Impact of Cachexia and First-Line Systemic Therapy for Previously Untreated Advanced Non-Small Cell Lung Cancer: NEJ050A.

BACKGROUND: Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy. METHODS: We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy. RESULTS: A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003). CONCLUSIONS: Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.

Impact of waitlist weight change on outcomes in heart transplant recipients: a UNOS database analysis.

BACKGROUND: While the effect of pre-transplant weight on patient outcomes following heart transplantation (HTx) has previously been studied, data regarding the impact of dynamic weight change prior to HTx are extremely limited. OBJECTIVES: We sought to elucidate the interaction between HTx listing weight and weight change while waitlisted, and explore how that interaction impacts post-HTx survival in a continuous manner. METHODS: Adult patients listed for HTx from 1987 to 2020 were identified from UNOS database. Three-dimensional restricted cubic spline analysis explored post-HTx survival relative to both changes in BMI/weight and BMI at time of HTx listing. Continuous predictor variables were analyzed with Cox proportional hazards method. RESULTS: 9,628 included patients underwent HTx. Median recipient age was 55 [IQR 46-62] years, and 21% were females. 53% of patients lost while 47% gained weight on the waitlist. Median BMI (27.6 kg/m2 [24.3-31.3] vs. 27.4 kg/m2 [24.2-30.9], paired p < 0.001) and weight (84.8 kg [73.0-98.0] kg vs. 84.4 kg [72.6-96.6], p < 0.001) were similar at listing and transplant. One-year survival was 89.3%. Weight loss over 3 BMI points or 10 kg was associated with higher hazard of death irrespective of listing BMI. In non-obese patients, some weight gain (1-4 BMI points or 5-15 kg) was associated with improved survival. In cachectic patients (BMI < 18.5), failure to gain weight was associated with worse survival. CONCLUSIONS: Impact of weight change varies depending on listing BMI. While a survival benefit is seen in non-obese patients who gain some weight, significant weight loss is associated with poorer survival.

Cachexia in tuberculosis in South-East Asian and African regions: knowledge gaps and untapped opportunities.

Tuberculosis (TB) and cachexia are clinical entities that have a defined relationship, making them often found together. TB can lead to cachexia, while cachexia is a risk factor for TB. This article reviews cachexia in Tuberculosis patients in Southeast Asian and African regions by conducting a comprehensive literature search across electronic databases such as PubMed, Google Scholar, and Research Gate between 2013 and 2024 using keywords including 'Africa', 'cachexia', 'prevalence', 'implications', 'tuberculosis', and 'Southeast Asia. This article utilized only studies that satisfied the inclusion criteria, revealing knowledge gaps and untapped opportunities for cachexia in TB across Southeast Asian and African regions. Many Southeast Asian and Western Pacific patients initially receive a tuberculosis diagnosis. Sub-Saharan African countries are among the 30 high TB burden nations, according to the WHO. Food inadequacy and heightened energy expenditure can impair the immune system, leading to latent TB and subsequently, active infection. Symptoms needing attention: shortness of breath, productive cough, hyponatremia at 131 mmol/l, hypoalbuminemia at 2.1 g/dl, elevated aspartate transaminase at 75 U/l, increased lactate dehydrogenase at 654, and normocytic anemia. Comorbidities, such as kidney disease, cardiovascular disease, and asthma, can influence the nutritional status of individuals with TB. While efforts like screening, contact tracing, and utilizing gene Xpert to detect TB cases were implemented, only a few proved effective. It is essential to conduct further studies, including RCTs, in Southeast Asia and Africa to evaluate and manage cachexia in TB patients.

Relationship between Survival Days, Cancer Cachexia, and Activities of Daily Living in Palliative Cancer Patients Undergoing Rehabilitation.

Objectives: Cancer cachexia has many effects on physical function and causes a decline in activities of daily living (ADL). Therefore, rehabilitation programs should be structured according to the degree of cancer cachexia. Currently, the evaluation of cancer cachexia is mainly based on body mass. However, there is no report on the use of the modified Glasgow Prognostic Score (mGPS) to evaluate the degree of cancer cachexia and survival prognosis in palliative cancer patients for whom rehabilitation has been prescribed. This study used mGPS to examine the prevalence of cancer cachexia in palliative cancer patients undergoing rehabilitation and the impacts of cancer cachexia, ADL, and complications on survival. Methods: The participants included 135 palliative cancer patients who were admitted to the hospital and underwent rehabilitation between 2020 and 2022. Cancer cachexia classification by mGPS was conducted, and logistic regression analysis was used to examine factors affecting the survival of palliative cancer patients undergoing rehabilitation. Results: The patients were grouped as follows: 6 (4.4%) normal, 13 (9.6%) undernourished, 12 (9.0%) pre-cachexia, and 104 (77.0%) refractory cachexia. Logistic regression analysis showed that the mGPS and BI affected survival. Conclusions: In a cohort of palliative cancer patients undergoing rehabilitation, 86% had cachexia. mGPS and BI were associated with survival outcomes. Combination of mGPS classification with ADL assessment may provide meaningful prognostic information in these patients.

Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors.

DESCRIPTION OF THE WORK: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia. PURPOSE: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment. PATIENTS AND METHODS: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life. RESULTS: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue. CONCLUSIONS: Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.

The lived experience of renal cachexia: An interpretive phenomenological analysis.

Background: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of 'life years lost' by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of 'renal cachexia' is poorly understood, under-diagnosed and even if recognised has limited treatment options. Objective: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. Design: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. Setting: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. Participants: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). Methods: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). Results: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. Conclusion: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. Registration: N/A.

The LEAP2 response to cancer-related anorexia-cachexia syndrome in male mice and patients.

The hormone ghrelin serves a protective role in cancer-related anorexia-cachexia syndrome (CACS) - a condition in which plasma levels of ghrelin rise, its administration lessens CACS severity, and experimentally-reduced signaling by its receptor (GHSR) worsens fat loss and anorexia and accelerates death. Yet, actions for the related hormone liver-expressed antimicrobial peptide-2 (LEAP2), which is an endogenous GHSR antagonist, are unexplored in CACS. Here, we found that plasma LEAP2 and LEAP2/ghrelin ratio were lower in Lewis Lung Carcinoma (LLC) and RM-9 prostate cancer CACS mouse models. Ghrelin deletion exaggerated losses of tumor-free body weight and fat mass, reduced food intake, reduced soleus muscle weight, and/or lowered grip strength in LLC or RM-9 tumor-bearing mice. LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake in LLC or RM-9 tumor-bearing mice. In a 55-subject cohort of patients with CACS or weight-stable cancer, the plasma LEAP2/total ghrelin ratio was negatively correlated with 6-month weight change preceding blood collection. These data demonstrate that ghrelin deletion exacerbates CACS in the LLC and RM-9 tumor-bearing mouse models while contrastingly, LEAP2 deletion reduces measures of CACS in these tumor-bearing mouse models. Further, they suggest that lower plasma LEAP2/ghrelin ratio protects against worsened CACS.

Mitochondrial antioxidant SkQ1 attenuates C26 cancer-induced muscle wasting in males and improves muscle contractility in female tumor-bearing mice.

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1x106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (~250 nmol/kg body weight/day) and administered to mice beginning seven days following tumor induction, while control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post-hoc test when interactions were significant (p≤0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1 and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC.

Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predicts Cachexia and Prognosis in Hepatocellular Carcinoma Patients.

OBJECTIVE: Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis. METHODS: Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS. RESULTS: Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0-4 vs. 5-6 points) (OR, 9.20; 95% CI: 4.68-18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13-7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0-4 vs. 5-6 points) (HR, 1.73; 95% CI: 1.19-2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0-4 points group had shorter OS than those in the FLIS 5-6 points group [20 months (95% CI, 14.7-25.3) vs. 43 months (95% CI, 27.7-58.3); P=0.001]. CONCLUSION: Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.

Mood, Anxiety, and Cognitive Alterations in Cancer Patients.

BACKGROUND AND OBJECTIVE: To analyze the cytokine profile in cerebrospinal fluid (CSF), as well as mood, anxiety, and cognition profiles in patients with CC. METHODS: One hundred and nine individuals were evaluated, 37 controls, 18 CWC, and 54 CC patients. Assessments included BDI, HADS, Digit Span, FAS-verbal, Animals/WMS-R, Matrix Reasoning and Vocabulary (WASI), and QLQ-C30. RESULTS: The CC group exhibited 62.96% depression and probable anxiety/depression, with 75.92% showing attention deficits. The CC and CWC groups demonstrated significant cognitive impairment on the WASI-Vocabulary test (CWC: 13.4 ± 2.2; CC: 15.9 ± 1.1) compared to the control group (Ct: 22.8 ± 1.6; p = 0.0002). In the QLQ-C30 scores, the CC group reported a greater perceived loss of quality of life and health deterioration (score of 17.5 ± 2.6) and lower scores on the Functional Scale (49.8 ± 4.5). The CC group had 18.52% illiteracy, 18.52% incomplete higher education, and 22.22% complete elementary education. The CC group also had lower weight (Ct: 67.8 ± 1.4; CWC: 61.7 ± 3.1; CC: 59.6 ± 1.7; p = 0.0023) and BMI (CC: 21.5 [18.3; 24.8]; Ct: 24.9 [23; 25.8]; p = 0.0021) compared to controls. Cytokines detected in the CSF were MCP-1, VEGF, IL-8, IP-10, and MIP-1ß. Higher concentrations of MCP-1 were found in cancer patients (CSC: 571.2 ± 105.8; CC: 399.5 ± 65.9; Ct: 1477 ± 0.1; p < 0.0001), along with lower levels of MIP-1ß (CC: 4345 [3060; 7353]) and VEGF (CC: 48.3 ± 2.0; CWC: 49.8 ± 3.8; Ct: 64.8 ± 3.2; p < 0.0001). CONCLUSIONS: The level of mental impairment (mood, anxiety, and cognitive deficits) correlated with cancer-associated and cachexia-associated inflammation, weight loss, low BMI, elevated C-reactive protein (CRP), leukocytosis, lymphopenia, anemia, hypoalbuminemia, and low scores on the QLQ-C30 questionnaire (Global Health Status, Functional Scale, Symptom Scale). The CC group exhibited a higher prevalence of depression/anxiety, a stronger correlation between depression and inflammation, and greater cognitive impairment in attention, reasoning, and language, alongside lower average educational attainment. The low concentration of certain cytokines in the CSF combined with elevated systemic CRP in cancer and cachexia, associated with mental disorders, presents a paradox that requires further investigation. Higher concentrations of the cytokine MCP-1 in cancer patient groups indicated a positive correlation with the preservation of language abilities in these patients.

Increased Myocardial MAO-A, Atrogin-1, and IL-1ß Expression in Transgenic Mice with Pancreatic Carcinoma-Benefit of MAO-A Inhibition for Cardiac Cachexia.

Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients' prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1ß+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1ß (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (-17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1ß+, and TNF+ cell fraction as well as in COX2, IL-1ß, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity.

The additional benefit of computed tomography in cancer patients: impacts of sarcopenia and cachexia on quality of life during chemotherapy.

Objective: This study evaluates the effects of sarcopenia and cachexia on the quality of life (QoL) of patients with gastrointestinal cancer during their initial cycle of chemotherapy, emphasizing the significance of computed tomography (CT) in assessing muscle mass. Materials and Methods: In this prospective study, we evaluated 60 adult patients with gastrointestinal cancer who started chemotherapy between January and December of 2017. Sarcopenia was diagnosed on the basis of CT findings, and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Results: The mean age was 60.9 years, and 33 (55.0%) of the patients were men. Of the 60 patients, 33 (55.0%) had cachexia and 14 (23.3%) had sarcopenia. Chemotherapy significantly reduced QoL, particularly in the physical, role functioning, and social domains, with no differences between the cachexia and sarcopenia groups. Conclusion: Among patients with gastrointestinal cancer submitted to chemotherapy, the chemotherapy-induced decline in QoL does not seem to differ significantly between those with cachexia or sarcopenia, as classified by CT-measured muscle mass, and those without. However, CT-based muscle mass evaluation remains crucial for guiding customized intervention strategies. Integrating this evaluation in radiological reports can provide valuable insights for planning specific care, thus improving patient QoL during treatment.

Objetivo: Este estudo avalia os efeitos da sarcopenia e da caquexia na qualidade de vida de pacientes com câncer gastrointestinal durante o ciclo inicial de quimioterapia, enfatizando a importância da tomografia computadorizada (TC) na avaliação da massa muscular. Materiais e Métodos: Estudo prospectivo com 60 pacientes adultos com câncer gastrointestinal que iniciaram quimioterapia de janeiro a dezembro de 2017. A TC foi utilizada para o diagnóstico de sarcopenia e o Quality of Life Questionnaire Core 30 da European Organization for Research and Treatment of Cancer foi utilizado para avaliar a qualidade de vida. Resultados: A média de idade dos pacientes foi 60,9 anos e 33 (55%) eram homens. Entre os pacientes, 33 (55%) eram caquéticos e 14 (24%) eram sarcopênicos. A quimioterapia reduziu significativamente a qualidade de vida, especialmente nos domínios físico, de desempenho de papéis e social, sem diferenças entre os grupos caquéticos e sarcopênicos. Conclusão: A diminuição da qualidade de vida não difere significativamente entre pacientes caquéticos/sarcopênicos e não caquéticos/não sarcopênicos com câncer gastrointestinal submetidos a quimioterapia, conforme classificado pela massa muscular medida por TC. No entanto, a avaliação da massa muscular por TC continua crucial para orientar estratégias de intervenção personalizadas. A integração dessa avaliação nos laudos radiológicos pode fornecer informações valiosas para o planejamento de cuidados específicos, melhorando a qualidade de vida dos pacientes durante o tratamento.

AB016. Intracranial tumor characteristics and the incidence of cachexia: a cross-sectional study.

BACKGROUND: Intracranial tumors constitute a significant burden on global morbidity and disability, posing a risk for the development of cachexia. Cancer cachexia is a multi-organ syndrome of systemic inflammation and negative energy balance which may lead to diminished treatment efficacy and reduced survival rates. The association between intracranial tumor features and incidence of cachexia remains unknown. The purpose of this study is to investigate the association between the characteristics of intracranial tumors and the incidence of cachexia in patients. METHODS: We conducted a retrospective cross-sectional study to observe hospitalized intracranial tumor patients at Dr. Cipto Mangunkusumo Hospital. This study described the prevalence and the percentage of baseline characteristics, the diagnosis of cachexia was based on Evans criteria. Kolmogorov-Smirnov for the normality test. Bivariate analysis was done using the Chi-square test for qualified categorical variables, the Fischer test for unqualified categorical variables, and the Mann-Whitney test for ordinal variables. RESULTS: Our study revealed of 36 subjects with intracranial tumor diagnosis, the incidence of cachexia was higher in secondary brain tumors compared to primary brain tumors [odds ratio (OR) 5.5; 95% confidence interval (CI): 1.28-23.69; P=0.02]. Cancer cachexia occurs through inflammation, autonomic, and neuroendocrine pathways, leading to increased energy expenditure and decreased energy intake. The burden of secondary brain tumor amplifies the overall metabolic demands and systemic inflammation thus contributing to cachexia progression, which is identified by significant weight loss in patients with secondary brain tumor groups compared to primary tumors (P=0.01). Patients with cachexia tend to experience malnutrition and fatigue (P=0.04), which may interfere with their survival rates and quality of life. The most common neurological deficit observed in our subjects is headache (72.2%), while patients presenting with clinical manifestations of extremity weakness were more likely to develop cachexia (OR 6.4; 95% CI: 1.23-35.44; P=0.04). There were no significant differences in age distribution, gender, and brain tumor location among the subject groups. CONCLUSIONS: Patients with secondary brain tumors and extremity weakness are more likely to develop cachexia. The severity of cachexia can help distinguish between primary and secondary brain tumors. Clinicians should pay attention to neurological deficits, particularly extremity weakness, as it can worsen cachexia.

JNK Kinase regulates cachexia like syndrome in scribble knockdown tumor model of Drosophila melanogaster.

Cachexia and systemic organ wasting are metabolic syndrome often associated with cancer. However, the exact mechanism of cancer associated cachexia like syndrome still remain elusive. In this study, we utilized a scribble (scrib) knockdown induced hindgut tumor to investigate the role of JNK kinase in cachexia like syndrome. Scrib, a cell polarity regulator, also acts as a tumor suppressor gene. Its loss and mis-localization are reported in various type of malignant cancer-like breast, colon and prostate cancer. The scrib knockdown flies exhibited male lethality, reduced life span, systemic organ wasting and increased pJNK level in hindgut of female flies. Interestingly, knocking down of human JNK Kinase analogue, hep, in scrib knockdown background in hindgut leads to restoration of loss of scrib mediated lethality and systemic organ wasting. Our data showed that scrib loss in hindgut is capable of inducing cancer associated cachexia like syndrome. Here, we firstly report that blocking the JNK signaling pathway effectively rescued the cancer cachexia induced by scrib knockdown, along with its associated gut barrier disruption. These findings have significantly advanced our understanding of cancer cachexia and have potential implications for the development of therapeutic strategies. However, more research is needed to fully understand the complex mechanisms underlying this condition.

GDF15 antagonism limits severe heart failure and prevents cardiac cachexia.

AIMS: Heart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A. METHODS AND RESULTS: Mice were irradiated and reconstituted with bone marrow cells. Mice lacking functional PPP1R15A, exhibited dilated cardiomyopathy and severe weight loss following irradiation, whilst wild-type mice were unaffected. This was associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in circulation. We provide evidence that the blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. We also show the relevance of GDF15 to lean mass and protein intake in patients with heart failure. CONCLUSION: Our data suggest that cardiac stress mediates a GDF15-dependent pathway that drives weight loss and worsens cardiac function. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.

Frequency of weight and body composition increases in advanced non-small cell lung cancer patients during first line therapy.

BACKGROUND: The primary objective of this study was to assess the frequency of body composition increases and their relationships to changes in body weight in two cohorts of real world, treatment-naïve, advanced non-small cell lung cancer (NSCLC) patients. One cohort received the current standard of care (CSOC), which consisted of immunotherapy and newer chemotherapy regimens, and the other cohort was treated with the former standard of care (FSOC), consisting only of older platinum-containing regimens. METHODS: CSOC (n = 106) and FSOC (n = 88) cohorts of advanced NSCLC patients were included in this study. Weights were collected at each clinical visit, and body composition analysis from routine chest computed tomography via automated segmentation software assessed at baseline and at 6 and 12 weeks. Standard statistical methods were used to calculate relationships between changes in weight and in body composition. RESULTS: The CSOC cohort contained 106 stage IV NSCLC patients treated between 16/12/2014 and 22/10/2020 while the FSOC cohort contained 88 stage III/IV NSCLC patients treated between 16/6/2006 and 18/11/2014. While each cohort exhibited decreases in median weight, body mass index (BMI), mean skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at the 6 and 12 week time points, a subset of patients experienced increases in these parameters. Using a threshold of ≥2.5% increase for weight, BMI, SMI, and SATI at the 12 week time point, both cohorts showed similar (20.5% and 27.3%) increases in these parameters. With a cut point of ≥5% increase at 12 weeks follow-up, 8.0% to 25.0% of the patients gained ≥5% in weight, BMI, SMI and SATI. Comparing these results in each cohort showed no significant differences. Pearson coefficients for weight change related to changes in SMI and SATI at 6 and 12 weeks ranged from 0.31 to 0.58 with all P values <0.02. Pearson coefficients for weight change at 12 weeks related to changes in VATI and IMATI ranged from 0.26 to 0.47 with all P values <0.05. Comparison of Pearson coefficients for each cohort showed no significant differences. CONCLUSIONS: Although decreases in median weight, BMI, SMI and SATI were observed in both cohorts, similar percentage of patients in each cohort experienced increases in these parameters. These findings, plus the positive correlations between longitudinal measurements of weight, muscle mass and adipose tissue, indicate that weight gain in these patients involves increases in both muscle mass and adipose tissue. Upon validation, these findings could have implications for clinical trial design and for translational research in cancer cachexia.

Immunomodulation: A new approach to cancer cachexia, potentially suitable for aging.

Cancer cachexia is the prototypical example of comorbidity, occurring in most of cancer patients. It is a direct consequence of tumor growth and of the associated inflammatory/immune response. Cachexia can be exacerbated by anti-cancer therapies, frequently resulting in dose limitation and/or treatment delay or discontinuation. The pathogenesis of cancer cachexia is still unclear and includes nutritional, metabolic, hormonal and immunological components. Tumor ability to shape the immune response to its own advantage is now well accepted, while the possibility that such an altered immune response could play a role in the onset of cachexia is still an undefined issue. Indeed, most of the immune-related research on cachexia mainly focused on pro-inflammatory mediators, almost totally disregarding the interactions among immune cells and the homeostasis of peripheral tissues. The present review provides an overview of the immune system dysregulations occurring in cancer cachexia, focusing on the possibility that immunomodulating strategies, mainly developed to stimulate the anti-cancer immune response, could be useful to counteract cachexia as well. Cancer and cachexia are frequent comorbidities of aging. Along this line, cancer- and aging-associated muscle wasting likely coexist in the same patients. Since both conditions share some of the underlying mechanisms, the potential effectiveness of immunomodulation on sarcopenia of aging is discussed.

[The frequency of cachexia and its associated factors in elderly diabetic patients with chronic diseases: A study using the diagnostic criteria of the Asian Working Group for Cachexia].

OBJECTIVE: To evaluate the frequency of cachexia and its associated factors using the Asian Working Group for Cachexia (AWGC) criteria in elderly patients with diabetes and chronic diseases. METHODS: The subjects were diabetic outpatients of ≥65 years of age who were managed at Ise Red Cross Hospital. Patients with chronic disease (chronic heart failure, cancer, or chronic renal failure). Cachexia was evaluated based on the AWGC criteria and was defined as a body mass index (BMI) <21 kg/m2 and one or more of the following: anorexia, elevated C-reactive protein, and decreased grip strength. A logistic regression analysis was used to identify cachexia-related factors, with cachexia as the dependent variable, and various variables (basic attributes, blood glucose-related parameters, diabetic complications, comorbidities, and treatment) as explanatory variables. RESULTS: Two hundred forty-two patients (male, n=164; female, n=78) were included in the study. Forty patients (16.5%) had cachexia. A logistic analysis revealed that age (odds ratio (OR), 1.16; P<0.001), type 1 diabetes (OR, 15.25; P=0.002), diabetic retinopathy (OR, 5.72; P=0.001), and physical frailty (OR, 7.06; P<0.001) were associated with cachexia. CONCLUSION: Elderly diabetics with chronic diseases were more likely to have cachexia. According to the AWGC criteria, the frequency of cachexia was 16.5% in elderly patients with diabetes and chronic diseases. Additionally, type 1 diabetes, diabetic retinopathy, age, and physical frailty were identified as factors associated with cachexia. In elderly diabetes patients with chronic diseases, it is therefore important to raise awareness regarding cachexia when these related factors are diagnosed.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia.

Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition. METHODS: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-ß) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. RESULTS: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-ß. Logistic regression analysis has identified salivary IL-13 and TGF-ß as independent factors for cancer cachexia. CONCLUSIONS: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-ß as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings.

Transdermal Fentanyl in Patients with Cachexia-A Scoping Review.

Cachectic patients frequently require transdermal fentanyl (TDF) for pain management, but data on its efficacy and safety are scarce and inconsistent. This scoping review aims to analyze the evidence concerning TDF administration in patients with cachexia irrespective of the underlying pathology. The primary objective is to assess the analgesic efficacy and tolerability of TDF in cachectic patients. The secondary objective is to identify cachexia characteristics that may influence fentanyl pharmacokinetics (PK). A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to March 2024. The review included observational and clinical studies on cachectic patients with moderate to severe pain treated with TDF patches at any dosage or frequency. Phase 1 trials, animal studies, case reports, preclinical studies and conference abstracts were excluded. Nine studies were included: four studies reported that cachexia negatively impacted TDF efficacy, increasing required doses and lowering plasma concentrations; three studies found minimal or no impact of cachexia on TDF efficacy and PK; two studies suggested that cachexia might improve TDF outcomes. Study quality ranged from moderate to high, according to the National Institutes of Health (NIH) Quality Assessment Tool. The current evidence is insufficient to provide any definitive recommendations for TDF prescribing in cachectic patients.