Change of geriatric morbidity and muscle mass of elderly patients with malignant disease after treatment with palliative and adjuvant chemotherapy

Ageing is an important phenomenon in the Dutch population. Cancer is the most
common cause of death since 2008 and we assume that the incidence of cancer
will increase because of this. More than half of the patients with oncologic
disease is at an advanced age. This leads to a serious increase of the elderly
population with oncologic disease in hospitals. In these vulnerable group of
patients there are large differences in physiologic reverse capacity because of
cognition, comorbidity, nutritional status and impaired mobility. Those
differences are not always corresponding with age. Identifying the people, who
will benefit from invasive oncologic treatment, is elusive. Geriatric
assessment is considered as gold standard of evaluating patient vitality and
physiological reserve and has shown to be an important diagnostic tool in the
prediction of all cause mortality and chemotherapeutic toxicity in elderly
patients undergoing oncologic treatment. Geriatric assessment prior to
oncologic treatment, however, has limitations. It can be executed in all
elderly people to predict clinical outcome and treatment tolerability, but the
assessment is time-consuming and the necessity of screening the entire elderly
population undergoing chemotherapy remains unclear. It is desirable to
determine a combination of markers that could be used during routine clinical
practice to assess the risk of complicated oncologic treatment.

Secondly, sarcopenic obesity is associated with impaired daily functioning en
the presence of sarcopenia could be a predictor of overall mortality. According
to the European concensus sarcopenia is defined as a loss of muscle due to age
in combination with impaired muscle power or function. In the literature
several methods to measure body composition are reported. Determination of the
lumbal skeletal index by slice o matic is internationally validated. There are
also signs that endocrinologic factors influence the development of sarcopenia.
Advanced age results in an increase of the amount of visceral adipose tissue.
This causes more production of pro-inflammatory cytokins. These biomarkers are
chronically elevated in elderly people and possibly cause the development of
sarcopenia as well. It is possible to determine the prevalence of cellular
senescence in skin biopsy. Senescence is defined as arrest during the cell
cycle and plays a role in cellular pathways in the process of aging. Senescence
will occur if DNA repair mechanisms are activitated. The cell looses the
ability to proliferate. The question is if could be a predictor of overall
surivival.

We hypothesize that geriatric markers, sarcopenia and biological markers
predict progression free and overall survival and chemotherapeutic toxicity in
elderly patients with cancer. This study is powered on the effect size of
sarcopenia on the overall survival as this is our primary question.

The aim of this study is to assess the prognostic value of sarcopenia and
geriatric markers for survival and treatment tolerability and fluctuation of
this value between several oncologic conditions. Secondly, we focus on the
value of repeated CGA as this is important for effective geriatric
interventions in routine geriatric care and the prognostic value of treatment
adjustments based on CGA.

Primary objective:
1. Is sarcopenia (by CT imaging) prior to chemotherapeutic treatment correlated
with overall survival?

Secundary objectives:
2. Is sarcopenia (by CT imaging) prior to chemotherapeutic treatment correlated
with PFS and grade 3-4 chemotherapeutic toxicity?
3. Is dosage of chemotherapy per cm2 lean body mass related to PFS, OS, grade
3-4 chemotherapeutic toxicity and dose density of chemotherapy?
4. What is the value of geriatric markers in the prediction of PFS, OS and
chemotherapeutic toxicity in older patients with malignant disease?
5. Which combined geriatric markers provide the most accurate prediction of
PFS, OS and chemotherapeutic toxicity in older patients with malignant disease?
6. Are biological markers (senescence in a skin biopt, single nucleotide
polymorphisms, interleukins or other laboratory markers) related to PFS, OS and
grade 3-4 chemotherapeutic toxicity?
7. Which definition of sarcopenia provides the best prediction of PFS, OS and
chemotherapeutic toxicity?

Prospective multi centre cohort study

Number of research moments: 4 during 1 year. Duration: 60-75 min each
Number of laboratory research: 4 times
Number of skin biopsies: Once after inclusion

Research persons fill independently 2 questionnaires per research moment.
Further questionnaires and examination take place together with the researcher
during research moments. Physical examiniation contains low invasive tests such
as gait speed, a short period of cycling and measuring muscle power.
Disadvantages contain time investment of the research person and some
questionnaires might be confronting. (for example: the geriatric depression
scale) Participation in laboratory research and donating biopsy of the skin is
voluntary. If the research person doesn't want to participatie it is still
possible to join other aspects of the study.

Diagnostic imaging (CT) is performed during routine patient care. If that is
not the case, measurement of muscle mass by slice-o-matic will be voided.
Therefore, research persons are not exposed to extra radiation. The study has
no influence on the regular oncologic treatment.