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Review Hematology
Onco-haematology geriatry: impact
of cognitive disorders
S. Dubruille, PhD1,2, Y. Libert, PhD2, D. Razavi, MD, PhD2, D. Bron, MD, PhD1
A Comprehensive Geriatric Assessment is recommended to detect vulnerable cancer patients for whom
chemotherapy may lead to severe impairment on functionality, quality of life, or survival. Although Comprehensive Geriatric Assessment is useful for better management of older patients with unsuspected
problems, little is known about the reliability of the Comprehensive Geriatric Assessment to optimise the
therapeutic approach in a specific patient with a malignant haemopathy. Particularly, the prognostic value
of cognitive impairment in clinically fit older patients with haematological malignancies admitted to receive
chemotherapy, are poorly investigated. This article investigated this question and tries to explain links
between cognitive impairment and poor overall survival. Finally, this article tries to propose supportive
interventions to reduce morbidity and mortality in older cancer patients with cognitive impairment.
(Belg J Hematol 2016;7(5):180-3)
Introduction
Over 50% of all new cancer diagnoses occur in older
patients.1 Predictions suggest that before 2050, there
will be a further 40% increase in the number of patients
living with cancer, of who one-third will be aged 80
years and older.2 Nevertheless, there is substantial underrepresentation of patients 65 years or older in studies
of treatment for cancer.3 Geriatric patients typically have
a greater burden of comorbid medical conditions; however, these may incompletely represent the spectrum of
physiologic age and vulnerability.4
Growing evidence suggests that a G8 screening tool and
a Comprehensive Geriatric Assessment (CGA) in older
patients with malignant haemopathies helps heamatologists detect ‘frailty’ in cancer patients leading to
useful interventions but less useful to identify patients
for whom chemotherapy should be avoided or reduced
as it could negatively impact functionality, quality of
life, treatment-related toxicity, or survival.5-9
Moreover, specific data are lacking on the use of the
G8 screening tool and CGA for specific older patients
with haematological malignancies assessed by their
physicians as clinically fit, meaning not exhibiting
geriatric syndromes and/or irreversible comorbidities
significantly impairing their daily function, and thus
able to receive chemotherapy. Detecting clinically fit older
patients is crucial because of the risks entailed by an
inadequate therapeutical approach. On one hand, undertreating a patient because of comorbidities – although
these could be reversible if due to the disease itself –
could prevent this patient from being cured. On the
other hand, treating undetected ‘vulnerable’ patients
with a standard chemotherapy regimen could result
in severe side effects ultimately leading to geriatric syndromes, dependence of the patient, and sometimes,
life-threatening adverse events.10
Results
Recently, we found that the G8 screening tool identified vulnerability in clinically fit older patients with
haematological malignancies with moderate diagnostic
accuracy.11 Indeed, neither the G8 nor the CGA total
score (>2 impairments) seems to predict intolerance
to treatment and survival among older patients with
Department of Haematology, Institut Jules Bordet, Université Libre de Brussels, Brussels, Belgium, 2Clinic of Psycho-Oncology, Institut Jules
1
Bordet, Université Libre de Brussels, Brussels, Belgium.
Please send all correspondence to: S. Dubruille, PhD, Institut Jules Bordet, Department of Haematology, 121 Boulevard de Waterloo, 1000 Brussels,
Belgium, tel: +32 2 541 37 28, email: [email protected].
Conflict of interest: The authors have nothing to disclose and indicate no potential conflict of interest.
Keywords: cancer, cognitive impairment, geriatric assessment, older, patients.
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Figure 1. Kaplan-Meir overall survival estimates between patients
without cognitive impairment (MMSE ≥27 and MoCA ≥26) and
patients with cognitive impairment (MMSE<27 or MoCA <26) in
one-year overall survival.
haematological malignancies admitted to receive chemotherapy.11,12 Regarding survival, we found in a multivariate analysis that only cognitive status (MMSE< 27
or MoCA<26) in the CGA had a predictive value for
one-year overall survival (Figure 1). This result is consistent with other studies that have demonstrated that
older patients with cancer who have cognitive impairment (CI) have a higher risk of death compared to those
with normal cognitive function.13-15 More recently, we
also found that CI has an impact on two-year overall
survival among older cancer patients at the start of their
onco-surgical treatment.16 In this study, CI detected
by the Mini Mental State Examination (<27) was not a
significant predictor of survival. Only, CI detected by
the Montreal Cognitive Assessment (<26) has an impact
on overall survival among this specific population. There
are two possible explanations that may account for these
results. First, few patients were found to be vulnerable
by the MMSE (13%), reducing the potential predictive
power of impairments detected by this scale. Second,
although the MMSE is useful to detect severe CI in clinical settings, it is less sensitive to subtle impairments,
such as Mild Cognitive Impairment (MCI), than the
MoCA.17
Regarding the impact of CI on overall survival, these
results are easily explained by the fact that CI is associated with biological, medical, psychological, and/or
social vulnerabilities. At the biological level, the presence
of CI has been associated with biomarkers that are
associated with reduced life-expectancy. These biomarkers indicate changes such as advanced cell senescence,
Belgian Journal of Hematology
181
increased inflammation, decreased hormonal level,
DNA damage, oxidative stress, or decrease in telomere
length.18-21 CI has also been associated with various
comorbidities (poor cardiovascular conditions, diabetes,
anaemia, hypertension, or vitamin D deficiency) and unhealthy lifestyle (low levels of physical activity, smoking,
or alcohol abuse) that have been shown to be associated
with shortened life-expectancies in older patients.21,22
At the medical level, a CI could be a risk factor for an
adjuvant under- or over-treatment of older patients. On
one hand, not giving chemotherapy to some patients
because of suspected CI may prevent them from potential remission. However, giving chemotherapy to patients
with a CI may result in severe side effects that ultimately
lead to life-threatening adverse events when the CI is a
marker of underlying frailty or deficit in physiological
function.
At the psychological level, the presence of a CI has
been associated with characteristics recognised as risk
factors for reduced life expectancies of older people in
general, and of older cancer patients in particular. These
include anxiety, depression, distress, fatigue, low cognitive reserve, or neuropsychological disorders.18 Finally,
at the social level, CIs have been associated with low
education levels and social isolation that have been
recognised as risk factors for reduced life expectancies
in older people.23 Moreover, CIs may impair the abilities
of older cancer patients to remember and implement
recommendations from their relatives or health care
professionals, specifically regarding cancer treatment
and the management of acute symptoms such as fever,
nausea, or pain. Figure 2 tries to explain the possible
contributors to CI and a poor overall survival in older
cancer patients.
As many patients with haematological malignancies die
from their disease and rarely from comorbidities, our
study suggests that all clinically fit patients without CI
could benefit from full dose chemotherapy and should
thus be appropriately screened for such impairment.24
This assumption needs further investigation, but could
be highly relevant for future treatment guidelines.11
Patients with CI should definitely be identified and
steered towards rehabilitation and adapted care, including (neuro)-psychological support.25,26 Firstly, the authors
suggest that physicians and health care professionals
inform older patients about their vulnerabilities and their
CI in particular. Furthermore, they should also have
the specific interventions that are needed explained
to them. Secondly, the authors suggest that physicians
propose to repeat cognitive assessments, at least one
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CANCER
?
Psychological
status
Social
status
Aging
Biomarkers
of aging
Comorbidities
Cognitive impairment
Genetic
variations
Unhealthy
life style
Treatment of cancer
?
Overall Survival
Figure 2. Possible contributors to cognitive impairment and a poor overall survival in older cancer patients.
year following treatment initiation in order to modify
the course of treatments according to the evolution of
impairments. These evaluations must be assessed with
an appropriate screening tool such as the MoCA, which
is more suitable for clinically fit patients who do not
present severe CI.17 Thirdly, the authors suggest proposing support interventions to increase compliance
among patients with CI regarding cancer treatment
and management of acute symptoms such as fever,
nausea, or pain. Potentially useful strategies that could
be considered to increase compliance among patients
with CI include comprehensive patient education,
neuro-psychological consultations, medication review,
intensive post-discharge follow-up, and home-based
interventions.27,28 Informal primary caregivers and
family doctors should be included in these supportive
interventions in order to maximise their usefulness
and potential benefits.
Future prospective studies should include an assessment of cancer treatment and assessments of patient
compliance with medical recommendations in order to
better understand the processes by which probable CIs
could reduce survival in older cancer patients. Among
these processes, prospective studies should also assess
biomarkers of aging that are also associated with prob-
Belgian Journal of Hematology
able CI and survival (i.e. cell senescence, inflammation,
hormone levels, DNA damage, oxidative stress, or telomere length). Prospective studies should also include
repeated measures for probable CI in order to investigate
the advancement of probable CI and its potential impact
on survival.
Conclusions
In conclusion, at treatment initiation, CI has an impact
on overall survival among clinically fit older patients with
malignant haemopathies. CI may be an indication of a
patient’s biological, medical, psychological, and social
vulnerabilities. Older patients should be screened for CI
at cancer treatment initiation in order to propose supportive interventions aiming to reduce morbidity and
mortality. Further studies should address processes
underlying the relationship between probable CI and an
increased risk of mortality among older cancer patients.
References
1. Repetto L, et al. Life expectancy, comorbidity and quality of life: the treatment
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2. Vercelli M, et al. Relative survival in elderly European cancer patients: evidence
for health care inequalities. The EUROCARE Working Group. Crit Rev Oncol
Hematol 2000;35:161-79.
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Key messages for clinical practice
1. Cognitive impairment can have an impact on overall survival among clinically fit older patients
with malignant haemopathies.
2. Older patients without cognitive impairment could benefit from a full dose of chemotherapy without
severe side effects.
3. Need to manage older patients with unsuspected cognitive impairment in order to avoid side effects
ultimately leading to dependence of the patient, and sometimes, life-threatening adverse events.
4. Need to implement supportive interventions in this specific population in order to improve tolerance
to treatment, survival, and quality of life.
5. Need to inform health care professionals about the importance of cognitive impairment.
6. The Montreal Cognitive Assessment is more sensitive and useful to detect subtle CI than the Mini
Mental State Examination.
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