Cancer-associated cachexia — understanding the tumour macroenvironment and microenvironment to improve management

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/281046/pdf (57).pdf

Reliability and Concurrent Validity of the SARC-F and Its Modified Versions: A Systematic Review and Meta-Analysis.

This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer-related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence-based guidelines, systematic reviews and meta-analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as "at risk" of malnutrition or with a high-risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment; people identified as "at risk" of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer-related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer-related malnutrition and sarcopenia should be individualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer-related malnutrition and sarcopenia.

/pdf/clinical-oncology-society-of-australia-position-statement-on-38i1208yyi.pdf

Clinical Oncology Society of Australia: Position statement on cancer-related malnutrition and sarcopenia.

Sarcopenia is associated with poor clinical outcomes of patients who underwent esophagectomy. The current diagnostic criteria for sarcopenia are complex and laborious. We aimed to employ the simple and economic indicator sarcopenia index (SI = creatinine/cystatin C ×100) to screen for sarcopenia and to evaluate its prognostic value in patients with esophageal cancer (EC).Older participants in the National health and nutrition examination survey (NHANES) database (1999-2002) were divided into three groups according to tertiles of the SI value to explore the feasibility of SI in the diagnosis of sarcopenia. Restricted cubic spline (RCS) was utilized to show the non-linear relationship between all-cause mortality and SI. Patients with EC admitted to Jinling Hospital were enrolled to validate the efficacy and prognostic value of SI. Cut-off values of SI were determined using receiver operating characteristic curves. Multivariable logistic analyses and Cox analyses were used to identify the independent factors of postoperative complications and long-term survival, respectively.A total of 989 participants were identified from the NHANES database. SI showed the diagnostic value of sarcopenia (tertile 1 vs. tertile 3: odds ratio [OR]=3.67, 95% confidence interval [CI]: 1.52-8.87, p=0.004; tertile 2 vs. tertile 3: OR=1.79, 95% CI: 0.75-4.28, p=0.191) adjusted for race, gender, and body mass index (BMI). Individuals with SI ≤ 68 had a poorer overall survival (OS) (hazard ratio [HR]=2.14, 95% CI: 1.71-2.68, p<0.001), and the RCS plot showed that the all-cause mortality risk gradually decreased with the increase in SI. Then, 203 patients with EC were enrolled, of which 76 patients were diagnosed with sarcopenia. There was a linear correlation between SI and skeletal muscle index and prealbumin, indicating that SI was reliable for diagnosing sarcopenia. Patients in the high sarcopenia risk group (Male: SI < 62; Female: SI < 55) showed a higher incidence of complications (OR=3.50, 95% CI: 1.85-6.61, p<0.001) and poorer long-term survival (HR=2.62, 95% CI: 1.02-6.77, p=0.046).SI could be used to identify sarcopenia in patients with EC, and it is a useful prognostic factor of postoperative complications and long-term survival. 

/pdf/serum-creatinine-cystatin-c-ratio-as-a-screening-tool-for-1mforbru.pdf

Serum creatinine/cystatin C ratio as a screening tool for sarcopenia and prognostic indicator for patients with esophageal cancer

Sarcopenia is an important prognostic factor of lung cancer. The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI, serum creatinine × cystatin C-based glomerular filtration rate) are novel screening tools for sarcopenia; however, the diagnostic accuracy of the CCR and SI for detecting sarcopenia remains unknown. We aimed to explore and validate the diagnostic values of the CCR and SI for determining sarcopenia in non-small cell lung cancer (NSCLC) and to explore their prognostic values for overall survival.We conducted a prospective cohort study of adult patients with stage IIIB or IV NSCLC. Levels of serum creatinine and cystatin C were measured to calculate the CCR and SI. Sarcopenia was defined separately using CCR, SI, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Participants were randomly sampled into derivation and validation sets (6:4 ratio). The cutoff values for diagnosing sarcopenia were determined based on the derivation set. Diagnostic accuracy was analysed in the validation set through receiver operating characteristic (ROC) curves. Cox regression models and survival curves were applied to evaluate the impact of different sarcopenia definitions on survival.We included 579 participants (women, 35.4%; mean age, 58.4 ± 8.9 years); AWGS-defined sarcopenia was found in 19.5% of men and 10.7% of women. Both CCR and SI positively correlated with computed tomography-derived and bioimpedance-derived muscle mass and handgrip strength. The optimal cutoff values for CCR and SI were 0.623 and 54.335 in men and 0.600 and 51.742 in women, with areas under the ROC curves of 0.837 [95% confidence interval (CI): 0.770-0.904] and 0.833 (95% CI: 0.765-0.901) in men (P = 0.25), and 0.808 (95% CI: 0.682-0.935) and 0.796 (95% CI: 0.668-0.924) in women (P = 0.11), respectively. The CCR achieved sensitivities and specificities of 73.0% and 93.7% in men and 85.7% and 65.7% in women, respectively; the SI achieved sensitivities and specificities of 75.7% and 86.5% in men and 92.9% and 62.9% in women, respectively. CCR-defined, SI-defined, and AWGS-defined sarcopenia were independently associated with a high mortality risk [hazard ratio (HR) = 1.75, 95% CI: 1.25-2.44; HR = 1.55, 95% CI: 1.11-2.17; and HR = 1.76, 95% CI: 1.22-2.53, respectively].CCR and SI have satisfactory and comparable diagnostic accuracy and prognostic values for sarcopenia in patients with advanced NSCLC. Both may serve as surrogate biomarkers for evaluating sarcopenia in these patients. However, further external validations are required. 

Serum creatinine and cystatin C‐based diagnostic indices for sarcopenia in advanced non‐small cell lung cancer

A new index based on serum creatinine and cystatin C is useful for assessing sarcopenia in patients with advanced cancer.

Comparing SARC-F with SARC-CalF for screening sarcopenia in advanced cancer patients.

Dach1 Deficiency Drives Alveolar Epithelium Apoptosis in Pulmonary Fibrosis via Modulating C-Jun/Bim Activity.

The effectiveness of corticosteroids (GCs) varies greatly in interstitial lung diseases (ILDs). In this study, we aimed to compare the gene expression profiles of patients with cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP) and identify the molecules and pathways responsible for GCs sensitivity in ILDs. Three datasets (GSE21411, GSE47460, and GSE32537) were selected. Differentially expressed genes (DEGs) among COP, IPF, NSIP, and healthy control (CTRL) groups were identified. Functional enrichment analysis and protein-protein interaction network analysis were performed to examine the potential functions of DEGs. There were 128 DEGs when COP versus CTRL, 257 DEGs when IPF versus CTRL, 205 DEGs when NSIP versus CTRL, and 270 DEGs when COP versus IPF. The DEGs in different ILDs groups were mainly enriched in the inflammatory response. Further pathway analysis showed that "interleukin (IL)-17 signaling pathway" (hsa04657) and "tumor necrosis factor (TNF) signaling pathway" were associated with different types of ILDs. A total of 10 genes associated with inflammatory response were identified as hub genes and their expression levels in the IPF group were higher than those in the COP group. Finally, we identified two GCs' response-related differently expressed genes (FOSL1 and DDIT4). Our bioinformatics analysis demonstrated that the inflammatory response played a pathogenic role in the progression of ILDs. We also illustrated that the inflammatory reaction was more severe in the IPF group compared to the COP group and identified two GCs' response-related differently expressed genes (FOSL1 and DDIT4) in ILDs. 

Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease

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A new index based on serum creatinine and cystatin C is useful for assessing sarcopenia in patients with advanced cancer.

Comparing SARC-F with SARC-CalF for screening sarcopenia in advanced cancer patients.

Dach1 Deficiency Drives Alveolar Epithelium Apoptosis in Pulmonary Fibrosis via Modulating C-Jun/Bim Activity.

Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease