Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

BACKGROUND: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. METHODS: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. RESULTS: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. CONCLUSION: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Clinicopathological Characteristics, Survival and Prognostic Factors in Gastrointestinal Large Cell Neuroendocrine Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Gastrointestinal large cell neuroendocrine carcinoma (GILCNEC) has a low incidence but high malignancy and poor prognosis.The main purpose of this study was to thoroughly investigate its clinicopathological features, survival and prognostic factors. METHODS: Information on patients with GILCNEC was extracted from the Surveillance, Epidemiology, and End Result program, and prognostic factors were analyzed by analyzing clinicopathological data and survival functions. Finally, multivariate analysis was applied to identify independent risk factors associated with survival. RESULTS: A total of 531 individuals were screened in our study from the Surveillance, Epidemiology, and End Result database. The primary sites are mainly from the following: esophagus in 39 (7.3%) patients, stomach in 72 (13.6%) patients, hepatobiliary in 51 (9.6%) patients, pancreas in 97 (18.3%) patients, small intestines in 27 (5.1%), and colorectum in 245 (46.1%) patients. Esophagus, stomach, pancreas, and colorectum large cell neuroendocrine carcinoma (LCNEC) were more common in males (P = 0.001). Esophagus LCNEC had inferior overall survival (OS), whereas small intestine LCNEC was associated with better OS. The results of multivariate analysis showed that the American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy were independent prognostic indicators of OS in patients with GILCNEC (P < 0.05). CONCLUSIONS: The prognosis of patients with GILCNEC varies depending on the primary tumor site. American Joint Committee on Cancer Sixth Edition stage, surgery, and radiotherapy are independent prognostic factors of patients with GILCNEC. Although surgery and radiotherapy can prolong the survival of patients with GILCNEC, their prognosis remains poor, and further prospectively designed multicenter clinical studies are needed to indicate the decision for clinicians.

Safety and efficacy of apatinib in combination with chemotherapy with or without immunotherapy versus chemotherapy alone as first-line treatment for advanced gastric cancer.

The specific first-line regimen for advanced gastric cancer (GC) is still controversial. The benefit of apatinib for first-line treatment of advanced GC remains unknown and needs to be further explored. Eighty-two patients with advanced GC treated in our institution from October 2017 to March 2023 were retrospectively reviewed. All individuals had her-2 negative GC and had received at least two cycles of first-line treatment, including 44 patients in the combination treatment group (apatinib in combination with chemotherapy with or without immunotherapy) and 38 patients in the simple chemotherapy group. We evaluated the efficacy and safety of apatinib in combination with chemotherapy with or without immunotherapy in the first-line treatment of advanced GC by comparing the efficacy, progression-free survival (PFS), and adverse events in two groups of patients. The median PFS of the simple chemotherapy group was 9.25 months (95% confidence interval (CI), 6.1-11.2 months), and that of the combination treatment group was 10.9 months (95% CI, 7.9-15.8 months), which was 1.65 months longer than the simple chemotherapy group. Statistically significant differences are shown (P = 0.022). The objective response rate (ORR) of the combination treatment group was 65.9%, and 36.8% in the simple chemotherapy group. Statistically significant differences are shown (P = 0.014). No serious (Grade IV) adverse events occurred in either group. Our study indicates that apatinib in combination with chemotherapy with or without immunotherapy as first-line treatment for advanced GC exhibits good anti-tumor activity and is well tolerated by patients.

Dynamic analysis of predictive biomarkers for radiation therapy efficacy in non-small cell lung cancer patients by next-generation sequencing based on blood specimens.

PURPOSE: Radiotherapy plays an important role in the treatment of non-small cell lung cancer, and the aim of this study was to explore the potential association of single gene mutation or pathway mutations with radiotherapy response using targeted next-generation sequencing (NGS) testing of peripheral blood specimens. MATERIAL AND METHODS: We performed NGS containing 425 genes on peripheral blood specimens from 13 NSCLC patients pre- and post-radiotherapy or post-radiotherapy. Patients whose tumors were in complete response or partial response within 1 month after radiotherapy were classified as a radiotherapy-sensitive group; otherwise, they were categorized as a radiotherapy-resistant group. The relationship between single gene mutations, signaling pathway mutations, dynamic fluctuations in circulating tumor DNA （ctDNA）, and radiotherapy response was investigated. RESULTS: Of these 13 patients，6 patients were categorized as a radiotherapy-sensitive group (46.2%), and 7 patients were categorized as a radiotherapy-resistant group (53.8%). No correlation between single gene mutations and response to radiotherapy. Mutations in the SWI/SNF complex were more likely to occur in the radiotherapy-sensitive group than in the other group (p = 0.07). Among all patients，9 patients underwent NGS tests pre- and post-radiotherapy. Dynamic analysis based on ctDNA before and after treatment revealed that a decrease in ctDNA abundance was observed in all patients in the radiotherapy-sensitive group. CONCLUSIONS: SWI/SNF complex mutations may be potential predictive biomarkers of radiotherapy response. Decreased ctDNA abundance after radiotherapy correlates with better efficacy of radiotherapy.

Association Between Online Health Information-Seeking Behaviors by Caregivers and Delays in Pediatric Cancer: Mixed Methods Study in China.

BACKGROUND: Pediatric cancer patients in China often present at an advanced stage of disease resulting in lower survival and poorer health outcomes. One factor hypothesized to contribute to delays in pediatric cancer has been the online health information-seeking (OHIS) behaviors by caregivers. OBJECTIVE: This study aims to examine the association between OHIS behaviors by caregivers and delays for Chinese pediatric cancer patients using a mixed methods approach. METHODS: This study used a mixed methods approach, specifically a sequential explanatory design. OHIS behavior by the caregiver was defined as the way caregivers access information relevant to their children's health via the Internet. Delays in pediatric cancer were defined as any one of the following 3 types of delay: patient delay, diagnosis delay, or treatment delay. The quantitative analysis methods included descriptive analyses, Student t tests, Pearson chi-square test, and binary logistic regression analysis, all performed using Stata. The qualitative analysis methods included conceptual content analysis and the Colaizzi method. RESULTS: A total of 303 pediatric cancer patient-caregiver dyads was included in the quantitative survey, and 29 caregivers completed the qualitative interview. Quantitative analysis results revealed that nearly one-half (151/303, 49.8%) of patients experienced delays in pediatric cancer, and the primary type of delay was diagnosis delay (113/303, 37.3%), followed by patient delay (50/303, 16.5%) and treatment delay (24/303, 7.9%). In this study, 232 of the 303 (76.6%) caregiver participants demonstrated OHIS behaviors. When those engaged in OHIS behaviors were compared with their counterparts, the likelihood of patient delay more than doubled (odds ratio=2.21; 95% CI 1.03-4.75). Qualitative analysis results showed that caregivers' OHIS behaviors impacted the cancer care pathway by influencing caregivers' symptom appraisal before the first medical contact and caregivers' acceptance of health care providers' diagnostic and treatment decisions. CONCLUSIONS: Our findings suggest that OHIS among Chinese pediatric caregivers may be a risk factor for increasing the likelihood of patient delay. Our government and society should make a concerted effort to regulate online health information and improve its quality. Specialized freemium consultations provided by health care providers via online health informatic platforms are needed to shorten the time for caregivers' cancer symptom appraisal before the first medical contact.

A Smart DNA-Based Nanosystem Containing Ribosome-Regulating siRNA for Enhanced mRNA Transfection.

Messenger RNA (mRNA) transfection is the prerequisite for the application of mRNA-based therapeutics. In hard-to-transfect cells, such as macrophages, the effective transfection of mRNA remains a long-standing challenge. Herein, a smart DNA-based nanosystem is reported containing ribosome biogenesis-promoting siRNA, realizing efficient mRNA transfection in macrophages. Four monomers are copolymerized to form a nanoframework (NF), including N-isopropylacrylamide (NIPAM) as the skeleton and acrydite-DNA as the initiator to trigger the cascade assembly of DNA hairpins (H1-polyT and H2-siRNA). By virtue of the phase transition characteristic of polymeric NIPAM, below the lower critical solution temperature (LCST, ≈34 °C), the NF swells to expose polyT sequences to hybridize with the polyA tail of mRNA. Above the LCST, the NF deswells to encapsulate mRNA. The disulfide bond in the NF responds to glutathione, triggering the disassembly of the nanosystem; the siRNA and mRNA are released in response to triphosadenine and RNase H. The siRNA down-regulates the expression of heat shock protein 27, which up-regulates the expression of phosphorylated ribosomal protein S6. The nanosystem shows satisfactory mRNA transfection and translation efficiency in a mouse model. It is envisioned that the DNA-based nanosystem will provide a promising carrier to deliver mRNA in hard-to-transfect cells and promote the development of mRNA-based therapeutics.

Prognostic Value of ctDNA Detection in Patients With Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) is increasingly used as a biomarker for metastatic rectal cancer and has recently shown promising results in the early detection of recurrence risk. METHODS: We conducted a systematic review and meta-analysis to explore the prognostic value of ctDNA detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT). We systematically searched electronic databases for observational or interventional studies that included LARC patients undergoing nCRT. Study selection according to the PRISMA guidelines and quality assessment of the REMARK tool for biomarker studies. The primary endpoint was the impact of ctDNA detection at different time points (baseline, post-nCRT, post-surgery) on relapse-free survival (RFS) and overall survival (OS). The secondary endpoint was to study the association between ctDNA detection and pathological complete response(pCR) at different time points. RESULTS: After further review and analysis of the 625 articles initially retrieved, we finally included 10 eligible studies. We found no significant correlation between ctDNA detection at baseline and long-term survival outcomes or the probability of achieving a pCR. However, the presence of ctDNA at post-nCRT was associated with worse RFS (HR = 9.16, 95% CI, 5.48-15.32), worse OS (HR = 8.49, 95% CI, 2.20-32.72), and worse pCR results (OR = 0.40, 95%CI, 0.18-0.89). The correlation between the presence of ctDNA at post-surgery and worse RFS was more obvious (HR = 14.94; 95% CI, 7.48-9.83). CONCLUSIONS: Our results suggest that ctDNA detection is a promising biomarker for the evaluation of response and prognosis in LARC patients undergoing nCRT, which merits further evaluation in the following prospective trials.

Establishment and validation of nomograms to predict survival probability of advanced malignant pleural mesothelioma based on the SEER database and a Chinese medical institution.

Objective: The purpose of this study was to build nomograms for predicting the survival of individual advanced pleural mesothelioma (MPM) patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: The 1251 patients enrolled from the SEER database were randomized (in a 7:3 ratio) to a training cohort and an internal validation cohort. Eighty patients were enrolled from the Harbin Medical University Cancer Hospital as the external validation cohort. Nomograms were constructed from variables screened by univariate or multivariate Cox regression analyses and evaluated by consistency indices (C-index), calibration plots, and receiver operating characteristic (ROC) curves. Patients from the SEER database who received chemotherapy alone and chemoradiotherapy were statistically paired using propensity score matching of the two groups and performed subgroup analysis in the screened variables. Results: The nomograms are well-structured and well-validated prognostic maps constructed from four variables: gender, histology, AJCC stage, and treatment. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort, with the high-risk group having worse OS and CSS in all three cohorts (P<0.05). The outcomes of the subgroup analysis indicated that the advanced MPM patients receiving chemotherapy with or without local radiotherapy do not affect OS or CSS. Conclusion: The accurate nomograms to predict the survival of patients with advanced MPM were built and validated based on an analysis of the SEER database with an external validation cohort. The study suggests that the additional local radiotherapy to chemotherapy does not increase the survival benefit of patients.

The prognostic value of the controlling nutritional status (CONUT) score in predicting outcomes of esophageal cancer patients receiving radiotherapy with or without chemotherapy.

Background: Controlling nutritional status (CONUT) scores and systemic immune-inflammation index (SII) values are associated with the prognosis of several common malignancies. The current study aimed to explore the prognostic value of CONUT scores and SII values in patients with esophageal cancer (EC) receiving radical radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods: We calculated the pre-RT CONUT scores and SII values of 62 patients with EC receiving RT or CCRT. Receiver operating characteristic (ROC) curves were used to determine the adequate cut-off values. The Kaplan-Meier method and Cox proportional hazard model were used to analyze the association between CONUT scores and SII values and prognosis. Results: The 1-year progression-free survival (PFS) and 1-year overall survival (OS) rates of the 62 patients were 51.61% and 66.13%, respectively. Based on the time-dependent ROC curve for the 1-year OS of all patients, the optimal cut-off value was 622.02 for the SII and a score of 1 for the CONUT score. The univariate analysis showed that the CONUT score (P=0.036), tumor-nodal-metastasis (TNM) stage (P<0.01), and CCRT (P=0.008) significantly affected the survival of EC patients. The multifactorial analysis showed that the CONUT score (P=0.041) and TNM stage (P<0.01) were independent prognostic factors affecting clinical outcomes in patients with EC undergoing radical RT or CCRT. Conclusions: The pre-RT CONUT score could be an effective predictor of prognosis in patients with EC receiving radical RT or CCRT; however, the pre-RT SII value had no clinical value in predicting survival in our study.

Prognostic Effect of the Controlling Nutritional Status Score in Patients With Esophageal Cancer Treated With Immune Checkpoint Inhibitor.

In recent years, a growing number of clinical studies have shown that immune checkpoint inhibitor (ICI) can increase the remission rate and improve the prognosis of patients with esophageal cancer. The Controlling Nutritional Status (CONUT) score is a novel nutritional indicator that can predict the prognosis of certain malignancies. We retrospectively analyzed the clinical data of 69 patients with advanced esophageal cancer treated with ICI and assessed the relationship between clinicopathological factors including CONUT score, systemic immune-inflammatory index (SII), and neutrophil-to-lymphocyte ratio and the prognosis. We found the CONUT score and SII, neutrophil-to-lymphocyte ratio were an independent prognostic factor for overall survival ( P <0.05). Furthermore, among patients treated with ICI, a high CONUT score was associated with a significantly worse progression-free survival (PFS) and overall survival compared with a low CONUT group. In conclusion, the CONUT can be used to predict the efficacy and prognosis of ICI therapy in patients with esophageal cancer. Our studies have shown that the CONUT score can be used as an effective indicator for the prognosis of patients with esophageal cancer receiving ICI.