Thromboembolic Events During Chemotherapy for Germ Cell Cancer: A Cohort Study and Review of the Literature

PURPOSE: To evaluate the risk of major thromboembolic complications in male germ cell cancer patients receiving cisplatin-based chemotherapy and to review the literature on this subject. PATIENTS AND METHODS: One hundred seventy-nine germ cell cancer patients treated between January 1979 and May 1997 in our hospital were analyzed with respect to risk factors for developing thromboembolic events, such as baseline tumor characteristics, prior tumor therapy, administration of cytostatic agents, and the use of antiemetic drugs. The patients were treated with a variety of combination chemotherapy regimens, primarily cisplatin-containing combination regimens. RESULTS: Of the 179 patients, 15 patients (8.4%) were identified who developed a total of 18 major thromboembolic complications in the time period between the start of chemotherapy and 6 weeks after administration of the last cytostatic drug in first-line treatment. Of these 18 events, three (16.7%) were arterial events, including two cerebral ischemic strokes, and 15 (83.3%) were venous thromboembolic events, including 11 pulmonary embolisms. One (5.6%) of the 18 events was fatal. Liver metastases (odds ratio, 4.9; 95% confidence interval, 1.1 to 20.8) and the administration of high doses of corticosteroids (≥ 80 mg dexamethasone per cycle; odds ratio, 3.5; 95% confidence interval, 1.2 to 10.3) as antiemetic therapy were identified as risk factors for the development of major thromboembolic complications. CONCLUSION: Germ cell cancer patients who receive chemotherapy, in particular those who have liver metastases or receive high doses of corticosteroids, are at considerable risk of developing thromboembolic complications.

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Risk factors for thromboembolic events in testicular cancer patients receiving chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16109 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16109-e16109

Author(s):

K. Shim ◽

K. R. Potvin ◽

K. Mills ◽

F. Whiston ◽

L. Stitt ◽

...

Keyword(s):

Risk Factors ◽

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Germ Cell Tumors ◽

Retrospective Chart Review ◽

Germ Cell Cancer ◽

Thromboembolic Events ◽

Increased Risk ◽

Risk Of Hemorrhage

e16109 Background: Cancer patients are at increased risk for thromboembolic events (TTEs), and those receiving chemotherapy are at even greater risk. Clinical experience and the literature have suggested that men receiving cisplatin-based chemotherapy for metastatic germ cell tumors are at particularly high risk. As TTEs can be fatal and treatment is curative, the stakes are high. Despite this, prophylactic anticoagulation (PA) is not routinely used. Methods: All men treated with cisplatin-based chemotherapy for metastatic germ cell cancer at the London Regional Cancer Program from January 1978 to December 2007 were identified from electronic databases. Data including type and timing of TTEs were extracted by retrospective chart review. Multivariable analyses were used to identify predictors of TTEs. Results: 196 eligible patients were identified with median age 31 years (range, 15–75). No patients received PA. Thirty-two TTEs were identified in 29 patients for an overall incidence of 14.8% (95% CI, 9.8–19.8%). The majority of events were deep venous thromboses, and five patients died due to TTE or its complications. Sixteen of the patients with TTE (55.2%) were diagnosed while on treatment (defined as TTE within 6 months of chemotherapy initiation); 8 (27.6%) had their TTE prior to, and 5 (17.2%) after this time period. Age greater than 30 years (OR = 3.02; 95% CI, 1.10–8.33; p = 0.033) and elevated LDH (OR = 1.93; 95% CI, 1.07–3.48; p = 0.029) were independently associated with an increased risk of TTE. If both adverse risk factors were present, the risk of TTE on treatment was 21.7% (95% CI, 9.8–33.7%). If neither were present, the negative predictive value was 97% (95% CI, 92–100%). Conclusions: The overall TTE incidence rate of 14.8% is consistent with prior reports (8.4–19%). The risk of TTE appears greatest during chemotherapy and shortly thereafter, and nearly one in 10 patients in this group had a TTE. These data support the concept of PA for selected patients starting chemotherapy for metastatic germ cell cancer. However, the efficacy of PA and risk of hemorrhage in this group is unknown. In this cohort, patients under 30 with normal LDH were at very low risk for TTE. Confirmation of these findings to help guide the study and optimal use of PA should be pursued. No significant financial relationships to disclose.

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Prognostic Significance of Venous Thromboembolic Events in Disseminated Germ Cell Cancer Patients

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djw265 ◽

2017 ◽

Vol 109 (4) ◽

pp. djw265 ◽

Cited By ~ 3

Author(s):

Enrique Gonzalez-Billalabeitia ◽

Daniel Castellano ◽

Nora Sobrevilla ◽

Josep Guma ◽

David Hervas ◽

...

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Prognostic Significance ◽

Germ Cell Cancer ◽

Thromboembolic Events ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

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The Risk of Vascular and Thromboembolic Events Is Increased In Young Low-Risk Germ Cell Cancer Patients by Cisplatin Containing Chemotherapy

Blood ◽

10.1182/blood.v116.21.5119.5119 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5119-5119

Author(s):

Leticia M Solari ◽

Kathrin Dollinger ◽

Jürgen Heinz ◽

Heike Reinhardt ◽

Susanne Rohdenburg ◽

...

Keyword(s):

Risk Factors ◽

Germ Cell ◽

Laboratory Tests ◽

Conflicts Of Interest ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Thromboembolic Events ◽

Vascular Events ◽

Nicotine Abuse ◽

Increased Risk

Abstract Abstract 5119 Introduction: It has been previously reported that both short and long term vascular and thromboembolic events (TEE) occur following cisplatin containing chemotherapy for germ-cell cancer (GCC) (Bokemeyer et al. 1998, Weijl et al. 2000, Diekmann et al. 2010). It has also been shown that patients with GCC are at higher risk of TEE than patients with non-GCC, while on cisplatin-based chemotherapy (Piketty et al. 2005). Method: We reviewed all GCC patients treated in our department from 2008 until 2010 with cisplatin-based chemotherapy and assessed the incidence of TEE. Cases were analyzed with respect to risk factors for vascular events (obesity, diabetes, nicotine abuse, prior cardiovascular disease, prior TEE), tumor characteristics (low- vs. intermediate/high-risk GCC) and age. In addition, further analysis of hemostasis laboratory tests of these patients is being performed. Result: Eight patients (8/50=16%) treated with cisplatin-containing chemotherapy developed TEE. Of these TEE, two were myocardial infarctions, four pulmonary embolisms, one patient showed thrombosis of the jugular vein and one a peripheral (femoral) arterial thrombosis. TE-risk factors included: nicotine abuse in two patients, obesity and nicotine abuse in one patient and no identifiable factors in the others (hemostasis laboratory tests are currently being performed). The median age of these 8 patients was 42 years (range 16–61). Patients were treated with PEB (cisplatin, etoposide, bleomycin) or PIV (cisplatin, ifosfamide, etoposide) initially applying continuous heparin prophylaxis with 15000IE/day (d), d1-5 only during PEB or PIV, but no low-molecular weight heparin (LMWH-) and/or aspirin (ASS-) medication for venous and arterial TEE prophylaxis thereafter. With these clinically very relevant and severe TEEs, we have adapted our PEB- and PIV protocols, adding a LMWH prophylaxis (enoxaparin 40mg d6-21 after chemotherapy). Conclusion: We observed an increased risk of major thromboembolic and vascular events with an incidence rate of 16% in GCC patients after cisplatin-containing chemotherapy. Prior studies have identified TEE-risks in GCC and with cisplatin-chemotherapy, albeit LMWH- and/or ASS-prophylaxis - without clinical trials - has not been recommended as yet. Prospective studies investigating thrombosis prophylaxis measures are currently performed in order to achieve the best standard of care for these patients. Currently an extensive hemostasis diagnostic testing from all patients with TEE is being performed. Disclosures: No relevant conflicts of interest to declare.

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Venous Thromboembolic Events in Germ Cell Cancer Patients Undergoing Platinum-Based Chemotherapy

Onkologie ◽

10.1159/000355652 ◽

2013 ◽

Vol 36 (11) ◽

pp. 7-7 ◽

Cited By ~ 9

Author(s):

Friedemann Honecker ◽

Daniel Koychev ◽

Anna D. Luhmann ◽

Florian Langer ◽

Klaus-Peter Dieckmann ◽

...

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Thromboembolic Events ◽

Platinum Based Chemotherapy ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

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437: Predictability of Androgen Deficiency in Testicular Germ Cell Cancer Patients by Residual Testicular Volume

The Journal of Urology ◽

10.1016/s0022-5347(18)34690-1 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 119-119 ◽

Cited By ~ 1

Author(s):

Gerald Puehse ◽

Armin Secker ◽

Sebastian Kemper ◽

Lothar Hertle ◽

Sabine Kliesch

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Testicular Volume ◽

Androgen Deficiency ◽

Testicular Germ Cell ◽

Testicular Germ Cell Cancer

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Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: A proof of principle

Molecular Oncology ◽

10.1016/j.molonc.2013.08.002 ◽

2013 ◽

Vol 7 (6) ◽

pp. 1083-1092 ◽

Cited By ~ 85

Author(s):

Ad J.M. Gillis ◽

Martin A. Rijlaarsdam ◽

Ronak Eini ◽

Lambert C.J. Dorssers ◽

Katharina Biermann ◽

...

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Testicular Germ Cell ◽

Serum Mirna ◽

Testicular Germ Cell Cancer ◽

Proof Of Principle

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A multi-center prospective phase II study of high-dose chemotherapy in germ-cell cancer patients relapsing from complete remission

Annals of Oncology ◽

10.1023/a:1008328012040 ◽

1999 ◽

Vol 10 (12) ◽

pp. 1467-1474 ◽

Cited By ~ 45

Author(s):

S. Rodenhuis ◽

R. de Wit ◽

P.H.M. de Mulder ◽

H.J. Keizer ◽

D.T. Sleijfer ◽

...

Keyword(s):

Complete Remission ◽

Germ Cell ◽

Cancer Patients ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Cancer ◽

High Dose Chemotherapy ◽

Germ Cell Cancer ◽

High Dose ◽

Prospective Phase

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A single centre retrospective review of testosterone deficiency in germ cell cancer patients

Annals of Oncology ◽

10.1093/annonc/mdx371.071 ◽

2017 ◽

Vol 28 ◽

pp. v325

Author(s):

L.S. Gibbs ◽

G.L. Gullick ◽

E. Allison ◽

S. Brand ◽

A. Addeo ◽

...

Keyword(s):

Germ Cell ◽

Cancer Patients ◽

Retrospective Review ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Testosterone Deficiency ◽

Single Centre

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Prognostic factors for relapse in patients with clinical stage I testicular cancer: protocol for a Danish nationwide cohort study

BMJ Open ◽

10.1136/bmjopen-2019-033713 ◽

2019 ◽

Vol 9 (10) ◽

pp. e033713 ◽

Cited By ~ 2

Author(s):

Thomas Wagner ◽

Birgitte Grønkær Toft ◽

Birte Engvad ◽

Jakob Lauritsen ◽

Michael Kreiberg ◽

...

Keyword(s):

Risk Factors ◽

Testicular Cancer ◽

Germ Cell ◽

Clinical Stage ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Stage I ◽

Testicular Germ Cell ◽

Testicular Germ Cell Cancer

IntroductionApproximately one-fourth of patients with clinical stage I testicular germ cell cancer will relapse within 5 years of follow-up. Certain histopathological features in the primary tumour have been associated with an increased risk of relapse. The available evidence on the prognostic value of the risk factors, however, is hampered by heterogeneity of the study populations included and variable reporting of the histopathological features. The aim of this study is to identify pathological risk factors for relapse in an unselected large nationwide cohort of patients with stage I disease.Methods and analysisAll incident cases of stage I testicular germ cell cancer diagnosed in Denmark between 2013 and 2018 will be identified using the nationwide prospective Danish Testicular Cancer (DaTeCa) database. Archived microscopic slides from the orchiectomy specimens will be retrieved through linkage to the Danish Pathology Data Bank and reviewed blinded to the clinical outcome. The DaTeCa database includes 960 stage I seminoma patients with expected 185 relapses and 480 patients with stage I non-seminoma with expected 150 relapses. A minimum follow-up period of 3 years of all patients will be ensured. Predefined prognostic variables will be investigated with regard to relapse in univariable and multivariable analysis using the Cox proportional hazards model.Ethics and disseminationThis study protocol has been approved by the Regional Ethics Committee (Region Zealand, Denmark) and the Danish Data Protection Agency. All data will be managed confidentially according to legislation. Study results will be presented at international conferences and published in peer-review journals.

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