Primary Tumor Fluorine‐18 Fluorodeoxydglucose (18F‐FDG) Is Associated With Cancer-Associated Weight Loss in Non-Small Cell Lung Cancer (NSCLC) and Portends Worse Survival

Olaechea, Santiago; Gannavarapu, Bhavani S.; Alvarez, Christian; Gilmore, L Anne; Sarver, Brandon; Xie, Daxing; Infante, Rodney E.; Iyengar, Puneeth

doi:10.3389/fonc.2022.900712

Cited by 4 publications

(5 citation statements)

References 38 publications

(61 reference statements)

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“…In cancer patients, the role of the Warburg effect in the pathogenesis of cancer cachexia is not studied as thoroughly, as in the nude mice. For instance, the Warburg effect was seen as responsible for weight loss in cancer patients 34–36 . In other studies, increased glucose turnover and hepatic gluconeogenesis were seen in cancer patients 12–14 …”

Section: Discussionmentioning

confidence: 86%

“…For instance, the Warburg effect was seen as responsible for weight loss in cancer patients. [34][35][36] In other studies, increased glucose turnover and hepatic gluconeogenesis were seen in cancer patients. [12][13][14] Only patients with early pancreatobiliary cancer are eligible for curative surgery, and such patients may not have cachectic states.…”

Section: Discussionmentioning

confidence: 93%

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The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma

Zhang

Sui

et al. 2023

The FASEB Journal

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We have studied whether the Warburg effect (uncontrolled glycolysis) in pancreatobiliary adenocarcinoma triggers cachexia in the patient. After 74 pancreatobiliary adenocarcinomas were removed by surgery, their glucose transporter‐1 and four glycolytic enzymes were quantified using Western blotting. Based on the resulting data, the adenocarcinomas were equally divided into a group of low glycolysis (LG) and a group of high glycolysis (HG). Energy homeostasis was assessed in these cancer patients and in 74 non‐cancer controls, using serum albumin and C‐reactive protein and morphometrical analysis of abdominal skeletal muscle and fat on computed tomography scans. Some removed adenocarcinomas were transplanted in nude mice to see their impacts on host energy homeostasis. Separately, nude mice carrying tumor grafts of MiaPaCa‐2 pancreatic adenocarcinoma cells were treated with the glycolytic inhibitor 3‐bromopyruvate and with emodin that inhibited glycolysis by decreasing hypoxia‐inducible factor‐1α. Adenocarcinomas in both group LG and group HG impaired energy homeostasis in the cancer patients, compared to the non‐cancer reference. The impaired energy homeostasis induced by the adenocarcinomas in group HG was more pronounced than that by the adenocarcinomas in group LG. When original adenocarcinomas were grown in nude mice, their glycolytic abilities determined the levels of hepatic gluconeogenesis, skeletal muscle proteolysis, adipose‐tissue lipolysis, and weight loss in the mice. When MiaPaCa‐2 cells were grown as tumors in nude mice, 3‐bromopyruvate and emodin decreased tumor‐induced glycolysis and cachexia, with the best effects being seen when the drugs were administered in combination. In conclusion, the Warburg effect in pancreatobiliary adenocarcinoma triggers cancer cachexia.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 93%

The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma

Zhang

Sui

et al. 2023

The FASEB Journal

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“…Through the development of a retrospective clinical data set of 3,180 patients with gastrointestinal and pulmonary cancer, we have previously evaluated associations between the incidence of cachexia with pretreatment patient medication use, laboratory values, and positron emission tomography imaging in a search for potential diagnostic and interventional tools against this syndrome. [5][6][7] In these projects, we have consistently detected a significant influence of patient demographic characteristics on cachectic weight loss at the time of cancer diagnosis. Consequently, this study intends to further characterize the relationship between cachexia and patient race, ethnicity, and socioeconomic factors.…”

Section: Introductionmentioning

confidence: 90%

Race, Ethnicity, and Socioeconomic Factors as Determinants of Cachexia Incidence and Outcomes in a Retrospective Cohort of Patients With Gastrointestinal Tract Cancer

Olaechea

Sarver

Liu

et al. 2023

JCO Oncology Practice

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PURPOSE Cachexia is a paraneoplastic syndrome of unintentional adipose and muscle tissue wasting with severe impacts to functionality and quality of life. Although health inequities across minority and socioeconomically disadvantaged groups are known, the role of these factors in cachexia progression is poorly characterized. This study aims to evaluate the relationship between these determinants and cachexia incidence and survival in patients with gastrointestinal tract cancer. METHODS Through retrospective chart review from a prospective tumor registry, we established a cohort of 882 patients with gastroesophageal or colorectal cancer diagnosed between 2006 and 2013. Patient race, ethnicity, private insurance coverage, and baseline characteristics were evaluated through multivariate, Kaplan-Meier, and Cox regression analyses to determine associations with cachexia incidence and survival outcomes. RESULTS When controlling for potentially confounding covariates (age, sex, alcohol and tobacco history, comorbidity score, tumor site, histology, and stage), Black (odds ratio [OR], 2.447; P < .0001) and Hispanic (OR, 3.039; P < .0001) patients are at an approximately 150% and 200%, respectively, greater risk of presenting with cachexia than non-Hispanic White patients. Absence of private insurance coverage was associated with elevated cachexia risk (OR, 1.439; P = .0427) compared to privately insured patients. Cox regression analyses with previously described covariates and treatment factors found Black race (hazard ratio [HR], 1.304; P = .0354) to predict survival detriments, while cachexia status did not reach significance ( P = .6996). CONCLUSION Our findings suggest that race, ethnicity, and insurance play significant roles in cachexia progression and related outcomes that are not accounted for by conventional predictors of health. Disproportionate financial burdens, chronic stress, and limitations of transportation and health literacy represent targetable factors for mitigating these health inequities.

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“…A recent review described how imaging modalities for quantitative and qualitative change in adipose tissue, organs, and muscle compartments are assessed for the diagnosis and monitoring of cancer cachexia [3]. Olaechea et al [4] reported a signi cant positive relationship between cancer-associated weight loss at diagnosis and increased primary tumor SUV max for 18 F-FDG uptake in patients with non-small cell lung cancer (NSCLC).…”

Section: Introductionmentioning

confidence: 99%

“…An experimental study has shown that 18 F-FDG uptake is higher in cachexia-inducing tumor cells than in non-cachexia tumor cells [5]. Potentially, escalated tumor glucose consumption, such as high 18 F-FDG uptake, is associated with the presence of a tumor phenotype that induces weight loss [4]. Previous studies have reported that body weight is closely related to physiological 18 F-FDG uptake by the liver [6,7].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of visual cardiac 18F-FDG uptake in advanced non-small cell lung cancer

Hashimoto,

Kaira,

Imai

et al. 2024

Preprint

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Background: Two-deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (PET) is useful for detecting malignant lesions; however, the clinical significance of cardiac 18F-FDG uptake in patients with cancer remains unclear. This preliminary study explored the relationship between cardiac 18F-FDG uptake and advanced diseases such as cancer cachexia in non-small cell lung cancer (NSCLC). Methods: Forty-three patients with advanced NSCLC who underwent 18F-FDG PET and complained of weight loss before the first-line systemic therapy were retrospectively included in this study. Visual assessment using a 5-point scale based on 18F-FDG uptake was performed; a cut-off score of 3 was determined, a low score was 1, 2, or 3, and a high score was 4 or 5). Results: High and low visual cardiac 18F-FDG uptakes were observed in 27 (62.8%) and 16 (37.2%) patients, respectively. Of the 43 patients, 17 (39.5%) definitely had cachexia, and 26 (60.5%) did not. A low visual score and standardized uptake valuemax for cardiac 18F-FDG uptake were significantly associated with high metabolic tumor activity and a high neutrophil-to-lymphocyte ratio, whereas a low visual score for cardiac 18F-FDG uptake and high metabolic tumor activity were significantly associated with cachexia. The amount of cardiac 18F-FDG accumulation depicted a close relationship with body mass index, low weight loss, and inflammation. The combination of cachexia and low visual cardiac 18F-FDG uptake was identified as a significant predictor for poor overall survival (OS). Conclusion: Decreased visual cardiac 18F-FDG uptake was associated with poor nutritional status and OS, and cachexia in patients with advanced NSCLC.

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Primary Tumor Fluorine‐18 Fluorodeoxydglucose (18F‐FDG) Is Associated With Cancer-Associated Weight Loss in Non-Small Cell Lung Cancer (NSCLC) and Portends Worse Survival

Cited by 4 publications

References 38 publications

The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma

The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma

Race, Ethnicity, and Socioeconomic Factors as Determinants of Cachexia Incidence and Outcomes in a Retrospective Cohort of Patients With Gastrointestinal Tract Cancer

Clinical significance of visual cardiac 18F-FDG uptake in advanced non-small cell lung cancer

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