Nutritional status of patients undergoing chemoradiotherapy for lung cancer.

Abstract

Impaired nutrition is an important predictor of perioperative complications in lung cancer patients, and preoperative chemoradiotherapy increases the risk of such complications. The goal of this study was to assess the effect of an immune-enhancing diet on nutritional status in patients undergoing lung resection after chemoradiotherapy. We compared the preoperative nutritional status in 15 patients with lung cancer undergoing lung resection without chemoradiotherapy and 15 who had chemoradiotherapy. Body mass index and lymphocyte counts were lower in patients who had chemoradiotherapy. Although there was no difference in the rate of postoperative morbidity between groups, the chemoradiotherapy patients were more likely to have severe complications postoperatively. After chemoradiotherapy in 12 patients, 6 received oral Impact for 5 days, and 6 had a conventional diet before surgery. Oral intake of Impact for 5 days before surgery modified the decrease in transferrin and lymphocytes after the operation. Preoperative immunonutrition may improve the perioperative nutritional status after induction chemoradiotherapy in patients undergoing lung cancer surgery, and reduce the severity of postoperative complications. These potential benefits need to be confirmed in a randomized controlled trial.

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DOI: 10.1177/0218492311435249
2012;20:172-176 Asian Cardiovasc Thorac Ann
Okumura, Yuko Ohno and Mitsunori Ohta
Yasushi Shintani, Naoki Ikeda, Tomoshige Matsumoto, Yoshihisa Kadota, Meinoshin
Nutritional status of patients undergoing chemoradiotherapy for lung cancer
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Original Article
Nutritional status of patients undergoing
chemoradiotherapy for lung cancer
Yasushi Shintani1,2, Naoki Ikeda2, Tomoshige Matsumoto3,
Yoshihisa Kadota2, Meinoshin Okumura1, Yuko Ohno4
and Mitsunori Ohta2
Abstract
Impaired nutrition is an important predictor of perioperative complications in lung cancer patients, and preoperative
chemoradiotherapy increases the risk of such complications. The goal of this study was to assess the effect of an immune-
enhancing diet on nutritional status in patients undergoing lung resection after chemoradiotherapy. We compared the
preoperative nutritional status in 15 patients with lung cancer undergoing lung resection without chemoradiotherapy and
15 who had chemoradiotherapy. Body mass index and lymphocyte counts were lower in patients who had chemor-
adiotherapy. Although there was no difference in the rate of postoperative morbidity between groups, the chemora-
diotherapy patients were more likely to have severe complications postoperatively. After chemoradiotherapy in 12
patients, 6 received oral Impact for 5 days, and 6 had a conventional diet before surgery. Oral intake of Impact for 5
days before surgery modified the decrease in transferrin and lymphocytes after the operation. Preoperative immunonu-
trition may improve the perioperative nutritional status after induction chemoradiotherapy in patients undergoing lung
cancer surgery, and reduce the severity of postoperative complications. These potential benefits need to be confirmed in
a randomized controlled trial.
Keywords
carcinoma, non-small-cell lung, chemotherapy, adjuvant, enteral nutrition
Introduction
A successful treatment protocol for patients with
locally advanced non-small-cell lung cancer (NSCLC)
remains controversial. The results of surgical resection
alone for locally advanced NSCLC are poor, thus the
option of induction chemoradiotherapy (CRT) has
been reported.1,2However, preoperative CRT increases
the risk of perioperative complications in patients
with lung cancer, with failure of antibiotics given for
pneumonia being the most common life-threatening
complication.3We speculated that infections occurring
after the operation might be related to poor nutritional
status caused by CRT. Although the role of nutrition in
the outcome of surgery for lung cancer has been
addressed in only a few studies, impaired nutrition is
reported to be associated with an increased risk of com-
plications after the operation.4The first purpose of this
study was to determine the preoperative nutritional
variables after CRT in patients with lung cancer.
Perioperative alimentation to reduce postoperative
complications and improve surgical outcome has been
extensivelystudied.Inaddition,
of immune-enhancing diets has raised the possibility of
decreasing the incidence of complications during the
theavailability
Asian Cardiovascular & Thoracic Annals
20(2) 172–176
? The Author(s) 2012
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DOI: 10.1177/0218492311435249
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1Department of Thoracic Surgery, Osaka University Graduate School of
Medicine, Osaka, Japan
2Department of General Thoracic Surgery, Osaka Prefectural Medical
Center for Respiratory and Allergic Disease, Osaka University
Graduate School of Medicine, Osaka, Japan
3Department of Clinical Research and Development, Osaka Prefectural
Medical Center for Respiratory and Allergic Disease, Osaka University
Graduate School of Medicine, Osaka, Japan
4DepartmentofMathematicalHealth
Graduate School of Medicine, Osaka, Japan
Science,Osaka University
Corresponding author:
Yasushi Shintani, MD, PhD, Department of General Thoracic Surgery,
Osaka University Graduate School of Medicine, Osaka, Japan
Email: yshintani@thoracic.med.osaka-u.ac.jp
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postoperative course. Impact (Ajinomoto Pharma,
Tokyo, Japan), which contains arginine, RNA, and
o-3 polyunsaturated fatty acids, has been reported to
reinforce immunological function as well as improve
nutritional status.5Preoperative Impact administration
in patients with gastrointestinal cancer was found to
decrease the incidence of postoperative complications.
Thus, we administered Impact after induction CRT in
patients with lung cancer. The second goal of this study
was to assess the effect of the immune-enhancing diet
provided by Impact in patients undergoing lung resec-
tion after CRT.
Patients and Methods
Weenrolled15patientswithsurgicallyresectableclinical
N2 or N3 NSCLC, treated at Osaka Prefectural Medical
Center for Respiratory and Allergic Disease or Osaka
University, who underwent preoperative concurrent
chemoradiotherapy before pulmonary resection. They
received 2 cycles of cisplatin-based chemotherapy every
4weeksaswellasradiotherapydirectedatthetumorand
mediastinal nodes,which was started onday 2of cycle 1.
A thoracotomy was performed 6 to 8 weeks after com-
pletion of CRT. We compared the perioperative
nutritional status of the enrolled patients after CRT
with that of 15 randomly selected patients treated with-
out CRT during the same period.
Twelve patients with NSCLC who underwent CRT
between March 2008 and May 2010 at Osaka
PrefecturalMedical Center
Allergic Disease were divided into 2 groups: an immu-
nonutrition group and a conventional diet group.
Patients in the immunonutrition group received oral
Impact (750–1,000mL per day) for 5 days before sur-
gery, with the amount determined by nutritionists,
based on the diet of each patient during that period.
We compared the perioperative nutritional status
between these 2 groups. An institutional review board
approved this study, and written informed consent for
surgical intervention was obtained from each patient.
Measurements of serum protein levels and lympho-
cyte counts were used in conjunction with other param-
eters to determine the overall nutritional status of each
patient before surgery and on postoperative days 1, 3,
and 7. Serum proteins used for nutritional assessment
included transferrin, prealbumin, and retinol-binding
protein.
Thechi-squaretest,
and Wilcoxon signed-ranks test were utilized to
compare the results using Statview version 5.0 for
forRespiratory and
Mann-WhitneyUtest,
Table 1. Patient characteristics and preoperative nutritional status according to administration of CRT
VariableCRT (n=15)No CRT (n=15)p Value
Age (years)
Sex (M/F)
62?8
10/5
62?6
11/4
0.83
0.69
<0.0001Clinical stage
I
II
9
53
III1
227?48
303?197
12
252?58
591?460
Operative time (min)0.27
Blood loss (mL)
Pathological stage
0.30
0.19
0
I
4
79
II
III
5
1
22.9?2.1
192?12
27.6?9.5
4.1?1.7
4.1?0.4
6,267?1971
1,837?431
3
1
20.8?2.1
158?14
23.1?5.9
4.2?1.0
3.9?0.3
5,388?1844
981?574
Body mass index (kg?m?2)
Transferrin (mg?dL?1)
Pre-albumin (mg?dL?1)
Retinol-binding protein (mg?dL?1)
Albumin (g?dL?1)
White blood cell count
Lymphocytes
0.02
0.38
0.14
0.44
0.06
0.6
< 0.0001
CRT=chemoradiotherapy.
Shintani et al.173
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Windows (Abacus Concepts, Berkeley, CA, USA). A p
value<0.05wasconsideredtobestatisticallysignificant.
Results
The preoperative nutritional variables in lung cancer
patients with and without induction CRT are listed in
Table 1. The clinical stage was more advanced in
patients with CRT. Although there was no significant
difference in the levels of rapid turnover protein, albu-
min, and white blood cells, both body mass index and
lymphocyte counts were lower in patients with CRT.
These data suggest that induction CRT impairs the pre-
operative nutritional status of patients with lung
cancer. Pneumonia, arrhythmia, and prolonged air
leakage were the main complications in both groups.
Pneumonia occurred in 5 of 15 patients with CRT (both
required mechanical ventilation) and in 1 of 15 without
CRT. Arrhythmia or prolonged air leakage occurred in
3 patients with CRT and 2 without CRT. Although
there was no difference between the 2 groups in the
rate of postoperative morbidity, the patients who had
CRT were more likely to have a severe complication
postoperatively.
All patients in the immunonutrition group were
administered Impact without complications, although
2 of them reduced the amount of their conventional
diet while taking Impact. There was no significant dif-
ference in patient background and nutritional status
between these 2 groups (Table 2). Although oral
Impact for 5 days before surgery did not cause changes
in pre-albumin and retinol-binding protein, immunonu-
trition alleviated the decrease of transferrin and lym-
phocytes after the operation,
conventional diet group (Figure 1). There were no
deaths in either group. Pneumonia and prolonged air
leakage were the main complications in both. Two
patients in the immunonutrition group suffered postop-
erative pneumonia, and 2 in the conventional diet
group had both postoperative pneumonia and pro-
longed air leakage. There was no difference between
these groups in the rate of postoperative morbidity.
compared to the
Discussion
Nutritional assessment is the first step in effective
treatment of malnutrition, during which specific data
are obtained to create a metabolic and nutritional pro-
file of the patient. The primary goal of nutritional
assessment is identification of patients who are at
risk of developing malnutrition. Some studies have
suggested that certain nutritional indicators such as
weight loss and serum albumin concentration may
predict complications after an operation, particularly
postoperative infections.6,7One mechanism by which
nutritional status may influence outcome is the effect
on respiratory muscle strength in generation of an effec-
tive cough.4Furthermore, Tewari and colleagues8
reported that nutritional status is a predictor of long-
term survival that is independent of tumor extension
and staging.
Table 2. Clinical data of patients given Impact or a conventional diet after induction chemoradiotherapy
Variable Impact (n=6) No Impact (n=6)p Value
Age (years)
Clinical stage
62.3?4.5 62.3?4.5 0.98
0.29
IIB
IIIA
0
5
2
3
IIIB11
Pathological stage
0
0.48
23
I
II
2
2
0
1
III0
257?105
675?403
21.2?3.6
222?17.6
22?8.6
4.2?1.8
1,018?772
2
252?66
482?312
20.5?1.5
205?22.3
22?4.8
4.2?1.0
896?421
Operative time (min)0.93
Blood loss (mL)
Body mass index (kg?m?2)
Transferrin (mg?dL?1)
Pre-albumin (mg?dL?1)
Retinol-binding protein (mg?dL?1)
Lymphocytes
0.45
0.76
0.16
0.63
0.97
0.89
174 Asian Cardiovascular & Thoracic Annals 20(2)
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We found no difference in preoperative nutritional
status between patients with NSCLC undergoing lung
resection with and without CRT, based on rapid turn-
over protein values, while body mass index and
lymphocyte counts were different. The patients who
received CRT were in more advanced stages and under-
went more invasive operations, so we could not
precisely compare the nutritional status between
the groups. However, these findings suggest that nutri-
tional status might be impaired in patients who
undergo CRT. If nutritional depletion has an impor-
tant relationship with complications after surgery,
improving oral intake in the period before the opera-
tion might be beneficial.
A 1-liter serving of Impact contains 1,000kcal, 12.5g
arginine, 2.8g o-3 polyunsaturated fatty acids, and
1.23g RNA, which not only ameliorate nutritional
status but also greatly reinforce immunological func-
tion.9Xu and colleagues5reported that a preoperative
immunonutrition diet in patients with gastrointestinal
cancer improved nutritional status and immunity, and
also decreased the incidence of postoperative complica-
tions and infections.5Lung cancer patients generally eat
soon after the operation, thus their nutritional status
may not significantly influence the outcome of surgery,
and severe nutritional depletion is uncommon in
patients with lung cancer.10Thus, we focused on
patients who received induction CRT, and evaluated
the effects of an immune-enhancing diet. Preoperative
supplementation with Impact was well tolerated by
our lung cancer patients who underwent induction
CRT. There were no differences regarding patient
background and nutritional status between the 2
groups. Oral intake of Impact for 5 days before the sur-
gical procedure resulted in modification of the decrease
in transferrin and lymphocytes after the operation,
although there was no difference in the rate of postop-
erative morbidity between groups. Our findings suggest
that preoperative immunonutrition may improve the
outcome of patients undergoing lung cancer surgery
after induction chemoradiotherapy. Our study has
some limitations because it was a preliminary report of
a small-scale study, and this potential benefit should be
confirmed in a larger randomized controlled trial.
Funding
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement
None declared.
Acknowledgment
We thank all members of the nutrition support team at Osaka
Prefectural Medical Center for Respiratory and Allergic
Disease; especially Kyoko Morimoto, Itsuko Fujii, Kyoko
Nishida, Yoko Kondo, and Mika Sakon for their assistance
and encouragement.
References
1. Friedel G, Budach W, Dippon J, Spengler W, Eschmann
SM, Pfannenberg C, et al. Phase II trial of a trimodality
Figure 1. Evaluation of nutritional status in patients given Impact (þ) and for those who consumed a conventional diet (?) following
induction chemoradiotherapy. Bars indicate mean?standard error. POD=postoperative day.
Shintani et al.175
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regimen for stage III non-small-cell lung cancer using che-
motherapy as induction treatment with concurrent hyper-
fractionated chemoradiation
paclitaxel followed by subsequent resection: a single-
center study. J Clin Oncol 2010; 28: 942–8.
2. Uy KL, Darling G, Xu W, Yi QL, De Perrot M, Pierre
AF, et al. Improved results of induction chemoradiation
before surgical intervention for selected patients with stage
IIIA-N2 non-small cell lung cancer. J Thorac Cardiovasc
Surg 2007; 134: 188–93.
3. Roberts JR, Eustis C, Devore R, Carbone D, Choy H and
Johnson D. Induction chemotherapy increases periopera-
tive complications in patients undergoing resection for
non-small cell lung cancer. Ann Thorac Surg 2001; 72:
885–8.
4. Jagoe RT, Goodship TH and Gibson GJ. The influence of
nutritional status on complications after operations for
lung cancer. Ann Thorac Surg 2001; 71: 936–43.
5. Xu J, Zhong Y, Jing D and Wu Z. Preoperative enteral
immunonutrition improves postoperative outcome in
patients with gastrointestinal cancer. World J Surg 2006;
30: 1284–9.
withcarboplatin and
6. Busch E, Verazin G, Antkowiak JG, Driscoll D and
Takita H. Pulmonary complications in patients undergo-
ing thoracotomy for lung carcinoma. Chest 1994; 105:
760–6.
7. Martin-Ucar AE, Nicum R, Oey I, Edwards JG and
Waller DA. En-bloc chest wall and lung resection for
non-small cell lung cancer. Predictors of 60-day non-
cancer related mortality. Eur J Cardiothorac Surg 2003;
23: 859–64.
8. Tewari N, Martin-Ucar AE, Black E, Beggs L, Beggs FD,
Duffy JP, et al. Nutritional status affects long term sur-
vival after lobectomy for lung cancer. Lung Cancer 2007;
57: 389–94.
9. Bozzetti F, Braga M, Gianotti L, Gavazzi C and Mariani
L. Postoperative enteral versus parenteral nutrition in
malnourished patients with gastrointestinal cancer: a ran-
domised multicentre trial. Lancet 2001; 358: 1487–92.
10. Hollaus PH, Wilfing G, Wurnig PN and Pridun NS. Risk
factors for the development of postoperative complica-
tions after bronchial sleeve resection for malignancy: a
univariate and multivariate analysis. Ann Thorac Surg
2003; 75: 966–72.
176 Asian Cardiovascular & Thoracic Annals 20(2)
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DOI: 10.1177/0218492311435249
2012;20:172-176 Asian Cardiovasc Thorac Ann
Okumura, Yuko Ohno and Mitsunori Ohta
Yasushi Shintani, Naoki Ikeda, Tomoshige Matsumoto, Yoshihisa Kadota, Meinoshin
Nutritional status of patients undergoing chemoradiotherapy for lung cancer
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