly significant differences in progression-free survival (P < 0.0001) and overall survival (P = 0.0005) were demonstrated. The test accuracy was 70% for both progression-free and overall survival, and it was slightly greater than the overall predictive value of the Medical Research Council prognostic classification. A combination of Medical Research Council criteria and MHL analysis allowed us to refine prognostic assessment. Because MHL analysis is able to complement pretreatment risk stratification and can support selection of patients for early-dose intensified chemotherapy, it should be included in prospective clinical trials for patients with poor-prognosis disease.

Central nervous system as sanctuary site of relapse in patients treated with chemotherapy for metastatic testicular cancer.

Isolated central nervous system relapse in patients treated successfully with cisplatin-based chemotherapy for testicular cancer has been described infrequently. In a retrospective analysis we identified this complication in six of 417 patients. Five of the six patients had advanced pulmonary dissemination at onset of chemotherapy, and post-chemotherapy surgery did not reveal viable tumour tissue in any of these cases. All six patients developed a single cerebral metastasis during complete remission a median four months after discontinuation of chemotherapy. Five patients were treated with surgery and subsequent radiotherapy, one patient with irradiation alone. Three patients are alive relapse-free 19, 62 and 86 months after diagnosis of cerebral relapse. One patient was alive with cerebral disease for 12 months without evidence of systemic recurrence. Our data demonstrate that the brain may act as a sanctuary site in chemotherapy-treated testicular cancer. A review of the literature shows that an isolated cerebral relapse is an extremely rare complication, but carries a relatively favourable prognosis.

Prognostic implications of tumour marker analysis in non-seminomatous germ cell tumours with poor prognosis metastatic disease.

86 unselected patients with poor risk metastatic non-seminomatous germ cell tumours (NSGCT) treated from 1979 to 1990 at a single institution were reviewed with regard to the prognostic relevance of tumour marker analysis. The number of elevated tumour markers was not able to distinguish patients into prognostic subgroups. Pretreatment levels of human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) did not have a significant influence on clinical outcome. HCG and AFP half-life analysis during the first chemotherapy cycles also failed to define prognostic subgroups. If early deaths within 90 days after the onset of chemotherapy were excluded, patients with a half-life of HCG decline greater than 3.5 days tended to have a poorer prognosis which did not reach significance.

Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.

From July 1986 to 1990, 65 patients with deep-seated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40 patients) had received ifosfamide-containing drug regimens before entering the RHT study, 26% (17 patients) were pretreated by surgery and/or radiation and 12% (8 patients) were treated primarily. A total of 426 RHT treatments (mean 6.6 RHT/patient) were applied predominantly within the pelvic region (82%) bearing relative large tumours (mean volume 500 cm3). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1-5), etoposide (100 mg/m2, days 1, 3, 5) and 2-mercaptoethanesulphonic acid (mesna; 300 mg/m2 x 4, days 1-5) with RHT only given on days 1 and 5 in repeated cycles every 4 weeks. Detailed thermal mapping by invasive thermometry was performed in all patients. In 61 patients evaluable for tumour control the overall objective response rate including 9 complete responders (CR), 4 partial responders (PR) and 8 patients with favourable histological response (FHR) was 34% (95% confidence limits, 23%-46%). Following CR, the patients are alive and remain disease-free (mean disease-free survival 15.6 months). Of the patients with PR and FHR, 3 died from metastatic and/or local disease after 4, 17, and 39 months, and 1 patient died from other disease (acute myelocytic leukemia) after 27 months. The other 8 patients remain stable at 29, 25, 17, 11, 10, 8, 7, and 6 months. Twenty-two patients revealed no change and 18 patients showed local tumour progression (PD). Side-effects of RHT were tolerable and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. By analysis of temperature parameters, the time-averaged temperatures of all RHT treatments calculated for 20% (T20), 50% (T50) or 90% (T90) of measured tumour sites differed significantly between responders (CR + PR + FHR) and non-responders (PD), respectively (T20, P = 0.001; T50, P = 0.0005; T90, P = 0.0001). the data further support a strong potential for ifosfamide plus etoposide combined with RHT in pretreated patients with advanced sarcomas.

Myocardial-infarction after adjuvant chemotherapy for resected stage-ii nonseminomatous testicular cancer.

Although acute toxicity of cisplatin-based chemotherapy of germ cell tumors is considerable, major vascular complications have been reported infrequently. This report describes the case of a 36-year-old man developing myocardial infarction after the first cycle of adjuvant cisplatin-based chemotherapy for resected stage II testicular cancer. A close temporal association between the administration of chemotherapy and the vascular event suggests a cause and effect relationship. A drug-induced endothelial cell damage may be an important pathogenetic factor. Although reports on vascular accidents following treatment of testicular cancer raise concern with regard to the safety of chemotherapy, at present the very low incidence of such complications should not enter into therapeutic decisions.

Adjuvant chemotherapy of stage-ii nonseminomatous testicular cancer.

85 patients with resected stage II non-seminomatous testicular cancer were treated with adjuvant cisplatin-based chemotherapy. Only one patient developed a relapse 14 months after discontinuation of adjuvant chemotherapy, which was successfully treated with salvage chemotherapy. One patient developed a contralateral testicular tumor 6 years after primary therapy. After a median observation time of 6 years (range 2 months to 13 years) 84 patients are alive without evidence of testicular cancer; one died from an unrelated cause. In conclusion, adjuvant cisplatin-based chemotherapy for resected stage Il nonseminomatous testicular cancer almost always prevents relapse.

Is serum tumor marker half-life a guide to prognosis in metastatic nonseminomatous germ cell tumors?

BACKGROUND: The value of serum tumor marker kinetics of AFP and HCG assessed by marker half-life (MHL) analysis for diagnosis and in the follow-up of patients with nonseminomatous germ cell tumors (NSGCT) is still debated controversally. The aim of this retrospective study was therefore to investigate the influence of serum MHL during the first two cycles of chemotherapy on the long-term outcome in metastatic NSGCT. MATERIAL AND METHODS: 147 patients with at least 2 abnormal marker values > 7 days after start of chemotherapy were investigated for HL analysis (HL cut off 3.5 days for HCG and 7 days for AFP). HCG and AFP determinations were performed by a double monoclonal IRMA (HCG) and conventional RIA (AFP) developed by our laboratory. RESULTS: According to these cut offs 35/108 patients (32.4%) had a prolonged HCG HL and 41/114 patients (36%) a prolonged AFP HL. Patients with either MHL prolonged had a significantly inferior overall survival (OS; 10 year OS 37% vs. 75%, p = 0.0005) and progression-free survival (PFS; 10 year PFS 29% vs. 69%, p < 0.0001) than those with a prolonged HCG MHL (OS; 10 year OS 36% vs. 65%, p = 0.003; 10 year PFS 28% vs. 56%; p = 0.001) and even more than those with a prolonged AFP MHL (10 year OS 39% vs. 70%, p = 0.02; 10 year PFS 32% vs. 56%, p = 0.01). CONCLUSION: The remarkable prognostic information assessed by MHL analysis in this retrospective study merits further confirmation by a prospective study for its appropriateness in selecting patients for high dose chemotherapy.

[Current status of therapy of CNS metastases of germ cell tumors]. / Derzeitiger Stand der Therapie von ZNS-Metastasen bei Keimzelltumoren.

The incidence of CNS metastases in germ cell tumors is 2-5% and in very advanced disease over 20%. We report on 37 patients in whom CNS metastases were diagnosed with the CAT scanner. Twenty-nine patients were subsequently treated. In 19 cases, treatment consisted of radiotherapy, 1 patient was only operated on, and in 9 cases patients received combined surgery and radiotherapy. Two patients had seminomatous germ cell tumors, 27 patients non-seminomatous tumors. HCG levels were high in 11 cases. In 31 patients the disease was in the advanced stages; in 6 the disease was at the early stage. If there was just a solitary tumor, operation was the preferred mode of treatment. Radiotherapy consisted of 50 GY whole-brain irradiation, with a tumor saturation up to 60 GY. In 2 cases we suspected radiogenic necrosis. There were no other severe side effects. Of the 37 patients, 4 obtained a long-term cure (observation time 34-90 months). Therapy must take all methods of treatment into consideration and should only be carried out in fully equipped medical centers. Only then can we hope to obtain long-term cures in individuals with this usually fatal disease.

[Primary extragonadal germ cell tumors. Clinical manifestations, differential diagnosis and therapy]. / Primär extragonadale Keimzelltumoren. Klinisches Erscheinungsbild, Differentialdiagnose und Therapie.

BACKGROUND: Primary extragonadal germ cell tumors are a rare malignant disease in young males. They account for only 1 to 4% of all germ cell tumors. PATIENTS AND METHODS: In this paper we describe three selected cases of primary extragonadal germ cell tumors. The literature is reviewed with regard to clinical features, differential diagnosis and treatment. RESULTS: Tumor markers alpha-fetoprotein and human chorionic gonadotropin are of considerable diagnostic value if disease distribution is considered. With cisplatin-based combination chemotherapy similar disease-free survival rates are achieved as for testicular tumors with poor-prognosis metastatic disease. Surgical procedures play a role as adjunctive modality. CONCLUSIONS: If young males present with a mass in the retroperitoneum or in the anterosuperior mediastinum, a primary extragonadal germ cell tumor, should be taken into consideration. Tumors of both localisations have distinct clinical features but carry a similar prognosis. Patients benefit from the cumulative experience of a specialist unit.