Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging.

The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15).

Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer.

Chemotherapy is associated with cognitive impairment in a subgroup of breast cancer survivors, but the neural circuitry underlying this side effect is largely unknown. Moreover, long-term impairment has not been studied well. In the present study, functional magnetic resonance imaging (fMRI) and neuropsychological testing were performed in breast cancer survivors almost 10 years after high-dose adjuvant chemotherapy (chemo group, n = 19) and in breast cancer survivors for whom chemotherapy had not been indicated (control group, n = 15).

Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial.

Purpose: To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer (BC).

Patients And Methods: Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch postmenopausal patients with BC, who did not receive chemotherapy. Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC.

Methotrexate reduces hippocampal blood vessel density and activates microglia in rats but does not elevate central cytokine release.

Methotrexate is a cytostatic drug applied in adjuvant chemotherapy and associated with cognitive impairment in part of the cancer patients. In this paper we studied in rats whether a reduction in blood supply to the brain or neuroinflammation are possible mediators of this cognitive dysfunctionality. Methotrexate reduced hippocampal blood vessel density 1 week and 3 weeks after treatment as measured immunohistochemically with an endothelial barrier antigen.

Inhibition of hippocampal cell proliferation by methotrexate in rats is not potentiated by the presence of a tumor.

Methotrexate is a widely used cytostatic in chemotherapy cocktails for the treatment of cancer but is associated with cognitive impairment. Previous animal studies indicated that methorexate decreases hippocampal cell proliferation, which might contribute to the observed cognitive impairment. However, clinical studies have shown that cognitive impairment can also be noticed in some cancer patients before any systemic treatment is initiated.

The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

Objective: Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment.

Methotrexate decreases hippocampal cell proliferation and induces memory deficits in rats.

Methotrexate (MTX) is a cytostatic agent used in adjuvant chemotherapy for treatment of breast cancer and is associated with cognitive impairment in a subgroup of patients. The aim of this paper is to test whether MTX can rapidly affect various brain structures resulting in decreased hippocampal cell proliferation and white matter damage. We also studied whether cell death occurs in the hippocampus following MTX.

Constructive Technology Assessment (CTA) as a tool in coverage with evidence development: the case of the 70-gene prognosis signature for breast cancer diagnostics.

Objectives: Constructive Technology Assessment (CTA) is a means to guide early implementation of new developments in society, and can be used as an evaluation tool for Coverage with Evidence Development (CED). We used CTA for the introduction of a new diagnostic test in the Netherlands, the 70-gene prognosis signature (MammaPrint) for node-negative breast cancer patients.

Methods: Studied aspects were (organizational) efficiency, patient-centeredness and diffusion scenarios.

[Dutch parliament legitimizes harmful quackery].

The Dutch parliament has recently accepted a tax law in which certain groups of alternative therapists can be exempt from VAT. To be eligible for this VAT exemption, the disciplines to which the therapists belong have to meet certain training requirements. In this article it is contended, in agreement with the Royal College of Physicians in the UK, that statutory regulation is inappropriate for disciplines whose therapies are neither of proved benefit nor appropriately tested.

The influence of priming and pre-existing knowledge of chemotherapy-associated cognitive complaints on the reporting of such complaints in breast cancer patients.

Objective: Many cancer patients report cognitive changes following chemotherapy. In social psychology, there is ample evidence that psychological and physical complaints can increase with increased accessibility of relevant schemata. The accessibility of related concepts in memory may be facilitated through priming or by pre-existing knowledge, resulting in an increase of reported complaints.

Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study.

Background: Previous studies have indicated that a subset of cancer patients treated with chemotherapy show cognitive deficits and/or experience cognitive complaints, whereas literature about the influence of hormonal therapies on cognition is sparse. Because of the accumulating knowledge about the importance of estrogen for cognitive functioning, there is growing concern about adjuvant hormonal therapy for breast cancer (BC) affecting cognition. We examined the cognitive functioning of postmenopausal BC patients who were, following doxorubicin/cyclophosphamide (AC) chemotherapy, randomized to tamoxifen or exemestane, and compared their performance with that of non-cancer controls.

Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer.

Background: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with cyclophosphamide/methotrexate/5-fluorouracil (CMF) at different time points.

Patients And Methods: Patients with breast cancer treated with adjuvant CMF chemotherapy (n = 63) were examined with neuropsychological tests 1 year after treatment and compared with healthy women (n = 60; T1 portion of the study).

Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER).

Background: A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment. The main aims of this MicroarRAy PrognoSTics in Breast CancER (RASTER) study were to assess prospectively the feasibility of implementation of the 70-gene prognosis signature in community-based settings and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement (CBO) and other guidelines.

Methods: Between January, 2004 and December, 2006, 812 women aged under 61 years with primary breast carcinoma (clinical T1-4N0M0) were enrolled.

Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer.

Introduction: There is growing concern that some cytotoxic regimens for cancer affect cognitive functioning. This study examined the prevalence of cognitive complaints and deficits in testicular cancer (TC) patients treated with the worldwide standard BEP (bleomycin, etoposide and cisplatin) chemotherapy.

Materials And Methods: Seventy TC patients treated with BEP chemotherapy after surgery (S + CT) were examined with interviews and neuropsychological tests.

Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat.

Methotrexate (MTX) is a cytostatic agent widely used in combination with other agents as adjuvant chemotherapy for breast cancer and is associated with cognitive impairment as a long-term side effect in some cancer patients. This paper aimed to identify a neurobiological mechanism possibly responsible for this cognitive impairment using an animal model. The first study explored the hypothesis that MTX reduces neuronal cell proliferation.

Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients.

Some breast cancer survivors experience cognitive decline following chemotherapy. We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60). All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval.

Effects of high-dose and conventional-dose adjuvant chemotherapy on long-term cognitive sequelae in patients with breast cancer: an electrophysiologic study.

Background: The mechanisms underlying cognitive deficits found in a number of patients with breast cancer treated with adjuvant chemotherapy are still unclear. In the current study, we used a combination of measures of brain electric activity and cognitive performance during information processing to elucidate the origin of these cognitive deficits.

Patients And Methods: Twenty-nine patients at high risk with breast cancer treated with adjuvant conventional-dose cyclophosphamide/epirubicin/5-fluorouracil or adjuvant high-dose cyclophosphamide/thiotepa/carboplatin were compared with 23 patients with stage I breast cancer not treated with chemotherapy approximately 4 years after completion of treatment.

Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy.

Cognitive deficits are found in a number of breast-cancer patients who have undergone adjuvant (Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)) chemotherapy, but the underlying mechanisms are still unclear. The objective of this study is to investigate information processing in these patients with concurrent registration of brain activity. Twenty-six breast-cancer patients treated with adjuvant CMF chemotherapy and a control group of 23 stage I breast-cancer patients not treated with chemotherapy were examined.

Hypnotherapy in radiotherapy patients: a randomized trial.

Purpose: To determine whether hypnotherapy reduces anxiety and improves the quality of life in cancer patients undergoing curative radiotherapy (RT).

Methods And Materials: After providing written informed consent, 69 patients were randomized between standard curative RT alone (36 controls) and RT plus hypnotherapy (33 patients). Patients in the hypnotherapy group received hypnotherapy at the intake, before RT simulation, before the first RT session, and halfway between the RT course.

Cognitive impairment associated with chemotherapy for cancer: report of a workshop.

Cognitive dysfunction may occur in some patients who receive chemotherapy. We provide a summary of an April 2003 workshop on this topic, that included medical oncologists, radiologists, clinical and experimental psychologists, and patient advocates. Current studies indicate that cognitive deficits are often subtle, although they are observed consistently in a proportion of patients, may be durable, and can be disabling.

Cognitive dysfunction and chemotherapy: neuropsychological findings in perspective.

Currently, the interest in cognitive functioning following chemotherapy is rapidly expanding as is reflected in a growing number of published studies on this topic. Although most studies are indicative of cognitive deficits after chemotherapy, definite conclusions on the role of chemotherapy on cognitive function can often not be drawn due to methodological problems. On the basis of the studies on cognitive functioning after chemotherapy that are conducted in The Netherlands Cancer Institute, the current article describes a number of such methodological topics that obscure straightforward interpretation of neuropsychological findings in toxicity research.

Long-term results of olfaction rehabilitation using the nasal airflow-inducing ("polite yawning") maneuver after total laryngectomy.

Objectives: To study the long-term results of the nasal airflow-inducing maneuver (NAIM) as an olfaction rehabilitation tool after laryngectomy and to investigate the effectiveness of a new, simpler odor detection test (ODT) called the smell disk test (SDT), or Zürcher Geruchstest.

Design: Intervention study.

Settings: National cancer center.