Testicular Cancer
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTSkin biopsy
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.
DIAGNOSTIC_TESTSubcutaneous fat 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.
Sponsors
Dutch Cancer Society
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
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
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in the cross-sectional part of this study, a subject must meet all of the following criteria: * Diagnosed with metastatic testicular cancer in 1999-2012 (stage II or higher) * Received first-line cisplatin-based chemotherapy * Was younger than 50 years of age at start of chemotherapy In order to be eligible to participate in the longitudinal part of this study, a subject must meet all of the following criteria: Chemotherapy-group: * Diagnosis of metastatic testicular cancer (stage II or higher) * Is about to start with first-line cisplatin-based chemotherapy * Younger than 50 years of age at diagnosis of metastatic testicular cancer Stage I control-group: * Diagnosis of testicular cancer stage I disease * Younger than 50 years of age at diagnosis of testicular cancer
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study: \- Not able to provide informed consent (in example in case of mental or psychiatric disability)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cellular senescence | 1 year | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Senescence-associated secretory phenotype (SASP) | 1 year | Change in levels of the cytokines: IL-6, IL-8, VEGF |
| Pulse-wave velocity | 1 year | Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV). |
| Platinum levels | 1 year | Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed. |
| Adipocytokines 1 | 1 year | Changes in levels of leptin and PAI-1 (ug/L) |
| Adipocytokines 2 | 1 year | Changes in levels of adiponectin (ug/mL) |
Countries
Netherlands
Contacts
Primary ContactJ. A. Gietema, prof.
Outcome results
None listed