Nomograms Predict PFS and OS for SCLC Patients After Standardized Treatment: A Real-World Study.

Purpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients. Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan-Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation. Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867-0.970), 0.908 (95% CI: 0.860-0.956) and 0.878 (95% CI: 0.798-0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736-0.892), 0.819 (95% CI: 0.749-0.889) and 0.809 (95% CI: 0.678-0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort. Conclusion: Based on the patients' treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort.

A multicenter, real-world study on effectiveness and safety of first-line modified PD-1 inhibitors with chemotherapy in advanced non-small cell lung cancer (aNSCLC) with drive gene-negative.

OBJECTIVES: The use of immune checkpoint inhibitors, particularly PD-1 inhibitors, has revolutionized the treatment of advanced tumors and shown significant improvements in patient survival rates. However, which PD-1 inhibitor is more effective and safer for a specific indication remains unclear. To address this problem, our study aimed to evaluate the effectiveness and safety of different PD-1 inhibitors in combination with chemotherapy as first-line therapy for individuals with advanced non-small-cell lung cancer (NSCLC) without driver genes in the real world. MATERIALS AND METHODS: We conducted a retrospective study of individuals diagnosed with aNSCLC who received immune checkpoint inhibitors (ICIs) with modified PD-1 inhibitors, including Sintilimab, Toripalimab, Tislelizumab, Camrelizumab, or Pembrolizumab as first-line treatment between March 5th, 2016 and October 20th, 2022. We assessed demographic and clinical information and analyzed clinical response, survival outcomes, and safety profiles. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: As of the date cut-off on October 20th, 2022, the median follow-up time was 20.62 months. A total of 204 patients were enrolled in the study, including 56 (27.5%) patients receiving modified PD-1 inhibitors (Sintilimab, Toripalimab, Tislelizumab, or Camrelizumab) in combination with chemotherapy and 148 (72.5%) patients receiving Pembrolizumab in combination with chemotherapy. In the overall cohort, the median overall survival (OS) was 26.9 months (95%CI, 22.3-31.6), the median progression-free survival (PFS) was 8.4 months (95%CI, 6.9-9.8), and the objective response rate (ORR) and disease control rate (DCR) were 47.6% (95%CI, 29.9-43.6) and 84.3% (95%CI, 78.4-88.9). The mOS of modified PD-1 inhibitors group and Pembrolizumab group were 30.7 (95%CI, 17.3-44.4) months and 26.8 (95%CI, 22.2-31.4) months. The mPFS of two groups were 8.3(95%CI, 6.9-9.6) months and 8.8 (95%CI, 6.9-10.7) months, respectively. There was no statistical difference between the two groups in terms of OS or PFS. The ORR for the two groups was 48.2% (95%CI, 34.8-61.8) and 47.3% (95%CI, 39.1-5.6), respectively. However, due to the limited sample size, the difference was not statistically significant. On the other hand, the DCR tended to be higher in the Pembrolizumab group (86.5%; 95%CI, 79.7-91.4) compared to the modified PD-1 inhibitors group (78.6%; 95%CI, 65.2-87.9), and this difference was statistically significant (p = 0.006). In terms of safety, both groups exhibited favorable clinical safety profiles. The only two types of potentially immune-related adverse events reported were pneumonitis and reactive cutaneous capillary endothelial proliferation (RCCEP). CONCLUSIONS: The modified PD-1 inhibitors showed comparable survival outcomes and manageable safety profiles in NSCLC compared to Pembrolizumab. Moreover, these inhibitors exhibited improved accessibility and economic outcomes compared to Pembrolizumab. While there were similarities in drug-related and immunotherapy-related adverse reactions between the modified PD-1 inhibitors and Pembrolizumab, there were some slight differences. Further prospective and retrospective studies would be necessary to validate these findings beyond the scope of the CTONG1901 study.

Clinical Significance and Immune Infiltration Analyses of a Novel Nerve-Related lncRNA Signature in Gastric Cancer.

Gastric cancer (GC) is a progressive disease with high morbidity and mortality. Accumulating evidence indicated that nervous system-cancer crosstalk can affect the occurrence and progression of GC. However, the role of nerve-related lncRNAs (NRLs) in GC remains largely unexplored. In this study, a total of 441 nerve-related genes were collected from the KEGG database, and two approaches, unsupervised clustering and WGCNA, were employed to identify NRLs. Lasso regression analysis was then used to construct the nerve-related lncRNA signature (NRLS). Based on the expression profiles of 5 lncRNAs, we developed a stable NRLS to predict survival in GC patients, and survival analyses showed significantly shorter overall survival (OS) in patients with high NRLS. In addition, the NRLS was found to be positively correlated with immune characteristics, including tumor-infiltrating immune cells, immune modulators, cytokines and chemokines. We then analyzed the role of NRLS in predicting chemotherapy and immunotherapy responses, and constructed the OS nomogram combining NRLS and other clinical features. In conclusion, we constructed a robust NRLS model to stratify GC patients and predict the outcomes of chemotherapy and immunotherapy. This study can provide a new perspective for future individualized treatment of GC.

Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study.

BACKGROUND: Renal angiomyolipoma (RAML) is the most common kidney lesion in patients with tuberous sclerosis complex (TSC), affecting about 80% of patients. It is a benign tumor that grows over time, usually bilaterally, and can easily lead to kidney complications such as acute hemorrhage. Herein, we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis. METHODS: A prospective cohort study was conducted. Sirolimus was initiated at 1 mg/(m2 × day), and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL. The disappearance of RAML in children after sirolimus treatment was observed, and Cox regression was used to screen the factors affecting tumor disappearance. RESULTS: One hundred and twenty-six patients who met the criteria were analyzed. After 3 months, 6 months, 12 months, and 24 months of follow-up, tumors disappeared in 18 (14.3%), 30 (23.8%), 39 (31.0%), and 42 (33.3%) children, respectively. Tumors disappeared in 50 (39.7%) children by the last visit of each individual, and 30 (60%) of them occurred within 6 months. The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate. Thirty-six (29%) patients had stomatitis during the entire treatment period, and no serious adverse reactions were observed. CONCLUSIONS: Sirolimus could promote the disappearance of TSC-related RAML. The disappearance rate was correlated with the maximum diameter at baseline, and the smaller the tumor was, the higher the disappearance rate. It is well tolerated in the treatment of RAML associated with TSC.

Nomogram for predicting survival in patients with advanced hepatocellular carcinoma treated with PD-1 inhibitors: incorporating pre-treatment and post-treatment clinical parameters.

BACKGROUND: Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications. METHODS: We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed. RESULTS: The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), hemoglobin (Hb) at 6-week (p = 0.042), neutrophil-to-lymphocyte ratio (NLR) at 6-week (p < 0.001), system immune inflammation index (SII) at 6-week (p = 0.125) as predictors of PFS, and alpha fetoprotein (AFP) (p = 0.035), platelet-to-lymphocyte ratio (PLR) (p = 0.012), Hb at 6-week (p = 0.010) and NLR at 6-week (p = 0.020) as predictors of OS. Furthermore, the results suggest that the OS and PFS nomogram model were in agreement with actual observations. CONCLUSION: Biomarkers in peripheral blood can predict the prognosis of patients with aHCC treated with anti-PD-1 antibody. The development of nomogram models can help us to screen potential patients who can benefit from immunotherapy.

Immune checkpoint inhibitors alone or in combination with chemotherapy for treatment of advanced non-small cell lung cancer after first-line platinum-based chemotherapy: A propensity score matching analysis.

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of several cancer types. However, data are lacking with regard to the clinical responsiveness of ICIs in patients with advanced non-small cell lung cancer (NSCLC) after standard first-line chemotherapy. Therefore, we aimed to evaluate the clinical efficacy of ICI alone or in combination with chemotherapy for patients with advanced NSCLC after first-line platinum-based chemotherapy. Methods: We retrospectively collected patients with confirmed advanced NSCLC who underwent ICI monotherapy or ICI plus chemotherapy after first-line platinum-based chemotherapy between January 2018 and December 2020. A propensity score matching analysis was used to balance baseline characteristics between the two treatment groups. Kaplan-Meier methods and multivariable Cox regressions were used for survival analyses. Results: Among 832 eligible patients, 222 received ICI monotherapy and 610 received ICI plus chemotherapy. The median overall survival (OS) of patients who received ICI plus chemotherapy was 16.0 months compared with 13.1 months in patients who received ICI monotherapy (HR: 0.64, 95% CI: 0.49-0.85, P = 0.002). After 1:1 propensity score matching, all baseline characteristics were well-balanced between the two treatment groups. Patients who received ICI plus chemotherapy had significantly longer OS than those who received ICI monotherapy (NR vs. 13.1 months, HR: 0.50, 95% CI: 0.34-0.71, P < 0.001). Meanwhile, the median time to treatment discontinuation was 4.4 months in the ICI-chemo group and 3.5 months in the ICI-mono group (HR: 0.72, 95% CI: 0.58-0.89, P = 0.002). The multivariate analysis indicated that treatment regimen was an independent prognostic factor for OS (HR: 0.488, 95% CI: 0.337-0.707, P < 0.001). Moreover, a nomogram that integrated both treatment regimens and clinicopathological factors was created for survival prediction. Conclusion: Our study indicated that patients with advanced NSCLC who received ICI plus chemotherapy after first-line platinum-based chemotherapy tended to have longer OS than those who received ICI monotherapy. The multivariate analysis showed that treatment regimen was an independent prognostic factor for OS. Future prospective studies are needed to confirm these findings.

Real-world treatment efficacy of anti-programmed death-1 combined with anti-angiogenesis therapy in non-small cell lung cancer patients.

Anti-programmed death-1 (PD-1) therapy has been extensively used to treat cancer. Recently, the combination of immunotherapy and anti-angiogenic therapy has emerged as a novel treatment approach. Therefore, we designed a study to evaluate the real-world benefit of the combination of anti-PD-1 and anti-angiogenesis therapy in patients with non-small cell lung cancer (NSCLC).We obtained the medical records of patients at the Chinese People's Liberation Army General Hospital who received either nivolumab or pembrolizumab combined with anti-angiogenesis therapy from January 2015 to December 2018. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated for all patients.Sixty-nine patients with NSCLC were included in our study. The ORR was 31.9% (95% CI: 20.6-43.2%) and the median PFS was 8.37 months (95% CI: 6.5-10.0 months). The subgroup analysis statistically revealed a significant difference in ORR for patients receiving first-line treatment vs other lines, and the values were 58.8% (95% CI: 32.7-84.9%) compared with 23.1% (95% CI: 11.2-34.9%). We also observed a significant improvement in PFS, with a median value of 10.5 months (95% CI: 7.4-13.1 months) for patients without EGFR mutations and 5.4 months (95% CI: 4.0-6.3 months) for patients with EGFR mutations.The real-world ORR, PFS, and OS were comparable to previous clinical trials, despite the patients' different baseline characteristics. Importantly, compared with patients having identified EGFR mutations, patients without EGFR mutations had a better PFS. Furthermore, these data support the use of anti-PD-1 combined with anti-angiogenesis therapy as a novel treatment approach for patients with NSCLC.