Effect of prophylactic anticoagulation on incidence of venous thromboembolism in testicular germ cell tumor patients.

422 Background: Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in GCT patients, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in cancer patients. In this retrospective study we evaluated the effect of low molecular weight heparin (LMWH) prophylaxis during hospitalization on incidence of VTE and outcome in GCT patients treated with first-line chemotherapy. Methods: Study population included 394 chemotherapy-naive GCT patients treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. No visceral thromboses were observed. Results: Forty-one out of 394 patients (10.4%) were diagnosed with VTE on initial staging and were excluded from the analysis. Final cohort included 353 patients. LMWH prophylaxis was administered to 104 patients (29.5%), 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% p = 0.37). We have observed a trend to longer overall survival in patients without prophylaxis (HR = 0.61, 95%CI = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival compared to patients without prophylaxis (HR = 0.29, 95%CI = 0.08-1.12, p = 0.04). Conclusions: LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, it was associated with shorter survival in extragonadal GCTs. Taking into account these data, LMWH prophylaxis during hospitalization should not be used in GCT patients receiving chemotherapy.

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Effect of prophylactic anticoagulation on incidence of venous thromboembolism in testicular germ cell tumor patients

10.21203/rs.3.rs-20044/v1 ◽

2020 ◽

Author(s):

Nikola Hapakova ◽

Michal Chovanec ◽

Katarina Rejlekova ◽

Katarina Kalavska ◽

Jana Obertova ◽

...

Keyword(s):

Venous Thromboembolism ◽

Confidence Interval ◽

Germ Cell ◽

Germ Cell Tumors ◽

Hazard Ratio ◽

First Line ◽

Testicular Germ Cell ◽

Vte Prophylaxis ◽

Prophylactic Anticoagulation ◽

Line Chemotherapy

Abstract Background Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in GCT patients, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in patients with malignancy. The aim of this retrospective study was to evaluate the effect of low molecular weight heparin (LMWH) prophylaxis on incidence of VTE and outcome in GCT patients treated with first-line chemotherapy. Methods Our study population included chemotherapy-naive GCT patients treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. Patients diagnosed with VTE on initial staging exam were excluded from the study. No visceral thromboses were observed. Results Our cohort included 353 GCT patients. LMWH prophylaxis was administered to 104 patients (29.5%), 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% P = 0.37). We have observed a trend to longer overall survival in patients without prophylaxis (hazard ratio = 0.61, 95% confidence interval = 0.32-1.13, P = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival. (hazard ratio = 0.29, 95% confidence interval = 0.08-1.12, P = 0.04). This effect was most likely driven by higher incidence of treatment related deaths in patients with extragonadal GCT receiving LMWH. ( P = 0.06) Conclusions LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, there was a higher incidence of treatment related deaths in patients with extragonadal tumor location. LMWH prophylaxis during hospitalization should not be used routinely in GCT patients receiving chemotherapy.

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Effect of prophylactic anticoagulation on the incidence of venous thromboembolism in patients with testicular germ cell tumor.

10.21203/rs.3.rs-20044/v2 ◽

2020 ◽

Author(s):

Nikola Hapakova ◽

Michal Chovanec ◽

Katarina Rejlekova ◽

Katarina Kalavska ◽

Jana Obertova ◽

...

Keyword(s):

Venous Thromboembolism ◽

Confidence Interval ◽

Germ Cell ◽

Germ Cell Tumors ◽

Hazard Ratio ◽

First Line ◽

Testicular Germ Cell ◽

Vte Prophylaxis ◽

Prophylactic Anticoagulation ◽

Line Chemotherapy

Abstract Background Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in patients with GCT, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in patients with malignancy. The aim of this retrospective study was to evaluate the effect of low-molecular-weight heparin (LMWH) prophylaxis on the incidence of VTE and outcome in patients with GCT treated with first-line chemotherapy. Methods Our study population included chemotherapy-naive patients with GCT treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia, from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. Patients diagnosed with VTE on initial staging exam were excluded from the study. No visceral thromboses were observed. Results Our cohort included 353 patients with GCT. LMWH prophylaxis was administered to 104 patients (29.5%), and 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% P = 0.37). We observed a trend toward longer overall survival in patients without prophylaxis (hazard ratio = 0.61, 95% confidence interval = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival (hazard ratio = 0.29, 95% confidence interval = 0.08-1.12, P = 0.04). This effect was most likely driven by a higher incidence of treatment-related deaths in patients with extragonadal GCT receiving LMWH ( P = 0.06). Conclusions LMWH prophylaxis was not associated with decreased VTE incidence.Moreover, there was a higher incidence of treatment-related deaths in patients with extragonadal tumor location. LMWH prophylaxis during hospitalization should not be used routinely in patients with GCT receiving chemotherapy.

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Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211024756 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110247

Author(s):

Hikmat Abdel-Razeq ◽

Faris Tamimi ◽

Rashid Abdel-Razeq ◽

Samer Salah ◽

Zaid Omari ◽

...

Keyword(s):

Venous Thromboembolism ◽

Germ Cell ◽

Metastatic Disease ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumor ◽

Tumor Burden ◽

Testicular Tumors ◽

Testicular Germ Cell ◽

Node Positive ◽

Age Range

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

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High Endogenous DNA Damage Levels Predict Hematological Toxicity in Testicular Germ Cell Tumor Patients Treated With First-Line Chemotherapy

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2019.06.004 ◽

2019 ◽

Vol 17 (5) ◽

pp. e1020-e1025

Author(s):

Nikola Hapakova ◽

Zuzana Sestakova ◽

Andrea Holickova ◽

Lenka Hurbanova ◽

Vera Miskovska ◽

...

Keyword(s):

Dna Damage ◽

Germ Cell ◽

Germ Cell Tumor ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Hematological Toxicity ◽

First Line ◽

Tumor Patients ◽

Testicular Germ Cell ◽

Line Chemotherapy

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Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first‐line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3)

Cancer Medicine ◽

10.1002/cam4.2674 ◽

2019 ◽

Vol 9 (1) ◽

pp. 116-124 ◽

Cited By ~ 3

Author(s):

Ben Tran ◽

Jose M. Ruiz‐Morales ◽

Enrique Gonzalez‐Billalabeitia ◽

Anna Patrikidou ◽

Eitan Amir ◽

...

Keyword(s):

Venous Thromboembolism ◽

Germ Cell ◽

Cell Cancer ◽

Germ Cell Tumors ◽

Germ Cell Cancer ◽

First Line ◽

Cancer Group ◽

Increased Risk ◽

Line Chemotherapy

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Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors

Current Medicinal Chemistry ◽

10.2174/0929867324666171003115807 ◽

2018 ◽

Vol 25 (5) ◽

pp. 575-583 ◽

Cited By ~ 1

Author(s):

Paolo Chieffi

Keyword(s):

Germ Cell ◽

Primordial Germ Cells ◽

Germ Cell Tumors ◽

Molecular Targets ◽

Testicular Germ Cell Tumor ◽

Research Literature ◽

Testicular Germ Cell ◽

Solid Malignancy ◽

Bibliographic Data ◽

New Biomarkers

Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Methods: I undertook a search of bibliographic data from peer-reviewed research literature. Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies. Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.

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Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples

Clinical Epigenetics ◽

10.1186/s13148-021-01048-y ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

João Lobo ◽

Vera Constâncio ◽

Pedro Leite-Silva ◽

Rita Guimarães ◽

Mariana Cantante ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumor ◽

Complete Response ◽

Differential Analysis ◽

Testicular Germ Cell ◽

Tissue Samples ◽

Tumor Patient ◽

Resistant Disease ◽

Response To Chemotherapy

AbstractTesticular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.

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Testicular Germ Cell Tumor and down Syndrome

Tumori Journal ◽

10.1177/030089160008600514 ◽

2000 ◽

Vol 86 (5) ◽

pp. 431-433 ◽

Cited By ~ 4

Author(s):

María José Villanueva ◽

Fátima Navarro ◽

Antonio Sánchez ◽

Mariano Provencio ◽

Félix Bonilla ◽

...

Keyword(s):

Down Syndrome ◽

Germ Cell ◽

Germ Cell Tumor ◽

Medical Literature ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

English Medical Literature

The association between Down syndrome and testicular germ cell tumors may be more frequent than expected according to chance, but few reports have focused on this excess. We report two cases of this association and review the English medical literature.

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Evidence for Altered Hypothalamic-Hypophyseal-Gonadal Axis in Untreated Patients with Testicular Germ-Cell Tumor

Tumori Journal ◽

10.1177/030089168907500523 ◽

1989 ◽

Vol 75 (5) ◽

pp. 505-509

Author(s):

Sergio Crispino ◽

Gabriele Tancini ◽

Sandro Barni ◽

Paolo Lissoni

Keyword(s):

Testicular Cancer ◽

Germ Cell ◽

Germ Cell Tumor ◽

Venous Blood ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumor ◽

Cell Tumor ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Significant Difference

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 μg as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, nonseminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the Physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.

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