Prediction of residual retroperitoneal mass histology following postchemotherapy retroperitoneal surgery for metastatic nonseminomatous germ cell tumors: Role of MDR-1 and mismatch repair genes

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5088-5088
Author(s):  
A. N. Heidenreich ◽  
D. Pfister ◽  
D. Thüer ◽  
U. H. Engelmann ◽  
C. H. Ohlmann
Keyword(s):  
Multivariate Analysis ◽  
Germ Cell ◽  
Statistical Significance ◽  
Mature Teratoma ◽  
Tumor Resection ◽  
Germ Cell Tumors ◽  
Staining Intensity ◽  
Predictive Values ◽  
Preoperative Serum ◽  
Mdr 1

5088 Background: Following inductive chemotherapy for metastatic nonseminomatous germ cell tumours (NSGCT) about 35% and 15% of patients undergoing residual tumor resection (RTR) demonstrate mature teratoma and vital cancer, respectively. It was the aim of our study to evaluate the expression of mdr-1, hMLH1 and hMLH2 in primary NSGCT and their resected residual tumors. Methods: 185 patients with NSGCT underwent RTR of retroperitoneal masses. Immunohistochemical investigations of mdr-1, hMLH1/2 were performed on paraffin-embedded tissue section of the primary tumour and the resected lymph nodes using monoclonal, commercially available antibodies. Staining was analysed according to a semiquantitative scoring system; furthermore, detailed morphometry was performed. Preoperative serum and clinical parameters were assessed to predict necrosis/fibrosis or teratoma in residual tumors. Statistical analysis was performed by uni- and multivariate analysis to correlate data with histology of the RTR specimens. Parameters were statistically significant if p<0.05. Results: A total of 122 patients (65.9%) had necrosis, 23 patients (12.4%) and 40 patients (21.6%) had viable cancer and mature teratoma, resp. After multivariate analysis pre-chemotherapeutic AFP-levels, tumor size before RTR, mature teratoma in the primary and mdr-1 expression in the primary were independent predictors of final necrosis. Positive predictive values were 74%, 76%, 78% and 88% resp., sensitivity was 81%, 52.8%, 65% and 86%, resp.; specificity was 59%, 79.3%, 81% and 90% resp.. Nonseminomatous elements demonstrated a significantly higher staining intensity for hMLH1 than seminomas, whereas staining intensity for hMLH2 was lower (p=0.03). IHC for hMLH1/2 of GCT with necrosis was higher as compared to GCT exhibiting mature teratoma or vital cancer approaching statistical significance (p=0.07). Conclusions: Pre-chemotherapy AFP levels < 15 ng/ml and a residual mass < 2 cm are associated with a favourable histology in the RTR specimen. The addition of mdr-1 expression in the primary NSGCT improves sensitivity to 88% and represents a clinically useful prediction marker. No significant financial relationships to disclose.

scholarly journals Intracranial teratomas in children: the role and timing of surgical removal

2008 ◽  
Vol 2 (5) ◽  
pp. 331-338 ◽  
Author(s):  
Rémy Noudel ◽  
Mathieu Vinchon ◽  
Patrick Dhellemmes ◽  
Claude Fabien Litré ◽  
Pascal Rousseaux
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Tumor Resection ◽  
Germ Cell Tumors ◽  
Timing Of Surgery ◽  
Surgical Removal ◽  
Primary Therapy ◽  
Large Tumor ◽  
Oncological Treatment ◽  
Malignant Germ Cell Tumors

Object In this study, the authors report their experience with the surgical treatment of intracranial teratomas with an emphasis on the indications for delayed resection after oncological treatment. Methods The authors retrospectively reviewed the cases of 14 children with intracranial teratomas. The mean age at diagnosis was 10.5 years (range 2 days–18 years), and 11 patients were male. The final histological analysis revealed pure mature teratoma in 5 cases, mixed teratoma with germinoma in 3 cases, and nongerminomatous malignant germ cell tumor in 6 cases. Thirteen patients underwent tumor resection, and these patients were divided into 2 subgroups according to the timing of surgery. In Group A, 10 patients underwent resection as the primary treatment because no tumor markers were detected in 4 patients, a teratomatous component was revealed on biopsy sampling in 3 patients, and a large tumor volume in 3 patients. In Group B, 3 patients underwent removal of residual pure mature teratoma after oncological treatment. Results Seven of the 8 patients (87.5%) with pure mature teratomas or with mixed teratoma and germinoma are currently alive (mean follow-up of 9 years); the eighth patient died of postoperative meningitis. Two of the 6 patients (33%) with mixed nongerminomatous malignant germ cell tumors died of tumor progression regardless of the timing of surgery. Conclusions The results of this study support the belief that microsurgical removal is the only effective treatment for intracranial teratomas. Surgery may be performed as the primary therapy when there is evidence of a noninvasive teratoma, and as a secondary therapy if there is only a partial response to neoadjuvant therapy or if progression is observed in mixed malignant germ cell tumors.

Novel Diagnostic Methods and Posttreatment Clinical Phenotypes Among Intracranial Germ Cell Tumors

Neurosurgery ◽  
2020 ◽  
Vol 87 (3) ◽  
pp. 563-572 ◽  
Author(s):  
Hirokazu Takami ◽  
Avital Perry ◽  
Christopher S Graffeo ◽  
Caterina Giannini ◽  
David J Daniels
Keyword(s):  
Cohort Study ◽  
Germ Cell ◽  
Statistical Significance ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Extent Of Resection ◽  
Diagnostic Methods ◽  
Cell Fraction ◽  
Clinical Phenotypes ◽  
Second Look

Abstract BACKGROUND Central nervous system (CNS) germ cell tumors (GCT) are rare and complex pediatric neoplasms, the optimal management of which remains an area of active investigation. OBJECTIVE To present an updated cohort study, with particular attention to novel diagnostic methods and posttreatment clinical phenotypes. METHODS A single-institution cohort study of 80 primary, neurosurgically managed, CNS GCTs was conducted at Mayo Clinic, 1988-2017. RESULTS Postchemotherapy resection (eg, second-look surgery) was frequently required (27.0%), especially after adjuvant therapies for nongerminomatous GCTs (NGGCTs; 14 of 28 cases, excluding mature teratoma) and significantly associated with pineal lesions, as compared to neurohypophyseal or bifocal lesions (43.6% vs 5.9% vs 6.7%, P = .004), a finding that retained statistical significance after adjusting for index extent of resection and histology (P = .04). Essentially every NGGCT case underwent at least 1 craniotomy, either on presentation, as second-look surgery, or following local recurrence. Mature teratomatous tissue was highly incident in second-look specimens (84.2%), even among lesions initially diagnosed as germinomas. Pretreatment cerebrospinal fluid (CSF) cell fraction analysis demonstrated an association between single lesions and neutrophil predominance, whereas nongerminomatous GCTs were associated with increased monocyte fractions. CONCLUSION CNS GCTs are clinically heterogeneous lesions, resulting in numerous opportunities for improved understanding and clinical management via novel diagnostic and therapeutic protocols. Samples from second-look surgeries for recurrent germinomas frequently demonstrate teratomatous tissue, suggesting possible underdiagnosis of mixed GCTs—particularly among pineal lesions. GCT subtypes demonstrate differential cell fraction distributions on CSF analysis, a novel and perhaps diagnostically helpful finding that requires validation in external cohorts.

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.

scholarly journals MPC-08 CLINICOPATHOLOGICAL ANALYSIS OF 12P GAIN IN INTRACRANIAL GERM CELL TUMORS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii23
Author(s):  
Kaishi Satomi ◽  
Hirokazu Takami ◽  
Shintaro Fukushima ◽  
Yoichi Nakazato ◽  
Shota Tanaka ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Copy Number ◽  
Mature Teratoma ◽  
Methylation Status ◽  
Germ Cell Tumors ◽  
Copy Number Variations ◽  
Cell Tumor ◽  
Testicular Germ Cell ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs. MATERIALS AND METHODS We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH). RESULT 12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P&lt;0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). DISCUSSION 12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.

Residual Tumor Resection After High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Cancer

2004 ◽  
Vol 22 (18) ◽  
pp. 3713-3719 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
S. Weinknecht ◽  
J. Schirren ◽  
T. Pottek ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Tumor Resection ◽  
Residual Tumor ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Incomplete Resection ◽  
Residual Tumor Resection

Purpose To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). Patients and Methods Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. Results Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. Conclusion Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.

scholarly journals Applying Radiomics to Predict Pathology of Postchemotherapy Retroperitoneal Nodal Masses in Germ Cell Tumors

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jeremy Lewin ◽  
Paul Dufort ◽  
Jaydeep Halankar ◽  
Martin O’Malley ◽  
Michael A.S. Jewett ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Area Under The Curve ◽  
Prediction Algorithm ◽  
Support Vector ◽  
Clinical Predictors ◽  
Testicular Germ Cell ◽  
Clinical Variables ◽  
Computed Tomography Images

Purpose After chemotherapy, approximately 50% of patients with metastatic testicular germ cell tumors (GCTs) who undergo retroperitoneal lymph node dissections (RPNLDs) for residual masses have fibrosis. Radiomics uses image processing techniques to extract quantitative textures/features from regions of interest (ROIs) to train a classifier that predicts outcomes. We hypothesized that radiomics would identify patients with a high likelihood of fibrosis who may avoid RPLND. Patients and Methods Patients with GCT who had an RPLND for nodal masses > 1 cm after first-line platinum chemotherapy were included. Preoperative contrast-enhanced axial computed tomography images of retroperitoneal ROIs were manually contoured. Radiomics features (n = 153) were used to train a radial basis function support vector machine classifier to discriminate between viable GCT/mature teratoma versus fibrosis. A nested 10-fold cross-validation protocol was used to determine classifier accuracy. Clinical variables/restricted size criteria were used to optimize the classifier. Results Seventy-seven patients with 102 ROIs were analyzed (GCT, 21; teratoma, 41; fibrosis, 40). The discriminative accuracy of radiomics to identify GCT/teratoma versus fibrosis was 72 ± 2.2% (area under the curve [AUC], 0.74 ± 0.028); sensitivity was 56.2 ± 15.0%, and specificity was 81.9 ± 9.0% ( P = .001). No major predictive differences were identified when data were restricted by varying maximal axial diameters (AUC range, 0.58 ± 0.05 to 0.74 ± 0.03). The prediction algorithm using clinical variables alone identified an AUC of 0.76. When these variables were added to the radiomics signature, the best performing classifier was identified when axial masses were limited to diameter < 2 cm (accuracy, 88.2 ± 4.4; AUC, 0.80 ± 0.05; P = .02). Conclusion A predictive radiomics algorithm had a discriminative accuracy of 72% that improved to 88% when combined with clinical predictors. Additional independent validation is required to assess whether radiomics allows patients with a high predicted likelihood of fibrosis to avoid RPLND.

scholarly journals Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors

2019 ◽  
Vol 37 (26) ◽  
pp. 2329-2337 ◽  
Author(s):  
Samuel A. Funt ◽  
Sujata Patil ◽  
Darren R. Feldman ◽  
Robert J. Motzer ◽  
Dean F. Bajorin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cumulative Incidence ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Adverse Outcomes ◽  
Term Survival ◽  
Risk Status ◽  
Primary Tumors ◽  
Platinum Based Chemotherapy

PURPOSE In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. METHODS Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. RESULTS Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status ( P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status ( P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). CONCLUSION The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.

scholarly journals Mature teratoma identified after postchemotherapy surgery in patients with disseminated nonseminomatous testicular germ cell tumors

Cancer ◽  
1998 ◽  
Vol 82 (7) ◽  
pp. 1343-1351 ◽  
Author(s):  
Dirk J.�A. Sonneveld ◽  
Dirk Th. Sleijfer ◽  
Heimen Schraffordt Koops ◽  
Mariel E. Keemers-Gels ◽  
Willemina M. Molenaar ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Management of Malignant Pineal Germ Cell Tumors with Residual Mature Teratoma

Neurosurgery ◽  
2001 ◽  
Vol 48 (3) ◽  
pp. 518-523 ◽  
Author(s):  
Jonathan A. Friedman ◽  
James J. Lynch ◽  
Jan C. Buckner ◽  
Bernd W. Scheithauer ◽  
Corey Raffel
Keyword(s):  
Magnetic Resonance Imaging ◽  
Radiation Therapy ◽  
Magnetic Resonance ◽  
Germ Cell ◽  
Neoadjuvant Therapy ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Response To Therapy ◽  
External Beam Radiation ◽  
Resonance Imaging

Abstract OBJECTIVE The treatment of intracranial mixed germ cell tumors presents a unique challenge, since eradication of malignant tumor by radiation and/or chemotherapy may spare the benign tumor component. We reviewed our surgical experience with residual malignant pineal germ cell tumors after neoadjuvant therapy. METHODS Between 1987 and 1997, 16 patients with malignant intracranial germ cell tumors were treated at the Mayo Clinic with a protocol of neoadjuvant chemotherapy and radiation therapy. After the diagnosis was confirmed by histopathological examination, all patients were treated with four cycles of etoposide and cisplatin as well as external beam radiation therapy (range, 3030–5940 cGy). Six patients had an incomplete response to therapy, as demonstrated by observation of residual tumor on magnetic resonance imaging scans. Initial pathology in these six patients was germinoma in four and combinations of yolk sac tumor, embryonal carcinoma, malignant teratoma, and germinoma in two. Two patients had synchronous pineal and suprasellar tumors, with leptomeningeal dissemination. Tumor markers were elevated in four of the six patients at presentation. RESULTS All patients with residual pineal tumors underwent surgical resection via an infratentorial, supracerebellar approach. Pathological examination revealed mature teratoma in five patients and amorphous debris in one patient. No patient had recurrent malignancy. Significant neurological morbidity occurred in one patient, with no mortality. At a mean follow-up of 23 months, no recurrence on magnetic resonance imaging has been documented. CONCLUSION Residual pineal tumor occurring after treatment of malignant intracranial germ cell tumor with neoadjuvant therapy is likely to be mature teratoma. Operative resection of these benign recurrences is safe and effective.

High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

1996 ◽  
Vol 14 (10) ◽  
pp. 2638-2645 ◽  
Author(s):  
J Beyer ◽  
A Kramar ◽  
R Mandanas ◽  
W Linkesch ◽  
A Greinix ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
The United States ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cell ◽  
Risk Category ◽  
High Dose ◽  
Prognostic Variables ◽  
Increased Risk

PURPOSE To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

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