Other Medical Disorders

Section

15

Charles F.P. George

123 Sleep and Fatigue in Cancer Patients
124 Fibromyalgia and Chronic Fatigue
125

Syndromes
Endocrine Disorders

126 Pain and Sleep

127 Gastrointestinal Disorders
128 Sleep in Chronic Kidney Disease

Sleep and Fatigue in Cancer Patients

Sonia Ancoli-Israel and Jose Savard
of life, to their tolerance to
treatment,
and
to
the
development of mood disorders,
Fatigue is a major complaint in patients with cancerbefore treatment, while undergoing particularly clinical depression.
chemotherapy or radiation therapy, and after the completion of therapy. The relation- Disrup-tions in circadian rhythms
ship, if any, between fatigue and the quality or quantity of sleep or between fatigue and themselves affect sleep quality
the sleepwake circadian rhythm cycle is unknown. One hypothesis is that some of the and
disrupt
many
other
cancer-related fatigue may be related to disturbed sleep or to dis-turbed sleepwake physiologic
mechanisms
that
rhythms. Different dimensions of fatigue (e.g., physical, attentional/cognitive, pertain to fatigue. Lack of
emotional/affective) are likely to be associated in some way with disrupted sleep and entrainment to the daynight
desynchronized sleepwake rhythms. In cancer patients, as in other medically ill cycle and not keeping regular
patients, disturbed sleep may be important not only to the expression of fatigue but to hours can lead to feelings of
the patients quality
grogginess, similar to the feelings
of jet lag. The degree of sleep

Abstract

was no difference in
sleep
complaints
between the cancer
and patients
Patients with cancer complain of fatigue before patients
with
medical
treatment, during chemotherapy or radiation therapy, and
conditions other than
1
after the completion of therapy. These patients also
cancer.5 Almost half
complain of sleep disruption.2 Both fatigue and poorof the group had a
sleep probably contribute to decreased quality of life. 3poor sleep efficiency
There is a growing body of literature on the relationship
between fatigue and the quality or quantity of sleep. This
chapter will review the evidence on cancer-related sleep
disruption and fatigue and their treatment, as well as the
possible contribution of poor sleep and desynchronized
circadian rhythms to cancer-related fatigue.

EPIDEMIOLOGY
Sleep Disruption
The prevalence of sleep complaints in cancer patients has
been studied primarily in cross-sectional studies using
con-venience samples with heterogeneous definitions and
mea-sures of sleep disturbances. In a large questionnaire
study of over 900 patients with different types of cancer,
fatigue (44%), leg restlessness (41%), insomnia (31%),
and exces-sive sleepiness (28%) were the most prevalent
complaints.4 Another survey showed that 61% of the
cancer patients had significant sleep deficits, but there

1416

Large-scale epidemiologic and longitudinal studies are needed to better

depict sleep difficulties in cancer patients, characterize the natural course
of sleep disturbances throughout cancer care in terms of incidence and
remis-sion, and enable comparison across cancer sites and other cancer
characteristics. One ongoing longitudinal study conducted among 998

Chapter

123

disrup-tion found in patients with

cancer is not trivial. Objectively
recorded sleep and biological
rhythms have not been well
investigated in patients with
cancer, but because it appears
that most may in fact not be
getting a good nights sleep, the
goal of future research should be
to better characterize the sleep
disruption and to find new
treatment
approaches
to
improve sleep in this population.

patients.
These
studies found prevalence
rates
of
(defined
as
theinsomnia symptoms
percentage of timeof 48% in breast
spent asleep) belowcancer survivors and
85%. Those patients32% in prostate
receiving radiationcancer survivors. 8,9
insomnia
or
chemotherapyWith
tended to have moresyndrome defined as
sleep disturbancessleep-onset latency or
than
those
notwake after sleep
greater than 30
receiving treatment.onset
minutes, at least 3
In addition, sleepnights per week,
problems predictedassociated with a
deficits in quality ofsleep
efficiency
life.
lower than 85% and
Prevalence ratessignificant daytime
or
of
insomniaimpairments
symptoms
havemarked distress, the
were
ranged from 30% toprevalences
and
18%,
50%.6,7 Only two19%
8,9
In
studies
haverespectively.
attempted
to95% of the cases, the
distinguish betweeninsomnia syndrome
having subclinicalwas chronic (i.e.,
and clinical levels ofduration 6 months).
insomnia in cancer Not
much
is

known about how

sleep
disturbances
vary as a function of
cancer sites. In one
study, the prevalence
of sleep disturbances
was greater in breast
cancer patients,4 but
in another study the
prevalence
was
greater in ovarian
cancer
patients.10
Moreover, as most
studies have been
conducted
several
months or even years
after patients completed their cancer
treatment, the extent
to which insom-nia
symptoms
are
exacerbated
by
cancer treatments is
unclear.

patients with mixed cancer sites has found that the overall prevalence
rates of the insomnia syndrome and of insomnia symptoms (including
those with an insomnia syndrome) at baseline (T1i.e., before or right
after the surgery) were 27.2% and 56.4%, and they decreased to 21.3%
and 39.5% 2 months later (T2), respectively.11 The prevalence rates of
insomnia symptoms were highest in patients with breast cancer and
gyneco-logic cancer and lowest in patients treated for prostate cancer. The

incidence of insomnia from T1 to T2 was 19%, and the remission rate

was 32.0%. Together, these data indicate that insomnia is already
prevalent at the time of cancer diagnosis and surgery. Future analyses will
deter-mine the course of insomnia symptoms as adjuvant treat-ments
(e.g., chemotherapy, radiation therapy, hormone therapy) are introduced.
Sleep disturbances are also very common in patients with advanced
cancer. In a study of patients with metastatic breast cancer, 63% reported
sleeping difficulties. Diffi-culty falling asleep was associated with both
depression and pain, whereas increased awakening during the night was
associated just with depression.12 In another study of 100 palliative care
patients attending a pain and symptom control clinic, 72% reported sleep
disturbances (63% reported difficulty staying asleep; 40% reported
difficulty falling asleep).13 Difficulty falling asleep was mostly associated with fatigue and anxiety, whereas early awakening was more
strongly associated with fatigue. In a prospective study, 25.9% of
terminally ill cancer patients reported sleep disturbances at admission to a
palliative care unit.14 Another study found that patients with advanced
lung cancer reported poorer sleep and more daytime sleepiness than
healthy controls, and that sleep disturbances of lung cancer patients were
characterized by breathing difficul-ties, cough, nocturia, and frequent
awakenings, all of which may be suggestive of sleep-disordered
breathing.15 Finally, a study suggested that poor sleep quality and use of
sleep medications were, along with hopelessness and depression, the best
predictors of desire for hastened death in 102 terminally ill patients
attending a palliative care unit,16 thus emphasizing the importance of
offering appropriate sleep management to these patients.
A few objective studies of cancer patients, using either
polysomnography or actigraphy, have been conducted to characterize the
sleep disturbances. When the sleep of patients with breast or lung cancer,
patients with insomnia, and volunteers with no sleep problems were
compared, the insomnia patients had the shortest total sleep time on polysomnography, but the lung cancer patients had the longest sleep onset
latency, the lowest sleep efficiency, and the greatest wake time during the
night.17 There were no dif-ferences in stress levels or emotional state
between the cancer patients and the volunteers. There also was no difference in reported total sleep time between the cancer patients and the
volunteers. Interestingly, unlike the insomnia patients, the cancer patients
did not underesti-

1418 PARTII / Section 15 Other Medical Disorders

PATHOGENESIS
Pathogenesis of Sleep Disruption
Patients with cancer may complain of insomnia, hyper-somnia, or both,
but the pathogenesis of this sleep disrup-tion can be quite varied.
Chemotherapy, radiation therapy, and hormone therapy may all contribute
to the problem, but studies looking at their different effects on sleep patterns are lacking. In addition, commonly administered analgesics such as
opioids, and antiemetic medications such as corticosteroids, are also
known to disrupt sleep.31 The estrogen deficiency induced by
chemotherapy and hormone therapy, the abrupt cessation of hormone
replace-ment therapy at cancer diagnosis, or an ovary removal may each
trigger or exacerbate preexisting hot flashes. A study using objective
measurements of both sleep and hot flashes in breast cancer survivors
showed that nocturnal hot flashes were associated with more wake time

CHAPTER 123 Sleep and Fatigue in Cancer Patients 1417

mate total sleep time or overestimate wake time during the night.
In the same study, although there was no difference in the amount of
sleep-disordered breathing, the cancer patients had a higher prevalence of
periodic limb move-ments in sleep (PLMS) than insomnia patients or
healthy volunteers.17 However, more recently, in two small-scale studies
(17 and 33 patients), an elevated prevalence of obstructive sleep apnea
(OSA), ranging from 12% to 91.7%, was found in patients with head and
neck cancer.18 Prospective studies are warranted to investigate to what
extent OSA is caused by the cancer itself or by the cancer treatment.
Sleep-disordered breathing also appears to be frequent in patients with
brain tumors, with tumor removal resulting in a significant decrease in the
apneahypopnea index.19 An ongoing research study indicates that the
prev-alence of OSA in women with breast cancer who have completed
chemotherapy was 48%, and the prevalence of PLMS was 36%.20 These
high prevalence rates of PLMS and OSA may help explain some of the
sleep disturbance found in this population.
Actigraphy, a noninvasive, continuous, ambulatory measure of
circadian restactivity rhythms, has also been used to characterize the
sleep and rhythms of patients with cancer.21-24 Studies comparing cancer
patients to healthy controls have consistently shown less contrast between
daytime and nighttime activity in cancer patients, a pattern indicative of
circadian disruption.21,25 In a study of 85 women with breast cancer, 72hour actigraphy before the start of chemotherapy demonstrated a mean
total sleep time of 6 hours, with only 76% of the night spent asleep. On
average, the women napped for about 1 hour a day.23
Fatigue
Fatigue is one of the most frequent and disturbing com-plaints of patients
with cancer3,26: more than 75% of patients who undergo chemotherapy or
radiation therapy report feeling weak and tired. Cancer-related fatigue has
been defined as a persistent, subjective sense of tiredness related to
cancer and cancer treatment that interferes with usual functioning. 27 It is
believed to be distinct from general fatigue, as it is unrelated to exertion
level and is not relieved by rest or sleep. It has been reported that 76% of
patients receiving chemotherapy report fatigue at least a few days each
month,28 interfering with daily life, reduc-ing quality of life, 3,29 and being
one of the key reasons for discontinuing treatment.
An increasing number of studies in the past few years have followed
cancer patients over time. Overall, these studies suggest that fatigue is
highly prevalent before as well as during and after treatment. 26,29 In one
study, 66% of the women reported at least some fatigue before treat-ment
and 84% reported fatigue during treatment.23 Addi-tionally, the
percentage of women reporting extreme fatigue doubled from
approximately 5% before treatment, to approximately 10% during
treatment. Several studies have suggested that fatigue can continue for
months, and even years, after the completion of therapy. A recent systematic review of the literature identified 10 longitudinal studies on
cancer-related fatigue and concluded that can-cer-related fatigue may
persist for up to 5 years after com-pletion of adjuvant treatments.30
and more stage changes to lighter sleep.32
The amount of insomnia in cancer patients can be as high as the
amount found in depressed patients, so clini-cians should not overlook the
possibility that poor sleep in cancer patients may indicate some
psychological distress. However, there is evidence that, although
insomnia and psychological distress are interrelated, there are still a significant proportion of patients who have only insomnia. In one sample of
newly diagnosed breast cancer patients, insomnia was the most frequent
symptom, reported by 88% of the patients, and was correlated with high
levels of distress and anxiety.33 However, contrary to the belief that
disturbed sleep before treatment is attributable to the increased stress and
anxiety resulting from a recent diag-nosis of a life-threatening illness,
insomnia and fatigue were rated high even in those patients who rated
them-selves low on anxiety. Similarly, another study revealed that 46% of
prostate cancer survivors with an insomnia syndrome did not have
clinical levels of anxiety or depres-sive symptoms.9

Pain has often been thought to be the cause of sleep disruption, not
only in patients with cancer but also in patients with a multitude of other
medical conditions.2 It is not yet known whether the pain contributes to
poor sleep or whether the pain medications contribute to poor sleep, or
both. One hypothesis is that pain may be the initial cause of the frequent
awakenings, but psychological distress prevents the patient from falling
back to sleep.34 A second hypothesis is that while sleep leads to recovery
and repair of tissue and may offer a temporary cessation of the
psychological awareness of pain, poor sleep leads to difficulty managing
pain.35 In this way, a cycle of pain and poor sleep may become selfperpetuating. In a study examining the relationship between pain and
sleep disrup-tion, patients with breast cancer, lung cancer, insomnia (with
no cancer) and normal controls were questioned. Although those with
breast cancer reported pain before bedtime, neither their poor sleep nor
that of the patients with lung cancer was associated with reports of pain. 17
Another study conducted in patients with advanced cancer showed
significant correlations between pain and poor sleep quality.36 Moreover,
those patients with poor quality of life had the most disturbed sleep and
the highest levels of pain.

series of studies.41 Women with breast cancer who were undergoing

adjuvant chemotherapy reported more fatigue during treatment, and less
fatigue at chemotherapy cycle midpoints, in a roller coaster pattern.
Activity levels were negatively correlated with reports of fatigue (i.e.,
those with more fatigue showed less activity). Activity levels were
reduced during the three treatment sessions compared with the cycle
midpoints, thus showing the reverse roller-coaster pattern, with inversely
changing fatigue scores. Patients tended to have more nighttime

Physiological factors
e.g., pain
anemia

Psychological factors
e.g., depression
anxiety

Fatigue

Social/cultural factors
e.g., education
socioeconomic status

Chronobiological factors
e.g., sleep
circadian rhythms

Figure 123-1 Diagrammatic representation of possible factors affecting fatigue.

(Reprinted with permission from Ancoli-Israel S, Moore P, Jones V. The relationship
between fatigue and sleep in cancer patients: a review. Eur J Cancer Care
2001;10[4]:245-255.)

Pathogenesis of Fatigue
Fatigue is believed to be caused by multiple factors, includ-ing physical
(e.g., cachexia, weight loss, and biochemical, hematologic, and endocrine
abnormalities) and psycho-logical (e.g., depression) and social factors
(Fig. 123-1). Anemia and other biochemical abnormalities are found in
cancer patients and cause fatigue, although hemoglobin levels are only
moderately related to fatigue and quality of life. One study examining the
incremental effect of increas-ing hemoglobin on quality of life found that
improving the anemia improved quality of life only to a point, beyond
which there was no further improvement.37 Alternative possible
physiologic mechanisms include inflammation (e.g., increased
proinflammatory cytokines), serotonin dys-regulation, hypothalamicpituitary-adrenal axis dysfunc-tion (e.g., altered cortisol response), and
altered muscle metabolism.38 Among these potential mechanisms, inflammation is probably the one currently receiving the most attention and is
believed to be a common pathway through which cancer and its treatment
would lead to a variety of behavioral consequences, including improved
fatigue and decreased sleep disturbances.38
Several studies have found significant relationships between reports of
fatigue and depression,26 but it is unclear to what extent these are
etiologically related. Indeed, depression is far less common than fatigue
in cancer patients, which suggests that fatigue often occurs independently.
Moreover, it has been shown that cancer-related fatigue is different from
fatigue experienced by patients with depression.
In addition, there is evidence that sleep disturbance is a significant
predictor of fatigue.39 Studies on symptom clus-ters have revealed that
sleep and fatigue are often part of a cluster of three or more symptoms. 40
Moreover, most cross-sectional and prospective studies found a strong
correlation between self-reported sleep complaints and fatigue.
Evidence on the relationship between circadian rhythms and subjective
ratings of fatigue have been mixed, with most studies finding a significant
relationship.24,41 Daytime inactivity and nighttime restlessness were
associated with higher subjective ratings of cancer-related fatigue in one
restlessness at treatment times compared with cycle midpoints when
higher activity during the day prevailed and there were fewer nighttime
awakenings.41,42 Others24 found that self-reported fatigue was
significantly associated with an actigraphy measure of sleepwake pattern
stability (i.e., similarity versus dissimilarity of rest and activity patterns
across time, a surrogate measure of circadian rhythm), but not with total
sleep time. Moreover, changes in fatigue from the second to the fourth
on-study chemotherapy cycles were significantly associated with changes
in the consistency of the sleepwake pattern. On the other hand, a study
of breast cancer patients before chemotherapy23 found no significant

relationship between any of the rhythm variables or objective sleep

variables assessed using a 72-hour actigraphy recording, and subjective
reports of fatigue. Another study conducted in breast cancer patients
before chemotherapy found that most actigraphy measures of sleepwake,
activityrest, and circadian rhythms derived from a 48-hour recording
were not significantly associated with fatigue. 22 Together, these studies
suggest that fatigue becomes a significant correlate of circadian rhythms
only after chemotherapy has been initiated in breast cancer patients.
However, longitudinal studies are needed to verify the extent to which the
relationship between circa-dian rhythms and fatigue varies as a function
of cancer treatments. Overall, it seems clear that more research is needed
to understand the pathogenesis of cancer-related fatigue.

TREATMENT
The complaints of sleep disturbances and fatigue in patients with cancer
are often overlooked in clinical practice and, when a treatment is initiated,
it is often a pharmacologic one (e.g., sedative-hypnotics for insomnia,
psychostimu-lants for fatigue). While pharmacologic therapy may be
appropriate at times, there is accumulating evidence sup-porting the
efficacy of alternative treatments including psychological treatments,
activity-based interventions, and bright-light therapy.
Sleep
PHARMACOTHERAPY
Hypnotic medications, particularly benzodiazepines, are by far the most
commonly prescribed treatment for sleep disturbances in cancer patients. 7
In 2005, the National Institutes of Health (NIH) State of the Science
Confer-ence on Insomnia concluded that the newer, shorter acting
nonbenzodiazepines were safer and more effective than the older, longeracting benzodiazepines for the treatment of insomnia. 43 More recently,
newer agents, such as a mela-tonin receptor agonist, have also been
approved by the

1420 PARTII / Section 15 Other Medical Disorders

intervention effects. Moreover, no study has yet investi-gated the

potentially superior effect of an approach com-bining psychological and
exercise-based interventions.
Not much is known about the possible mechanisms of
nonpharmacologic interventions for cancer-related fatigue. Biological,
environmental, behavioral, and cognitive factors are all potential
candidates.50 For example, an exer-cise program may be beneficial for a
variety of reasons, including the resynchronization of the restactivity
rhythms. A second benefit of outdoor exercises would be the increased
exposure to bright light, which may promote greater daytime alertness.
Patients who report more fatigue tend to be exposed to less light. 51
Although the causality of fatigue and light exposure in breast cancer

CHAPTER 123 Sleep and Fatigue in Cancer Patients 1419

U.S. Food and Drug Administration for the treatment of insomnia.

Although the efficacy of such medications is well established for primary
insomnia, its usefulness has yet to be investigated in patients with
comorbid cancer and insomnia.

BEHAVIORAL THERAPY
The NIH State-of-the-Science Conference on Insomnia also concluded
that cognitive-behavioral therapy (CBT) is the most effective treatment
for primary insomnia.43 There is now also accumulating evidence
supporting its efficacy for insomnia in cancer survivors. 44,45 Overall,
these studies have been quite consistent in demonstrating that CBT
(combining stimulus control, sleep restriction, cognitive restructuring,
and sleep hygiene) results in increased sleep efficiency and reduced total
wake time, decreased psycho-logical distress, and improved general
quality of life. One study also showed changes in immune functioning 46
associ-ated with CBT for insomnia, but the clinical relevance of these
changes in terms of cancer prognosis or other health outcomes is
unknown. Although replication is needed, it appears that the effects of
CBT in improving sleep would be mediated by both nonspecific (i.e.,
treatment expectan-cies) and specific (i.e., reduced maladaptive sleep
habits and dysfunctional beliefs) factors.47
Some evidence from uncontrolled studies suggests that mindfulnessbased stress reduction interventions in cancer patients result in improved
daily sleep quality.48 However, as none of these studies selected patients
on the basis of a minimal insomnia severity, it is unclear whether this
inter-vention is potent enough to treat syndromal or chronic insomnia.
Fatigue
Numerous medications have been investigated for the treatment of
cancer-related fatigue, including hematopoi-etics (e.g., epoetin alfa,
darbepoetin alfa), psychostimulants (methylphenidate), antidepressants
(e.g., bupropion, par-oxetine), corticosteroids (e.g., methylprednisolone,
pred-nisone), L-carnitine, and modafinil. A recent literature review
concluded that hematopoietics are effective in reducing fatigue in patients
with anemia.49 Promising results have been obtained in open-label
prospective studies investigating the efficacy of other medication classes,
in particular psychostimulants and modafinil. However, data from
placebo-controlled trials, which would allow counterbalancing beneficial
and adverse effects, are warranted, as many of these drugs have
significant side effects.49
Several nonpharmacologic interventions for fatigue have been assessed
in cancer patients. A recent review of the literature identified a total of 41
publications, 24 assess-ing the efficacy of various psychological
interventions (e.g., cognitive-behavioral therapy) and 17 reporting on the
effi-cacy of activity-based interventions. 50 Overall, the effect size
obtained was of a small magnitude across all types of intervention and
outcome measures (e.g., fatigue, vigor). When types of intervention were
compared, a greater effect size was found for psychological interventions
than for activity-based interventions. It is noteworthy, however, that none
of these studies used heightened levels of fatigue as an inclusion criterion,
thus limiting the power to detect
patients is not confirmed, there may be a negative feedback loop such that
less light exposure desynchronizes patients circadian rhythms, which
then causes or deteriorates to fatigue, and fatigue further leads to less
light exposure.51

DIFFERENTIAL DIAGNOSIS: IS IT
SLEEPINESS, FATIGUE, OR SOMETHING
ELSE?
The clinician needs to determine the cause of a patients symptoms,
recognizing that the words used by the patient to describe the symptoms
may be vague. Is the symptom related to sleepiness (the patient may
describe unintended episodes of falling asleep in the daytime or have an
elevated Epworth Sleepiness Scale score), or to fatigue (complaints of
muscular weakness, or lack of energy but not weakness)? Patients may

also have symptoms attributable to specific effects of cancer or its

treatment. When the patient has complaints in one or more of these
realms, they may become very difficult to manage.
Sleepiness or Insomnia
When daytime sleepiness can be attributed to a specific sleep disorder,
treatment should target that sleep disorder. If a patient has restless legs
syndrome, the clinician should make sure that the patient does not have
iron deficiency, which commonly occurs in patients with gastrointestinal
carcinomas. If the patient has developed movement disor-ders secondary
to a chemotherapeutic agent, then a trial of a dopaminergic agent should
be initiated. If a patient has developed obstructive sleep apneafor
example, sec-ondary to enlarged lymph nodes in the pharynx, as might
occur with lymphoma or with nasopharyngeal carcinoma then
continuous positive airway pressure treatment as well as specific
treatment directed at these areas should be initi-ated. If the patient has
developed clinical depression along with insomnia, then concurrent
therapy for the mood dis-order as well as for the insomnia should be
initiated.
Fatigue
As described earlier, fatigue, weakness, and loss of energy are all
hallmarks of cancer. Although the pathophysiology is still poorly
understood, the clinician should try to deter-mine if the fatigue is caused
in part by a correctable factor such as electrolyte imbalance (this might
occur in a patient on chemotherapy with severe nausea or vomiting), an
underlying infection, or an undiagnosed metabolic disor-der such as
thyroid disease or diabetes mellitus. The latter

may develop as a result of some types of therapy, such as large doses of

corticosteroids. The fatigue might also be exacerbated by poor sleep, in
which case treating the insomnia might result in improvements in the
fatigue.
Direct Effect of Cancer
If the cancer is causing pain that is disturbing sleep, the pain needs to be
treated concurrently with the insomnia. Hypoxemia caused by spread of
cancer to the lung, or the development of lung fibrosis in response to
chemotherapy or radiation therapy, may require treatment, as patients
with hypoxemia are known to have disturbed sleep.

PITFALLS AND CONTROVERSIES

Although the numbers of research studies in the past few years have
increased, there is still much that remains unknown about the cause,
consequences, and cures of sleeping difficulties and fatigue in patients
with cancer. In particular, more longitudinal studies are needed to characterize the natural course of sleep complaints, circadian rhythms
impairments, and fatigue during the cancer trajec-tory, and to better
understand how these disturbances are interrelated. Areas for future
research also include a better characterization of those disorders across
cancer sites. More research is also warranted on patients with advanced
cancer, including clinical studies investigating the efficacy of
nonpharmacologic interventions for sleep disturbances and fatigue, as it is
unclear whether the same treatment modalities can be offered to these
patients. Finally, mecha-nisms through which these interventions are
effective also deserve investigation.

Fatigue and sleep disturbances are among the most common and
most distressing complaints of patients with cancer. When left
untreated, these symptoms can significantly impair patients
quality of life. Clini-cians should screen more routinely for these
distur-bances
and
administer
evidence-based
treatment
strategies to help patients coping with them.

Acknowledgements
Supported by: NCI CA112035, NIA AG08415, Moores UCSD Cancer
Center, the Research Service of the Veter-ans Affairs San Diego
Healthcare System, the Canadian Institutes of Health Research, the
Canadian Breast Cancer Research Alliance, and the Fonds de la
recherche en sant du Qubec.
This chapter is dedicated to the memory of Dr. J. Christian Gillin,
dear friend and colleague, who died of cancer. He was fatigued but he
never let it get to him. He was an inspiration and a role model to us
all.
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