Optimization of systemic treatment strategies in elderly patients with advanced solid malignancies: OptiMal trial

The incidence of cancer increases with age. More than fifty percent of all
newly diagnosed patients in the Western world is older than 60 years of age.
Treatment with a combination of cytotoxic agents is often indicated as
(palliative) treatment in patients with advanced malignancies. It is unclear to
what extent older patients should receive similar treatment as younger
patients, because in most randomized clinical trials in which standard
treatment strategies have been established, the mean age of patients was below
60 years. Apart from the fact that elderly patients are often less resilient,
sometimes even frail and have more co-morbidity, including impaired cognitive
function, also other factors may play a role in potential serious toxicities
compared to younger patients.
Myelotoxicity is an important factor in the completion of treatment in these
patients and may often lead to dose reduction, postponement of therapy and
hospitalization. There is consistent evidence that patients with sarcopenia
present with more severe toxicity during treatment with cytotoxic agents. This
muscle depletion is age related and may be an indication for dose adjustment
especially in the elderly. We assume that the myelodysplastic syndrome may
contribute to myelotoxicity in this group of patients as well. It*s occurrence
increases with age and its incidence and prevalence have increased
significantly over the past 20 years. It is often underdiagnosed and
unrecognized.
Considering the increasing age of the entire population, it is of utmost
importance to develop accurate methods to individualize treatment strategies in
elderly patients. We hypothesize that a Comprehensive Geriatric Assessment with
measurement of human body composition with computerized tomography and / or a
standardized flow cytometry test to determine bone marrow capacity will provide
an accurate tool to optimize treatment strategies in elderly patients with
advanced malignancies.

To assess whether the presence of a myelodysplastic syndrome, idiopathic
cytopenia of undetermined significance (ICUS) or idiopathic dysplasia of
undetermined significance (IDUS), correlates with treatment intensity and
clinical outcome in older patients with advanced malignancies receiving
palliative chemotherapy.
We will study the relation between sarcopenia, comprehensive geriatric
assessment en pharmacokinetics with treatment related toxicity as well.

A prospective clinical trial is designed. Patients will be treated according to
current standard of care. Included patients will undergo a geriatric assessment
prior to treatment. This assessment consists of several questionnaires and
functional tests, assessment of body composition (CT scan) and a peripheral
blood and (optional) bone marrow examination including a flow cytometric
assessment of hematopoietic cells. The latter will be used to determine whether
myelodysplasia or ICUS or IDUS can be diagnosed. We will monitor patients*
charts during treatment and post treatment for a maximum of 6 months. We will
register toxicity, termination, postponement or dose modifications of treatment
due to any cause.
During follow up we will ask patients to fill out the EORTC QLQ C-30
questionnaire.

Patients will be submitted to a geriatric assessment. The assessments consits
of various questionnaires and functional tests and will have a total duration
of about 30 minutes. After that a venapunction will be taken, potentially
followed by the bone marrow aspirate, which will also take 15 minutes. After
the aspirate patient wll have to lay down for 10 minutes to apply pressure to
the punctionwound.

In a review by the British Society of Haematology on adverse events (AE)
associated with a diagnostic bonemarrow aspirate / biopsy in 0.08% of
procedures an AE was seen. In most cases there was bleeding (0.06%) en in fewer
cases pain (0.01%). In 0.015% of cases a serious AE occured. In a study on pain
in bone marrow aspiration and biopsies in 120 patients, patients reported a low
painscore and most patients (97%) were satisfied with local anaesthesia during
the procedure.