Available
evidence supports the hypothesis that adjuvant chemotherapy for
breast cancer can produce cognitive deficits, and that these
deficits may have a significant impact on patients' quality of
life. Studies have generally compared the results of a variety of
cognitive measures performed following treatment to standardized
population-based norms or to cancer patients who received local
therapy, rather than to the individual's baseline level of
functioning. Several longitudinal studies are in progress or in
the planning stages to better quantify and understand the
incidence and impact of cognitive effects of adjuvant
chemotherapy, and to identify possible susceptibility factors in
subgroups. Although the neurocognitive changes appear to be
subtle, there may be enough data to consider discussing the
possibility of cognitive dysfunction as an adverse effect when
assessing the risks and benefits of adjuvant chemotherapy.
Likewise, as the aromatase inhibitors are increasingly given to
larger numbers of women in the adjuvant setting, it will be
important to understand the cognitive impact of estrogen
deprivation. Finally, there is interest in examining supportive
pharmacologic or behavioral measures that might prevent or
decrease cognitive effects in this setting. Herein, the data on
cognitive changes associated with chemotherapy for breast cancer,
current and future research directions, as well as possible
treatments are reviewed.
Department
of Medicine, University of California Comprehensive Cancer
Center, San Francisco 94115, USA
Cunningham RS.
Anemia
in the oncology patient: cognitive function and cancer.
Cancer
Nurs. 2003 Dec;26(6 Suppl):38S-42S.
Cancer-related
anemia often develops from the infiltration of marrow by
malignant cells, impaired hemoglobin (Hb) production related to
chemotherapy or radiation therapy, iron deficiency, or low
endogenous erythropoietin levels. Patients with cancer-related
anemia may experience cognitive dysfunction including decreased
mental alertness, poor concentration, and memory problems.
Anemia-mediated cerebral hypoxia may cause symptoms such as
headache, vertigo, tinnitus, and dizziness. These symptoms often
are exacerbated in the elderly patient with cancer and related
to underlying low Hb concentrations. Restoring Hb levels via the
administration of iron supplements, blood transfusions, or, more
recently, erythropoiesis-stimulating therapy (epoetin alfa)
results in significant improvement of cognitive function. The
use of epoetin alfa as a treatment option for patients with
chemotherapy-associated anemia and an Hb concentration less than
10 g/dL has been recommended by the American Society of Clinical
Oncology and the American Society of Hematology. Erythropoiesis-stimulating
therapies are a promising treatment option for cancer-related
anemia that may improve cognitive function and quality of life
for patients with cancer.
Cancer
Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901,
USA.
Tchen
N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, Clemons M,
Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF.
Cognitive
function, fatigue, and menopausal symptoms in women receiving
adjuvant chemotherapy for breast cancer.
J
Clin Oncol. 2003 Nov 15;21(22):4175-83.
PMID: 14615445 [PubMed - indexed for MEDLINE]
PURPOSE: There is evidence that cognitive dysfunction, fatigue,
and menopausal symptoms may occur in women receiving adjuvant
chemotherapy for breast cancer. Here, we determine their incidence
and severity, and interrelationships between them and quality of
life. PATIENTS AND METHODS: In this study, 110 women receiving
adjuvant chemotherapy each nominated a female relative, friend, or
neighbor (matched by age) as a control; 100 eligible matched pairs
were evaluated. Patients and controls completed the following
assessments: the High-Sensitivity Cognitive Screen, and the
Functional Assessment of Cancer Therapy-General (FACT-G) quality
of life scale with subscales for fatigue (FACT-F) and endocrine
symptoms (FACT-ES). They also performed tests of attention and
reaction time. RESULTS: Patients and controls were well matched
for age and level of education. There was a higher incidence of
moderate or severe cognitive impairment in the patient group (16%
v 4%; P =.008). Patients experienced much more fatigue than
controls (median FACT-F scores, 31 v 46; P <.0001) and more
menopausal symptoms (median FACT-ES scores, 58 v 64; P <.0001).
Self-reported quality of life of the patients was poorer than for
controls, especially in physical and functional domains (median
FACT-G scores, 77 v 93; P <.0001). There was strong correlation
between fatigue, menopausal symptoms, and quality of life (P
<.0001 for each pair), but none were significantly associated
with the presence of cognitive dysfunction. CONCLUSION: Adjuvant
chemotherapy causes cognitive dysfunction, fatigue, and menopausal
symptoms in women with breast cancer. Priority should be given to
the study of strategies that might reduce these toxic effects.
Princess
Margaret Hospital and University of Toronto, Toronto, Ontario,
Canada.
O'Shaughnessy, JA.
Chemotherapy
induced cognitive dysfunction: a clearer picture
Clin
Breast Cancer. 2003 Nov;4 Suppl 2:S89-94. Review.
PMID: 14705598 [PubMed - indexed for MEDLINE]
Chemotherapy-associated
cognitive dysfunction occurs in a subset of patients treated with
adjuvant chemotherapy. Recent data suggest that development of
chemotherapy-related anemia predisposes patients to cognitive
dysfunction. Endogenous erythropoietin (EPO) is well recognized
for its central role in erythropoiesis, and recombinant human EPO
(epoetin alfa) is established as a safe and effective treatment
for chemotherapy-related anemia. Treatment with epoetin alfa also
improved health-related quality of life in anemic cancer patients
undergoing chemotherapy, and several controlled studies have
documented increases in quality-of-life scores correlated with
increases in hemoglobin. Erythropoietin also plays a role in
neuroprotection, presumably by activation of antiapoptotic genes.
Erythropoietin and its receptor are expressed in neural cells of
the human brain, and their expression is upregulated after hypoxic
or ischemic injury. In animal models, systemic administration of
epoetin alfa protects against such neural injury. Ongoing and
future studies will determine whether epoetin alfa can provide
neuroprotection with respect to the development of cognitive
dysfunction in patients undergoing adjuvant chemotherapy treatment
for breast cancer.
Baylor
Sammons Cancer Center, US Oncology, 3535 Worth Street,
Collins Building 5th Floor, Dallas, TX 75246, USA.
joyce.o'shaughnessy@usoncology.com
Morse
R, Rodgers J, Verrill M, Kendell K.
Neuropsychological functioning following
systemic treatment in women treated for breast cancer: a
review.
The aim of this review was to evaluate the effect of treatment and
illness-related factors on neuropsychological functioning in women
treated for breast cancer. Eight studies were identified examining
neuropsychological test performance following systemic treatment.
Six of the eight studies suggest that neuropsychological
functioning may be impaired following treatment. However, there
are a number of important methodological issues which limit
interpretation of these results. Therefore, it is unclear whether
neuropsychological outcome differs according to a range of
treatment, biomedical and psychological factors. Larger samples
with longitudinal follow-up are required in order to examine the
treatment-related factors that best predict cognitive deficits.
Department
of Clinical Psychology, School of Neurology, Neurobiology and
Psychiatry, Ridley Building, University of Newcastle, NE1 7RU,
Newcastle upon Tyne, UK.
Waldstein
SR, Elias MF.
Introduction to the special section on
health and cognitive function.
Health
Psychol. 2003 Nov;22(6):555-8.
PMID: 14640851 [PubMed - indexed for MEDLINE]
Numerous factors related to health and diseases have been studied
in relation to cognitive function. It has been shown that across
the life span, systemic medical diseases can negatively impact
cognitive function. Factors that influence the development of
medical diseases, such as poor health habits, biological risk
factors, hormones, genetic factors, exposure to environmental
toxins, and certain treatments for disease, can also have an
adverse effect on cognitive function. Conversely, factors such as
high levels of education, good health habits, and some treatments
for disease can be protective. Included in this special section
are 6 empirical articles that examine the relation of health or
disease to cognitive function.
Department
of Psychology, University of Maryland, Baltimore County, and
Geriatric Research Educational and Clinical Center, Baltimore
Veterans Affairs Medical Center, Baltimore, MD 21250, USA.
waldstei@umbc.edu
O'Shaughnessy
J.
Chemotherapy-related cognitive dysfunction
in breast cancer.
OBJECTIVES: To provide an overview of chemotherapy-related
cognitive dysfunction in breast cancer survivors, focusing on its
pathophysiology, risk factors, assessment, and management. DATA
SOURCES: Published biomedical literature. CONCLUSION:
Chemotherapy-related cognitive dysfunction in patients with breast
cancer is multifactorial and possibly related to anemia or a
direct effect of chemotherapy on brain function. Clinical
observation and subjective reports are useful assessments.
Therapies directed at alleviating or preventing cognitive deficits
are being investigated. IMPLICATIONS FOR NURSING PRACTICE:
Oncology nurses are important in monitoring cognitive function in
patients with breast cancer receiving chemotherapy. Nurses who are
aware of the risks, assessment, and management of cognitive
impairment are better able to discuss these issues with patients
and caregivers.
Baylor
Sammons Cancer Center, US Oncology, Dallas, TX, USA.
Saykin
AJ, Ahles TA, McDonald BC.
Mechanisms of chemotherapy-induced cognitive
disorders: neuropsychological, pathophysiological, and
neuroimaging perspectives.
Recent studies have indicated the frequent occurrence of
neuropsychologic deficits and cognitive complaints after systemic
cancer chemotherapy. Most early reports were retrospective, but
prospective longitudinal studies are underway. Although the
available evidence suggests a fairly diffuse pattern of changes,
memory and executive functions could be preferentially affected.
Preliminary data also suggest that some individuals might be more
vulnerable than others, leading to investigation of genetic and
other risk factors. The greatest gap in our knowledge regarding
chemotherapy-related cognitive changes is a lack of understanding
of the mechanism or mechanisms that account for the observed
changes. Several pathophysiological candidates include direct
neurotoxic effects leading to atrophy of cerebral gray matter (GM)
and/or demyelination of white matter (WM) fibers, secondary
immunologic responses causing inflammatory reactions, and
microvascular injury. Altered neurotransmitter levels and
metabolites could constitute an additional mechanism related to
neurotoxic effects. Advanced brain imaging techniques can directly
or indirectly assess many of these mechanisms, but to date there
has been very limited application of these tools. Morphometric
magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion
tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive
techniques that could yield important complementary data regarding
the nature of neural changes after chemotherapy.
Electrophysiological studies and targeted molecular imaging with
positron emission tomography (PET) could also provide unique
information. We review the minimal imaging data available at
present and also note studies of other brain disorders or
treatment effects that might serve as a model for imaging
chemotherapy-induced changes. Large-scale prospective studies are
needed to help isolate the pathophysiological mechanisms
underlying the cognitive deficits associated with chemotherapy.
Brain
Imaging Laboratory, Dartmouth Medical School, Lebanon, NH 03756,
USA. saykin@dartmouth.edu
Salminen
E, Portin R, Korpela J, Backman H, Parvinen LM, Helenius
H, Nurmi M.
Androgen deprivation and cognition in
prostate cancer.
Androgen deprivation (AD) is commonly used in neoadjuvant and
adjuvant setting with prostate cancer (PC) radiotherapy. This
prospective study assessed whether cognitive functioning is
impaired during 12 months of AD therapy. Longitudinal testing of
25 patients treated with AD and curative radiotherapy was
undertaken at baseline, and at 6 and 12 months. CogniSpeed
software was used for measuring attentional performances. Other
cognitive performances were evaluated using verbal, visuomotor and
memory tests. The Beck depression inventory was employed to
evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL).
During longitudinal testing of the AD group, no impairment in
cognitive performances was found. Instead, improvement was
observed in object recall (immediate, P=0.035; delayed,
P<0.001), and in semantic memory (P=0.037). In QoL, impairment
in physical function was observed. Androgen deprivation of 12
months appears to be associated with preserved cognitive
functioning, although physical impairment occurs. These results
have implications for counseling and psychosocial support of
patients in the context of treatment options in PC.
Department
of Oncology, Turku University Hospital, Kiinamyllynkatu 4-8,
Fin-20520 Turku, Finland. eevsal@utu.fi
Shilling
V, Jenkins V, Fallowfield L, Howell T.
The effects of hormone therapy on cognition
in breast cancer.
The use of hormonal therapies for the treatment of breast cancer
is common, yet few studies have examined the possible cognitive
effects. Several regions of the brain, important in memory and
cognition, are rich in oestrogen receptors. As a result, the
long-term use of anti-oestrogens may have potential consequences
for cognition. This project aims to establish whether
significant cognitive deficit exists in women receiving hormone
therapy for breast cancer and to develop a cognitive package
that is sensitive to the potential effects of oestrogen
deficiency on cognition. Cognitive assessments measured a range
of memory and attention functions in patient and control groups
to identify whether cognitive impairment, if apparent, occurs at
a widespread or function specific level. Ninety-four patients
from the anastrozole, tamoxifen and combined (ATAC) trial and 35
non-cancer controls were assessed. Groups did not differ
significantly in age or estimated full-scale intelligence. The
patient group did not differ from controls on measures of
working memory, attention and visual memory but was
significantly impaired compared to the control group on measures
of verbal memory (P=0.026) and processing speed (P=0.032).
Cognitive performance in the patient group was not significantly
related to length of time on trial or measures of psychological
morbidity. As more and more hormonal agents are used in clinical
trials of both adjuvant and preventive settings it is of vital
importance that any potentially deleterious effects on cognitive
function are measured adequately. Preliminary results from this
study suggest that anti-oestrogen therapy may cause a specific
deficit in verbal memory that corroborates the links between
oestrogen levels and verbal memory often reported in studies of
the cognitive benefits of hormone replacement therapy.
Psychosocial Oncology Group (Cancer Research UK), Brighton
and Sussex Medical School, University of Sussex, Falmer, East
Sussex, BN1 9QG, UK. v.shilling@biols.susx.ac.uk
The relationship of APOE genotype to
neuropsychological performance in long-term cancer
survivors treated with standard dose chemotherapy.
Psychooncology.
2003 Sep;12(6):612-9.
PMID: 12923801 [PubMed - indexed for MEDLINE]
PURPOSE: The primary purpose of this study was to compare the
neuropsychological performance of long-term survivors of breast
cancer and lymphoma treated with standard dose chemotherapy who
carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene
to those who carry other APOE alleles. PATIENTS AND METHODS:
Long-term survivors (mean=8.8+/-4.3 years post-treatment) of
breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29,
age=55.8+/-11.6) who had been treated with standard-dose
chemotherapy completed a standardized battery of
neuropsychological and psychological tests. Survivors were also
classified into two groups based on the presence (N=17) or
absence (N=63) of at least one epsilon 4 allele of APOE.
RESULTS: Analysis of covariance, controlling for age, gender,
education, diagnosis, and WRAT-3 reading subtest (a proxy
measure of baseline IQ), indicated that survivors with at least
one epsilon 4 allele scored significantly lower in the visual
memory (p<0.03) and the spatial ability (p<0.05) domains
and tended to score lower in the psychomotor functioning
(p<0.08) domain as compared to survivors who did not carry an
epsilon 4 allele. No group differences were found on depression,
anxiety, or fatigue. CONCLUSIONS: The results of this study
provide preliminary support for the hypothesis that the epsilon
4 allele of APOE may be a potential genetic marker for increased
vulnerability to chemotherapy-induced cognitive decline.
Copyright 2003 John Wiley & Sons, Ltd.
Department of Psychiatry and Center for Psycho-Oncology
Research, USA. tim.a.ahles@dartmouth.edu
Caffo
O, Amichetti M, Ferro A, Lucenti A, Valduga F, Galligioni
E.
Pain and quality of life after surgery for
breast cancer.
Breast
Cancer Res Treat. 2003 Jul;80(1):39-48.
PMID: 12889597 [PubMed - indexed for MEDLINE]
BACKGROUND: In breast cancer (BC) patients, conservative
surgery (CS) followed by irradiation or immediate breast
reconstruction (IBR) after modified radical mastectomy (MRM) has
been proposed in the attempt to avoid the negative impact of MRM
on feminine body image. Regardless of the type of operation, BC
patients may feel pain even without recurrent disease with poor
adjustment in terms of quality of life (QL). METHODS: We adopted
a questionnaire comprising the short form of the McGill Pain
questionnaire, and a previously validated questionnaire able to
identify four subscales exploring physical well-being, physical
autonomy, relational life and psychological well-being. The
questionnaire was mailed in 1999 to a consecutive series of 757
(CS: 481 cases; MRM + IBR with skin expander: 93 cases; MRM: 183
cases) disease-free patients treated for BC between March 1995
and March 1998. RESULTS: The final analysis assessed the data
relating to 529 patients who underwent axillary dissection. Pain
was reported by 39.7% of women with higher incidence in patients
who underwent CS than in those who underwent MRM +/- IBR, but
this difference did not reach statistical significance (p =
0.07). The only statistically significant difference (p <
0.05) between the surgical groups was the pain appearance that
occurred earlier in the CS patients and later in the MRM + IBR
patients. No other differences were observed. The women with
pain had significantly worse QL scores on all of the subscales
than those without. CONCLUSION: Pain after surgery for BC
distress almost one-third of patients, regardless of the type of
treatment, and had a negative effect on patients' QL. The
different surgical procedures may marginally influence the
quantitative characteristics of pain.
Department
of Medical Oncology, Largo Medaglie d'Oro, Santa Chiara
Hospital, Trento, Italy. caffo@tn.apss.tn.it
Denison
U, Baumann J, Peters-Engl C, Samonigg H, Krippl P, Lang A,
Obermair A, Wagner H, Sevelda P.
Incidence of anaemia in breast cancer
patients receiving adjuvant chemotherapy.
Breast
Cancer Res Treat. 2003 Jun;79(3):347-53.
PMID: 12846419 [PubMed - indexed for MEDLINE]
Anaemia is frequent in breast cancer patients but often remains
undiagnosed and untreated. To determine the incidence of anaemia
a prospective survey of primary non-metastatic breast cancer
patients who received at least four cycles of adjuvant,
non-platinum multi-agent chemotherapy was conducted at 47
centres in Austria. Two hundred and forty seven patients were
prospectively included between October 1999 and December 1999.
Haemoglobin (Hb) levels were determined after surgery and prior
to each cycle of chemotherapy. Treatment of anaemia (blood
transfusion or epoetin alfa) during the observation period was
at the physician's discretion. For the purpose of this study,
patients were considered to be anaemic if their Hb was below 12
g/dl. At baseline (after surgery and before the first cycle of
chemotherapy), 28.7% of all patients were anaemic. The only
significant differentiating factor was the type of surgery.
37.9% of patients who underwent mastectomy were anaemic, whereas
only 22.8% of patients who underwent breast conserving surgery
were anaemic. Forty two percent of 176 patients with a Hb level
of > or = 12 g/dl at baseline developed anaemia during
adjuvant chemotherapy. The only factor that significantly
influenced the development of anaemia during chemotherapy was
the Hb level at baseline. The total incidence of anaemia in
patients with primary breast cancer who underwent surgery
followed by adjuvant multi-agent chemotherapy was 58.7%. Forty
nine patients (20.2%), 48 patients (19.2%) and 48 patients
(19.2%) showed a decrease in Hb levels by 1 g/dl, 1-2 g/dl and
> 2 g/dl, respectively. Only 18.6% of the patients who were
found to be anaemic received anaemia treatment. The two most
important factors for developing anaemia are the kind of surgery
and the Hb level prior to chemotherapy.
Department of Obstetrics & Gynecology, General Hospital
Lainz, Vienna, Austria. ursula.denison@chello.at
OBJECTIVE: To describe the neuropsychological functioning of
children treated with surgery only for localized brain tumors in
Dana-Farber Cancer Institute Protocol 92-077. Subsequent reports
will describe the neuropsychological functioning of children
treated with surgery and stereotactic radiation therapy on
Dana-Farber Cancer Institute 92-077. METHODS: The intellectual
functioning of 106 patients was evaluated within 3 months after
surgery. An in-depth assessment of the neuropsychological
functioning, including an impairment index, was conducted for a
subset of 77 school-age children (6-16 yr old) across six
functional domains. Descriptive statistics were generated;
binomial distribution analyses were performed to assess whether
the proportion of individuals with impaired performance on each
measure exceeded normative expectations. The impairment index
assessed whether poor performance was attributable to a few
children or reflected the performance of the cohort as a whole.
RESULTS: Although the Full Scale IQ was within normative
expectations, the Verbal IQ was higher than the Performance IQ
with 45% of individuals showing a significant discrepancy (P
< 0.01) between these scales. There was an increased
prevalence of poor performance for measures of motor output,
verbal memory, and visuospatial organization. The distribution
of the impairment index indicated moderate impairment across the
school-age cohort rather than severe impairment in a few
patients. CONCLUSION: The results document a moderate level of
neuropsychological morbidity among children with brain tumors
before stereotactic radiation therapy, presumably referable to
the tumor itself and the surgery. The extent to which
stereotactic radiation therapy may increase this burden will be
assessed in follow-up studies evaluating the longitudinal
neuropsychological data.
Division of Psychology, Department of Psychiatry, Children's
Hospital, Boston, MA, USA. sarah.carpentieri@carpenburymed.com
Ferguson
RJ, Ahles TA.
Low neuropsychologic performance among adult cancer
survivors treated with chemotherapy.
Decline in neuropsychologic test performance following adjuvant
chemotherapy for various types of cancer has gained much
research attention over the past decade. From available data,
about one fourth to one third of individuals undergoing systemic
chemotherapy exhibit measurable decrements in performance of
standard tests of cognitive function. Many cancer survivors
report that cognitive problems interfere with function and
compromise quality of life. However, these declines appear
subtle and there are little available longitudinal data
examining pre- to post-treatment cognitive change. Further,
there is little available evidence identifying the causes of
cognitive decline. This paper reviews current literature on low
neuropsychologic performance following systemic chemotherapy and
hypotheses on the causes of cognitive symptoms following
chemotherapy. Future research directions, with emphasis on
longitudinal research design as well as treatment implications,
are discussed.
Department of Psychiatry & Center for Psycho-Oncology
Research, Dartmouth-Hitchcock Medical Center, One Medical Center
Drive, Lebanon, NH 03756, USA. robert.j.ferguson@dartmouth.edu
Paraska
K, Bender CM.
Cognitive dysfunction following adjuvant
chemotherapy for breast cancer: two case studies.
PURPOSE/OBJECTIVES: To describe the cognitive dysfunction
experienced by two women after they received adjuvant
chemotherapy for breast cancer and to discuss the potential role
of changes in reproductive status and depression in the
development of cognitive dysfunction. DATA SOURCES: Journal
articles, research data, and clinical experience. DATA
SYNTHESIS: Following chemotherapy, 17%-50% of women with breast
cancer experience cognitive dysfunction that may include
decrements in memory, attention, and psychomotor efficiency. One
mechanism that may contribute to cognitive dysfunction involves
changes in reproductive status resulting from chemotherapy.
Additionally, the presence of depression may confound the
experience of cognitive dysfunction. CONCLUSIONS: A
comprehensive description of cognitive dysfunction and improved
understanding of the interrelationships among cognitive
dysfunction, reproductive hormone levels, and depression in
women with breast cancer receiving adjuvant chemotherapy may
hasten the development of interventions for the management of
cognitive dysfunction. IMPLICATIONS FOR NURSING: Nurses should
teach women with breast cancer and their families about the
potential for cognitive dysfunction after chemotherapy so the
problem can be recognized and interventions can be implemented
to help women compensate for the dysfunction.
School of Nursing, University of Pittsburgh, Pittsburgh,
Pennsylvania, USA. kparaska@libcom.com
Fliessbach
K, Urbach H, Helmstaedter C, Pels H, Glasmacher A, Kraus JA,
Klockgether T, Schmidt-Wolf I, Schlegel U.
Cognitive performance and magnetic resonance imaging
findings after high-dose systemic and intraventricular
chemotherapy for primary central nervous system lymphoma.
BACKGROUND: Long-term neurotoxicity is a frequent complication
of combined radiotherapy and chemotherapy in patients with
primary central nervous system lymphoma. Treatment protocols
without radiotherapy have been implemented to avoid this;
however, little detailed neuropsychologic and neuroradiologic
data exist to assess the frequency of long-term treatment
sequelae in this patient group. OBJECTIVE: To determine whether
a polychemotherapy regimen based on high-dose methotrexate
results in cognitive impairment and/or changes detectable by
magnetic resonance imaging of the brain during long-term
follow-up. PATIENTS AND METHODS: Twenty patients with
histologically proven primary central nervous system lymphoma
were treated with a novel chemotherapy protocol that included
systemic and intraventricular administration of methotrexate and
cytarabine (ara-C). Standardized neuropsychologic testing and
magnetic resonance imaging investigations were performed prior
to therapy and prospectively during a median follow-up period of
36 months (range, 21-69 months). RESULTS: Ten patients achieved
durable remissions without relapse for more than 1 year after
completion of chemotherapy. There was no gross cognitive decline
in any of these patients during the follow-up period. In
contrast, magnetic resonance imaging revealed therapy-induced
white matter changes in 5 of these patients. CONCLUSIONS: We
conclude that chemotherapy alone is associated with a low risk
of long-term neurotoxicity in primary central nervous system
lymphoma. Methotrexate-induced white matter lesions detectable
on magnetic resonance imaging are not inevitably associated with
significant cognitive decline.
Department of Neurology, University of Bonn, Bonn, Germany.
Friedman
MA, Meyers CA, Sawaya R.
Neuropsychological
effects of third ventricle tumor surgery.
OBJECTIVE: This study assessed the neuropsychological outcome of
patients after surgical treatment for third ventricle brain
tumors. Neuropsychological consequences of surgical intervention
can have a major impact on patients' quality of life and
therefore have important implications for treatment planning.
METHODS: A retrospective analysis of 33 patients'
neuropsychological data was performed. All patients received a
comprehensive neuropsychological evaluation after treatment for
a primary brain tumor in the third ventricular region.
Twenty-six patients underwent surgery, 14 via the transcallosal
approach and 12 via a subfrontal, left transcortical, right
pterional, or infratentorial supracerebellar approach. Seven
patients were not treated by surgical intervention. RESULTS:
There was a significantly elevated frequency of cognitive
impairment relative to normative values in memory, executive
functioning, and fine manual speed and dexterity. There were no
differences in mean neuropsychological scores between patients
who underwent surgery and those who did not. There were no
differences in mean performance on the basis of surgical
approach, tumor infiltration, or history of cranial irradiation.
Repeated measures data available for two patients revealed
memory impairment before and after surgery, and one patient
experienced major improvement after surgery on a measure of
mental flexibility and problem solving. CONCLUSION: Patients
with third ventricle tumors are at risk for developing
impairments in memory, executive function, and fine manual speed
and dexterity, which are domains associated with frontal
subcortical functions. In the current study, different types of
treatment were not associated with differential cognitive
sequelae, and surgical intervention did not account for
cognitive deficits.
The Brain and Spine Center, The University of Texas M. D.
Anderson Cancer Center, Houston 77030, USA.
Hahn
CA, Dunn RH, Logue PE, King JH, Edwards CL, Halperin EC.
Prospective study of neuropsychologic testing and
quality-of-life assessment of adults with primary malignant brain
tumors.
Int
J Radiat Oncol Biol Phys. 2003 Mar 15;55(4):992-9.
PMID: 12605978 [PubMed - indexed for MEDLINE]
PURPOSE: To identify the characteristics of adult patients with
newly diagnosed primary brain tumors associated with
identifiable deficits in neuropsychologic function to target
interventions to improve function and quality of life (QOL).
MATERIALS AND METHODS: Adult patients with newly diagnosed
primary brain tumors and their caregivers were enrolled and
underwent a battery of standardized neuropsychologic tests,
allowing for qualitative and quantitative assessment and
sensitive to the effects of the brain tumor, QOL, or caregiver
stress. RESULTS: We enrolled 68 patients with no prior
radiotherapy. Patients with left hemisphere tumors reported
significantly more memory problems and depressive symptoms. They
also exhibited poorer attention and were more distractible, with
poorer verbal fluency and poorer verbal learning. Patients with
glioblastoma multiforme demonstrated poorer psychomotor speed
and visual tracking than patients with non-glioblastoma
multiforme histologic features. Patients and caregivers
perceived QOL in a similar fashion, with significant correlation
between patient and caregiver on hope testing and general QOL on
the Linear Analog Self-Assessment Scale. CONCLUSIONS: Patients
with left hemisphere tumors and glioblastoma multiforme
histologic features demonstrated testable differences in
neuropsychologic function and QOL that may be amenable to
improvement with medical therapy or tailored rehabilitation
programs. Caregiver assessments can predict patient QOL, which
may be useful in patients with declining status.
Department of Radiation Oncology, Duke University Medical
Center, Durham, NC 27710, USA. hahn@radonc.duke.edu
Fuh
JL, Wang SJ, Lu SR, Juang KD, Lee SJ.
Alterations in cognitive function during the
menopausal transition.
J
Am Geriatr Soc. 2003 Mar;51(3):431-2. No abstract
available.
PMID: 12588594 [PubMed - indexed for MEDLINE]
Gottschalk
LA, Holcombe RF, Jackson D, Bechtel RJ.
The effects of anticancer chemotherapeutic drugs on
cognitive function and other neuropsychiatric dimensions in breast
cancer patients.
This preliminary study aimed to apply a novel computerized
measure derived from the content analysis of 5-min speech
samples from patients with breast cancer to measure cognitive
impairment and other neuropsychiatric dimensions during the
course of anticancer chemotherapeutic treatment. Since such
patients are often administered other pharmacological agents to
alleviate their symptoms in addition to anticancer
chemotherapeutic agents, another aim was to try to distinguish
the mental effects of the anticancer drugs from the effects of
any other drugs administered. Before and during the course of
their anticancer chemotherapy, 12 breast cancer patients gave
5-min verbal samples, elicited by purposely ambiguous
instructions, to talk about any personal life experiences. The
recorded verbal samples were scored by a computer program (PCAD
2000) to measure the magnitude of cognitive impairment and other
relevant neuropsychiatric dimensions. All of the pharmacological
agents administered to the patients were recorded. The computer
program automatically compared the scores derived from each
verbal sample to already established norms to determine whether
each score was within normal limits or one to three standard
deviations from the norms. Significantly elevated Cognitive
Impairment Scale scores were found in the verbal samples of 9 of
the 12 patients. All patients had instances of elevated
Health/Sickness Content Analysis Scale scores as well as
frequent significantly elevated scores in shame anxiety and in
death anxiety. In the Quality of Life Content Scale, the scores
were uniformly low, ranging from +1.64 to -9.11. Further studies
are being carried out to determine which patients are especially
susceptible to cognitive impairment under these treatment
conditions.
Department of Psychiatry, College of Medicine, University of
California, Irvine, USA. gottsch@uci.edu
Phillips
KA, Bernhard J.
Adjuvant breast cancer treatment and cognitive
function: current knowledge and research directions.
J
Natl Cancer Inst. 2003 Feb 5;95(3):190-7. Review.
PMID: 12569140 [PubMed - indexed for MEDLINE]
Evidence is mounting that potentially curative systemic adjuvant
therapy for early-stage breast cancer may result in cognitive
impairment. Five published studies have investigated cognitive
function in this setting, and the consistent results of all five
studies suggest an adverse effect of adjuvant chemotherapy.
These studies are reviewed with particular attention to their
methodologic limitations. For example, all five studies used
cross-sectional designs, none controlled for possible
confounding hormonal factors, and three examined patients who
had not received a uniform chemotherapy regimen. The potential
roles of chemotherapy-induced menopause and of adjuvant hormonal
therapy in cognitive impairment are also discussed. Priorities
for future research include confirmation of an effect of
adjuvant chemotherapy in a study with a longitudinal design,
closer examination of the potential contribution of hormonal
factors, and similar studies on the effect of adjuvant therapy
on cognitive function in other cancer types. If an effect of
systemic adjuvant therapy on cognitive function is confirmed,
such an effect will have implications for informed consent. It
may also result in incorporation of objective measures of
cognition in clinical trials of adjuvant therapy and in the
investigation of preventive interventions that might minimize
the impact of cognitive dysfunction after cancer treatment.
Department of Haematology and Medical Oncology, Peter
MacCallum Cancer Institute, St. Andrew's Place, East Melbourne,
Victoria, Australia. Kelly.Phillips@petermac.org
George
AP, Kuehn SM, Vassilyadi M, Richards PM, Parlow SE, Keene DL,
Ventureyra EC.
Cognitive sequelae in children with posterior fossa
tumors.
Late effects of radiotherapy on intellectual functioning have
been well documented in children treated for posterior fossa
tumors. Other aspects of cognitive functioning, such as memory,
have not been adequately assessed in this population. This
retrospective review reports on 15 children diagnosed with
medulloblastoma or cerebellar astrocytoma who were administered
a norm-referenced standardized test of memory functioning (i.e.,
Wide Range Assessment of Memory and Learning) an average of 3.5
years after treatment. Analyses revealed that sample means of IQ
and memory were significantly lower than those of the normative
population. No significant differences were found between the
verbal and nonverbal IQ, or verbal and visual memory. Age at
diagnosis accounted for a significant proportion of variability
in the intelligence ratings but not in the memory indexes. The
IQ scores of children less than 6 years of age at diagnosis were
significantly lower than those of children diagnosed when over 6
years of age. Given the substantial variability within the older
age group, there was insufficient power to detect true
differences between memory index means for children by age at
diagnosis. Follow-up assessments over 5 years may better
identify the long-term effects of radiotherapy on memory
functioning
Mental Health Patient Service Unit, Children's Hospital of
Eastern Ontario, Ottawa, Canada.
Note
If
you experience symptoms of chemobrain, I strongly
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professional about your specific medical condition and
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If
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