The prognostic effect of increased resting energy expenditure prior to treatment for lung cancer

doi:10.1016/S0169-5002(99)00008-2

Lung Cancer

Volume 23, Issue 2, February 1999, Pages 153-158

https://doi.org/10.1016/S0169-5002(99)00008-2 Get rights and content

Abstract

Objective: Increased resting energy expenditure (REE) is thought to confer a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, no study has validated this hypothesis to date. This study’s objective was to examine the prognostic significance of REE in NSCLC. Methods: Seventeen patients with NSCLC (stages IA–IIIB) underwent measurement of REE with indirect calorimetry before the initiation of cancer treatment. Similar measurements were performed in 17 control subjects, each of whom was matched to a cancer patient by age (±5 years), sex and body mass index (±3 kg/m²). Patients were classified as hypermetabolic or hypometabolic based on a direct comparison of measured REE between cancer patients and their matched controls. After cancer treatment, these 17 patients were followed for evidence of metastatic disease for up to 32 months. Results: Six patients developed metastatic disease. The eight hypometabolic cancer patients had a significantly shorter mean disease-free survival compared to the nine hypermetabolic cancer patients: 19 months (95% confidence interval (CI) 12, 26) versus 29 months (95% CI 24, 34), respectively (P<0.05 by log-rank test). In contrast, Cox regression showed no relationship between disease-free survival and differences in REE between cancer patients and their matched controls (P=0.20). Conclusions: These results suggest that hypermetabolism may predict a longer disease-free survival in NSCLC patients. This finding differs from the prevailing hypothesis that hypometabolic patients with NSCLC survive longer, and deserves further investigation.

Introduction

Weight loss confers a poor prognosis in patients with non-small cell lung cancer (NSCLC) [1]. Earlier studies have hypothesized that an increase in resting energy expenditure (REE) confers a similar poor prognosis [2], [3], [4]. The basis for this hypothesis is that an increase in REE leads to energy deficits, which in turn promote weight loss, and thereby worsen prognosis. Although this theory is widely accepted because of its plausibility, no study has yet proven its validity.

We therefore chose to examine REE and its prognostic significance in patients with NSCLC. We studied patients with early-stage disease (stages IA–IIIB). We determined whether each patient was hypermetabolic or hypometabolic based on a direct comparison of measured REE between the individual patient and a control subject who had been matched to the cancer patient on the basis of age, sex and body mass index (BMI). These NSCLC patients were then followed over a period of 13–32 months to determine the predictive capability of metabolic status with respect to disease-free survival.

Section snippets

Recruitment of cancer patients and control participants

This study was part of a much larger research project, which had been approved by the Human Investigation Review Committee at the Tufts-New England Medical Center. Patients were recruited from the Lung Tumor Evaluation Center at New England Medical Center. Patients with either a tissue-confirmed diagnosis of NSCLC or a high clinical suspicion for NSCLC were approached for recruitment. All patients had undergone clinical staging prior to their participation and were found to have stage IA–IIIB

Results

Between September 1995 and June 1997, a total of 24 consecutive patients were recruited. Of these 24 patients, seven were excluded for one of the following reasons: benign diagnosis after surgical resection (2), tumor other than NSCLC diagnosed after surgical resection (1), hyperthyroidism (1), fever at the time of REE measurement (1), inability to be matched to a control subject on the basis of BMI, sex, or age (2). The remaining 17 cancer patients completed all aspects of the study and were

Discussion

This study is the first to examine the prognostic significance of hypermetabolism in patients with NSCLC and to suggest that hypermetabolic patients with early-stage NSCLC might have a significantly longer disease-free survival compared to patients who are hypometabolic. In our cohort, metabolic status conferred prognostic significance even when other well-described prognosticators, such as tumor stage and history of weight loss, did not.

Our results differed from what we had expected to find

Conclusions

In summary, our results suggest that hypermetabolism may predict a longer disease-free survival in patients with NSCLC. This finding differs from the prevailing hypothesis that hypometabolic patients with NSCLC do better and deserves further investigation.

Acknowledgements

The authors gratefully acknowledge the generosity of patients in the Lung Tumor Evaluation Center at the New England Medical Center for their willingness to participate in this research study. The authors also thank Reva McCarthy for her assistance in coordinating certain aspects of the study protocol. This study was supported by NIH grants F32CA69742 (A.J.) and M01RR00054-36A1 and USDA contract 53-3K06-5-10.

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Hypermetabolism is an independent prognostic factor of survival in metastatic non-small cell lung cancer patients
2020, Clinical Nutrition
Citation Excerpt :
Jatoi et al. included 17 NSCLC patients with early-stage disease (stages IA–IIIB) before treatment initiation. Although the statistical power was limited by the small number of patients included, hypermetabolic patients surprisingly showed a significantly longer disease-free survival than hypometabolic patients [15]. However, hyper- and hypometabolism were defined by the simple existence of a positive or negative difference between patient's REE and that of a matched (sex, age ± 5 years, and BMI ± 3 kg/m2) healthy control.
Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients.
This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE).
144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p = 0.007), histo-molecular subtype (p < 10⁻³), performance status (p = 0.04), weight loss (p < 10⁻⁴), albumin (p < 10⁻⁴), CRP (p = 0.001) and mREE/pREE ratio (>vs ≤ 120%: HR = 2.16, p < 10⁻³) were significant prognostic factors of OS. Median OS were 6.1 and 17.3 months in patients with mREE/pREE ratio > and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR = 0.25, p = 0.006), weight loss (>vs ≤ 5%: HR = 1.98, p = 0.004), albumin (≥vs < 35 g/L: HR = 0.56, p = 0.02) and mREE/pREE ratio (> vs ≤120%: HR = 1.90, p = 0.004) were identified as independent prognostic factors.
Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC.
Indirect calorimetry as point of care testing
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Citation Excerpt :
On the contrary, a small trial documented that hypometabolism lung cancer patients had a shorter mean disease-free survival than those with a hypermetabolic state. However they defined hypometabolic patients by comparing patient mREE to matched controls [85]. Many pharmacologic treatments with the aim of modifying metabolism in cancer patients are promising.
Determining energy requirement is a fundamental of nutrition support. Indirect calorimetry (IC) has been long recognized as the gold standard for assessing basal or resting energy expenditure (REE). The measurement of REE is recommended particularly in the situation where adjustment of energy provision is critical. The result of the IC measurement can lead to changes in treatment and since the change can be carried out immediately at the bedside, this may be considered as point-of-care testing. Beyond the nutritional aspects, studies of energy expenditure with IC have brought out more understanding of the metabolic changes during the natural course of diseases or conditions as well as those related to the intervention. The literature in various disease states has shown that changes in energy expenditure may reveal hidden metabolic information that might be translated into clinical information and have the potential of being both prognostic indicators and/or treatment targets.
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The aim of this study was to examine the inter-relationship between the inflammatory response and resting energy expenditure in patients with non-small cell lung cancer (NSCLC) before and after the onset of weight loss. Healthy subjects (n=7) and patients with NSCLC without weight loss (n=12) were studied. Resting energy expenditure adjusted for metabolically active tissue, as measured by total body potassium, was approximately 15% higher in the NSCLC group (P<0.01). Moreover, the resting energy expenditure, correlated with the magnitude of the inflammatory response (r=0.753, P<0.01). Six cancer patients subsequently lost weight and the relationship between resting energy expenditure and the inflammatory response was maintained. These results highlight the impact of the inflammatory response on the increase in the resting energy expenditure which precedes the onset of weight loss in patients with NSCLC.
Lean body mass changes in cancer patients with weight loss
2000, Clinical Nutrition
Background and Aims: Metabolic measurements (e.g. resting energy expenditure) are adjusted to lean body mass to account for body composition differences. Usually lean body mass is estimated from total body water. However, this may be compromised in weight-losing cancer patients owing to alterations in the degree of hydration of the lean body mass. This study examined the relationship between two independent estimates of lean body mass in healthy subjects and cancer patients with weight loss.
Methods and Results: Height, weight, total body water and total body potassium were measured in healthy subjects (n=9) and weight losing cancer patients (n=13). They were similar in terms of age and gender. However, the cancer group had a significantly lower percentage ideal body weight (P<0.001). The measured total body water values in both groups were similar to those predicted. In contrast, measured total body potassium values in the cancer group were significantly lower than predicted (P<0.001). There was a correlation between the ratio of measured lean body mass (water/lean bodymass (potassium) and the percentage weight loss (r=0.698,P <0.001).
Conclusions: These results suggest that total body water significantly overestimates metabolically active tissue in weight-losing cancer patients and therefore its use as the basis for metabolic requirements in this group of patients is questionable.
Resting energy expenditure based on equation estimation can predict renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease
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The prognostic effect of increased resting energy expenditure prior to treatment for lung cancer☆

Abstract

Introduction

Section snippets

Recruitment of cancer patients and control participants

Results

Discussion

Conclusions

Acknowledgements

Am J Med

Metabolism

Metabolism

Am J Clin Nutr

Metab Clin Exp