Extracranial Malignant Germ Cell Tumors Research Articles

Current surgical approach: Extracranial malignant germ cell tumors.

Germ cell tumors (GCT) are a complex, heterogeneous collection of tumors that may present in either gonadal or extragonadal sites. They consist of a variety of benign and malignant histologies that can occur at several locations throughout the body. An important component of treatment is surgical resection, and while the key components of resection are site specific, the universal goals of GCT resection include the complete resection of tumor without violating the tumor capsule, while preserving function of surrounding organs, minimizing morbidity, and assessing for regional spread.

Treatment results of childhood extracranial malignant germ cell tumors and the salvage approach for recurrent and refractory cases: a single-center report

Abstract Objective The aim of this study is to report the treatment result of childhood excranial malignant germ cell tumors and discuss the experience for recurrent and refractory cases treatment from our center. Methods We have retrospectively analyzed 58 extracranial malignant germ cell tumor patients treated with surgery and chemotherapy from our center over a 9-year period. Another 14 recurrent and refractory cases referred from other centers were added to the study for salvage approach. We evaluated the treatment results for primary cases and relapsed cases with a median follow-up of 61.5 months. Several factors were analysed to evaluate their power to the outcome of these cases. Results The 5-year event-free and overall survival for primary cases were 74.1±5.7% and 86.2±4.5%, respectively. 25 recurrent or refractory cases entered the salvage approach study, and 17 patients were alive till the end of follow-up. We demonstrated superior survival outcome for those with successful local control through pre-operative and post-operative radiotherapy, second-look surgery and multi-drug second-line chemotherapies. Conclusion The outcome for childhood extracranial malignant germ cell tumors is generally favorable. For recurrent and refractory cases, multi-modality treatment approaches including radiotherapy, salvage chemotherapy and secondlook surgery are important for better local control.

Results from the UK Children's Cancer and Leukaemia Group study of extracranial germ cell tumours in children and adolescents (GCIII)

BackgroundFor extracranial malignant germ cell tumours (MGCTs) in the UK, the GCII study used carboplatin-based chemotherapy (JEb) and demonstrated equivalent survival to cisplatin-containing protocols. GCIII, a single-arm observational study, used new risk stratification, replaced consolidation chemotherapy with a standard number of cycles and introduced surveillance for all stage I MGCTs. Pure teratomas were registered to understand their natural history. MethodsPatients with MGCTs were stratified to three risk groups – low risk (LR), intermediate risk (IR) and high risk (HR), using stage and prognostic factors. Patients with alpha fetoprotein (AFP) >10,000 kU/L, stage IV disease (except testis <5 years and all germinomas) or stage II-IV mediastinal tumour were classified HR. Stage I tumours (LR) received chemotherapy only if disease progressed. IR and HR patients received 4 and 6 JEB cycles, respectively. Carboplatin dose was calculated using glomerular filtration rate to give an area under the curve of 7.9 ml/m2.min. ResultsEighty-six patients with MGCTs were enrolled from 2005 to 2009: 59% female, median age, 5.7 years. Twenty-five patients were LR, 21 IR and 38 HR. Seven LR patients had disease progression; all were successfully treated with chemotherapy. Overall survival (OS) for the whole group was 97%; 5-year event-free survival for JEb-treated patients was 92%, and OS, 95%. JEb was well tolerated with no observed significant hearing or renal side-effects. There was no discernible difference in carboplatin dose whether calculated by body surface area or creatinine clearance. Forty-seven patients with teratoma were managed with surgery and one had malignant transformation. ConclusionCarboplatin-based chemotherapy as part of a risk-stratified approach leads to excellent survival in paediatric MGCTs, minimising potential burden of long-term effects.

Outcomes of adolescent males with extracranial malignant germ cell tumors compared with children and young adults: A report from the Malignant Germ Cell Tumors International Consortium (MaGIC) group.

10022 Background: Adolescents with extracranial malignant germ cell tumors (GCTs) are often treated on the same regimens developed for children, but more closely resemble the clinical characteristics of young adult patients. We sought to determine whether event-free survival (EFS) for adolescents with GCTs was more like that of children or young adults. Methods: We assembled an individual patient database of ten GCT trials: seven conducted by pediatric cooperative groups and three by an adult group. We selected male patients aged 0-30 years old treated with platinum-based chemotherapy for non-seminomatous malignant GCTs of the testis, retroperitoneum, or mediastinum. We categorized age-group as children (0 to &lt; 11 years), adolescents (11 to &lt; 18 years), or young adults (18 to &lt; 30 years old). We compared EFS among age groups, and adjusted for calculated IGCCCG risk-group using Cox proportional hazards analysis. Results: 593 patients met inclusion criteria, of whom 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS for adolescents (72%; CI = 62-79%) was significantly lower than for children (90%; CI = 81-95%, p = 0.003) and for young adults (88%; CI = 84-91%, p &lt; 0.001). Risk-group was significantly associated with EFS in the adolescent age-group (p = 0.002). In a Cox multivariable analysis, the difference between adolescents and children remained statistically significant (HR = 0.30, p = 0.001), but the difference between adolescents and young adults did not (HR 0.66, p = 0.114). Conclusions: EFS for adolescent patients with extracranial malignant GCTs was similar to young adults but significantly worse than children. This finding may have important implications for how adolescent patients are treated.

Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium

PurposeTo compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG). MethodsThe Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC ‘risk’ groups: standard risk ((SR) 1 (EFS >80%; age <11 years), SR2 (EFS >80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y). ResultsCisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83–89% versus carboplatin 4-year EFS 86%; 95% CI 79–90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients. ConclusionsIn these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway.

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

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.

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.

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.

Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration.

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.

Postrecurrence survival for pediatric extracranial malignant germ cell tumors: A report from the Malignant Germ Cell Tumors International Collaborative (MaGIC) Group.

10074 Background: Post-recurrence survival (PRS) of children and adolescents with malignant germ cell tumors (MGCTs) has not previously been described, due to the limited sample size of relapsed pa...

Extracranial Malignant Germ Cell Tumors

The outstanding clinical trials undertaken for the management of pediatric extracranial malignant germ cell tumors (GCTs) in the developed world in the last three decades has led to excellent longterm outcomes. The scenario in developing country like India is different; results are poor owing to multiple factors such as delayed presentation, misdiagnosis, and early abandonment of the therapy. The authors address here several aspects of this heterogeneous group of malignant tumors in children and adolescents such as the different staging systems, the risk stratification, the guidelines to treatment modalities, the outcome and prognostication.

Brain metastases during follow‐up of children and adolescents with extracranial malignant germ cell tumors: Risk adapted management decision tree analysis based on data of the MAHO/MAKEI‐registry

The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. Pediatr Blood Cancer 2013;60:217-223. © 2012 Wiley Periodicals, Inc.

Carboplatin (CBP) versus cisplatin (CP) within prognostic groups in pediatric extracranial malignant germ cell tumors (MGCTs).

9539 Background: It is established that CBP is inferior to CP in adult MGCTs when used at AUC 5 or 400mg/m2. There are no randomised data for paediatric MGCTs, so conclusions from adult MGCTs have been generalised despite differences in site, histology and biology. A database, pooling patients from US and UK paediatric MGCT studies, was established to determine prognostic factors in paediatric MGCTs. We examined the effect of CBP and CP in identified prognostic groups. Methods: A dataset of 1110 paediatric MGCTs was created, treated 1983 to 2009. Treatment was CBP (JEB, AUC 7.9) in the UK and CP (PEB) in the US. After excluding patients with surgery only, pure germinoma or immature teratoma , 697 patients remained. The cure model was used to assess the prognostic significance of chemotherapy regimen after adjustment for patient characteristics. Results: Analysis stratified prognosis according to age (0-10 v 11+yrs) and stage (1-3 v 4) at diagnosis by site (testis: ovary: extragonadal). Outcome for CBP and CP in these prognostic groups is shown in the table. Conclusions: Interpretation of the results of this nonrandomised comparison requires caution. However, after adjustment for other prognostic factors, the risks of failure for JEB and PEB were not statistically different . This is particularly true for 0-10yrs. At AUC7.9 CBP is tolerable in paediatric patients, with potentially fewer late toxicities than CP. [Table: see text]

334 Pediatric extracranial non-gonadal malignant germ cell tumors (EMGCT): Implication of site, age and dissemination

334 Pediatric extracranial non-gonadal malignant germ cell tumors (EMGCT): Implication of site, age and dissemination

Management of germ cell tumours in childhood

Germ cell tumours are a group of rare benign and malignant neoplasms of unknown cause, and may be gonadal or extragonadal (intracranial or extracranial). Teratomas are the most common and are usually benign. Malignant germ cell tumours often secrete the tumour markers alpha-fetoprotein and human chorionic gonadotrophin, which are useful in diagnosis and monitoring. The treatment is surgical for teratoma and non-metastatic gonadal tumours. Chemotherapy, reserved in the UK for stage 2–4 extracranial malignant germ cell tumours, achieves a 5-year survival of around 90%. Intracranial tumours are typically pineal or suprasellar. Intracranial germinomas are cured in over 90% of cases with radiotherapy or combined chemoradiotherapy, whereas non-germinomatous tumours fare less well despite combination chemotherapy and radiotherapy.