Abstract
Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95% CI [0.71-0.89]) and 0.59 (95% CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage.
Highlights
Aging is associated with a progressive decline in the functional reserve of multiple organ systems [1]
Duplicate telomere length (TL) distribution measurements were performed on blood samples from 109 of the 111 patients included between August 2007 and January 2010
We can identify two groups of patients with different treatment completion rates according to their TL distribution: 80% (95%confidence intervals (CIs): 71% to 89%) in the group with telomeres longer than 5·77 kb (LT group) versus 59% (95%CI: 41% to 76%) in the group with shorter telomeres (ST group, P=0·02)
Summary
Aging is associated with a progressive decline in the functional reserve of multiple organ systems [1]. Given that the process of aging is heterogeneous, this decline should ideally be assessed individually and care of an elderly person adapted rather than solely on the basis of chronological age. Such assessments are currently entirely clinical, based on a geriatric evaluation. The gradual loss of telomeric DNA in dividing somatic cells contributes to replicative senescence [2]. This telomere length dynamics plays an important signaling role in determining cell fate during aging and cancer [3]. Patients with shorter telomeres tend to develop more functional disabilities [4], have increased cognitive loss [5], higher cardiovascular morbidity [6], more degenerative diseases [7] and higher mortality [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
