Normal Weight Cancer Patients Research Articles

Toxicity and effectiveness of carboplatin in obese or overweight patients.

To evaluate the efficiency and toxicity of carboplatin using actual body weight in obese/overweight patients using the Calvert formula with Cockcroft-Gault for CrCl estimation. We evaluated the association of BMI in regards to efficiency and toxicity in a retrospective cohort study of patients who started treatment with carboplatin between 2012 and 2013. Cohorts included obese/overweight patients and normal-weight patients. Efficiency was measured by overall survival, progression-free survival and response rate. Toxicity was measured by the proportion of dose reductions and delays of chemotherapy cycles. We utilized a bivariate and multivariate analysis. Eighty-six patients were included in the study (50% obese/overweight). There was not a statistically significant difference in effectiveness and toxicity between the two groups in BMI. In the multivariate analysis, BMI not was associated with overall survival (hazard ratio: 0.95, 95% CI: 0.54-1.66, p = 0.849), progression-free survival (hazard ratio: 0.91; 95% CI: 0.54-1.54; p = 0.732), cycle delays (odds ratio (OR): 1.47, 95% CI: 0.80-2.69, p = 0.218) or carboplatin dose reductions (OR: 0.87, 95% CI: 0.35-2.15, p = 0.760). Response rate was 53.5% in both groups. In our study, obese and overweight cancer patients did not show a statistically significant difference in terms of effectiveness and toxicity compared to normal-weight cancer patients who were treated with carboplatin using their actual body weight with the Calvert formula and Cockcroft-Gault for CrCl estimation. Therefore, it was appropriate to use the actual body weight for our patients.

Evidence for an Overweight Paradox in Cancer: Insights from Body Composition—Reply to Counterpoint

See Counterpoint by Caan, et al., [p. 1906][1] Dr. Caan and colleagues state that the overweight paradox does in fact exist and that overweight cancer patients have better survival than normal weight cancer patients because of muscle mass and a potential role of subcutaneous fat as nutritional

Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer

Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS compared to obese only or normal weight cancer patients (P < 0.005). There was no difference in intratumoral leptin adiponectin or its ligand receptors in the same groups. Individual features of MetS correlated with Ob and ObR expression, but not obesity markers (BMI, waist circumference). mRNA expression of leptin (Ob) and ObR, in adipose tissue and matched tumor samples, respectively, appear to be associated with obesity status in breast cancer. Increasing insulin resistance is a predominant feature of this higher Ob/ObR expression observed. These novel data indicate that the MetS may be an amenable risk factor for breast cancer.

Abstract LB-291: Central obesity drives oesophageal tumor cell growth through VEGF-mediated mechanisms

Abstract Introduction: Obesity is a risk-factor for both esophageal/colorectal adenocarcinoma. Adipose tissue is an endocrine organ secreting numerous factors, including Vascular Endothelial Growth Factor (VEGF). VEGF was identified to be up-regulated in cancer cells by affymetrix-array following co-culture with human omental adipose tissue (OAT). An understanding of the mechanisms driving obesity-related disease is needed to uncover pathways and develop new targets for therapy. In this study, we aimed to investigate the effect of OAT-derived VEGF on tumor growth and the potential of bevacizumab to block this effect. Methods: Matched subcutaneous and omental adipose tissue, serum and tumor were harvested from oesophageal/colorectal cancer patients undergoing resective surgery. VEGF was quantified in adipose conditioned media (ACM) and serum by ELISA. Proliferation of esophageal (OE33, JH-ESO) and colorectal (HCT15, SW480) cells following culture with ACM was assessed by BrdU assay. The protective effect of ACM on chemotherapy (cisplatin and 5FU) induced death was assessed. The effect of bevacizumab in attenuating these effects was also examined. VEGF and VEGF receptor 2 (KDR) expression was assessed in tumor tissue by qPCR. In a 200-patient tissue microarray, VEGF and VEGFR expression was related to clinico-pathological parameters and obesity status. Results: ACM from omental adipose tissue of obese patients significantly (p&amp;lt;0.05) increased proliferation in oesophageal (313%) and colorectal (424%) adenocarcinoma cell lines relative to omental adipose tissue from non-obese cancer patients (180% and 157% respectively). Interestingly, this effect was not observed in ACM from matched subcutaneous depots indicating that omental adipose tissue is more pro-tumor and metabolically active. Omental ACM from obese patients contained significantly higher levels of VEGF (p&amp;lt;0.05). In our patient cohort, serum VEGF was significantly elevated in centrally obese relative to normal weight cancer patients (determined by CT). There was a significant (p&amp;lt;0.05) higher expression of VEGF and KDR expression in esophageal tumours from centrally obese patients. The expression of KDR was higher in the leading edge of tumors from patients classified as obese, and was associated with decreased survival and increased nodal involvement. ACM from omental adipose tissue protected against 5FU-induced cell death (P&amp;lt;0.01), an effect which could be blocked by treatment with bevacizumab. Conclusion: VEGF from OAT increased proliferation in oesophageal/colorectal cancer cells. VEGF and KDR expression in oesophageal cancer was higher in centrally obese patients. ACM protected against chemotherapy-induced death, an effect that was mediated through VEGF. These findings suggest anti-VEGF strategies are warrented in obesity-associated malignancies, alone or in combination with conventional chemotherapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-291. doi:10.1158/1538-7445.AM2011-LB-291

Metabolic Syndrome in Breast Cancer: Paracrine Mediators in Mammary Adipose Tissue Mediated by Metabolic Dysfunction Influence Tumour Cell Proliferation.

Abstract Introduction:Obesity and it's associated metabolic syndrome are known epidemiological risk factors for breast cancer.¹ Adipose tissue is a potent endocrine organ secreting many factors that can potentially regulate tumour growth. The breast constitutes an excellent model to determine the paracrine mediators of adiposity on breast cancer. The aim of this preliminary study was thus to describe the adipocytokine milieu in the breast and determine what influence adiposity and metabolic dysfunction played in tumour progression.Methods:Adipose conditioned media (ACM) was produced by harvesting adipose tissue from sites adjacent to (peritumoural PT) and distal (D) to tumour in 20 fresh mastectomy specimens and cultured in serum free media for 72hrs. MDA-MB 231 and MCF-7 cell lines were then cultured with this ACM for 24-48hrs. Cell survival/proliferation was determined by BrDU assay. An in depth characterisation of adipocytokine production from each adipose depot was performed using multiplex bead arrays.Results:ACM from peritumoural/distal adipose tissue promoted cell proliferation in both cell lines. The greatest proliferative effect was observed in ER+ve MCF-7 cell line relative to controls (151.9±7.3% and 150.8±9.8% in peritumoural and distal ACM respectively), compared to ER-ve MDA-MB-231 cells (111.4±5.0, 112.0±2.5%).PT ACM from metabolically unhealthy/obese patients significantly increased proliferation in MCF-7 cells, compared to normal weight cancer patients (171±12.6% vs 135.3±9.3%, p=0.034). Similarly, adipocytokine expression reflected these changes with expression differences in IL-6 (6.72±0.09, 6.31±0.16 ng/ml p=0.028), HGF (7.5±1.3, 3.98±0.43 ng/ml p=0.028).Conclusion:Peritumoural adipose tissue from metabolically unhealthy and obese patients increased cell proliferation compared to normal weight patients. Metabolic dysfunction influenced expression of several adipocytokines in ACM. A thorough analysis of this milieu should lead to a greater understanding of how obesity/metabolic dysfunction regulate tumourigenesis in breast cancer.

Transdermal fentanyl in cachectic cancer patients

Fentanyl is an opioid with high lipid solubility, suitable for intravenous, spinal, transmucosal and transdermal administration. The transdermal fentanyl patch has become widely used in the treatment of both malignant and non-malignant chronic pain. The absorption of fentanyl from the patch is governed by the surface area of the patch, by skin permeability and by local blood flow. The aim of this study is to find out whether absorption of fentanyl in cachectic patients with cancer-related pain is different from that of normal weight cancer patients. We recruited ten normal weight (mean body mass index (BMI) 23kg/m2) and ten cachectic (mean BMI 16kg/m2) cancer pain patients. A transdermal fentanyl patch with a dose approximately equianalgesic to the patients’ previous opioid dose was administered to the upper arm of the patient for 3days. Prior to patch application, the height, weight and BMI of the patient, as well as upper arm skin temperature, local sweating, thickness of skin fold and local blood flow were measured. Plasma fentanyl concentrations were analyzed from blood samples taken at baseline, 4, 24, 48 and 72h. Plasma fentanyl concentrations adjusted to dose were significantly lower at 48 and 72h in cachectic patients than normal weight patients. The cachectic patients had a significantly thinner upper arm skin fold, but no differences were found in local blood flow, sweating, or skin temperature. Absorption of transdermal fentanyl is impaired in cachectic patients compared with that of normal weight cancer pain patients.

Estimation of total body water from bioelectrical impedance spectroscopy in oncology outpatients receiving radiotherapy and agreement with three prediction equations

Bioelectrical impedance spectroscopy (BIS) may be more accurate in determining total body water (TBW) than bioelectrical impedance analysis (BIA). The present study compared the agreement between three TBW prediction equations developed using BIA and BIS-derived TBW in oncology outpatients. A cross-sectional, observational study was conducted in 37 outpatients receiving radiotherapy (27 males/10 females, aged 68.3 +/- 10.2 years). TBW was estimated by BIS (TBW(BIS)) and three BIA TBW prediction equations (TBW(ca-u): underweight cancer patients; TBW(ca-n): normal-weight cancer patients; and TBW(rad): patients receiving radiotherapy). Bland-Altman analyses determined agreement between methods. BIS-derived TBW using new resistivity constants was calculated. The mean +/- SD of TBW estimated by BIS was 39.8 +/- 8.3 L, which was significantly different from the prediction equations; TBW(rad) 35.1 +/- 7.9 L, TBW(ca-u) 33.1 +/- 7.5 L and TBW(ca-n) 32.3 +/- 7.3 L, (P < 0.001). Using new resistivity constants, TBW was 36.2 +/- 8.1 L but this still differed from the equations (P < 0.001). Bias between TBW(BIS) and that predicted by the equations was in the range 4.7-7.4 L or 1.1-3.9 L using new resistivity constants. TBW estimated by BIS cannot be directly compared with oncology-specific BIA equations, suggesting that BIS cannot be used at the group level in outpatients receiving radiotherapy. There was a reduced bias with BIS using new resistivity constants; however, further research should determine any advantage of BIS over BIA in this population.

Estimation of total body water from bioelectrical impedance analysis in patients with pancreatic cancer -- agreement between three methods of prediction.

Bioelectrical impedance analysis (BIA) is a useful field measure to estimate total body water (TBW). No prediction formulae have been developed or validated against a reference method in patients with pancreatic cancer. The aim of this study was to assess the agreement between three prediction equations for the estimation of TBW in cachectic patients with pancreatic cancer. Resistance was measured at frequencies of 50 and 200 kHz in 18 outpatients (10 males and eight females, age 70.2 +/- 11.8 years) with pancreatic cancer from two tertiary Australian hospitals. Three published prediction formulae were used to calculate TBW - TBWs developed in surgical patients, TBWca-uw and TBWca-nw developed in underweight and normal weight patients with end-stage cancer. There was no significant difference in the TBW estimated by the three prediction equations - TBWs 32.9 +/- 8.3 L, TBWca-nw 36.3 +/- 7.4 L, TBWca-uw 34.6 +/- 7.6 L. At a population level, there is agreement between prediction of TBW in patients with pancreatic cancer estimated from the three equations. The best combination of low bias and narrow limits of agreement was observed when TBW was estimated from the equation developed in the underweight cancer patients relative to the normal weight cancer patients. When no established BIA prediction equation exists, practitioners should utilize an equation developed in a population with similar critical characteristics such as diagnosis, weight loss, body mass index and/or age. Further research is required to determine the accuracy of the BIA prediction technique against a reference method in patients with pancreatic cancer.

Bioelectrical impedance analysis to assess changes intotal body water in patients with cancer

Predominantly based on studies in obese individuals, the applicability of single-frequencybioelectrical impedance analysis (BIA) to measure changes in total body water and fat-free mass has been questioned. To further clarify this issue, we compared changes in BIA-derived height 2/resistance (ht 2/R) with changes in total body water (deuterium dilution, Δ-TBWdeu) in cancer patients participating in a clinical trial. Thirty-three patients (mean body mass index 23.2 ± 3.5 kg /M2) were studied after an average follow-up of 11 weeks. Changes in TBW-deu occurred in both directions (mean 0.2 ± 1.6 L, range −3.3 to 3.1 L). These changes were significantly predicted by changes in ht 2/R ( r 2 0.43, P < 0.0001, SEE 1.22 L), although precision was poor (residual SD 1.2 L). There were in this regard no significant differences between patients with and without underweight. We conclude that in underweight and normal-weight cancer patients, BIA-derived changes in ht 2/R significantly predict changes in total body water assessed by deuterium dilution.

Insulin secretion, glucose production, and insulin sensitivity in underweight and normal-weight volunteers, and in underweight and normal-weight cancer patients: A Clinical Research Center Study

Severe malnutrition (< 65% ideal body weight [IBW]) is associated with reduced insulin secretion, decreased receptor affinity, and glucose intolerance. To characterize the abnormality of mild malnutrition in terms of insulin action, both the insulin sensitivity index and insulin secretion were measured in 15 underweight and 15 normal-weight volunteers. Ten patients had localized squamous cell carcinomas of the head and neck, and 20 were normal controls. After a 10-hour overnight fast, all volunteers were studied using Bergman's modified intravenous (IV) glucose tolerance test (IVGTT). Body weight and diagnosis were compared using a 2 × 2 ANOVA. The acute insulin response to IV glucose was reduced in normal-weight and underweight cancer patients by approximately 40% to 50% ( P < .05). Both groups of cancer patients had a significantly reduced rate of glucose disposal (1.25 ± 0.29 and 1.27 ± 0.23 %/min) compared with the healthy volunteers (1.82 ± 0.21 and 1.81 ± 0.24 %/min, respectively, P < .05). Glucose production (GP) was significantly increased in the underweight cancer patients versus the weight-matched volunteers (13.9 ± 1.3 v 10.8 ± 0.5 μmol/kg/min, P < .05). Normal-weight and underweight cancer patients had a 32% to 44% reduction in insulin sensitivity ( P < .05). In contrast to the effects of cancer, underweight controls had twice the insulin sensitivity compared with normal-weight controls ( P < .01). Since insulin secretion decreased in underweight controls, the increased insulin sensitivity may have been due to an increased insulin action and to factors associated with leanness.