Cancer Cachexia
Possible Role for Tocilizumab, an Anti–Interleukin-6 Receptor Antibody,
Treating Cancer Cachexia JCO Feb 20, 2013:e69-e72;
published online on November 5, 2012
Saturday, August 31, 2013
Systematic Monitoring and Treatment of Physical Symptoms to Alleviate Fatigue in Patients With Advanced Cancer:
A Randomized Controlled Trial
- Pleun J. de Raaf⇓,Cora de Klerk, Reinier Timman, Jan J.V. Busschbach,
- Wendy H. Oldenmenger and Carin C.D. van der Rijt
© 2013 by American Society of Clinical Oncology+ Author Affiliations
- Corresponding author: Pleun J. de Raaf, MD, Department of Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Room G0-03, PO Box 5201, Rotterdam, the Netherlands 3008 AE; e-mail: p.deraaf@erasmusmc.nl.
Abstract
Purpose Several
guidelines on the treatment of cancer-related fatigue recommend
optimizing treatment of accompanying symptoms. However,
evidence for this recommendation from randomized
clinical trials is lacking. We investigated whether monitoring and
protocolized
treatment of physical symptoms alleviates
fatigue.
Patients and Methods
In all, 152 fatigued patients with advanced cancer were randomly
assigned to protocolized patient-tailored treatment (PPT)
of symptoms or care as usual. The PPT group had
four appointments with a nurse who assessed nine symptoms on a 0 to 10
numeric
rating scale (NRS). Patients received a
nonpharmacologic intervention for symptoms with a score ≥ 1 and a
medical intervention
for symptoms with a score ≥ 4. Fatigue
dimensions, fatigue NRS score, interference of fatigue with daily life,
symptom burden,
quality of life, anxiety, and depression were
measured at baseline and after 1, 2, and 3 months. Differences between
the groups
over time were assessed by using mixed modeling.
Results
Seventy-six
patients were randomly assigned to each study arm.
Mean age was 58 ± 10
years, 57% were female, and 65% were
given palliative chemotherapy.
We found
significant improvements over time in favor of PPT for the primary
outcome general
fatigue (P = .01), with significant group differences at month 1 (effect size, 0.26; P = .007) and month 2 (effect size, 0.35; P
= .005). Improvements in favor of PPT were also found for the following
secondary outcomes: fatigue dimensions “reduced activity”
and “reduced motivation,” fatigue NRS, symptom
burden, interference of fatigue with daily life, and anxiety (all P ≤ .03).
Conclusion In fatigued patients with advanced cancer, nurse-led monitoring and protocolized treatment of physical symptoms is effective
in alleviating fatigue.
Footnotes
-
Supported by the Erasmus Medical Center, University Medical Center, and by The Netherlands Organization for Health Research and Development.
Effects of Psycho-Oncologic Interventions on Emotional Distress and Quality of Life in Adult Patients With Cancer:
Systematic Review and Meta-Analysis
© 2013 by American Society of Clinical Oncology+ Author Affiliations
- Corresponding author: Hermann Faller, MD, PhD, Department of Medical Psychology, Medical Sociology and Rehabilitation Sciences, and Comprehensive Cancer Center Mainfranken, University of Würzburg, Klinikstr. 3, D 97070 Würzburg, Germany; e-mail: h.faller@uni-wuerzburg.de.
-
Presented in part at the 30th Annual Meeting of the German Cancer Society, Berlin, Germany, February 22-25, 2012.
Abstract
Purpose This study aimed to evaluate the effects of psycho-oncologic interventions on emotional distress and quality of life in adult
patients with cancer.
Methods Literature
databases were searched to identify randomized controlled trials that
compared a psycho-oncologic intervention
delivered face-to face with a control condition.
The main outcome measures were emotional distress, anxiety, depression,
and
quality of life. Outcomes were evaluated for
three time periods: post-treatment, ≤ 6 months, and more than 6 months.
We applied
standard meta-analytic techniques to analyze
both published and unpublished data from the retrieved studies.
Sensitivity analyses
and meta-regression were used to explore reasons
for heterogeneity.
Results We retrieved
198 studies (covering 22,238 patients) that report 218 treatment-control
comparisons. Significant small-to-medium
effects were observed for individual and group
psychotherapy and psychoeducation. These effects were sustained, in
part, in
the medium term (≤ 6 months) and long term (>
6 months). Short-term effects were evident for relaxation training.
Studies
that preselected participants according to
increased distress produced large effects at post-treatment. A moderator
effect
was found for the moderator variable “duration
of the intervention,” with longer interventions producing more sustained
effects.
Indicators of study quality were often not
reported. Small-sample bias indicative of possible publication bias was
found for
some effects, particularly with individual
psychotherapy and relaxation training.
Conclusion
Various
types of psycho-oncologic interventions are associated with significant,
small-to-medium effects on emotional distress
and quality of life.
These results should be
interpreted with caution, however, because of the low quality of
reporting in
many of the trials.
Footnotes
-
Supported in part by Grants No. 108883 and 110002 from German Cancer Aid, the German Cancer Society, and the Association of Scientific Medical Societies within the Research Program for the Development of Guidelines in Oncology.
-
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline
- Christopher R. Flowers, Jerome Seidenfeld⇓, Eric J. Bow, Clare Karten, Charise Gleason, Douglas K. Hawley, Nicole M. Kuderer,
- Amelia A. Langston, Kieren A. Marr, Kenneth V.I. Rolston and Scott D. Ramsey
+ Author Affiliations
- Corresponding author: Jerome Seidenfeld, PhD, American Society of Clinical Oncology, 2318 Mill Rd, Suite 800, Alexandria, VA 22314; e-mail: jerry.seidenfeld@asco.org.
© 2013 by American Society of Clinical OncologyAbstract
Purpose To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment
as outpatients of those with fever and neutropenia.
Methods A literature
search identified relevant studies published in English. Primary
outcomes included: development of fever and/or
infections in afebrile neutropenic outpatients
and recovery without complications and overall mortality in febrile
neutropenic
outpatients. Secondary outcomes included: in
afebrile neutropenic outpatients, infection-related mortality; in
outpatients
with fever and neutropenia, defervescence
without regimen change, time to defervescence, infectious complications,
and recurrent
fever; and in both groups, hospital admissions,
duration, and adverse effects of antimicrobials. An Expert Panel
developed
guidelines based on extracted data and informal
consensus.
Results Forty-seven articles from 43 studies met selection criteria.
Recommendations
Antibacterial and antifungal prophylaxis are only recommended for
patients expected to have < 100 neutrophils/μL for > 7
days, unless other factors increase risks for
complications or mortality to similar levels. Inpatient treatment is
standard
to manage febrile neutropenic episodes, although
carefully selected patients may be managed as outpatients after
systematic
assessment beginning with a validated risk index
(eg, Multinational Association for Supportive Care in Cancer [MASCC]
score
or Talcott's rules).
Patients with MASCC scores ≥
21 or in Talcott group 4, and without other risk factors, can be
managed
safely as outpatients.
Febrile neutropenic
patients should receive initial doses of empirical antibacterial therapy
within
an hour of triage and should either be monitored
for at least 4 hours to determine suitability for outpatient management
or
be admitted to the hospital.
An oral
fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if
penicillin allergic)
is recommended as empiric therapy, unless
fluoroquinolone prophylaxis was used before fever developed.
Footnotes
-
See accompanying article in J Oncol Pract doi: 10.1200/JOP.2012.000815
-
American Society of Clinical Oncology Clinical Practice Guideline Committee approved: September 5, 2012.
-
Editor's note: This represents a brief summary overview of the complete American Society of Clinical Oncology Clinical Practice Guideline and provides the recommendations with brief discussions of the relevant literature for each. The complete guideline, which includes comprehensive discussions of the literature, methodology information, and all cited references, plus Data Supplements with evidence tables the committee used to formulate these recommendations and a list of all abbreviations used in the text, tables, and figures are available at www.asco.org/guidelines/outpatientfn.
-
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this articl
Why Is Spiritual Care Infrequent at the End of Life?
Spiritual Care Perceptions Among Patients, Nurses, and Physicians and the Role of Training
© 2012 by American Society of Clinical Oncology
- Michael J. Balboni, Adam Sullivan, Adaugo Amobi, Andrea C. Phelps, Daniel P. Gorman,
- Angelika Zollfrank, John R. Peteet, Holly G. Prigerson, Tyler J. VanderWeele and
- Tracy A. Balboni⇓
+ Author Affiliations
- Corresponding author: Tracy A. Balboni, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute, Dana 1101, 450 Brookline Ave, Boston, MA 02115; e-mail: tbalboni@lroc.harvard.edu.
Abstract
Purpose To determine factors contributing to the infrequent provision of spiritual care (SC) by nurses and physicians caring for
patients at the end of life (EOL).
Patients and Methods
This is a survey-based, multisite study conducted from March 2006
through January 2009. All eligible patients with advanced
cancer receiving palliative radiation therapy
and oncology physician and nurses at four Boston academic centers were
approached
for study participation; 75 patients (response
rate = 73%) and 339 nurses and physicians (response rate = 63%)
participated.
The survey assessed practical and operational
dimensions of SC, including eight SC examples. Outcomes assessed five
factors
hypothesized to contribute to SC infrequency.
Results
-Most patients with advanced cancer had never received any form of spiritual care from their oncology nurses or physicians
(87% and 94%, respectively; P for difference = .043).
-Majorities of patients indicated that SC is an important component of cancer care from nurses and
physicians (86% and 87%, respectively; P = .1).
- Most nurses and physicians thought that SC should at least occasionally be provided (87% and 80%, respectively; P = .16).
- Majorities of patients, nurses, and physicians endorsed the appropriateness of eight examples of SC (averages, 78%,
93%, and 87%, respectively; P = .01).
In adjusted analyses, the strongest predictor of SC provision by nurses
and physicians was reception of SC training
(odds ratio [OR] = 11.20, 95% CI, 1.24 to 101;
and OR = 7.22, 95% CI, 1.91 to 27.30, respectively).
Most nurses and
physicians
had not received SC training (88% and 86%,
respectively; P = .83).
Conclusion Patients,
nurses, and physicians view SC as an important, appropriate, and
beneficial component of EOL care.
SC infrequency
may be primarily due to lack of training,
suggesting that SC training is critical to meeting national EOL care
guidelines.
Footnotes
-
Supported in part by an American Society of Clinical Oncology Young Investigator Award and Career Development Award (T.A.B.), a Templeton Foundation Award (T.J.V.), and a University of Chicago Program in Religion and Medicine Faculty Scholars Award (M.J.B.).
Treating Cancer-Related Fatigue: The Search for Interventions That Target Those Most in Need
+ Author Affiliations
- Corresponding author: Julienne E. Bower, PhD, Psychiatry and Behavioral Sciences, University of California, Los Angeles, 300 UCLA Medical Plaza, Rm 3306, Box 987076, Los Angeles, CA 90095-7076; e-mail: jbower@ucla.edu.
© 2012 by American Society of Clinical Oncology
Fatigue is one of the most common and distressing adverse effects of cancer treatment. Up to 99% of patients experience some
level of fatigue during treatment with radiation, chemotherapy, and biologic therapies.1 Fatigue typically resolves in the year after treatment completion, but approximately 30% of patients experience more persistent
fatigue that may endure for 10 years or more.2 Fatigue is associated with decrements in all aspects of quality of life, and many patients report that they are unable to
lead a normal life because of their fatigue.3 Fatigue has also been associated with shorter recurrence-free and overall survival in patients with cancer.4 Given its prevalence and impact, fatigue is an important target for identification and treatment.
What are effective treatments for
cancer-related fatigue (CRF)? A diverse range of treatment strategies
has been evaluated,
including pharmacologic and nonpharmacologic
approaches. Indeed, a recent review of the literature indicated that
more than
170 intervention studies that have included fatigue as
a primary or secondary outcome have been conducted in patients with
cancer.5
At this point, exercise has the strongest empirical support, with
several recent meta-analyses concluding that physical activity
has a moderate beneficial effect on CRF (effect sizes
in the range of −0.30 to −0.38).6–11 There is also some support for psychological interventions, with meta-analyses showing a small to moderate beneficial effect
(effect sizes in the range of −0.10 to −0.30).10,12,13 The more modest effect sizes that were seen in the psychological studies may be a result of the fact that many did not include
a CRF-related aim or hypothesis13; the few trials that explicitly focused on fatigue, providing education about fatigue and instruction in self-care, coping
techniques, and activity management, were more effective than nonspecific interventions.14 There is more limited support for pharmacologic approaches to treating fatigue.15 Although some trials have found beneficial effects for psychostimulants,16 results are quite mixed, and a recent phase III, randomized, double-blind, placebo-controlled trial found no benefit for
methylphenidate versus a placebo in treating CRF.17
On the basis of this literature, it would be
reasonable to recommend physical activity to patients during and after
cancer
treatment (preferably under the supervision of a
rehabilitation professional) and to provide them with targeted education
about CRF. However, we do not know whether these
strategies will be helpful for patients with more severe or persistent
fatigue,
given that very few intervention studies have
specifically targeted these patients. This is particularly true for
nonpharmacologic
treatments; although trials of such treatments are
often described as interventions for cancer-related fatigue, the
presence
of fatigue is not a criterion for trial entry. Thus,
it is unclear whether the interventions examined in these studies will
be feasible and effective for those most in need. For
example, fatigue was one of the primary barriers to adherence in an
exercise trial that was conducted with survivors of
prostate cancer.18
Only a handful of randomized controlled
trials have targeted patients with moderate to severe fatigue and used
presence of
fatigue as a criterion for study entry. Results from
these studies provide preliminary evidence that psychological (cognitive
behavioral therapy19,20) and integrative medicine approaches (yoga, biofield therapy, mindfulness-based therapy21–24)
may have beneficial effects on persistent post-treatment fatigue, but
conclusions are limited by small sample sizes in several
trials. There is a critical need for larger-scale
studies that target patients with moderate to severe fatigue,
particularly
fatigue that does not remit after treatment
completion.
The article by Molassiotis et al25
that accompanies this editorial addresses this gap in the literature in
its investigation of acupuncture for post-treatment
fatigue in survivors of breast cancer. This was a
large, multicenter trial that focused specifically on patients with
moderate
to severe fatigue. The authors enrolled 302 women who
had been diagnosed with stage I to IIIA breast cancer, completed
chemotherapy,
and scored 5 or greater on a single-item 10-point
fatigue scale. The mean duration of fatigue was 15 to 18 months, with a
maximum duration of 69 months, indicating the chronic
nature of the symptom in this sample. Results showed that 6 weeks of
acupuncture, provided for 20 minutes per week, led to
significant improvements in general fatigue as assessed by the
Multidimensional
Fatigue Inventory. The intervention also led to
significant improvements in anxiety, depression, and quality of life.
Patients
in the control group received a detailed information
booklet about coping with fatigue, which was likely comparable or
superior
to what typically would be provided in the
post-treatment setting.
Findings from the study by Molassiotis et al,25 together with earlier trials,24,26
provide compelling evidence that acupuncture may be effective for
reducing CRF, at least in the short term. It will be important
to determine how enduring the effects of this
treatment are, given that only the immediate post-treatment effects were
described
in this report, and to identify the frequency and
duration of acupuncture that are necessary for improvement. In addition,
it was unclear whether fatigue levels in the
acupuncture group decreased to pretreatment levels; if not, more
intensive treatment
may be indicated. Other treatments that have been
developed for persistent CRF are more time consuming (eg, 6 months for
cognitive
behavioral therapy,19 3 months for yoga21), but these approaches also teach patients techniques that can be used after the intervention is completed, and both led
to sustained improvements in fatigue.20,21
Future trials should also compare acupuncture (and other promising
treatments) with an active control arm as well as a no-treatment
control arm to better evaluate treatment-specific
effects.
Intervention trials with fatigued patients are challenging to conduct—as noted by Molassiotis et al,25
they had to screen “many hundreds” of patients to accrue their desired
sample size—but they are vital for identifying interventions
that will work for those most in need. The study by
Molassiotis et al represents an important advance in the literature and
will hopefully motivate other investigators to
undertake conceptually driven, methodologically rigorous trials that
target
patients with moderate to severe CRF. There is also a
critical need for basic research on mechanisms underlying fatigue onset
and persistence that will guide development of
targeted therapies. In addition, determination of risk factors for
persistent
fatigue may allow us to intervene earlier with the
most susceptible patients.
For now, what advice can we offer patients
with persistent fatigue?
- Acupuncture may be helpful, particularly for
women with
nonmetastatic breast cancer, although patients should
be urged to follow the specific protocol that was found to be safe and
effective in the study by Molassiotis et al.25
-In our trial of Iyengar yoga for persistent CRF, a number of our participants had attempted other types of yoga with no relief21;
similarly, not all types of acupuncture are likely to be effective for
reducing CRF.
As more intervention studies specifically
target patients with fatigue, the range of empirically
supported treatment options for this group should expand, ultimately
leading to enhanced quality of life for the growing
population of survivors of cancer.
AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
REFERENCES
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