scholarly journals Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

2021 ◽  
pp. JCO.20.03296
Author(s):  
Silke Gillessen ◽  
Nicolas Sauvé ◽  
Laurence Collette ◽  
Gedske Daugaard ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Prognostic Model ◽  
Lung Metastases ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Data Set ◽  
Nonseminomatous Germ Cell Tumors

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

The Second Medical Research Council Study of Prognostic Factors in Nonseminomatous Germ Cell Tumors

1992 ◽  
Vol 10 (5) ◽  
pp. 867-867 ◽  
Author(s):  
G.M. Mead ◽  
S.P. Stenning ◽  
M.C. Parkinson ◽  
A. Horwich ◽  
S.D. Fossa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Medical Research ◽  
Research Council ◽  
Embryonal Carcinoma ◽  
Medical Research Council ◽  
Lung Metastases ◽  
Fibrous Tissue ◽  
Germ Cell Tumors ◽  
Nonseminomatous Germ Cell Tumors

In the report entitled, "The Second Medical Research Council Study of Prognostic Factors in Nonseminomatous Germ Cell Tumors" by Mead et al (J Clin Oncol 10:85–94, 1992), the second sentence in the Results section of the abstract should have read: "The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level > 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] > 10,000 IU/L); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor."

The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.

1992 ◽  
Vol 10 (1) ◽  
pp. 85-94 ◽  
Author(s):  
G M Mead ◽  
S P Stenning ◽  
M C Parkinson ◽  
A Horwich ◽  
S D Fossa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Medical Research ◽  
Research Council ◽  
Medical Research Council ◽  
Lung Metastases ◽  
Large Population ◽  
Germ Cell Tumors ◽  
Cox Regression Analysis ◽  
Nonseminomatous Germ Cell Tumors

PURPOSE To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.

scholarly journals Low Survival in Poor Prognosis Metastatic Germ Cell Cancer in Belarus

2021 ◽  
pp. 63-71
Author(s):  
Alexander I. Rolevich ◽  
Denis M. Borodin ◽  
Anton N. Rabcheuski ◽  
Tatsiana A. Ivanitskaya ◽  
Sviataslau A. Semenov ◽  
...  
Keyword(s):  
Germ Cell ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Germ Cell Cancer ◽  
High Income ◽  
Collaborative Group ◽  
Entire Cohort

PURPOSE Since the development of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification in a 1997 study, high-income countries have reported a significant increase in survival for poor prognosis patients. There are scant data on IGCCCG risk-stratified survival from low- and middle-income countries. We assessed the progression-free survival (PFS) and overall survival (OS) rates in a contemporary cohort of Belarusian patients with advanced germ cell cancer (GCC) stratified by the IGCCCG prognostic classification and analyzed prognostic factors for survival. MATERIALS AND METHODS The consecutive cohort of patients with clinical stage IIb-III testicular GCC or extragonadal germ cell tumors who received treatment or consultation in our two centers between 2010 and 2015 was included. All patients underwent primary chemotherapy. The patients were divided into seminoma and nonseminomatous germ cell carcinoma (NSGCC) subgroups. The Kaplan-Meier method was used to estimate 5-year PFS and OS. RESULTS This study included 111 patients with a median age of 32 years, 95% of whom were diagnosed with testicular cancer. Seminoma and NSGCC were identified in 32 (29%) and 79 (71%) patients, respectively. The median follow-up was 6.1 years. The 5-year PFS and OS rates for the entire cohort were 70% and 77%, respectively. In patients with good prognosis seminoma and good, intermediate, and poor prognosis NSGCC, the estimated PFS rates were 76%, 88%, 74%, and 39% and those for OS were 83%, 97%, 83%, and 38%, respectively. CONCLUSION In our cohort of Belarusian patients with advanced germ cell tumors, we failed to demonstrate an improvement in PFS and OS compared with the 1997 IGCCCG study. Moreover, survival in poor prognosis group is inferior to that in IGCCCG and all contemporary series from high-income countries.

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

1997 ◽  
Vol 15 (2) ◽  
pp. 594-603 ◽  
Keyword(s):  
Survival Rate ◽  
Prognostic Factor ◽  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Staging System ◽  
Lactic Dehydrogenase ◽  
Good Prognosis ◽  
Collaborative Group ◽  
Data Set

PURPOSE 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. MATERIALS 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. RESULTS 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. CONCLUSION 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.

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

Actionable targets in patients with cisplatin-resistant advanced germ cell tumors.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Aditya Bagrodia ◽  
Samuel D. Kaffenberger ◽  
Byron Lee ◽  
William Lee ◽  
Eugene K. Cha ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Germ Cell ◽  
Cell Cancer ◽  
Significant Proportion ◽  
Germ Cell Tumors ◽  
Targeted Sequencing ◽  
Collaborative Group ◽  
First Line ◽  
Kras Mutations ◽  
Cell Functions

473 Background: Approximately 30% of patients with advanced germ cell tumor (aGCT) will progress after first-line chemotherapy. Nearly half of these patients will die of progressive GCT. We describe potentially actionable mutations in a cohort of patients with platinum-resistant aGCT through targeted sequencing. Methods: 76 patients with cisplatin-resistant (CR) disease were sequenced using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines 341 cancer-related genes. Patients were categorized as CR if they met any of the following criteria: 1) incomplete response to first-line cisplatin-based chemotherapy; 2) nonteratomatous tumor progression after standard chemotherapy; 3) nonteratomatous GCT identified at postchemo surgery. We grouped all somatic mutations into core signal transduction pathways or canonical cell functions to identify potential precise targets for therapy. Results: The majority of patients had nonseminoma histology (n = 64, 84%). International Germ Cell Cancer Collaborative Group risk was good, intermediate, and poor in 34%, 13%, and 53% of patients. 17 patients died of disease. In total, 51 potentially actionable alterations were identified in 36/76 (47%) patients. In the TP53 pathway, 7 MDM2 amplifications and 4 MYCN amplifications that may sensitize to nutlin-3 inhibitors were identified. Within the receptor tyrosine kinase pathway, 3 KIT mutations, 1 KDR amplification, and 1 MET amplification were seen that may sensitize to tyrosine kinase inhibitors. Eleven KRAS mutations, 3 NRAS mutations, 3 BRAF mutations, and 2 RAC1 mutations were see among the RAS pathway with preclinical data suggesting efficacy towards respective inhibitors. Actionable targets were also among the PI3-K, WNT, and cell cycle pathways. Potential targets with chromatin modifying or tumor suppressor functions were also seen. Conclusions: We describe actionable alterations that may guide treatment selection in a significant proportion of patients with CR aGCT. Targeted sequencing of these patients may allow us to enrich future clinical trials with patients whose tumors harbor alterations in the drug target of interest.

Prognostic factors and efficacy of different chemotherapeutic regimens in patients with mediastinal nonseminomatous germ cell tumors

2013 ◽  
Vol 140 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Mikhail Fedyanin ◽  
Alexey Tryakin ◽  
Yana Mosyakova ◽  
Ilya Pokataev ◽  
Anatoly Bulanov ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Nonseminomatous Germ Cell Tumors

scholarly journals Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors

2016 ◽  
Vol 34 (33) ◽  
pp. 4000-4007 ◽  
Author(s):  
Aditya Bagrodia ◽  
Byron H. Lee ◽  
William Lee ◽  
Eugene K. Cha ◽  
John P. Sfakianos ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cisplatin Resistance ◽  
Residual Disease ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Collaborative Group ◽  
Resistant Disease ◽  
Exon Capture ◽  
Whole Exome ◽  
Risk Of Cancer

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture–based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic profiling of patients with advanced GCT could improve current risk stratification and identify novel therapeutic approaches for patients with cisplatin-resistant disease.

Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16063-e16063
Author(s):  
M. Fedyanin ◽  
A. Tryakin ◽  
D. Titov ◽  
T. Zakharova ◽  
I. Fainstein ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Limited Data ◽  
Prognostic Groups ◽  
Prognostic Group

e16063 Background: Cisplatin- and etoposide-based CT allows curing the majority of patients (pts) with metastatic germ cell tumor. There are limited data concerning the importance of maintenance of DI during iCT. In the retrospective study we analyzed the role of DI of iCT on metastatic NSGCT. Methods: 589 chemotherapy-naïve pts with advanced NSGCT received induction iCT from 1987 to 2006 in our center. We compared data of all pts who relapsed after iCT (147 pts) with data of 159 randomly sampled pts without relapses. During iCT all pts received classical E500P (24%) or BE500P (76%) regimens. Median follow-up time was 49 (range, 3–218) months. Eighty four (27.5%) of 306 pts, 107 (35%) and 115 (37.5%) were from good, intermediate and poor prognostic groups, respectively. DI was calculated for every drug and expressed in mg/m2 per week. Multivariate Cox stepwise regression analysis was performed to determine independent prognostic factors in each IGCCCG prognostic group. Progression free survival was used as endpoint of the analysis. Results: Multivariate analysis revealed the following negative prognostic factors as independent: in pts of the IGCCCG good prognostic group: retroperitoneal lymph nodes >5 cm (HR 3.53, 95% Cl 1.66–7.51). In pts with the intermediate prognosis: DI of etoposide <80% (HR 4.73; 95 % CI 4.85–25.04) and presence of pulmonary metastases (HR 0.45, 95% Cl 0.203–0.977). In IGCCCG poor prognostic group: DI of etoposide <80% (HR 1.82, 95% Cl 1.143–2.913). Conclusions: Maintaining a DI of greater then 80% of etoposide during iCT, for the treatment metastatic NSGCT, is one of the crucial factors for pts outcome, particularly in intermediate and poor IGCCCG prognostic groups. No significant financial relationships to disclose.

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