Finding biomarkers to assess frailty in cancer patients
Dr Bruna Dalmasso - Katholieke Universiteit Leuven, Leuven, Belgium
We evaluated potential biological frailty markers in both elderly and young persons because many biomarkers have been studied in geriatrics as biomarkers of frailty but the oncological patient has many differences with respect to the general geriatric patients so findings from general geriatrics cannot be extrapolated and just applied to the oncological patients.
What biomarkers have you been looking for?
We focussed mainly on the immunitary aging, so immunosenescence and inflammaging; telomere length in leukocytes which can be a marker of immunosenescence because leukocytes tend to be less active in the elderly. The CD8/CD4 ratio is altered and so we wanted to see if relative telomere length in leukocytes, shortening of telomere length, could correlate with frailty.
Have you been able to correlate these with clinical markers of frailty?
Yes, there are also other biomarkers – interleukin-6, MCP-1 and RANTES and IGF-1 which is a molecule involved in the insulin IGF growth factor pathway which is altered in the elderly. We correlated them both with chronological age and with clinical global health that we measured, mainly by comprehensive geriatric assessment, all the subtypes of the comprehensive geriatric assessment.
Have you been able to correlate the molecular markers with the clinical factors?
Not all of them. All the biomarkers except RANTES correlated with chronological age but only interleukin-6 correlated with frailty, with clinical frailty.
Has this provided you with a molecular signature for frailty?
Not really a molecular signature because just one of the molecules correlated with frailty in our study so we couldn’t make that sort of signature because telomere length correlated only with chronological age as well as the other molecules except interleukin-6. RANTES did not correlate either with chronological age or with frailty so we just had one biomarker of frailty and that was significant, interleukin-6.
Are you now able to tell doctors to look for one biomarker in particular?
It’s too early because it is true that in our study interleukin-6 correlated with frailty but we still don’t have a cut-off so first we will need to do further research focussing now just on interleukin-6 and then try to find a cut-off for frailty for that molecule. So now it’s still not ready for the clinic, however it will be useful in the future to have frailty biomarkers in the clinic easily measurable in blood because a comprehensive geriatric assessment is now the clinical gold standard but it doesn’t have a validated end score and it takes 45 minutes to be performed.
What contribution might this molecular assessment make to treatment decisions?
Now we’re looking also at other biomarkers in other projects. It will be very useful to find molecular biomarkers because then a patient wouldn’t have to come for another visit for a geriatric evaluation or biomarkers could be additive to geriatric assessment. In this study interleukin-6 was not additive to comprehensive geriatric assessment, they were the same, but we don’t know if interleukin-6 or also the other biomarkers could be predictive of death during chemotherapy of short- or long-term toxicities. We’re doing it in another project and that will be interesting and it will be useful in the clinic.
Some of these markers could be predictive?
It could be predictive of toxicity but we still don’t know, we’re evaluating it now. We’re doing another study of biomarkers during chemotherapy follow-up, both plasmatic inflammatory molecules and micro-RNAs have just finished, a micro-RNA experiment and also the analysis gene expression but we still don’t have the results.
What are the key messages?
The majority of cancer patients are older than 70 years, especially breast cancer patients because breast cancer is a disease that increases with age and life expectancy is increasing as well. Making a treatment programme for an elderly patient is very often challenging for the clinician because frailty patients could have more toxicity during cancer chemotherapy and it cannot be done solely based on chronological age. You can distinguish between very fit and very frail old patients but there is an in-between grey zone that is very difficult to set. Then there is a clinical method, which is the comprehensive geriatric assessment, but it’s time-consuming. So the research we’re doing is due to give the clinician more easily and fast ways to assess frailty in order to make the best decisions for patients and avoid over-treatment or under-treatment which is what frequently happens more in elderly patients with breast cancer.