Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

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Testicular Neoplasms

Endocrine Gland Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Central Nervous System Depressants

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Insulin

Insulin, Globin Zinc

Cisplatin

Plasminogen Activator Inhibitor 1

Testicular cancer survivors who were treated between 2000 and 2005 or between 2006 and 2012 with cisplatin-combination chemotherapy and who were extensively phenotypically mapped within two longitudinal trials (15,16) will be invited to participate in a single cross-sectional follow-up study visit 5-20 years after chemotherapy.

Patients with metastasized testicular cancer who are about to start with cisplatin-combination chemotherapy will be invited in the longitudinal part of this study. Study participation involves four study visits:

Visit 1: before start of chemotherapy Visit 2:before third cycle of chemotherapy Visit 3: one month after completion of chemotherapy Visit 4: one year after start of chemotherapy

Patients with stage I testicular cancer will serve as control group with three study visits:

Visit 1: at time of orchidectomy Visit 2: one month Visit 3: one year after orchidectomy

A 4 mm skin biopsy will be performed at the upper leg of the patient. Before the skin biopsy local anesthesia is applied subcutaneously. In these skin biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels in the skin biopsies.

Skin biopsy

An abdominal subcutaneous fat biopsy will be performed 7-10 cm on the right side of the umbilicus. Before the fat biopsy local anesthesia is applied subcutaneously. An amount of 30 mg fat tissue will be collected using needle aspiration.

In these fat biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels (ICP-MS), adipocytokines (leptin, adiponectin, interleukin-6, PAI-1, TNF-α), p53 activation indirectly by measuring p21 or mdm2 expression using immunohistochemistry, microRNA regulation of insulin signaling in adipose tissue: miR-103, miR-107, miR-29.

Subcutaneous fat biopsy

J. A. Gietema, prof.

J. A. Gietema, Prof.

Cisplatin-combination chemotherapy causes inevitably DNA damage by platinum-DNA adduct formation of both tumor cells but also healthy cells. It therefore stands to reason that testicular cancer treatment causes an increased burden of senescent cells, which causes upregulation of the SASP resulting in a pro-inflammatory phenotype. The investigators hypothesize that this may be an important mechanism behind development of late effects and an early ageing phenotype after treatment for testicular cancer.

A study will be performed consisting of two cohorts. Cross-sectional study Testicular cancer survivors treated between 2000 and 2005 or between 2006 and 2012 with cisplatin-combination chemotherapy and were extensively phenotypically mapped within two longitudinal trials will be invited to participate in a single cross-sectional follow-up study visit 5-20 years after chemotherapy.

Longitudinal study

Patients with metastasized testicular cancer who are about to start with cisplatin-combination chemotherapy will be invited. Study participation involves four study visits:

Visit 1: before start of chemotherapy Visit 2: before third cycle of chemotherapy Visit 3: one month after completion of chemotherapy Visit 4: one year after start of chemotherapy

Patients with stage I testicular cancer will serve as control group with three study visits:

Visit 1: at time of orchidectomy Visit 2: one month after orchidectomy Visit 3: one year after orchidectomy

Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study

The change in the amount of senescent cells in skin and fat tissue (defined as % of cells in which nucleus is stained positive for P16, P21 and yH2Ax)

Change in levels of the cytokines: IL-6, IL-8, VEGF

Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV).

Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed.

Changes in levels of leptin and PAI-1 (ug/L)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study	NCT04113122	Testicular Canc...	Skin biopsy Subcutaneous fa...	18 Years - 50 Years	University Medical Center Groningen
Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study	NCT04113122	Testicular Canc...	Skin biopsy Subcutaneous fa...	18 Years - 50 Years	University Medical Center Groningen

Spots Global Cancer Trial Database for subcutaneous fat biopsy