Male Germ Cell Tumors Research Articles

Emerging Therapeutic Targets for Male Germ Cell Tumors.

Male germ cell tumors (GCTs) are curable cancers, yet 10-15% of patients with metastatic disease fail cisplatin-based first-line treatments. While therapeutic options have increased for various other cancers, little progress has been made in the management of GCT in the last decades. A better understanding of the molecular alterations underlying the disease and identification of new therapeutic targets are needed. Several phase I/II studies with promising new agents are ongoing or have been completed, but most of those trials have been small and have not included translational research. Therefore, molecular profiles predictive for response or new agents have not been identified in male GCT so far. The purpose of this review is to highlight emerging targets and therapies with the potential to improve systemic treatment of metastatic male GCT and to develop strategies for future clinical trials.

Pre-pubertal and adolescent germ cell neoplasms in Taiwan: time trends and geographic variation.

Evidence from our previous study suggested that the incidence of germ cell neoplasms in children and adolescents is increasing. The objectives of this analysis were to quantify this trend in patients aged 0-9 and 10-19years (pre-pubertal and adolescent groups, respectively) and compare rates in Taiwan according to geographic distribution. Germ cell neoplasm frequencies among 1267 patients aged 0-19years spanning 1995-2009 were obtained from the population-based Taiwan Cancer Registry. The incidence patterns according to sex, age, disease subgroup, and geographic distribution were analyzed. The incidence rates in the pre-pubertal and adolescent groups were 10.58 and 16.06 per million person-years, respectively. The overall rates increased significantly by 3.2% annually in the adolescent group during the 15-year study period, and increased only among the males. In contrast, no change in trend was observed in the pre-pubertal group. Subgroup analysis showed significant upward trends in the incidence rates of intracranial/intraspinal and testicular germ cell tumors (GCTs) in the adolescent males and extracranial/extragonadal GCTs in the pre-pubertal boys. The most striking differences between the study population and white Americans were that the rates of testicular GCTs were 5-fold higher and 4-fold lower in the Taiwanese pre-pubertal and adolescent groups, respectively. Significantly higher rates were found in Hualien and Chiayi Counties compared with the other areas of Taiwan. The upward trend of testicular GCTs in the adolescent males is consistent with findings from Western countries. The underlying causes that led to the high rate of testicular GCTs in the pre-pubertal boys and significantly higher rates in specific counties warrant further investigation.

Development of a risk stratification system to guide treatment for female germ cell tumors

ObjectiveDue to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. MethodsChart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome. ResultsOf 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76–92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12). ConclusionsModified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT.

Epidemiology of male seminomatous (SGCT) and non-seminomatous germ cell tumours (NSGCT) and response to first line chemotherapy (CT) from a tertiary cancer centre in India.

e15553 Background: Unlike the developed countries, there is lack of good epidemiologic data for testicular GCTs in India. The epidemiology tends to differ from that of developed countries with a fa...

Update in germ cell tumours.

The purpose of this study is to update the reader on advances in postpubertal male germ cell tumours (GCTs) over the last 18 months. Single nucleotide polymorphisms, including in four sex-determination genes, have been identified as additional genetic susceptibility loci to testicular GCT development. New insights into cisplatin resistance implicate the PDGFR-PIK3CA-AKT and RAS pathways. Circulating tumour cells and circulating microRNAs are potential new biomarkers. In clinical stage I (CS-I) GCT, two large studies have confirmed the excellent outcomes achieved with surveillance, which is now the management option of choice for CS I-A nonseminoma and all CS-I seminomas; CS I-B nonseminoma remains controversial. First-line trials of dose-dense multidrug regimens reported promising results but have not yet supplanted BEPx4. Survivorship issues, including secondary malignancies from chemotherapy, remain important in this disease and are a continuing focus of ongoing research. Important research questions remain across all aspects of GCT. The next decade is likely to produce many new and exciting discoveries that will benefit GCT patients.

The efficacy of radio-frequency ablation for metastatic lung or liver tumors of male germ cell tumors as an alternative minimally invasive therapy after salvage chemotherapy.

The aim of this study was to assess the efficacy of radio-frequency ablation (RFA) for metastatic lung or liver tumors of germ cell tumors (GCTs) after chemotherapy. RFA with computed tomography guidance and monitoring was performed in 24 patients with 48 metastatic lung or liver tumors of GCTs. Group A consisted of 9 patients with tumor marker normalization after salvage chemotherapy and group B consisted of 15 patients without tumor marker normalization in spite ofintensive treatment. Out of 48 tumors, 41 tumors in 21 patients were evaluated for the efficacy of the RFA treatment. Of the 41 tumors, successful ablation was achieved in 34 (82.9 %). The patients in group A had significantly better survival than the patients in group B (p = 0.0003). In group A, all 9 patients are still alive with no evidence of disease (NED). Patients with a solitary tumor had significantly better survival than those with multiple tumors (p = 0.0247). In group B, 2 patients are alive with NED, 1 patient is alive with disease, and the remaining 12 patients have died a tumor-related death. Three cases of pneumothorax requiring intubation were observed. RFA is less invasive than surgery and is an effective treatment option for curative and palliative therapy as an alternative to invasive salvage surgery for post-chemotherapeutic metastatic lung or liver lesions from GCT.

Interrogation of a context-specific transcription factor network identifies novel regulators of pluripotency.

The predominant view of pluripotency regulation proposes a stable ground state with coordinated expression of key transcription factors (TFs) that prohibit differentiation. Another perspective suggests a more complexly regulated state involving competition between multiple lineage-specifying TFs that define pluripotency. These contrasting views were developed from extensive analyses of TFs in pluripotent cells in vitro. An experimentally validated, genome-wide repertoire of the regulatory interactions that control pluripotency within the in vivo cellular contexts is yet to be developed. To address this limitation, we assembled a TF interactome of adult human male germ cell tumors (GCTs) using the Algorithm for the Accurate Reconstruction of Cellular Pathways (ARACNe) to analyze gene expression profiles of 141 tumors comprising pluripotent and differentiated subsets. The network (GCT(Net)) comprised 1,305 TFs, and its ingenuity pathway analysis identified pluripotency and embryonal development as the top functional pathways. We experimentally validated GCT(Net) by functional (silencing) and biochemical (ChIP-seq) analysis of the core pluripotency regulatory TFs POU5F1, NANOG, and SOX2 in relation to their targets predicted by ARACNe. To define the extent of the in vivo pluripotency network in this system, we ranked all TFs in the GCT(Net) according to sharing of ARACNe-predicted targets with those of POU5F1 and NANOG using an odds-ratio analysis method. To validate this network, we silenced the top 10 TFs in the network in H9 embryonic stem cells. Silencing of each led to downregulation of pluripotency and induction of lineage; 7 of the 10 TFs were identified as pluripotency regulators for the first time.

A 20-year retrospective study of histopathologic patterns of gonadal germ cell tumors in males in the University of Benin Teaching Hospital.

Background:Localization of germ cells tumors to the gonads is not uncommon and has been shown to possess good prognosis with appropriate treatment. Studies on the prevalence and histopathologic features of these tumors in Nigerians are, however, rare. This study was, therefore, aimed at determining the pattern of gonadal germ cell tumors (GGCTs) in Benin and environs.Materials and Methods:This was a 20-year retrospective study conducted at the University of Benin Teaching Hospital 9-(UBTH), a tertiary health facility in Benin City. Data were obtained from the histopathology day book of the Department of Morbid Anatomy of the UBTH, and permission was obtained from the UBTH Ethics Committee protocol number ADM/E 22/A/VOL.VH/928 with results displayed in tables and figures.Results:Intratubular germ cell neoplasms (ITGN) was the most common GGCT with about 33.3% of the total and was distributed within the fourth to fifth decades of life; benign cystic teratoma and choriocarcinoma were observed to have a low occurrence with 8.3% each found in age groups 11–20 and 21–30 years, respectively. The studied gonadal lesions were most frequent at the left testis and were predominantly premalignant forms.Conclusion:This was an index study on patterns of GGCTs in males in UBTH, and it showed that GGCTs in males were predominantly premalignant with ITGN as the most common type of testicular germ cell tumors.

Use of appropriate initial treatment among adolescents and young adults with cancer.

There has been little improvement in the survival of adolescent and young adult (AYA) cancer patients aged 15 to 39 years relative to other age groups, raising the question of whether such patients receive appropriate initial treatment. We examined receipt of initial cancer treatment for a population-based sample of 504 AYAs diagnosed in 2007-2008 with acute lymphoblastic leukemia (ALL), Hodgkin's or non-Hodgkin's lymphoma, germ cell cancer, or sarcoma. Registry data, patient surveys, and detailed medical record reviews were used to evaluate the association of patient demographic, socioeconomic, and health care setting characteristics with receipt of appropriate initial treatment, which was defined by clinical specialists in AYA oncology based on adult guidelines and published literature available before 2009 and analyzed with multivariable logistic regression. All statistical tests were two-sided. Approximately 75% of AYA cancer patients in our sample received appropriate treatment, 68% after excluding stage I male germ cell patients who all received appropriate treatment. After this exclusion, appropriate treatment ranged from 79% of sarcoma patients to 56% of ALL patients. Cancer type (P < .01) and clinical trial participation (P = .04) were statistically significantly associated with appropriate treatment in multivariable analyses. Patients enrolled in clinical trials were more likely to receive appropriate therapy relative to those not enrolled (78% vs 67%, adjusted odds ratio = 2.6, 95% confidence interval = 1.1 to 6.4). Except for those with early stage male germ cell tumors, approximately 30% (or 3 in 10) AYA cancer patients did not receive appropriate therapy. Further investigation is required to understand the reasons for this potential shortfall in care delivery.

813PD - Brain Metastases in Male Germ Cell Tumors (Gct): a Large Retrospective Analysis on Behalf of the Swenoteca and the G3 Consortium

ABSTRACT Aim: Characteristics, treatment and outcome of patients (pts) with brain metastases (BMet) from GCT are largely unknown due to a lack of data. We addressed these issues in a large international retrospective cohort. Methods: Data on pts diagnosed with BMet between 1990 and 2013 was retrospectively collected across 46 institutions worldwide. Data collection and analyses followed a predefined protocol and had obtained appropriate ethical approval. Univariate analysis was used to identify prognostic factors. The Kaplan Meier method was used to assess outcome. Results: Data on 523 patients were collected: 228 (44%) in pts with BMet at initial diagnosis (group A) and 295 (56%) in pts with BMet at relapse (group B), 150 (31%) pts were asymptomatic at presentation. Median age was 29 years (range 16-67 years). Median follow-up after diagnosis of BMet was 7 years. Pts from group A had a significantly better PFS (median 6.9 versus 3.6 months, HR 0.60: 95%CI; 0.49 – 0.73; P Conclusions: Conclusions: Pts with GCT and BMet can be cured. Pts with BMet at initial diagnosis and those with solitary BMet have superior outcomes compared to pts with BMet at relapse or with multiple BMet lesions. Surgery and/or radiotherapy in addition to chemotherapy as well as HDCT in pts with BMet at relapse may improve survival. Disclosure: All authors have declared no conflicts of interest.

Female germ cell tumors (GCT): The Memorial Sloan Kettering Cancer Center (MSKCC) experience.

5539 Background: Due to their rarity, little is known about female GCT biology and response to therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer. Methods: We...

Aza-deoxycytidine induces apoptosis or differentiation via DNMT3B and targets embryonal carcinoma cells but not their differentiated derivatives

Background:Teratocarcinoma is a malignant male germ cell tumour, which contains stem cells and differentiated cancer tissues. DNMT3B has been shown to be highly expressed in human teratocarcinoma stem cells, and to mediate cytotoxicity of Aza-deoxycytidine (Aza-dC) in a pluripotent stem cell line NTERA2.Methods:We have established DNMT3B or POU5F1 (hereafter referred to as OCT4) knockdown in teratocarcinoma stem cells N2102Ep and TERA1 and in the pluripotent NTERA2 by a doxycycline-inducible system, and tested the cytotoxicity induced by Aza-dC.Results:Silencing of DNMT3B led to apoptosis of human teratocarcinoma stem cells N2102Ep and TERA1. Further, we found that induction of apoptosis or differentiation in NTERA2 and human embryonic stem cells by Aza-dC requires DNMT3B. To test whether Aza-dC inhibits proliferation of differentiated teratocarcinoma cells, we depleted OCT4 expression in N2102Ep and TERA1 cells treated with Aza-dC. Treatment with Aza-dC reduced cell number of differentiated cells to a lesser extent than their undifferentiated parental stem cells. Moreover, in contrast to the stem cells, Aza-dC failed to induce apoptosis of differentiated cells.Conclusions:Our finding suggests that DNMT3B acts as an antiapoptotic gene in teratocarcinoma stem cells, and mediates apoptosis and differentiation of human pluripotent stem cells induced by Aza-dC, and that Aza-dC specifically induces apoptosis of teratocarcinoma stem cells.

All-trans-retinoic acid antagonizes the hedgehog pathway by inducing patched

Male germ cell tumors (GCTs) are a model for a curable solid tumor. GCTs can differentiate into mature teratomas. Embryonal carcinomas (ECs) represent the stem cell compartment of GCTs and are the malignant counterpart to embryonic stem (ES) cells. GCTs and EC cells are useful to investigate differentiation therapy and chemotherapy response. This study explored mechanistic interactions between all-trans-retinoic acid (RA), which induces differentiation of EC and ES cells, and the Hedgehog (Hh) pathway, a regulator of self-renewal and proliferation. RA was found to induce mRNA and protein expression of Patched 1 (Ptch1), the Hh ligand receptor and negative regulator of this pathway. PTCH1 is also a target gene of Hh signaling through Smoothened (Smo) activation. Yet, this observed RA-mediated Ptch1 induction was independent of Smo. It occurred despite co-treatment with RA and Smo inhibitors. Retinoid induction of Ptch1 also occurred in other RA-responsive cancer cell lines and in normal ES cells. Notably, this enhanced Ptch1 expression was preceded by induction of the homeobox transcription factor Meis1, a direct RA target. Direct interaction between Meis1 and Ptch1 was confirmed using chromatin immunoprecipitation assays. To establish the translational relevance of this work, Ptch1 expression was shown to be deregulated in human ECs relative to mature teratoma and the normal seminiferous tubule. Taken together, these findings reveal a previously unrecognized mechanism through which RA can inhibit the Hh pathway via Ptch1 induction. Engaging this pathway is a new way to repress the Hh pathway that can be translated into the cancer clinic.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes

BackgroundSince 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over the original regimen. Patients and MethodsPatients received four cycles of ifosfamide at 2.5 g/m2 on days 1–2, etoposide, and cisplatin at 100 and 33 mg/m2, respectively, on days 3–5 every 21 days, followed by surgery. Results were stratified according to the International Germ Cell Consensus Classification Group-2 (IGCCCG-2). ResultsFrom February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm-). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4–232.0). Two-year progression-free and 5-year overall survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively. Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3–4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded. ConclusionDose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage setting.

RETRACTED ARTICLE: Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

BackgroundDNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation.CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners.In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors.MethodsTo achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses.ResultsThe analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H2O2, the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased.ConclusionsTherefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants and contributes to testicular neoplastic growth.

Current controversies in the management of germ cell ovarian tumours

Fewer than 70 new cases of malignant ovarian germ cell tumours (MOGCTs) are seen each year in the UK. Because of their rarity, no randomized trials have been reported and many of the advances in management have arisen from adopting practices developed for managing male germ cell tumours (GCTs). Not surprisingly, there have been few important publications related to ovarian germ cell tumuors over the past 2 years. We have therefore included some relevant male germ cell publications. The area in which there is greatest variability in practice globally is in the proportion of patients with stage 1a disease who go on surveillance rather than receiving adjuvant chemotherapy. Although there is increasing agreement about the best management of ovarian GCTs amongst those who treat more than five per year, many patients are still treated by doctors who usually manage epithelial ovarian cancer but rarely see these patients. Novel biomarkers including microRNA profiles and DICER1 mutations, identify potential diagnostic and therapeutic targets in this group of tumours. The role of KIT mutation and amplification in the development of ovarian dysgerminoma and the use of Sunitinib, a receptor tyrosine kinase inhibitor with an effect on vascular endothelial growth factor, platelet-derived growth factor and KIT receptors in patients with platinum-resistant GCT, are novel promising approaches. We will therefore highlight some key differences in management of epithelial and germ cell ovarian tumours.

747 MODIFIED CISPLATIN, ETOPOSIDE AND IFOSFAMIDE (PEI) SALVAGE THERAPY FOR MALE GERM-CELL TUMORS (GCT). LONG-TERM EFFICACY AND SAFETY OUTCOMES

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disease (II)1 Apr 2013747 MODIFIED CISPLATIN, ETOPOSIDE AND IFOSFAMIDE (PEI) SALVAGE THERAPY FOR MALE GERM-CELL TUMORS (GCT). LONG-TERM EFFICACY AND SAFETY OUTCOMES Andrea Necchi, Luigi Mariani, Patrizia Giannatempo, Nicola Nicolai, Daniele Raggi, Elena Fare', Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Giorgio Pizzocaro, Alessandro Gianni, and Roberto Salvioni Andrea NecchiAndrea Necchi Milan, Italy More articles by this author , Luigi MarianiLuigi Mariani Milan, Italy More articles by this author , Patrizia GiannatempoPatrizia Giannatempo Milan, Italy More articles by this author , Nicola NicolaiNicola Nicolai Milan, Italy More articles by this author , Daniele RaggiDaniele Raggi Milan, Italy More articles by this author , Elena Fare'Elena Fare' Milan, Italy More articles by this author , Luigi PivaLuigi Piva Milan, Italy More articles by this author , Davide BiasoniDavide Biasoni Milan, Italy More articles by this author , Mario CatanzaroMario Catanzaro Milan, Italy More articles by this author , Tullio TorelliTullio Torelli Milan, Italy More articles by this author , Silvia StagniSilvia Stagni Milan, Italy More articles by this author , Giorgio PizzocaroGiorgio Pizzocaro Milan, Italy More articles by this author , Alessandro GianniAlessandro Gianni Milan, Italy More articles by this author , and Roberto SalvioniRoberto Salvioni Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.310AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. METHODS We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide, and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. RESULTS From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm-were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP>1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. CONCLUSIONS Dose-modified Italian PEI showed activity comparable with the best one achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e307-e308 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Necchi Milan, Italy More articles by this author Luigi Mariani Milan, Italy More articles by this author Patrizia Giannatempo Milan, Italy More articles by this author Nicola Nicolai Milan, Italy More articles by this author Daniele Raggi Milan, Italy More articles by this author Elena Fare' Milan, Italy More articles by this author Luigi Piva Milan, Italy More articles by this author Davide Biasoni Milan, Italy More articles by this author Mario Catanzaro Milan, Italy More articles by this author Tullio Torelli Milan, Italy More articles by this author Silvia Stagni Milan, Italy More articles by this author Giorgio Pizzocaro Milan, Italy More articles by this author Alessandro Gianni Milan, Italy More articles by this author Roberto Salvioni Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1055 Modified cisplatin, etoposide and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT). Long-term efficacy and safety outcomes

1055 Modified cisplatin, etoposide and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT). Long-term efficacy and safety outcomes

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT): Long-term efficacy and safety outcomes.

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP&gt;1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.

Post-orchidectomy retroperitoneal seminoma: A case report

Between 2 and 5% of malignant germ cell tumors in males arise at extragonadal sites. The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether these develop primarily in the retroperitoneum or are metastases of a primary testicular tumor has long been debated. We report a 38-year-old male who presented with abdominal pain and was diagnosed with retroperitoneal seminoma. The patient gave a history of having undergone a right orchidectomy for an undescended testis via the inguinal route 10 years previously with a reported histology of benign inflammatory mass.