Resting energy expenditure in lung and colon cancer

Resting Energy Expenditure Daniel W. Nixon, Michael William

K. Evans, Khursheed

Kutner,

Steven Heymsfield,

N. Jeejeebhoy,

in Lung and Colon Cancer Ann T. Foltz, Chandra Carty, Susan Seitt,

John M. Daly, David Heber, Heinz Poppendiek,

Katie Casper,

and Freddie A. Hoffman

Elevated resting energy expenditure (REEj is a possible mechanism of cancer cachexia. We measured REE by whole-body direct calorimetry in patients with colon and non-small cell lung cancer and compared the results with REE in groups of healthy subjects and in patients with anorexia nervosa, with nonmalignant gastrointestinal (GI) disease, with miscellaneous reasons for weight loss, and with chronic lung disease. The mean REE of the cancer patients was not different from healthy subjects, those with GI disease, miscellaneous causes of cachexia, and chronic lung disease, and there was no significant difference in REE between those cancer patients with weight loss and controls with weight loss, except for the anorexia nervosa patients. The REE of the anorexia nervosa patients (female) was significantly lower than the REE of females with lung cancer. Weight loss correlated with REE in female lung cancer patients. Serial comparison of REE of ten cancer patients who lost 5% to 18% of their body weight during study showed no consistent change in REE. We conclude that patients with colon and non-small cell lung cancer, including those with weight loss, have REE similar to normal controls. Relative hypermetabolism may contribute to cancer cachexia. as may absolute hypermetabolism in some subsets of cancer patients. o 1999 by Grune & Stratton, Inc.

ROGRESSIVE loss of fat and lean body mass is common in advanced cancer.“’ Cachectic patients tolerate vigorous antineoplastic treatment poorly, and, when cachexia is extreme, survival is decreased.’ Attempts to replete the undernourished advanced cancer patient in order to improve treatment response rates and survival have been largely unsuccessful.3-5 Most investigators now agree that effective nutritional repletion requires an improved understanding of cancer cachexia. A possible cause of negative energy balance in the cancer patient is increased basal or resting thermogenesis.@ To examine this postulated mechanism, we measured resting energy expenditure (REE) by direct, whole-body calorimetry in two groups of cancer patients (colon and non-small cell lung cancer) and in five groups of controls without cancer. The study addressed the following questions: (I) Is there increased thermogenesis in lung and colon cancer patients compared with controls? (2) How does REE correlate with clinical parameters?

P

MATERIALS

I year prior to the study. Controls with nonmalignant disease were admitted to the study if their attending physician verified the diagnosis. There were five separate control groups in all: (1) Healthy normal subjects (n = 60). This group included 17 men and 43 women in good health who were 40 years old or older. Women were evaluated without regard to the phase of the menstrual cycle. (2) Patients with anorexia nervosa (n = 5). All were women; none were known bulemics, and all were underweight. (3) Patients with weight loss due to nonneoplastic gastrointestinal (Cl) disorders (n = 9). The diagnoses in this group included chronic inflammatory bowel disease, short bowel syndrome, and chronic pancreatic insufficiency. (4) Patients with miscellaneous nonmalignant causes of weight loss from chronic protein malnutrition (n = 21). (5) Patients with advanced chronic lung disease (n = 9). Spirometric and radiographic evaluation of the patients in this group indicated a combination of severe restrictive and obstructive lung disease. Groups 2 to 4 were studied because they had lost weight, whereas group 5 had diseases frequently associated with weight loss. Group 5 was also studied because lung cancer and chronic lung disease

AND METHODS

Patient Population We studied 98 cancer patients and 104 controls without cancer between 1982 and 1987 in the Emory Human Calorimetry Laboratory. Cancer. Forty-six patients had carcinoma of the colon and 52 had non-small cell carcinoma of the lung. Patients came from the Winship Clinic for Neoplastic Diseases and were hospitalized in the Emory Clinical Research Facility or the Emory Oncology Ward for calorimetry. Patients were chosen who had no mechanical interference with intake, had not undergone surgery for at least 21 days, had no significant acute or chronic disease (endocrinopathy, renal disease, heart disease, lung disease, or infection), and had no history of alcohol or tranquilizer abuse. Prior treatment was recorded. Location of metastases was determined by history and physical examination, chest radiography, radioisotope scans, and computerized axial tomography. Each patient had histologic confirmation of disease. Controls. Healthy controls were eligible for the study if their weight was within 20% of their ideal body weight without recent weight loss or gain, and if they had no evidence of acute or chronic disease, did not take any regular medication, and had not smoked for Mefabolism, Vol37,

No 11 (November), 1988: pp 1059-1064

From the Departments of Medicine and Biometry, and the Clinical Research Facility. Emory University School of Medicine, Atlanta; University of Toronto, Toronto: Memorial Sloan-Kettering Cancer Center, New York; University of California, L.os Angeles; Thermonetics Corporation, San Diego: and Division of Cancer Treatment, National Cancer Institute, Washington, DC. This is a publication of the Nutrition Oncology Research Cooperative Agreement (NORCA). Supported by the National Cancer Institute (NCI No. NOICM-25603: Calorimetry in Cancer Patients, and NC1 Nos. SUIO-CA34515, CA34748. CA34430: Nutritional Assessment of Cancer Patients), the State of Georgia (Nutrition-Oncology Research Contract), and the General Clinical Research Center Public Health Service Grant 5-MOI-RRO0039. Address reprint requests to Daniel W. Nixon, MD, Cancer Prevention Research Program, Division of Cancer Prevention and Control, National Cancer Institute. Blair Building, 9000 Rockville Pike, Bethesda, MD 20892-4200. o 1988 by Grune & Stratton, Inc. 0026-0495/ss/37II-00I1$03.00/a

1059

NIXON ET AL

1060

frequently coexist, making comparison with non-cancer-bearing chronic lung disease patients useful. Nutritional Evaluation Current nutritional status of the cancer patients was evaluated by assessing dietary intake prior to calorimetry (three-day diet diary), weight loss history, creatinine/height index (an average of three 24-hour urine collections), serum albumin, and transferrin. The study nutritionist gave each participant detailed instructions on keeping the three-day diet diary. The participants were shown how to weigh and measure food using a scale and measuring cups and spoons. They were also given two-dimensional food models. Portion sizes were recorded in household measurements for standardization. Participants were instructed to collect their records before chemotherapy and prior to calorimetry. The study nutritionist reviewed each record. The participant was contacted immediately to clarify ambiguous entries. Each entry was coded and then analyzed using USDA Nutrient Data Set 456-3. In addition, the cancer patients and control subjects underwent an anthropometric survey by a single observer.9 Skinfold thickness was measured to the nearest millimeter using the Lange caliper (Cambridge Scientific Industries Inc, Cambridge, MD). Triplicate readings were taken, and the results in millimeters were averaged. Four sites were measured: (1) Triceps: a vertical fold midway between the tip of the acromion and olecranon process on the right side; the measurement was made posteriorly, over the long head of the triceps. (2) Biceps: a vertical fold over the head of the biceps, at the same level as the triceps, with the midarm held vertically. (3) Subscapular: two centimeters under the inferior angle of the right scapula with fold running 45” diagonally between the shoulder and opposite hip. (4) Iliac crest: a vertical fold taken on the tubercle of the right iliac crest. The circumference of the upper arm, midway between the tip of the acromion and olecranon process, was measured in centimeters using a nonstretchable cloth tape. Midarm muscle area (MAMA), in square centimeters, was calculated from triceps skinfold thickness and midarm circumference according to the equation of Jelliffe and Jelliffe.“’ Body weight was measured to the nearest 0.1 kg on a calibrated physician’s scale. Total body fat (kilograms) and fat-free body mass (FFM), in kilograms. were derived from body weight and the four skinfold measurements by applying the method developed by Durnin and Womersley. ” Body surface area (BSA) was calculated in square meters using standard height/weight charts. Table 1. Clinical Features

Calorimetry Methods The direct gradient-layer whole-body calorimeter was assembled in collaboration with Thermonetics Corporation, San Diego, California. Calorimetry with this instrument, a 1 x 1 x 2.5 m chamber with an entry door at one end and an open plastic head canopy at the other, is well tolerated by most subjects. The gradient layer is calibrated with a standard heat-source electrical manniken, and airflow is maintained through the open-circuit system at 120 L/min. Wet bulb thermometers at the entry and exit ports of the system allow partition of heat losses into wet and dry components. Data were collected, displayed, and stored in an on-line computer. Previous serial study of cancer and non-cancer-bearing patients has confirmed the reproducibility and accuracy of the calorimeter measurements. Accuracy of the unit is within 2% to 3% of a known heat input, and repeated calibration measurements over time show differences of <1%.12 Following an overnight fast, each subject arrived at the calorimetry facility between 8 AM and lo:30 AM. Participants were not permitted to smoke for 12 hours. After putting on a standard hospital gown, each subject rested quietly for 15 minutes before the calorimetry study was initiated. In general, patients receiving chemotherapy were studied just prior to a chemotherapy cycle. At the beginning of the calorimetry study, the subject reclined on a stretcher that wheels directly into the calorimeter chamber. A core temperature (tympanic membrane) probe was applied, and the stretcher was then rolled into position so that the subject’s head fit into the plastic canopy at the rear of the calorimeter. The door was then sealed, and total heat losses were recorded until a steady-state output (defined as a plateau of calorimetry readings for at least 15 minutes) was reached, usually after 40 to 90 minutes. Fourteen cancer patients who did not reach a steady-state output within 90 minutes were restudied at intervals of 4 to 8 weeks. On repeat calorimetry, 12 reached steady state and are included in the analysis; the other two are excluded.

Statistical

Methods

Pearson product-moment correlational analyses were utilized to assess the linear associations between REE and the clinical parameters. Comparative analyses were performed using ANOVA techniques followed by the Tukey pairwise multiple comparison proceof the Two Cancer Groups LungCancer

ColonCancer

Total no, Age (yr, mean r SD)

Female

Male

Female

M&l

30

15

27

11

58 * 8

59 k 16

58 + 9

57 k 9

Metastatic or Recurrent Disease Site* Lung

9

4

21

Liver

13

7

8

3

Bone

1

0

8

3

Brain

3

0

2

2

Other

4

3

4

0

-

-

18

12

25

11

Surgery, prior curative

9

7

3

2

Surgery. palliative

4

3

Therapyt Radiation Chemotherapy

*Some patients had more than one metastatic site. tSome patients had mwe than one therapy.

1

9

1

RESTING ENERGY EXPENDITURE

IN CANCER

1061

Table 2.

Nutrition

Data for the Two Cancer Groups by Gender LungCancer

Colon Cancer M&Z

Weight (kg)

Female

75.9 f 12.7

NO.

62.1

t 17.3

30

Height (cm1

177.8

No. 2,501

NO. % Preillness weight

+ 7.1

152.8

-c_5.6

1,787

_t 637

2,415

? 1,040

1,897

-+ 561

93 * 21

91 _t 17

95 2 IO

55.6

No.

9 21.2

i

i 7.5

40.7

49.2

No. 4.16

No.

& 8.8

32.9

283.6

4.37

51.6

2 .49

290.6

3.95

-t 37.7

256.2

+

c 6.1 12

3.6

31.5

t 6.3 11

+ .45

4.02

f .45 10

i: 59.3

241.3

19

6.7 ? 2.3

7

38.5

23

7

9.0 t 2.3

1.0

18

9

f 80.5

+

t 6.4 12

25

r 10.5

13

No.

58.6

9

+ .54

20.4

25

? 8.1

21

No.

19.9 * 1 1.3

10.6

13

13

10

17

13

28

Creatinine/height (mg/cm)

+ 7.9 12

84 + 26

28

Serum transferrin (mg/dL)

161.8

11

No.

Serum albumin (gm/dL)

+ 7.6 21 23

19.9 t 6.5

MAMA (cm21

179.1

i: 12.0 12

11

17

FM (kg)

58.9

29

15

+I 698

FWll&

i 20.6

19

NO. Total body fat (kg)

80.5

15

30

Daily calorie intake (kcal/d)

Mdl?

i 62.2 9

9.3 + 2.4

8.8 + 2.2

14

10

5

Values represent the mean ? SD.

dure using the 0.05 level of significance. Frequency data compared using the Chi-square

were

test.

RESULTS

Calorimetry results for 83 cancer patients were usable (45 adenocarcinoma of colon, 38 non-small cell lung cancer). Reasons for exclusion included fever at the time of calorimetry (n = l), failure to fast as instructed (n = 4), inability to lie quietly in the calorimeter (n = 4), failure to reach a steady-state plateau of calorimeter readings (n = 2), technical problems with the calorimeter (n = l), or lack of necessary clinical or anthropometric data (n = 3). Six control patients were excluded for similar reasons (two healthy controls, one with chronic lung disease, one with GI disease, two with miscellaneous causes of undernutrition).

Table 3. Clinical and Nutritional

Clinical and nutritional data of the study subjects are provided in Tables I, 2, and 3. Three cancer patients were receiving maintenance steroids, and five were receiving replacement thyroid hormone at the time of study; none were clinically hypothyroid or hyperthyroid. Fifty-three smoked ‘/I pack of cigarettes per day or more. The majority of the cancer subjects (83% of the colon patients and 93% of the lung cancer patients) had known active metastatic or recurrent disease at the time of study; 37% had liver metastases. Weight (P < .05, both male and female), MAMA (P < .05, both male and female), and FFM (P < .OS, both male and female) were reduced in anorexia nervosa patients and those with GI disorders and miscellaneous causes of weight loss relative to the cancer patients, normal control subjects, and chronic lung disease patients. The average age of the

Data of the Control Groups by Gender Total Body

Group

Age W

Height(cml

Weight (kg)

Fat (kg)

% Ideal

FFM (kg)

Weight

Healthy (Age 2 40) Male (n = 16)

52.5

+ 9.4

178.4

t 7.1

84.0

t 11.3

24.1

f 6.6

59.8

? 7.5

115.6

i- 13.3

Female (n = 42)

50.5

t 7.7

163.5

t 5.4

67.1

& 8.4

24.8

t 5.5

42.4

2 4.1

115.0

* 14.9

Anorexia Nervosa Female (n = 5)

26.4

_t 7.2

163.1

+ 3.4

41.2

? 4.9

5.4 t 2.0

35.8

i 3.6

71.2

+ 7.2

GI disease Male (n = 3)

46.3

_c 17.2

179.6

+ 6.1

57.4

2 5.6

7.7 ? 2.6

49.7

* 4.5

80.0

* 4.8

48.7

t 16.5

160.9

+ 5.3

38.5

_t 5.8

7.6 i- 2.4

30.9

-f 4.5

66.8

+ 11.2

56.2

f 9.9

178.1

_t 4.3

62.4

? 13.3

13.4 i 7.4

49.0

* 6.8

86.2

t 19.3

52.9

c 8.6

163.2

? 7.7

48.8

f 22.7

14.2 ? 12.9

34.5

+_ 10.3

84.1

+ 35.4

Female (n = 5) Miscellaneous weight loss Male (n = 9) Female (n = 10) Chronic lung disease Male (n = 5)

62.7

+ 11.6

177.2

? 6.2

71.8

t 11.7

15.2 + 8.1

56.6

r 4.3

100.8

f 15.4

Female (n = 3)

60.3

t 8.1

163.2

f 2.3

60.9

? 10.2

17.9 t 3.1

42.9

t 7.2

103.7

? 16.0

Values represent the mean 2 SD

NIXON ET AL

1062

Table 4. Calorimetry

Results for Males and Females Separately RestingEnergyExpenditure

kcal/h

kcal/h/kg

kcal/h/BSA

kcal/h/FFM

Controls Healthy (Age 2 40) Male (n = 16)

62.8

& 8.0

0.75

_t 0.10

31.1

f 3.8

1.06 + 0.17

Female (n = 42)

47.2

? 6.4

0.71

+ 0.09

27.3

t 3.3

1.12 + 0.16

34.7

f 3.9

0.84

+ 0.05

24.7

+ 1.9

0.97*

Male (n = 3)

55.3

? 6.2

0.97

+ 0.12

32.0

+ 2.9

1.11 f 0.09

Female b-r = 5)

40.3

f 8.0

1.03 * 0.09

29.6

f 4.2

1.27 f 0.10

Anorexia Nervosa Female (n = 5)

& 0.08

GI Disease

Miscellaneous weight loss Male (n = 9) Female (n = 10) Chronic lung disease Male (n = 5) Female (n = 3) Cancer

56.4

t 13.1

0.92

? 0.18

31.8

f 5.8

1.15 +- 0.17

43.8

+ 8.3

0.94

+ 0.23

29.3

? 4.9

1.26 f 0.21

65.2

+ 11.2

0.89

r 0.09

38.4

+ 4.4

1.13 * 0.17

47.0

? 8.9

0.77

* 0.07

18.3 + 3.5

1.09 f 0.10

Colon Male (n = 30)

59.6

+ 20.8

0.79

f 0.10

30.8

+ 4.0

1.07 * 0.14t

Female (n = 15) Lung

47.9

r 10.3

0.80

-e 0.20

29.0

+ 5.4

1.17 * 0.20$

Male (n = 27)

64.3

+ 9.8

0.84

t 0.16

32.6

+ 3.1

1.09 f 0.12§

Female (n = 1 I)

48.6

t 8.4

0.85

-c 0.16

30.3

f 4.6

1.28 f 0.20

Values represent the mean i SD. *Statistically lower than female lung cancer patients and females with GI disease (P < .05). tn = 28. $n = 13. On = 24.

anorexia nervosa patients was lower than the other study groups. Group comparisons were made between REE as kcal/h, kcal/h/kg, kcal/h/BSA and kcal/h/FFM; results were similar regardless of denominator. Weight-losing cancer patients’ REE is shown as kcal/h/FFM, and correlations between disease type and clinical parameters were made with REE as kcal/hr/FFM. No significant difference in REE was found between the colon and lung cancer patients, the healthy controls, and those with benign GI disease, miscellaneous causes of undernutrition, and chronic lung disease when REE was analyzed according to gender (Table 4). Cancer patients with reliable weight histories on recall who had lost 5% or more of their premorbid weight (n = 29) had REE similar to the weightlosing groups with GI disease and miscellaneous causes of weight loss (Tables 4 and 5). The anorexia nervosa patients’ REE was significantly lower than that of the female lung Table 5. REE (kcal/h/FFM)

for Cancer Patients

With >5% and ~5% Weight Patients

~5% Weight Loss

Loss ~5% Weight Loss

Lung cancer

DISCUSSION

Male

1.15 + 0.15 (n = 9)

1 .Ol * 0.07 (n = 8)

Female

1.33 r 0.16 (n = 6)

1.12 f 0.09 (n = 4)

Male

1.01 * 0.12 (n = IO)

1.07 * O.lO(n

Female

1.29 * 0.29 (n = 4)

1.18 + 0.1 1 (n = 5)

Colon cancer

Values represent the mean ? SD.

cancer patients (P < .05) (Table 4). Weight-losing cancer patients’ REE did not fall relative to non-weight-losing cancer patients (Table 5). Cancer patients with low body mass indices (wt/ht*) had REE similar to those with normal and high body mass indices. Calorimetry was repeated in ten patients (six lung, four colon) who lost substantial amounts of weight during the study (from 5.2% to 18.6% of body weight at study entry). The time interval between calorimetry studies ranged from 1 to 10 months. Initial REE in these ten patients did not differ from the group as a whole or from weight-losing non-cancer-bearing controls, and the change in REE with weight loss varied unpredictably from patient to patient (Table 6). There was no significant correlation between the healthy control subjects’ REE (as kcal/h/FFM) and weight, BSA, FFM, and age. Likewise, there were no significant correlations between REE, liver metastases, serum albumin, creatinine/height index, caloric intake, core temperature, and weight loss in the male and female colon cancer patients and males with lung cancer. The greater the weight loss, the higher the REE in females with lung cancer (r = -0.61; P-c .05).

= 7)

It is widely accepted that malignancy is associated with cachexia, but the exact mechanisms for this relationship are uncertain. Nitrogen trapping by the tumor, altered glucose and fat metabolism, and a number of other aberrant processes have been proposed.2v’3*‘4 If altered thermogenesis and

RESTING ENERGY EXPENDITURE

IN CANCER

1063

Table 6. Change in REE of Patients Who Lost More Than 5% of Their Initial Entry Weight Weight LOSS

During Study

Time Interval Between Calorimet~

Change In

Age lvrl

sex

Lung

71

F

5.7

3

0.99

Lung

50

F

6.6

1

1.37

0.25

lung

67

M

7.8

5

1.13

0.25

Lung

64

M

11.7

6

1.15

0.06

Lung

42

M

5.2

8

1.15

Lung

67

M

13.7

3

1.14

-0.14

Colon

67

F

12.6

10

1.12

-0.02

Colon

75

F

18.6

4

1.20

Colon

76

F

13.7

7

1.06

Colon

66

M

5.2

9

0.96

Malignancy

(%I

cachexia in cancer are related, several explanations are possible: (1) Elevated REE may be a characteristic part of the tumor-host relationship and precede cachexia. Some patients may delay cachexia by increasing caloric intake. (2) REE may remain normal as cancer progresses with weight decline, thus becoming relatively elevated. (3) Elevated REE may occur only in a subset of cancer patients. Others could lose weight from other causes such as pain with anorexia or treatment-related nausea and vomiting. (4) Elevated REE may appear late in the natural history of cancer cachexia and be unimportant as a mechanism. (5) There may be an abnormal thermic effect of food leading to weight loss. Indirect calorimetry techniques have been available for decades, and many investigators have used these methods to examine the effects of abnormal host-tumor interactions on thermogenesis. Boothby and Sandiford reported in 1922 that the majority of 16 lymphatic and myelogenous leukemia patients had basal metabolic rates 20% above normal.” Other investigators have found an elevated basal metabolic rate in leukemia patients,i6,” and in 1950 Silver’* reported a 14% to 60% elevation in basal energy expenditure in 11 patients with multiple myeloma. In a 1954 review, Fenninger and Mider listed a number of studies, some as early as 1869, that demonstrated an increased metabolic rate in patients with carcinoma of the stomach, leukemia, and various other malignancies.* Nevertheless, Young in 1977 reviewed some of the same and later studies and concluded that, because of limited information in many papers and because of multiple factors that affect metabolic rates, it was not certain that resting metabolism was consistently increased in patients with cancer.13 More recently, Bozzetti et al (1980) reported, again with indirect techniques, that resting metabolic rate was abnormally high in 60% of a mixed group of cancer patients.6 Included in this group were patients with lymphoma, colon and stomach cancer, hypernephroma, breast cancer, and unknown primary cancer as well as a miscellaneous category. In a study at the University of Pennsylvania that included patients with cancers of GI, gynecologic and genitourinary origin, more than 50% had abnormal REE compared with values predicted by the Harris-Benedict equation, but more

(mol

lnltial REE fkcal/h/FFM)

REE (kcal/h/FFMl

0.37

0.02

0.04 0.16 -0.14

were hypometabolic than were hypermetabolic.‘9*20 Axelrod et al” found that five fasted patients with non-small cell lung cancer had elevated basal energy expenditure compared with normal subjects, and Russell et a12’ determined that REE was higher than predicted in 31 small cell lung cancer patients. Patients in the Pennsylvania study had a mean weight loss in excess of 10% of their usual body weight, but no correlation was seen between energy expenditure and weight loss. All of Axelrod’s five patients had lost weight; the degree of weight loss ranged from 7% to 28%. Fifteen of the 3 1 patients in Russell’s study had lost more than 5% of preillness weight, but no correlation was reported between weight loss and metabolic rate. Bozzetti found a strong correlation between basal metabolic rate and weight loss. Published indirect calorimetry studies, therefore, indicate a wide range of metabolic rates in numerous cancer types, including colon and lung cancer, with variable information concerning metabolic rate and weight loss. We cannot account for the difference between our findings and those of some indirect calorimetry studies, although types of disease, degree of disease, and techniques of measurement may contribute. In addition, some studies compared results with normal values predicted by published equations. We have demonstrated’j that the Harris-Benedict equation systematically overestimated REE and therefore did not use this equation for comparison. Because protein calorie undernutrition is common during the natural history of colon and non-small cell lung cancer, we chose these diseases for study with a modern whole-body direct calorimeter to investigate hypermetabolism as a potential cachectic mechanism. For comparison, we studied control groups of normal subjects and patients with weight loss from nonmalignant diseases or with disease frequently associated with weight loss (chronic lung disease). We were unable to detect absolute elevations in REE in this cancer population when these comparisons were made. We conclude, therefore, that REE higher than that in controls is not a characteristic tumor-host phenomenon in patients with non-small cell lung and colon cancer (explanation 1, above). Nevertheless, our data raise the theoretical possibility that REE, even though normal, might be high for the population in question (explanation 2). When starved, normal subjects’ REE should decline,24 as did the REE of the

NIXON

1064

anorexia nervosa patients in our study. The REE of the anorexia nervosa patients was significantly lower than that of the female lung cancer patients and of the females with GI disease, but the REE of weight-losing cancer patients did not fall relative to non-weight-losing cancer patients or to controls. Therefore, even though the REE of the cancer patients was not higher than the normal subjects, it could be greater than expected in those who exhibit weight loss. That the REE of the patients with weight loss from GI disease and those with miscellaneous causes of undernutrition was not different from the REE of weight-losing cancer patients suggests that, if real, relative hypermetabolism with cachexia may not be a cancer-specific phenomenon. It also remains possible that truly elevated REE may occur in subsets of cancer patients (explanation 3). The REE of female lung cancer patients differed significantly from the REE of the anorexia nervosa patients, and higher REE correlated with weight loss in the female lung cancer patients. We recognize that comparison between cancer patients and subjects with anorexia nervosa and other groups with greatly decreased caloric intake may be confounded by

ET AL

differences in immediate prior intake of energy. Two of the three weight-losing patients whose REE increased substantially with weight loss during the study were female lung cancer patients. The significance of elevated REE as weight loss progresses is uncertain, and this may not be an important cachectic mechanism (explanation 4). Our study did not address the possible abnormal thermic effect of food in cancer patients (explanation 5). Our conclusions can be summarized as follows: An absolute increase in resting energy expenditure over controls was not common in our subjects with cancer of the colon and lung. Relative hypermetabolism, perhaps as a general phenomenon of weight-losing disease, and absolute hypermetabolism in subsets of cancer patients, remain as potential cachectic mechanisms.

ACKNOWLEDGMENT

The authors thank Dr William DeWys (National Cancer Institute), Senator Paul Broun (Georgia State Senate) and Joe Jean Borowski (Emory University) for their assistance in this study.

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