Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.

Background: Cognitive complaints are common in cancer survivors. We aimed to assess cognitive complaints in cancer survivors and the associated factors using a large web–based survey.Methods: This online survey was proposed to cancer survivors. Participants completed several questions on cognitive complaints experience, expectations for support of cognitive difficulties, preexisting knowledge about chemotherapy–associated cognitive problems and demographic and medical variables. We used multivariable logistic regression models to estimate Odds Ratios and 95% confidence intervals to estimate associations.Results: Among 1610 eligible participants (median age 52 [21‐84]), >85% (n = 1393) were breast cancer survivors. Median postcancer treatment time (excluding hormone therapy) was 2.83 years [0.8‐33]. Seventy five percent of the participants (n = 1214) reported cognitive complaints related to cancer treatments. Cognitive difficulties had an impact on work resumption for 76% of the participants (n = 754/982). Most cancer survivors would like to receive support (75%, n = 909) and especially cognitive training (72%, n = 658). Chemotherapy was strongly associated with cognitive complaints (multivariable OR = 3.67, 95% CI: 2.80‐4.82). Self–reported sleep difficulties (OR_{often vs. never} = 2.84, 95% CI: 1.80‐4.47), preexisting knowledge about chemotherapy–associated cognitive problems (OR_{No vs. Yes} = 1.69, 95% CI: 1‐29‐2.22) and age (OR_{21‐64 vs. ≥65} = 0.37, 95% CI: 0.23‐0.58) were also associated with cancer–related cognitive complaints.Conclusions: According to this large web–based survey including mainly breast cancer survivors, cognitive complaints were reported by three quarters of participants, which reinforces that cognitive difficulties are a major issue in cancer survivors. Chemotherapy, self–reported sleep difficulties and preexisting knowledge about chemotherapy–associated cognitive problems were strongly associated with cancer–related cognitive complaints. Most cancer survivors wished to receive support and especially cognitive training.

Survivors of early-stage breast cancer may report treatment-related side effects that persist for several years after the end of primary treatment. Among these, fatigue and cognitive disorders are frequent complaints and can negatively impact quality of life. Cancer-related fatigue is a very prevalent and distressing long-term side effect among breast cancer survivors that typically improves after completion of treatment, although many patients report severe fatigue several years post-treatment. Cognitive disorders are also common among survivors of breast cancer, especially if treated with chemotherapy. These symptoms are usually mild-to-moderate and often transient. Cognitive recovery is frequently observed within months or a few years after completion of chemotherapy or endocrine therapy. However, some breast cancer survivors may have persistent cognitive difficulties. Several types of interventions have proved to be beneficial in reducing cancer-related fatigue and cognitive difficulties. Most of these interventions for cancer-related fatigue are thought to be effective by reducing inflammation or disrupting pro-inflammatory circuits. Further studies are needed on cognitive management that has showed promising results. This narrative review summarizes the state of the art regarding long-term fatigue and cognitive disorders in patients with early breast cancer, describing prevalence, impact, pathophysiology, and risk factors, and focusing on available interventions.

Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM. The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa. Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer. NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

Cognitive complaints are common adverse effects in cancer patients. Identifying subjects at risk could make it possible to limit their impact. We aimed to explore the relationship between current cognitive complaints and demographic and psychological factors in a group of breast cancer survivors. Through an online survey, cancer survivors reported current cognitive complaints using the FACT-Cog questionnaire (Perceived Cognitive Impairment) and answered questions about their demographics, lifestyle and cancer-related characteristics. Anxiety, depression, fatigue and post-traumatic stress symptoms were also assessed. We used multivariable logistic regression models to explore the relationships between current cognitive complaints and social and psychological factors. Among the 1393 breast cancer survivors, 47.2% (n = 657) reported current cognitive complaints. Chemotherapy (OR = 2.26, 95%CI = 1.67–3.05), age (OR_{21-44 vs. >65} = 0.14, 95%CI = 0.07–0.27), sleep difficulties (OR_{never vs. often} = 2.41, 95%CI = 1.47–3.95), frequency of psychotropic treatments (OR_{never vs. >1/week} = 1.70, 95%CI = 1.23–2.36), post-traumatic stress symptoms (OR = 2.05, 95%CI = 1.57–2.69) and employment status (OR_{full-time or part-time vs. sick leave} = 1.64, 95%CI = 1.08–2.49) were strongly associated with current cognitive complaints. In this large study, about half of breast cancer survivors reported cognitive complaints, particularly after chemotherapy. Some risk factors should be detected early to reduce persistent cognitive complaints after cancer: mainly sleep difficulties, post-traumatic stress symptoms and psychotropic medications.

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.