"Chemobrain" in childhood cancer survivors-the impact on social, academic, and daily living skills: a qualitative systematic review.

PURPOSE: To examine children's experiences of chemotherapy-induced cognitive impairment--colloquially "chemobrain"--and the impact on children's social, academic, and daily living skills via a qualitative systematic review. Experiencing chemotherapy as a child, when the brain is still developing, may cause lifelong detriment to survivors' lives. There is a significant gap in understanding their lived experience, including the self-identified barriers that children face following treatment. Such a gap can only be fully bridged by listening to the child's own voice and/or parent proxy report through an exploration of the qualitative research literature. METHODS: A search of MEDLINE, Embase, PsycINFO, and CINAHL databases was conducted. Inclusion criteria were qualitative studies with a focus on children (0-18 years) during and/or following chemotherapy treatment and explored children's experiences of chemobrain. RESULTS: Two synthesized findings were identified from six studies. (1) Chemobrain has an academic and psychosocial impact, which may not be understood by education providers. (2) Children and their parents have concerns about their reintegration and adaptation to school, social lives, and their future selves as independent members of society. Children's experiences primarily related to changes in their academic and social functioning. CONCLUSION: This review highlights two important considerations: (1) the lived experiences of pediatric childhood cancer survivors guiding where future interventions should be targeted, and (2) a need to perform more qualitative research studies in this area, as well as to improve the quality of reporting among the existing literature, given that this is a current gap in the field.

The effectiveness of anti-inflammatory agents in reducing chemotherapy-induced cognitive impairment in preclinical models - A systematic review.

Chemotherapy-induced cognitive impairment (CICI) is a debilitating condition resulting from chemotherapy administration for cancer treatment. CICI is characterised by various cognitive impairments, including issues with learning, memory, and concentration, impacting quality of life. Several neural mechanisms are proposed to drive CICI, including inflammation, therefore, anti-inflammatory agents could ameliorate such impairments. Research is still in the preclinical stage; however, the efficacy of anti-inflammatories to reduce CICI in animal models is unknown. Therefore, a systematic review was conducted, with searches performed in PubMed, Scopus, Embase, PsycInfo and Cochrane Library. A total of 64 studies were included, and of the 50 agents identified, 41 (82%) reduced CICI. Interestingly, while non-traditional anti-inflammatory agents and natural compounds reduced impairment, the traditional agents were unsuccessful. Such results must be taken with caution due to the heterogeneity observed in terms of methods employed. Nevertheless, preliminary evidence suggests anti-inflammatory agents could be beneficial for treating CICI, although it may be critical to think beyond the use of traditional anti-inflammatories when considering which specific compounds to prioritise in development.

Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis.

Breast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequel of treatment is chemotherapy-induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers, hence a systematic review of prevalence data was performed. Medline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests. The review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21-34% respectively (very low GRADE evidence). Synthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.

Impact of "chemobrain" in childhood cancer survivors on social, academic, and daily living skills: a qualitative systematic review protocol.

OBJECTIVE: The objective of this review is to examine children's experiences of chemotherapy-induced cognitive impairment (also known as "chemobrain") and the impact of chemobrain on children's social, academic, and daily living skills. INTRODUCTION: The effect of childhood chemotherapy treatment on cognition is of concern because of the vulnerable nature of children's developing brains and the potential to cause lifelong detriments socially, academically, and economically. Furthermore, this population is under-represented in the chemobrain literature and in survivorship care plans. As cancer survivorship among this group increases, it is important to understand childhood experiences so that rehabilitation strategies and suitable supports can be put in place. INCLUSION CRITERIA: This review of qualitative studies will focus on the pediatric population (0 to 18 years of age) during and/or following chemotherapy treatment to identify their experiences with chemobrain. The review will include any studies using a qualitative research methodology (eg, surveys, focus groups, interview transcripts), conducted in any geographic location, where experiences are presented from the child's perspective. Studies assessing children's experiences of cancer, other chemotherapy-related side effects, or the parent's personal experience will be excluded. METHODS: A search of MEDLINE, Embase, PsycINFO, and CINAHL databases will be conducted. Full-text, English-only articles employing a qualitative research methodology will be included in the screening process. Two independent reviewers will retrieve and screen full-text studies, and assess methodological quality of the included studies. Meta-aggregation will be performed and a ConQual Summary of Findings will present the confidence in the findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021240573.

Reporting in rodent models of 'chemobrain': a systematic review assessing compliance with the ARRIVE guidelines.

Patients diagnosed with cancer are often plagued with debilitating side effects post-chemotherapy treatment. One such side effect is chemotherapy-induced cognitive impairment or 'chemobrain'. Rodent models are commonly used to investigate pathogenesis and potential therapeutic strategies. However, concerns have been raised regarding inadequacies in reporting of animal studies rendering them unreliable and irreproducible. The aim of this systematic review was to assess compliance with the ARRIVE reporting guidelines in peer-reviewed publications evaluating chemotherapy-induced cognitive changes in rodent models, and to determine if the introduction of the ARRIVE guidelines has improved quality of reporting. A comprehensive search was conducted to identify relevant peer-reviewed publications. Ninety-seven studies met the eligibility criteria, and publication compliance with the ARRIVE guideline reporting was assessed. No studies achieved full adherence with the ARRIVE guidelines. Furthermore, no significant improvement was demonstrated in the overall compliance score post-ARRIVE. Given the lack of standardisation of animal models in this research area, these results pose particular threat to future progress and translation of findings in this area of research. These results highlight the need for stricter adherence to the ARRIVE guidelines by journal editors and reviewers. Animal Ethics Committees also have an important educative role in improving knowledge and awareness of the guidelines amongst researchers.

Neuroimmune reactivity marker expression in rodent models of chemotherapy-induced cognitive impairment: A systematic scoping review.

BACKGROUND: Chemotherapy-induced cognitive impairment (CICI) is a debilitating side effect arising from chemotherapy treatments. The condition is characterised by a range of cognitive deficits including impairment to memory, attention, and concentration. Whilst the underlying mechanisms that contribute to CICI remain unclear, neuroinflammation has been suggested as one key contributor. METHOD: A comprehensive systematic search of EMBASE and Medline via PubMed was conducted to identify studies on neuroimmune reactivity marker expression changes and resulting cognitive changes in preclinical rodent models of CICI. RESULTS: A total of twenty studies met the eligibility criteria and were included in the scoping review. There was significant heterogeneity in the methodology employed in the included studies. Our findings demonstrate that widespread changes in cytokines, chemokines, microglia reactivity, and astrocyte reactivity are observed in CICI in the brain regions expected to be affected, given the nature of the cognitive impairment observed in CICI. CONCLUSIONS: Although there was considerable heterogeneity in study design that made comparisons between studies difficult, our findings suggest that neuroinflammation commonly occurs in CICI preclinical rodent models and shows an association with cognitive impairment.

Use of the Rat Grimace Scale to Evaluate Visceral Pain in a Model of Chemotherapy-Induced Mucositis.

The rat grimace scale (RGS) is a measure of spontaneous pain that evaluates pain response. The ability to characterize pain through a non-invasive method has considerable utility for numerous animal models of disease, including mucositis, a painful, self-limiting side-effect of chemotherapy treatment. Preclinical studies investigating novel therapeutics for mucositis often focus on pathological outcomes and disease severity. These investigations fail to measure pain, in spite of reduction of pain being a key clinical therapeutic goal. This study assessed the utility of the RGS for pain assessment in a rat model of mucositis, and whether changes in disease activity index (DAI) and open field test (OFT) reflected the grimace responses recorded. Sixty tumor-bearing female Dark Agouti rats were injected with either saline or 5-Fluourouracil alone, or with co-administration of opioid analgesics. Whilst differences in DAI were observed between treatment groups, no difference in RGS scores or OFT were demonstrated. Significant increases in grimace scores were observed across time. However, whilst a statistically significant change may have been noted, the biological relevance is questionable in terms of practical usage, since an observer is only able to score whole numbers. Development of effective pain assessment methods in animal models is required to improve welfare, satisfy regulatory requirements, and increase translational validity of the model to human patients.

A Judgement Bias Test to Assess Affective State and Potential Therapeutics in a Rat Model of Chemotherapy-Induced Mucositis.

Chemotherapy-induced mucositis is an extremely painful condition that occurs in 40-60% of patients undergoing chemotherapy. As mucositis currently has no effective treatment, and due to the self-limiting nature of the condition, the major treatment aims are to manage symptoms and limit pain with significance placed on improving patient quality of life. Rodent models are frequently used in mucositis research. These investigations typically assess pathological outcomes, yet fail to include a measure of affective state; the key therapeutic goal. Assessment of cognitive biases is a novel approach to determining the affective state of animals. Consequently, this study aimed to validate a cognitive bias test through a judgement bias paradigm to measure affective state in a rat model of chemotherapy-induced intestinal mucositis. Rats with intestinal mucositis demonstrated a negative affective state, which was partially ameliorated by analgesic administration, whilst healthy rats showed an optimistic response. This study concluded that the judgement bias test was able to evaluate the emotional state of rats with chemotherapy-induced mucositis. These findings provide a foundation for future refinement to the experimental design associated with the animal model that will expedite successful transitioning of novel therapeutics to clinical practice, and also improve humane endpoint implementation.