Saturday, August 31, 2013

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

Systematic Monitoring and Treatment of Physical Symptoms to Alleviate Fatigue in Patients With Advanced Cancer: 

A Randomized Controlled Trial

  1. Wendy H. Oldenmenger and Carin C.D. van der Rijt
  1. Pleun J. de Raaf, Wendy H. Oldenmenger, and Carin C.D. van der Rijt, Daniel den Hoed Cancer Center; Pleun J. de Raaf, Cora de Klerk, Reinier Timman, and Jan J.V. Busschbach, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  1. 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:


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. 

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.


  • 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

  1. Roland Küffner
  1. Hermann Faller, Michael Schuler, Matthias Richard, and Roland Küffner, University of Würzburg, Würzburg; and Ulrike Heckl and Joachim Weis, Tumor Biology Center, University of Freiburg, Freiburg, Germany.
  1. 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:
  1. Presented in part at the 30th Annual Meeting of the German Cancer Society, Berlin, Germany, February 22-25, 2012.


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.
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.


  • 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

  1. Amelia A. Langston, Kieren A. Marr, Kenneth V.I. Rolston and Scott D. Ramsey
+ Author Affiliations
  1. Christopher R. Flowers, Charise Gleason, and Amelia A. Langston, Emory University School of Medicine, Atlanta, GA; Jerome Seidenfeld, American Society of Clinical Oncology, Alexandria, VA; Eric J. Bow, CancerCare Manitoba and University of Manitoba, Winnipeg, Manitoba, Canada; Clare Karten, Leukemia and Lymphoma Society, White Plains, NY; Douglas K. Hawley, Onc Heme Care, Cincinnati, OH; Nicole M. Kuderer, Duke University Comprehensive Cancer Center, Durham, NC; Kieren A. Marr, Johns Hopkins School of Medicine, Baltimore, MD; Kenneth V.I. Rolston, University of Texas MD Anderson Cancer Center, Houston, TX; and Scott D. Ramsey, Fred Hutchinson Cancer Research Center, Seattle, WA.
  1. Corresponding author: Jerome Seidenfeld, PhD, American Society of Clinical Oncology, 2318 Mill Rd, Suite 800, Alexandria, VA 22314; e-mail:

© 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.


  • 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
  • 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

  1. Tracy A. Balboni
+ Author Affiliations
  1. Michael J. Balboni, Adaugo Amobi, John R. Peteet, Holly G. Prigerson, and Tracy A. Balboni, Harvard Medical School; Michael J. Balboni, Andrea C. Phelps, Daniel Gorman, John R. Peteet, Holly G. Prigerson, and Tracy A. Balboni, Dana-Farber Cancer Institute; Michael J. Balboni, John R. Peteet, and Holly G. Prigerson, Brigham and Women's Hospital; Adam Sullivan and Tyler J. VanderWeele, Harvard School of Public Health; and Angelika Zollfrank, Massachusetts General Hospital, Boston, MA.
  1. Corresponding author: Tracy A. Balboni, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute, Dana 1101, 450 Brookline Ave, Boston, MA 02115; e-mail:


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.

-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.


  • 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

  1. Julienne E. Bower
+ Author Affiliations
  1. Cousins Center for Psychoneuroimmunology, Semel Institute at University of California, Los Angeles; Jonsson Comprehensive Cancer Center at University of California, Los Angeles, Los Angeles, CA
  1. 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:
© 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).611 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 therapy2124) 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.


The author(s) indicated no potential conflicts of interest.


  • See accompanying article on page 4470