Background Altered adipose tissue (AT) metabolism in cancer‐associated weight loss via inflammation, lipolysis, and white adipose tissue (WAT) browning is primarily implicated from rodent models; their contribution to AT wasting in cancer patients is unclear. Methods Energy expenditure (EE), plasma, and abdominal subcutaneous WAT were obtained from men (aged 65 ± 8 years) with cancer, with (CWL, n = 27) or without (CWS, n = 47) weight loss, and weight‐stable non‐cancer patients (CON, n = 26). Clinical images were assessed for adipose and muscle area while plasma and WAT were assessed for inflammatory, lipolytic, and browning markers. Results CWL displayed smaller subcutaneous AT (SAT; P = 0.05) and visceral AT (VAT; P = 0.034) than CWS, and displayed higher circulating interleukin (IL)‐6 (P = 0.01) and WAT transcript levels of IL‐6 (P = 0.029), IL‐1β (P = 0.042), adipose triglyceride lipase (P = 0.026), and browning markers (Dio2, P = 0.03; PGC‐1a, P = 0.016) than CWS and CON. There was no difference across groups in absolute REE (P = 0.061), %predicted REE (P = 0.18), circulating free fatty acids (FFA, P = 0.13) or parathyroid hormone‐related peptide (PTHrP; P = 0.88), or WAT protein expression of inflammation (IL‐6, P = 0.51; IL‐1β, P = 0.29; monocyte chemoattractant protein‐1, P = 0.23) or WAT protein or gene expression of browning (uncoupling protein‐1, UCP‐1; P = 0.13, UCP‐1, P = 0.14). In patients with cancer, FFA was moderately correlated with WAT hormone‐sensitive lipase transcript (r = 0.38, P = 0.018, n = 39); circulating cytokines were not correlated with expression of WAT inflammatory markers and circulating PTHrP was not correlated with expression of WAT browning markers. In multivariate regression using cancer patients only, body mass index (BMI) directly predicted SAT (N = 25, R2 = 0.72, P < 0.001), VAT (N = 28, R2 = 0.64, P < 0.001), and absolute REE (N = 22, R2 = 0.43, P = 0.001), while BMI and WAT UCP‐1 protein were indirectly associated with %predicted REE (N = 22, R2 = 0.45, P = 0.02), and FFA was indirectly associated with RQ (N = 22, R2 = 0.52, P < 0.001). Conclusions Cancer‐related weight loss was associated with elevated circulating IL‐6 and elevations in some WAT inflammatory, lipolytic and browning marker transcripts. BMI, not weight loss, was associated with increased energy expenditure. The contribution of inflammation and lipolysis, and lack thereof for WAT browning, will need to be clarified in other tumour types to increase generalizability. Future studies should consider variability in fat mass when exploring the relationship between cancer and adipose metabolism and should observe the trajectory of lipolysis and energy expenditure over time to establish the clinical significance of these associations and to inform more mechanistic interpretation of causation.
Background: There is a need to better understand the relationship between functional impairment and muscle mass in cancer cachexia. This study aimed to establish the relationship between computed tomography (CT)-derived muscle cross-sectional area (CSA), radiodensity, and skeletal muscle index (SMI) and dual energy X-ray absorptiometry (DXA) parameters with functional performance in cancer patients.Materials and Methods: Handgrip strength, stair climb power (SCP), onerepetition maximum (1RM) strength, and body composition (CT and DXA) were compared across cancer patients with cachexia (CAC; N = 28), without cachexia (CNC; N = 28), and non-cancer patients (CON; N = 19). Multivariate regression was performed to find predictors of function. Results: CAC had lower CT muscle CSA and SMI and lower DXA appendicular lean mass (ALM) than CNC or CON (p ≤ 0.011). Muscle radiodensity was not different across groups despite larger proportion of low CT SMI in CAC, and CAC performed worse in SCP than CON (p = 0.018). In cancer patients, DXA ALM and CT muscle CSA each predicted physical function (p ≤ 0.05); muscle radiodensity did not, and DXA ALM explained more variability in SCP and 1RM than CT muscle CSA. Conclusions: Stair climb power was reduced in cancer cachexia; muscle radiodensity was not. Muscle mass by CT or DXA, but not radiodensity, predicted functional performance in cancer patients.
IMPORTANCEThere is substantial evidence demonstrating racial disparities in the survival outcomes of patients with head and neck cancer. The reporting and representation of race and ethnicity in cancer trials is crucial for generalizability of trial results to patient care and reduction of racial health disparities in head and neck cancers. Racial disparities in oncologic outcomes across various therapeutic interventions may only manifest when diverse races are appropriately represented in trials.OBJECTIVE To characterize the reporting and representation of race and ethnicity in head and neck cancer clinical trials.EVIDENCE REVIEW A systematic search of published trials and those available on ClinicalTrials.gov was conducted to identify 3973 studies from 2010 to 2020. Title, abstract, and full-text review yielded 155 trials for data extraction of patient demographics. Year of publication, type of intervention, publication source, and funding source were also collected. Race and ethnicity data were compared with Surveillance, Epidemiology, and End Results (SEER) Program cancer registry data. FINDINGS Of the 155 included studies, only 89 (57%) reported race or ethnicity. Only 81 (52%) of the studies reported detailed classification of race or ethnicity per the US Census Bureau classification scheme. Race and ethnicity reporting varied considerably with year of publication, type of intervention, data source, and funding source. Studies in the latter half of the decade were more likely to report race or ethnicity (odds ratio, 2.78; 95% CI, 1.33-5.80), with the highest number in 2019 (24 of 30 [80%] trials), followed by 2020 (20 of 29 [69%] trials). Among the possible interventions, trials on therapeutic chemoradiation most frequently reported race or ethnicity (11 of 12 [92%]), followed by supportive drug trials (22 of 31 [71%]), and then therapeutic chemotherapy trials (28 of 48 [58%]). When compared with SEER data, race and ethnicity distribution in clinical trials showed fewer Black patients (10% vs 8%) and Asian or Pacific Islander patients (6% vs 2%). CONCLUSIONS AND RELEVANCEIn this systematic review, nearly half of head and neck cancer trials in the past decade did not report the race or ethnicity of participants. Participation of Black and Asian or Pacific Islander patients does not adequately reflect the US population's head and neck cancer demographics, limiting the generalizability of trial results and adding to racial health disparities in patients with head and neck cancers.
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