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      Testicular Cancer — Discoveries and Updates

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      New England Journal of Medicine
      Massachusetts Medical Society

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          International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group.

          Cisplatin-containing chemotherapy has dramatically improved the outlook for patients with metastatic germ cell tumors (GCT), and overall cure rates now exceed 80%. To make appropriate risk-based decisions about therapy and to facilitate collaborative trials, a simple prognostic factor-based staging classification is required. Collaborative groups from 10 countries provided clinical data on patients with metastatic GCT treated with cisplatin-containing chemotherapy. Multivariate analyses of prognostic factors for progression and survival were performed and models were validated on an independent data set. Data were available on 5,202 patients with nonseminomatous GCT (NSGCT) and 660 patients with seminoma. Median follow-up time was 5 years. For NSGCT the following independent adverse factors were identified: mediastinal primary site; degree of elevation of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactic dehydrogenase (LDH); and presence of nonpulmonary visceral metastases (NPVM), such as liver, bone, and brain. For seminoma, the predominant adverse feature was the presence of NPVM. Integration of these factors produced the following groupings: good prognosis, comprising 60% of GCT with a 91% (89% to 93%) 5-year survival rate; intermediate prognosis, comprising 26% of GCT with a 79% (75% to 83%) 5-year survival rate; and poor prognosis, comprising 14% of GCT (all with NSGCT) with a 48% (42% to 54%) 5-year survival rate. An easily applicable, clinically based, prognostic classification for GCT has been agreed on between all the major clinical trial groups who are presently active worldwide. This should be used in clinical practice and in the design and reporting of clinical trials to aid international collaboration and understanding.
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            Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors.

            Remarkably little is known about the transcriptional profiles of human embryonic stem (ES) cells or the molecular mechanisms that underlie their pluripotency. To identify commonalties among the transcriptional profiles of different human pluripotent cells and to search for clues into the genesis of human germ cell tumors, we compared the expression profiles of human ES cell lines, human germ cell tumor cell lines and tumor samples, somatic cell lines, and testicular tissue samples by using cDNA microarray analysis. Hierarchical cluster analysis of gene expression profiles showed that the five independent human ES cell lines clustered tightly together, reflecting highly similar expression profiles. The gene expression patterns of human ES cell lines showed many similarities with the human embryonal carcinoma cell samples and more distantly with the seminoma samples. We identified 895 genes that were expressed at significantly greater levels in human ES and embryonal carcinoma cell lines than in control samples. These genes are candidates for involvement in the maintenance of a pluripotent, undifferentiated phenotype.
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              High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors.

              Metastatic testicular tumors that have not been successfully treated by means of initial chemotherapy are potentially curable with salvage chemotherapy. We conducted a retrospective review of 184 consecutive patients with metastatic testicular cancer that had progressed after they received cisplatin-containing combination chemotherapy. We gave 173 patients two consecutive courses of high-dose chemotherapy consisting of 700 mg of carboplatin per square meter of body-surface area and 750 mg of etoposide per square meter, each for 3 consecutive days, and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells; the other 11 patients received a single course of this treatment. In 110 patients, cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin preceded the high-dose chemotherapy. Of the 184 patients, 116 had complete remission of disease without relapse during a median follow-up of 48 months (range, 14 to 118). Of the 135 patients who received the treatment as second-line therapy, 94 were disease-free during follow-up; 22 of 49 patients who received treatment as third-line or later therapy were disease-free. Of 40 patients with cancer that was refractory to standard-dose platinum, 18 were disease-free. A total of 98 of 144 patients who had platinum-sensitive disease were disease-free, and 26 of 35 patients with seminoma and 90 of 149 patients with nonseminomatous germ-cell tumors were disease-free. Among the 184 patients, there were three drug-related deaths during therapy. Acute leukemia developed in three additional patients after therapy. Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease. Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                November 20 2014
                November 20 2014
                : 371
                : 21
                : 2005-2016
                Article
                10.1056/NEJMra1407550
                25409373
                d36d019e-4d87-4d97-9350-9a40e4eaefb6
                © 2014
                Product
                Self URI (article page): http://www.nejm.org/doi/10.1056/NEJMra1407550

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