Changes to the mitochondrial DNA in non-cancer cells induced by chemotherapy and the relation with fatigue in men with germ-cell cancer of the testis: a feasibility study.

Cancer-related fatigue is experienced in all stages of the disease trajectory.
Despite much research, the pathogenesis of fatigue is still unknown. Cancer
patients indicate that fatigue is more troublesome and has a greater negative
influence on quality of life and daily activities than any other cancer-related
symptom, including pain, nausea and depression.

One of the working mechanism of chemotherapeutic regimen is severe damage to
the nuclear genome of the tumor cell to impair cell division. Studies indicate
that chemotherapy does not only damage the nuclear genome, but also affects the
mitochondrial DNA. Mitochondria, small organelles found in eukaryotic cells,
are responsible for the energy production of the cell by the respiratory chain.
Mitochondrial DNA is responsible for the production of 13 polypeptides involved
in the respiratory chain. The consequence of changes in mitochondrial DNA is
illustrated by mitochondrial myopathies with symptoms including experiences of
fatigue.

Because cancer patients undergoing chemotherapy can become fatigued and
chemotherapy might induce mitochondrial impairment via changes in mitochondrial
DNA, it could be hypothesized that cancer-related fatigue is due to functional
impairment of mitochondria caused by chemotherapy. Therefore, we want to
perform a feasibility study in a small but homogeneous group of cancer patients
treated with chemotherapy. We aim to include men with metastatic germ cell
cancer of the testis, planned to be treated with chemotherapy. These relatively
young patients become severely fatigued during chemotherapy and the prevalence
of chronic fatigue ten years after completing treatment in this population is
almost twice as high as in the general population.

In this pilot study, we want to investigate whether it is feasible to study the
accumulation of changes in mtDNA in non-cancer cells as a possible explanation
for the development of fatigue in patients treated with chemotherapy for
metastatic testicular cancer.

We aim to conduct an observational study with four measurement points:
1) Before the administration of the first cycle chemotherapy
2) Before the administration of the second cycle chemotherapy
3) Before the administration of the third cycle chemotherapy
4) At the second follow-up visit after completing chemotherapy (±14 weeks)

Limited burden: Blood sampling is part of the regular care and thus no
additional invasive investigation.
Limited risk: Blood sampling is part of the regular care.