Mediastinal Nonseminomatous Germ Cell Tumors Research Articles

Extragonadal germ cell tumors

The extragonadal germ cell tumors (EGCTs) represent a unique entity, and as such require specialized management. This review article will discuss the diagnosis, prognosis and treatment modalities for EGCTs. The anterior mediastinal germ cell tumors (GCTs) are the most common EGCT. These tumors originate in the anterior mediastinum without any testis primary. Mediastinal nonseminomatous GCTs carry a poor prognosis with 40-50% overall survival and should be treated with cisplatin-based chemotherapy followed by surgical resection of the residual tumor. At Indiana University, we recommend etoposide (VP-16), ifosfamide and cisplatin (VIPx4) instead of bleomycin, etoposide and platinum (BEPx4) to prevent pulmonary complications, as these patients require extensive thoracic surgical resection. Patients who relapse have a dismal outcome with only 10% long-term survival. Our preferred treatment option is surgery for localized relapse; if surgery is not feasible, then high-dose chemotherapy with stem cell transplant in an experienced center is a reasonable approach. Retroperitoneal GCT should be treated in a similar fashion to primary testis cancer. The utilization of cisplatin-based chemotherapy is associated with the best chance of cure for EGCTs. This should be followed by surgical resection of residual tumor in nonseminomatous GCT.

The Transdifferentiation of Mediastinal Germ Cell Tumor into a Myeloid Neoplasm in the Bone Marrow-Report of a Case and Short Review of a Diagnostic Pitfall

We present the case of a young male with a mediastinal non-seminomatous germ cell tumor who developed a severe thrombocytopenia, one year after initial diagnosis and surgical treatment and chemotherapy. Bone marrow morphology suggested myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia). Cytogenetics of bone marrow showed near tetraploid karyotype, raising concerns about the diagnosis of MDS. The patient died within one month due to refractory disease and autopsy revealed a highly invasive germ cell tumor in the mediastinum and chest wall which showed the same cytogenetic abnormality seen in the bone marrow. The bone marrow collected at autopsy showed features compatible with acute myeloid leukemia. The implications of this transdifferentiation of a mediastinal germ cell tumor into an apparent hematological malignancy for correct diagnosis and appropriate treatment are discussed.

Salvage Therapy with High-Dose Chemotherapy and Peripheral Blood Stem Cell Transplant in Patients with Primary Mediastinal Nonseminomatous Germ Cell Tumors

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 malignancies associated with germ cell tumors

Germ cell tumor (GCT)-associated hematologic malignancies present a unique challenge to hematologists and hematopathologists. As most GCTs are of gonadal origin, only a small percentage occur at extragonadal sites in the midline. Extragonadal GCTs are believed to originate from the ectopic primordial germ cells that fail to migrate to the urogenital ridge during development. An overactive KIT pathway and overexpression of genes on chromosome 12p are strongly implicated in GCT development. Approximately 54% of extragonadal GCTs are located in the anterior mediastinum. This is disproportionally high among the midline structures, presumably due to a favorable microenvironment for GCT development in the developing thymus. The mediastinal nonseminomatous GCTs have two unique features. First, they are often refractory to current treatment modality with the worst prognosis among GCTs of all sites. Second, they have a tendency to give rise to secondary hematologic neoplasia. The outcome is grave for patients with GCT-associated hematologic malignancies. As standard chemotherapy used to treat their bone marrow-derived counterparts has been ineffective, the best treatment modality to achieve long-term survival is allogeneic hematopoietic stem cell or cord blood transplant for a very limited number of cases.

The “growing teratoma syndrome” in primary mediastinal nonseminomatous germ cell tumors: Criteria based on current practice

Criteria for the growing teratoma syndrome in patients with primary mediastinal nonseminomatous germ cell tumors have not been well established according to current practice. An institutional database identified 188 patients who underwent postchemotherapy surgery for primary mediastinal nonseminomatous germ cell tumors from 1981 to 2009. We reviewed the subset of patients who underwent urgent surgery for tumor growth resulting in cardiopulmonary deterioration secondary to mediastinal compression precluding safe completion of 4 cisplatin-based chemotherapy cycles with rapidly declining serum tumor markers. Five men (2.6%) with an average age of 25.8 years were identified. All patients initially presented with a large symptomatic anterior mediastinal mass and elevated serum tumor markers. Patients received an average of 2.4 chemotherapy cycles of a scheduled 4 courses before cardiopulmonary deterioration. Pathology of the resected specimens demonstrated mature teratoma in all patients; however, it was admixed in 4 patients with foci of immaturity (n=1), malignant transformation of teratoma to sarcoma (n=2), and nonseminomatous germ cell tumor (n=2). There was 1 operative death. Three of the 4 operative survivors subsequently completed a total of 4 cycles of chemotherapy after recovery. Two patients are alive and well after an average of 14 years. Two patients died of metastatic disease. The growing teratoma syndrome should be defined not only as a growing mediastinal mass but also with secondary cardiopulmonary deterioration precluding safe completion of planned chemotherapy in the presence of declining serum tumor markers. Prompt recognition of this syndrome, discontinuation of chemotherapy, and surgical intervention can result in cure.

Phase II study of everolimus (E) in refractory germ cell tumors (GCTs).

TPS4677 Background: GCTs represent a model for the cure of cancer. Nonetheless, a small proportion of patients (pts) develop disease recurrence. Because of insufficient results in the treatment of relapsed GCTs, evaluation of new treatments is a priority. Loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog) marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive GCTs. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not in early event in GCTs development, but is associated with disease progression. PTEN inactivation is associated with dysregulation of PI3K/Akt pathway and increased mTOR signalling. We hypothesize that dysregulation of PI3K/Akt pathway due to PTEN inactivation in GCTs suggests that these pts could have greater benefit from mTOR inhibition. Methods: In December 2011, National Cancer Institute of Slovakia launched an one arm, two-staged phase II study aimed to evaluate the efficacy and toxicity of E in pts with refractory GCTs. The primary objective is to determine the efficacy of E in patients with refractory GCTs. Secondary objectives includes favourable response rate, time to progression and safety. The pts with radiological and/or serological proof of relapsed GCTs, who were not amenable to be cured by chemotherapy or surgery and who failed at least two platinum-based regimens or one platinum regimen in case of platinum-refractory disease or primary mediastinal non-seminomatous GCTs were eligible. All other standard inclusion and exclusion criteria for study of salvage treatment in refractory GCTs pts were applied. E will be administered at a dose of 10mg daily until progression or unacceptable toxicity. Assuming a response rate of clinical interest of ≥40%, a minimal response rate of 20%, a probability of 5% for rejecting an active drug, and a probability of 20% to further evaluate an ineffective drug, 18 pts will be enrolled into the first cohort. If <4 responses will be observed, the study will be terminated, otherwise, it will be continued with a second cohort of 20 pts.

Surgical outcomes in patients with primary mediastinal non-seminomatous germ cell tumours and elevated post-chemotherapy serum tumour markers

Platinum-based chemotherapy followed by surgical resection of residual masses has become the standard treatment of patients with primary mediastinal non-seminomatous germ cell tumours (NSGCTs). Persistent serum tumour marker (STM) elevation after chemotherapy usually indicates a poor prognosis. We retrospectively assessed surgical outcomes in patients with high STM levels after chemotherapy for primary mediastinal NSGCT. Between 1983 and 2010, residual tumour excision was performed in 21 patients, 20 men and one woman with a median age of 30 years (range: 19-49 years), with primary mediastinal NSGCTs and high STM levels after platinum-based chemotherapy, followed by second-line chemotherapy in 11 patients. Alpha-fetoprotein was elevated in all 21 patients and β-human chorionic gonadotropin in three patients. Permanent histology demonstrated viable germ cell tumour (n=13), teratoma (n=3) or necrosis (n=5). After surgery, the STM levels returned to normal in 11 patients. Eight patients are alive with a median follow-up of 98 months. The 5-year survival rate was 36% and was not significantly affected by the use of preoperative second-line chemotherapy. At univariate analysis, only postoperative STM elevation and residual viable tumour, indicating incomplete resection, were significantly associated with lower survival (P=0.018 and P=0.04, respectively). In patients with primary mediastinal NSGCTs and elevated post-chemotherapy STMs, surgery is warranted when complete resection is deemed feasible. In specialized oncology centres, this aggressive approach can provide a cure in some patients.

Resection of Primary Mediastinal Non-Seminomatous Germ Cell Tumors: A 28-Year Experience at Memorial Sloan-Kettering Cancer Center

Surgical resection of residual tumor mass in responders to platinum-based chemotherapy has evolved as the preferred treatment of primary mediastinal nonseminomatous germ cell tumors (PMNGCTs). We reviewed a single institution's operative experience with these rare tumors. We reviewed charts of patients resected for PMNGCT at Memorial Sloan-Kettering Cancer Center between July 1980 and April 2008. Analyses included Kaplan-Meier survival with univariate log-rank comparisons and Cox multivariate regression. Fifty-seven patients were identified and followed up for a median of 5.3 years. Fifty-four of them received platinum-based preoperative chemotherapy, and 28 (49%) had limited stage I/II disease. Preoperative tumor markers normalized or decreased in 79% of patients. The most common surgical approach was anterolateral thoracotomy with partial sternotomy ("hemiclamshell," 38.6%). An R0 resection was achieved in 91% of the patients with a major morbidity of 17.5% and no postoperative deaths. The median overall survival was 31.5 months. Factors correlating with better survival on univariate analyses were necrosis or teratoma versus residual cancer on final pathology (p = 0.001), R0 resection (p = 0.03), normalized or decreased postchemotherapy/preoperative tumor markers (p < 0.001), normalized postoperative tumor markers (p = 0.004), stage I/II disease (p = 0.03), and surgery after 2000 versus 1980-1999 (p = 0.01). An exploratory multivariate analysis suggests that normalized or decreased postchemotherapy/preoperative tumor markers is the strongest independent predictor of improved survival. In a cohort of PMNGCT patients in which 91% of the patients underwent complete posttherapy resection, response to chemotherapy, measured by normalized or decreased preoperative tumor markers, was the strongest predictor of improved survival.

Salvage therapy with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) in patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT).

e15119 Background: 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. Patients with primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) have had poor results with any form of salvage chemotherapy including HDCT. From 1986 to 1996, we included 13 patients with PMNSGCT in our series treated with HDCT and BMT. All died from progressive cancer. Methods: We switched from BMT to PBSCT in 1996, allowing more rapid engraftment and earlier initiation of the second course of HDCT with tandem transplant. 116 of 184 (63%) patients with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease free (NEJM 357:340-348, 2007). PMNSGCT patients were excluded. In 2006, we resumed treating patients with recurrent PMNSGCT with salvage HDCT with PBSCT. Carboplatin 700mg/m2 x 3 plus etoposide 750mgs/m2 x3 were given with second course 3-4 weeks later. Results: 12 patients were treated, 11 as initial salvage chemotherapy and one as 4th line therapy. Eight patients had major thoracic resections prior to HDCT. 3 of the 12 achieved complete remission (52, 12 and 12 weeks duration) but all have relapsed. 10 of the 12 have died; one is lost to follow-up at 44 weeks, and one patient is currently disease free at 176 weeks from HDCT, treated with subsequent salvage surgery. However, he developed secondary acute myeloid leukemia and underwent allogeneic BMT. Median survival for the 12 patients was 41 weeks (range 14-176). Conclusions: In our experience with tandem transplant, recurrent PMNSGCT continues to have a low probability for cure.

Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT).

4579 Background: Salvage chemotherapy with Ifosfamide based regimen or high dose chemotherapy (HDCT) has curative potential in GCTs. We still need novel therapies for patients where cure is not possible. Oxaliplatin has single agent activity in refractory GCTs. Bevacizumab in combination with chemotherapy has activity in many solid tumors but has not been studied in GCTs. This is the first study of bevacizumab in refractory GCT patients. Methods: Patients with serologically or histologically proven metastatic GCT who have failed cisplatin based combination chemotherapy and progressed on salvage therapy were eligible. Prior HDCT and paclitaxel plus gemcitabine were required unless late relapse or primary mediastinal non-seminomatous GCT (NSGCT). Oxaliplatin was given 85 mg/m2 and bevacizumab 10 mg/kg every 2 weeks with a maximum of 14 cycles. Results: 25 total patients have been enrolled with 24 evaluable and 1 too early to evaluate. 9 were late relapses and 5 with primary mediastinal NSGCT. Median number of previous chemotherapies was 4 including 13 with prior HDCT. Median number of cycles administered was 5. There were 7 (29%) objective responders. Median duration of response was 6 months (range 4 to 22 months). Of these 7 patients 3 had normalization of HCG and/or AFP. One additional patient had serologic response (>1 log reduction in HCG) for 5 months with stable radiographic lesions. Median survival was 8 months (range 2 to 40 months). Four patients had Grade 3 adverse events (peripheral neuropathy, hypertension, seizures and DVT). Conclusions: Oxaliplatin plus bevacizumab has promising activity in heavily pretreated GCTs with manageable toxicity.

Mediastinal Growing Teratoma Syndrome Succesfully Treated by Multiple Modality Therapies

A 43-year-old-man was diagnosed as having primary mediastinal nonseminomatous germ cell tumor based on percutaneous biopsy and an elevated serum concentration of alpha-fetoprotein (AFP). Although AFP decreased after chemotherapy, the mass size grew and developed tracheal compression by the tumor. The patient was treated with mechanical ventilation and subsequent stent implantation for keeping airway patency. After three cycles of chemotherapy and normalization of AFP, the increased mass was successfully resected and the pathological examination demonstrated a mature teratoma. This case showed a rare clinical manifestation of mediastinal growing teratoma syndrome and successful outcome by multimodal therapies.

Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide for Patients With Relapsed Primary Mediastinal Nonseminomatous Germ Cell Tumors: Benefit From Chemotherapy, Surgery, or Both?

Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide for Patients With Relapsed Primary Mediastinal Nonseminomatous Germ Cell Tumors: Benefit From Chemotherapy, Surgery, or Both?

Survival outcomes for men with mediastinal germ-cell tumors: The University of Texas M. D. Anderson Cancer Center experience

ObjectivePrimary mediastinal germ-cell tumors are rare, and the effect of newer drugs and treatment strategies in this disease on overall survival is not known. We retrospectively assessed treatment outcomes at a single institution. Materials and methodsWe identified men seen at our institution from 1998 through 2005 for mediastinal germ-cell tumors. Medical records were reviewed for patient characteristics, histology, tumor markers, treatment, and survival outcome. ResultsThirty-four patients met study criteria, of whom 27 had nonseminomatous germ-cell tumor (NSGCT) and 7 had pure seminoma. Eleven patients (41%) with NSGCT were alive at last contact with a median overall survival time of 33.5 months. Among 13 patients with NSGCT referred to us at initial diagnosis, 7 (54%) were alive and recurrence-free at a median follow-up of 56.5 months. Progression-free survival was associated with absence of risk factors (any histology other than endodermal sinus tumor, β-hCG > 1000 mIU/mL, or disease outside the mediastinum). For the patients whose disease progressed (n = 5) or who had been referred to us for salvage treatment (n = 14), the 3-year overall survival from the date of first progression was 23%. Conversely, patients with seminoma did uniformly well with platinum-based chemotherapy; most did not undergo radiation or surgery. ConclusionChemotherapy given to maximum effect followed by surgical consolidation resulted in long-term progression-free survival for 54% of patients with mediastinal NSGCT. The number of risk factors present at diagnosis may be associated with survival outcome and should be studied in a larger test group.

Mediastinal Germ Cell Tumor With Somatic-Type Malignancy: Report of 5 Stage I/II Cases

Among 15 patients with primary mediastinal nonseminomatous germ cell tumors experienced during the past 12 years, 5 were diagnosed with germ cell tumors with somatic-type malignancy. The pretreatment stages were stage I in 2 patients and stage II in 3. All 5 patients received perioperative chemotherapy plus surgical resection, and 4 remain alive without relapse, with a mean follow-up of 60 months.

Phase II study of oxaliplatin (O) and bevacizumab (B) chemotherapy in refractory germ cell tumors (GCT).

e15054 Background: Approximately 80% of patients (pts) with metastatic GCT are cured with first line cisplatin based chemotherapy or subsequent salvage therapy. However, there remains a cohort of pts with incurable refractory and late relapse disease. Single agent O has demonstrated response rate of 13-19% in this setting. VEGF overexpression appears to have a role in GCT progression, and there may be synergy between anti-VEGF therapy and certain cytotoxic agents. This is the first clinical study evaluating B in refractory GCT. Methods: Eligibility required prior cisplatin combination chemotherapy, salvage therapy with high dose chemotherapy (HDC) and prior paclitaxel and gemcitabine. Pts with late relapse or primary mediastinal nonseminomatous GCT (PMNGCT) required failure of at least one prior salvage chemotherapy regimen. Pts received O 85mg/m2 IV and B 10mg/kg IV on a q2wk cycle for up to 14 cycles. Toxicity, response (including serologic) and duration of remission were evaluated. Tumor response was evaluated by RECIST criteria. Serologic response was defined as normalization of markers > 4 wks (CR) and 1 log reduction in hCG or 50% reduction in AFP lasting > 4 wks (PR). Results: Since 11/2006, 19 pts have been enrolled, 18 are evaluable and enrollment continues. Median age was 42y (range 21-55). 2 women with PMNGCT were entered. Median number of prior treatments was 3.5 (range 2-6). There were 8 pts with late relapse and 8 had prior salvage HDC. Therapy was well tolerated. The most common all grade toxicities were nausea (66.7%), sensory neuropathy (61%) and fatigue (55.6%). G3/4 toxicities (seen in late relapse only) were fatigue (11%), pulmonary HTN and laryngitis (6% each). 16 pts were evaluated for serologic response; there were 3 CRs (16.7%) and 3 PRs (16.7%). 10 pts had measurable disease for RECIST evaluation, and no CRs were seen. 1 pt had PR per RECIST and serologic criteria (6%). Median duration of response was 29.3 wks (95% CI 10-36.9). 5 of 8 pts (62.5%) with late relapse responded (3 CR, 2PR). Conclusions: The combination of O+B is well tolerated in a heavily pretreated pt population. The response rate is encouraging when compared to previous trials with O alone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Biogen Idec, GlaxoSmithKline

TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis

We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients. Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed. Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models. TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.

Paclitaxel (T) plus ifosfamide (I) followed by high-dose carboplatin (C) and etoposide (E) with autologous stem cell support for patients (pts) with previously treated germ cell tumors (GCT): TI-CE results and prognostic factor analysis in 107 pts

5027 Background: Pts with incomplete response (IR) to first-line chemotherapy or relapsed primary mediastinal non-seminomatous GCT (NSGCT) have &lt;10% 3-year (yr) survival with conventional-dose salvage regimens (Cancer. 67:1305). The doses, schedule, and safety of TI-CE in this population were previously reported (J Clin Oncol. 25: 85). Efficacy and prognostic factor analysis are now presented. Methods: Phase I/II trial of TI-CE conducted in GCT pts with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, IR to first-line therapy, or relapse/IR to ifosfamide/cisplatin-based conventional-dose salvage). Univariate and multivariate analyses of prognostic factors were performed. Einhorn (N Eng J Med. 357:340) and Beyer (J Clin Oncol. 14: 263) prognostic models were also assessed. Results: Of 107 pts, primary site was testis in 72, mediastinum (all NSGCT) in 21, and other in 14. 81 had 1 prior line of therapy and 26 had ≥2. 79 were platinum-refractory and 7 had late relapses. A complete response was achieved in 54 (50%) and partial response with negative markers in 8 (8%). 5-yr disease-free survival (DFS) was 47% and overall survival 52% with a median follow-up of 61 months (m). No relapses occurred after 2 yrs. 5/21 (24%) primary mediastinal NSGCT and 2/7 late relapses are continuously disease-free. On multivariate analysis, primary mediastinal site (p = 0.0002), ≥2 lines of prior therapy (p = 0.0005), baseline HCG &gt;1000 (p = 0.01), and lung metastases (p = 0.02) significantly predicted adverse DFS. By Beyer model, 79% were intermediate and 21% poor risk (0 good risk). DFS was better for intermediate than poor risk pts (p &lt; 0.002), with 2-year rates of 54% and 23%, respectively. By Einhorn model, 15% pts were good, 38% intermediate, and 47% poor risk; good/intermediate risk pts had superior DFS compared to poor risk pts (p &lt; 0.05) with DFS at 2 yrs of 69% vs. 44%. Conclusions: TI-CE is effective salvage therapy for GCT pts with poor prognostic features. Mediastinal primary site and ≥2 lines of prior therapy were most predictive of adverse DFS. Beyer &amp; Einhorn models can assist in predicting outcome. No significant financial relationships to disclose.

Compression extrinsèque de l’artère pulmonaire secondaire à une tumeur germinale non séminomateuse médiastinale

Acquired arterial pulmonary stenosis is rarely found in adults. Reviews and case reports suggest that tumours of the mediastinum (teratomatas and Hodgkin's disease) are the most frequent culprits leading to compression of the main pulmonary artery. We present the case of a young patient with chest pain. Compression of the main and left pulmonary artery by an anterior mediastinal nonseminomatous germ cell tumors (GCTs) was diagnosed by transthoracic echocardiography and CT scan.

Rapid enlargement of mediastinal nonseminoma due to hemorrhagic necrosis induced by chemotherapy: CT findings

Rapid enlargement of mediastinal nonseminomatous germ cell tumor (mediastinal NSGCT) with a fall in tumor marker levels was noted in a 43-year-old man. The patient was treated with chemotherapy (bleomycin, etoposide and cisplatin, BEP) to downsize the tumor preoperatively. The mediastinal NSGCT, however, increased in size aggressively despite decline in tumor markers, provoking critical respiratory failure that resulted in the patient's death. We describe computed tomography (CT) findings of a case of enlarging mediastinal NSGCT due to postchemotherapeutic tumor necrosis that progressed rapidly before initiation of subsequent regression.

Primary Mediastinal Non-seminomatous Germ Cell Tumor Associated with Hemophagocytic Syndrome

A 20-year-old man with a primary non-seminomatous mediastinal germ cell tumor (yolk sac tumor and immature teratoma) developed hemophagocytic syndrome (HPS) three months after surgical resection. Around the same time, the patient was found to have bone metastases of the germ cell tumor. No other hereditary or acquired diseases related to HPS were found. The thrombocytopenia was refractory to corticosteroid therapy but improved after chemotherapy performed for germ cell tumor progression. Only three cases of germ cell tumor associated with reactive hemophagocytosis have been previously reported. Successful treatment of the present case by chemotherapy for HPS suggests a close relationship between this rare complication and germ cell tumor.