non-CNS Cancer Research Articles

Barriers to T Cell Functionality in the Glioblastoma Microenvironment.

Glioblastoma (GBM) is an aggressive primary brain tumor depicted by a cold tumor microenvironment, low immunogenicity, and limited effective therapeutic interventions. Its location in the brain, a highly immune-selective organ, acts as a barrier, limiting immune access and promoting GBM dissemination, despite therapeutic interventions. Currently, chemotherapy and radiation combined with surgical resection are the standard of care for GBM treatment. Although immune checkpoint blockade has revolutionized the treatment of solid tumors, its observed success in extracranial tumors has not translated into a significant survival benefit for GBM patients. To develop effective immunotherapies for GBM, it is vital to tailor treatments to overcome the numerous immunosuppressive barriers that inhibit T cell responses to these tumors. In this review, we address the unique physical and immunological barriers that make GBM challenging to treat. Additionally, we explore potential therapeutic mechanisms, studied in central nervous system (CNS) and non-CNS cancers, that may overcome these barriers. Furthermore, we examine current and promising immunotherapy clinical trials and immunotherapeutic interventions for GBM. By highlighting the array of challenges T cell-based therapies face in GBM, we hope this review can guide investigators as they develop future immunotherapies for this highly aggressive malignancy.

B - 97 On the Rebound: Resilience and Subjective Cognitive Concerns in Cancer

Abstract Objective There is a connection between resilience and subjective cognitive symptoms in medical populations. However, there is limited understanding of this relationship in cancer survivors, and no studies examine whether subjective cognition may change from pre- to post-resilience training in these patients. This study examined the relationship between subjective cognitive function and resilience in non-CNS cancer survivors who participated in a resiliency training intervention and investigated potential influences of change in subjective cognition. Method Adult cancer survivors at Massachusetts General Hospital (N = 275, Mage = 55.2, 87.3% female) participated in the Stress Management and Resilience Training-Relaxation Response Resilience Program (SMART-3RP) and completed self-report measures assessing subjective cognitive function, resilience, depression, and worry at pre-post the group intervention. Cross-sectional relationships were evaluated using hierarchical regression modeling. Repeated measures ANCOVA assessed differences in subjective cognition from pre-post, controlling for age and time since diagnosis. Mediation modeling assessed whether mental health symptoms change alongside subjective cognition and account for the relationship with resilience. Results Results revealed a significant relationship between subjective cognitive function and resilience at baseline (β = 0.35, p < 0.001) and a significant change post-SMART-3RP (F(1, 77) = 6.09, p = 0.016). Patients experienced a decrease in cognitive concerns while making gains in resilience (β = 0.39, p < 0.001). Changes in depression and anxiety did not mediate the relationship between resilience and subjective cognitive function (p’s > 0.05). Conclusion It may be possible to refer survivors to programs, such as the SMART-3RP, to manage their subjective concerns, in the absence of objective cognitive deficits.

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.

Cognitive Dysfunction in Non-CNS Metastatic Cancer: Comparing Brain Metastasis, Non-CNS Metastasis, and Healthy Controls

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

MDB-48. A SINGLE INSTITUTION EXPERIENCE OF CIPN MEASURED BY THE PED-MTNS IN CHILDREN AND ADOLESCENTS WITH MEDULLOBLASTOMA TREATED ON A TRIAL USING SIMILAR DOSING OF VINCRISTINE AND CISPLATIN FOR ALL PATIENTS

Abstract BACKGROUND Standard treatment for medulloblastoma in patients &amp;gt;3 years of age consists of tumor resection, radiation and chemotherapy using vincristine, cisplatin, cyclophosphamide +/- CCNU. Vincristine and Cisplatin are known to cause chemotherapy induced peripheral neuropathy (CIPN). The prevalence of CIPN in children with non-CNS cancers can be measured using the pediatric-modified Total Neuropathy Score (ped-mTNS). The purpose of this observational, retrospective pilot design is twofold: to investigate the prevalence of CIPN in children with medulloblastoma receiving neurotoxic chemotherapy, and to examine the feasibility of using the ped-mTNS as a measurement tool in this population. METHODS Data was manually extracted from medical records and entered into a REDCap database for analysis. The percent of patients successfully tested and clinical inferences made from ped-mTNS testing results were used to determine feasibility and barriers to use. A total of 33 medulloblastoma patients &amp;gt;3 years of age were treated from 6/2013 - 6/2021 at Children’s Minnesota. Of those, 18 received testing using the ped-mTNS during chemotherapy treatment. RESULTS During cancer treatment, 54.5% of the cohort of patients received ped-mTNS testing. The average age of children tested was 10.26 (4.39) years with a majority being male (79%), and non-Hispanic white race/ethnicity (89%). Of the tested participants, 61.1% had more than one measurement. For those patients tested at multiple timepoints, 72.7% demonstrated worsening ped-mTNS scores while on chemotherapy treatment. Therapists recorded inferences relating to neuropathy in 88.1% of testing occurrences with questions of accuracy recorded in 31.3% of testing occurrences. Barriers to use of results included confounding impairments that may occur as a result of the primary tumor, post-surgical changes, and radiation. CONCLUSIONS Using the ped-mTNS is feasible in children and adolescents with medulloblastoma. The ped-mTNS scores indicated that children with medulloblastoma, treated with Vincristine and Cisplatin, experience worsening neuropathy while undergoing chemotherapy treatment.

DIPG-89. ENHANCEMENT OF BLOOD-BRAIN BARRIER PENETRATION AND TUMOR TARGETED DRUG DELIVERY FOR DMG USING A P-SELECTIN TARGETED NANOMEDICINE APPROACH

Abstract The blood-brain barrier (BBB) is one of the greatest barriers for the effective treatment of brain tumors, including H3K27-altered diffuse midline glioma (DMG), a near universally fatal childhood brain cancer. The BBB typically requires drugs to be given at maximally tolerated doses that are limited by systemic toxicities, particularly in settings of combination therapy. We have developed a clinically compatible fucoidan nanoparticle (Fi-NP) that homes to P-selectin on tumor vasculature after low-dose radiation (RT) to breach the BBB through an active caveolin-1-dependent mechanism and deliver several classes of targeted therapies. In non-CNS cancer xenograft models and a transgenic mouse model of SHH-driven medulloblastoma with an intact BBB, this approach improved survival while eliminating on-target systemic toxicities. We have now applied this approach to both brainstem and non-brainstem RCAS-TVA mouse models of DMG with an intact BBB. Specifically, we have found that DMG tumor vasculature expresses P-selectin, and that a single low-dose 2 Gy fraction of ionizing radiation further enhances it in a time-dependent manner up to 24 hours post-treatment. Importantly, we have also found that this P-selectin targeted drug delivery approach facilitates DMG tumor localization of Fi-NP encapsulated EZH2 inhibitor tazemetostat (EPZ-6438) as well as larger macromolecules including the PROTAC BET degrader dBET6, two promising targeted therapies for DMG limited by extremely poor BBB-penetration, while sparing drug delivery to non-tumor healthy brain regions. Work to measure PK, biodistribution, survival benefit, and drug target inhibition is ongoing. Our findings will provide the foundation for this P-selectin targeted Fi-NP approach to be evaluated in clinical trials for children with this lethal cancer.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression invivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and Tcell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

Process models of verbal memory in cancer survivors: Bayesian process modeling approach to variation in test scores

ABSTRACT Introduction Verbal memory is a complex and fundamental aspect of human cognition. However, traditional sum-score analyses of verbal learning tests oversimplify underlying verbal memory processes. We propose using process models to subdivide memory into multiple processes, which helps in localizing the most affected processes in impaired verbal memory. Additionally, the model can be used to address score and process variability. This study aims to investigate the effects of cancer and its treatment on verbal memory, as well as provide a demonstration of how process models can be used to investigate the uncertainty in neuropsychological test scores. Method We present an investigation of memory process scores in non-CNS cancer survivors (n = 184) and no-cancer controls (n = 204). The participants completed the Amsterdam Cognition Scan (ACS), in which classical neuropsychological tests are digitally recreated for online at-home administration. We analyzed data from the ACS equivalent of a Verbal Learning Test using both traditional sum scores and a Bayesian process model. Results Analysis of the sum score indicated that patients scored lower than controls on immediate recall but found no difference for delayed recall. The process model analysis indicated a small difference between patients and controls in immediate retrieval from both the partially learned and learned states, with no differences in learning or delayed retrieval processes. Individual-level analysis shows considerable uncertainty for sum scores. Sum scores were more certain than single trials. Retrieval parameters also showed less uncertainty than learning parameters. Conclusion The Bayesian process model increased the informativity of Verbal Learning test data, by showing uncertainty of the traditional sum score measurements as well as how the underlying processes differed between populations. Additionally, the model grants insight into underlying memory processes for individuals and how these processes vary within and between them.

Neurocognitive Dysfunction and predictors in non-CNS cancer patients: Rationale and methods for the neuro-oncology research at a South African academic hospital

BackgroundThe focus on central nervous system (CNS) malignancies has overshadowed scant but substantial research that suggests non-central nervous cancer patients experience cancer-related cognitive impairment (CRCI), which affects higher-order brain function and influences their quality of life. Despite such evidence of the occurrence of CRCI among non-CNS cancer patients, the factors associated with the CRCIs remain a highly debated issue with discrepancies noted. Whether non-CNS cancer itself can affect the brain independent of cancer treatment is an important question to unpack. This necessitates further research, particularly in the sub-Saharan region where the evidence is limited. MethodsThis study aims to assess the effect of chemotherapy-associated cognitive and affective changes in non-CNS cancer patients. A non-experimental, time-series, correlational design will be used, in which a battery of computerized neuropsychological tests will be administered, including the e-MoCA, the CNS Vital Signs, the Patient Health Questionnaire-4, the Center for Epidemiologic Studies Depression Scale, the Hamilton Anxiety Rating Scale, the Functional Assessment of Cancer Therapy-Fatigue, and the Semi-structured Interview Schedule. Descriptive and inferential statistical analysis will be conducted, as well as NVivo thematic analysis of the qualitative data. The scope of the neurocognitive issues and risk factors that may be present in cancer patients and survivors in a developing environment could be determined by this study. ImplicationsThe study is expected to extend research on the extent at which cancer and cancer treatments are associated with neurocognitive changes among non-CNS cancer patients and their impact on their quality of life in the local context. The results are expected to inform treatment providers to develop treatment guidelines tailored for individuals diagnosed with cancer and who have received cancer treatment, as well as individualized psychosocial interventions aimed at addressing psychological challenges associated with quality of life among cancer survivors.

NCOG-34. BRAIN PET IMAGING OF PAIRED HELICAL FILAMENT TAU IN OLDER ADULTS WITH CANCER: PILOT STUDY TO IDENTIFY MECHANISMS OF COGNITIVE IMPAIRMENT AFTER CANCER THERAPY

Abstract BACKGROUND Cancer-related cognitive impairment (CRCI) occurs in up to 75% of patients treated with chemotherapy for systemic cancer, and older patients treated for CNS cancer receiving brain radiation therapy (RT) and chemotherapy are particularly at risk. The mechanisms of injury and CRCI remain unknown. In neurodegenerative disorders, deposition of paired helical filament tau (PHFTau) is correlated with nature and extent of cognitive symptoms. The role of PHFTau in CRCI has not been elucidated. We conducted a pilot study to determine whether CRCI is associated with PHFTau. METHODS Patients (age &amp;gt;60) diagnosed with mild cognitive impairment (MCI) or dementia after chemotherapy and/or brain RT underwent Tau PET imaging using [F18]Flourtaucipir. Cortical [F18]Flourtaucipir binding was quantified by standard uptake value ratio (SUVR) in 68 regions of interest (ROIs) and compared to a control group (n=22). SUVR in each ROI for each subject was considered significantly elevated when it was &amp;gt;2SD above the control group (p&amp;lt; 0.05). Neuropsychological test scores were correlated with PHFTau distribution. RESULTS Five patients with MCI/Dementia following cancer therapy participated. Two patients with prior chemo-RT for CNS cancer and prominent executive dysfunction had no significant F[18]T807 uptake. However, three patients treated with systemic chemotherapy for non-CNS cancer and neuropsychological profiles dominated by episodic memory impairment showed F[18]T807 uptake in patterns typical of AD dementia in temporal, parietal and cingulate ROI’s (n=2), or uptake in the entorhinal and inferior temporal ROIs (n=1). DISCUSSION In this pilot study, [F18]Flourtaucipir imaging of patients with cancer and MCI/Dementia showed that executive dysfunction after RT was not associated with abnormal PHFTau whereas amnestic declines after chemotherapy were associated with PHFTau in medial temporal lobes and beyond. Given the cross-sectional study, timing of tau accumulation in relation to cancer/treatment is unknown. Prospective studies are needed to understand the relevance of PHFTau in CRCI.

CE Workshop 07: Cognitive Effects of Cancer and Treatment: “Chemobrain” and Beyond

Abstract &amp; Learning Objectives:Improvements in treatment for non-CNS cancer have greatly improved survivorship, allowing increased attention to cancer- and treatment-related sequelae. Cognitive symptoms (cancer-related cognitive impairment, or CRCI) are reported by a large percentage of cancer survivors, and can have a clinically meaningful impact on educational, vocational, and social functioning, and thus overall quality of life. Better understanding of these concerns is therefore of critical importance, and is needed to guide treatment and potential prevention strategies. Neuropsychological studies over the past 40 years have demonstrated cognitive domains commonly affected in cancer patients treated with chemotherapy, but have also shown cognitive differences in patients not treated with systemic therapy and those receiving other types of treatment (e.g., hormonal therapies) relative to non-cancer control groups. More recently, structural and functional neuroimaging research has added to our understanding of the neural substrate of these cognitive symptoms. This course will describe various neuroimaging modalities used to investigate CRCI, including examination of grey and white matter volume and structural integrity, blood flow, brain activation during cognitive processing and at rest, and structural and functional connectivity. The presentation will also review how neuroimaging findings relate to objective and self-reported cognition and clinical and treatment factors, and discuss potential approaches currently being investigated to treat CRCI. Upon conclusion of this course, learners will be able to:1.Explain commonly affected cognitive domains after non-CNS cancer and treatment2.Discuss structural and functional brain changes related to cancer, chemotherapy, and other treatments3.Describe treatment interventions being investigated to treat cancer- and treatment-related cognitive symptoms.

12 Differential Processing Efficiency Skills in Survivors of Pediatric Primary CNS Cancer and Cancers of non-CNS Origin

Objective:Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.Participants and Methods:Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores &gt;1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.Results:The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p &lt; 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p &lt; 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p &lt; 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p &lt; 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p&lt;.001) and semantic fluency (ß=7.59, p=.007).Conclusions:These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

8 Computational Modeling of Memory Processes in non-CNS Cancer Survivors

Objective:Cognitive impairment is an often-overlooked issue that non-CNS cancer survivors face. Our current understanding of their issues is lacking, as traditional memory sum scores grant us little insight into the underlying cognitive processes of memory and its impairment. We can improve the informativity of memory impairment studies by isolating which cognitive processes are impaired.Participants and Methods:Participants were breast cancer survivors who received chemotherapy (n=68), and women controls (n=157). The participants completed the Amsterdam Cognition Scan (ACS), in which classical neuropsychological tests are digitally recreated for online at-home administration. Online administration reduces the burden on patients and allows for recording measurements with greater precision. The specific test used to illustrate the effectiveness of our computational modeling approach was the ACS equivalent of the Rey Auditory Verbal Learning Test, in which participants are tasked with recalling a list of 15 words five times. We formulated a Hierarchical Bayesian Cognitive Model to replace traditional sum scores and disentangle performance into the more theoretically meaningful concepts of 'memory storage’ and 'memory retrieval'.Results:A traditional analysis of the sum of trials 1-5 indicated no significant difference between patients and controls (t(223)=-0.99, p = 0.323), with a small effect size (Cohen’s d = -0.14).For the newly isolated cognitive process “memory storage”, a non-significant difference was found between patients and controls (d=0.10, 95% credible interval on Cohen’s d: [0.25, 0.43]). On the “memory retrieval” process, a medium significant difference was found between patients and controls (d = -0.57, 95% credible interval on Cohen’s d: [-1.00, -0.19]).Conclusions:The results indicate that the impaired memory processes in cancer patients are not a general impairment across all memory functions, but rather a selective impairment of memory retrieval. Our method of analysis revealed information that would have been left unnoticed had we relied on traditional sum over trials 1-5.

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.

Risk of developing glioblastoma following non-CNS primary cancer: a SEER analysis between 2000 and 2018.

Patients with a prior malignancy are at elevated risk of developing subsequent primary malignancies (SPMs). However, the risk of developing subsequent primary glioblastoma (SPGBM) in patients with a prior cancer history is poorly understood. We used the Surveillance, Epidemiology, and End Results (SEER) database and identified patients diagnosed with non-CNS malignancy between 2000 and 2018. We calculated a modified standardized incidence ratio (M-SIR), defined as the ratio of the incidence of SPGBM among patients with initial non-CNS malignancy to the incidence of GBM in the general population, stratified by sex latency, and initial tumor location. Of the 5,326,172 patients diagnosed with a primary non-CNS malignancy, 3559 patients developed SPGBM (0.07%). Among patients with SPGBM, 2312 (65.0%) were men, compared to 2,706,933 (50.8%) men in the total primary non-CNS malignancy cohort. The median age at diagnosis of SPGBM was 65years. The mean latency between a prior non-CNS malignancy and developing a SPGBM was 67.3months (interquartile range [IQR] 27-100). Overall, patients with a primary non-CNS malignancy had a significantly elevated M-SIR (1.13, 95% CI 1.09-1.16), with a 13% increased incidence of SPGBM when compared to the incidence of developing GBM in the age-matched general population. When stratified by non-CNS tumor location, patients diagnosed with primary melanoma, lymphoma, prostate, breast, renal, or endocrine malignancies had a higher M-SIR (M-SIR ranges: 1.09-2.15). Patients with lung cancers (M-SIR 0.82, 95% CI 0.68-0.99), or stomach cancers (M-SIR 0.47, 95% CI 0.24-0.82) demonstrated a lower M-SIR. Patients with a history of prior non-CNS malignancy are at an overall increased risk of developing SPGBM relative to the incidence of developing GBM in the general population. However, the incidence of SPGBM after prior non-CNS malignancy varies by primary tumor location, with some non-CNS malignancies demonstrating either increased or decreased predisposition for SPGBM depending on tumor origin. These findings merit future investigation into whether these relationships represent treatment effects or a previously unknown shared predisposition for glioblastoma and non-CNS malignancy.

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.

How much does having a neurologic disease affect QoL in non-CNS cancer patients? (P7-13.002)

<h3>Objective:</h3> To measure the impact of having an active neurologic disease (ND) in the quality of life (QoL) of patients with systemic cancer (non-CNS cancer). <h3>Background:</h3> The burden from neurologic symptoms in cancer patients has scantly been studied <h3>Design/Methods:</h3> Patients with systemic cancer sent for Neuro-oncologic evaluation at a single cancer center were prospectively invited to respond the QLQ-C30 and QLQ-BN20 questionnaires. Associations of the questionnaire’s items were blindly measured for the following groups: active ND (+) or not (ND−) and active cancer (AC+) or not (AC−) <h3>Results:</h3> Of 205 patients, mean age 55.6 ± 15.8 years, 122 (60%) had a ND+ and 107 (52%) an AC+. QoL, measured by the QLQ-C30, was significantly worse in the ND+ group in the following scales/items: role (P &lt;0.001), pain (P &lt; 0.001), fatigue (P &lt;0.001), cognitive (P &lt; 0.001), appetite loss (P = 0.003), N/V (P = 0.006), emotional (P = 0.007), physical (P = 0.021), global health (P = 0.021), and insomnia (P = 0.040). For the BN20 scales/items, the ND+ group had worse scores in headache (P &lt; 0.001), weakness (P &lt; 0.001), motor (P = 0.002), visual (P = 0.015), alopecia (P = 0.019), and communication (P = 0.039) <h3>Conclusions:</h3> In cancer patients quality of life is significantly worse for patients with an active neurologic disease; therefore, an early referral and approach is recommended for all patients with neurologic symptoms <b>Disclosure:</b> Dr. Cacho Diaz has nothing to disclose.

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.

Are neurologic symptoms associated with worse QoL in non-CNS cancer patients?

BackgroundThe burden of having neurologic symptoms (NS) in cancer patients has scantly been studied; therefore, we performed a study whose purpose was to measure the impact of having clinically active (NS) on the quality of life (QoL) of non-primary CNS cancer patients. MethodsPatients with systemic cancer (non-primary CNS cancer) sent for neurological evaluation at a single cancer center (INCAN) were prospectively invited to respond the EORTC-QLQ-C30 and BN20 questionnaires. Associations of the questionnairés items were blindly measured for the following groups: NS+ or not (NS−) and having active cancer (AC+) or not (AC−). ResultsOf 205 patients aged 55.4 ± 15.4 years, 122 (60%) had NS+ and 107 (52%) AC +. The NS+ group (compared with the NS−) showed a significant worse perception in the following scales/items of the EORTC QLQ-C30: physical functioning (median 86 vs. 92, P = 0.012), role functioning (66 vs. 100, P < 0.001), emotional functioning (75 vs. 83, P = 0.005), cognitive functioning (66 vs. 83, P < 0.001), fatigue (33 vs. 22, P < 0.001), nausea and vomiting (P = 0.021), pain (33 vs. 16, P < 0.001), insomnia (33 vs. 0, P = 0.011), appetite loss (P = 0.021), and global health (66 vs. 75, P = 0.001). ConclusionIn patients with systemic (non-CNS) cancer, the QoL is significantly worse for patients with active neurologic symptoms.