Mapping Ferroelectric Fields Reveals the Origins of the Coercivity Distribution.

Better techniques for imaging ferroelectric polarization would aid the development of new ferroelectrics and the refinement of old ones. Here we show how scanning transmission electron microscope (STEM) electron beam-induced current (EBIC) imaging reveals ferroelectric polarization with obvious, simply interpretable contrast. Planar imaging of an entire ferroelectric hafnium zirconium oxide (Hf0.5Zr0.5O2, HZO) capacitor shows an EBIC response that is linearly related to the polarization determined in situ with the positive-up, negative-down (PUND) method. The contrast is easily calibrated in MV/cm. The underlying mechanism is magnification-independent, operating equally well on micrometer-sized devices and individual nanoscale domains. Coercive-field mapping reveals that individual domains are biased "positive" and "negative", as opposed to being "easy" and "hard" to switch. The remanent background E-fields generating this bias can be isolated and mapped. Coupled with STEM's native capabilities for structural identification, STEM EBIC imaging provides a revolutionary tool for characterizing ferroelectric materials and devices.

The rupture risk of intracranial saccular aneurysm: a case-control study based on a three-dimensional computed tomography angiography model.

Background: Assessing the risk of rupture in intracranial aneurysms is crucial. Advancements in medical imaging now allow for three-dimensional (3D) assessments of aneurysms, providing a more detailed understanding of their morphology and associated risks. This study aimed to compare the 3D morphological parameters of ruptured and unruptured intracranial saccular aneurysms (ISAs) using computed tomography angiography (CTA) and to analyze risk factors linked to ISA rupture. Methods: This retrospective case-control study included patients diagnosed with ISAs via CTA, for which data were sourced from both the Emergency Department and Inpatient Unit in The First Affiliated Hospital of Jinan University. The patients were categorized into rupture and unrupture groups. We used 3D-Slicer (version 5.2.2, Slicer Community) to construct morphological models of the ISAs and their parent arteries. These models facilitated assessments of intracranial aneurysmal volume (IAV), aneurysmal surface area (ASA), and maximum sectional area (MSA). Differences in 3D morphological parameters between ruptured and unruptured ISAs were then analyzed. For statistical analysis, we first performed single factor analysis on the data, constructed a receiver operating characteristic (ROC) curve one by one with statistically significant parameters, and screened out ROC curves that met the sample requirements. Second, we performed multiparameter logistic regression analysis to construct a ROC curve model and analyzed its predictive performance. Results: The analysis encompassed 97 patients comprising 97 ISAs diagnosed from March 2016 to March 2022. Significant differences in morphological parameters were observed between the rupture and unrupture groups (P<0.05), including IAV, ASA, MSA, IAV/diameter (IAV/D), IAV/neck width (IAV/N), MSA/diameter (MSA/D), MSA/neck width (MSA/N), ASA/neck width (ASA/N), and ASA/MSA. It was found that the IAV, ASA, and MSA values of the rupture group were larger than those of the unrupture group. Meanwhile, the IAV/D, IAV/N, MSA/D, MSA/N, and ASA/N values were larger in the rupture group, while ASA/MSA and ASA/IAV were smaller. Conclusions: This study underscores the significance of specific morphological indicators, such as ASA/N and ASA/MSA, in predicting the rupture risk of ISAs. The IAV, MSA, and ASA parameters, especially in relation to diameter and neck width, provide crucial insights into the rupture potential of ISAs.

Poor Efficacy of Immune Checkpoint Inhibitors Plus Chemotherapy in Lung Cancer Patients with EGFR/ERBB2 Exon 20 Insertion.

BACKGROUND: EGFR and ERBB2 exon 20 insertion (Ex20ins) account for a small fraction of patients with EGFR mutations. The efficacy of immune checkpoint inhibitors (ICIs) for these patients was still controversial. METHODS: This retrospective study enrolled lung cancer patients harboring either EGFR or ERBB2 Ex20ins mutations. All the patients were treated with platinum-based chemotherapy plus ICIs, or platinum-based chemotherapy. The demographic features and clinical outcome of each patient were reviewed and analyzed. RESULTS: When treated with immunochemotherapy, patients with EGFR/ERBB2 Ex20ins mutations (n = 31) had poor PFS compared with those without EGFR mutations (n = 141, 5.0 mon and 11.2 mon, p < 0.001). When compared with those with EGFR classic mutations who received immunotherapy as the salvage therapy (n = 24), these patients with EGFR/ERBB2 Ex20ins mutations had similar PFS (5.0 mon and 4.1 mon, p = 0.625), ORR (37.5% vs. 48.4%), and DCR (70.8% vs. 77.4%). In the patients with EGFR/ERBB2 Ex20ins mutations, the PFS of those treated with chemotherapy (n = 54) and those treated with immunochemotherapy (n = 31) was 6.5 mon vs. 5.0 mon (p = 0.066). In the EGFR Ex20ins subgroup, the PFS of addition of bevacizumab to chemotherapy (n = 20) and chemotherapy alone (n = 16) was 8.8 mon and 5.2 mon, respectively (p = 0.082) or immunochemotherapy (n = 15, 8.8 mon and 5.0 mon, p = 0.097). Similarly, in the ERBB2 subgroup, the combination of bevacizumab and chemotherapy achieved a numerically longer PFS over chemotherapy alone (9.1 mon and 4.5 mon, p = 0.253), but there was no statistical significance. CONCLUSIONS: This study showed that platinum-based chemotherapy plus ICIs had limited efficiency compared to platinum-based chemotherapy for patients with EGFR/ERBB2 Ex20ins. Chemotherapy plus bevacizumab may be a potential scheme for these patients.

Operando spectral imaging of the lithium ion battery's solid-electrolyte interphase.

The lithium-ion battery is currently the preferred power source for applications ranging from smart phones to electric vehicles. Imaging the chemical reactions governing its function as they happen, with nanoscale spatial resolution and chemical specificity, is a long-standing open problem. Here, we demonstrate operando spectrum imaging of a Li-ion battery anode over multiple charge-discharge cycles using electron energy-loss spectroscopy (EELS) in a scanning transmission electron microscope (STEM). Using ultrathin Li-ion cells, we acquire reference EELS spectra for the various constituents of the solid-electrolyte interphase (SEI) layer and then apply these "chemical fingerprints" to high-resolution, real-space mapping of the corresponding physical structures. We observe the growth of Li and LiH dendrites in the SEI and fingerprint the SEI itself. High spatial- and spectral-resolution operando imaging of the air-sensitive liquid chemistries of the Li-ion cell opens a direct route to understanding the complex, dynamic mechanisms that affect battery safety, capacity, and lifetime.

Device-Free Tracking through Self-Attention Mechanism and Unscented Kalman Filter with Commodity Wi-Fi.

Recent advancements in target tracking using Wi-Fi signals and channel state information (CSI) have significantly improved the accuracy and efficiency of tracking mobile targets. However, there remains a gap in developing a comprehensive approach that combines CSI, an unscented Kalman filter (UKF), and a sole self-attention mechanism to accurately estimate the position, velocity, and acceleration of targets in real-time. Furthermore, optimizing the computational efficiency of such approaches is necessary for their applicability in resource-constrained environments. To bridge this gap, this research study proposes a novel approach that addresses these challenges. The approach leverages CSI data collected from commodity Wi-Fi devices and incorporates a combination of the UKF and a sole self-attention mechanism. By fusing these elements, the proposed model provides instantaneous and precise estimates of the target's position while considering factors such as acceleration and network information. The effectiveness of the proposed approach is demonstrated through extensive experiments conducted in a controlled test bed environment. The results exhibit a remarkable tracking accuracy level of 97%, affirming the model's ability to successfully track mobile targets. The achieved accuracy showcases the potential of the proposed approach for applications in human-computer interactions, surveillance, and security.

Comparison of clinicopathological features and survival analysis between esophageal neuroendocrine carcinoma and esophageal squamous cell carcinoma based on the SEER database, alongside nomogram analysis for esophageal neuroendocrine carcinoma.

Background: Esophageal neuroendocrine carcinoma (ENEC) is a rare subtype of esophageal cancer (EC). It presents distinctive clinical and pathological features in comparison to esophageal squamous cell carcinoma (ESCC). To better elucidate the disparities between the two and establish a prognostic prediction model for ENEC, we conducted this study. Methods: Data of ENEC and ESCC patients (1975 to 2016) were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Patients with a confirmed pathological diagnosis of ENEC and ESCC were enrolled in the study. The Chi-square test was employed to compare categorical variables, and the median survival time was analyzed using the Kaplan-Meier curve. Training and validation groups were randomly assigned at a ratio of 7:3. Factors with a significance level of <0.05 in the multifactor regression model as well as age were integrated into the nomogram model. Concordance index (C-index), calibration curves, and decision curve analyses (DCA) were generated for model validation. Results: This study encompassed a total of 737 ENEC patients and 29,420 ESCC. Compared to ESCC, ENEC patients had higher probability of liver metastasis (13.8% vs. 1.9%, P<0.001), poor differentiation (68.0% vs. 37.1%, P<0.001), and late SEER stage (52.8% vs. 26.9%, P<0.001). Patients who received either surgery, radiotherapy (RT), or chemotherapy had a significantly longer disease-specific survival (DSS) and overall survival (OS) (all P<0.001). After propensity score matching (PSM), ENEC patients were associated with shorter DSS (7.0 months vs. not reached, P<0.0001) and OS (7.0 vs. 12.0 months, P<0.0001) compared to ESCC. Race, SEER stage, surgery, RT, and chemotherapy were identified as predictors of DSS and were incorporated into the nomogram model together with age. The validation of the model using C-index (0.751 and 0.706, respectively) and calibration curves reflected the better discrimination power of the model. In addition, DCA supported the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on the nomogram also verified the reliability of the model. Conclusions: ENEC and ESCC exhibit distinct clinicopathological features. Patients with ENEC experience significantly poorer survival outcomes compared to those with ESCC. Surgical intervention, radiation therapy, and chemotherapy significantly improve OS and DSS for ENEC patients. The nomogram prediction model, constructed based on age, race, stage, and treatment regimen, demonstrates accurate and effective predictive capabilities for prognostic factors in ENEC patients.

Brain parenchymal and leptomeningeal metastasis in non-small cell lung cancer.

Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p < 0.0001). The median time to the onset of PM and LM from the diagnosis of advanced NSCLC was 0 months and 8.3 months, respectively. Patients with LM had a statistically shorter over survival (OS) compared to either No-BM or PM patients (p < 0.0001). Based on independent predictive variables, two nomogram models were constructed to predict the development of PM and LM in advanced NSCLC patients, and the C-indexes were 0.656 and 0.767, respectively. Although both considered as BM, PM and LM had different clinical characteristics. And the nomogram showed good performance in predicting LM development, but not PM.

Dramatic response to neoadjuvant savolitinib in marginally resectable lung adenocarcinoma with MET exon 14 skipping mutation: A case report and literature review.

Mesenchymal-epithelial transition (MET) exon 14 skipping mutation (METex14) is a low-frequency driver mutation in metastatic non-small cell lung cancer (NSCLC) (3%-4%) and is associated with a poor prognosis. With the advent of selective MET inhibitors such as capmatinib, tepotinib, and savolitinib, the outcome for these patients was significantly improved. Here, we report a 76-year-old male patient with marginally resectable stage IIIB lung adenocarcinoma harboring METex14 who was successfully treated with savolitinib for neoadjuvant therapy. An 82% shrinkage of the primary tumor was observed, and only 5% of the tumor was viable by pathology in the following radical surgery. A dozen of studies tested the efficiency of neoadjuvant immunotherapy or immunochemotherapy, but for NSCLC with driver mutations, neoadjuvant targeted therapy might be more appropriate. We advocated the neoadjuvant MET TKI treatment for NSCLC.

Zoledronic acid enhances the efficacy of immunotherapy in non-small cell lung cancer.

BACKGROUND: Only a minority of patients benefit from immune checkpoint inhibitors (ICIs) therapy, although they have become the standard of care for patients of non-small cell lung cancer (NSCLC) without driver mutations. Zoledronic acid (ZA) enhances the anti-tumor efficacy of endocrine therapy, chemotherapy and targeted therapy. However, little is known about the effect of ZA on the clinical outcomes of ICIs, or its possible mechanisms. METHODS: Patients with advanced NSCLC treated with ICIs alone or in combination with ZA were recruited. The clinical efficacy was compared between the two cohorts. We used an LL2 mouse model to confirm the combined effects of ZA with ICIs. Immune cell populations and cytokines in the tumor microenvironment and circulation were assayed and analyzed. RESULTS: The median PFS for the patients treated with and without ZA was 5.4 months and 2.8 months, respectively. The combination group showed a higher rate of disease control. In the mouse LL2 lung cancer model, tumor growth was significantly inhibited in mice treated with the combination treatment. More CD8 + IFN-γ + T cells and γδ T cells, and fewer CD11b cells were found in the circulation and TILs in the combination group. Anti-tumor cytokines INF-γ and IL-18 were elevated in the sera after combination therapy. CONCLUSION: Our study provides preclinical and clinical evidence to show that ZA could improve the therapeutic effects of ICIs. This effect was likely related to the activation of immune cells and elevated cytokines, which provided a new way to improve the effect of ICIs therapy, and is worth exploring further.

Epidemiology, Treatment, and Outcome of Pancreatic Squamous Cell Carcinoma and Pancreatic Adenocarcinoma: A Propensity Score-Matching Analysis Based on SEER-Database.

Background: Pancreatic squamous cell carcinoma (PSCC) is a rare pancreatic malignancy compared to most common pancreatic adenocarcinoma (PAC). Aims: To analyze the prognostics factors of PSCC and compare PAC with PSCC in demographic patterns, clinicopathologic characteristics and treatment modalities. Methods: Data of PSCC and PAC patients from January 1, 2004 to December 31, 2015 were extracted from Surveillance, Epidemiology and End Results (SEER) database for case-control study. Kaplan-Meier method and Cox proportional hazards analysis were used in survival analysis. A 1:3 propensity-score matching (PSM) was performed to compare the overall survival (OS) and cancer specific survival (CSS) between PAC and PSCC in each variable. Results: PAC patients (n = 38 968) and PSCC patients (n = 124) were analyzed. After PSM, 372 PAC patients and 124 PSCC patients were obtained. PSCC tends to happen to elders, white and female with a predilection site of pancreatic head, followed by tail, then body. PSCC have a higher proportion to be poorly differentiated and metastatic when diagnosed. The prognosis of PSCC patients was significantly worse than PAC patients in both univariate and multivariate analyses. Surgery and chemotherapy were independent prognostic factors for PSCC. Conclusions: PSCC patients were identified associated with a worse prognosis than PAC patients. PSCC tend to be poorly differentiated and more easily to be metastatic. Surgery and chemotherapy may be effective therapies to improve the OS of PSCC significantly.

Immunotherapy for a POLE Mutation Advanced Non-Small-Cell Lung Cancer Patient.

Currently, the predictive role of POLE mutations for immunotherapy is under intense investigation. The POLE gene encodes one of the four subunits of DNA polymerase important for DNA replication and repair. POLE mutations are related to other favorable predicative factors such as high expression of PD-L1, high TMB, and infiltration of CD8+ cells in the tumor microenvironment. No formal clinical trials studied the efficacy of immunotherapy in lung patients harboring POLE mutation, and only few cases were mentioned in the literature. Moreover, lung cancer patients are prone to brain metastasis, which is notorious for the unresponsiveness to chemotherapy. The efficacy of immunotherapy for brain metastasis is still controversial. Here, we described a case of a POLEmt non-small-cell lung cancer (NSCLC) patient with brain metastasis who was treated with immunotherapy. His brain lesions disappeared after treatment. Our report strongly supported the benefit of immune-combined therapy for advanced NSCLC patients with POLE mutation, even with brain metastasis.

Systematic Immunological Level Determined the Prognosis of Leptomeningeal Metastasis in Lung Cancer.

Background and Purpose: Leptomeningeal metastases (LM) is the end-event of lung cancer and the prognosis is dismal. Few studies explored the prognostic performance of systematic immunological levels in lung cancer patients with LM. Our study aimed to explore the possible relationship between the prognosis of LM and systematic immunological level and other clinical characteristics. Methods: This retrospective, multi-institutional, observational study was conducted in 4 tertiary centers in China. Patients were screened from January 2009 to May 2019. Patients with radiographically or histologically confirmed LM were enrolled. The data of systematic immunological level and other clinical characteristics of each patient were extracted and statistically analyzed to establish a prognostic model based on statistical analysis results. The predictive accuracy and discriminative capability of the model were evaluated by the calibration curve and concordance index (C-index). Results: A total of 109 patients were enrolled in the study. Patients with adenocarcinoma, tumors harboring EGFR mutation, at their age of 50-59, with either bone, brain, or lung metastases, were enriched in this cohort. The median overall survival (OS) was 20.4 months (95% CI: 15.2-25.6). Cox univariate and multivariate analysis revealed better PS (0-1), no distant lymph nodes metastasis (DLNM), simultaneous diagnosis of lung cancer and leptomeningeal metastasis (SDLL), and lower neutrophil to lymphocyte ratio (NLR), were associated with better OS. Based on these independent prognostic variables, a prognostic nomogram model with a C-index for OS prediction of 0.71, was constructed. The actual probability of survival at 1-, 2- and 3-year showed good concordance with the prediction curve of our nomogram. Conclusion: The systematic immunological level was an independent prognostic factor of lung cancer patients with LM. The prognostic model based on statistical analysis had a good ability to predict the OS of patients.

Clinicopathologic features, treatment, survival, and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study.

PURPOSE: The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort. RESULTS: A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model. CONCLUSION: CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.

Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma.

BACKGROUND: Immune checkpoint (IC) blockades (ICBs) significantly improve patients' clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy. METHODS: RNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center. RESULTS: The results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence. CONCLUSION: High expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.

Identification of Epithelial-Mesenchymal Transition- (EMT-) Related LncRNA for Prognostic Prediction and Risk Stratification in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is significantly associated with the invasion and development of esophageal squamous cell carcinoma (ESCC). However, the importance of EMT-related long noncoding RNA (lncRNA) is little known in ESCC. METHODS: GSE53624 (N = 119) and GSE53622 (N = 60) datasets retrieved from the Gene Expression Omnibus (GEO) database were used as training and external validation cohorts, respectively. GSE53624 and GSE53622 datasets were all sampled from China. Then, the prognostic value of EMT-related lncRNA was comprehensively investigated by weighted coexpression network analysis (WGCNA) and COX regression model. RESULTS: High expression of PLA2G4E-AS1, AC063976.1, and LINC01592 significantly correlated with the favorable overall survival (OS) of ESCC patients, and LINC01592 had the greatest contribution to OS. Importantly, ESCC patients were divided into low- and high-risk groups based on the optimal cut-off value of risk score estimated by the multivariate COX regression model of these three lncRNA. Patients with high risk had a shorter OS rate and restricted mean survival time (RMST) than those with low risk. Moreover, univariate and multivariate COX regression revealed that risk stratification, age, and TNM were independent prognostic predictors, which were used to construct a nomogram model for individualized and visualized prognosis prediction of ESCC patients. The calibration curves and time-dependent ROC curves in the training and validation cohorts suggested that the nomogram model had a good performance. Interestingly, clear trends indicated that risk score positively correlated with tumor microenvironment (TME) scores and immune checkpoints TIGIT, CTLA4, and BTLA. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that PLA2G4E-AS1, AC063976.1, and LINC01592 were primarily associated with TNF signaling pathway, NF-kappa B signaling pathway, and ECM-receptor interaction. CONCLUSION: We developed EMT-related lncRNA PLA2G4E-AS1, AC063976.1, and LINC01592 for prognostic prediction and risk stratification of Chinese ESCC patients, which might provide deep insight for personalized prognosis prediction in Chinese ESCC patients and be potential biomarkers for designing novel therapy.

Viral infections and the efficacy of PD-(L)1 inhibitors in virus-related cancers: Head and neck squamous cell carcinoma and hepatocellular carcinoma.

PURPOSE: This study aimed to test the interaction between viral infections and immune checkpoint inhibitor (ICI) efficacy for two virus-associated tumors, head and neck squamous carcinoma (HNSCC) and hepatocellular carcinoma (HCC), by conducting a systematic review and meta-analysis. METHODS: We searched databases from inception until December 30, 2020 to identify phase 2 or 3 randomized clinical trials involving ICI treatments with data on hazard ratios (HRs) for survival according to viral infection status. We evaluated the heterogeneity between patients with and without viral infections using an interaction test. Subgroup analyses were conducted to explore variations in the efficacy of immunotherapy according to viral infection status. RESULTS: Six phase 3 trials with 3672 patients (1382 with viral infections [38%] and 2115 without viral infections [57%]) were included. Among these patients, the pooled HR for survival was 0.69 (95% confidence interval [CI], 0.60-0.79) for those with viral infections and 0.84 (95% CI, 0.77-0.91) for those without infections after ICI treatment. Patients with viral infections achieved a better prognosis after ICI therapy than those without infections (P = 0.018). This was evident in patients with hepatitis B virus-associated HCC (P = 0.016), but not in patients with hepatitis C virus-associated HCC (P = 0.081) or in patients with human papillomavirus-positive HNSCC (P = 0.67). CONCLUSION: Patients with advanced HNSCC and HCC, regardless of viral infection status, could benefit from ICI treatment. Patients with hepatitis B virus-associated HCC were more likely to benefit from ICI treatment than patients without viral infections. REGISTRATION: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews on March 27, 2020 (registration number CRD42020155326).

Inferior outcome of bone metastasis in non-small-cell-lung-cancer patients treated with epidermal growth factor receptor inhibitors.

BACKGROUND: Targeted therapy has been established as the standard-of-care for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Among patients with advanced lung cancer, 30-40% have bone metastases (BoM) at first diagnosis. However, little is known on the clinical characteristics and prognostic factors of BoM in patients with NSCLC harboring EGFR mutations. METHODS: Treatment-naive patients with advanced NSCLC harboring EGFR mutations who were prescribed tyrosine kinase inhibitors (TKIs) were screened and enrolled between June 2009 and April 2019 from West China Hospital. Patients were dichotomized according to whether they had BoM. The demographic characteristics, gene mutation status and therapeutic efficacy, including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), were collected. RESULTS: A cohort of 604 patients were enrolled. The BoM group had worse PFS (11.7 vs. 14.0 months, HR = 0.73, p = 0.00013) and OS (32.8 vs. 46.1 months, HR = 0.54, p < 0.0001) compared with the non-BoM group. No significant differences were observed in disease control rate (p = 0.407) or ORR (p = 0.537) between the two groups. The metastatic sites in the two groups exhibited obvious differences. In multivariate analysis, BoM was found to be an independent factor of worse prognosis. CONCLUSION: BoM was identified as an independent inferior prognostic factor for EGFR-TKI treatment, and may have complex biological implications.

Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy.

Immunotherapy has significantly improved the clinical outcome of patients with cancer. However, the immune response rate varies greatly, possibly due to lack of effective biomarkers that can be used to distinguish responders from non-responders. Recently, clinical studies have associated high tumor neoantigen burden (TNB) with improved outcomes in patients treated with immunotherapy. Therefore, TNB has emerged as a biomarker for immunotherapy and other types of therapy. In the present review, the potential application of TNB as a biomarker was evaluated. The methods of neoantigen prediction were summarized and the mechanisms involved in TNB were investigated. The impact of high TNB and increased number of infiltrating immune cells on the efficacy of immunotherapy was also addressed. Finally, the future challenges of TNB were discussed.

Clinical features, treatment, and prognosis of different histological types of primary small bowel adenocarcinoma: A propensity score matching analysis based on the SEER database.

PURPOSE: This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). METHODS: Information on patients with SBA, MSBA, and SRCSB (2004-2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan-Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. RESULTS: In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. CONCLUSION: Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.