Non-central Nervous System Cancer Research Articles

Cancer-related cognitive impairment: updates to treatment, the need for more evidence, and impact on quality of life-a narrative review.

Due to advances in early detection and treatment options, non-central nervous system (non-CNS) cancer survivors are living longer, even those with metastatic disease. Many of these survivors will experience enduring symptoms of breast cancer, such as cancer-related cognitive impairment (CRCI). Although CRCI is bothersome and, in some cases, potentially debilitating, little research has been done to address this symptom. Thus, the overarching goal of this narrative review is to provide both an overview of the problem of CRCI and its impact and focus on the latest research aimed at addressing CRCI in non-CNS cancer survivors. A MEDLINE database (PubMed) search was conducted for terms related to non-CNS cancer, cognition, impacts of CRCI, and interventions. The English-language articles published until April 8th, 2024, were included in the search. CRCI includes self-reported cognitive complaints and/or impaired performance in multiple cognitive domains, including memory, processing speed, attention, and executive function. CRCI, in turn, can have a significant impact on everyday functioning, work ability, work engagement and productivity, and overall quality of life (QoL) of cancer survivors. While some researchers have examined pharmacological approaches, the vast majority of the interventional studies to date to address CRCI has focused on non-pharmacological approaches. Three of the most common non-pharmacological approaches are physical activity or exercise, mind-body approaches [e.g., mindfulness-based stress reduction (MBSR)], and cognitive rehabilitative approaches [e.g., cognitive training (CT) and cognitive behavioral therapy (CBT)]. Addressing the cognitive health of cancer survivors is imperative but has only recently been the focus of interventional research. More research in larger and more diverse samples of non-CNS cancer survivors is needed to identify effective ways to manage CRCI for all cancer survivors. Overall, maintaining cognitive health, especially in cancer survivors who are at increased risk for deficits, is a national health care priority that should not be ignored.

ImmunoPET imaging of TIGIT in the glioma microenvironment

Glioblastoma (GBM) is the most common primary malignant brain tumor. Currently, there are few effective treatment options for GBM beyond surgery and chemo-radiation, and even with these interventions, median patient survival remains poor. While immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy against non-central nervous system cancers, ICI trials for GBM have typically had poor outcomes. TIGIT is an immune checkpoint receptor that is expressed on activated T-cells and has a role in the suppression of T-cell and Natural Killer (NK) cell function. As TIGIT expression is reported as both prognostic and a biomarker for anti-TIGIT therapy, we constructed a molecular imaging agent, [89Zr]Zr-DFO-anti-TIGIT (89Zr-αTIGIT), to visualize TIGIT in preclinical GBM by immunoPET imaging. PET imaging and biodistribution analysis of 89Zr-αTIGIT demonstrated uptake in the tumor microenvironment of GBM-bearing mice. Blocking antibody and irrelevant antibody tracer studies demonstrated specificity of 89Zr-αTIGIT with significance at a late time point post-tracer injection. However, the magnitude of 89Zr-αTIGIT uptake in tumor, relative to the IgG tracer was minimal. These findings highlight the features and limitations of using 89Zr-αTIGIT to visualize TIGIT in the GBM microenvironment.

Improve the management of cancer-related cognitive impairment in clinical settings: a European Delphi study.

Cancer-related cognitive impairment (CRCI) is under-addressed by healthcare professionals owing to a lack of clinical management guidelines. This European Delphi study proposes recommendations to healthcare professionals for the management of CRCI in patients with non-central nervous system (non-CNS) cancers. Twenty-two recommendations were developed based on a literature review and authors' clinical experience, split into three categories: screening, cognitive assessment, intervention. The survey included European professionals, experts in CRCI. The Delphi method was used: experts rated the clinical relevancy of recommendations on a 9-point Likert scale in three rounds. A recommendation was accepted if all votes were between 7 and 9. Recommendations not accepted in round 1 and round 2 were deleted, or modified and rated in round 3. Eighteen professionals (psychologists, physicians, researchers) voted and accepted 15 recommendations. Experts recommended the systematic screening of CRCI, followed by a short objective cognitive assessment, if complaints screened. A comprehensive evaluation is recommended if CRCI persists 6 months post-treatment. Cognitive rehabilitation, physical activity, meditative-movement therapy, and multimodal intervention should be offered. Recommendations about frequency and duration of interventions, the professional to administer cognitive rehabilitation and the use of meditation and cognitive training without psychoeducation were not accepted. This survey provides 15 recommendations to assist healthcare professionals in detecting, assessing and offering interventions for CRCI. These recommendations should be included in supportive care to help healthcare professionals to detect CRCI and propose the best available intervention for patients with cognitive complaints. Developing CRCI management in clinical settings would improve patients' quality of life.

462P Cognitive function of survivors with non-central nervous system cancer and its correlates: A community rehabilitation perspective

462P Cognitive function of survivors with non-central nervous system cancer and its correlates: A community rehabilitation perspective

Neurocognitive Impairment in Non-Central Nervous System Cancer Survivors

Abstract: Cancer and its treatments entail a profound inflammatory response of the central nervous system (CNS). This intense neurotoxic process can lead to significant neurocognitive impairment even in non-CNS cancers. Few studies have examined this domain, and data available is based on limited designs using neuropsychological assessments comprising self-report or traditional testing batteries that capture basic response data. Here, we leverage cognitive electrophysiology, specifically Event-Related Potentials (ERPs), to examine and delineate neurocognitive impairments in non-CNS cancer survivors. Eleven survivors, who were on average 4.6 years in remission from head and neck cancer and 10 matched healthy controls underwent standardized cognitive and emotional “Go-Nogo” paradigms concomitant to EEG recording. Significant differences in amplitude morphology in the very early ERP components (C1, N1, P1) and middle ERP component (N2), were apparent between non-CNS cancer survivors and controls. Later ERP components (P3, N4) did not show amplitude differences. Non-CNS cancer survivors yielded faster latencies in the early components for pain-related stimuli during the emotional paradigm, albeit tended to yield slower ERP latencies overall across both experiments. These findings suggest that early gating and inhibitory control are dysregulated in non-CNS cancer survivors, which can impact executive functioning and cognitive processing involved in everyday activities for many years post-treatment. The findings do not fully align with ERP morphologies associated with neurocognitive impairment in degenerative conditions (such as dementia and Alzheimer’s disease), affecting later-stage ERP components. Our initial results suggest that (1) cognitive impairments in cancer survivors do not follow a degenerative trajectory, (2) rather are in line with “lesion” related damage (such as stroke, epilepsy), and as such, (3) have the potential for treatments involving neurocognitive plasticity.

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Research Trends on Cancer-Related Cognitive Impairment in Patients with Non-Central Nervous System Cancer: Text Network Analysis and Topic Modeling

Purpose: This study aimed to understand the knowledge structure and trends in research on cancer-related cognitive impairment (CRCI) in patients with non-central nervous system (non-CNS) cancer through text network analysis and topic modeling.Methods: From 2011 to 2021, studies on CRCI in patients with non-CNS cancer registered in databases including Ovid-MEDLINE, EMBASE, Cochrane, CINAHL, CENTRAL, and PsycInfo, were extracted and cleaned into words using Python’s natural language toolkit package. Text network analysis was performed using the NetworkX library, and topic modeling analysis based on the latent Dirichlet allocation algorithm was carried out using the Gensim library.Results: In total, 24,030 keywords were extracted from the abstracts of 490 selected papers, of which “chemotherapy,” “breast cancer,” and “quality of life” showed high frequency and centrality. As a result of the topic modeling analysis, four subject groups were derived, including cognitive impairment due to chemotherapy, breast cancer and cognitive impairment, factors related to cognitive impairment, and symptom experience.Conclusion: These findings will help cancer researchers to understand the trends and insights of research on CRCI in patients with non-CNS cancer and suggest important areas and directions for future studies.

Abstract 755: The impact of cancer treatment on cognitive function and quality of life in patients undergoing treatment at a tertiary care hospital in New Delhi, India

Abstract Background: Cognitive dysfunction is becoming a more well-known complication of cancer and its treatment. Cancer-related cognitive changes and impairment have also been documented in non-central nervous system (non-CNS) cancer patients. The majority of research in this area has discovered that a subset of patients appear to be vulnerable to this complication even after treatment has ended, and they frequently struggle with multitasking, short-term memory, word-finding, attention, or concentration. It is critical to investigate the possible link between cancer and cognitive impairment because it can have a serious impact on quality of life. Methods: This cross-sectional study between May 2022 and October 2022, included patients who were referred to the dental outpatient department as part of a preventive/prophylactic evaluation at the tertiary care centre in New Delhi, India. After receiving informed consent, the oral health impact profile-14 instrument to assess participants' oral health-related quality of life (OHRQoL) and the Montreal Cognitive Assessment (MOCA) for cognitive evaluation were used. Results: Out of 283 patients 77% males and 23% females and vast majority had Stage III cancer. All patients' OHRQoL was hampered, but it was higher in those who developed visible oral changes during treatment versus those who did not (P =.001). Taking painkillers, losing sexual interest, difficulty in social contact, loss of taste and smell senses were the main factors affecting oral health related QoL (OHRQoL). A significant relationship was discovered between pain, speech, social eating, dry mouth, sticky saliva, and weight loss in relation to various treatment modalities. Those who were treated surgically alone had better QoL than others, according to the OHRQoL scores. In terms of delayed recall, 55% were found to be cognitively impaired, which was associated with lower OHRQoL. Conclusion: Cognitive impairment is common in cancer patients, which may be caused by the cancer itself. It is also linked to OHRQoL and psychosocial variables. There has been little research into the relationships between cognitive function and quality of life (OHRQoL) in cancer patients. Together with previous research indicating that cognitive function and OHRQoL can influence treatment adherence and outcomes, the findings support the inclusion of cognitive screening and OHRQoL assessment as part of patient pretreatment assessment. Citation Format: Delfin Lovelina Francis. The impact of cancer treatment on cognitive function and quality of life in patients undergoing treatment at a tertiary care hospital in New Delhi, India [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 755.

Binary classification threatens the validity of cognitive impairment detection.

Neuropsychological literature reports varying prevalence of cognitive impairment within patient populations, despite assessment with standardized neuropsychological tests. Within the domain of oncology, the International Cognition and Cancer Task Force (ICCTF) proposed standard cutoff points to harmonize the operationalization of cognitive impairment. We evaluated how this binary classification affects agreement between two highly comparable test batteries. Two hundred non-central nervous system (non-CNS) cancer patients who finished treatment (56% females; median age 53 yrs) completed traditional tests and their online equivalents in a counterbalanced design. Following ICCTF standards, impairment was defined as a score of ≥ 1.5 standard deviations (SDs) below normative means on two tests and/or ≥ 2 SDs below normative means on one test. Agreement of classification between traditional and online assessment was evaluated using Cohen's κ. Additional Monte Carlo simulations were conducted to demonstrate how different cutoff points and test characteristics affect agreement. The correlation between total scores of traditional and online assessment was .78. Proportions of impaired patients did not differ between assessment methods: 40% using traditional tests and 38% using online equivalents, χ²(1) = .17, p < .68. Nevertheless, within-person agreement in impairment classification between traditional and online assessment was merely fair (K = .35). Monte Carlo simulations showed similarly low agreement scores (K = .41 for 1.5 SD; K = .33 for 2 SD criterion). Our results show that binary classification can lead to a situation where two highly similar batteries fail to identify the same individuals as impaired. Additional simulations suggest that within-person agreement between assessment methods using binary classification is inherently low. Modern statistical tools may help to improve validity of impairment detection. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of cognitive rehabilitation interventions on non-central nervous system cancer survivors: A meta-analysis

IntroductionCancer treatments can have a detrimental impact on cancer survivors’ cognitive function. Cognitive rehabilitation is considered the first-line intervention to address cognitive difficulties of cancer survivors. Nevertheless, its efficacy remains unclear.ObjectivesThis meta-analysis aimed to understand the effects of cognitive rehabilitation in non-central system (non-CNS) cancer survivors, through the assessment of the overall efficacy on subjective cognitive outcomes.MethodsThis meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. An electronic search on the databases PubMed, Scopus, and Web of Science was conducted in May 2021, considering the past 15 years, by two independent authors. Studies were eligible if they included cancer survivors (excluding CNS cancers) who were exposed to cognitive rehabilitation interventions, in which the subjective cognitive effects were measured through self-report questionnaires. The quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomized Trials. The effect size was the standardized mean difference in the cognitive assessment, between baseline and post-intervention. Statistical heterogeneity was assessed using I2 Statistic. Publication bias was evaluated with Egger’s test. P&lt;0.05 was considered statistically significant. The meta-analysis was performed using R software.ResultsAmong 14 studies, with 1115 cancer survivors, one study included a pediatric population, other young adult survivors, and the remaining adult population. The most used scale for measuring cognitive changes was the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and, as recommended, the Perceived Cognitive Impairments (PCI) subscale was used as the primary measure of subjective cognitive function. Results indicated beneficial effects following cognitive rehabilitation, with an overall standard mean difference between pre- and post-treatment of 3.4447, with CI95% [1.5543; 5.3350], p-value&lt;0.0004. The subgroup analysis between the measures of cognitive outcomes showed that the heterogeneity is Group=Other 0.00% (I2) and for the Group=FACT-Cog PCI is 86% (I2). Analyzing the FACT-Cog PCI, the CI95% [-2.93; 6.43] includes 0, meaning that the overall effect in this subgroup is non-significant. The meta-analysis does not demonstrate publication bias (p-value of the Egger test=0.3220).ConclusionsImprovement of cognitive function in non-CNS survivors throughout cognitive rehabilitation appears to be effective. The findings of this meta-analysis can help inform clinical practice and assist practitioners in recommending and developing interventions of cognitive rehabilitation and deciding how to evaluate them. Further research is required to strengthen this evidence.Disclosure of InterestNone Declared

Occurrence of non-central nervous system cancers during postoperative follow-up of patients who underwent surgery for a WHO grade II glioma: implications for therapeutic management.

Survival is currently prolonged in WHO grade II glioma (GIIG). Although exceptionally described, long-term survivors may develop second primary cancers outside the central nervous system (CNS). Here, a consecutive series explored the association between non-CNS cancers (nCNSc) and GIIG in patients who underwent glioma resection. Inclusion criteria were adult patients operated for a GIIG who experienced nCNSc following cerebral surgery. Nineteen patients developed nCNSc after GIIG removal (median time 7.3years, range 0.6-17.3years), including breast cancers (n = 6), hematological cancers (n = 2), liposarcomas (n = 2), lung cancers (n = 2), kidney cancers (n = 2), cardia cancers (n = 2), bladder cancer (n = 1), prostate cancer (n = 1) and melanoma (n = 1). The mean extent of GIIG resection was 91.68 ± 6.39%, with no permanent neurological deficit. Fifteen oligodendrogliomas and 4 IDH-mutated astrocytomas were diagnosed. Adjuvant treatment was administrated in 12 patients before nCNSc onset. Moreover, 5 patients underwent reoperation. The median follow-up from initial GIIG surgery was 9.4years (range 2.3-19.9years). Nine patients (47%) died in this period. The 7 patients who deceased from the second tumor were significantly older at nCNSc diagnosis than the 2 patients who died from the glioma (p = 0.022), with a longer time between GIIG surgery and the occurrence of nCNSc (p = 0.046). This is the first study investigating the combination between GIIG and nCNSc. Because GIIG patients are living longer, the risk to experience second neoplasm and to die from it is increasing, especially in older patients. Such data may be helpful for tailoring the therapeutic strategy in neurooncological patients developing several cancers.

Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier.

Brain tumors are one of the leading causes of cancer related death in both the adult and pediatric patient population. Gliomas represent a cohort of brain tumors derived from glial cell lineages which include astrocytomas, oligodendrogliomas and glioblastomas (GBMs). These tumors are known to grow aggressively and have a high lethality with GBM being the most aggressive tumor in this group. Currently, few treatment options exist for GBM outside of surgical resection, radiation therapy and chemotherapy. While these measures have been shown to marginally improve patient survival, patients, especially those diagnosed with GBM, often experience a recurrence of their disease. Following disease recurrence, treatment options become more limited as additional surgical resections can pose life threatening risk to the patient, patients may be ineligible for additional radiation, and the recurrent tumor may be resistant to chemotherapy. Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy as many patients with cancers residing outside the central nervous system (CNS) have experienced a survival benefit from this treatment modality. It has often been observed that this survival benefit is increased following neoadjuvant administration of immune checkpoint inhibitors as tumor antigen is still present in the patient which enables a more robust anti-tumor immune response. Interestingly, results for ICI-based studies for patients with GBM have been largely disappointing which is a stark contrast from the success this treatment modality has had in non-central nervous system cancers. In this review, we will discuss the various benefits of neoadjuvant immune checkpoint inhibition such as how this approach reduces tumor burden and allows for a greater induction of an anti-tumor immune response. Additionally, we will discuss several non-CNS cancers where neoadjuvant immune checkpoint inhibition has been successful and discuss why we believe this approach may provide a survival benefit for GBM patients. We hope this manuscript will foster future studies aimed at exploring whether this approach may be beneficial for patients diagnosed with GBM.

A Systematic Review on the Potential Acceleration of Neurocognitive Aging in Older Cancer Survivors.

As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer's disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies.

Validation study of the Functional Assessment of Cancer Therapy-Cognitive Function-Version 3 for the Portuguese population

BackgroundCancer-related cognitive impairment is a common and potentially debilitating symptom experienced by patients with non-central nervous system (CNS) cancers, with negative impact on their quality of life. The Functional Assessment of Cancer Therapy-Cognitive Function-Version 3 (FACT-Cog-v3) is the most extensively used instrument specifically developed to evaluate cognitive complaints in adult cancer patients. Nevertheless, this self-report measure is not yet validated for the Portuguese population. Therefore, the purpose of this study was to evaluate the psychometric properties of the FACT-Cog-v3 among patients with non-CNS cancers in Portugal.MethodsThe validation study was conducted based on a convenience sample of 281 patients with non-CNS cancers, aged between 18 and 65 years, recruited online. A confirmatory factor analysis (CFA) was used to test the factor structure of the Portuguese FACT-Cog-v3 version; internal consistency analysis was also conducted. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30–version 3) and the Hospital Anxiety and Depression Scale (HADS) were also used to test the concurrent, convergent, and discriminant validity of the scale.ResultsCFA supported a four-factor model with good fix indexes and internal consistencies: perceived cognitive impairments (α = 0.97), comments from others (α = 0.92), perceived cognitive abilities (α = 0.93), and impact on quality of life (α = 0.92). Concurrent, convergent, and discriminant validities were confirmed. Moderate and strong correlations were found between the FACT-Cog-v3 subscales and the QLQ-C30 cognitive functioning subscale. Good convergent validity, with moderate correlations, was found between the FACT-Cog-v3 subscales and the HADS-A, HADS-D, and QLQ-C30 fatigue, sleep disturbance, and global health status subscales. Acceptable discriminant validity, with weak and moderate correlations, was demonstrated between the FACT-Cog-v3 subscales and the QLQ-C30 pain and nausea/vomiting subscales.ConclusionsThe Portuguese FACT-Cog-v3 version can be considered a reliable and valid measure to assess cognitive concerns of patients with non-CNS cancers, with relevance for research and clinical practice.

Associations between disrupted functional brain network topology and cognitive impairment in patients with rectal cancer during chemotherapy.

Cognitive impairment has been identified in patients with non-central nervous system cancer received chemotherapy. Chemotherapy-induced changes in the brain are considered as the possible causes of the cognitive deficits of patients. This study aimed to explore chemotherapy-related functional brain changes and cognitive impairment in rectal cancer (RC) patients who had just finished chemotherapy treatment. In this study, RC patients after chemotherapy (on the day patients received the last dose of chemotherapy) (n=30) and matched healthy controls (HCs) (n=30) underwent cognitive assessments, structural magnetic resonance imaging (MRI) and resting-state functional MRI. The functional brain networks were constructed by thresholding the partial correlation matrices of 90 brain regions in the Anatomical Automatic Labeling template and the topologic properties were evaluated by graph theory analysis. Moreover, correlations between altered topological measures and scores of cognitive scales were explored in the patient group. Compared with HCs, RC patients had lower scores of cognitive scales. The functional brain network had preserved small-world topological features but with a tendency towards higher path length in the whole network. In addition, patients had decreased nodal global efficiency (Eglo(i)) in the left superior frontal gyrus (dorsolateral), superior frontal gyrus (orbital part), inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part) and right inferior frontal gyrus (triangular part). Moreover, values of Eglo(i) in the superior and inferior frontal gyrus were positively associated with cognitive function in the patient group. These results suggested that cognitive impairment was associated with disruptions of the topological organization in functional brain networks of RC patients who had just finished chemotherapy, which provided new insights into the pathophysiology underlying acute effects of chemotherapy on cognitive function.

P01.18.B Structural abnormalities related to chemotherapy in cancer survivors: an ALE meta-analysis of neuroimaging studies

Abstract Background Chemotherapy induced cognitive impairment (CICI) is a term used for the cognitive dysfunction reported with non-central nervous system cancer patients during or after chemotherapy. Recent neuroimaging studies have shown decreased activation in cancer patients during cognitive tasks post-chemotherapy. Structural changes are sought to be associated with cognitive decline in cancer survivors after chemotherapy. Here we aim to investigate the neuroimaging findings of structural abnormalities and gray matter alterations associated with chemotherapy in cancer survivors. Material and Methods A systematic search through PubMed database for peer-reviewed English-language studies yielded a total of 302 studies. Eligible studies were included in the activation likelihood estimation (ALE) meta-analysis if they reported coordinates in a stereotactic format (MNI or Talairach space) for voxel-based morphometric (VBM) studies on gray matter volume and post-chemotherapy cancer survivors compared to matched healthy controls. GingerALE (3.0.2) software from Brainmap.org was used to perform the ALE meta-analysis with threshold settings of uncorrected P-value &amp;lt; 0.001 for multiple comparisons. Results The study sample included 299 patients comprised of breast cancer survivors (BCS), childhood acute lymphocytic leukemia (ALL) survivors, ovarian cancer survivors (OCS) and lung cancer with 279 matched healthy controls from 12 studies and 21 experiments. ALE-maps for post-chemotherapy cancer survivors showed reduced gray matter volume in comparison to healthy controls in the left inferior frontal gyrus, right thalamus, right superior frontal gyrus, right medial frontal gyrus and right cerebellum (peak coordinates: [-43,40,-6], [23,-29,2], [14,30,55], [9,57,-16], [9,-78,-41] respectively, and cluster size of 544 mm3, 312 mm3 and 257 mm3, 296 mm3, 297 mm3 respectively). Conclusion This is the first ALE meta-analysis that studied the converged areas of reduced gray matter volume in post-chemotherapy cancer survivors. Our findings of reduced gray matter volume in frontal regions and cerebellum might be responsible for the cognitive dysfunction in executive function, attention, and memory observed in cancer survivors. Further studies are needed to assess the impact of different chemotherapeutic regimens related to CICI .

Next Steps for Immunotherapy in Glioblastoma.

Simple SummaryPrognosis for glioblastoma patients remains poor despite the current standard of care treatments. More recent investigations have focused on immunotherapy, which utilizes a patient’s immune system to target cancer cells. Though proven to be successful in non-central nervous system cancers, immunotherapies have yielded disappointing results for glioblastoma thus far. A variety of factors play into the efficacy of immunotherapy for glioblastoma and have become new areas of interest. Here we review both historical and emerging immunotherapeutic approaches, as well as the molecular factors that have been shown to impact the efficacy of immunotherapies.Outcomes for glioblastoma (GBM) patients undergoing standard of care treatment remain poor. Here we discuss the portfolio of previously investigated immunotherapies for glioblastoma, including vaccine therapy and checkpoint inhibitors, as well as novel emerging therapeutic approaches. In addition, we explore the factors that potentially influence response to immunotherapy, which should be considered in future research aimed at improving immunotherapy efficacy.

Cancer‐related cognitive impairment in survivors of adolescent and young adult non‐central nervous system cancer: A scoping review

Cancer-related cognitive impairments (CRCI) are common after treatment and can have important impacts on the lives of adolescent and young adult (AYA) cancer survivors-those cancer survivors diagnosed between ages 15 and 39. However, most research focuses on survivors diagnosed under age 15 or over age 39 so we know relatively little about CRCI among AYA survivors of non-central nervous system (CNS) cancers. Here we review the research on CRCI among AYA survivors of non-CNS cancers to determine prevalence, associated factors, and impact on survivors' lives as well as implications for future research. In November 2021 we performed a systematic search of the literature in MEDLINE, Web of Science, PsycInfo, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials to identify peer-reviewed English language articles describing original research with at least one cognitive outcome and conducted with AYA survivors of non-CNS cancer diagnosed as AYAs. We screened 6003 articles and 21 met eligibility criteria. Guided by the PRISMA-ScR Checklist, we extracted study information to meet review objectives. Most studies employed cross-sectional surveys or interviews, though some employed longitudinal methods, neurocognitive assessments, or brain imaging. From the subset of articles that reported a prevalence we calculated a weighted mean prevalence of 25.75% and weighted median prevalence of 27.8%. The factors associated with CRCI included female gender, higher dose chemotherapy, and comorbidities. CRCI impacted the lives of AYA survivors through impaired role functioning, financial toxicity, and unmet needs. CRCI is highly prevalent among non-CNS cancer survivors diagnosed as AYAs and impacts quality of life and role functioning. This review suggests a need for further longitudinal, imaging, and mixed methods research and provision of resources to help achieve better quality of life and educational and occupational attainment during what is potentially a decades-long survivorship period. However, although interventions might improve cognition and functioning, the review identified only one pilot study. Digital interventions may be a practical and effective option for this age group, but they have yet to be adequately investigated.

Cognitive functioning and work-related outcomes of non-central nervous system cancer survivors: protocol for a systematic review with meta-analysis

IntroductionIn recent years, growing attention has been given to the study of the impact of cancer-related cognitive impairment (CRCI) in working non-central nervous system (CNS) cancer survivors. Available literature has...

OTHR-31. The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system (CNS) cancers

Abstract INTRODUCTION: Secondary meningiomas are a late effect in children who received cranial irradiation, frequently with a long latency. The molecular genetic profile of primary meningiomas is well studied; however, few studies describe the genomic landscape of radiation-induced meningiomas (RIM). METHODS: Patients followed at the Stollery Children’s Hospital (Edmonton, Canada) with a history of non-CNS malignancies who received cranial irradiation and then developed meningiomas between 1971 and 2013 were identified. Whole exome sequencing (WES), RNA sequencing as well as DNA methylation profiling were performed for patients with available tumor tissue and germline DNA. RESULTS: Of 96 patients who received cranial irradiation for non-CNS tumors, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients identified received 2000-2400 cGy of cranial irradiation, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) of meningiomas infiltrated other tissues. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. NF2 mutations were identified in 50% (8; 4 DNA,4 fusion). Other meningioma related genes with mutations identified in other cohorts were not identified. Copy number alternations were noted in all 16 patients in chromosomes 1p and 22q. 850k methylation analysis with PCA as well as UMAP and tSNE did not demonstrate clustering. Ongoing additional studies include examining tumor mutation burden and the radiation mutational profile. CONCLUSIONS: This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counselling, prognostication, and treatment.