Sequential vs. concurrent systemic therapies in combination with FOLFOX-HAIC for locally advanced hepatocellular carcinoma: a single-center, real-world cohort study.

BACKGROUND: Tri-combination therapy based on hepatic arterial infusion chemotherapy (HAIC) of infusion fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) plus immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the locally advanced hepatocellular carcinoma (HCC) patients have been proven effective. However, whether it was best for these HCC patients to start with the most potent therapeutic pattern was still under debate. This retrospective study evaluated the efficacy and safety of FOLFOX-HAIC combined with systemic therapies in the patterns of sequential and concurrent schedules. METHODS: This real-world study included 117 unresectable HCC patients who initially received either FOLFOX-HAIC monotherapy (HAIC group, n = 44) or concurrent ICIs and TKIs (ConHAIC group, n = 73) from March 2020 and June 2022, during the period of FOLFOX-HAIC monotherapy in HAIC group, patients in the HAIC group (n = 30) experienced progressive disease (PD) would have their treatment pattern converted from the FOLFOX-HAIC monotherapy to the combination of FOLFOX-HAIC plus ICIs and TKIs sequentially (SeqHAIC group). The progression-free survival (PFS) and overall survival (OS), as primary outcomes, were compared between patients in the SeqHAIC and ConHAIC groups. RESULTS: The median follow-up time of the SeqHAIC group was 24.92 months (95% CI, 12.74-37.09 months) and of the ConHAIC group was 17.87 months (95% CI, 16.85-18.89 months) and no significant difference was observed in both PFS (HR, 1.572; 95% CI, 0.848-2.916; p = 0.151) and OS (HR, 1.212; 95% CI, 0.574-2.561; p = 0.614) between the SeqHAIC and the ConHAIC groups. As for the tumor responses, there was no significant difference between the two groups regarding tumor responses, overall response rates (p = 0.658) and disease control rates (p = 0.641) were 50.0%, 45.2%, and 83.3%, 89.0% for the SeqHAIC and the ConHAIC groups, respectively. CONCLUSION: Our study revealed that sequential systemic ICIs and TKIs in combination with FOLFOX-HAIC provides similar long-term prognosis and better tolerability compared to concurrent therapy for locally advanced HCC patients. Prospective studies with a larger sample size and longer follow-up are required to validate these findings.

Development and validation of an online dynamic nomogram system for predicting cancer cachexia among inpatients: a real-world cohort study in China.

BACKGROUND: Early recognition of cachexia is essential for ensuring the prompt intervention and treatment of cancer patients. However, the diagnosis of cancer cachexia (CC) usually is delayed. This study aimed to establish an accurate and high-efficiency diagnostic system for CC. METHODS: A total of 4834 cancer inpatients were enrolled in the INSCOC project from July 2013 to June 2020. All cancer patients in the study were randomly assigned to a development cohort (n=3384, 70%) and a validation cohort (n=1450, 30%). The least absolute shrinkage and selection operator (LASSO) method and multivariable logistic regression were used to identify the independent predictors for developing the dynamic nomogram. Discrimination and calibration were adopted to evaluate the ability of nomogram. A decision curve analysis (DCA) was used to evaluate clinical use. RESULTS: We combined 5 independent predictive factors (age, NRS2002, PG-SGA, QOL by the QLQ-C30, and cancer categories) to establish the online dynamic nomogram system. The C-index, sensitivity, and specificity of the nomo-system to predict CC was 0.925 (95%CI, 0.916-0.934, P < 0.001), 0.826, and 0.862 in the development set, while the values were 0.923 (95%CI, 0.909-0.937, P < 0.001), 0.854, and 0.829 in the validation set. In addition, the calibration curves of the diagnostic nomogram also presented good agreement with the actual situation. DCA showed that the model is clinically useful and can increase the clinical benefit in cancer patients. CONCLUSIONS: This study developed an online dynamic nomogram system with outstanding accuracy to help clinicians and dieticians estimate the probability of cachexia. This simple-to-use online nomogram can increase the clinical benefit in cancer patients and is expected to be widely adopted.

The Enhanced Cardiac Outcome of Conjugated SGLT2 Inhibitors and GLP-1RA Therapy in Diabetic Patients.

PURPOSE OF REVIEW: Cardiovascular disease secondary to diabetes continues to threaten the survivability of many people all over the world. We assess the most recent findings of synergistic effects of combined glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in lowering cardiac complications in the diabetic population. We describe drug therapies' mechanism of action, postulated cardioprotective process, the additive value of conjugated therapy, and analyze recently reported study and its limitation. RECENT FINDINGS: SGLT2 inhibitors and GLP-1RAs have gained popularity due to their ability to reduce major adverse cardiovascular events in diabetic patients. There is emerging evidence of the additional cardiovascular benefit from the combined application of SGLT2 inhibitors and GLP-1RAs therapy demonstrated by a recent real-world cohort study. Reducing cardiac mortality in patients with diabetes by administering dual antihyperglycemic therapies (GLP-1Rs and SGLT2 inhibitors) might play a key role in the future treatment of the diabetic population.

Development and validation of a prognostic model to predict the prognosis of patients who underwent chemotherapy and resection of pancreatic adenocarcinoma: a large international population-based cohort study.

BACKGROUND: Pancreatic cancer (PaC) remains extremely lethal worldwide even after resection. PaC resection rates are low, making prognostic studies in resected PaC difficult. This large international population-based study aimed at exploring factors associated with survival in patients with resected TNM stage I-II PaC receiving chemotherapy and at developing and internationally validating a survival-predicting model. METHODS: Data of stage I-II PaC patients resected and receiving chemotherapy in 2003-2014 were obtained from the national cancer registries of Belgium, the Netherlands, Slovenia, and Norway, and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program. Multivariable Cox proportional hazards models were constructed to investigate the associations of patient and tumor characteristics with overall survival, and analysis was performed in each country respectively without pooling. Prognostic factors remaining after backward selection in SEER-18 were used to build a nomogram, which was subjected to bootstrap internal validation and external validation using the European datasets. RESULTS: A total of 11,837 resected PaC patients were analyzed, with median survival time of 18-23 months and 3-year survival rates of 21-31%. In the main analysis, patient age, tumor T stage, N stage, and differentiation were associated with survival across most countries, with country-specific association patterns and strengths. However, tumor location was mostly not significantly associated with survival. Resection margin, hospital type, tumor size, positive and harvested lymph node number, lymph node ratio, and comorbidity number were associated with survival in certain countries where the information was available. A median survival time- and 1-, 2-, 3-, and 5-year survival probability-predictive nomogram incorporating the backward-selected variables in the main analysis was established. It fits each European national cohort similarly well. Calibration curves showed very good agreement between nomogram-prediction and actual observation. The concordance index of the nomogram (0.60) was significantly higher than that of the T and N stage-based model (0.56) for predicting survival. CONCLUSIONS: In these large international population-based cohorts, patients with resected PaC receiving chemotherapy have distinct characteristics independently associated with survival, with country-specific patterns and strengths. A robust benchmark population-based survival-predicting model is established and internationally validated. Like previous models predicting survival in resected PaC, our nomogram performs modestly.

Development and validation of a diagnostic nomogram for frailty in cancer patients.

BACKGROUND: The presence of frailty decreases the overall survival of cancer patients. An accurate and operational diagnostic method is needed to help clinicians choose the most appropriate treatment to improve patient outcomes. METHODS: Data were collected from 10 649 cancer patients who were prospectively enrolled in the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers (INSCOC) project in China from July 2013 to August 2022. The training cohort and validation cohort were randomly divided at a ratio of 7:3. The multivariable logistic regression analysis, multivariate Cox regression analyses, and the least absolute shrinkage and selection operator (LASSO) method were used to develop the nomogram. The concordance index and calibration curve were used to assess the diagnostic utility of the nomogram model. RESULTS: The 10 risk factors associated with frailty in cancer patients were age, AJCC stage, liver cancer, hemoglobin, radiotherapy, surgery, hand grip strength (HGS), calf circumference (CC), PG-SGA score and QOL from the QLQ-C30. The diagnostic nomogram model achieved a good C index of 0.847 (95% CI, 0.832-0.862, P < 0.001) in the training cohort and 0.853 (95% CI, 0.83-0.876, P < 0.001) in the validation cohort. The prediction nomogram showed 1-, 3-, and 5-year mortality C indices in the training cohort of 0.708 (95% CI, 0.686-0.731), 0.655 (95% CI, 0.627-0.683), and 0.623 (95% CI, 0.568-0.678). The 1-, 3-, and 5-year C indices in the validation cohort were similarly 0.743 (95% CI, 0.711-0.777), 0.680 (95% CI, 0.639-0.722), and 0.629 (95% CI, 0.558-0.700). In addition, the calibration curves and decision curve analysis (DCA) were well-fitted for both the diagnostic model and prediction model. CONCLUSIONS: The nomogram model provides an accurate method to diagnose frailty in cancer patients. Using this model could lead to the selection of more appropriate therapy and a better prognosis for cancer patients.

Efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate for adult patients with human immunodeficiency virus-1 in China: a retrospective real-world cohort study.

BACKGROUND: This study aimed to evaluate the therapeutic effect and tolerance of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) use for 24 weeks in anti-retroviral therapy (ART)-naïve patients in China. METHODS: This single-center retrospective cohort study included ART-naïve patients who received BIC/FTC/TAF from July 2021 to April 2022. The proportion of patients with HIV RNA < 50 copies/mL at the end point of 24 weeks (virological suppression rate) was the primary outcome, and the changes in CD4 cell count, CD4/CD8 ratio, weight, blood lipid, and safety were secondary outcomes. RESULTS: A total of 80 ART-naïve patients were enrolled. The virological suppression rate was 86.3% at 24 weeks. The median CD4 cell count increased from 212 cells/µL (interquartile range [IQR]: 90.3-398.3) at baseline to 348 cells/µL (IQR: 219.8-541.0) at 24 weeks. The median CD4/CD8 ratio increased from 0.25 (IQR: 0.13-0.37) at baseline to 0.40 (IQR: 0.26-0.66) at 24 weeks. During the follow-up of 80 ART-naïve patients using BIC/FTC/TAF, 16 participants had adverse events; however, these events did not lead to drug withdrawal. CONCLUSION: This real-world cohort study showed that BIC/FTC/TAF could achieve good immunological and virological responses in ART-naïve patients. In addition, this study also shows good safety.

Effect of Online Clinic on Follow-Up Compliance and Survival Outcomes in Nasopharyngeal Carcinoma: Real-World Cohort Study from Endemic Area.

Nasopharyngeal carcinoma (NPC) requires regular follow-up to detect recurrence as early as possible. However, many patients are unable to regularly follow up due to the inconvenience of the conventional approach. Therefore, this study was designed to investigate the impact of the online clinic on follow-up compliance and prognosis in NPC patients. Patients who were first diagnosed with NPC between April 2019 and November 2019 were enrolled. Good follow-up compliance was defined as having at least one follow-up visit every 6 months within 2 years after treatment completion. Sensitivity analyses were performed using a propensity score matching model. A total of 539 (42%) patients used online follow-up while 731 (58%) used traditional follow-up. The median age of patients in the online cohort was lower than that in the traditional cohort (44 vs. 47, p < 0.001). Compared with the traditional cohort, the online cohort had significantly better follow-up compliance (57.3% vs. 17.1%, p < 0.001) and a higher 2-year PFS rate (98.1% vs. 94.4%, p = 0.003). Survival analysis showed that online follow-up was an independent factor for better survival prognosis (HR 0.39, 95%CI 0.20-0.74, p = 0.004). Sensitivity analysis further confirmed these results. Our study found that the online clinic increased follow-up compliance and improved prognosis in NPC patients.

An IFN-γ-related signature predicts prognosis and immunotherapy response in bladder cancer: Results from real-world cohorts.

Bladder cancer (BLCA) is featured with high incidence and mortality. Whether the IFN-γ signaling could be used as an immunotherapy determinant for BLCA has not been fully confirmed. In this study, the transcriptome data and clinical information of BLCA samples were collected from The Cancer Genome Atlas (TCGA). Besides, four immunotherapy cohorts including IMvigor210 cohort, Gide cohort, Van Allen cohort, and Lauss cohort were collected. The Xiangya real-world cohort was used for independent validation. An IFN-γ-related signature was developed and validated in BLCA for predicting prognosis, mutation, tumor microenvironment status, and immunotherapy response. This is the first study focusing on the comprehensive evaluation of predictive values on the IFN-γ-related signature in BLCA. The potential clinical application of the IFN-γ-related signature was expected to be further validated with more prospective clinical cohorts.

Sorafenib for the treatment of hepatocellular carcinoma: a single-centre real-world study.

Background Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma. Its efficacy in randomised controlled trials was demonstrated in patients with well-preserved liver function and good functional status. In the real-world setting, treatment is often offered to patients outside these criteria. We therefore performed a single-centre real-world cohort study on the efficacy of sorafenib in patients with hepatocellular carcinoma. Patients and methods We identified all patients with hepatocellular carcinoma initiating treatment with sorafenib between January 2015 and January 2018. The primary endpoint was overall survival (OS) since starting sorafenib. Clinical and demographic variables associated with survival were studied. Results The median OS was 13.4 months (95% CI 8.2-18.6). Multivariable Cox's regression identified worse ECOG performance status (HR 2.21; 95% CI 1.56-3.16; P < 0.0001), Child-Pugh class C (HR 52.4; 95% CI 3.20-859; P = 0.005) and absence of prior locoregional treatment (HR 2.30; 95% CI 1.37-3.86; P = 0.002) to be associated with increased mortality. Conclusions Careful selection of patients for treatment with sorafenib is of paramount importance to optimize outcomes.