Publications by authors named "Sabine Noal"

13 Publications

  • Page 1 of 1

Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial.

Cancer 2020 Dec 30;126(24):5328-5336. Epub 2020 Sep 30.

Clinical Research Department, Centre François Baclesse, Caen, France.

Background: There is no treatment for cancer-related cognitive impairment, an important adverse effect that negatively impacts quality of life (QOL). We conducted a 3-arm randomized controlled trial to evaluate the impact of computer-assisted cognitive rehabilitation (CR) on cognition, QOL, anxiety, and depression among cancer patients treated with chemotherapy.

Methods: Patients who reported cognitive complaints during or after completing chemotherapy were randomly assigned to 1 of 3 12-week CR programs: computer-assisted CR with a neuropsychologist (experimental group A), home cognitive self-exercises (active control group B), or phone follow-up (active control group C). Subjective cognition was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), objective cognition was assessed by neuropsychological tests, QOL was assessed by the FACT-General, and depression and anxiety were assessed by psychological tests. The primary endpoint was the proportion of patients with a 7-point improvement in the FACT-Cog perceived cognitive impairment (PCI) score.

Results: Among the 167 enrolled patients (median age, 51 years), group A had the highest proportion of patients with a 7-point PCI improvement (75%), followed by groups B (59%) and C (57%), but the difference was not statistically significant (P = .13). Compared with groups B and C, the mean difference in PCI score was significantly higher in group A (P = .02), with better perceived cognitive abilities (P < .01) and a significant improvement in working memory (P = .03). Group A reported higher QOL related to cognition (FACT-Cog QOL) (P = .01) and improvement in depression symptoms (P = .03).

Conclusions: These results suggest a benefit of a computer-based CR program in the management of cancer-related cognitive impairment and complaints.
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December 2020

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level.

Brain Imaging Behav 2020 Feb;14(1):226-241

Normandie Univ, UNICAEN, PSL University, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000, Caen, France.

Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.
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February 2020

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

Oncologist 2019 01 22;24(1):62-68. Epub 2018 Jun 22.

INSERM, U1086, ANTICIPE, Caen, France

Background: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls.

Patients And Methods: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status.

Results: The sample consisted of women newly diagnosed with EBC ( = 118) and healthy controls ( = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline.

Conclusion: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC.

Implications For Practice: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy.
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January 2019

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

Eur Urol Focus 2016 Dec 17;2(6):642-649. Epub 2016 May 17.

Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.

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.
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December 2016

Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.

Oncologist 2016 Nov 29;21(11):1337-1348. Epub 2016 Jul 29.

Normandie University, UNICAEN, INSERM, U1086, Caen, France

Background: The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC).

Patients And Methods: The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, = 61), and at the same interval for the healthy controls ( = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index.

Results: Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment ( = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel ( = .05).

Conclusion: This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel.

Implications For Practice: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.
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November 2016

A Phase I, Dose-Escalation Trial of Pazopanib in Combination with Cisplatin in Patients with Advanced Solid Tumors: A UNICANCER Study.

Oncol Ther 2016 18;4(2):211-223. Epub 2016 Aug 18.

Institut Claudius Regaud, Inserm, UMR1037 CRCT, Université Toulouse III-Paul Sabatier, Toulouse, France.

Introduction: To determine the feasibility, maximum-tolerated dose (MTD), and dose-limiting toxicities (DLT) of pazopanib in combination with cisplatin.

Methods: Patients with advanced malignancies were included in a 3 + 3 dose-escalation phase I study. Pazopanib administration started 8 days before the first infusion of cisplatin; some patients were treated according to a reverse sequence (cisplatin first). Five dose levels (DLs) were planned. MTD was based on DLT observed during cycles 1 and 2.

Results: Thirty-five patients were enrolled. The MTD was reached at the first DL, (pazopanib 400 mg daily + cisplatin 75 mg/m every 21 days). Main DLTs were pulmonary embolism, neutropenia, thrombocytopenia, and elevation of liver enzymes. Overall, most common adverse events were anemia (83%), fatigue (80%), thrombocytopenia (80%), neutropenia (73%), hypertension (59%), neurotoxicity (56%), and anorexia (53%). Sixteen patients (46%) discontinued the study due to toxicity. One patient (sarcoma) had a complete response, and three patients (one with breast cancer and two with ovarian cancers) had a partial response. Pharmacokinetic (PK) analyses showed interactions with aprepitant, resulting in increased exposure to pazopanib, which might explain partly the poor tolerance of the combination.

Conclusion: Cisplatin and pazopanib could not be administered at their single agent full doses, partly due to a PK interaction between pazopanib and aprepitant.

Funding: This work was funded by GlaxoSmithKline and by the charity Ligue Nationale de Lutte Contre le Cancer.

Trial Registered: identifier, NCT01165385.
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August 2016

How to improve the prevention of chemotherapy-induced nausea and vomiting? The French NAVI study.

Support Care Cancer 2016 Mar 14;24(3):1131-8. Epub 2015 Aug 14.

Centre François Baclesse, Clinical Research Department, av général Harris, Caen, 14000, France.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients' satisfaction with the PAD.

Methods: This prospective multicentre study assessed the frequency and intensity of CINV among chemonaïve patients during the first cycle of treatment. CINV was defined by ≥1 emetic episode or reported nausea intensity ≥3 on a 0-10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score ≥the median on a 0-10 scale).

Results: Data from 291 patients (women, 85.2%; mean age, 57 years) were analyzed. Most patients (69.4%) received highly emetogenic chemotherapy regimens and 77.7% received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4% of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors.

Conclusions: Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed.
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March 2016

Emotional specificities of autobiographical memory after breast cancer diagnosis.

Conscious Cogn 2015 Sep 16;35:42-52. Epub 2015 May 16.

U1077, INSERM, Caen, France; U1077, University of Caen Lower Normandy, Caen, France; U1077, Ecole Pratique des Hautes Etudes, Caen, France; U1077, Caen University Hospital, Caen, France. Electronic address:

Cancer involves stressful events. One aspect of cognition that is impacted by stress is episodic autobiographical memory (EAM). EAM is intimately linked to self-representation. Some studies have revealed impairment of EAM in patients with breast cancer in remission. Yet, these studies failed to differentiate between the influence of adjuvant treatments and that of psychosocial factors. We therefore assessed the psychological impact of breast cancer diagnosis on EAM and self-representation profiles prior to any adjuvant treatment. Patients newly diagnosed with breast cancer (n=31) and women without any history of cancer (n=49) were compared on state anxiety, EAM and its emotional characteristics, and self-representations. The most anxious patients retrieved fewer emotional details for memories than the controls, and had lower self-representation scores than the least anxious patients, who had no deficits in emotional detail retrieval. Our results revealed distinct EAM profiles for patients, reflecting two contrasting modes of coping with breast cancer.
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September 2015

Two cases of fatal encephalopathy related to Ifosfamide: an adverse role of aprepitant?

Case Rep Oncol 2014 Sep 25;7(3):669-72. Epub 2014 Sep 25.

Departments of Oncology, University Hospital Amiens, Amiens, France.

Ifosfamide is used in the treatment of sarcomas and other tumors. It sometimes provokes encephalopathy, which is a serious complication even if it is usually reversible within 48-72 h after drug cessation. Ifosfamide is required to be activated by hepatic cytochrome P450 (CYP), especially the 3A4 subtype, leading to 4-hydroxy-ifosfamide. Ifosfamide is also converted by CYP3A4 to inactive but neurotoxic metabolites. Aprepitant is a neurokinin-1 receptor antagonist that is a potent antiemetic used in combination with 5-HT3 antagonists and corticosteroids. Aprepitant has an inhibitory effect, as well as a possible inductive effect, on CYP3A4. Since ifosfamide and aprepitant are both substrates of CYP3A4, a pharmacokinetic interaction could result in secondary effects such as the potentialization of neurological side effects. In this report, we describe 2 cases of fatal encephalopathy in patients who have received both ifosfamide and aprepitant, and we discuss the mechanisms that could be involved. Our observations draw attention to the fact that aprepitant must be avoided, or at least used with caution, in patients who are receiving ifosfamide due to the risk of severe neurological side effects.
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September 2014

Baseline cognitive functions among elderly patients with localised breast cancer.

Eur J Cancer 2014 Sep 20;50(13):2181-9. Epub 2014 Jun 20.

Normandie Université, UMR-S1077, Caen, France; INSERM, U1086, Caen, France; Unité de Recherche Clinique, Centre François Baclesse, Caen, France; CHU de Caen, Service d'Oncologie, Caen, France. Electronic address:

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.
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September 2014

Cognitive dysfunction and cancer: which consequences in terms of disease management?

Psychooncology 2011 Dec 21;20(12):1251-8. Epub 2011 Jan 21.

Department of Medical Oncology, Centre François Baclesse, Caen, France.

Objectives: The aim of this review is to stress the importance of cognitive dysfunction in cancer survivors, and to discuss the way of assessing and managing these troubles in clinical practice.

Method: Original studies and reviews reporting the effect of cancer and chemotherapy on cognition and published since January 2000 were selected from the Medline(®) database using 'cognition' or 'cognitive function' and 'cancer' as subject headings.

Results: Main reports concerned women with advanced breast cancer or children with hematological or brain cancers. Overall, chemotherapy was found to be associated with subtle and transient cognitive dysfunctions, which were detectable only with neuropsychological testing and affected most particularly memory, concentration and speed of information processing. Some factors associated with the patient, like depression, may favor cognitive impairment, while the role of others, like age or educational level, remains to be defined. Screening of patients at risk remains limited due to the lack of standardized neuropsychological tests in clinical oncology practice. Few studies have addressed the benefits of interventional strategies but methylphenidate, modafinil and erythropoietin, as well as rehabilitation in children, have shown encouraging results. Formal studies assessing the value of a multidisciplinary approach to detect and manage cognitive impairment must be recommended.

Conclusion: Cognitive dysfunction induced by cancer or the treatment represents a real challenge in clinical practice. Based on limited published data, few clinical recommendations can be made regarding prevention, evaluation and management of this trouble. Longitudinal studies must be conducted to evaluate its real impact on quality of life.
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December 2011

One-year longitudinal study of fatigue, cognitive functions, and quality of life after adjuvant radiotherapy for breast cancer.

Int J Radiat Oncol Biol Phys 2011 Nov 1;81(3):795-803. Epub 2010 Oct 1.

Medical Oncology Department, Centre François Baclesse, Caen, France.

Purpose: Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life.

Methods And Materials: Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules.

Results: At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment.

Conclusions: Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.
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November 2011

Do patients with advanced urothelial carcinoma benefit from weekly paclitaxel chemotherapy? A GETUG phase II study.

Clin Genitourin Cancer 2009 Aug;7(2):E28-33

Département d'oncologie Médicale, Centre François, Baclesse, France.

Background: There is no standard second-line chemotherapy for patients who relapse with advanced urothelial carcinoma. A GETUG phase II clinical trial was designed to evaluate the response rate and the palliative clinical benefit of weekly paclitaxel.

Patients And Methods: Paclitaxel (80 mg/m2, 1 hour) was administered on day 1, 8, and 15 (28-day course) to 45 patients. The primary endpoint was disease control rate (objective response and stable disease). Response rate was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria; quality of life (QOL) assessment used FACT-B1 and FACT-Taxane questionnaires.

Results: Characteristics of the patients were: M/F, 36/9; mean age, 64 years; performance status (PS) 0-1, 82%; metastatic disease, 93%; gemcitabine/platinum first-line chemotherapy, 89%; median number of cycles, 2. Grade 3/4 toxicity was uncommon. The disease control rate was 47%. One patient achieved a complete response, 3 a partial response (objective response, 9%) and 17 (38%) a stable disease. Median time to progression or death were 3 and 7 months. Among the 21 patients with controlled disease, 10% displayed QOL improvement, and 14% decreased their analgesic consumption.

Conclusion: Weekly paclitaxel is associated with limited objective response but a high rate of stabilization; QOL assessment indicates that a small group of patients might experience a clinical benefit.
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August 2009