The effect of tumor bulk on the metabolic response to cancer.

Abstract

The aim of this study was to examine the association between tumor bulk and degree of metabolic abnormalities in patients with cancer. Patient data were obtained from a retrospective review of metabolic data collected from patients over a 5‐year period. Some of the data have been used in other previously published studies.1, 2, 3 Patients were included in this study if metabolic data had been collected preoperatively, if they had no “significant” sepsis and concurrent endocrine disease, and if they had not received total parenteral nutrition. Solid tumor volume was calculated based on the tumor dimensions recorded in the pathologic records of the patients reviewed. The authors made the assumption that solid tumors were uniformly spherical and 1 cm3 of tumor tissue weighed 1 g. The volume and weight of hepatic or pulmonary metastases were similarly calculated using dimensions obtained with ultrasound or computed tomographic scanning. The volume of myeloproliferative tumors was calculated assuming that all hematopoietic tissue, except the spleen, was uniformly malignant and the myeloid tissue composed 5.9% of the patient's body weight. The following metabolic parameters were measured: oxygen consumption, rates of plasma glucose appearance and clearance, rate of plasma glucose oxidation and recycling, and rate of net protein catabolism. Glucose kinetics were measured by using primed constant infusions of [14C]glucose and [6‐3H]glucose. The rate of protein catabolism was determined by using primed constant infusions of [14C]urea or [di‐15N]urea. Blood samples were drawn after 120 minutes of isotope infusion over a 60‐minute interval. Indirect calorimetry was performed and oxygen consumption determined.Eighty‐five patients were included in the study. Approximately 81% were patients with solid tumors. The majority of these patients had gastrointestinal and head and neck malignancies. The remaining 19% had leukemias or lymphomas. The rates of plasma glucose appearance and clearance were determined in all 85 patients as was the rate of net protein catabolism. However, the rates of plasma glucose oxidation and recycling were determined in only 52 patients (61%).A positive correlation was found between the rate of plasma urea appearance and the rate of net protein catabolism and tumor bulk (r 2 =.80). The bulk of tumor present was positively correlated with the rate of plasma glucose appearance (r 2 =.72) and the rate of plasma glucose clearance (r 2 =.70). However, a negative correlation was demonstrated when the percentage of glucose uptake oxidized by tissue was compared to tumor bulk (r 2 =.75); this was associated with an increase in the percentage of tissue glucose uptake recycled to lactate (r 2 =.62). Oxygen consumption was also positively correlated with tumor bulk (r 2 =.79).Based on these data, the authors concluded that progressive increase in tumor size is associated with an increase in peripheral substrate mobilization, an increase in the rate of glucose production, an increase in the rate of tissue glucose uptake, and an increase in glucose recycling and protein loss.