Circulating tumor DNA (ctDNA) is emerging as a minimally invasive biomarker for risk stratification and treatment-response assessment in lung cancer immunotherapy, but its routine use for treatment selection has not been established. This review critically evaluates evidence across neoadjuvant, adjuvant, consolidation after definitive chemoradiotherapy, and advanced/metastatic settings, with emphasis on serial sampling and on the distinction among prognostic, response-associated, and predictive roles. Across disease stages, baseline or post-definitive-treatment ctDNA detectability consistently identifies patients at increased risk of recurrence or death and is therefore principally prognostic. Early on-treatment decline or clearance frequently precedes radiographic change and is associated with pathological response, progression-free survival, and overall survival, supporting ctDNA as a response-associated biomarker. By contrast, evidence that ctDNA identifies differential benefit from a specific immunotherapy remains limited, because most analyses are single-arm and/or retrospective, formal treatment-by-biomarker interaction tests are uncommon, and prospective ctDNA-guided trials have not yet demonstrated clinical utility. Nevertheless, ctDNA dynamics provide a biologically and clinically coherent framework for future risk-adapted strategies, including enrichment of molecular residual disease-positive patients, early identification of resistance, and prospective testing of treatment escalation, de-escalation, or duration. Translation into routine care will require harmonized assays and sampling time points, improved sensitivity at low disease burden, control of clonal hematopoiesis, and randomized interventional validation. Thus, ctDNA currently functions mainly as a prognostic and response-associated biomarker in lung cancer immunotherapy, while its predictive, decision-defining role remains an important but investigational objective.

8587 Background: Cancer-related sarcopenia impairs treatment tolerance and survival in advanced NSCLC. This Phase II trial evaluated IMPACT (arginine and omega-3 enriched formula) in driver gene-negative advanced NSCLC patients receiving chemoimmunotherapy. Methods: Single-center, open-label, randomized Phase II study. Eligible patients: driver gene-negative advanced NSCLC with sarcopenia (AWGS criteria). Randomization 1:1 to IMPACT plus chemoimmunotherapy (Arm A, n=59) versus chemoimmunotherapy alone (Arm B, n=49). IMPACT administered continuously during treatment. Primary endpoint: PFS. Secondary endpoints: body composition (BIA, CT-L3), inflammatory markers (NLR), nutritional status (PG-SGA), safety. Statistical design: 80% power, HR=0.60, alpha=0.05. Dropouts: 7 (11.9%) in Arm A, 5 (10.2%) in Arm B. Modified ITT: 96 patients (52 vs 44). Results: Baseline characteristics balanced. Median PFS: not reached (Arm A) versus 7.0 months (95% CI: 5.2-8.8, Arm B); HR=0.45 (95% CI: 0.23-0.88), P=0.018. Six-month PFS: 82.7% versus 54.5%; 12-month PFS: 59.6% versus 31.8%. NLR change: -1.28 versus +0.16 (P=0.0045). Lean mass change: +0.59 kg versus -1.00 kg (P<0.05). L3 skeletal muscle density: +1.93 HU versus +0.37 HU (P<0.05). PG-SGA improved in Arm A (9.1±5.6 to 6.4±5.1, P<0.001) but not Arm B (8.9±5.8 to 8.2±5.5, P=0.156). Elderly subgroup (≥65y) showed enhanced benefit: HR=0.23 (95% CI: 0.06-0.95), P=0.043. Grade 3-4 AEs: 38.5% versus 52.3% (P=0.156). No IMPACT-related SAEs. Conclusions: IMPACT immunonutrition with chemoimmunotherapy significantly improved PFS, preserved lean mass, reduced inflammation, and enhanced nutritional status in driver gene-negative advanced NSCLC with sarcopenia. Well-tolerated with favorable safety. Phase III evaluation warranted. Clinical trial information: ChiCTR2300078741. Key efficacy outcomes. Endpoint Arm A (Sustagen, n=52) Arm B (Control, n=44) P value edian PFS, months NR 7.0 (5.2-8.8) 0.018 6-month PFS, % 82.7 54.5 - 12-month PFS, % 59.6 31.8 - NLR change -1.28 +0.16 0.0045 Lean mass change, kg +0.59 -1.00 <0.05 L3 SMD change, HU +1.93 +0.37 <0.05

PurposeCombination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach.MethodsTwenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses.ResultsThe median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity.ConclusionThe combination of autologous NK cells with Sintilimab significantly enhances long-term survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment.Clinical trial registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03958097, identifier NCT03958097.

Background Previous studies have suggested oxidative stress may play a key role in the pathogenesis of diabetic retinopathy, while evidence from observational studies directly linking oxidative biomarkers to clinically relevant outcomes has been limited. This study aims to investigate the association between an integrated oxidative balance score (OBS) and risk as well as severity of diabetic retinopathy. Methods National Health and Nutrition Examination Survey (NHANES) participants between 2005–2008 were included and the weighted logistic regression model based on digital imaging of the retina was utilized to investigate the association between OBS and retinopathy. The multifactorial Cox regression model was developed to explore the correlation between OBS and all-cause mortality among individuals with diabetic retinopathy. Results In the adjusted multifactorial logistic regression model, participants in the top OBS quartile demonstrated a 25% lower risk of diabetic retinopathy compared to those in the bottom quartile (OR 0.75, 95%CI 0.57–0.99, P = 0.041). In the multifactorial Cox regression model, among those with diabetic retinopathy in the top OBS quartile exhibited a 51% lower risk of mortality compared to those in the bottom quartile (HR 0.49, 95%CI 0.32–0.74, P < 0.001). Conclusion Our study suggests that higher cumulative antioxidant exposure assessed by OBS is associated with a reduced risk and severity of diabetic retinopathy in U.S. adults.

BackgroundMetabolic syndrome is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular disease and mortality. The identification of novel biomarkers associated with mortality in patients with metabolic syndrome could facilitate early risk stratification and targeted interventions.MethodsWe conducted a large prospective cohort study using data from five cycles (2009-2016) of the National Health and Nutrition Examination Survey (NHANES) database, including a total of 40,439 participants. Logistic regression analysis was used to assess the association between serum klotho protein levels and metabolic syndrome, while Cox regression analysis was employed to examine the correlation between serum klotho levels and all-cause mortality. Mortality data were updated until December 31, 2019.ResultsAfter adjusting for demographic and socioeconomic confounders, the logistic regression model demonstrated that higher serum klotho levels were significantly associated with a decreased prevalence of metabolic syndrome (OR [95% CI] Highest vs. lowest quartile: 0.84 [0.70-0.99], P=0.038). In the Cox regression model, elevated klotho levels were found to significantly reduce the risk of all-cause mortality among individuals with metabolic syndrome (HR [95% CI] Highest vs. lowest quartile: 0.68 [0.51-0.90], P=0.006).ConclusionSerum klotho levels were found to be inversely associated with the prevalence of metabolic syndrome, independent of potential confounding factors such as demographics, socioeconomic status, and lifestyle factors. Furthermore, higher klotho levels strongly indicated a lower risk of all-cause mortality in individuals with metabolic syndrome.

BackgroundThe occurrence of metabolic dysfunction-associated fatty liver disease (MASLD) is driven by multiple factors including obesity, hypertension, dyslipidemia, and insulin resistance. However, epidemiological research investigating the association between metal exposure and MASLD occurrence remains limited.MethodsWe conducted a large cross-sectional study with 6,520 participants who were involved in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Using generalized linear regression, we examined the relationship between five heavy metals (mercury, manganese, lead, selenium, cadmium) and MASLD. Furthermore, restricted cubic spline models and weighted quantile sum (WQS) analysis were employed to characterize the exposure-response relationship between the five metals and MASLD.ResultsHigher blood selenium levels were associated with an increased likelihood of MASLD among US adults. Blood lead exposure was also positively correlated with MASLD risk. However, there was no significant association observed between blood cadmium, mercury, manganese levels, and MASLD risk. Among the five metals, blood cadmium exposure accounted for the highest proportion of MASLD risk.ConclusionOur study indicated the significant association between blood cadmium and lead exposure levels and the occurrence of MASLD in a representative sample of US adults.

Objective:Patient-Generated Subjective Global Assessment (PG-SGA) was a nutritional status assessment technique specifically tailored for patients with oncology. The goal of this study was to develop a machine learning (ML) prediction model for predicting PG-SGA categorization of patients with tumor.Methods:From 2014 to 2020, patients at the First Hospital of Jilin University performed laboratory testing, bioelectrical impedance, physical measures, and the PG-SGA scale. A total of 8230 patients were involved in the study. Patients with missing or partial data were removed, leaving 7287 patients, of which 3743 were males and 3544 were females. ML was used to design a clinical prediction model for PG-SGA categories.Results:Through the least absolute shrinkage and selection operator (LASSO) and the correlation matrix, 135 variables were screened and 6 variables were retained; ML was performed among the remaining variables. The accuracy of neural network prediction models was 70.3% and 70.4% for males and females in the training cohort, respectively, and 74.4% and 73.2% for males and females in the validation cohort, respectively. The area under curve (AUC) of males was 0.87 for PG-SGA scores "0-3", 0.70 for PG-SGA scores "4-8" and 0.74 for PG-SGA scores ">8". As for females, the AUC was 0.85 for PG-SGA scores "0-3", 0.65 for PG-SGA scores "4-8" and 0.76 for PG-SGA scores ">8". The results of confusion matrix showed that the models were of good predictive validity. The prediction model was nearly 90% accurate for predictions that do not require nutritional support.Conclusion:We demonstrated that neural network learning is the best clinical prediction model using ML. The model can work as a prediction for the PG-SGA classification of patients with cancer and can be promoted further in the clinic.

Objectives: Body-composition analysis using bioelectrical impedance analysis is gradually becoming more widely used in clinical practice. The ratio of extracellular water (ECW) to total body water (TBW) is thought to be related to the prognosis of a variety of diseases. However, its performance in people with advanced can-cer deserves further discussion. Methods: A retrospective analysis was performed on 784 people with advanced cancer. Anthropometric indi-cators, serologic indicators, nutritional status, health-related quality of life, and body composition were ana-lyzed. Participants were grouped into two groups according to ECW/TBW ratio. We used t tests and chi(2) tests to analyze differences between the groups. Univariate and multivariate Cox regressions were conducted to analyze the factors influencing overall survival. Logistic regression was used to analyze the related factors of malnutrition, and linear regression for factors of health-related quality of life. Results: Age, body mass index, Patient-Generated Subjective Global Assessment score, Karnofsky Performance Status questionnaire score, skeletal muscle mass index, and fat-free mass index were statistically different between the non-overhydrated and overhydrated groups. Univariate and multivariate Cox regression models showed that an ECW/TBW >= 0.40 isa risk factor for poor prognosis in people with advanced cancer (hazard ratio =1.511; 95% confi-dence interval, 1.103-2.070; P = 0.010). Subgroup analyses were next conducted according to tumor type, with ECW/TBW >= 0.40 emerging as a risk factor for poor prognosis for people with advanced breast cancer and advanced gastric cancer. Logistic regression showed that ECW/TBW >= 0.40 is a risk factor for malnutrition in people with advanced cancer (odds ratio =1.988; 95% confidence interval, 1.049-3.767; P = 0.035). The univariate and multivari-ate linear regression models showed that the ECW/TBW ratio is an influencing factor for health-related quality of life in the domains of physical functioning, role functioning, and constipation. Conclusion: We found that in people with cancer, an ECW/TBW >= 0.40 was a risk factor for malnutrition and lower health-related quality of life, and in people with advanced cancer, it was a risk factor for poor prognosis. (C) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background & aims: The current criteria for defining sarcopenic obesity (SOB) combines the threshold criteria for sarcopenia and obesity, but no consensus has been reached on the criteria. Given the variations among ethnic groups and in the prevalence of sarcopenia, the study aim was to establish sexspecific cutoff points for Chinese cancer patients and investigate the effect of SOB on clinical consequences. Methods: A prospective study of 2480 cancer patients was conducted. Clinical materials, bioelectrical impedance analysis measurements, and follow-up data were analyzed. The survival receiver operating characteristic curve was used to determine threshold values. The odds ratios for nutrition risk, severe malnutrition, and quality of life were calculated. The global and sex-specific survival statistics were extracted from the Kaplan-Meier curve and Cox proportional hazard regression models. Results: The cutoff points of visceral fat area to best classify patients regarding time to death were >75.6 cm2 for males and >61.2 cm2 for females. And the cutoff points of percent of body fat were 15% in males and 25% in females. Among all participants, the prevalence of SOB was 3.03% in males and 4.46% in females. SOB significantly increased the nutrition risk and severe malnutrition probability and worsened quality of life. Finally, SOB was significantly associated with overall cancer mortality [hazard ratio 2.772, 95% confidence interval 2.080-3.694, P < 0.001]. Conclusions: On the basis of sex-specific cutoff values, SOB was strongly associated with unfavorable clinical consequences and mortality in cancer patients. These results indicate the importance of SOB detection in routine clinical practice for improving patient assessments, cancer prognosis, and intervention. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Studies have shown that the skeletal muscle index at the third lumbar vertebra (L3 SMI) had reasonable specificity and sensitivity in nutritional assessment and prognostic prediction in digestive system cancers, but its performance in lung cancer needs further investigation. Methods A retrospective study was performed on 110 patients with advanced lung cancer. The L3 SMI, the Patient-Generated Subjective Global Assessment score (PG-SGA score), body mass index (BMI), and serological indicators were analyzed. According to PG-SGA scores, patients were divided into severe malnutrition (≥9 points), mild to moderate malnutrition (≥3 points and ≤ 8 points), and no malnutrition (≤2 points) groups. Pearson correlation and logistic regression analysis were adopted to find factors related to malnutrition, and a forest plot was drawn. The receiver operating characteristic (ROC) curve was performed to compare the diagnostic values of malnutrition among factors, which were expressed by the area under curve (AUC). Results 1. The age of patients in the severe malnutrition group, the mild to moderate malnutrition group, and the no malnutrition group significantly differed, with mean ages of 63.46 ± 10.01 years, 60.42 ± 8.76 years, and 55.03 ± 10.40 years, respectively (OR = 1.062, 95%CI: 1.008 ~ 1.118, P = 0.024; OR = 1.100, 95%CI: 1.034 ~ 1.170, P = 0.002). Furthermore, the neutrophil to lymphocyte ratio (NLR) of the severe malnutrition group was significantly higher than that of the no malnutrition group, with statistical significance. The difference between the mild to moderate malnutrition group and the no malnutrition group were not statistically significant, with NLR of 4.07 ± 3.34 and 2.47 ± 0.92, respectively (OR = 1.657,95%CI: 1.036 ~ 2.649, P = 0.035). The L3 SMI of patients in the severe malnutrition and mild to moderate malnutrition groups were significantly lower than that of the patients in the no malnutrition group, with statistical significance. The L3 SMI of patients in the severe malnutrition group, mild to moderate malnutrition group, and no malnutrition group were 27.40 ± 4.25 cm 2 /m 2 , 38.19 ± 6.17 cm 2 /m 2 , and 47.96 ± 5.02 cm 2 /m 2 , respectively (OR = 0.600, 95%CI: 0.462 ~ 0.777, P < 0.001; OR = 0.431, 95%CI: 0.320 ~ 0.581, P < 0.001). 2. The Pearson correlation analysis showed that the PG-SGA score positively correlated with age ( r = 0.296, P < 0.05) but negatively correlated with L3 SMI ( r = − 0.857, P < 0.05). The L3 SMI was also negatively correlated with age ( r = − 0.240, P < 0.05). 3. The multivariate analysis showed that the L3 SMI was an independent risk factor for malnutrition (OR = 0.446, 95%CI: 0.258 ~ 0.773, P = 0.004; OR = 0.289, 95%CI: 0.159 ~ 0.524, P < 0.001). Conclusion 1. The differences in the L3 SMI was statistically significant among advanced lung cancer patients with different nutritional statuses. 2. In the nutritional assessment of patients with lung cancer, the L3 SMI was consistent with the PG-SGA. 3. The L3 SMI is an independent predictor of malnutrition in patients with advanced lung cancer.

Hepatocellular carcinoma (HCC) has a poor prognosis due to its high malignancy, rapid disease progression, and the presence of chemotherapy resistance. Long-stranded non-coding RNAs (lncRNAs) affect many malignant tumors, including HCC. However, their mechanism of action in HCC remains unclear. This study aimed to clarify the role of DUXAP8 in regulating the malignant phenotype and chemotherapy resistance in HCC. Using an in vivo xenograft tumor model, the regulatory functions and mechanisms of lncRNA DUXAP8 in the progression and response of HCC to chemotherapy were explored. It was found that DUXAP8 was significantly upregulated in a patient-derived xenograft tumor model based on sorafenib treatment, which is usually associated with a relatively poor prognosis in patients. In HCC, DUXAP8 maintained its upregulation in the expression by increasing the stability of m6A methylation-mediated RNA. DUXAP8 levels were positively correlated with the proliferation, migration, invasion, and chemotherapy resistance of HCC in vivo and in vitro. In the mechanistic study, it was found that DUXAP8 competitively binds to miR-584-5p through a competing endogenous RNA (ceRNA) mechanism, thus acting as a molecular sponge for miR-584-5p to regulate MAPK1 expression, which in turn activates the MAPK/ERK pathway. These findings can provide ideas for finding new prognostic indicators and therapeutic targets for patients with HCC.