Marie Lange

Cognitive dysfunctions in elderly cancer patients: A new challenge for oncologists

While chemotherapy is more commonly proposed to the elderly population with cancer, little is known about the impact of therapy on cognitive functions and the way of managing such dysfunctions in clinical practice among this population. Aging by itself is associated with cognitive modifications, comorbidities and functional decline, which may have a significant impact on the autonomy. In elderly patients with cancer, several factors like the biologic processes underlying the disease and therapies will contribute to favor the cognitive decline. The chemobrain phenomenon, referring to the chemotherapy-induced impairment of memory, executive function or information processing speed has been extensively described in patients with breast cancer, and the few studies available in older patients suggest that the impact could be more pronounced in patients with pre-existing troubles. Because cognitive dysfunction may impact the quality of life as well as compliance to treatment, assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice as it should influence the choice of the most appropriate therapy, including oral drugs. In that respect, geriatric assessment in oncology should include more sensitive screening tests than Mini Mental State Examination (MMSE) and if needed they have to be completed with a more detailed assessment of subtle disorders.

Impact of Cancer and Its Treatments on Cognitive Function: Advances in Research From the Paris International Cognition and Cancer Task Force Symposium and Update Since 2012

CONTEXT Although cognitive impairments have been identified in patients with non-central nervous system cancer, especially breast cancer, the respective roles of cancer and therapies, and the mechanisms involved in cognitive dysfunction remain unclear. OBJECTIVES To report a state-of-the-art update from the International Cognitive and Cancer Task Force conference held in 2012. METHODS A report of the meeting and recent new perspectives are presented. RESULTS Recent clinical data support that non-central nervous system cancer per se may be involved in cognitive dysfunctions associated with inflammation parameters. The role of chemotherapy on cognitive decline was confirmed in colorectal and testicular cancers. Whereas the impact of hormone therapy remains debatable, some studies support a negative impact of targeted therapies on cognition. Regarding interventions, preliminary results of cognitive rehabilitation showed encouraging results. The methodology of future longitudinal studies has to be optimized by a priori end points, the use of validated test batteries, and the inclusion of control groups. Comorbidities and aging are important factors to be taken into account in future studies. Preclinical studies in animal models highlighted the role of cancer itself on cognition and support the possible benefits of prevention/care during chemotherapy. Progress in neuroimaging will help specify neural processes affected by treatments. CONCLUSION Clinical data and animal models confirmed that chemotherapy induces direct cognitive deficit. The benefits of cognitive rehabilitation are still to be confirmed. Studies evaluating the mechanisms underlying cognitive impairments using advanced neuroimaging techniques integrating the evaluation of genetic factors are ongoing.

Baseline cognitive functions among elderly patients with localised breast cancer.

PURPOSE Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients. METHODS Women >65years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD). RESULTS Among the 123 elderly EBC patients (70±4years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P<.0001). Verbal episodic memory was mainly impaired (21% of patients). No correlation was observed between objective CD and cancer stage or geriatric assessment. Subjective CD only correlated with verbal episodic memory (P=.01). CONCLUSIONS This is the first large series assessing baseline cognitive functions in elderly EBC patients. More than 40% presented objective CD before any adjuvant therapy, which is higher than what is reported among younger patients. Our results reinforce the hypothesis that age is a risk factor for CD in EBC patients.

Prospective Evaluation of the Impact of Antiangiogenic Treatment on Cognitive Functions in Metastatic Renal Cancer

BACKGROUND Little is known about the cognitive effects of antiangiogenic therapies (AATs) in metastatic renal cell carcinoma (mRCC) and their relation with fatigue. OBJECTIVE To evaluate the impact of AATs on cognition and its connection with fatigue and quality of life (QoL) in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS This prospective study enrolled 75 patients starting AAT as first or second line for mRCC and assessed them at 3 mo (n=58) and 6 mo (n=50). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We assessed objective cognitive decline with a neuropsychological battery of tests and cognitive complaint, fatigue, and QoL with validated self-reported questionnaires using the Fisher exact test, Wilcoxon test, and Spearman correlation coefficient. RESULTS AND LIMITATIONS A decline of cognitive functions was observed in 18 patients (31%) including 13 without cognitive impairment at baseline. The score of fatigue was increased in all patients except one. A relationship between cognitive complaints and fatigue was observed (p<0.05) but not with objective cognitive decline. Cognitive complaints and fatigue had a significant impact on most of the domains of QoL (p<0.01). A positive correlation was found between fatigue and inflammatory markers but not with cognition. The main limitation of this study is the absence of a control group. CONCLUSIONS AAT induced cognitive decline in patients with mRCC independently of fatigue. These side effects affecting QoL should be better assessed in clinical trials and taken into account in routine practice. PATIENT SUMMARY Fatigue is a well-known effect of antiangiogenic therapies (AATs) of cancer. The study performed in patients with treated metastatic renal cancer shows a decline of cognitive functions induced by AATs, such as information-processing speed or working memory, in a third of patients, independently of fatigue. Patients on AATs should be informed of these possible adverse effects.

Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors

Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: “cognition disorders,” “predictive factors”/“biological markers,” and “neoplasms,” searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological circulating factors and genetic polymorphisms, can predispose to the development of cognitive disorders. However, many predictive factors remain unproven and discordant findings are frequently reported, warranting additional clinical and preclinical longitudinal cohort studies, with goals of better characterization of potential biomarkers and identification of patient populations at risk and/or particularly deleterious treatments. Research should focus on prevention and personalized cancer management, to improve the daily lives, autonomy, and return to work of patients.

Cognitive complaints in cancer: The French version of the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog), normative data from a healthy population

Cancer patients often report cognitive changes after chemotherapy. The Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) is a self-report questionnaire that assesses these changes. The aims of the present study were (1) to establish normative data, and (2) to compare the scores of patients and healthy controls to assess whether or not the questionnaire is able to discriminate between these populations. The normative sample included 213 healthy participants. The patient group included 63 cancer patients treated with chemotherapy, who were compared to a subsample of 63 matched healthy controls. The questionnaire had good internal consistency reliability (Cronbachs alphas = .74–.91). The oldest patients had significantly more cognitive complaints (p < .001). Cognitive complaints were significantly related with Trail Making Test scores (p < .001). Furthermore, the FACT-Cog subscales correlated significantly with anxiety and depression. Patients had more complaints than matched controls on the subscales Perceived Cognitive Impairments (p = .01), Impact on Quality of Life (p = .001) and Perceived Cognitive Abilities (p = .027). The reference values from the healthy population reported here could be used for comparison with the values measured in French-speaking cancer patients. The values provide a benchmark against which clinicians can evaluate the impact of the disease and/or the treatments on cognitive complaints and help to improve quality of life by providing appropriate care.

Prospective comparison of the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Examination (MMSE) in geriatric oncology

INTRODUCTION Among the various instruments recommended by the International Society of Geriatric Oncology, the Mini Mental State Examination (MMSE) is the most commonly used cognitive screening test before oncological treatment. Although the Montreal Cognitive Assessment (MoCA) has been shown to be more sensitive than the MMSE in several pathologies, no specific data exist for older patients with cancer. We aimed to compare the proportions of older patients with cancer who had screened positive for cognitive impairment according to the MMSE and MoCA scores obtained during a pretherapeutic geriatric assessment (GA) in oncology. PATIENTS AND METHODS This prospective study was conducted among 66 patients older than 70 years who were candidates for a first-line treatment for either a solid tumor or hematological malignancy. Patients with brain tumor or previously known dementia were ineligible. During GA, cognitive function was assessed using both the MoCA and the MMSE tests administered in a random order. RESULTS Median age was 78 years. Most patients (n = 43, 65.2%) had a solid tumor. The median scores were 26 [11-30] for MMSE and 24 [8-30] for MoCA. Thirteen (19.7%) and 44 (66.7%) patients were screened positive for cognitive impairment according to MMSE and MoCA scores, respectively. Overall, 55 (66.7%) patients were screened positive: 12 (21.8%) on both scores, 32 (70.5%) with the MoCA only, and one patient with MMSE only (p < 0.0001). CONCLUSION The MoCA test seems to be most relevant to screen for cognitive impairment in older patients with cancer.

Sexual Disorders of Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Antiangiogenic Therapies

Micro‐Abstract Anti‐angiogenic therapies may induce sexual disorders. This longitudinal study evaluated the impact of anti‐angiogenic agents on the sexual life of 75 patients with metastatic renal cancer. After 3 months of treatment, 69% of patients reported changes in their sexual life (mainly decrease of pleasure, interest) independently of the other side effects. Sexual disorders should be taken into account in oncology supportive care departments. Background Targeted therapies, in particular antiangiogenic therapies (AATs), have become the standard of treatment for metastatic renal cell carcinoma (mRCC). Although common adverse effects like fatigue have been well‐established, sexual disorders induced by these treatments, although often reported, have been poorly evaluated. The aim of this study was to evaluate the impact of AATs on the sexual life of patients with mRCC and the relationships with quality of life (QoL), fatigue, and biologic parameters. Patients and Methods This longitudinal study included patients with mRCC on first‐ or second‐line AATs. Sexuality was evaluated by the French version of Changes in Sexual Functioning Questionnaire short‐Form (CSFQ); QoL and fatigue were measured by the Functional Assessment of Cancer Therapy General (FACT‐G) and the Multidimensional Fatigue Inventory (MFI‐20), respectively. Biologic parameters were also assessed. Results Among 75 patients included in the study, 39 agreed to respond to the sexual functioning questionnaire (CSFQ). At baseline, all patients had at least 1 sexual dysfunction. No relationship with QoL, fatigue, and biologic parameters was shown. After 3 months of treatment, a decrease in at least 1 sexual dimension was observed in 69% of patients. The most affected sexual dimensions were pleasure (34%) and desire/interest (38%). No significant relationship between sexual dysfunctions and biologic parameters was found. The percentage of non‐participants (50%) and the absence of a control arm are the main limitations. Discussion Patients with mRCC exhibit sexual dysfunction that could be increased by AATs independently of the impact on fatigue and QoL. Further studies aiming to define the role of biologic parameters like inflammatory markers and thyroid parameters are warranted. Conclusion Sexual disorders induced or degraded by AAT are an independent side effect that should be taken into account in oncology supportive care departments.

Cognitive complaints in breast cancer patients treated with chemotherapy: a reality?

Memory and attention dysfunction is a common complaint among cancer survivors, named “chemobrain”, which can be reported during and even several years after treatment. These disorders have a negative impact on patients’ quality of life (1) and can disturb ability to work (2). Recent studies assessed self-reported cognitive function in cancer patient cohorts, mainly in breast cancer women, and showed that 46% to 60% of survivors had cognitive complaints (3-5). However, these studies did not use a validated questionnaire specifically constructed to assess cognitive complaints.

Cognitive Function During and After Treatment in Elderly Ovarian Cancer Patients

Beyond the difficulties with attention, concentration and memory reported by cancer patients, it has become increasingly apparent that cytotoxic drugs given for non-central nervous system tumors might have side-effects on cognitive functioning. Nevertheless, in comparison to breast cancer patients, very few studies have concerned cognition in ovarian cancer patients despite the multiple courses of chemotherapy included in their management. Furthermore, no study has directly investigated elderly patients, even though age is a risk factor for ovarian cancer and cognitive impairment. Additional research is needed to apprehend the impact of cancer treatments on these women. Regarding oncologic practice, more detailed cognitive assessment of cognitively frail subjects would help oncologists to choose the most appropriate therapy.