The Association Between Modified Albumin-Bilirubin (mALBI) and Survival in Advanced Non-small Cell Lung Cancer Patients Treated With Immunotherapy.

OBJECTIVE: This study aimed to assess the clinical value of the modified albumin-bilirubin (mALBI) grade in predicting the survival of patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy. METHODS: We conducted a retrospective cohort study of patients with advanced NSCLC who received immune checkpoint inhibitors (ICIs) from January 2020 to May 2022. The primary endpoints were overall survival (OS), treatment response, and the association between different mALBI grades and survival. RESULTS: In these 67 patients, 85.1% (57/67) were male, and the median age was 63 years. The patients with mALBI grades 1 and 2a at baseline had a median OS of 12.83 months (95% CI: 9.4 to 16.27 months), whereas it was 3.2 months (95% CI: NA to 11.59 months) for patients with mALBI grades 2b and 3. The OS for patients with dynamic mALBI grades 1 and 2a was 13.27 months (95% CI: 8.72 to 17.81 months), significantly longer than five months (95% CI: 2.47 to 7.53 months) for dynamic mALBI grades 2b and 3 patients (p<0.01).  Conclusion: In conclusion, mALBI grade may be a potential dynamic biomarker for predicting the prognosis in advanced NSCLC patients treated with immunotherapy.

Comparative analysis of upper aerodigestive tract and non-upper aerodigestive tract in NK/T-cell lymphoma.

OBJECTIVE: Nasal or extranasal natural killer/T-cell lymphoma (NKTCL) is a very rare aggressive lymphoma, but it is increasingly diagnosed. To evaluate some specificity by comparative analysis between primary upper aerodigestive tract (UAT) and non-upper aerodigestive tract (NUAT)NKTCL. METHODS: A retrospective analysis was performed on NKTCL patients from January 2013 to November 2022 in our cancer center. RESULTS: The majority of the lesions were UAT-NKTCL 70 cases (92.1%), the primary NUAT occurred in 6 cases. Patients in the UAT group were mainly in the early stage and in the low and medium risk, while those in the NUAT group were late stage and in high risk (p = 0.000). The expressions of CD3 and TIA-1 in UAT group were higher than those in NUAT group (p = 0.031, p = 0.003), while CD7 was dominant in NUAT group (p = 0.009). For early stage NKTCL, multivariate analysis suggested that gender and PINK score were independent factors affecting PFS and OS (p < 0.05). The 3 year OS rate in initial CR group was 90.1% versus 46.4% in non-CR group (p = 0.000). In advanced stage, KI67% and bone marrow involvement were independent factors affecting OS (p = 0.022, p = 0.038). CONCLUSION: It was difficult to distinguish between UAT and NUAT-NKTCL from histopathology. NUAT-NKTCL patients did have advanced stage and poor outcome. The prognostic value of PINK score and bone marrow involvement was proposed. We aimed to improve initial CR rates, as well as to find new predictive models to predict the whole population.

Effects of LINC00261 targeting miR-148a/WNT10b axis on the proliferation and apoptosis of colorectal cancer cells.

Objective: Colorectal cancer remains a significant challenge with high mortality rates. The aim of this study was to investigate the effect of targeting the microRNA-148a/WNT10b axis with the long non-coding RNA LINC00261 on the proliferation and apoptosis of colorectal cancer cells. Methods: In vitro, small interfering RNA-LINC00261 and microRNA-148 inhibitor sequences were synthesized and transfected into SW480 cells. The study groups included a control group, small interfering RNA negative control group, small interfering RNA group, small interfering RNA negative control + microRNA -inhibitor group, small interfering RNA + microRNA -inhibitor group, and small interfering RNA + microRNA-negative control group. The transfection efficiency and expression levels of LINC00261 and miR-148a were evaluated by quantitative reverse transcription polymerase chain reaction. Cell proliferation, apoptosis, cell cycle distribution, and protein expression levels of WNT10b and ß-catenin were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and Western blot, respectively. Results: After small interfering RNA-LINC00261 transfection, a significant decrease in cell proliferation (p < 0.05) and an increase in apoptosis (p < 0.05) were observed, accompanied by cell cycle arrest in the G1 phase. Inhibition of LINC00261 by small interfering RNA resulted in increased microRNA-148a expression and decreased protein expression of WNT10b and ß-catenin. However, the small interfering RNA + microRNA inhibitor group showed significantly increased levels of WNT10b and ß-catenin protein expression. Conclusions: These results suggest that silencing of long non-coding RNA LINC00261 could potentially affect the proliferation of SW480 cells by regulating the micro RNA -148a/WNT10b axis.

Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. METHODS: PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger's and Begg's test were used to evaluate publication bias. RESULTS: A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22-18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68-3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16-2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15-2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37-3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45-5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71-5.46, P = 0.19). CONCLUSIONS: The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib.

The safety and efficacy of immunotherapy and palliative radiotherapy in patients with metastatic non-small cell lung cancer: a systematic review and meta-analysis of 13 prospective studies.

OBJECTIVE: Whether palliative RT (pRT) can influence the prognosis of mNSCLC patients who are treated with immune checkpoint inhibitors (ICIs) is still under debate. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of pRT plus ICIs in mNSCLC patients. METHODS: PubMed, Cochrane, and Embase databases were searched, and only prospective studies and randomized controlled trials (RCTs) were included. All data were analyzed with Stata 14.0 and Review Manager Version 5.4 software. RESULTS: A total of 13 studies were included. The combined ORRs for the ICIs group, cRT plus ICIs group, and SBRT plus ICIs group were 0.22 (95% CI: 1.27, 4.04), 0.26 (95% CI: 0.04, 0.49), and 0.29 (95% CI: 0.17, 0.40), respectively. And PFS were 2.21 (95% CI: 1.71, 2.70), 4.63 (95% CI: 2.16, 7.09), and 7.38 (95% CI: 2.16, 12.60) months, respectively. OS was 5.96 (95% CI: 3.85, 8.07), 9.04 (95% CI: 6.49, 11.59), and 7.96 (95% CI: 4.02, 11.91) months for the above groups, respectively. For safety terms, patients receiving ICIs plus SBRT had an incidence of 5% (95% CI: 2%, 9%) for pneumonia. CONCLUSION: Patients with mNSCLC may benefit from the combination of ICIs and pRT therapy, but these findings need further validation.

Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis.

OBJECTIVE: It is not well determined whether liver metastasis is a prognostic factor for survival of metastatic non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitors (ICIs). We compared the efficacy of ICIs in patients with NSCLC with or without liver metastases, aiming to evaluate the impact of liver metastasis on survival of NSCLC. METHODS: We systematically searched Pubmed, Embase, and the Cochrane library databases for randomized controlled trials (RCTs) on the efficacy of ICIs in the treatment of NSCLC patients with or without liver metastases. The duration of this search was from January 1, 2000 to June 1, 2022. The reviewers screened the literature, extracted data and conducted quality assessment, and used RevMan 5.4 software and Stata 14 to perform analyses. RESULTS: A total of 17 RCTs were included, published from 2019 to 2022. For NSCLC patients with liver metastases, the risk of disease progression decreased by 36% (HR = 0.64; 95% CI: 0.55-0.75; P < .01) when treated with ICIs, and the death risk (HR = 0.82; 95% CI: 0.72-0.94; P < .01) was also reduced after ICIs treatment. For those without liver metastases, they had significantly improved PFS (HR = 0.56; 95% CI: 0.52-0.60; P < .01) and OS (HR = 0.73; 95% CI: 0.67-0.80; P < .01), compared to those of the control group. Subgroup analysis of OS in liver metastases patients suggested that OS benefit was associated with treatment strategy (for anti-PD-L1 plus chemotherapy versus chemotherapy, HR=1.04; 95% CI: 0.81-1.34; P =.75). CONCLUSION: For NSCLC patients with or without liver metastases, ICIs administration could improve both PFS and OS, especially for those without liver metastases. More RCTs are essential to verify these findings.

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis.

Objective: Recent evidence suggests that combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) may result in better outcomes. In this study, we assessed the efficacy and safety of ICI plus radiation versus ICI alone and explored potential factors affecting its efficacy in advanced non-small-cell lung cancer (NSCLC) patients. Methods: The databases including PubMed and Embase were searched to retrieve eligible studies comparing the efficacy and safety outcomes in advanced NSCLC patients after ICIs ± RT treatments. We performed subgroup analyses to identify potential prognostic factors from radiation details and study types. The odds ratio (OR) of objective response rate (ORR) and disease control rate (DCR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS), and risk ratio (RR) of adverse events were used to represent the outcome effects. Results: 26 eligible studies with 14192 cases were included. The results showed that the ORR (OR = 0.63, 95% CI: 0.42, 0.93; p = 0.02) and DCR (OR = 0.55, 95% CI: 0.36, 0.82; p < 0.01) of RT + ICIs groups were significantly higher than those of the ICIs alone group. The median PFS and OS for ICIs versus RT + ICIs were 2.2 versus 4.4 months and 9.0 versus 13.4 months, respectively. Patients in the ICIs plus RT group had a significantly better PFS (HR = 0.72, 95% CI: 0.64, 0.81; p < 0.01) and OS (HR = 0.74, 95% CI: 0.65, 0.83; p < 0.01) when compared to those in the ICIs group. In terms of adverse events, the risk of pneumonia was not significantly increased in patients treated with both ICIs and RT when compared to ICIs group alone (risk ratio = 0.89; 95% CI: 0.55, 1.44; p = 0.63). The correlation analysis found that PFS was significantly correlated with OS (p = 0.02). The subgroup analysis results showed that significant improvements in OS were observed in non-palliative RT group (HR = 0.29, 95% CI: 0.13, 0.65; p < 0.01) and extracranial RT group (HR = 0.70, 95% CI: 0.59, 0.83; p < 0.01). RT type could also be a prognostic factor associated with the OS (for conventional RT: HR = 0.68 and p = 0.22; for stereotactic body radiation therapy: HR = 0.77 and p < 0.01). However, concerning RT timing, the results showed a similar trend in reducing mortality risk (for previous RT: HR = 0.64 and p = 0.21; for concurrent RT: HR = 0.35 and p = 0.16). Conclusion: RT plus ICIs is associated with improved survival for advanced NSCLC patients, especially for those with non-palliative RT. Further clinical trials are needed to validate its effect on survival outcomes.

The application of nanoparticles in immunotherapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, however, current clinical diagnostic and treatment approaches remain relatively limited, creating an urgent need for the development of effective technologies. Immunotherapy has emerged as a powerful treatment strategy for advanced cancer. The number of clinically approved drugs for HCC immunotherapy has been increasing. However, it remains challenging to improve their transport and therapeutic efficiency, control their targeting and release, and mitigate their adverse effects. Nanotechnology has recently gained attention for improving the effectiveness of precision therapy for HCC. We summarize the key features of HCC associated with nanoparticle (NPs) targeting, release, and uptake, the roles and limitations of several major immunotherapies in HCC, the use of NPs in immunotherapy, the properties of NPs that influence their design and application, and current clinical trials of NPs in HCC, with the aim of informing the design of delivery platforms that have the potential to improve the safety and efficacy of HCC immunotherapy，and thus, ultimately improve the prognosis of HCC patients.

The efficacy and safety of anlotinib for subsequent line treatment of small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Anlotinib is one of the tyrosine kinase inhibitors that exhibits promising anti-tumor effect in several cancers. However, the efficacy and safety of anlotinib in pre-treated small cell lung cancer (SCLC) is not well determined. Herein, we performed this meta-analysis to summarize the effectiveness and safety of anlotinib in the treatment of pre-treated SCLC. METHODS: The databases, such as PubMed and Embase, were searched to identify eligible studies. Clinical studies reporting the efficacy and safety of anlotinib in the treatment of patients with pre-treated SCLC were included. The main endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. The Review Manager 5.4 and STATA 14 statistical software were used to perform the meta-analysis. RESULTS: A total of 13 studies were included, involving 779 patients with SCLC. The ORR and DCR for the anlotinib group were 0.21 (95%CI: 0.12- 0.31; p < 0.01) and 0.76 (95%CI: 0.69- 0.83; p < 0.01), respectively. The summarized PFS and OS for the anlotinib group were 3.46 (95%CI: 2.68-4.24), and 6.86 (95%CI: 5.79-7.93) months, respectively. Compared with control group, the PFS in the anlotinib group was significantly longer standard mean difference(SMD)=0.76, 95%CI: 0.11, 1.41; p = 0.02). In terms of safety, the most common grade 3 or higher adverse events in the anlotinib group were hypertension (9%; 95%CI: 6%-13%), hand-foot syndrome (6%; 95%CI: 2%-9%), and fatigue (4%; 95%CI: 2%-7%). CONCLUSIONS: Anlotinib may be associated with favorable efficacy outcomes in pre-treated SCLC patients with acceptable safety.

Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers.

Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.

Phagocytosis-Regulators-Based Signature to Predict the Prognosis and Chemotherapy Resistance for Breast Cancer Patients.

Phagocytosis is crucial in tumor surveillance and immune function. The association between phagocytosis and the outcomes of breast cancer patients has not been well-determined. In this study, data were downloaded from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases to investigate the role of phagocytosis in breast cancer. Data from the TCGA and GEO databases were used to investigate the prognostic role of phagocytosis in breast cancer. Then, we performed pathway enrichment analysis, copy number variation (CNV) and single-nucleotide variant (SNV) analyses, immune infiltration analysis, calculation of tumor purity, stromal score, and immune score, and consistent clustering. We also constructed a phagocytosis-regulators-based signature system to examine its association in survival and drug response. The genomic and expression differences in the phagocytosis regulators in breast cancer were systematically analyzed, explaining the widespread dysregulation of phagocytosis regulators. Using the investigated association of phagocytosis regulators with the prognosis and tumor immune environment, we constructed a prognostic model based on phagocytosis regulators. We discovered that patients with high risk scores had a poor prognosis and were negatively associated with immune functions. The model had preferential predictive performance and significantly consistent drug-resistance prediction results. Our findings suggest that the phagocytosis-factors-based scoring system can be used as a novel prognostic factor, serving as a powerful reference tool for predicting prognosis and developing methods against drug resistance.

Clinical Features Analysis and Survival Nomogram of Primary Small Intestinal Diffuse Large B-Cell Lymphoma.

Purpose: This study aimed to analyze the clinical features and survival of primary small intestinal diffuse large B-cell lymphoma (PsI-DLBCL), and establish and independently validate a prognostic nomogram for individual risk prediction. Patients and methods: Data for 24 patients from the Renmin Hospital of Wuhan University were used as an independent validation cohort, data for 1144 patients with PsI-DLBCL from the SEER database were randomly assigned to training (N=817) and internal validation (N=327) sets. The survival nomogram was constructed with the most significant factors associated with OS using Univariate and multivariate analyses on the training set. Decision curve analysis (DCA) was conducted. Internal validation was SEER validation set. Our cancer center cohort was used as an external validation set to further verify the survival nomogram. Results: Five clinicopathological feature factors associated with OS of the training set yielded (age, marital status, Ann Arbor stage, surgery for primary site and chemotherapy), which were used to create a survival nomogram. Additionally, the calibration curves of the prognostic nomogram revealed good agreement between the predicted survival probabilities and the ground truth values. The stability of our survival nomogram was explained by internal and external validation data. Conclusion: Our nomogram proposes the clinical and therapeutic factors affecting OS for patients with PsI-DLBCL. It shows that chemotherapy and surgery are beneficial to patients in the choice of treatment options. These results suggest that a survival nomogram may be better at predicting OS for PsI-DLBCL patients.

The prognostic role of neutrophil-to-lymphocyte ratio and C-reactive protein in metastatic colorectal cancer using regorafenib: a systematic review and meta-analysis.

Background: The application of regorafenib has changed the landscape of subsequent-line treatment in metastatic colorectal cancer (mCRC). Baseline neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP), as two of the most common inflammatory factors, are suggested to be potential prognostic factors for mCRC patients treated with regorafenib, but the results are conflicting. In this study, we conducted a meta-analysis to evaluate the prognostic role of NLR and CRP in mCRC patients treated with regorafenib. Methods: We searched online databases such as Embase, PubMed, and the Cochrane library up to April 2022, without language limitation, to identify clinical studies evaluating the prognostic role of NLR or CRP in regorafenib treated mCRC patients. The main endpoints were hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS). The associations between NLR, CRP, and the above endpoints were extracted. Review Manager 5.4 was used to conduct the combined analysis. The Newcastle-Ottawa Scale (NOS) was applied for assessing the quality of included studies. Heterogeneity was detected by chi-square-based Q test and I2 statistic, and publication bias was evaluated by funnel plot asymmetry and Egger's test. Results: Eight studies involving 1,287 cases were included, with 5 reporting survival outcomes based on NLR level and 4 reporting survival according to CRP level. The results of meta-analysis showed that the calculated HR of OS for subsequent-line regorafenib in mCRC patients with high versus low NLR was 2.52 [I2=52%, 95% confidence interval (CI): 1.75-3.64; P<0.00001]. The combined HR of PFS with high versus low baseline NLR was 2.11 (I2=12%, 95% CI: 1.80-2.48; P<0.00001). For patients with a high level of CRP, the OS was significantly shorter when compared with patients with a low level of CRP (I2=0%, HR =1.88; 95% CI: 1.55-2.29; P<0.00001). Conclusions: High level of NLR could be associated with OS in mCRC patients treated with regorafenib. It is suggested that the impact of regorafenib on OS may vary according to the baseline NLR.

Immune-related gene signature predicts clinical outcomes and immunotherapy response in acute myeloid leukemia.

BACKGROUND: The immune response in the bone marrow microenvironment has implications for progression and prognosis in acute myeloid leukemia (AML). However, few immune-related biomarkers for AML prognosis and immunotherapy response have been identified. We aimed to establish a predictive gene signature and to explore the determinants of prognosis in AML. METHODS: Immune-related genes with clinical significance were screened by a weighted gene co-expression network analysis. Seven immune-related genes were used to establish a gene signature by a multivariate Cox regression analysis. Based on the signature, low- and high-risk groups were compared with respect to the immune microenvironment, immune checkpoints, pathway activities, and mutation frequencies. The tumor immune dysfunction and exclusion (TIDE) method was used to predict the response to immune checkpoint blockade (ICB) therapy. The Connectivity Map database was used to explore small-molecule drugs expected to treat high-risk populations. RESULTS: A seven-gene prognostic signature was used to classify patients into high- and low-risk groups. Prognosis was poorer for patients in the former than in the latter. The high-risk group displayed higher levels of immune checkpoint molecules (LAG3, PD-1, CTLA4, PD-L2, and PD-L1), immune cell infiltration (dendritic cells, T helper 1, and gamma delta T), and somatic mutations (NPM1 and RUNX1). Moreover, hematopoietic stem cell/leukemia stem cell pathways were enriched in the high-risk phenotype. Compared with that in the low-risk group, the lower TIDE score for the high-risk group implied that this group is more likely to benefit from ICB therapy. Finally, some drugs (FLT3 inhibitors and BCL inhibitors) targeting the expression profiles associated with the high-risk group were generated using Connectivity Map. CONCLUSION: The newly developed immune-related gene signature is an effective biomarker for predicting prognosis in AML and provides a basis, from an immunological perspective, for the development of comprehensive therapeutic strategies.

Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI. METHODS: Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation. RESULTS: 74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14-18%) and 52% (95% CI: 47-57%), and the median PFS and OS were 3.75 (95% CI: 2.88-4.90) months, and 13.20 (95% CI: 11.88-14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p < 0.05), 0.43 (R2 = 0.18, p < 0.05), and 0.50 (R2 = 0.33, p < 0.05), respectively. Further, the association between PFS and OS of the combination strategy showed a better correlation (rs = 0.79, R2 = 0.75, p < 0.05). CONCLUSION: These results suggest that PFS could be potential surrogates for OS, especially PFS for patients who treated with ICI combination regimen.

Epidemiological and clinical characteristics of 214 families with COVID-19 in Wuhan, China.

OBJECTIVE: To investigate the epidemiological dynamics, transmission patterns, and the clinical outcomes of Coronavirus disease 2019 (COVID-19) in familial cluster patients in Wuhan, China. METHODS: Between January 22, 2020, and February 4, 2020, we enrolled 214 families for this retrospective study. The COVID-19 cases were diagnosed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The number of COVID-19 subjects in a family, their relationship with index patients, the key time-to-event, exposure history, and the clinical outcomes were obtained through telephone calls. RESULTS: Overall, 96 families (44.9%) met the criteria of a familial cluster, which is at least one confirmed case in addition to the index patient in the same household. The secondary attack rate was 42.9%, and nearly 95% of index patients transmitted the infection to ≤2 other family members. High transmission pattern was noted between couples (51.0%) and among multi-generations (27.1%). The median serial interval distribution in familial clusters was 5 days (95% CI, 4 to 6). The case fatality rate was 8.7% in index patients and 1.7% in non-familial clusters patients (p = 0.023). CONCLUSIONS: There is a related higher attack rate and worse clinical outcomes in COVID-19 family clusters.

SR18292 exerts potent antitumor effects in multiple myeloma via inhibition of oxidative phosphorylation.

AIMS: Multiple myeloma (MM) was recently reported to rely on increased oxidative phosphorylation (OXPHOS) for survival, providing a potential opportunity for MM therapy. Herein, we aimed to propose a novel targeted drug for MM treatment, followed by the exploration of reason for OXPHOS enhancement in MM cells. MATERIALS AND METHODS: The expression of OXPHOS genes and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) was analyzed using bioinformatics analyses, followed by verification in MM cell lines. The effects of SR18292 on OXPHOS were measured by qRT-PCR, Western blot, transmission electron microscopy, oxygen consumption rate and so on. The proliferation and apoptosis were evaluated by CCK-8, flow cytometry and Western blot. The efficiency and safety of SR18292 were assessed in a mouse model of MM. KEY FINDINGS: The OXPHOS genes were generally overexpressed in MM cells, which was associated with poorer prognosis of MM patients. PGC-1α, a transcriptional coactivator, was upregulated in MM cells, and MM patients with higher PGC-1α expression exhibited increased enrichment of the OXPHOS gene set. Treatment with SR18292 (an inhibitor of PGC-1α) significantly impaired the proliferation and survival of MM cells due to OXPHOS metabolism dysfunction, which leads to energy exhaustion and oxidative damage. Besides, SR18292 potently inhibited tumor growth at a well-tolerated dose in MM model mice. SIGNIFICANCE: The overexpression of OXPHOS gene set mediated by upregulated PGC-1α provides a structural basis for enhanced OXPHOS in MM cells, and SR18292 (a PGC-1α inhibitor) exerts potent antimyeloma effects, offering a potential tangible avenue for MM therapy.

The association between antibiotics use and outcome of cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was to evaluate the impact of antibiotics use on survival of cancer patients with immune checkpoint inhibitors (ICIs). METHODS: Electronic databases including Pubmed, Emabse, and the Cochrane library were searched. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 20 retrospective studies were included. The median OS (7.9 months versus 17.65 months) and PFS (2.4 months versus 4.4 months) of the antibiotics use group were shorter compared to control group. Meta-analysis also showed that the risks of death (HR = 1.90, 95 % CI: 1.55-2.34; P < 0.01) and disease progression (HR=1.53, 95 % CI: 1.30-1.79; P < 0.01) in antibiotics positive group were significantly higher than that of the negative group. The prognostic role of antibiotics use was still significant regardless of cancer types and timing of antibiotics (P < 0.01 for all). CONCLUSION: Use of antibiotics may be associated with worse outcomes in cancer patients treated with ICIs.