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Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1’s pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.

Mediastinal neurogenic tumors primarily originate from the intercostal and sympathetic nerves, whereas schwannomas originating from the brachial plexus are rare. Surgical intervention for such tumors is complex and associated with the risk of postoperative upper limb dysfunction due to their unique anatomical location. In this report, we present the case of a 21-year-old female diagnosed with a mediastinal schwannoma, who underwent a novel surgical approach combining cervical incision and intercostal uniportal video-assisted thoracoscopic surgery (VATS). Our study reviewed the patient’s clinical presentation, treatment approach, pathology, and prognosis. The findings of this study demonstrate that the cervical approach, combined with intercostal uniportal VATS, is a feasible surgical method for the removal of mediastinal schwannomas originating from the brachial plexus.

BackgroundThe addition of bevacizumab was found to be associated with prolonged survival whether in combination with chemotherapy, tyrosine kinase inhibitors or immune checkpoint inhibitors in the treatment landscape of advanced non-small cell lung cancer (NSCLC) patients. However, the biomarkers for efficacy of bevacizumab were still largely unknown. This study aimed to develop a deep learning model to provide individual assessment of survival in advanced NSCLC patients receiving bevacizumab.MethodsAll data were retrospectively collected from a cohort of 272 radiological and pathological proven advanced non-squamous NSCLC patients. A novel multi-dimensional deep neural network (DNN) models were trained based on clinicopathological, inflammatory and radiomics features using DeepSurv and N-MTLR algorithm. And concordance index (C-index) and bier score was used to demonstrate the discriminatory and predictive capacity of the model.ResultsThe integration of clinicopathologic, inflammatory and radiomics features representation was performed using DeepSurv and N-MTLR with the C-index of 0.712 and 0.701 in testing cohort. And Cox proportional hazard (CPH) and random survival forest (RSF) models were also developed after data pre-processing and feature selection with the C-index of 0.665 and 0.679 respectively. DeepSurv prognostic model, indicated with best performance, was used for individual prognosis prediction. And patients divided in high-risk group were significantly associated with inferior PFS (median PFS: 5.4 vs 13.1 months, P

BackgroundHitherto, no study has evaluated postoperative pain in patients with non-small cell lung cancer (NSCLC) treated with video-assisted mini-thoracotomy (VAMT). In this study, we aimed to assess postoperative pain related to the width of the metal rib spreader in patients who underwent lobectomy using VAMT.MethodsWe retrospectively analysed the data of 94 consecutive patients with NSCLC who underwent lobectomy using VAMT at our institution between March 2019 and May 2022. We divided the patients into groups according to the width ratio of the rib spreader to that of a single intercostal space. Patients with width ratios ≤ 2.5 times were assigned to group A, and those with width ratios > 2.5 times were assigned to group B. Pre-, intra-, and postoperative data were collected and reviewed.ResultsWe successfully performed VAMT in 94 patients with NSCLC. Forty-five patients were in group A, and 49 were in group B. There were no intraoperative mortalities, although one patient, due to respiratory failure, experienced 30-day mortality. There were no significant differences between the two groups in terms of the blood loss volume, operative time, drainage time, postoperative complications, length of hospital stay, or number of lymph node stations explored and retrieved. The drainage volumes (Day 1–Day 3) were higher in group B than in group A (P < 0.05). The postoperative visual analogue scale (VAS) pain scores were significantly lower in Group A than in Group B at 12, 24, and 48 h (P < 0.05), although there was no significant difference in the VAS scores between the two groups at 72 h and 1 week postoperatively (P > 0.05).ConclusionThe smaller the width of the metal rib spreader used in surgery, the less pain experienced by the patient and the faster the recovery. Multicentre, randomised, controlled trials should be conducted in the future.

PurposeThe aim of this study is to develop an augmented reality (AR)–assisted radiotherapy positioning system based on HoloLens 2 and to evaluate the feasibility and accuracy of this method in the clinical environment.MethodsThe obtained simulated computed tomography (CT) images of an “ISO cube”, a cube phantom, and an anthropomorphic phantom were reconstructed into three-dimensional models and imported into the HoloLens 2. On the basis of the Vuforia marker attached to the “ISO cube” placed at the isocentric position of the linear accelerator, the correlation between the virtual and real space was established. First, the optimal conditions to minimize the deviation between virtual and real objects were explored under different conditions with a cube phantom. Then, the anthropomorphic phantom–based positioning was tested under the optimal conditions, and the positioning errors were evaluated with cone-beam CT.ResultsUnder the normal light intensity, the registration and tracking angles are 0°, the distance is 40 cm, and the deviation reached a minimum of 1.4 ± 0.3 mm. The program would not run without light. The hologram drift caused by the light change, camera occlusion, and head movement were 0.9 ± 0.7 mm, 1.0 ± 0.6 mm, and 1.5 ± 0.9 mm, respectively. The anthropomorphic phantom–based positioning errors were 3.1 ± 1.9 mm, 2.4 ± 2.5 mm, and 4.6 ± 2.8 mm in the X (lateral), Y (vertical), and Z (longitudinal) axes, respectively, and the angle deviation of Rtn was 0.26 ± 0.14°.ConclusionThe AR-assisted radiotherapy positioning based on HoloLens 2 is a feasible method with certain advantages, such as intuitive visual guidance, radiation-free position verification, and intelligent interaction. Hardware and software upgrades are expected to further improve accuracy and meet clinicalbrendaannmae requirements.

Defects in DNA repair pathways are emerging hallmarks of cancer. Accurate DNA repairs and replications are essential for genomic stability. Cancer cells require residual DNA repair capabilities to repair the damage from replication stress and genotoxic anti-tumor agents. Defective DNA repair also promotes the accumulation of genomic changes that eventually lead to tumorigenesis, tumor progression, and therapeutic resistance to DNA-damaging anti-tumor agents. Rad51 recombinase is a critical effector of homologous recombination, which is an essential DNA repair mechanism for double-strand breaks. Rad51 has been found to be upregulated in many malignant solid tumors, and is correlated with poor prognosis. In multiple tumor types, Rad51 is critical for tumor metabolism, metastasis and drug resistance. Herein, we initially introduced the structure, expression pattern of Rad51 and key Rad51 mediators involved in homologous recombination. Additionally, we primarily discussed the role of Rad51 in tumor metabolism, metastasis, resistance to chemotherapeutic agents and poly-ADP ribose polymerase inhibitors.

Background and PurposeThis study aims to develop a risk model to predict esophageal fistula in esophageal cancer (EC) patients by learning from both clinical data and computerized tomography (CT) radiomic features.Materials and MethodsIn this retrospective study, computerized tomography (CT) images and clinical data of 186 esophageal fistula patients and 372 controls (1:2 matched by the diagnosis time of EC, sex, marriage, and race) were collected. All patients had esophageal cancer and did not receive esophageal surgery. 70% patients were assigned into training set randomly and 30% into validation set. We firstly use a novel attentional convolutional neural network for radiographic descriptor extraction from nine views of planes of contextual CT, segmented tumor and neighboring structures. Then clinical factors including general, diagnostic, pathologic, therapeutic and hematological parameters are fed into neural network for high-level latent representation. The radiographic descriptors and latent clinical factor representations are finally associated by a fully connected layer for patient level risk prediction using SoftMax classifier.Results512 deep radiographic features and 32 clinical features were extracted. The integrative deep learning model achieved C-index of 0.901, sensitivity of 0.835, and specificity of 0.918 on validation set with superior performance than non-integrative model using CT imaging alone (C-index = 0.857) or clinical data alone (C-index = 0.780).ConclusionThe integration of radiomic descriptors from CT and clinical data significantly improved the esophageal fistula prediction. We suggest that this model has the potential to support individualized stratification and treatment planning for EC patients.

Lymph node metastasis (LNM) of tumors is an established indicator of poor prognosis in patients. Tumor-associated lymphangiogenesis is a key step in LNM and has gained much attention. However, currently, there is no anti-tumor lymphangiogenesis drug used in clinical practice. Recently, studies on extracellular vesicles (EVs) have shown that different types of cells in the tumor microenvironment can release EVs that encapsulate a variety of molecules, including proteins, nucleic acids, and metabolites. Lymph endothelial cells (LECs) regulate tumor lymphangiogenesis through the uptake of EVs packed with different biologically active contents. In this review, we will discuss the possible mechanisms by which EVs participate in the regulation of tumor-associated lymphangiogenesis and LNM, summarize the potential value of EVs that can be used as biomarkers for the determination of tumor LNM, and indicate the potential anti-tumor lymphangiogenesis therapy.

BackgroundImmune related interferon regulatory factor 4 (IRF4) is a member of the IRF family, whereas the clinical significance and possible role of IRF4 in lung adenocarcinoma (LUAD) remains unclear. We aimed to investigate the role of IRF4 in predicting the prognosis of LUAD patients.MethodsUsing The Cancer Genome Atlas (TCGA) database and our immunohistochemical (IHC) cohort, we analyzed the correlation between IRF4 expression and clinical characteristics, and the prognostic value of IRF4 was also evaluated in LUAD. The potential biological functions of IRF4 in LUAD were analyzed by Gene Set Enrichment Analysis (GSEA). The relationship between IRF4 and immune cell infiltration were evaluated by TISIDB database and our own IHC cohort. In addition, an immune checkpoint inhibitor (ICI) treated cohort from Gene Expression Omnibus database was used to determine the role of IRF4 in LUAD patients with immunotherapy.ResultsWe found that either mRNA or protein expression level of IRF4 was significantly higher in LUAD than in normal tissues (P < 0.001). The elevate in IRF4 expression in LUAD was significantly associated with the earlier clinical stage (P = 0.002). Patients with LUAD and IRF4 high expression correlated with significant longer overall survival in both TCGA database (P < 0.05) and our IHC-cohort (P = 0.001). Our results also demonstrated that IRF4 could serve as an independent favorable prognostic factor in patients with LUAD. GSEA analysis indicated that high IRF4 expression group enriched with several immune-related pathways, such as B cell receptor signaling pathway, T cell receptor signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LUAD, IRF4 positively correlated with several different immune infiltrations including various B cells, CD8+ T cells and CD4+ T cells both in mRNA and protein levels. Additionally, we found that the expression of IRF4 was positively associated with PD-1 and PD-L1 mRNA expression levels, and IRF4 high expression predicted moderate better survival in LUAD with immunotherapy (P = 0.071).ConclusionsOur results suggested that IRF4 was associated with higher B cells and T cells infiltration levels and might be a favorable prognostic biomarker in LUAD patients, whereas the potential prognostic role of IRF4 in ICI-treated patients needed further exploration.

BackgroundUnderstanding the safety and adverse event profiles of PD-1/PD-L1 inhibitors is important in guiding cancer immunotherapy. Consequently, we designed this meta-analysis to evaluate the safety of PD-1/PD-L1 inhibitors in clinical trials involving cancer patients.MethodsFour safety indicators comprising treatment-related adverse events, death, discontinuation of therapy and grades 3–5 adverse events were evaluated using the random effect model. The quality of enrolled trials was assessed using the Newcastle Ottawa Scale (NOS).ResultsForty-four clinical trials were included in the final meta-analysis. Compared with chemotherapy, the risk of death due to the use of PD-1/PD-L1 inhibitors was much lower than that experienced in the control group (OR = 0.65, 95%CI: [0.47, 0.91], I2 = 0%, Z = 2.52 (P = 0.01)). Similar observations were apparent regarding the other three indicators of safety and also when the use of PD-1/PD-L1 inhibitors alone is compared with the combined use of PD-1/PD-L1 and CTLA-4. When used together with chemotherapy, PD-1/PD-L1 inhibitors increased the incidence of the adverse events as compared to the use of chemotherapy alone. Increased risks for adverse events were also noticed with the use of PD-1/PD-L1 inhibitors over the use of a placebo.ConclusionThe use of PD-1/PD-L1 inhibitors alone is associated with a better safety profile compared to either the use of chemotherapy or the use of PD-1/PD-L1 inhibitors with other anticancer regimens.

IntroductionThe immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients.MethodsIn this study, 100 patients who were diagnosed as having inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A five immune features-based signature was then constructed using the nested repeat 10-fold cross validation with least absolute shrinkage and selection operator (LASSO) Cox regression model. Nomograms were then established for predicting prognosis.ResultsThe immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of −0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively. Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value.ConclusionMultiple immune features-based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients and complemented the prognostic value of the TNM staging system.

Aim: To develop and validate a deep learning radiomics model, which could predict the lymph node metastases preoperatively in cervical cancer patients.Patients and methods: We included a cohort of 226 pathological proven operable cervical cancer patients in two academic medical institutions from December 2014 to November 2017. Then this dataset was split into training set (n = 176) and independent testing set (n = 50) randomly. Five radiomic features were selected and a radiomic signature was established. We then combined these five radiomic features with the preoperative tumor histology and grade of these patients together. Baseline logistic regression model (LRM) and support vector machine model (SVM) were established for the comparison. We then explored the performance of a deep neural network (DNN), which is a popular deep learning model nowadays. Finally, performance of this DNN was validated in another independent test set including 50 cases of operable cervical cancer patients.Results: One thousand forty-five radiomic features were extracted for each patient. Twenty-eight features were found to be significantly correlated with the lymph node status in these patients (P < 0.05). Five radiomic features were further selected for further study due to their higher predictive powers. Baseline LRM incorporating these five radiomic and two clinicopathological features was established, which had an area under receiver operating characteristic curve (ROC) of 0.7372 and an accuracy of 89.20%. The established DNN model had four neural layers, in which layer there were 10 neurons. Adagrad optimizer and 1,500 iterations were used in training. The trained DNN had an area under curve (AUC) of 0.99 and an accuracy of 97.16% in the internal validation. To exclude the overfitting, independent external validation was also performed. AUC and accuracy in test set could still retain 0.90 and 92.00% respectively.Conclusion: This study used deep learning method to provide a comprehensive predictive model using preoperative CT images, tumor histology, and grade in cervical cancer patients. This model showed an acceptable accuracy in the prediction of lymph node status in cervical cancer. Our model may help identifying those patients who could benefit a lot from radiation therapy rather than primary hysterectomy surgery if this model could resist strict testing of future randomized controlled trials (RCTs).

Mediastinal neurogenic tumors primarily originate from the intercostal and sympathetic nerves, whereas schwannomas originating from the brachial plexus are rare. Surgical intervention for such tumors is complex and associated with the risk of postoperative upper limb dysfunction due to their unique anatomical location. In this report, we present the case of a 21-year-old female diagnosed with a mediastinal schwannoma, who underwent a novel surgical approach combining cervical incision and intercostal uniportal videoassisted thoracoscopic surgery (VATS). Our study reviewed the patient's clinical presentation, treatment approach, pathology, and prognosis. The findings of this study demonstrate that the cervical approach, combined with intercostal uniportal VATS, is a feasible surgical method for the removal of mediastinal schwannomas originating from the brachial plexus. [ABSTRACT FROM AUTHOR]

Background: Hitherto, no study has evaluated postoperative pain in patients with non-small cell lung cancer (NSCLC) treated with video-assisted minithoracotomy (VAMT). In this study, we aimed to assess postoperative pain related to the width of the metal rib spreader in patients who underwent lobectomy using VAMT. Methods: We retrospectively analysed the data of 94 consecutive patients with NSCLC who underwent lobectomy using VAMT at our institution between March 2019 and May 2022. We divided the patients into groups according to the width ratio of the rib spreader to that of a single intercostal space. Patients with width ratios ≤ 2.5 times were assigned to group A, and those with width ratios > 2.5 times were assigned to group B. Pre-, intra-, and postoperative data were collected and reviewed. Results: We successfully performed VAMT in 94 patients with NSCLC. Fortyfive patients were in group A, and 49 were in group B. There were no intraoperative mortalities, although one patient, due to respiratory failure, experienced 30-day mortality. There were no significant differences between the two groups in terms of the blood loss volume, operative time, drainage time, postoperative complications, length of hospital stay, or number of lymph node stations explored and retrieved. The drainage volumes (Day 1-Day 3) were higher in group B than in group A (P < 0.05). The postoperative visual analogue scale (VAS) pain scores were significantly lower in Group A than in Group B at 12, 24, and 48 h (P < 0.05), although there was no significant difference in the VAS scores between the two groups at 72 h and 1 week postoperatively (P > 0.05). Conclusion: The smaller the width of the metal rib spreader used in surgery, the less pain experienced by the patient and the faster the recovery. Multicentre, randomised, controlled trials should be conducted in the future. [ABSTRACT FROM AUTHOR]