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Cognitive Impact of Intensive Treatments for Chronic Illness
J. Aubrey Burhart, Ed.M., Doctoral Student
James P. Donnelly, Ph.D., Assistant Professor
University at Buffalo/SUNY
Counseling Educational School of Psychology
Sally Speed, Office of Medicaid Management Unit Director
Award: 31177
Project: 1037112
Task: 2
Funding for this research project was provided by NYS Office of Children and Family
Services, Contract year 2004: Project 1037122, Award 31177, through the Center for
Development of Human Services, College Relations Group, Research Foundation of
SUNY, Buffalo State College.
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
INTRODUCTION
Although the 2004 Annual Report to the Nation from the National Cancer
Institute reported a decrease in the risk of getting and dying from cancer, it is predicted
that the number of new cancer cases to arise in 2004 is upwards of one million. Close to
600,000
people
are
expected
to
die
from
cancer
in
2004
(http://seer.cancer.gov/csr/1975_2001/results_single/sect_01_table.01.pdf).
Cognitive
dysfunction is a frequently observed complication in cancer patients (Pereira, Hanson, &
Bruera, 1997; Meyers & Abbruzzese, 1992; Ahles, Tope, Furstenberg, Hann, & Mills,
1996; Andrykowski, Schmitt, Gregg, Brady, & Lamb, 1992; Sjogren, Olsen, Thomsen, &
Dalberg, 2000). It is associated with increased distress for both patient and caregivers,
and impacts patients’ ability to sufficiently comprehend the information necessary to
make informed decisions regarding their healthcare. Intact cognitive functioning is
imperative for adhering to treatment regimens and medication compliance (Folstein,
Fetting, Lobo, Niaz, & Capozzoli, 1984). Cognitive functioning is also essential for
carrying out activities of daily living, intellectual development, success in the workplace,
and maintenance of social relationships (Walch, Ahles, & Saykin, 1998). Cognitive
impairment can be acute or chronic, subtle or pronounced, temporary or permanent,
stable or progressive (Walch, Ahles, & Saykin, 1998). While cognitive dysfunction is
common in cases central nervous system (CNS) metastases, involvement of CNS does
not have to be present for impairment to occur. A host of factors may be detrimental to
cognitive functioning. They can be classified on an etiologic basis as either disease
induced or treatment induced factors (Sjogren et al., 2002; Andrykowski et al., 1992).
Disease induced factors include brain metastases, infections, nutritional deficiencies,
disturbances in the metabolic/endocrinologic systems, and pain. Chemotherapy,
radiation, bone marrow transplant, medications and biologic response modifiers are
among the treatment induced factors and have been implicated as risk factors for
neurocognitive impairment (Walch, Ahles, & Saykin, 1998). Furthermore, total dose of
therapeutic agent, time of administration, and volume of tissue affected may impact the
severity of neurotoxicity (Walch, Ahles, & Saykin, 1998). Cognitive dysfunction in
cancer patients has been noted for many years. The deficits can be attributed to a variety
of causes which can be classified as either disease-induced factors, such as infection,
metabolic disruptions, brain metastasis, pain, etc., or treatment related factors including
various drug, chemotherapy, and radiation therapies. Medical interventions that are
employed for cancer can be extremely toxic, thus imposing measurable cognitive deficits
in patients (Walch, Ahles, & Saykin, 1998; Garofalo & Baum, 2001). Radiation therapy,
although often deemed an integral component of cancer treatment, has been highlighted
as a primary cause of compromised cognitive functioning (Walch, Ahles, & Saykin,
1998; Garofalo & Baum, 2001). This type of treatment entails the use of radiation waves
to destroy or weaken cancer cells. Although malignant cells are more prone to become
the target of radiation waves, the radiation does not entirely distinguish between
malignant cells and healthy cells. Therefore, patients are at risk for losing cells from
healthy issue as well.
Standard chemotherapy treatment also appears to put cancer patients at risk for
cognitive impairment, however drawing conclusions about its neurotoxic effects is
challenging due to the great number of chemotherapy drugs used on various schedules
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
and dosages (Walch, Ahles, & Saykin, 1998; Garofalo & Baum, 2001). Advances in the
medical field have led to combination therapy treatment in which both chemotherapy and
radiation therapy are administered. While this could prove to be more efficacious in
conquering the disease, increased exposure to these toxic agents subjects patients to
greater risk for neuropsychological impairments. Bone marrow transplantation (BMT) is
yet another therapy that is increasingly used in the treatment of cancer. The presence of
cognitive dysfunction in BMT patients is not surprising considering the pre-transplant
treatment regimen that they must undergo. Patients are treated with high-dose
chemotherapy involving various toxic agents, often coupled with total body irradiation
(TBI; et al, 1992). This conditioning regimen is then followed by the BMT itself, which
involves reinfusement of bone marrow or peripheral stem cells. BMT can be
characterized as autologous or allogeneic with the former referring to a procedure by
which the patient’s bone marrow is harvested and then reinfused; the latter type employs
an unrelated, but matched, donor’s bone marrow. Both types of BMT pose risks for
recipients, however there is evidence that allogeneic transplants impose greater
neurologic complications due to the potential for graft-versus-host disease and severe
immunosuppression (Ahles et al., 1996). Bone marrow transplantation (BMT) is an
aggressive cancer treatment often implemented when patients with hematologic or solid
malignancies do not respond to typical treatment modalities (Ahles, Tope, Furstenberg,
Hann, & Mills, 1996). The BMT procedure makes patients potentially susceptible to
many risk factors including infections related to a compromised immune system, graft
versus host disease, and neurotoxic effects of immunosuppressive therapy (Harder et al.,
2002). The multiple risk factors involved for patients treated with BMT makes BMT a
unique treatment modality for cancer compared with other treatments that potentially
induce neurotoxic effects. Cognitive deficits have been reported in the literature as one
of many potential devastating consequences following BMT (Meyers, Weitzner, Byrne,
Valentine, Champlin & Przepiorka, 1994; Ahles et al., 1996; Andrykowski, Schmitt,
Gregg, Brady, Lamb, & Henslee-Downey, 1992). Unfortunately, the studies that have
examined neuropsychological functioning of these particular patients have been, most
often, retrospective and lack a quantitative, systematic protocol (Meyers et al., 1994;
Padovan, Yousry, Schleuning, Holler, Kolb, & Straube, 1998). Few studies have
systematically assessed changes in patients cognitive functioning with standardized tests
across various points in time. An abundance of research has documented the effects of
BMT on children, but the nature of cognitive impairment in adults is unclear. Potential
bone marrow transplant recipients must be able to adequately comprehend, process, and
remember substantial amounts of disease and treatment-related information in order to
make informed decisions regarding their health care. BMT patients must exercise precise
self-care behaviors during and following bone marrow transplantation. Thus, it is
imperative that these patients retain the capacity to understand their necessary self-care
regimen (Andrykowski et al., 1992).
Greater understanding of the potential cognitive effects that these aforementioned
treatments can have on patients is warranted. As the number of people diagnosed with
cancer increases, more and more patients will suffer with cognitive deficits. Cognitive
deficiencies can affect patients’ abilities to make informed treatment decisions.
Furthermore, the educational and employment opportunities for cancer survivors may be
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
limited by the presence of cognitive dysfunction. By researching the impact that cancer
treatment modalities can have on patients cognitively, interventions that have proven
efficacious in other types of patients with cognitive deficits could be employed in this
population with hopes of similar success. Finally, the quality of patients’ lives following
treatment should not be dismissed. Attempting to maintain a previous standard for
quality of life can become quite challenging and frustrating for the patient that is
suffering cognitively. Quantifying the cognitive effects that chemotherapy, radiation
therapy, and bone marrow transplantation have on some patients could lead physicians to
modifying treatment regimens. Research in children regarding this topic has resulted in
such treatment modifications that illustrated maintenance of treatment efficacy while
simultaneously reducing the negative cognitive side effects (Ahles, Saykin, Furstenberg,
Cole, Mott, et al., 2002). Literature that has documented the effects of various treatment
modalities for cancer on cognitive functioning will now be reviewed.
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
Literature Review
Chemotherapy
Tannock, Ahles, Ganz, and van Dam (2004) reported the results of a workshop
that was held to review literature regarding cognitive effects of chemotherapy, construct
hypotheses to be tested as to what the underlying mechanisms are for cognitive
impairment, and establish priorities for future research. The clinicians present at this
workshop reviewed the literature that had evaluated cognitive functioning in adult cancer
patients treated with cytotoxic agents. Some patients experienced cognitive dysfunction
as late as ten years, and for those whose cognitive function was determined to be within
normal limits, there was an association between low-normal functioning and previous
chemotherapy treatment. It was determined that the most appropriate method for
assessing cognitive function depends on the question being asked and the context of the
study. When seeking to evaluate which cognitive domains are affected by chemotherapy,
a traditional, comprehensive neuropsychological battery was deemed necessary.
However, if the goal is to simply evaluate whether patients suffer from cognitive deficits,
then a brief, validated assessment battery is permissible.
Ahles and colleagues (2003) compared the neuropsychological performance of
long term breast cancer and lymphoma survivors treated with standard dose
chemotherapy who carried the apolipoprotein E e4 (APOE e4) allele to those whom had
other APOE alleles present. The presence of the APOE e4 allele has been associated
with greater risk for Alzheimer’s disease, neuropsychological deficits following cardiac
bypass surgery, and traumatic brain injury (Ahles et al., 2003).
A total of 80 survivors (Breast cancer N=51; Lymphoma N=29) with no evidence
of disease and at least five years post-diagnosis consented to the study. None of the
sample was receiving cancer treatment throughout the duration of the investigation. A
neuropsychological test battery was administered by superior technicians under the
supervision of a board certified neuropsychologist. Survivors’ treatment history and
APOE status was not known to neuropsychology technicians. The test battery measured
several neuropsychological domains. Verbal ability was measured using the Vocabulary
subtest from the Wechsler Adult Intelligence Scale-III (WAIS-III), the Reading subtest of
the Wide Range Achievement Test-III (WRAT-III), Boston Naming Test, and the
Controlled Oral Word Association Test. Block Design, another subtest from the WAISIII, was employed to assess spatial ability. Indices of the California Verbal Learning Test
(CVLT) were used to assess verbal learning. Verbal memory was measured using
Logical Memory I, Stories A and B and Logical Memory Multiple Choice Story B (30’
delay) from the Wechsler Memory Scale-Revised (WMS-R). The Visual Reproduction I
and Visual Reproduction II (30’ delay) subtests were also used from the WMS-R to
assess visual memory. Psychomotor function was measured by the Digit Symbol subtest
of the WAIS-III and Trails A & B. Finger Tapping and Thumb-Finger Sequencing were
employed to measure motor functioning. Vigilance and Distractibility subtests from the
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
Continuous Performance Test (CPT) were used to measure two dimensions of attention,
accuracy and reaction time. The CES-D, Spielberger State-Trait Anxiety Inventory, and
Fatigue Symptom Inventory were also administered as measures of depression, anxiety,
and fatigue, respectively (Ahles et al., 2003). Z-scores from a sample of cancer survivors
that completed the same neuropsychological assessment battery were used as a reference
to calculate nine domain scores. Ten milliliters of blood was drawn for APOE testing. As
expected according to the population distribution, 21% of the survivors carried at least
one e4 allele, and this group performed significantly lower than those without this gene
on visual memory (p<.03) and spatial ability (p<.05) tasks. Compared to the reference
normative data, however, performance across domains was within normal limits,
regardless of APOE status (Ahles et al., 2003). This study provides evidence to support
the hypothesis that carriers of the e4 allele are more susceptible to chemotherapy-induced
cognitive deficits. This conclusion should be considered in light of the fact that the
investigation lacked pretreatment neuropsychological assessment (Ahles et al., 2003).
Brezden et al., (2000) examined the effects of chemotherapy on cognitive functioning
across three treatment groups. Group A (n=31) consisted of breast cancer patients
currently undergoing adjuvant chemotherapy (at testing, median number of cycles
completed was three); Group B (n=40) was comprised of breast cancer patients who
completed chemotherapy at least one year prior (median time since chemotherapy was 25
months) and had no evidence of relapse; Group C (n=36) contained healthy controls with
no history of major illnesses. The entire sample was female. Individuals in Groups A
and B had a diagnosis of early-stage breast cancer with no previous major medical
history.
To assess neuropsychological functioning, the High Sensitivity Cognitive Screen
(HSCS) was employed. This measure tests six cognitive domains including memory,
language, visual-motor, spatial, attention and concentration, and self-regulation and
planning. It is reported to have 93% accuracy when distinguishing between normal and
abnormal results of a neuropsychological exam (Brezden et al., 2000). By totaling the
scores across the six domains, the authors yielded an overall cognition score for each
subject on the HSCS. Higher scores were indicative of greater deficits. In addition, the
Profile of Mood States (POMS) was administered to each subject. This self-administered
questionnaire detects fluctuating mood patterns and is capable of detecting mood
disorders (Brezden et al., 2000). Six dimensions measure various derivatives of anxiety
and depression, and, when totaled, yield a total score. Higher scores represent greater
mood disturbance. Both of the aforementioned assessment tools were administered under
the supervision of the primary investigator of the study.
The age of individuals in Group C was significantly younger than those in other
groups and significantly more patients in Groups A and B were postmenopausal
than in the control group. The results should be considered in light of these
findings. Overall scores on the HSCS were significantly lower in Group A than
in Group C, above and beyond age, education, and menopausal status (p=.046).
The HSCS allows for classification of individuals by degree of impairment as
mild, moderate, severe, based on their total score. Treatment groups A and B
consisted of significantly more individuals with moderate or severe cognitive
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
impairment (15 out of 31 patients and 20 out of 40, respectively) than in the
control group (four out of 36). In terms of specific neuropsychological domains,
patients in group A had significantly different scores on memory and language
domains than those in group C. Furthermore, analysis of scores in the language
and visual-motor skills domains yielded significant differences between groups B
and C. Analyses of the POMS scores resulted in no significant differences
between groups, suggesting that mood disturbance cannot explain the observed
differences in cognitive functioning. This study contributes to the body of
literature that illustrates significant effects of chemotherapy on cognitive
functioning (Brezden, 2000).
Capuron and her cohort (2001) sought to determine the timing and specificity of
alterations in neuropsychological functioning of cancer patients as a result of two
different types of chemotherapy, IL-2 and IFN-[alpha]. Three specific tests from the
CANTAB battery were utilized to assess patients’ reaction time, working memory and
strategy performance, and spatial planning. The tests were computerized assessments.
Over a two-year period, 47 consecutive patients consented to the study and were assigned
to four different treatment regimens: The IL-2 group consisted of 17 metastatic renal cell
carcinoma patients. A group of seven patients with renal cell carcinoma were subjected
to subcutaneous injections of IL-2 and IFN-[alpha]. Another group of seven patients
with renal cell carcinoma were administered low doses of IFN-[alpha] subcutaneously.
Finally, 16 patients with metastatic melanoma received high IV doses of IFN-[alpha]
(Capuron et al., 2001).
Patients were tested on three occasions: on day 1 prior to treatment initiation; on
day 5 of treatment; and at the completion of month one of treatment. Due to medical
complications and/or termination of treatment, 32 out of the 47 patients were tested at the
end of the first month. Statistical analyses were computed independently between day 1
and day 5 and day 1 and 1 month (Capuron et al., 2001).
Patients treated with IFN-[alpha] demonstrated deficits in reaction time,
particularly as a task became increasingly difficult) in the early stages of treatment.
Greater deficits were noted on tasks of reaction time in the patients to whom IFN-[alpha]
was delivered intravenously. Impairment on tasks of spatial working memory was
prominent in the IL-2 group, recognized as early as day 5 of treatment. There was a
direct relationship between extent of impairment and task difficulty. This finding was not
present among other treatment groups. The IL-2 group also had compromised problem
solving abilities which were highlighted at day 5 but remained at one month of treatment.
Interestingly, no impairment was documented during the first month of treatment in the
group receiving both IL-2 and IFN-[alpha]. Finally, mood and sleep disturbance was
present in patients treated with IL-2 alone and IL-2 with IFN-[alpha] early in treatment
(day 5) and remained at one month. Psychomotor retardation was prominent at day 5 in
the group receiving IFN-[alpha] intravenously and was related to depressive symptoms
that evolved after one month. These findings highlight the detrimental effects of both IL2 and IFN-[alpha] on cognitive functioning (Capuron et al., 2001).
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
The potential neurological complications, and subsequent neuropsychological
deficits, resulting from treatment with the chemotherapeutic agent cisplatin were
documented in a review paper by Troy and his colleagues (2000). Although cisplatin has
been deemed a successful chemotherapeutic agent in the treatment of various cancers, it
often has devastating neurotoxic effects on the peripheral and central nervous systems
(PNS and CNS, respectively). Troy et al. (2000) highlighted the consistency in studies
reporting the direct relationship between incidence of neurotoxicity and cisplatin dose.
While the ability of cisplatin to cross the blood-brain barrier has been doubted and
debated in previous research, Troy et al. (2000) reported that studies exist suggesting that
repeatedly high doses of cisplatin may result in increased platinum in the CNS, and,
consequently, central neurotoxicity.
Troy et al. (2000) found that impairment following neurotoxin treatment is most
commonly reported on neuropsychological tasks measuring visuoperceptual skills,
psychomotor skills, reaction time, verbal conceptualization, short-term memory, and
attention and executive functioning. Given the neuroanatomical structures that
chemotherapeutic agents target, specifically the hippocampus, amygdala, striatal and
basal ganglia areas, and frontal lobes, deficits in those domains could be expected.
Emesis is experienced by most, if not all, patients with neurotoxin exposure. The
influence and severity of delayed emesis depends on the dose of cisplatin and extent to
which emesis was present in the initial stages of treatment. Peripheral neuropathy is not
at all a rare side-effect, often characterized by sensory disturbance and fine motor
coordination deficits. Troy et al. (2000) notes that neuropsychological measures utilized
must be sufficiently sensitive to subtle sensory impairment, as cognitive tests are
dependent on adequate fine motor activity and efficient somato-sensory functioning, and
impaired cognitive performance may be mistaken for motor dexterity problems.
Ototoxicity, high frequency hearing loss, has been reported as an irreversible side effect.
Ophthalmologic consequences can vary from decreased visual acuity to transient
blindness (Troy et al., 2000).
Chronic myelogenous leukemia (CML) patients (n=25) treated with interferon
alfa (IFN-[alpha]) were evaluated neuropsychologically, in an investigation led by Pavol
and colleagues (1995), to determine changes in cognitive functioning. The sample
consisted of men and women aged 24 to 70 years, with an average of 14.8 years of
education. Since diagnosis, an average of 32.8 months had passed, and the length of
IFN-[alpha] treatment ranged from 1 week to 84 months (mean = 26.1; median = 18).
IFN-[alpha] was administered subcutaneously, averaging a weekly dose of 51 million
international units. A battery of neuropsychological tests was designed to assess a broad
range of cognitive functioning. Intelligence was measured using subtests of the Wechsler
Adult Intelligence Scale-Revised (WAIS-R), including information, digit span,
arithmetic, similarities, block design, and digit symbol. The Verbal Selective Reminding
Test and the Nonverbal Selective Reminding Test was employed to test memory. Motor
dexterity was assessed using the Grooved Pegboard. Language was tested with a verbal
fluency task from the Multilingual Aphasia Examination (COWAT). Part B of the Trail
Making Test and the Booklet Category Test was utilized to assess executive function.
The personality domain was measured using the Minnesota Multiphasic Personality
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
Inventory (MMPI). To simplify comparisons across measures, all scores were converted
into standardized T scores (Pavol et al., 1995). A control group was employed that
consisted of 16 patients diagnosed with CML, but had not yet undergone IFN-[alpha]
treatment.
Test means for the IFN-[alpha] patients fell into the below average performance
range (more than one SD below normative values) for verbal memory and both executive
function tasks. An unusually high number of IFN-[alpha] patients (compared to the
expected 2.1% of population) scored in the impaired range (two or more SD below the
normative mean) on tests of verbal memory, delayed visual memory, verbal fluency,
visual scanning and sequencing, executive function, and motor dexterity in the dominant
hand (Pavol et al., 1995). The control group performed significantly better on Trail
Making Test, Part B (p=.004) and the Digit Symbol subtest of the WAIS-R (p=.003).
Dose of IFN-[alpha] was not related to test performance. Time since diagnosis, however,
was highly correlated with tests of verbal memory and graphomotor speed in the IFN[alpha] group. Time since diagnosis was not correlated with test scores in the control
group. Within the treatment group, scores on the hypochondriasis, depression, and
hysteria scales of the MMPI were significantly higher than compared to scores of the
control group.
This study demonstrates impaired performance on several
neuropsychological tests, across various domains (verbal learning, delayed recall of
verbal information, speed and efficiency of cognitive processing, and executive function),
after initiating treatment with IFN-[alpha]. These patients also demonstrated personality
disturbances which were not evident in the control group (Pavol et al., 1995).
Ahles and colleagues (2002) initiated another study that examined
neuropsychological functioning in cancer survivors who were treated with systemic
chemotherapy or local therapy (surgery or radiation therapy) and at least five years out
from diagnosis. Among the systemic chemotherapy group were 35 breast cancer
survivors and 36 lymphoma survivors. The local therapy group consisted of 35 breast
cancer survivors and 22 lymphoma survivors. Individuals that had undergone CNS
radiation were excluded. A thorough neuropsychological battery was employed that
included tests in the following domains: verbal ability, spatial ability, verbal learning,
verbal memory, visual memory, psychomotor function, motor functioning, attention
(vigilance and accuracy), and attention (reaction time). In addition, measures of affective
variables and fatigue were included. Statistical analysis included MANCOVA which was
conducted with treatment (chemotherapy vs. local therapy) and diagnosis (breast cancer
vs. lymphoma) as independent variables, the nine domain scores as dependent variables,
and age and education as covariates. Findings provided support for the hypothesis that
deficits in cognitive functioning are associated with systemic chemotherapy. The overall
MANCOVA highlighted a significant effect for treatment (p< .04) but not for diagnosis
(p< .15). The specific domains of neuropsychological functioning that revealed
significant treatment differences were verbal memory (p<.01) and psychomotor
functioning (p< .03). Although differences did not reach significance status, an overall
trend was noted for group differences in spatial ability (p< .10) and visual memory (p<
.12). It is important to note that the deficits revealed in the survivors of this study were
detected approximately 10 years after chemotherapy, on average. This suggests that the
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
effects of chemotherapy may persist long after treatment. A relatively large sample,
coupled with strong statistical results, contributes to the strengths of this study. The
major weakness lies in the lack of pretreatment assessment of cognitive functioning. This
methodological flaw precludes detection of individuals that possessed cognitive deficits
prior to treatment and may have actually demonstrated improvement at the ten year mark,
despite still falling below normal cut-offs on testing. Some of these people may have
experienced a decline in cognitive functioning, but were not detected because their
pretreatment level of functioning was above normal, and, following treatment, they fell
into a normal range.
Radiation Therapy
Cancer patients are often subjected to radiotherapy as part of their treatment.
Radiation can affect the neural structures directly or indirectly when radiation therapy
damages large blood vessels supplying the brain or endocrine organs. Secondary tumors
can also result (Keime-Guibert, 1998). While radiation is more likely to target malignant
cells, it does not distinguish between cancerous cells and those of healthy tissue, thereby
producing side-effects. Cognitive deficits are just one side effect of this treatment that
has been documented in the literature (Garofalo & Baum, 2001). Cognitive dysfunction
may be noted immediately after treatment or several years or months later (KeimeGuibert, 1998; Garofalo & Baum, 2001). There are a vast number of potential
complications that can occur following radiotherapy which include encephalopathy,
somnolence syndrome, radionecrosis, cognitive dysfunction, radiation-induced dementia,
radiation-induced tumors, and damage to the endocrine glands (Keime-Guibert, 1998).
The following reviews some literature pertinent to the effects of radiation on cognitive
functioning.
Keime-Guibert and colleagues (1998) presented a review of potential neurological
complications following radiotherapy in a timeline fashion. According to these
researchers, complications can occur momentarily after radiation or as far removed as 30
years later. Acute encephalopathy is characterized by headache, nausea, drowsiness,
fever, and occasionally worsening neurological signs, and typically sets in within 2 weeks
of radiation. The clinical picture can be much more severe for patients with a more
complicated medical and treatment history. Between two weeks and three to four months
after radiation, early-delayed complications might occur. These complications vary in
their presentation but may include a somnolence syndrome (e.g. hypersomnia,
drowsiness, irritability), recurrent tumor, or leukoencephalopathy coupled with cognitive
dysfunction and pseudobulbar syndrome. The onset of brain stem encephalopathy is also
possible, yet rare. Although most patients recover from this complication, it can be fatal.
Complications are classified as “delayed” if they occur four months to many years after
completion of radiotherapy. The likelihood of delayed damage depends on the dosage
variables of radiation delivered, presence of other systemic diseases, and whether
concurrent chemotherapy was administered (Keime-Guibert, 1998). The primary
complications of brain radiation include radiation necrosis and cognitive
dysfunction/leukoencephalopathy. Patients with necrosis typically fare well if the
damaged area is resected. Corticosteroids have also proven effective, though patients
easily become dependent. Cognitive dysfunction and leukoencephalopathy without
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
necrosis is among the most frequent complication in long-term survivors. Symptoms can
be as pronounced as dementia or less overt, representing a mild or moderate
neuropsychological impairment. The neuropsychological impairment is typically
characterized by memory dysfunction, attention deficits, and immediate problem solving
ability. The dementia includes severe cognitive deterioration characterized by dramatic
intellectual deficits, memory impairment, decreased attention, emotional lability and
apathy. Depression is also common, subsequent to preserved insight. Prognosis is poor
for radiation-induced dementia patients, as there is no effective therapy. Patients usually
die within 48 months after onset of symptoms. The risk for this dementia increases with
abnormal or unsafe doses of whole brain irradiation, concurrent chemotherapy, and age.
Other possible delayed complications include radiation-induced tumors, vascular
complications, and damage to the endocrine system.
A study lead by Andrykowski and his group (1990) sought to highlight the extent
to which allogeneic BMT patients experienced cognitive dysfunction, as well as examine
the relationship between total body irradiation (TBI) and cognitive difficulties. This
retrospective study recruited 30 patients who had undergone allogeneic BMT at least one
year earlier. All of the patients were treated with BMT for varying types of leukemia.
The majority of patients received TBI concurrent with high-dose chemotherapy, however
three patients received solely chemotherapy. Patients completed questionnaires including
the Profile of Mood States (POMS), Psychological Adjustment to Illness Scale (PAIS),
and five subscales from the Sickness Impact Profile (SIP). The POMS includes a
Confusion subscale, with higher scores indicating greater dysfunction. The SIP yields an
index of Alertness Behavior that assesses illness-related cognitive dysfunction with
questions regarding memory, attention and concentration, and cognitive processing.
Analyses revealed a significant relationship between dose of TBI and increased
dysfunction in the Alertness Behavior subscale of the SIP. Furthermore, a significant
main effect was in place for increased dose of TBI and increased cognitive dysfunction
above and beyond age, time post-BMT, primary disease diagnosis, sex, education, or
HLA-typing. Items regarding slowed reaction time, reduced attention and concentration,
and difficulties with reasoning and problem-solving demonstrated the strongest
relationship to dose of TBI. These results should be considered in light of the
methodological shortcomings that include the retrospective quality and self-administered
questionnaires that were employed for data collection.
Medications and other risk factors for neuropsychological deficits
Meyers and Abbruzzese (1992) tested the cognitive functioning of 47 cancer
patients who were not acutely ill, and had no history of CNS therapy or treatment with
neurotoxic agents. All patients had varying metastatic solid tumors that did not respond
to previous treatment and were being considered for chemotherapy. Patients were
enrolled in an exploratory investigation of difluorodeoxycytidine (dFdC), but had not
been subjected to any therapy for at least three weeks prior to the baseline
neuropsychological exam. Biologic response modifiers had been implemented in the
treatment of 19 patients. A neuropsychological battery was administered before and
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
during treatment, however the authors only reported the results of the baseline assessment
in this article. The neuropsychological battery consisted of Digit Span, Arithmetic, and
Digit Symbol subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R)
(attention); Similarities and Block Design from the WAIS-R (reasoning); the Logical
Memory subtest of the Wechsler Memory Scale, (WMS) and the Revised Benton Visual
Retention Test (memory); Trail Making Test Part A (visual-perception); Grip strength
and Finger Tapping (motor); Trail Making Test Part B and Controlled Oral Word
Association Test (executive functioning).
Abnormal test performance (at least 1.5 standard deviations from the age-adjusted
normative data) was demonstrated by 32% of patients on one or more tests. Impaired
performance was most prominent in the memory domain (53%), followed by executive
dysfunction (47%), visual-motor scanning deficits (40%), and attention problems (33%).
There was a significant difference between the number of patients previously treated with
biologic response modifiers in the group with normal neuropsychological performance
(28%) as compared to the patients with impaired performance (67%). The incidence of
patients with abnormal neuropsychological performance without previous biologics
treatment was only 18%, whereas 53% of patients with a positive previous biologics
treatment history had performed in the abnormal range on testing. These results support
the suggestion that the risk for developing persistent neurobehavioral disorders increases
with the presence of a history of previous biologics treatment (Meyers & Abbruzzese,
1992).
Cyclosporine A (CsA) is an immunosuppressant drug commonly employed in the
treatment of bone marrow or solid tumor transplant patients (Shah, 1999). CsA
neurotoxicity is widely observed in these types of patients and can be marked by a variety
of disturbances including encephalopathy, coma, seizure, blindness, and hemiparesis
(Shah, 1999). Shah (1999) retrospectively reviewed the charts of five bone marrow
transplant patients to explore in greater detail the clinical, electrophysiologic,
neuroimaging, and laboratory data in the presence of CsA neurotoxicity. The criteria
used to diagnosis the presence of CsA neurotoxicity included the following: “neurologic
deterioration occurred with an increase in the dose of CsA or rise in serum CsA level, and
neurologic improvement occurred following a dose reduction or cessation of CsA,
concomitant metabolic variables being stable, and when known side effects of other
medications could not explain the neurological deficits” (p.67). Except for one patient,
relatively full recoveries were made from the neurotoxicity.
Shah (1999) reported that the most common neurologic complications observed
with CsA neurotoxicity include seizures, confusion, disorientation, psychiatric symptoms,
headache, decreased responsiveness, paralysis, and, less commonly, coma, cortical
blindness, akinesia, parkinsonism, and pseudobulbar palsy. The onset of these
complications is typically one to three days following drug initiation, but may also follow
dose or method of administration manipulations. The cases reviewed in this study
demonstrated that CsA neurotoxicity is reversible (4 out of 5 cases) if the drug is
terminated or a lower dose is given. Furthermore, even after extended use, permanent
neurological damage can be prevented with discontinuation of CsA (Shah, 1999). EEG
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
studies were abnormal in all patients selected for this review. Neuroimaging revealed
hyperintense lesions on T2 weighted MRI involving the cerebral white matter (Shah,
1999). Shah (1999) reported that the posterior regions may be most affected and
involvement may also involve gray matter. Lab tests revealed that CsA neurotoxicity is
not totally dose dependent, as even patients with serum CsA level in the normal range
(<339 ng/mL) can display prominent neurological abnormalities. While the exact cause
of CsA neurotoxicity is not known, hypotheses have been generated. While very little
CsA is found has been found in the brain due to the challenge of crossing the blood-brain
barrier, impairment of the blood-brain barrier has been found in patients receiving the
drug. Thus it is possible that patients with defective CsA binding are predisposed to CsA
neurotoxicity (Shah, 1999). The inhibition of calcineurin, which is essential for signaling
in the central nervous system, by CsA, might explain the presence of CsA neurotoxicity.
Another suggested mechanism of CsA neurotoxicity involves the inhibitory effects of
CsA on nitrous oxide synthatase which is a potent vasodilator (Shah, 1999). In
conclusion, this review highlights the difficulty in detecting CsA toxicity, however, if
suspected, withdrawal should be executed (despite a normal serum CsA level) as it can
have devastating neurological effects (Shah, 1999).
Lawlor (2002) reviewed the available literature surrounding the opioid-associated
cognitive deficits in cancer patients. Opioids are frequently prescribed for pain
management in the cancer population (Lawlor, 2002). Due to the complicated nature of
cancer and multiple factors that can contribute to cognitive dysfunction (e.g. disease and
treatment variables), it is difficult to highlight the specific contribution of opioids to
problematic cognitive functioning. Studies have suggested that psychomotor retardation
and cognitive impairment in opioid-naïve, healthy volunteers was greatest in the presence
of meperidine, followed by hydromorphone, and then morphine (Lawlor, 2002). The
studies reviewed provided conflicting results, most likely due to method limitations
including variations in neuropsychological batteries (short and global versus lengthy
detailed assessments), and opioid doses, administration routes and intervals, time of
testing in relation to opioid administration, other medications, anxious and depressive
patient symptoms, and conflicting variables regarding the disease process and
progression (Lawlor, 2002). Lawlor (2002) suggested that the following general
conclusions can be drawn but considered with caution: opioid administration route has an
effect on cognitive functioning, with parenteral injections producing greater cognitive
impairment than oral administration; opioid-related impairment appears to be doserelated and cognitive impairment can occur in varying degrees with dose increases of at
least 30% (Lawlor, 2002).
Another investigation by Sjogren and colleagues (2000) sought to assess the
potential contribution of oral opioids, as well as pain and performance status, on
particular aspects of psychomotor and cognitive functioning in cancer patients. Patients
(N=130) were consecutively accrued over a three period and designated to one of five
groups depending on pain, performance status, and presence of oral opioid medication.
Karnofsky Performance Status (KPS) was deemed ‘A’ or ‘B’, with members of the
former group requiring no special care and able to carry out activities of daily living and
those in latter group characterized by inability to work but able to live at home with a
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
varying degree of assistance needed (Sjogren et al., 2002). Group 1 (N=40) consisted of
a control group of individuals who were KPS A, had no pain, and received no oral opioid
medication; group 2 (N=19) were KPS B, no pain, no opioids; group 3 (N=19) were KPS
B, positive for pain, but not receiving opioid medication; group 4A (N=31) was
characterized by being in KPS B, had pain, and received oral opioid medication; group
4B (N=21) was characterized by KPS B; no pain, and received oral opioid medication.
Patients in groups 4A and 4B had receiving stable opioids for more than two weeks. All
assessments were conducted by three of the authors. Opioid side effects were deemed
present or not by a physician, while sedation and pain level were determined by the
patient with the assistance of visual analogue scales (“SVAS” and “PVAS”,
respectively).
The neuropsychological testing battery consisted of the Continuous
Reaction Time test (CRT), finger tapping test (FTT), and paced auditory serial addition
test (PASAT). The CRT was employed as a measure of vigilance, requiring the
examinee to respond to auditory signals delivered at random intervals through
headphones. Percentile values, instead of cut-off scores, have demonstrated the ability to
enhance the discriminative capacity of the test. Hence, CRT values were summarized
using 10th, 50th, and 90th percentiles, representing the fastest to slowest values,
respectively (Sjogren et al., 2002). The FTT was selected for an index of psychomotor
slowing. This test requires the patient to tap a key as quickly as possible for five 10
second intervals. The PASAT, designed to assess the working memory component of
attention, necessitates the addition of consecutive pairs of digits presented 2.4 seconds
apart verbally, followed by a 2.0 second trial (Sjogren et al., 2002). The KPS is a
popular, well-validated observer measure that yields a percentage reflecting a host of
factors including disease status, independence, and role functioning. The resulting score
lies on a continuum ranging from “normal” presentation characterized as no disease
present and no complaints (100%) to “Dead” (0%). Those allocated to KPS A fell
between 80 to 100% and those in KPS B lie in the 50-70% range (Sjogren et al., 2002).
There were no statistically significant differences between groups except for significantly
higher sedation-visual analogue scores and opioid doses in group 4A than in group 4B.
No differences existed, however, in time from opioid ingestion to testing between these
two groups. Each group was compared to group 1 as the control group; in addition,
groups were compared with respect to the hierarchy of stigmatizing factors (e.g. group 1
compared to group 2, group 2 with group 3, etc.). On the CRT, group 1 was statistically
significantly faster than groups 2 and 4B at the 90th percentile (P=0.043 and 0.05,
respectively), and than group 4A at both 50th and 90th percentiles (P=0.032 and 0.001,
respectively). Group 1 was significantly faster than group 3 (P=0.016) with the dominant
hand and than group 4A with both dominant and non-dominant hands (P=0.00004 and
0.006, respectively) on the FTT. On the 2.4 second trial of the PASAT, group 1
performed significantly better than group 4A (P=0.004). Group 4B also performed
statistically significantly better than group 4A on this trial also (P=0.007). Additional
analyses were performed among groups 2, 3, 4A, and 4B who had KPS B status to obtain
more information regarding potential influence of pain and opioid treatment on
neuropsychological functioning. Groups 2 and 3 (non-opioid) examined against groups
4A and 4B (opioid treatment) did not reveal statistically significant differences in the
three tests. Groups 2 and 4B (no pain), however, did demonstrate significantly better
performance (P= 0.022) on the 2.0 second trial of the PASAT when compared to groups
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
3 and 4A (pain). Thus, the Sjogren et al. (2002) suggest that perhaps pain itself
deteriorates working memory more than oral opioids. The only side effect that correlated
with the tests (CRT and FTT) was drowsiness in group 4B (Sjogren et al., 2002).
Overall, all groups were statistically significantly different from group 1 in one or
more tests and group 4A, potentially the most troubled group of patients, differed most
significantly in number and severity of poorly performed tests (Sjogren et al., 2002).
Statistically significant differences between group 1 and other groups appeared on
different tests. Specifically, group 2 was slower in CRT, group 3 was slower in FTT,
group 4B was slower in CRT and group 4A performed poorer in all the tests (Sjogren et
al., 2002). It is worthy to note that no statistically significant differences existed between
groups 2 and 3 which lends itself to the suggestion that pain itself may not deteriorate
neuropsychological performance. In essence, this study did not provide evidence for any
statistically significant effects of oral opioids on neuropsychological test performance
(Sjogren et al., 2002).
Bone Marrow Transplantation
Ahles et al. (1996) investigated the impact of autologous BMT (ABMT) on the
psychological and neuropsychological functioning of patients that had either hematologic
disorders or breast cancer. A battery of neuropsychological tests was administered to 54
patients before ABMT, one to three days following bone marrow reinfusion, and at
predischarge (one to two days before discharging from the hospital).
Neuropsychologically, both groups of patients demonstrated a decline, over time, on
tasks of higher order cognitive processing. No differences were found at baseline
between patients with a history of radiation and/or intrathecal therapy and those without.
Interestingly, performance declined across the three assessment periods that were
relatively close together. With a normal sample, practice effects would be expected,
however, with this sample, none were observed. Although this research highlights the
effects of transplant treatment regimens, a lack of long-term follow up data precludes any
conclusions regarding the persistence of cognitive deficits. In addition, no measures of
quality of life, fatigue, or other affective variables were administered. (Ahles, Tope,
Furstenberg, Hann, & Mills, 1996).
Visual memory, verbal learning, and verbal short-term and long-term memory,
attention or executive functions, and speed of information processing were most affected
in a sample of BMT survivors (n = 40) who were tested neuropsychologically, on
average, three years post-treatment. Harder et al. (2002) employed a neuropsychological
test battery that assessed general intelligence and conceptual reasoning, verbal function,
memory, attention and concentration, executive functions, visuospatial and
visuoconstructive ability, psychomotor function, and speed of information processing.
Information was also collected regarding QOL (quality of life) and mood states via selfadministered questionnaires. The entire sample was subjected to a conditioning regimen
with high-dose chemotherapy and total body irradiation. Standard regression coefficients
were examined to determine the strongest predictors of the proportion of impaired tests.
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
Fatigue and global health were the main disease and treatment related predictors, while
higher educational level was the most predictive regarding demographics. Like the Ahles
et al (2002) research, this investigation lacked a pretreatment baseline assessment,
thereby precluding conclusions regarding the amount of change in cognitive functioning.
Andrykowski and colleagues (1992) were interested in the extent to which
patients’ pre-BMT treatment regimen affected cognitive functioning. The treatment
regimens that the researchers listed as potentially detrimental to patients’ cognitive
functioning included disease involvement in the central nervous system (CNS),
intrathecal chemotherapy and/or radiation to the cranium as either treatment or
prophylaxis for disease in the CNS, and intravenous high-dose ara-C. Using a sample of
55 patients with malignant diagnoses such as acute or chronic leukemia, lymphomas,
myelodysplastic syndromes, multiple myeloma, and myelofibrosis, a standardized
neuropsychologic battery was employed. The protocol of tests was designed to assess a
mixture of cognitive functioning across four domains: motor, memory, attention, and
complex attention/motor. Specifically, the grooved pegboard and finger oscillation tests
were employed to assess the motor domain; patients’ memory was tested utilizing the
Buschke selective reminding test and the Benton visual retention test; digit span and Ruff
two and seven test were chosen to measure attention; the complex attention/motor
domain was tested with the trailmaking B and digit symbol tests. A total of 11 test
indexes were compiled for each patient (based on these eight tests) and translated into zscores. An overall neuropsychologic performance score was computed for each patient
by adding the z-scores for each of the 11 test indexes available for each patient and then
dividing by the number of such indexes (Andrykowski, Schmitt, Gregg, Brady, Lamb, &
Henslee-Downey, 1992).
Analyses revealed that age was the only control variable associated with cognitive
impairment. Cranial radiation, as well as CNS disease coupled with intrathecal
chemotherapy, was positively associated with poorer test performance. Impairment in
the memory domain was significantly associated with cranial radiation, while CNS
disease/intrathecal chemotherapy combination was significantly associated with motor
impairment. At least one out of the 11 indexes were impaired in 75% of the sample and
56% of the sample was impaired (greater than 1.5 standard deviations below test norms)
on at least two out of 11 indexes. While the memory domain was most affected (more
than 33% of patients scored in the impaired range on the three tests in this domain), the
attention domain only yielded 6% of patients scoring in the impaired range (Andrykowski
et al, 1992).
In addition, the authors (Andrykowski et al., 1992) examined the extent to which
the risk factors were predictive of cognitive impairment using logistic regression. Risk
factor frequency was significantly predictive of cognitive impairment. Patients with one
risk factor were 5.8 times more likely to have cognitive impairment. The odds ratio
increased to 33.3 times more likely to have cognitive impairment in the context of two
risk factors.
In another study, BMT patients were cognitively and emotionally evaluated at
four different time periods: at pre-admission; on average, twelve days after admission; at
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
discharge (on average 29 days after admission); and at a mean of eight months following
discharge. Meyers and associates (1994) recruited 61 patients throughout a one year
period. There were 25 allogeneic transplant patients, 19 undergoing autologous
transplantation, and 17 whom had a matched unrelated donor. The Dementia Rating
Scale (DRS) was employed as the measure of cognitive functioning. This assessment
tool is comprised of five subscales, each measuring a different ability, including
attention, initiation/perseveration, construction, conceptualization, and memory. Mood
was examined via measuring anxiety and depression using the State-Trait Anxiety
Inventory (STAI) and the Zung Depression Inventory, respectively. Indices of locus of
control and social support were also obtained (Meyers, Weitzner, Byrne, Valentine,
Champlin, & Przepiorka, 1994).
Due to death, disease progression, and inability to return for follow-up, there was
a high rate of attrition in this study. Consequently, only 21 of the patients completed
testing at all time periods. It is worthy to note that the attrition rate could be indicative of
a better performance status in these 21 patients (Meyers et al., 1994).
On the DRS, 20% of patients scored in the impaired range (2 SD below the mean)
before admission. The percentage of patients impaired in the memory domain more than
doubled throughout hospitalization, increasing from 11 to 26 percent. At the eight month
follow-up, memory impairment was present in nearly 20% of patients, all of whom fell
into the normal range for memory at baseline. Within the group of 21 individuals that
completed testing at all four assessment periods, the DRS total score demonstrated
significant changes over time (P = .046). The perseveration (P<.001) and memory
(P<.001) subtests also showed significant changes over time in this group of individuals
(Meyers et al., 1994).
Significant changes over time were highlighted for state anxiety (P<.001) and
depression (P<.001). Specifically, anxiety decreased significantly between baseline and
discharge assessments (P=.006), whereas depression increased significantly during
hospitalization (P=.007). Compared with baseline assessment, anxiety was significantly
lower (P<.001) at follow-up. There was no significant difference between these two
assessments on depression scores. A significant negative correlation was noted between
anxiety at pre-admission and cognitive performance after BMT (r=.50, P<.05),
suggesting that pretransplant anxiety was associated with poorer cognitive outcomes after
BMT. Furthermore, baseline cognitive status was negatively correlated with anxiety (r =
-.62, P<.01) and depression (r = -.70, P<.01) at follow-up. Type of BMT was irrelevant
in terms of cognitive status performance.
Age was not correlated with any
neurobehavioral functioning either. A positive correlation existed between social support
and cognitive functioning (r=.72), but analysis of social support and anxiety yielded a
negative correlation (r=-.74).
The frequency and characteristics of neurologic complications on a sample of 115
leukemia patients was investigated by Antonini and colleagues (1998). This sample was
recruited consecutively over a four year period and underwent an allogeneic BMT. Total
body irradiation and chemotherapy was administered to 48 of the patients, while the
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
remaining 67 patients received chemotherapy alone.
Patients were evaluated
neurologically on a daily basis by two independent clinicians until discharge. Neurologic
complications were only considered present when both clinicians agreed on a diagnosis.
The complications were catalogued according to severity. Major complications were
defined as “…a definite clinical picture that required treatment.” Complications were
denoted as “minor” in the presence of “..time-limited symptoms not accompanied by
anatomic or functional changes nor requiring diagnostic examinations or treatment.” Out
of 115 patients, 64(56%) had complications involving the central nervous system,
peripheral nervous system, or both. Major complications were documented in 27 patients
(23%). Minor complications were found in 40 patients (35%). Major complications
within the CNS included metabolic encephalopathy, seizures, psychiatric complications,
cerebral hemorrhage, cerebral abscess, and leukemia meningitis.
Minor CNS
complications included headache and tremor. Peripheral neuropathies were another
complication. Disease type and preparatory regimen were not significantly associated
with the presence of neurologic complications. At 90 days, 16.5% of the patient sample
died. Results showed that patients with major CNS complications had only a 63%
chance of survival at day 90, significantly lower compared to an 87.5% chance in the
absence of major CNS complications.
Given that 55% of the leukemia patients in this study experienced either major or
minor complications following BMT within 90 days from transplant, and neurologic
complications directly caused death in a small percentage of patients, the authors
concluded that not only are neurologic complications common in this post-transplant
period, but they also significantly affect the fatality of transplant recipients.
A retrospective study conducted by Graus and associates (1996) also examined
the neurologic complications of leukemia patients treated with a BMT. Both autologous
and allogeneic transplant recipients were included in the study, so as to enable the
investigators to compare the frequency and type of complications between the patients.
A database was reviewed that detailed treatment variables and complications of the 425
patients included in the study.
Overall, neurologic complications occurred in 11% of patients. Type of
transplant was not significantly related to frequency of neurologic complications.
Autologous BMT was most frequently accompanied by CNS hemorrhage complications.
CNS infections and treatment-related neurologic complications were most common in
allogeneic BMT. Intracranial hemorrhage was the most common complication. Out of
11 patients with subdural hematomas, nine had autologous BMT. Other complications
included seizures, CNS infections, and peripheral neuropathies. The authors suggested
that the percentage of patients with complications was lower in this study than previous
investigations potentially because they excluded episodes that occurred at the time of
BMT or after.
Conclusion
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
As new patients will continue to develop cancer, it is essential for clinicians and
healthcare providers to recognize the neuropsychological consequences of cancer
treatment and intervene to minimize long-term effects. While efficacy of treatment
modality was most commonly considered in the past for deeming a particular treatment
appropriate, quality of life has become an increasingly important consideration. Given
the adverse effects that cognitive dysfunction can have on quality of life, the potential
likelihood of cognitive impairment should be considered when choosing a treatment
regimen. As patients are followed once cancer treatment is complete, family members
should be vigilant of subtle changes that may take place in patients’ cognitive
functioning. Cognitive impairment is often more apparent to others than to the patients
themselves and, thus, family members reports should be an integral component of
patients’ long-term following.
Studies seeking to document the deleterious effects of cancer treatments on
cognitive functioning should be systematic. Standardized neuropsychological tests that
have established reliability and validity should be implemented at various points in time,
such as baseline, during treatment, immediately following completion of treatment, and
then months later. Many tests designed to measure cognitive functioning detect gross
cognitive changes that are obvious anyway, but are not sensitive enough to highlight
subtle changes (Oxman, Schnurr, & Silberfarb, 1986). Test development is warranted in
this arena.
Over the past three decades, there has been dramatic improvement in the use of
cancer therapies to increase survival rates. The therapies often involve both increasingly
toxic agents, considerable doses of those toxic agents, and combination treatments
consisting of surgery, radiation, and chemotherapy. Now that survival rates have
improved, we must strive to selectively implement treatment regimens designed to
minimize the potential neurotoxic side effects.
© 2004 CDHS/College Relations Group BSC/Research Foundation SUNY
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