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      Prognostic factors in patients with poor-risk germ-cell tumors: a retrospective analysis of the Indiana University experience from 1990 to 2014

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          Abstract

          <p class="first" id="d5619115e191">Survival outcomes for poor-risk germ-cell tumor treated at Indiana University (1990–2014) were improved from historical dataset in the International Germ Cell Cancer Collaborative Group (1975–1990). Among the poor-risk category, patients with primary mediastinal nonseminomatous germ-cell tumor, brain metastasis, or increasing age have a worse overall survival. </p><div class="section"> <a class="named-anchor" id="d5619115e194"> <!-- named anchor --> </a> <h5 class="section-title" id="d5619115e195">Background</h5> <p id="d5619115e197">Based on the risk stratification from the International Germ Cell Cancer Collaborative Group (IGCCCG), only 14% of patients with metastatic germ-cell tumors (GCT) had poor-risk disease with a 5-year progression-free survival (PFS) rate of 41% and a 5-year overall survival (OS) rate of only 48%. This analysis attempts to identify prognostic factors for patients with poor-risk disease. </p> </div><div class="section"> <a class="named-anchor" id="d5619115e199"> <!-- named anchor --> </a> <h5 class="section-title" id="d5619115e200">Patients and methods</h5> <p id="d5619115e202">We conducted a retrospective analysis of all patients with GCT diagnosed and treated at Indiana University from 1990 to 2014. Clinical and pathological characteristics were available for all patients and all of them were treated with cisplatin–etoposide-based chemotherapy. Cox proportional hazards models were used to target significant predictors of disease progression and mortality. A significance level of 5% was used in the analysis. </p> </div><div class="section"> <a class="named-anchor" id="d5619115e204"> <!-- named anchor --> </a> <h5 class="section-title" id="d5619115e205">Results</h5> <p id="d5619115e207">We identified 273 consecutive patients with poor-risk GCT (PRGCT). Median follow-up time was 8 years (range 0.03–24.5). The 5-year PFS and OS rates were 58% [95% confidence interval (CI) 51% to 63%] and 73% (95% CI 67% to 78%), respectively. In multivariate survival analyses, multiple risk factors were associated with disease progression, including liver metastasis, brain metastasis, primary mediastinal nonseminomatous GCT (PMNSGCT), and elevation in logarithmic β-hCG. Significant predictors of mortality were PMNSGCT [hazard ratio (HR) 4.63, 95% CI 2.25–9.56; <i>P</i> &lt; 0.001], brain metastasis (HR 3.30, 95% CI 1.74–6.23; <i>P</i> &lt; 0.001), and increasing age (HR 1.03, 95% CI 1.01–1.06; <i>P</i> = 0.02). </p> </div><div class="section"> <a class="named-anchor" id="d5619115e218"> <!-- named anchor --> </a> <h5 class="section-title" id="d5619115e219">Conclusions</h5> <p id="d5619115e221">Patients with PMNSGCT, brain metastasis, or with increasing age are at higher risk of death than their counterparts. This contemporary cohort (1990–2014) of 273 patients with PRGCT had improved PFS and OS outcomes than those from the historical IGCCCG group of patients (1975–1990). </p> </div>

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          Most cited references 13

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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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            Testicular germ-cell tumours in a broader perspective.

            The germ-cell tumours are a fascinating group of neoplasms because of their unusual biology and the spectacular therapeutic results that have been obtained in these tumours. Traditionally, this group of neoplasms is presented in an organ-oriented approach. However, recent clinical and experimental data convincingly demonstrate that these neoplasms are one disease with separate entities that can manifest themselves in different anatomical sites. We propose five entities, in which the developmental potential is determined by the maturation stage and imprinting status of the originating germ cell. Recent progress begins to explain the apparent unpredictable development of germ-cell tumours and offers a basis for understanding their exquisite sensitivity to therapy.
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              Increasing incidence of testicular cancer worldwide: a review.

              Testicular cancer (TC) is the most common malignancy in 20 to 34-year-old men. Numerous publications have shown an increase in the incidence of testis cancer in the last 40 years with substantial differences among countries. We evaluated worldwide variations in testicular cancer incidence and compared trends in different regions in the world. We reviewed 441 studies provided by a MEDLINE search using the key words testis/testicular, cancer/tumor and incidence that were published between 1980 and 2002. From these articles we selected only those devoted to testis cancer incidence and of them only the most recent studies from each country or region. Nevertheless, articles using the same data base but providing new and additional information, for example differences among ethnic groups or controversial explanations for trends, were also retained. We selected 30 articles and analyzed their methodological approach and main results. Worldwide we observed a clear trend toward an increased TC incidence in the last 30 years in the majority of industrialized countries in North America, Europe and Oceania. Nevertheless, surprising differences in incidence rates were seen between neighboring countries (Finland 2.5/100,000 cases versus Denmark 9.2/100,000) as well as among regions of the same country (2.8 to 7.9/100,000 according to various regional French registers). In addition, substantial differences in the TC incidence and trends were observed among ethnic groups. The increase in the TC incidence was significantly associated with a birth cohort effect in the United States and in European countries. To date except for cryptorchidism no evident TC risk factor has been clearly demonstrated, although the environmental hypothesis with a key role of endocrine disrupters has been put forward by several groups. Such a recent increase in the TC rate in most industrialized countries should lead urologists and andrologists to give more attention to testicular cancer symptoms in adolescents and young adults. In a public health perspective further research using cases collected through national and regional population based registers and case-control studies must be strongly encouraged if we wish to be able to assess future trends in TC incidence rates and also identify risk factors.
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                Author and article information

                Journal
                Annals of Oncology
                Ann Oncol
                Oxford University Press (OUP)
                0923-7534
                1569-8041
                April 21 2016
                May 09 2016
                : 27
                : 5
                : 875-879
                Article
                10.1093/annonc/mdw045
                4843188
                26861605
                ef15dfe2-e48e-45fd-8c3f-e82fe3071614
                © 2016

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