Primary Mediastinal Germ Cell Tumors Research Articles

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15-yr-old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW-MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto-PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto-PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.

Histiocytic Sarcoma and Indeterminate Cell Tumor in a Young Adult With Mediastinal Germ Cell Tumor

Germ cell tumors (GCTs) are unique in their ability to differentiate along multiple cell lineages. The strong association between primary mediastinal non-seminomatous germ cell tumors and hematologic malignancies is well known. The most common hematologic neoplasms seen with GCTs are acute megakaryoblastic leukemia and histiocytic sarcoma. GCT patients with hematologic malignancies have a much worse prognosis than patients …

Salvage high-dose chemotherapy for primary mediastinal nonseminomatous germ cell tumors: Single institute experience.

e15503 Background: Primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) bear a worse prognosis than stage-matched testicular primaries, with a five year survival rate of 50%. In contrast to relapsed testicular NSGCT, retrospective analyses have not shown benefit to high-dose chemotherapy and autologous stem-cell transplant (HDCT/ ASCT) in PMNSGCT patients. Since publication of these studies, advancements in treatment regimens and supportive care have occurred, with emerging evidence suggesting HDCT/ASCT may benefit patients with PMNSGCT - both as first-line sequential treatment after standard-dose chemotherapy and at relapse. Objectives: Review the experience of patients presenting with PMNSGCT to a regional referral cancer center as a quality control assessment. Assess the benefit of salvage HDCT/ASCT to relapsed PMNSGCT patients. Methods: Patients presenting with PMNSGCT from 1980-2010 were abstracted from a Provincial cancer registry and records were retrospectively reviewed. Data includes patient demographics, cancer treatments and outcomes. Results: Fourteen male patients (median age 29; range: 17-54 years) with PMNSGCT were identified. Seven of 13 (54%) patients remain continuously disease-free with 1 patient lost to follow-up. Mean duration of follow-up in these patients is 57 (34-100) months. Three patients died having received ≤ 1 cycle of chemotherapy; exclusion of these patients results in a treatment failure rate of 30%. Six of the 7 cancer-free patients required salvage surgery. Three patients received tandem HDCT/ASCT (carboplatin 550 mg/m2 and etoposide 150 mg/m2daily for 4 days) at subsequent relapse despite second-line chemotherapy. Two remain disease-free at 45 and 74 months respectively, while the third patient died of their disease 14 months post-transplant. Conclusions: Our experience with PMNSGCT is generally consistent with published outcomes in that ≈50% of patients are cured. However, in this series 2/3 heavily pretreated patients were salvaged with HDCT/ASCT, refuting the published historical experience. This study is limited by its small sample size, but provides impetus to re-examine HDCT/ASCT for high-risk patients.

A retrospective analysis of patients with poor-risk germ cell tumor (PRGCT) treated at Indiana University from 2000 to 2010.

4557 Background: PRGCT represents 14% of germ cell tumors, with 2-year PFS of 50%. PRGCT is defined by primary mediastinal non-seminomatous germ cell tumor (PMNSGCT), non-pulmonary visceral metastasis (NPVM), AFP > 10,000 or hCG > 50,000. This analysis attempts to identify subsets of patients with more or less favorable outcomes among the poor risk groups. Methods: Retrospective analysis of all patients with testicular cancer seen at Indiana University (IU) from 2000-2010. 291 patients with PRGCT identified of whom 79 received initial therapy at IU. We analyzed the following variables: primary site testis/retroperitoneal (T/RP) vs. PMNSGCT, pulmonary vs. NPVM, and the amplitude of serum tumor markers. We identified groups of patients according to the level of tumor marker elevation with cutoff points of AFP 20,000 and hCG 200,000. Results: Mean age 29, mean AFP 8,283, mean hCG 185,667. 24% had PMNSGCT, 48% NPVM, 11% AFP>20,000, and 25% hCG>200,000. When hCG was analyzed as a continuous variable, every 10,000 unit increase in hCG caused the hazard of progression to increase by 1% (p value 0.01). Patients with NPVM had significantly worse PFS. NPVM with elevated hCG had worse outcome than NPVM with normal hCG. This did not correlate as well with AFP. PFS was worse with NPVM than elevated pre-chemotherapy tumor markers. Multiple different criteria for poor risk disease carried significantly worse impact on PFS and OS when compared to having a single criterion for poor risk disease. Conclusions: Our data indicate that patients with NPVM or more than one criteria for PRGCT have a worse outcome compared to other PRGCT subgroups. [Table: see text]

A Case of Sarcoidosis Disseminated to Skeletal Tissues

Sarcoidosis is a systemic granulomatous disease of unknown etiology that typically affects young adults. Diagnostic criteria for sarcoidosis include involvement of two or more of the following organ systems: 1) pulmonary infiltrates; 2) bilateral hilar adenopathy; and 3) skin and/or eye lesions. Musculoskeletal system is less commonly involved. For that reason potential presenting symptoms can vary and make the diagnosis very challenging; particularly if a patient has symptoms that mimic other conditions. Musculoskeletal involvement for example can mimic malignancy. The following case describes a patient with known history of primary metastatic mediastinal Germ Cell Tumor (GCT) with teratomatous elements who is diagnosed with sarcoidosis involving skeletal tissues.

Outcomes of combined modality therapy for patients with stage III or IV mediastinal malignant germ cell tumors

The treatment of primary mediastinal germ cell tumors with cisplatin-based chemotherapy followed by surgery is an established practice; however, the prognosis has remained poor. This study reviews the survival outcomes of patients with primary mediastinal germ cell tumors to evaluate the efficacy of our treatment. We retrospectively reviewed 11 consecutive patients with primary mediastinal germ cell tumors. We had treated four patients with seminomas and seven patients with non-seminomas. Ten patients had undergone cisplatin-based chemotherapy. All patients underwent complete resection. Two patients showed a failure of first-line chemotherapy and thus received salvage chemotherapies, including paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide (TI-CE) with stem cell transplantation. One of them died of relapse 29 months later; while the other patient remained disease-free for 56 months postoperatively. The postoperative overall 3-year survival rates of the patients with non-seminomas and seminomas were 83 and 100%, respectively. Complete resection after establishing normalized or decreased at a low-level serum tumor markers plateau plays a crucial role in the management of patients with primary mediastinal malignant germ cell tumors.

Long-term mortality in patients with germ cell tumors: Effect of primary cancer site on cause of death

ObjectivesTo examine the effect of extragonadal tumor site on the risk for cardiovascular, hematopoietic malignancies, and solid cancer-related causes of death. Patients and methodsMale patients diagnosed with germ cell tumors (GCTs) between 1973 and 2008 were identified from the Surveillance, Epidemiology and End Results database, and stratified by the site of primary cancer (mediastinal and nonmediastinal extragonadal vs. gonadal). Using competing risk analysis restricted to events that happened at least 5 years after diagnosis, we examined the possible effect of primary tumor site on the risk for death related to hematopoietic malignancies, cardiovascular disorders, and solid cancers in the study cohort. ResultsOf 37,283 patients included in our analysis, 17,715 were diagnosed with nonseminomas and 19,568 with seminomas. Eight hundred and twenty four patients (2%) were diagnosed with primary mediastinal GCTs and 1,469 (4%) with nonmediastinal extragonadal tumors. Patients with mediastinal GCTs had an increased risk for death related to hematopoietic malignancies (hazard ratio [HR] = 8.84; 95% confidence interval [CI]: 3.16–24; P<0.0001) and cardiovascular disorders (HR = 4.45; 95% CI: 2.52–8.0; P<0.0001), but no significant difference in risk of dying of solid cancers (HR = 1.46; 95% CI: 0.36–5.9; P = 0.59) compared to patients with gonadal GCTs. Patients with nonmediastinal extragonadal GCTs had a significantly increased risk for dying of cardiovascular disorders (HR = 2.75; 95% CI: 1.67–4.51; P<0.0001), but not a significantly different risk for dying of hematopoietic malignancies (HR = 0.93; 95% CI: 0.13–6.84; P = 0.94) or solid cancers (HR = 1.45; 95% CI: 0.68–5.0; P = 0.23) compared with patients with gonadal GCTs. ConclusionsPatients with GCTs and extragonadal primary sites have an increased risk for death from cardiovascular disease and hematopoietic malignancies compared to those with gonadal GCTs, and could benefit from more intense preventive measures to decrease the risk of death related to these disorders.

集学的治療を行ったSomatic-type malignancyを伴う縦隔原発胚細胞性腫瘍の1例

背景：Somatic-type malignancyを伴う縦隔原発胚細胞性腫瘍は稀であり予後が不良とされている．症例：18歳男性．主訴は右前胸部痛．前縦隔に14×11 cmの腫瘍を指摘された．経皮的針生検で縦隔原発胚細胞性腫瘍と診断され，BEP療法（bleomycin, etoposide, cisplatin）を4コース施行した．腫瘍マーカー（AFP）は低下したが，頭部MRIで数ミリ大の多発転移を指摘された．縦隔の腫瘍は巨大で，脳以外の転移を認めないことから，脳転移に対しガンマナイフ治療後，縦隔腫瘍切除術，心嚢肺合併切除を行い，完全切除が可能であった．組織学的に大部分は成熟奇形腫で，免疫組織学的にgerm cell tumor with somatic-type malignancyと診断された．多発脳転移の再発に対して定位放射線照射を行い，その後再発病巣を認めていない．

Staging of Primary Mediastinal Tumors

Primary mediastinal tumors, with the exception of lymphoma, are generally rare neoplasms. The diagnosis, classification, and treatment of these tumors still cause some degree of difficulty due to their low incidence and morphologic heterogeneity. This is particularly true for thymic epithelial neoplasms, that is, thymoma and thymic carcinoma, and also applies to primary neuroendocrine carcinomas of the thymus and primary mediastinal germ cell tumors. The appropriate staging of these tumors, likewise, has been a matter of debate over the years and numerous proposals for the staging of thymic epithelial neoplasms have been put forward in the last few decades. Unfortunately, variations of such proposals have been used in some instances to stage other tumors such as thymic neuroendocrine carcinomas and germ cell tumors, which has led to the often inappropriate use of a single staging system for different types of tumors with different biological behavior. This review will provide an overview of the staging of primary mediastinal tumors with special emphasis on more recent assessments in this particular area.

P2-139 - Acute Megakaryocytic Leukemia Associated with Primary Mediastinal Germ Cell Tumor: A Case Report

ABSTRACT A 29-year-old man was referred to our hospital complaining of chest pain and dyspnea on exercise. Computed tomography (CT) scan demonstrated a 9 × 8 cm mass in the left-sided anterior mediastinum. An ultrasonography showed no mass in the bilateral testis. A CT-guided biopsy was carried out twice but a few clusters of malignant tumor cells from uncertain histology could be obtained. On the basis of predominant midline tumor distribution, relatively young patient's age, male sex and increased serum hCG, b-hCG, AFP and LDH, we diagnosed primary mediastinal germ cell tumor (PMGCT), cT1N0M0S2, stage IIIB, with IGCCCG poor risk. He received standard cisplatin, etoposide and bleomycin (BEP) chemotherapy and the tumor markers returned to the normal level after two cycles of BEP. After he received four cycles of BEP, the tumor markers remain within normal range but a CT scan showed increased size of the mass. He underwent surgical resection of the mass. The pathologic examination revealed a remaining non-seminomatous tumor mainly composed of teratoma. He was planned to receive additional two cycles of BEP. Approximately one month after surgery, the serum LDH level rose. The hCG and AFP remained within normal ranges and a CT scan showed no evidence of recurrence of PMGCT. After he received an additional cycle of BEP, the serum LDH continued to rise for a month and finally large atypical cells appeared in the peripheral blood, which were count for 3% of the whole blood cells. Bilateral bone marrow aspiration resulted in dry tap, and bone marrow biopsy confirmed a diagnosis of acute megakaryocytic leukemia (M7) by the French–American–British (FAB) classification. He received induction chemotherapy of idarubicin–cytarabine for the leukemia.

1539P - Primary Mediastinal Germ Cell Tumour in Pakistani Population; a Single Center Experience

ABSTRACT Introduction Primary mediastinal germ cell tumor (PMGCT) constitutes a rare malignancy and is a diagnostic challenge because of the difficult approach and often small size of the biopsy specimen. These tumours have a worse prognosis than their gonadal counterparts. This study was performed to review clinical characteristics, therapeutic strategies and outcome of patients with PMGCT at Shaukat Khanum Memorial Cancer Hospital and Research Center Lahore Pakistan. Patient and method Medical records of patients treated in our hospital during 1996 to 2012 were retrospectively studied. Results Of 25 patients, 23 were males with a median age of 23 years (range 16–48). Forty percent were seminoma and 60% were nonseminoma. More than 80% of nonseminoma had raised baseline alpha feto protein. The clinical presentation in order of frequency included; dyspnea (72%), cough (68%), chest pain (56%), pleural/pericardial effusion (44%), weight loss (32%), fever (28%), superior vena-caval obstruction (24%), cervical node metastasis (20%) and pulmonary metastasis (12%). All were treated with initial standard platinum based chemotherapy. Eighty percent of our patients achieved biochemical complete response and 80% achieved radiological response (67% Partial response, 13% complete response). Median survival of patients with seminoma was 37 months with three year survival rate of 60%. Median survival of patients with nonseminoma was 13 months with three year survival rate of 31%. During study period eleven patients died (seven had disease progression, 02 had bleomycin lung toxicity and two had neutropenic sepsis). Conclusion Nonseminoma constitutes the majority of primary mediastinal germ cell tumors, with prominent male preponderance. Seminomas had a better outcome than nonseminomas. Cisplatin based chemotherapy continues to be an effective treatment for these tumours. Disclosure All authors have declared no conflicts of interest.

789O - The TAXIF II Protocol Final Results: A Phase II Trial of High-Dose Chemotherapy Supported by Haematopoietic Stem Cell Transplantation in Patients with Disseminated Germ-Cell Tumors Failing Chemotherapy and with Adverse Prognostic Factors

ABSTRACT Background High-dose chemotherapy (HDCT) has been shown to circumvent resistance in poor-prognosis germ cell tumors (GCT), mainly for patients whose relapses occur more than 4 weeks after cisplatin-based CT. Patients and methods This multicentric phase II trial was addressed to patients with poor-prognosis non-refractory GCTs. The main objectives were to determine the complete response rate and to monitor treatment-associated toxicities. Patients with adverse prognostic factors failing CT were to receive 2 cycles combining Epirubicin and Paclitaxel (EpiTax), followed by 3 consecutive HDCT [one using a Paclitaxel/Thiotepa association, 2 using the 5-day Ifosfamide-Carboplatine-Etoposide regimen]. Inclusion criteria included seminomatous GCT in relapse after 2 lines of CT, non-seminomatous GCT in relapse after 1 or 2 lines, partial remission after 1 line, primary mediastinal GCT in first relapse. Peripheral blood stem cells were collected after the EpiTax cycles. Results Between 09/2004 and 12/2007, 45 patients were included: 45 received 1 HDCT, 39 two HDCT, 29 patients received the complete protocol. Sixteen patients did not received the entire protocol, 8 (53%) for toxic side effects. Two patients (4.4%) died of toxicities, 17 (37.7%) of disease progression. For a median follow-up time of 26 months (4–51 m), the final overall response rate was 66,7% (CR, 20,6%). The median PFS was 16 months (95%CI, 9-NA) and the median OS was 32 months (95%CI, 32–49). The 2-year PFS was a plateau set up at 50% (95%CI, 32-67%) and the 2-year OS was 71% (95%CI, 52–83%). Conclusion The TAXIF II protocol was highly effective in non-refractory GCT patients failing CT. Disclosure F. Selle: consultancy for roche and Pharmamar. All other authors have declared no conflicts of interest.

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.

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.

Endocrine dysfunction in Taiwanese children with human chorionic gonadotropin-secreting germ cell tumors

Human chorionic gonadotropin (HCG)-secreting germ cell tumors (GCTs) are rare childhood malignancies with unique clinical manifestations but delayed diagnosis is common. The purpose of this study is to investigate the clinical manifestations and endocrine dysfunction of Taiwanese children with HCG-secreting GCTs. From 1991 to 2011, 24 children (19 boys and five girls) with HCG-secreting GCTs were evaluated for their clinical findings and endocrine functions. The mean age at diagnosis of the study patients was 10.8±3.1 years. Of the 24 patients, 20 had central nervous system (CNS) GCTs and four had primary mediastinal GCTs (PMGCTs). The most common pathologic findings were germinomas and mixed type GCTs. The common initial symptoms and signs included polyuria, polydipsia, rapid growth, neurologic deficit,sexual precocity, and growth retardation. There was a delay in diagnosis in about 60% of patients. Diabetes insipidus and hypopituitarism were common endocrine dysfunctions in patients with CNSGCTs. Twelve boys had gonadotropin-independent puberty upon diagnosis, which were related to their high serum β-hCG levels. None of the five girls had this disorder despite their high serum β-hCG levels. Three of the four PMGCTs patients had the classic form of Klinefelter syndrome. Taiwanese children with HCG-secreting GCTs often have clinical manifestations related to endocrine dysfunction. High index of suspicion is important to avoid delayed diagnosis in these children.

Successful treatment of a primary mediastinal germ cell tumour complicated by hemophagocytic syndrome

Asia-Pacific Journal of Clinical OncologyVolume 8, Issue 4 p. e97-e98 Other topics in cancer Successful treatment of a primary mediastinal germ cell tumour complicated by hemophagocytic syndrome Matthew BURGE, Corresponding Author Matthew BURGE Royal Brisbane and Women's Hospital, BrisbaneDr Matthew Burge MD, Cancer Care Services, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia. Email: [email protected]Search for more papers by this authorMohammed F ISLAM, Mohammed F ISLAM Gold Coast Hospital, Gold CoastSearch for more papers by this authorKirk MORRIS, Kirk MORRIS Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this authorMorgan WINDSOR, Morgan WINDSOR The Prince Charles Hospital, Brisbane, Queensland, AustraliaSearch for more papers by this authorJoanna PERRY-KEENE, Joanna PERRY-KEENE Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this authorCameron CURLEY, Cameron CURLEY Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this author Matthew BURGE, Corresponding Author Matthew BURGE Royal Brisbane and Women's Hospital, BrisbaneDr Matthew Burge MD, Cancer Care Services, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia. Email: [email protected]Search for more papers by this authorMohammed F ISLAM, Mohammed F ISLAM Gold Coast Hospital, Gold CoastSearch for more papers by this authorKirk MORRIS, Kirk MORRIS Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this authorMorgan WINDSOR, Morgan WINDSOR The Prince Charles Hospital, Brisbane, Queensland, AustraliaSearch for more papers by this authorJoanna PERRY-KEENE, Joanna PERRY-KEENE Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this authorCameron CURLEY, Cameron CURLEY Royal Brisbane and Women's Hospital, BrisbaneSearch for more papers by this author First published: 19 April 2012 https://doi.org/10.1111/j.1743-7563.2011.01460.xCitations: 1 The authors confirm that no potential conflicts of interest exist. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume8, Issue4December 2012Pages e97-e98 RelatedInformation

Germ cell tumour compressing the right atrium

Germ cell tumours are relatively rare and most commonly described in the gonads. These tumours can also be seen in other locations, such as in the retroperitoneum, the pineal gland, mediastinum, and sacral area. Primary mediastinal germ cell tumours are very rare and have been documented in the literature as only sporadic cases [1].

Combination of paclitaxel, cisplatin, and gemcitabine (TPG) as third- to fourth-line therapy for male germ cell tumors (GCT).

341 Background: Rescue of patients (pts) who fail to be cured following 2–3 chemotherapy (CT) combinations ± high dose CT (HDCT) or who are cisplatin-refractory is still an unmet need. The identification of novel active agents/combinations is a priority. Methods: We reviewed the characteristics of consecutive pts who received TPG combination at our Institution for relapse/progression after 2 or 3 previous platinum-based CT lines. Treatment consisted of the administration of paclitaxel 80 mg/m2 IV, cisplatin 50 mg/m2 IV and gemcitabine 800 mg/m2 IV on days 1 and 8 q3w. Program provided up to 8 administrations of TPG followed by surgery of all resectable masses. Paraffin slides of all cases with residual viable cancer after TPG were retrieved: CD30 staining and somatic mutation analysis by Sequenom OncoCarta Panel v.1.0 were planned. Results: From 04/1999 to 07/2011, 74 pts have been treated with TPG, 64 in 3rd and 10 pts in 4th line. Median age was 32 (20–55), median number of prior CDDP cycles was 7 (4–10), 10 pts (13%) had already received HDCT, 4 pts had primary mediastinal GCT, 42 (57%) were CDDP-refractory/abs refractory, 25 pts (34%) had either liver, bone or brain metastases before TPG. 40% developed G3-4 hematologic and 2 pts G3 renal toxicity, none of them being dose-limiting. No treatment delays have been observed. Median number of administrations was 7 (1–10). 8 complete responses (CR), 28 partial responses with normal markers (PRm-) and 13 incomplete response/stable disease have been recorded, for a major response rate (CR+PRm-) of 49%. 34 pts (46%) underwent post-CT surgery which was radical in 15 cases (44%) and led to 7 pathologic CR. 3-, 6- and 12-month PFS was 68% (95% CI 55–76%), 31% (21–42) and 20% (12–30), respectively. 1-yr PFS after HDCT only was 24% (4–53). 12- and 24-month OS was 46% (34–57) and 26% (16–37), respectively. Median PFS and OS were 5 (1–104) and 12 mos (1–116). Conclusions: TPG combination rates first among salvage therapies for refractory GCT, even after failure of HDCT. Benchmark survival endpoints for trials on new agents/combinations have been set. Results of the biomarker analysis will be available in Feb 2012 and may help to corroborate a window of opportunity for targeted agents in GCT.

Attenuation of Spermatogonial Stem Cell Activity in Cryptorchid Testes

To elucidate the mechanism of infertility caused by cryptorchidism we focused on early stage spermatogenesis and spermatogonial stem cell activity in undifferentiated spermatogonia in cryptorchid testes. Histological findings and expression patterns of the stem cell marker undifferentiated embryonic cell transcription factor 1 were examined in a unilateral cryptorchid rat model. We removed unilateral descended testis and contralateral descended testis from cryptorchid and normal rats (control), respectively, 18 days postcoitum to 144 days postpartum. In descended testes gonocyte differentiation into early A spermatogonia occurred at 9 days postpartum. However, this transformation was altered in undescended testes. Furthermore, the undifferentiated embryonic cell transcription factor 1 negative early A spermatogonia-to-positive early A spermatogonia ratio was significantly higher in the undescended testis group (mean ± SD 0.69 ± 0.04) than in the control (0.46 ± 0.10, p = 0.037) and descended testis (0.44 ± 0.05, p = 0.022) groups, indicating decreased early A spermatogonia with spermatogonial stem cell activity in cryptorchid testes. In cryptorchid testes the differentiation from gonocytes into early A spermatogonia and the stem cell activity of early A spermatogonia were altered during the early stage of spermatogenesis, suggesting that the loss of spermatogonial stem cell activity in cryptorchid rats resulted in altered spermatogenesis, thus interfering with fertility.

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.