Download Improved Outcomes in the Malnourished Patient

DOI: 10.1093/jnci/djs031
Advance Access publication on February 15, 2012.
Published by Oxford University Press 2012.
EDITORIALS
Improved Outcomes in the Malnourished Patient: We’re Not
There Yet
Ann O’Mara, Diane St. Germain
Correspondence to: Ann O’Mara, PhD, RN, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group, National Cancer
Institute, National Institutes of Health, 6130 Executive Blvd, MSC-7340, Bethesda, MD 20892-7340 (e-mail: [email protected]).
Malnutrition in the setting of cancer treatment is often foreboding
and for good reasons, as it is an independent predictor of poor
outcomes (ie, decreased survival, poor response to cancer therapies,
increased symptomatology, and impaired functional abilities). Nor
is the scope of the problem insignificant, as it has been estimated
that when malnutrition progresses to cachexia, it accounts for
approximately 30% of cancer-related deaths overall (1,2). Treating
malnutrition and ideally preventing its unrelenting transition to
cancer cachexia is a goal that clinicians have been seeking for
decades. Despite the array of oral therapies available, not all
patients will benefit, either in improved survival or improved
quality of life (QOL). Several systematic reviews during the past
decades have shown that a number of considerations must be taken
into account when treating patients at risk for or suffering from
cancer-related malnutrition (3–5). These include type and stage of
disease, treatment modalities, patient comorbidities, functional
performance, and psychosocial status. Research aimed at preventing and treating weight loss, and malnutrition must incorporate
these factors, beginning with restrictive eligibility criteria and
meaningful patient reported outcomes. With this approach, other
endpoints that heretofore have eluded the research community,
such as improved survival and weight gain or maintenance, might
be achieved. Unfortunately, in this issue of the Journal, results from
the meta-analysis of Baldwin et al. (6) suggest these changes and
achievements have yet to occur.
The authors are to be commended for their thorough and
rigorous review and meta-analysis of oral nutritional interventions
in malnourished cancer patients or those at risk for malnourishment. Thirteen randomized controlled studies were included in the
analysis representing 1414 participants. Study participants were
adults with cancer (all sites and stages) receiving active treatment,
including palliative treatment, and an oral nutritional intervention
consisting of dietary advice, oral nutritional supplements, or both.
All studies compared one of these nutritional interventions with
usual care. The outcomes included in the analyses were mortality,
QOL, weight loss, and energy intake. QOL was measured using
the European Organization for Research and Treatment of Cancer
(EORTC) questionnaire, which consists of 30 items assessing five
functions, eight symptoms, global QOL, and perceived financial
impact. The number of studies used to analyze each outcome varied depending on clinical and statistical heterogeneity. Analyses of
mortality (15 studies), QOL (five studies), weight (eight studies),
and energy intake (10 studies) were done. Overall, the analyses
revealed no effect on mortality, no statistically significant difference
in body weight or energy intake, and improvement in global QOL,
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EORTC domain of emotional functioning, dyspnea, and loss of
appetite. These results reflect reanalyzed data excluding studies
responsible for heterogeneity.
There are several limitations to the review that the authors
carefully outline. With regard to nutritional status, the patient
population was very heterogeneous, including those at risk for
malnourishment, those who were malnourished, and those who
were cachectic. These nutritional statuses are often used interchangeably; yet, they constitute very distinct entities, possibly
requiring very different interventions. Experts agree that conventional nutritional support cannot fully reverse the process of cachexia
(7). Might the results of the analysis have been more promising if
the eligibility criterion for weight loss had been more restrictive?
Patients also varied in terms of cancer type, stage, and treatment.
Though the authors believe this is justified, Santarpia et al. (8)
advocate a tailored/personalized nutritional approach dictated by
the underlying etiology. Nutritional deficits resulting from cancer
and its treatment vary widely, as do their interventions, which may
account for the variation seen in the duration, nature, and intensity
of the nutritional interventions in the meta-analyses, which the
authors cite as a factor contributing to heterogeneity. The most
important limitation is the inclusion of studies that were of poor
quality because of inadequate blinding, high risk of bias, small
sample sizes, and inadequate power. Regrettably, these limitations
reduce the clinical applicability of the findings and underscore the
inherent challenges in conducting a meta-analysis in this area of
research. Moreover, it speaks to the need for further research in
this area.
By outlining the limitations, the authors provide direction for
future researchers. A key point made by the authors is that despite
the statistical significance of some aspects of QOL, it is unclear
how meaningful these changes are to the patient. The challenge
that researchers face is explaining how improved emotional
well-being resulted from taking an oral nutritional supplement
and/or receiving dietary counseling. Was the improvement from
the nutritional counseling, the supplement, the combination, or
the extra attention to and clinical involvement with the patient?
Was the improvement seen in cachectic patients only? If the goal
of nutritional clinical studies is to improve QOL, more work is
needed to define what aspects of QOL are clinically significant and
meaningful to the patient and most importantly, to gain a better
understanding of the underlying mechanisms. Consideration must
also be given to a uniform definition of malnourishment that
should be an eligibility criterion. Future studies should use a
common QOL scale so data can be analyzed across multiple
Vol. 104, Issue 5 | March 7, 2012
studies, a standard baseline assessment, and standard clinical nutrition guidelines. A thorough psychosocial and symptom assessment
including functionality and financial concerns is critical.
Selecting the right patient for nutritional interventions both in
everyday practice as well in the clinical research setting, cannot be
overstated. Oral nutritional supplements are often recommended
likely, in part, because they are perceived to carry no harm, but
who will likely benefit remains an important question. Nutritional
supplements may indeed improve outcomes for some patients
experiencing malnutrition but not cachexia. Dietary counseling
may be beneficial for patients at high risk for malnutrition and their
caregivers. However, the research conducted to date is fraught with
limitations; hence, it is challenging for clinicians to apply these
results to everyday practice. Until future research provides clearer
answers regarding who will benefit from nutritional interventions,
the use of a comprehensive assessment, published nutritional
guidelines, and early interventions are essential.
References
1. Inui A. Cancer anorexia-cachexia syndrome: current issues in research and
management. CA Cancer J Clin. 2002;52(2):72–91.
2. Palesty JA, Dudrick SJ. Cachexia, malnutrition, the refeeding syndrome,
and lessons from Goldilocks. Surg Clin North Am. 2011;91(3):653–673.
jnci.oxfordjournals.org 3. Elia M, Van Bokhorst-de van der Schueren MA, Garvey J, et al. Enteral
(oral or tube administration) nutritional support and eicosapentaenoic
acid in patients with cancer: a systematic review. Int J Oncol. 2006;
28(1):5–23.
4. Locher JL, Bonner JA, Carroll WR, et al. Prophylactic percutaneous
endoscopic gastrostomy tube placement in treatment of head and neck
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JPEN J Parenter Enteral Nutr. 2011;35(3):365–374.
5. Baker A, Wooten LA, Malloy M. Nutritional considerations after gastrectomy and esophagectomy for malignancy. Curr Treat Options Oncol. 2011;
12(1):85–95.
6. Baldwin C, Spiro A, Ahern R, Emery PW. Oral nutritional interventions
in malnourished patients with cancer: a systematic review and metaanalysis. J Natl Cancer Inst. 2012;104(5):371–385.
7. Fearon K, Strasser F, Anker SD, et al. Definition and classification of
cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):
489–495.
8. Santarpia L, Contaldo F, Pasanisi F. Nutritional screening and early treatment of malnutrition in cancer patients. J Cachexia Sarcopenia Muscle.
2011;2(1):27–35.
Notes
The authors have no conflicts of interest to declare.
Affiliations of authors: Division of Cancer Prevention, Community Oncology
and Prevention Trials Research Group, National Cancer Institute, National
Institutes of Health, Bethesda, MD (AO’M, DSG).
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