TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects

Testicular cancer (TC) is a rare disease, which mostly affects young men aged 15-35 years. Their life expectancy has greatly improved due to the introduction of platinum-containing chemotherapy for disseminated TC in the late 1970s. Given the good prognosis of TC nowadays, prevention or early detection of late adverse effects of TC treatment has become increasingly important. Current literature suggests that TC treatment, and specifically exposure to platinum agents, is associated with increased risk of cardiovascular morbidity and mortality. The precise role of treatment components like platinum in the pathogenesis of cardiometabolic changes and cardiovascular disease (CVD) warrants further investigation, since it is not known if CVD develops through direct platinum-induced damage of the vascular wall or by mediation through development of cardiometabolic riskfactors. The aim of this study is to identify risk factors for development for CVD after treatment for TC. A more profound insight into pathophysiologic mechanisms and identification of risk factors for CVDs is needed to facilitate development of preventive strategies and to optimize survivorship care.

Design: The investigators will perform a multicenter case-cohort study. Patients treated for TC who developed cardiac disease ((either myocardial infarction, proven coronary artery disease (grade ≥2) or congestive heart failure (grade ≥2)) will be invited by their (former) treating oncologist to participate in this study (cases). Furthermore, in each hospital a random sample of 15% of the total population treated for TC will be invited (the subcohort). The investigators will collect detailed diagnostic- and treatment data on TC and on (risk factors for) CVD for all cases as well as for all subcohort members. All cases and subcohort members will be approached to complete a questionnaire and to donate a blood sample for DNA analysis, after written informed consent. Patients who were younger than 40 years at TC diagnosis and younger than 75 years at moment of study contact will be asked to participate in the cardiometabolic risk inventory sub study. For this, participants have to undergo a basic study assessment consisting of physical examination, venapuncture and handing in a morning urine sample. This assessment can be performed at the participating hospital, their general practitioner or during a home visit by a member of the investigators research team. Additional (non-invasive) cardiovascular function measurements (IMT and AGEs) are only performed in the UMCG.

Eligibility Criteria:
All participating patients have to meet the following criteria:

* Alive
* TC diagnosis between 01-01-1976 to 31-12-2007
* TC treatment center: UMCG, NKI/AVL, Erasmus MC, UMCN, LUMC
* Younger than 50 years of age at TC diagnosis
* Written informed consent

Cases have to fulfill, beside the aforementioned criteria, the following criteria:

* Diagnosed with either myocardial infarction (MI), proven coronary artery disease (CAD) (CTCAE-4 grade 2 or higher) or congestive heart failure (CHF) (CTCAE-4 grade 2 or higher).
* No medical history of CVD before diagnosis of TC

In order to be eligible to participate in the cardiometabolic risk inventory study (and to be invited to a study assessment), a subject must meet, next to the criteria mentioned in "1)", the following inclusion criteria:

* Younger than 40 years of age at TC diagnosis
* Younger than 75 years of age at moment of inclusion

Exclusion criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Mental disorder (no informed consent available)
* Presence of active malignant disease