Relapses in metastatic germ-cell tumors and relationship to international guidelines compliance: A study from the Institut Gustave Roussy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 323-323 ◽  
Author(s):  
Constance Thibault ◽  
Yohann Loriot ◽  
Daniel Barrios Gonzales ◽  
Christophe Massard ◽  
Mario Di Palma ◽  
...  
Keyword(s):  
Germ Cell ◽  
Residual Disease ◽  
Tumor Biology ◽  
Germ Cell Tumors ◽  
Public Hospitals ◽  
Strong Argument ◽  
International Guidelines ◽  
Residual Mass ◽  
Set Up ◽  
Number Of Cycles

323 Background: Germ-cell tumors (GCT) are rare but highly curable cancers even in patients with metastatic spread. We aimed at assessing whether relapse after upfront treatment could be explained by low compliance with international guidelines. Methods: All patients (pts) who were referred to Institut Gustave Roussy from 2000 to 2010 with progression or relapse after treatment for metastatic GCT were included. International guidelines available at the time of diagnosis were used as reference. A list of noncompliant criteria defined as disagreement with the recommendations with a potential impact on outcome was set up. Results: 78 pts were included. According to the IGCCCG classification, 18 pts (23.1%) had good, 25 pts (32%) had intermediary and 34 pts (43.6%) had poor prognosis. The first-line chemotherapy administered consisted of PEB regimen (70.5%) , PE regimen (15.4%) or other regimen (12.8%). Most patients were treated in cancer centers (52.5%, n=41), whereas 26.9% and 17.9% pts were treated in private or public general hospitals, respectively. Only 50% pts received treatment according to guidelines recommendations. This percentage was significantly higher in cancer centres than in public hospitals (75.6% versus 28.6%, p< 0.001) or also when compared with private hospitals (75.6% versus 14,3%, p<0.001). The most frequent noncompliance criteria were: time to surgery for residual mass (over 6 weeks after the latest chemotherapy cycle)(20.3%) and respected chemotherapy schedule (20.3%). Other noncompliance findings were: inadequate chemotherapy dose (15.6%), number of cycles (12.5%), decision regarding residual disease (12.5%), chemotherapy regimen (6.3%), follow up (4.6%), type of surgery (3.1%), staging(1.6%), IGCCCG classification (1.6%), or decision regarding chemotherapy after residual mass surgery (1.6%). Conclusions: This study suggests that the majority of relapse for metastatic GCT may be explained by a poor conformity to international guidelines and not only by aggressive tumor biology. These data represent a strong argument for treatment centralization in reference centers in patients with GCT.

Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial.

1995 ◽  
Vol 13 (2) ◽  
pp. 470-476 ◽  
Author(s):  
P J Loehrer ◽  
D Johnson ◽  
P Elson ◽  
L H Einhorn ◽  
D Trump
Keyword(s):  
Germ Cell ◽  
Residual Disease ◽  
Eastern Cooperative Oncology Group ◽  
Germ Cell Tumors ◽  
Staging System ◽  
Patient Characteristics ◽  
Significant Incidence ◽  
Stage Disease ◽  
Radiographic Disease ◽  
Clinically Significant

PURPOSE This prospective, randomized trial was designed to determine if three cycles of cisplatin plus etoposide (PVP16) can produce therapeutic results comparable to three cycles of cisplatin, etoposide, and bleomycin (PVP16B) in patients with disseminated germ cell tumors. PATIENTS AND METHODS One hundred seventy-eight patients with minimal- or moderate-stage disease (Indiana staging system) were randomized to receive cisplatin (20 mg/m2 on days 1 to 5) plus etoposide (100 mg/m2 on days 1 to 5) with or without weekly bleomycin (30 IU/wk for 9 consecutive weeks). Following three cycles of chemotherapy over 9 weeks, patients with residual radiographic disease underwent surgical resection. If persistent carcinoma was noted, two additional 3-week courses of chemotherapy were administered. RESULTS One hundred seventy-one patients were fully assessable for response and survival. The two treatment groups were similar with respect to patient characteristics. The toxicities were comparable between the two arms. No clinically significant incidence of pulmonary toxicity occurred with PVP16B. Overall, 81 of 86 patients (94%) who received PVP16B and 75 of 85 patients (88%) who received PVP16 achieved a disease-free status with chemotherapy and/or surgery. However, greater numbers of treatment failures, including persistent carcinoma in postchemotherapy resected residual disease and relapses from complete remission, occurred on the arm without bleomycin (overall adverse outcome, P = .004). The failure-free (86% v 69%; P = .01) and overall survival (95% v 86%; P = .01) rates were inferior on the PVP16 arm. CONCLUSION Bleomycin is an essential component of PVP16B therapy in patients who receive three cycles of treatment for minimal- or moderate-stage disseminated germ cell tumors.

scholarly journals Testicular tumors

2011 ◽  
pp. 28-35
Author(s):  
Giovanni Rosti ◽  
Ornella Carminati ◽  
Claudia Casanova ◽  
Giorgio Papiani
Keyword(s):  
Germ Cell ◽  
Residual Disease ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Prognostic Scores ◽  
Retroperitoneal Lymph Node Dissection ◽  
High Dose ◽  
Advanced Phase ◽  
Response To Chemotherapy

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.

Post-chemotherapy modified template retroperitoneal lymph node dissection in patients with nonseminomatous germ cell tumours

2021 ◽  
Author(s):  
Murat Zor ◽  
Sercan Yilmaz ◽  
Bahadir Topuz ◽  
Engin Kaya ◽  
Serdar Yalcin ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Germ Cell ◽  
Residual Disease ◽  
Germ Cell Tumors ◽  
Operation Time ◽  
Long Term Results ◽  
Perioperative Outcomes ◽  
Retroperitoneal Lymph Node Dissection

Abstract Introduction/background: Although a full bilateral template RPLND is thought to be the standard of care for the management of postchemotherapy retroperitoneal residual masses for nonseminomatous germ cell tumors (NSGCT), in the past decade modified templates have become increasingly popular. In this study, we aimed to present our oncological and perioperative outcomes of consecutive seventeen NSGCT patients who underwent a modified template unilateral PC-RPLND for retroperitoneal residual disease. Materials and Methods: We retrospectively evaluated the medical records of 17 consecutive NSGCT patients who underwent modified template unilateral PC-RPLND in our university hospital between 2017 and 2020. All patients had normal serum tumour markers with residual disease in the retroperitoneum. Surgical characteristics including the size of the retroperitoneal residual mass, residual tumor pathology, removed lymph nodes, positive percentage of removed lymph nodes, accompanying operations, complications, mean operation time and hospital stay, and long-term results including survival and antegrade ejaculation were evaluated. Results: Eleven patients underwent left and six right-sided surgery. Median residual lymph node diameter was 41mm. Median hospitalisation time was 3.5 days. Median follow-up time was 10.5 months. Necrosis/fibrosis was seen in 6 patients, and teratoma in 11 patients. No viable tumour was seen. No patients died in the follow-up period. None of the patients relapsed during follow-up. Ten/seventeen patients had antegrade ejaculation. Conclusions: Modified template unilateral PC-RPLND leads to very good oncological outcomes with decreased perioperative morbidity as well as better antegrade ejaculation rates. Low volume retroperitoneal disease seems to fit this procedure best.

scholarly journals Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group

2017 ◽  
Vol 35 (11) ◽  
pp. 1203-1210 ◽  
Author(s):  
Furqan Shaikh ◽  
John W. Cullen ◽  
Thomas A. Olson ◽  
Farzana Pashankar ◽  
Marcio H. Malogolowkin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Children And Adolescents ◽  
Statistical Significance ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Stage Ii ◽  
Intermediate Risk ◽  
Historical Cohort ◽  
Number Of Cycles ◽  
Malignant Germ Cell Tumors

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

Management of Residual Mass in Germ Cell Tumors After Chemotherapy

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Costantine Albany ◽  
Kenneth Kesler ◽  
Clint Cary
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Residual Mass

Gynecologic Cancer Intergroup (GCIG) Consensus Review for Ovarian Germ Cell Tumors

2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S48-S54 ◽  
Author(s):  
Jubilee Brown ◽  
Michael Friedlander ◽  
Floor J. Backes ◽  
Philipp Harter ◽  
Dennis M. O’Connor ◽  
...  
Keyword(s):  
Germ Cell ◽  
Early Stage ◽  
Gynecologic Cancer ◽  
Tumor Biology ◽  
Germ Cell Tumors ◽  
Clinical Trial Design ◽  
Cooperative Groups ◽  
Stage Disease ◽  
Fertility Sparing ◽  
Collaborative Efforts

AbstractMost women diagnosed with malignant ovarian germ cell tumors have curable disease and experience excellent survival with manageable treatment-associated morbidity, related both to tumor biology and improvements in treatment over the last 4 decades. Malignant ovarian germ cell tumors occur predominantly in girls, adolescents, and young women and are often unilateral tumors of early stage, although advanced-stage disease occurs in approximately 30% of patients. Tumors are usually chemosensitive, thereby allowing fertility-sparing surgery in most women with high chance of cure. Differences in practice do exist among providers in various subspecialties and geographic areas. In most settings, collaborative efforts among specialties allow the optimal treatment of women with these rare tumors, and implementation of standard guidelines at an international level should translate to effective clinical trial design, rapid accrual to clinical trials, and universally improved patient outcomes.This consensus guideline represents a summary of recommendations for diagnosis and management that has been agreed upon by cooperative groups worldwide. It builds upon individual publications including previously published summary documents and provides the most current practice standards validated worldwide.

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.

Outcome of Patients With Residual Germ Cell or Non-Germ Cell Malignancy After Resection of Primary Mediastinal Nonseminomatous Germ Cell Cancer

2004 ◽  
Vol 22 (7) ◽  
pp. 1195-1200 ◽  
Author(s):  
Bryan P. Schneider ◽  
Kenneth A. Kesler ◽  
Jo Ann Brooks ◽  
Constantin Yiannoutsos ◽  
Lawrence H. Einhorn
Keyword(s):  
Germ Cell ◽  
Residual Disease ◽  
Cell Cancer ◽  
Elevated Serum ◽  
Germ Cell Tumors ◽  
Term Survival ◽  
Poor Risk Patient ◽  
Nonseminomatous Germ Cell Tumor ◽  
Alive With Disease

PurposeTo identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer.Patients and MethodsForty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed.ResultsAt diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively.ConclusionThe presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.

Germ Cell Tumors: Looking to the Future

2015 ◽  
pp. e253-e258
Author(s):  
George J. Bosl
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cells ◽  
Tumor Biology ◽  
Chemotherapy Resistance ◽  
Germ Cell Tumors ◽  
Late Relapse ◽  
Malignant Neoplasms ◽  
Second Malignant Neoplasms ◽  
Near Term

Our knowledge about the management of men with germ cell tumors (GCTs) and its tumor biology continues to evolve. Vascular disease, metabolic syndrome, second malignant neoplasms, and hypogonadism occur after treatment for GCTs and the latency pattern resembles that seen in patients treated for Hodgkin lymphoma. Patients receiving treatment for GCTs should be informed not only of the near-term toxicity (experienced during or shortly after administration), but also the delayed and late effects of chemotherapy and the need for lifelong surveillance for all late outcomes, including late relapse. Recent data suggest that the treatment outcome of patients with intermediate-risk, poor-risk, and relapsed GCTs can be improved through multicenter trials that include the general oncology community. Finally, GCTs are a malignancy of primordial germ cells. Programmed differentiation is clinically evident in vivo and probably related to chemotherapy resistance. This biology has much clinical relevance, some of which is already in use.

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