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Publication of the International Union Against Cancer
Publication de l’Union Internationale Contre le Cancer
Int. J. Cancer: Supplement 11, 66–68 (1998)
r 1998 Wiley-Liss, Inc.
BENEFITS OF NUTRITIONAL INTERVENTION ON NUTRITIONAL STATUS,
QUALITY OF LIFE AND SURVIVAL
Jan VAN EYS*
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA
Most cancers in children are acute diseases. Therefore, the
incidence of malnutrition, in general, is not different from the
incidence in the referral population. Some specific tumors,
such as neuroblastoma and those resulting in the diencephalic
syndrome, can be exceptions. By contrast, malnutrition is a
frequent problem during modern intensive cancer treatment
as the result of the associated anorexia, altered taste sensations and catabolic effects of drugs. In addition, there are
psychogenic factors and metabolic consequences associated
with the tumor itself. Nutritional support does improve the
feeling of well-being and performance status, while maintaining or improving the immune competence, thereby potentially affecting survival by limiting infectious episodes. There
is no convincing evidence to date that nutritional support has
an antineoplastic effect per se, but deficiency of a specific
nutrient might be beneficial because of a differential requirement between tumor and normal cells. Theoretically, nutritional support might enhance tumor growth but also susceptibility to chemotherapy. In either case, nutrition is a support
modality that must be given with appropriate tumor-directed
therapy if curative intent is the goal of treatment. Nutrition
remains a consideration after therapy is completed. This
generates different challenges. If further tumor-directed
therapy is futile, the decision to continue nutritional support
is difficult, but if the child is well, nutritional rehabilitation
must be pursued. Finally, the cured child continues to benefit
from dietary advice. Nutrition should be viewed for what it is:
supplying the most basic need of children. Int. J. Cancer
Supplement 11:66–68, 1998.
r 1998 Wiley-Liss, Inc.
Malnutrition and cancer are linked very closely in the minds of
many, professional and lay persons alike. Most would agree that
nutritional support is in the best interest of the child afflicted with
cancer, though there are many who worry that feeding the child
feeds the cancer, and so nutritional support may be counterproductive. In either case, people usually have a simple picture of what
malnutrition is and why it is linked to cancer. In this report, I would
like to indicate that this simple link is not a valid view. Malnutrition
and cancer are interrelated in varying ways, depending on the stage
of cancer evolution and therapy.
The stages of cancer evolution which one can distinguish are
diagnosis, therapy, completion of therapy with success or failure
and, finally, off-therapy cancer survival. Each of these stages has
specific etiologies for malnutrition and may require different
approaches to nutritional challenges. Table I summarizes these
stages and approaches to nutritional support. I would like to
elaborate on this theme in some detail.
One caveat: a communication problem can arise when nutrition
is viewed at the cellular level instead of at the level of the whole
person. This may seem to make sense in our era of molecular
medicine. However, it is analogous to treating a disease instead of
treating a patient who is ill. This report stresses the feeding of a
child, though I touch upon nutrition at the cellular level.
THE CHILD NEWLY DIAGNOSED WITH CANCER
Cancer in children is more often than not an acute disease. The
impact of the cancer on nutritional status is likely to be minimal at
the time of diagnosis, if the diagnosis is made in a reasonably
timely manner. A cooperative study of the nutritional status of
pediatric cancer patients showed that the incidence of malnutrition
at the time of diagnosis did not differ from that seen in patients with
benign tumors, referred to the same institutions (Donaldson et al.,
1981). The conclusion, that children newly diagnosed with cancer
were not particularly predisposed to malnutrition, was drawn also
from our own experience at the University of Texas M.D. Anderson
Cancer Center (Carter et al., 1983a,b). Nevertheless, a heavy tumor
burden might induce a catabolic state. The largest tumor burdens
are found in hematologic malignancies. However, in one study, the
nutritional status of untreated children with acute leukemia was no
different from that of children with benign acute diseases (Uderzo
et al., 1996). On the other hand, solid tumors in adolescents can
predispose to malnutrition because of the competing metabolic
demand for body growth. It might be added that all too often we
ignore incipient malnutrition but we discriminate against obesity.
When we analyzed our study population in Houston (Carter et al.,
1983b), we found that children with cancer who were obese at the
time of diagnosis fared somewhat better than their non-obese
counterparts, though the differences in event-free survival were not
statistically significant (37 obese vs. 110 normal weight children,
p ⫽ 0.178; data not shown).
There are a few exceptions to these generalizations. Most
spectacular is the diencephalic syndrome, wherein a tumor in the
anterior floor of the third ventricle on the anterior portion of the
hypothalamus results in a wasting syndrome in spite of seemingly
adequate intake of food. Occasionally, neuroblastoma results in the
secretion of a vasoactive intestinal peptide, resulting in profuse
watery diarrhea. However, paraneoplastic syndromes are the exception rather than the rule in pediatric oncology. Likewise, malnutrition in children newly diagnosed with cancer is the exception and
not the rule in societies in which malnutrition is uncommon in the
general population.
Nevertheless, malnutrition is common in children on therapy.
Therefore, it follows that early and close attention to nutritional
status is essential for optimal outcome. Intervention for the newly
diagnosed child with cancer and malnutrition ought to include the
raising of the caloric and nutrient intake to the age-appropriate
demands for growth and development.
ATTEMPTS AT CURATIVE THERAPY
Therapy for pediatric cancers is intensive. While surgery and
radiotherapy are used commonly, the vast majority of pediatric
oncology regimens are based primarily on chemotherapy. In
addition, over the years those regimens have become more and
more intensive. As a result, children who receive such treatment
need careful monitoring and early nutritional intervention. This is
all the more important because malnutrition is a contributing factor
to the immunological deficiencies encountered in children with
cancer who are on antineoplastic therapy.
Etiologic considerations
As in all diseases or disorders, therapy should be directed to the
cause. However, there are layers of etiology. Nausea and vomiting
are major contributors to the development of malnutrition. These
symptoms are most often induced by chemotherapy and therefore
iatrogenic. Antiemetics may not be effective and the management
of iatrogenic malnutrition is not always simple. First, the concerns
*Correspondence to: 3504 Ruland Place, Nashville, TN 37215-1812,
USA. Fax: (615) 298-5414.
NUTRITIONAL SUPPORT IN CHILDREN WITH CANCER
67
TABLE I – STAGES OF CANCER EVOLUTION AND APPROACHES TO NUTRITIONAL SUPPORT
Evolution of cancer
Time of diagnosis
Administration of therapy with curative
intent
Completion of therapy
Remission
Persistent or progressive disease
Cure
Nutritional issues
Approach to nutritional intervention
Malnutrition is generally independent of
cancer
Malnutrition is multifactorial but often
iatrogenic
Address malnutrition independent of
cancer therapy
Nutritional support must include attention
to social and psychogenic factors
Malnutrition is multifactorial but often
iatrogenic
Malnutrition is multifactorial but often
iatrogenic
Malnutrition is sometimes tumor-induced
Malnutrition is usually independent of
previous cancer
Unusual dietary habits may occur
Nutritional rehabilitation must address
psychogenic and social factors
Nutritional support may be desirable
of the family may result in counterproductive control issues.
Nutrition and nurture are synonymous in the minds of many
parents. Second, anticipatory vomiting is a real phenomenon,
conditioned by chemotherapy. Third, bribing with favorite foods
(to which parents often resort), and the association of these foods
with nausea and vomiting, result in the phenomena of learned food
aversions and psychogenic food refusal. The classical studies of
Bernstein (1978, 1982) brought these problems to the attention of
pediatric oncologists.
It is a truism that a malnourished child needs to be refed, even
when that child is undergoing intensive cancer therapy. However,
that may be a far more difficult task than merely supplying the
requisite calories and nutrients. When you add to that task the
tendency of families toward non-compliance with medical advice,
the challenge becomes even more daunting. Just feeding without
social and psychological support is often doomed to failure.
Nutritional considerations in chemotherapy
Much of chemotherapy is based on ‘‘nutritional’’ principles.
When we talk about nutrition we should mean overall, whole body
nutrition. However, chemotherapy often exploits nutrition at the
cellular level. A specific nutrient, considered to be required in the
overall intake, may be of greater importance for one cell than
another. Some compounds are not dietary essentials because they
are manufactured in one organ, but they are necessary for another.
We exploit those observations in chemotherapy. Methotrexate (a
dihydrofolate reductase inhibitor) and other antifolates are effective
because cancer cells need more tetrahydrofolate than ‘‘normal’’
cells. If we overdo the methotrexate-induced block we can bypass
the effect of the drug by giving tetrahydrofolic acid in the form of
leucovorin (citrovorum factor). Asparaginase is an effective antineoplastic agent because of the dependence of certain malignant cells
on preformed asparagine, in contrast to normal tissues, which can
synthesize this ‘‘non-essential’’ amino acid.
To translate this approach to chemotherapy into nutritional
manipulation as anticancer treatment remains an area that requires
much more research. For example, iron deprivation can result in
tumor regression. But iron overload can promote infection, while
iron deficiency predisposes to bacterial growth. Furthermore,
during formative years, iron deficiency can cause significant
developmental deficiencies. All this is complicated by the fact that
measures of iron status in the child with cancer are difficult to
interpret, because ferritin is a tumor marker and, like transferrin, is
an acute phase reactant that is sensitive to protein/calorie malnutrition (Garcia et al., 1989). Dietary iron was the nutrient lowest in
intake for 277 patients at referral to the University of Texas M.D.
Anderson Cancer Center for both children with solid tumors and
those with hemopoietic malignancies, with a range of 70–78% of
the recommended dietary requirement (Carter et al., 1983b; Garcia
et al., 1989). It is not immediately clear whether iron supplementation in such circumstances is warranted.
Such considerations may seem very different from the use of the
many supplements and special diets that parents are prone to give
Social and psychogenic factors must be
addressed
TABLE II – RATES OF SEPSIS IN CHILDREN WITH CANCER ON
HYPERALIMENTATION1
Patient group
All well-nourished
All malnourished
All control
All IVH3
Well-nourished on IVH
Malnourished on IVH
Days on
protocol2
Cases
with
sepsis
Sepsis rate
per 100
protocol
days2
p
99.5 ⫾ 89.8 4 0.12 ⫾ 0.44
72.7 ⫾ 57.5 10 1.07 ⫾ 0.74 ⬍0.001
113.5 ⫾ 97.2 1 0.01 ⫾ 0.05
74.7 ⫾ 62.3 13 0.71 ⫾ 1.44 ⬍0.01
79.5 ⫾ 67.0 3 0.25 ⫾ 0.63
71.2 ⫾ 58.3 10 0.98 ⫾ 1.75 ⬍0.05
1Derived from Van Eys et al. (1980).–2Mean ⫾ SD.–3IVH, intravenous hyperalimentation.
their children. The notion that a special diet can cure cancer is alive
and well among the laity. However, if physicians view nutritional
support too much from the viewpoint of influencing the tumor, they
are no better. Viewing nutritional support as a way of improving the
well-being of a child is, in the final analysis, more helpful.
Individual nutrients
Finally, certain nutrients are especially beneficial to certain
organs. The classical example is glutamine, which is considered
valuable in the protection of the intestinal mucosa during radiation
and chemotherapy (Wilmore, 1997).
In the selection of nutritional support, one has to take into
account that specific deficiencies of individual nutrients may exist.
Again, a classical example may suffice: magnesium deficiency
occurs frequently after the use of platinum-containing chemotherapeutic regimens.
Intervention strategies
There are 3 dogmas to remember in nutritional support: (1)
Nutrition is not medicine in the eyes of the patient and his family.
You are feeding a person. (2) Nutritional support must be tailored to
the needs of the individual patient. This includes his psychosocial
and specific nutrient needs. (3) Nutrition should be supplied in the
least invasive and most physiological way. The gut should be used
if at all possible.
Management should always be proactive. The intervention
should be predicated on the future health status of the patient and
not just on his or her status before therapy starts. Support personnel
often try to bargain with patients about feeding tubes or hyperalimentation, even when it is certain that these are going to be needed.
Hyperalimentation does result in a heightened exposure to infection because of the venous access required. However, not to feed
results in a heightened susceptibility to infection also. In a
prospective randomized trial of hyperalimentation, as adjuvant to
chemotherapy for children with a bone tumor relapse, the increased
number of infections did not correlate primarily with intravenous
VAN EYS
68
hyperalimentation but with the nutritional status of the patient (Van
Eys et al., 1980). This experience is summarized in Table II.
In pediatric bone marrow transplantation protocols, proactive
initiation of intravenous hyperalimentation remains routine (Weisdorf et al., 1987). The conditioning regimen for bone marrow
transplantation is a severe physiological insult and thermodynamic
deaths will occur if nutritional status is not maintained. A thermodynamic death is a death caused by insufficient energy being available
to sustain the function and/or survival of vital cells.
There was a time when intravenous hyperalimentation was
thought to be beneficial per se in cancer therapy. However, its use is
generally limited now to patients with specific indications (Archer
et al., 1996) for metabolic complications and infectious problems
are still all too frequent.
It has been suggested that intravenous hyperalimentation be used
to improve the effectiveness of cytotoxic therapy by giving the
intravenous nutrients intermittently, just before a chemotherapeutic
cycle. It was reasoned that the stimulus nutrition might give the
tumor cells may make the cells more susceptible to chemotherapy
(Copeman, 1994). Again, this misses an important point. It is true
that the more invasive the intervention, the more likely that
complications will arise. However, it is also true that the more
malnourished a child is, the more complications arise. Nutrition is
essential to staying alive. In the context of cancer therapy, that
reality does not change. The emphasis should be on the child, not
the cancer.
COMPLETION OF THERAPY
Remission
When a child has finished treatment, remaining in continuous
complete remission, nutritional rehabilitation still may be needed.
By this time, the family dynamics may be such that severe
abnormal feeding and eating patterns exist. Nutritional guidance
and graded intervention are extremely important in order to
minimize the long-term effects of cancer and its therapy.
Relapsed, progressive cancer
Unfortunately, some children have unrelentingly progressive
cancer. In that instance, tumor-induced cachexia can become a
major issue. While malnutrition is often iatrogenic, the tumor
burden can add an extra demand. If further therapy is planned, the
approach ought not to be any different from that taken for a child
undergoing therapy with curative intent. If a phase I evaluation of a
potential new therapy is planned, other challenges arise. Nutritional
status should be documented carefully. These reports should
indicate whether nutritional support was instituted and, if so, what
was given and how. This is especially important when pharmacokinetics are to be determined.
When the child is considered beyond hope, the decision for
nutritional support can become both agonizing and confused. It is
extremely important that communication among caregivers is
explicit and that values are clarified. Is nutritional support a
medical intervention or an act of compassion and nurture? The
American Medical Association has taken the position that nutritional support is a medical intervention.
As an illustration of how confused the discussion can become, I
recall the circumstances in Houston, where we cared for a child
with a relentlessly progressive tumor of the cervical spinal cord
which was unresponsive to radiation and chemotherapy and not
amenable to surgery. The child was considered socially unacceptable for inclusion in a home hyperalimentation program, especially
given his incurable status. Over staff objections, it was instituted
nevertheless. The boy had 18 months of totally uneventful home
hyperalimentation and was satisfied with his quality of life. The
same staff, who objected to keeping him alive with intravenous
nutrition, instituted totally futile cardiopulmonary resuscitation
when he arrested in the hospital (Van Eys, 1987).
THE CHILD CURED OF CANCER
Once a child is cured of cancer, it would seem that he or she
should revert to the status of the average member of the general
population. However, long-term sequelae are frequent. The incidence of second malignancies exceeds that of primary tumors
found in age-matched controls. Known dietary carcinogens should
be avoided. Permanent malabsorption can persist. More importantly, psychosocial idiosyncrasies are very common in cancer
survivors. Nutrition remains a challenge. The use of self-imposed
special diets or nutritional supplements continues far beyond the
time of cure. We need careful, long-term follow-up to gauge the
late effects of our therapy. Dietary evaluation and nutritional advice
should be integral parts of this process.
CONCLUDING REMARKS
Nutrition is basic to the care of any individual, let alone a sick
child. Having cancer constitutes no exception. There is no magic
diet that cures cancer. Nutritional therapy, in the sense of maintaining or restoring adequate nutritional status, is a form of supportive
care. Were our primary therapy truly effective, such supportive
therapy would not be needed.
Nutrition should be viewed for what it is: supplying the most
basic needs of children. No child has died from being fed
appropriately, but many die of starvation. The practice of pediatric
oncology should not contribute to that statistic.
REFERENCES
ARCHER, S.B., BURNETT, R.J. and FISCHER, J.E., Current uses and abuses of
total parenteral nutrition. Adv. Surg., 29, 165–189 (1996).
BERNSTEIN, I.L., Learned taste aversions in children receiving chemotherapy. Science, 200, 1302–1303 (1978).
BERNSTEIN, I.L., Physiological and psychological mechanisms of cancer
anorexia. Cancer Res., 42(Suppl.), 715s–720s (1982).
CARTER, P., CARR, D., VAN EYS, J. and COODY, C., Nutritional parameters in
children with cancer. J. Amer. diet. Assoc., 82, 616–622 (1983a).
CARTER, P., CARR, D., VAN EYS, J., RAMIRAZ, I., COODY, D. and TAYLOR, G.,
Energy and nutrient intake of children with cancer. J. Amer. diet. Assoc., 82,
610–615 (1983b).
COPEMAN, M.C., Use of total parenteral nutrition in children with cancer: a
review and some recommendations. Pediatr. Hematol. Oncol., 11, 463–470
(1994).
DONALDSON, S.S., WESLEY, M.N., DEWYS, W.D., SUSKIND, R.M., JAFFE, N.
and VAN EYS, J., A study of the nutritional status of pediatric cancer
patients. Amer. J. Dis. Child., 135, 1107–1112 (1981).
GARCIA, M.E., VAN EYS, J. and WANG, Y.-M., Iron nutrition in childhood
malignancy. J. parenter. enteral Nutr., 13, 162–167 (1989).
UDERZO, C., ROVELLI, A., BONOMI, M., BARZAGHI, A., STRADA, S.,
BALDUZZI, A., PIROVANO, L. and MASERA, G., Nutritional status in untreated
children with acute leukemia as compared with children without malignancy. J. pediatr. Gastroenterol. Nutr., 23, 34–37 (1996).
VAN EYS, J., Extraordinary therapy and social status—an instructive
example. J. psychosoc. Oncol., 5, 31–38 (1987).
VAN EYS, J., COPELAND, E.M., CANGIR, A., TAYLOR, G., TEITELL-COHEN, B.,
CARTER, P. and ORTIZ, C., A clinical trial of hyperalimentation in children
with metastatic malignancies. Med. pediatr. Oncol., 8, 68–73 (1980).
WEISDORF, S.A., LYSNE, J., WIND, D., HAAKE, R.J., SHARP, H.L., GOLDMAN,
A., SCHISSEL, K., MCGLAVE, P.B., RAMSEY, N.K. and KERSEY, J.H., Positive
effect of total parenteral nutrition on long-term outcome of bone marrow
transplantation. Transplantation, 43, 833–838 (1987).
WILMORE, D.W., Metabolic support of the gastrointestinal tract: potential
gut protection during intensive cytotoxic therapy. Cancer, 79, 1794–1803
(1997).
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