Impairment In Cancer Patients Research Articles

L-carnitine Modulates Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights to Oxidative Stress, Inflammation, Synaptic Plasticity, Liver/brain, and Kidney/brain Axes.

Chemotherapy-induced cognitive impairment in cancer patients is known as "chemobrain". Doxorubicin and Cyclophosphamide are two chemotherapeutic agents used in combination to treat solid tumors. L-carnitine was reported for its anti-oxidant and anti-inflammatory activities. The goal of the present study was to elucidate the neuroprotective effect of L-carnitine against chemobrain induced by Doxorubicin and Cyclophosphamide in rats. Rats were divided into five groups: Control group; Doxorubicin (4mg/kg, IV) and Cyclophosphamide (40mg/kg, IV)-treated group; two L-carnitine-treated groups (150 and 300mg/kg, ip) with Doxorubicin and Cyclophosphamide; and L-carnitine alone-treated group (300mg/kg). Doxorubicin and Cyclophosphamide induced histopathological changes in rats' hippocampi and prefrontal cortices, as well as reduced memory as evidenced by behavioural testing. L-carnitine treatment showed opposite effects. In addition, chemotherapy treatment enhanced oxidative stress via reducing catalase and glutathione levels, and inducing lipid peroxidation. By contrast, L-carnitine treatment showed powerful antioxidant effects reversing chemotherapy-induced oxidative damage. Moreover, chemotherapy combination induced inflammation via their effect on nuclear factor kappa B(p65), interleukin-1β, and tumor necrosis factor-α. However, L-carnitine treatment corrected such inflammatory responses. Furthermore, Doxorubicin and Cyclophosphamide reduced synaptic plasticity via hindering expression of brain-derived neurotrophic factor, phosphorylated cyclase response element binding protein, synaptophysin, and postsynaptic density protein 95 whereas protein expression of such synaptic plasticity biomarkers was enhanced by L-carnitine treatment. Finally, acetylcholinesterase activity was found to be enhanced by chemotherapy treatment affecting rats' memory while L-carnitine treatment reduced acetylcholinesterase activity. L-carnitine also showed hepatoprotective and renal protective effects suggesting liver/brain and kidney/brain axes as possible mechanisms for its neuroprotective effects.

Nephrotoxicity associated with anticancer agents: perspective on onconephrology from nephrologists.

Nephrotoxicity is one of the most important complications in cancer patients. In particular, acute kidney injury (AKI) is known to be associated with discontinuing effective oncological treatments, longer hospitalizations, increased costs, and a higher risk of death. In addition to acute kidney injury, clinical signs associated with nephrotoxicity during treatment with anticancer agents include chronic kidney disease, proteinuria, hypertension, electrolyte abnormalities, and other characteristic manifestations. Many of these signs are caused both by cancer treatment as well as by cancer itself. Therefore, it is important to carefully recognize whether the underlying causes of renal impairment in cancer patients are cancer-related, treatment-related, or both. This review describes the epidemiology and pathophysiology of anticancer agent-induced acute kidney injury, proteinuria, hypertension, and other characteristic manifestations.

Insomnia in cancer patients.

e18657 Background: As new treatments extend patient survival, the quality of their lives (QoL) grows in importance. QoL may differentiate alternative treatments, and QoL assessment has become a standard component of treatment evaluations. Sleep is a key component of QoL. Insomnia can worsen pain, fatigue, depression and cognitive impairments in cancer patients. Inappropriate treatments for insomnia can further worsen these and interact with chemotherapy medications. Recognizing this, in 2019 the American Society of Clinical Oncology identified Insomnia as a key patient-reported outcome performance measure (PRO-PM) for the National Quality Forum to consider. Methods: Through review of the scientific literature the project identified specific cancers and their treatments where treating Insomnia can have a significant impact on patient QoL. PubMed, Pharmapendium, and Science Direct databases were used. Search terms included “insomnia demographics, epidemiology of insomnia in cancer, insomnia in tumor types, cancer insomnia, insomnia associated hormonal treatment, insomnia in patients awaiting cancer diagnosis; insomnia in cancer care-givers, insomnia in cancer survivors, cancers treated with corticosteriods”. Original research articles in English that used human subjects between January 1, 1993 and January 31, 2020 were included. Results: Insomnia is associated with specific tumor types: brain tumors, breast cancer, gastrointestinal cancer, leukemia, lymphoma, multiple myelomaand terminal cancer. Autoimmune causes of insomnia in paraneoplastic syndromes. Insomnia is prevalent in oncology patients being evaluated, awaiting diagnosis and treatment. Age and gender are demographic factors associated with oncology insomnia. Insomnia is associated with specific antineoplastic agents. Corticosteroid use is associated with insomnia, before, during and after cancer treatment. Insomnia in cancer survivors starts during their treatment and may persist for years. Conclusions: Specific demographics, cancers and treatments are associated with insomnia. Insomnia often occurs in patients undergoing evaluations for cancer. Insomnia is often not recognized and not treated in oncology patients. Insomnia that is not addressed during cancer treatment often persists in cancer survivors. There is the need to investigate whether treating insomnia early in cancer patients during their course of treatment can reduce symptoms such as fatigue and improve their QOL.

Effects of the epidermal growth factor receptor inhibitor, gefitinib, on lipid and hyaluronic acid synthesis in cultured HaCaT keratinocytes.

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used for treating various cancers, including lung, colon, head and neck cancers. However, EGFRIs have unique dermatological side effects, including acneiform eruption, dry skin, paronychia and pruritus. In this study, we investigated the molecular changes induced by an EGFRI, gefitinib, in the expression of lipogenic enzymes and hyaluronic acid (HA) regulatory proteins in HaCaT keratinocytes, and whether EGF restored these changes. HaCaT cells were treated with gefitinib, with or without EGF, and treated with tumor necrosis factor α (TNFα) for inducing an inflammatory response. The mRNA and protein expression was analyzed by real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA) and western blotting. Gefitinib enhanced the TNFα-induced expression of C-C motif chemokine ligand 2 (CCL2), CCL5 and C-X-C motif chemokine ligand 10 (CXCL10), and the expression of TNFα in HaCaT cells, while EGF restored these changes. At a similar concentration range, gefitinib reduced the mRNA and/or protein expression of various lipogenic enzymes for fatty acid, cholesterol and ceramide synthesis, except acidic sphingomyelinase. Gefitinib suppressed the mRNA and protein expression of HA synthase 2 (HAS2), HAS3, cluster of differentiation 44 (CD44), hyaluronidase 1 (HYAL1) and HYAL2, except the mRNA expression of HYAL1. EGF restored the changes induced by gefitinib, except for the mRNA expression of fatty acid synthase (FASN) and elongation of very long-chain fatty acid protein (ELOVL) 6. In conclusion, EGFRIs suppress lipogenesis and HA metabolism, which may contribute to adverse dermatological effects, including barrier function impairment in cancer patients treated with EGFRIs.

Nose-to-brain delivery of chrysin transfersomal and composite vesicles in doxorubicin-induced cognitive impairment in rats: Insights on formulation, oxidative stress and TLR4/NF-kB/NLRP3 pathways

Many cancer survivors suffer from chemotherapy-induced cognitive impairment known as ‘Chemobrain’. Doxorubicin -topoisomerase II inhibitor- is widely used in breast cancer, hematological cancers and other neoplasms. However, it is reported to precipitate cognitive impairment in cancer patients via inducing oxidative stress and inflammatory response. Chrysin −5,7 dihydroxyflavone- has promising antioxidant, anti-inflammatory and anticancer properties, but suffers low bioavailability owing to its poor solubility and extensive metabolism. In the present study, chrysin was successfully formulated as transfersomal lipid vesicles and chitosan composite vesicles (CCV) exhibiting a nanometric size range, high drug entrapment efficiency, and controlled release over a 72h period. Intranasal administration of optimized chrysin formulations at a reduced dose of 0.5 mg/kg improved doxorubicin-induced memory impairment in rats evidenced by behavioral testing, inhibition of acetylcholinesterase activity and oxidative stress markers; catalase, reduced glutathione, lipid peroxidation and hydrogen peroxide. This could reduce caspase-3 expression inhibiting apoptosis. Moreover, chrysin formulations were able to inhibit doxorubicin-induced Tol-like receptor 4 (TLR4) and p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) protein expression which in turn, reduced procaspase-1, Cysteinyl Aspartate Protease-1 (caspase-1) and Interleukin-1β (IL-1β) protein expression via inhibiting Nod-like receptor pyrin containing 3 (NLRP3) inflammasome. Collectively, our findings suggest the enhanced therapeutic potential of chrysin when formulated as transfersomes and CCV against chemotherapy-induced chemobrain via hindering acetylcholinesterase, oxidative stress and TLR4-NF-kB(p65)-NLRP3 pathways.

CMF and MET treatment induce cognitive impairment through upregulation of IL-1α in rat brain.

Cyclophosphamide (CYP), methotrexate (MTX) and 5-fluorouracil (5-FU) (CMF) are chemotherapeutic agents known to cause acute and long-term cognitive impairment in cancer patients. Cognitive function is regulated mainly by neuronal circuitry in the brain, especially the cortex and hippocampus as well as other components of the limbic area. Neuroinflammation mediated by proinflammatory cytokines is a well-known cause of cognitive impairment. Our previous study showed that metformin induced cognitive impairment and neuroinflammation in CMF-treated rats. Understanding the effects and mechanisms of CMF and MET treatment on chemotherapy-related cognitive impairment and the relationship with neuroinflammation may help prevent some of the adverse effects of this type of chemotherapy in cancer patients. Rats were divided into four groups: control (normal saline), CMF (50 mg/kg CYP, 2 mg/kg MTX, 50 mg/kg 5-FU; two doses administered by intraperitoneal injection over two weeks), MET (2.5 mg/ml - oral administration daily), and CMF+MET group. IL-1α, IRS-1, Akt-a and TNF-α levels in brain tissues were measured by ELISA and data were analyzed by one-way ANOVA test followed by Tukey's test. Compared with the control group, IL-1α levels were significantly increased in the CMF+MET group, whereas there were no significant differences in the MET and CMF groups. On the other hand, IRS-1, TNF-α and Akt-a expression and mitochondrial complex 1 activity indicated that systemic CMF and MET treatment did not change the expression of these proteins in the brain compared to the control group. Our results indicate that cognitive function is impaired by the administration of two doses of CMF and MET over a period of two weeks as a result of IL-1α overexpression in the brain.

MO507ROCK STUDY: RESEARCH STUDY OF CANCER ASSOCIATED KIDNEY DISEASES

Abstract Background and Aims The improvement in the survival rates of cancer patients due to the new oncological and biological agents has led to an increase in those who develop kidney diseases. It is now well known that chronic kidney disease (CKD) and cancer are connected in several ways. Nevertheless, although emerging evidence suggests that the risk of renal impairment in cancer patients is high and increasing, the overall incidence and prevalence of CKD in this population are still uncertain. The purpose of the study is to provide data on the prevalence and incidence of CKD in patients included in the Cancer Registry of the province of Reggio Emilia, Italy, since January, 1st to December, 31st 2016. Method single-center, observational and retrospective study. For all patients included, data on sex, age, ethnicity, serum creatinine and related eGFR, type and number of tumors, diagnosis of diabetes mellitus were collected. The main cancer sites considered were breast, colorectal, lung, pancreas, stomach, prostate, lymphomas and leukemias. An eGFR ≥ 60 ml/min1.73m2 was indicative of a normal kidney function, while an eGFR <60 ml/min/1.73m2 as kidney impairment. All the eGFR data were calculated not only with the CKD-EPI formula, now recognized as the reference formula for estimating eGFR in the general population, but also with the Wright formula which seems to provide the best estimate in cancer patients. Results 4254 patients with a cancer diagnosis were identified between January 1st and December 31st 2016; of these, 171 patients were excluded due to lack of data. Of the remaining 4083 patients, 776 (19%) had at least an eGFR value <60 mL/min/1.73m2 prior to cancer diagnosis and 497 patients (11.7%) were identified as affected by CKD. The incidence of new-onset CKD in the following 24 months since cancer diagnosis was 4.4% (186 patients) [95% CI 3.9-5.3] using CKD-EPI formula; using Wright formula, we identified 140 (3.4%) [95% CI 2.9-4.0] new cases of CKD in the same period. For both cohorts of patients (pre-existing CKD and CKD diagnosed after cancer diagnosis), descriptive analyzes were conducted related to demographic and clinical data. Referring to the CKD-EPI formula, in patients with pre-existing CKD (497 patients, 11.7%), the mean age was 81 years (SD ± 8.4), 53.7% were men, 18.3% had a known diagnosis of type 2 diabetes mellitus, 3.6% of these patients had 2 or more cancer diagnosis in the study period. 44.3% were alive at the end of the follow-up (December 31st, 2018). Using Wright formula, 504 (11.8%) patients with CKD already present at the time of cancer diagnosis were identified; these patients had an average age of 82 years (SD ± 8.4) and in 55.4% of cases were men; 18.8% had type 2 diabetes mellitus and 3.8% had 2 or more cancer diagnosis. Conclusion The ROCK study is the first large cohort study that allows a clearer estimation of the frequency of CKD in Italian cancer patients. Knowledge of the prevalence of CKD in cancer patients is essential for proper clinical and therapeutic management and implementation of preventive strategies.

Cognitive impairment in cancer patients and survivors—clinical presentation, pathophysiology, diagnosis and management

Cognitive impairment by neurotoxic substances, administered alone or in a multidrug regimen, affects a large number of patients treated for noncentral nervous system cancer during and after chemotherapy with variable onset, severity and duration, but sustainably affecting the patients’ individual health-related quality of life. Depending on the mechanism of action, the ability to cross the blood–brain barrier into the central nervous system and the cumulative total dose of the cytotoxic drugs results in functional and structural brain changes. This neurotoxicity leads to negative effects on neural precursor cells (neurogenesis), microglia (neuroinflammation), neurons (cortical dysfunction with altered brain networks), and astro-/oligodendroglia (white matter tract demyelination) and therefore on patients’ cognitive performance. Memory and executive functions, attention/concentration, and processing speed are the cognitive domains commonly impaired by chemotherapy. Importantly, numerous simultaneously occurring risk factors may also have distinct restrictions on cognitive function. For this reason, the term cancer-related cognitive impairment (CRCI), implicating neurotoxicity in cancer patients with simultaneous consideration of other causes on cognitive performance, should be used. The aim of this review is to provide an update of the most recent clinical and pathophysiological findings, self-reported and neuropsychological testing methods, and the current management strategies of CRCI.

Probiotics in Health and Disease: Distinct Roles of Different Strains in Natural Killer Cell Activation and Regulation.

Elucidating the role of probiotic bacteria in health and disease perhaps constitutes one of the most exciting and fastest growing fields in medicine as we uncover the beneficial roles of these bacteria in many disease processes including cancer. We and others have reported previously that probiotic bacteria play a significant role in the activation of many cells including the cancer fighting natural killer (NK) cells. NK cells are the key immune effectors which control tumor growth and metastasis due to their ability to mediate direct cytotoxicity and/or differentiation of cancer stem cells/undifferentiated tumors through secreted and membrane bound interferon-gamma and tumor necrosis factor-alpha. In this review, we present an overview of recent studies from our laboratory and those of the others on their beneficial effects on immune cell function in particular on NK cells. In addition, we also highlight the current understanding of the role of probiotics in enhancement of the effectiveness of cancer therapeutics. Moreover, we discuss the functional impairment of cancer patients' NK cells and the role of probiotics in reversal of such functional impairment. NK cell-based immuno-therapies in combination with well-selected strains of probiotic bacteria may probably represent one of the best adjunct therapeutic approaches to prevent and treat cancer in the future.

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study.

Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.

The Anti-Inflammatory Drug Aspirin Does Not Protect Against Chemotherapy-Induced Memory Impairment by Paclitaxel in Mice.

Inflammation has been proposed to play a causal role in chemobrain which—if true—would represent an opportunity to repurpose existing anti-inflammatory drugs for the prevention and treatment of chemobrain. Here, we show that the chemoagent paclitaxel induces memory impairment and anhedonia in mice within 24 h of treatment cessation, but inflammation is not present until 2 weeks after treatment. We find no evidence of brain inflammation as measured by cytokine analysis at any time point. Furthermore, treating with aspirin to block inflammation did not affect paclitaxel-induced memory impairment. These findings suggest that inflammation may not be responsible for memory impairment induced by paclitaxel. These results contrast with recent findings of a causal role for inflammation in cancer-induced memory deficits in mice that were prevented by treatment with oral aspirin, suggesting that cognitive impairment in cancer patients undergoing treatment may arise from multiple convergent mechanisms.

Determinants of the Higher Prevalence and Severity of Subjective Cognitive Impairment in Cancer Patients Compared to Healthy Subjects: Fatigue and Stress.

This study examined whether (a) cancer patients in two cohorts reported greater subjective cognitive impairment (SCI) in prevalence and severity than noncancer healthy controls; and (b) selected psychoneurological factors (fatigue, stress, and sleep disturbance) contribute to such differences. Data from 60 prechemotherapy cancer patients, 81 active-chemotherapy cancer patients, and 116 noncancer healthy controls were analyzed using hierarchical regressions. The prevalence rate of SCI was higher in the prechemotherapy cancer cohort (41.6%) and in the active-chemotherapy cancer cohort (46.9%) than in healthy controls (21.5%; p < .001). SCI severity was also higher in two cancer cohorts than noncancer controls (p < .001). The two cancer cohorts were similar to each other in severity and prevalence of SCI. The two cancer cohorts experienced higher fatigue, stress, and sleep disturbance than healthy controls. After controlling for psychoneurological factors, however, the two cancer cohorts did not differ from healthy controls in experiencing SCI in prevalence and severity. Psychoneurological factors may be a major determinant of the higher prevalence and severity of SCI in cancer patients.

Muscle function impairment in cancer patients in pre-cachexia stage

Cancer cachexia has been reported to be directly responsible for at least 20% of cancer deaths. Management of muscle wasting in cancer-associated cachexia appears to be of pivotal importance for survival of patients. In this regard, it would be interesting to identify before its patent appearance eventual functional markers of muscle damage, to plan specific exercise protocols to counteract cachexia. The muscle function of 13 oncologic patients and 15 controls was analyzed through: i) analysis of the oxidative metabolism, indirectly evaluated trough dosage of blood lactate levels before and after a submaximal incremental exercise on a treadmill; ii) analysis of strength and, iii) endurance, in both lower and upper limbs muscles, employing an isokinetic dynamometer. Statistical analyses were carried out to compare the muscle activities between groups. Analysis of oxidative metabolism during the incremental exercise on a treadmill showed that patients performed a shorter exercise than controls. Lactate levels were significantly higher in patients both at baseline and after the task. Muscle strength analysis in patients group showed a reduction of Maximum Voluntary Contraction during the isometric contraction and, a tendency to fatigue during endurance task. Data emerging from this study highlight an impairment of muscle oxidative metabolism in subjects affected by a pre-cachexia stage of cancer. A trend of precocious fatigability and an impairment of muscle strength production were also observed. This evidence underlines the relevance of assessing muscle function in order to develop novel rehabilitative approaches able to counteract motor impairment and eventually to prevent cachexia in these patients.

Muscle function impairment in cancer patients in pre-cachexia stage

Cancer cachexia has been reported to be directly responsible for at least 20% of cancer deaths. Management of muscle wasting in cancer-associated cachexia appears to be of pivotal importance for survival of patients. In this regard, it would be interesting to identify before its patent appearance eventual functional markers of muscle damage, to plan specific exercise protocols to counteract cachexia. The muscle function of 13 oncologic patients and 15 controls was analyzed through: i) analysis of the oxidative metabolism, indirectly evaluated trough dosage of blood lactate levels before and after a submaximal incremental exercise on a treadmill; ii) analysis of strength and, iii) endurance, in both lower and upper limbs muscles, employing an isokinetic dynamometer. Statistical analyses were carried out to compare the muscle activities between groups. Analysis of oxidative metabolism during the incremental exercise on a treadmill showed that patients performed a shorter exercise than controls. Lactate levels were significantly higher in patients both at baseline and after the task. Muscle strength analysis in patients group showed a reduction of Maximum Voluntary Contraction during the isometric contraction and, a tendency to fatigue during endurance task. Data emerging from this study highlight an impairment of muscle oxidative metabolism in subjects affected by a pre-cachexia stage of cancer. A trend of precocious fatigability and an impairment of muscle strength production were also observed. This evidence underlines the relevance of assessing muscle function in order to develop novel rehabilitative approaches able to counteract motor impairment and eventually to prevent cachexia in these patients.

Assessing the roles of inflammation and blood brain barrier permeability in cognitive impairment: A nationwide longitudinal study of patients receiving chemotherapy and non-cancer controls.

12070 Background: Cognitive impairment is a prevalent side effect of chemotherapy. We have previously shown that chemotherapy treatment is associated with worse performance on the Rapid Visual Processing test (RVP), an objective measure of sustained attention, over time compared to non-cancer controls. Better understanding of the biologic mechanisms underlying cognitive impairment in cancer patients is needed. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) has been implicated in increasing blood brain barrier (BBB) permeability, which in turn is associated with cognitive impairment. This study assessed the relationships of TNFα and S100β, a biomarker of BBB permeability, to each other and to RVP performance over time. Methods: We analyzed a subset of participants (n = 89 patients, n = 52 controls, mean age = 60) from a prospective longitudinal study of women with breast cancer receiving chemotherapy and non-cancer controls. TNFα and S100β were measured in serum pre-chemotherapy (T1, ≤7 days before first treatment) and post-chemotherapy (T2, ≤1 month after last treatment) and at corresponding times for controls. Sustained attention was assessed by total correct rejections on the RVP test at T1 and T2. Separate linear regression models including all participants were used to relate 1) baseline TNFα and S100β levels to change in RVP performance over time, 2) change in TNFα and S100β to change in RVP performance over time, and 3) change in TNFα to change in S100β. Models were adjusted for age. 4) T-tests were used to compare the TNFα and S100β change scores (T1 to T2) of patients vs controls. Results: Greater increase (T1 to T2) in the pro-inflammatory cytokine TNFα was associated with worse cognition, measured by performance on RVP over time (p = 0.02). Higher baseline S100β, a biomarker of BBB permeability, was associated with worse performance on RVP over time (p = 0.09). Increase in TNFα was associated with increase in S100β (p = 0.11). S100β increased from T1 to T2 in patients relative to controls (p = 0.09). Conclusions: These results suggest that higher TNFα may be related to increases in blood brain barrier permeability and worse cognition. Future studies will further define the link between inflammation, blood brain barrier permeability and chemotherapy-related cognitive decline, with the goal of informing the development of new interventions. Funding: R01CA231014, T32CA102618, DP2CA195765, UG1CA189961.

Abstract P2-12-05: Neuropsychological assessment, neuroimaging, and tumor markers to explore cognitive decline in early stage breast cancer patients

Abstract Background. It is widely demonstrated that a high percentage of early stage breast cancer patients achieves a long-term survival. However, it seems that some of them show a cognitive decline during and after the oncology treatment, affecting their quality of life. Fortunately, the neuropsychological impairment in cancer patients is nowadays a known issue in oncology literature. Our aim is to assess the effects of chemotherapy and endocrine therapy on neurocognitive functions in patients with early stage breast cancer. If the hypothesis that the patients suffer from neurocognitive impairments related to the oncology treatment will be confirmed, this would imply the possibility of an early neuropsychological rehabilitation since the first diagnosis, to prevent the worsening of the quality of life and to avoid the use of additional medications to regulate for example the severity of fatigue and mood. Methods. The study population includes 45 patients diagnosed of breast cancer undergoing chemotherapy +/- endocrine treatment (CT), 15 patients undergoing endocrine treatment (HT), and 9 healthy controls (HC). Throughout each evaluation at three points time, we administered the Mini-Mental State Examination (MMSE), some tests of the Cogstateneurocognitive battery, the Trail Making Test (TMTA and TMTB), and the Controlled Oral Word Association Test (COWAT). Moreover, each subject was asked to complete the EORTC QLQ-C30 and the QLQ-BR23 quality of life tests, the MD Anderson Symptoms Inventory questionnaire, the Hospital Anxiety and Depression scale, and a self-report of the neurocognitive impairment perceived. In addition, we are performing a pilot neuroimaging study aimed to enroll 20 patients with early stage breast cancer, of whom 10 treated with chemotherapy, and 10 with hormone therapy alone. Patients undergo a structural and functional brain magnetic resonance imaging (fMRI). S100 protein, and neuro specific enolase are also collected to explore their possible relationship with the neurocognitive decline. Results. Both CT and HT Groups performed lower results than HC in visuo-motor processing speed test (TMTA) at baseline and at month 12 (p=0.00). At month 6 only the HT Group had lower results than HC (p=0.00). We found a correlation between the lower results of TMTA and the level of depression (p=0.02), distress (p=0.00), anxiety (p=0.01), severity of symptoms (p=0.00) in CT Group at baseline. The MMSE scores were slightly lower in both CT and HT Groups compared to HC (p=0.04) at month 6. The MMSE results at month 12 were lower in HT Groups compared to HC (p=0.04). In addition, the neurocognitive impairment perceived is higher in CT Group (p&amp;lt;0.00) once having stopped the chemotherapy treatment until the last follow up. The results of TMTB and COWAT increased in CT Group during the last follow up (p=0.00), and it seems to have a positive correlation with the neurocognitive tasks the patients performed (p=0.02 and p=0.03 respectively). Concerning the pilot study, we analysed the first 10 patients enrolled in the study: 5 subjects treated with chemotherapy and 5 with hormone therapy alone. No statistically significant differences were found concerning the alteration of the tumor markers values. On the contrary, we found changes between the baseline and the post-treatment brain fMRI. Conclusions. Our results suggest a decline in few cognitive domains in cancer patients as consequence of the oncology treatment. In some tests the neurocognitive decline was also observed in cancer groups at baseline, and it was associated with the low state of mind in CT Group. We infer that the increasing of scores in CT Group at month 12 was positively associated with the cognitive tasks the patients were performing during the study-period. Citation Format: Claudia Panciroli, Carles Biarnes, Josep Puig, Jose Anton Anton, Vanesa Quiroga, Eudald Felip, Beatriz Cirauqui, Margarita Romeo, Iris Teruel, Salvador Pedraza, Mireia Margeli. Neuropsychological assessment, neuroimaging, and tumor markers to explore cognitive decline in early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-05.

Systematic review of longitudinal studies on chemotherapy‐associated subjective cognitive impairment in cancer patients

This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues. Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors). Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed. More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI.

The Brief Perceived Cognitive Impairment Scale-Korean: A Validation Study.

Practical brief measures are needed for clinicians and researchers to identify and effectively manage cognitive impairment in cancer patients. This study evaluated the reliability (ie, internal consistency reliability) and validity (ie, construct, convergent, concurrent, and known-group validity) of the Brief Perceived Cognitive Impairment Scale-Korean (BPCIS-K). From a university hospital, 249 cancer patients participated. The BPCIS-K was constructed with 6 items evaluating key aspects of cognitive impairment in cancer patients. For internal consistency reliability, Cronbach's α and item-total correlations were evaluated. For construct validity, confirmatory factor analysis was performed. For convergent validity, Pearson correlations were tested with the Functional Assessment of Cancer Therapy-Cognitive Function. For concurrent validity, Pearson correlations were tested with the Functional Assessment of Chronic Illness Therapy-Fatigue. For known-group validity, t tests were performed. The BPCIS-K showed high internal consistency reliability (Cronbach's α = .92; item-total correlations ranged from 0.76 to 0.81). Factor analysis confirmed the scale is unidimensional. It is highly associated with another validated cognitive impairment measure (r = -0.91, P < .001) and moderately correlated with a fatigue measure (r = -0.52, P < .001). In known-group validity, female and patients undergoing treatment experienced more severe impairment than did male patients and patient awaiting treatment (P = .05, P = .08, respectively). The BPCIS-K is valid and reliable for assessing cancer patients' perceived cognitive impairment, particularly in concentration, memory, and executive functions. This study introduces a practical brief measure to clinicians and researchers.

Magnesium Supplementation and Cisplatin-Induced Renal Impairment in Cancer Patients

Cisplatin-induced renal dysfunction represents a limiting complication in patients receiving chemotherapy. Various preventive strategies have been implemented and various guidelines recommend magnesium supplementation. Twenty-four patients receiving cisplatin regimens and magnesium supplementation were assessed before, during and at the end of chemotherapy cycles. Renal impairment is generally expected to occur in up to 75% of the patients; our study reports this side effect in 20.8%, with a median decrease in the creatinine clearance of 11.2%.

Prospective memory impairment following whole brain radiotherapy in patients with metastatic brain cancer.

ObjectiveTo investigate the prospective memory (PM) impairment following whole brain radiotherapy (WBRT) in cancer patients with brain metastases.MethodEighty‐one patients with metastatic brain cancer, agreeing to undergo WBRT, were enrolled and subjected to a battery of cognitive neuropsychological tests, including the mini‐mental state examination (MMSE), verbal fluency test (VFT), digit span test (DST), and event‐based and time‐based prospective memory (EBPM and TBPM) tasks, before and after radiotherapy.ResultsThe patients with metastatic brain cancer after WBRT exhibited a significant decrease in the MMSE, DST, VFT, and EBPM scores (t = 6.258, 10.192, 5.361, −5.892, P < 0.01), but nonsignificant decrease in the TBPM scores (t = −1.172, P > 0.05).ConclusionThere is significant EBPM impairment in cancer patients with brain metastases after WBRT, whereas that in the TBPM remained relatively unaffected. The result suggests that EBPM impairment may be as an early cognitive impairment marker in patients with BM who undergo WBRT.