scholarly journals Cognitive impairment after cytotoxic chemotherapy

2019 ◽  
Vol 7 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Petra Huehnchen ◽  
Antonia van Kampen ◽  
Wolfgang Boehmerle ◽  
Matthias Endres

Abstract Background Neurotoxicity is a frequent side effect of cytotoxic chemotherapy and affects a large number of patients. Despite the high medical need, few research efforts have addressed the impact of cytotoxic agents on cognition (ie, postchemotherapy cognitive impairment; PCCI). One unsolved question is whether individual cytotoxic drugs have differential effects on cognition. We thus examine the current state of research regarding PCCI. Neurological symptoms after targeted therapies and immunotherapies are not part of this review. Methods A literature search was conducted in the PubMed database, and 1215 articles were reviewed for predefined inclusion and exclusion criteria. Thirty articles were included in the systematic review. Results Twenty-five of the included studies report significant cognitive impairment. Of these, 21 studies investigated patients with breast cancer. Patients mainly received combinations of 5-fluorouracil, epirubicin, cyclophosphamide, doxorubicin, and taxanes (FEC/FEC-T). Five studies found no significant cognitive impairment in chemotherapy patients. Of these, 2 studies investigated patients with colon cancer receiving 5-fluorouracil and oxaliplatin (FOLFOX). Independent risk factors for PCCI were patient age, mood alterations, cognitive reserve, and the presence of apolipoprotein E e4 alleles. Conclusions There is evidence that certain chemotherapy regimens cause PCCI more frequently than others as evidenced by 21 out of 23 studies in breast cancer patients (mainly FEC-T), whereas 2 out of 3 studies with colon cancer patients (FOLFOX) did not observe significant changes. Further studies are needed defining patient cohorts by treatment protocol in addition to cancer type to elucidate the effects of individual cytotoxic drugs on cognitive functions.

2015 ◽  
Vol 107 (7) ◽  
pp. djv099-djv099 ◽  
Author(s):  
K. Hermelink ◽  
V. Voigt ◽  
J. Kaste ◽  
F. Neufeld ◽  
R. Wuerstlein ◽  
...  

2016 ◽  
Vol 108 (8) ◽  
pp. djw048 ◽  
Author(s):  
Amir Ali Sepehry ◽  
Scott Tyldesley ◽  
Margot Kathleen Davis ◽  
Christine Simmons ◽  
Alexander Rauscher ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandre Chan ◽  
Angie Yeo ◽  
Maung Shwe ◽  
Chia Jie Tan ◽  
Koon Mian Foo ◽  
...  

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.


Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.


2021 ◽  
Author(s):  
Eva Roy ◽  
Jennifer Hall ◽  
Xiao Zhu ◽  
Francesco M. Egro ◽  
Carolyn De La Cruz

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.


2021 ◽  
Vol 155 ◽  
pp. 28-37
Author(s):  
Conny Vrieling ◽  
Samson Y. Assele ◽  
Lotte Moser ◽  
Nicolas Sauvé ◽  
Saskia Litière ◽  
...  

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