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Abstract Objective To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. Methods A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. Results A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1–128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p

Abstract Background Engrailed homeobox 1 (EN1) is a candidate oncogene that is epigenetically modified in salivary adenoid cystic carcinoma (SACC). We investigated the expression of EN1 in SACC tissues and cells, EN1 promoter methylation, and the role of EN1 in tumour progression in SACC. Methods Thirty-five SACC samples were screened for key transcription factors that affect tumour progression. In vitro and in vivo assays were performed to determine the viability, tumorigenicity, and metastatic ability of SACC cells with modulated EN1 expression. Quantitative methylation-specific polymerase chain reaction analysis was performed on SACC samples. Results EN1 was identified as a transcription factor that was highly overexpressed in SACC tissues, regardless of clinical stage and histology subtype, and its level of expression correlated with distant metastasis. EN1 promoted cell invasion and migration through epithelial-mesenchymal transition in vitro and enhanced SACC metastasis to the lung in vivo. RNA-seq combined with in vitro assays indicated that EN1 might play an oncogenic role in SACC through the PI3K-AKT pathway. EN1 mRNA levels were negatively correlated with promoter hypermethylation, and inhibition of DNA methylation by 5-aza-dC increased EN1 expression. Conclusions The transcription factor EN1 is overexpressed in SACC under methylation regulation and plays a pivotal role in SACC progression through the PI3K-AKT pathway. These results suggest that EN1 may be a diagnostic biomarker and a potential therapeutic target for SACC.

Objective: Accurate prognostic predictions and personalized decision-making on induction chemotherapy (IC) for individuals with locally advanced nasopharyngeal carcinoma (LA-NPC) remain challenging. This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival (OS) and their value in guiding treatment in patients with LA-NPC. Methods: Individuals with LA-NPC were reviewed retrospectively. Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods, the interpretable eXtreme Gradient Boosting (XGBoost) risk prediction model, and DeepHit time-to-event neural network. The models' prediction performances were compared using the concordance index (C-index) and the area under the curve (AUC). The patients were divided into two cohorts based on the risk predictions of the most successful model. The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone. Results: The 1 221 eligible individuals, assigned to the training (n = 813) or validation (n = 408) set, showed significant respective differences in the C-indices of the XGBoost, DeepHit, and nomogram models (0.849 and 0.768, 0.811 and 0.767, 0.730 and 0.705). The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS (0.881 and 0.760, 0.845 and 0.776, and 0.764 and 0.729, P < 0.001). IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group. Conclusion: This research used machine-learning algorithms to create and verify a comprehensive model integrating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC. This model could be valuable for delivering patient counseling and conducting clinical evaluations.

Background The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10–15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.Methods This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.Results A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.Conclusion Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.

PurposeDysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study.Patients and methodsA total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database.ResultsmiR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121).ConclusionUpregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

Abstract Background Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA. Methods In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro. Results Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines. Conclusions In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.

BackgroundTreatment-related lymphopenia (TRL) is common in patients with lung cancer, particularly in those with radiotherapy. However, the influence of TRL on the efficacy of immune checkpoint inhibitors (ICIs) for patients with lung cancer remains poorly understood. We performed a systematic review and meta-analysis to investigate the influence of TRL on survival of lung cancer patients on ICIs.MethodsIn order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and the Web of Science to identify observational studies with longitudinal follow-up. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity.ResultsTen cohort studies with 1130 lung cancer patients who were treated with ICIs were included. Among them, 427 (37.8%) had TRL. Pooled results showed that compared to patients without TRL, patients with TRL were associated with poor progression-free survival (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.62 to 2.60, p < 0.001; I2 = 22%) and overall survival (HR: 2.69, 95% CI: 2.10 to 3.43, p < 0.001; I2 = 0%). Sensitivity analysis limited to patients with non-small cell lung cancer showed similar results (HR: 2.66 and 2.62, both p < 0.05). Moreover, subgroup analyses according to the diagnostic criteria of TRL, regression analysis model (univariate or multivariate), and indications of ICIs (for locally advanced or advanced lung cancer) showed consistent results (p for subgroup difference all > 0.05).ConclusionTRL was associated with poor survival of lung cancer patients who were treated with ICIs.

Abstract Background This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. Methods We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan–Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. Results With a median follow‐up of 60 months (range: 1–128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty‐three patients experienced recurrence or metastasis. The total 10‐year progression‐free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka–Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka–Koga stage in the type B2 subgroup. Conclusion Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.

ObjectiveIn recent years, the utilization of indocyanine green near-infrared (ICG NIR) light imaging-guided lymph node dissection in the context of minimally invasive radical gastric cancer has emerged as a novel avenue for investigation. The objective of this study was to assess the influence of employing this technique for guiding lymph node dissection on the short-term clinical outcomes of minimally invasive radical gastric cancer surgery.MethodsThe present study conducted a comprehensive search for short-term clinical outcomes, comparing the group undergoing ICG NIR light imaging-guided lymph node dissection with the control group, by thoroughly examining relevant literature from the inception to July 2023 in renowned databases such as PubMed, Embase, Web of Science, and Cochrane Library. The primary endpoints encompassed postoperative complications, including abdominal infection, abdominal bleeding, pneumonia, anastomotic fistula, and overall incidence of complications (defined as any morbidity categorized as Clavien-Dindo class I or higher within 30 days post-surgery or during hospitalization). Additionally, secondary outcome measures consisted of the time interval until the initiation of postoperative gas and food intake, as well as various other parameters, namely postoperative hospital stay, operative time, intraoperative blood loss, total number of harvested lymph nodes, and the number of harvested metastatic lymph nodes. To ensure methodological rigor, the Cochrane Collaboration Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were employed to assess the quality of the included studies, while statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0 software.ResultsA total of 19 studies including 3103 patients were ultimately included (n=1276 in the ICG group and n=1827 in the non-ICG group). In this meta-analysis, the application of ICG near-infrared light imaging in minimally invasive radical gastric cancer surgery effectively improved the occurrence of postoperative Clavien-Dindo grade II or higher complications in patients (RR=0.72, 95% CI 0.52 to 1.00) with a statistically significant P=0.05; in reducing intraoperative blood loss and shortening While reducing intraoperative blood loss and shortening postoperative hospital stay, it could ensure the thoroughness of lymph node dissection in minimally invasive radical gastric cancer surgery (MD=5.575, 95% CI 3.677-7.473) with significant effect size (Z=5.76, p

Abstract Purpose To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-world data. Method and materials Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06 Gy/1.82 Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96 Gy/1.82 Gy per fraction. In center 2, all received 50 Gy/2 Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan–Meier method. Result Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N + tumor. The median follow-up was 45 months (range 1–163 months). There were no significant differences in terms of OS (p = 0.126), RC (p = 0.514), PFS (p = 0.195) and DMFS (p = 0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p = 0.009). While the rates of LRL control (98.4%) were equal between the two centers. Conclusion Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50 Gy for HRL may be an unfavorable treatment option for SC.

Abstract Background The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. Methods The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P

Abstract Purpose Concurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma. Methods and materials Patients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS), distant metastasis-free survival (DMFS), and toxicities. Results Ultimately, 113 of the 142 patients were analyzed. With a median follow-up of 45.6 months (interquartile range 26.8–57.8 months), the 3-year OS was 53.1% in the IC + CCRT group compared with 54.8% in the CCRT group (hazard ratio, 1.004; 95% confidence interval, 0.573–1.761; P = 0.988). There were no statistically significant differences in PFS, DMFS, and the larynx-preservation rate between the two groups. The incidence of grade 3–4 hematological toxicity was much higher in the IC+ CCRT group than in the CCRT group (54.7% vs. 10%, P

Abstract Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity. Then we review recent progress concerning the complex role of pyroptosis in various tumours. Importantly, we summarise various FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties by inducing pyroptosis of cancer cells. Moreover, we also focus on the current application of nanotechnology-induced pyroptosis in tumour therapy. In addition, some unsolved problems and potential future research directions are also raised.

Background and purpose: Anatomical changes may compromise the planned target coverage and organs-at-risk dose in particle therapy. This study reports on the practice patterns for adaptive particle therapy (APT) to evaluate current clinical practice and wishes and barriers to further implementation. Materials and methods: An institutional questionnaire was distributed to PT centres worldwide (7/2020–6/2021) asking which type of APT was used, details of the workflow, and what the wishes and barriers to implementation were. Seventy centres from 17 countries participated. A three-round Delphi consensus analysis (10/2022) among the authors followed to define recommendations on required actions and future vision. Results: Out of the 68 clinically operational centres, 84% were users of APT for at least one treatment site with head and neck being most common. APT was mostly performed offline with only two online APT users (plan-library). No centre used online daily re-planning. Daily 3D imaging was used for APT by 19% of users. Sixty-eight percent of users had plans to increase their use or change their technique for APT. The main barrier was “lack of integrated and efficient workflows”. Automation and speed, reliable dose deformation for dose accumulation and higher quality of in-room volumetric imaging were identified as the most urgent task for clinical implementation of online daily APT. Conclusion: Offline APT was implemented by the majority of PT centres. Joint efforts between industry research and clinics are needed to translate innovations into efficient and clinically feasible workflows for broad-scale implementation of online APT.

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment.

PurposeThis study aimed to investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with PD-1 inhibitor or anti-EGFR in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Methods and materialsWe retrospectively reviewed the clinical data of 206 patients with LA-NPC, including IC combined with anti-PD-1 (57 patients), IC combined with anti-EGFR (28 patients), and IC alone (121 patients). The short-term efficacy was assessed at the end of IC and one month after overall treatment. According to the RECIST v1.1, the short-term efficacy of cervical lymph nodes and primary nasopharynx foci was divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall response (ORR) was defined as the sum of CR and PR. Acute toxicities were graded according to the CTCAE v5.0. One-way analysis of variance (ANOVA) was used to compare differences in the numerical variables among groups. Fisher Freeman-Halton test or Pearson Chi-square test was used to compare classified variables.ResultsThe ORR rates of primary nasopharynx foci in IC, anti-EGFR, and anti-PD-1 group were 68.60%, 67.9%, and 94.7%, respectively, and the corresponding rates of ORR in cervical lymph nodes were 78.5%, 71.4%, and 93.0%, respectively. There was a statistical difference in the ORR between the three groups. Further analysis showed that after IC or overall treatment, the CR rate of primary nasopharynx foci in the anti-PD-1 group was significantly higher than the other two groups. The most common adverse effects were hematotoxicity, gastrointestinal toxicity, and transaminase elevation. However, there were no statistical differences in the frequency of any common adverse effects between the three groups.ConclusionsThe addition of anti-PD-1 based on IC significantly improved the short-term efficacy of LA-NPC and toxicities were tolerable.

Background and purpose: Organ motion compromises accurate particle therapy delivery. This study reports on the practice patterns for real-time intrafractional motion-management in particle therapy to evaluate current clinical practice and wishes and barriers to implementation. Materials and methods: An institutional questionnaire was distributed to particle therapy centres worldwide (7/2020–6/2021) asking which type(s) of real-time respiratory motion management (RRMM) methods were used, for which treatment sites, and what were the wishes and barriers to implementation. This was followed by a three-round DELPHI consensus analysis (10/2022) to define recommendations on required actions and future vision. With 70 responses from 17 countries, response rate was 100% for Europe (23/23 centres), 96% for Japan (22/23) and 53% for USA (20/38). Results: Of the 68 clinically operational centres, 85% used RRMM, with 41% using both rescanning and active methods. Sixty-four percent used active-RRMM for at least one treatment site, mostly with gating guided by an external marker. Forty-eight percent of active-RRMM users wished to expand or change their RRMM technique. The main barriers were technical limitations and limited resources. From the DELPHI analysis, optimisation of rescanning parameters, improvement of motion models, and pre-treatment 4D evaluation were unanimously considered clinically important future focus. 4D dose calculation was identified as the top requirement for future commercial treatment planning software. Conclusion: A majority of particle therapy centres have implemented RRMM. Still, further development and clinical integration were desired by most centres. Joint industry, clinical and research efforts are needed to translate innovation into efficient workflows for broad-scale implementation.

BackgroundThe ability of cancer-associated fibroblasts (CAFs) to encourage angiogenesis, tumor cell spread, and increase treatment resistance makes them pro-tumorigenic. We aimed to investigate the CAF signature in Bladder urothelial carcinoma (BLCA) and, for clinical application, to build a CAF-based risk signature to decipher the immune landscape and screen for suitable treatment BLCA samples.MethodsCAF-related genes were discovered by superimposing CAF marker genes discovered from single-cell RNA-seq (scRNA-seq) data taken from the GEO database with CAF module genes discovered by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data from TCGA. After identifying prognostic genes related with CAF using univariate Cox regression, Lasso regression was used to build a risk signature. With microarray data from the GEO database, prognostic characteristics were externally verified. For high and low CAF-risk categories, immune cells and immunotherapy responses were analyzed. Finally, a nomogram model based on the risk signature and prospective chemotherapeutic drugs were examined.ResultsCombining scRNA-seq and bulk-seq data analysis yielded a total of 124 CAF-related genes. LRP1, ANXA5, SERPINE2, ECM1, RBP1, GJA1, and FKBP10 were the seven BLCA prognostic genes that remained after univariate Cox regression and LASSO regression analyses. Then, based on these genes, prognostic characteristics were created and validated to predict survival in BLCA patients. Additionally, risk signature had a strong correlation with known CAF scores, stromal scores, and certain immune cells. The CAF-risk signature was identified as an independent prognostic factor for BLCA using multifactorial analysis, and its usefulness in predicting immunotherapy response was confirmed. Based on risk classification, we projected six highly sensitive anticancer medicines for the high-risk group.ConclusionThe prognosis of BLCA may be accurately predicted using CAF-based risk signature. With a thorough understanding of the BLCA CAF-signature, it might be able to explain the BLCA patients’ response to immunotherapy and identify a potential target for BLCA treatment.

Objective: This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index (SII) in non-metastatic nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions. The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution, respectively. The optimal cut-off value of SII was determined, and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort. The propensity score matching (PSM) method was applied to minimize the confounding effects of unbalanced covariables. Results: The optimal cut-off value of the SII in the training cohort was 686, which was confirmed using the validation cohort. Multivariate analysis showed that both before and after PSM, SII values > 686 were independently associated with worse progression-free survival (PFS) ratio in both cohorts (before PSM, P = 0.008 and P = 0.008; after PSM, P = 0.008 and P = 0.007, respectively). Based on the analysis of independent prognostic factors of SII and N stage, we developed a categorical risk stratification model, which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival (DMFS) in the training cohort. There was no significant difference in PFS between RT alone and combined therapies within the low- and intermediate-risk groups (5-year PFS, 77.5% vs. 75.3%, P = 0.275). Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies (5-year PFS, 64.9% vs. 40.3%, P = 0.003). Conclusion: Pretreatment SII predicts PFS of patients with non-metastatic NPC. Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.

Immune evasion through up-regulating checkpoint inhibitory receptors on T cells plays an essential role in tumor initiation and progression. Therefore, immunotherapy, including immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) and chimeric antigen receptor T cell (CAR-T) therapy, has become a promising strategy for hematological malignancies. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a novel checkpoint inhibitory receptor expressed on immune cells, including cytotoxic T cells, regulatory T cells, and NK cells. TIGIT participates in immune regulation via binding to its ligand CD155. Blockage of TIGIT has provided evidence of considerable efficacy in solid tumors in preclinical research and clinical trials, especially when combined with PD-1 inhibition. However, the mechanism and function of TIGIT in hematological malignancies have not been comprehensively studied. In this review, we focus on the role of TIGIT in hematological malignancies and discuss therapeutic strategies targeting TIGIT, which may provide a promising immunotherapy target for hematological malignancies.

Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. Local combined systemic therapy is widely used in the treatment of unresectable hepatocellular cancer (uHCC). This retrospective study was to investigate the prognostic effect and prognostic factors of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICIs) in the treatment of uHCC. A retrospective analysis of 171 patients with uHCC was performed in our hospital from April 27, 2015 to October 18, 2021. According to different treatment options, patients were divided into TACE group (n=45), TACE+TKI group (n=76) and TACE+TKI+ICIs group (n=50). In this study, we found that, the median overall survival (mOS) of TACE+TKI+ICIs group was significantly better than TACE+TKI group and TACE group [24.1 (95% CI 15.1-33.1) months vs 14.9 (95% CI 10.7-19.1) months vs 11.4 (95% CI 8.4-14.5) months, hazard ratio (HR) 0.62; 95% CI 0.47-0.81; P=0.002]. A visible difference in the median progression-free survival (mPFS) interval between the groups was discovered [10.6 (95% CI6.5-14.7) months in TACE+TKI+ICIs group vs. 6.7 (95% CI 5.5-7.9) months in the TACE+TKI group vs. 6 (95% CI 2.3-9.7) months in the TACE group (HR 0.66; 95% CI 0.53-0.83; P

Abstract Background To investigate the clinical characteristics of metachronous second primary malignancies (Met‐SPMs) and its impact on prognosis in hypopharyngeal carcinoma (HPC). Methods We reviewed 593 newly diagnosed HPC patients without invasive synchronous SPMs (Syn‐SPMs) who were treated in our cancer center between 2009 and 2019. According to the status during follow‐up, patients were classified into three groups: (a) without SPMs (No‐SPMs, n = 440), (b) with tumors in situ in the esophagus or stomach (Tis, n = 80), or (c) with Met‐SPMs (n = 73). Results The median follow‐up time for entire cohort (n = 593) was 66.7 months. Met‐SPMs were present in 12.3% of the cohort (73/593). The predominant site of SPMs was esophagus, followed by lung, oral cavity, thyroid, stomach, and oropharynx. In Met‐SPMs group, both index tumor and SPMs were the main causes of death. Tis group exhibited comparable 5‐year overall survival (OS) and disease‐specific survival (DSS) with that of No‐SPMs group. The Met‐SPMs group had similar 5‐year OS rate and better 5‐year DSS rate of 47.3% versus 43.6% (odds ratio [OR], 0.931; 95% confidence interval [CI], 0.681–1.274, p = 0.657) and 66.3% vs. 46.2% (OR, 0.600; 95% CI, 0.402–0.896, p = 0.012), respectively, compared with the No‐SPMs group. Conclusion The overall incidence of Met‐SPMs in HPC was 12.3%. The occurrence of Met‐SPMs does not jeopardize the survival outcome of HPC. Routine surveillance of Met‐SPMs was requisite for patients with HPC.

Abstract Retinal neurodegeneration develops early in the course of diabetic retinopathy (DR), and our previous research showed that succinate accumulation results in retinal ganglion cells (RGCs) dysfunction in the retinas of rats with DR. Succinate can enhance lysine succinylation, but the succinylation of DR is not well understood. In this study, we investigated the role of the succinylome in DR and identified the key factor in this process. TMT labeling and LC–MS/MS analysis were combined to quantify the differentially succinylated proteins between vitreous humor (VH) samples from DR and non-DR patients. A total of 74 sites in 35 proteins were differentially succinylated between DR and non-DR vitreous humor samples, among which succinylation of the K108 site of optineurin (OPTN K108su) in the defense response was enriched by GO analysis based on the biological process category. Then, using a streptozotocin (STZ)-induced diabetic rat model, R28 cells and primary rat RGCs (rRGCs), we demonstrated that OPTN underwent lysine succinylation in the retinas of rats with DR and that OPTN K108su mediated autophagic flux blockade under high-glucose (HG) conditions. Sirt5 can desuccinylate OPTN K108su, thus protecting RGCs function from high glucose-induced RGCs autophagic flux blockade in the diabetic retina. Overall, desuccinylation of OPTN is an essential adaptive mechanism for ameliorating autophagic flux blockade in RGCs under DR conditions, and targeting the Sirt5-desuccK108-OPTN axis may thus open an avenue for therapeutic intervention in RCGs dysfunction.

Lung cancer ranks the first cancer-related morbidity and mortality in China. With the development and penetration of imaging technology, increasing small pulmonary peripheral Nodules (SPPNs) have been detected. However, precise location and diagnosis of SPPNs is still a tough problem for clinical diagnosis and treatment in department of thoracic surgery. With the development of electromagnetic navigation bronchoscopy (ENB), it provides a novel minimally invasive method for the diagnosis and treatment of SPPNs. In this review, we summarized the application and progress of ENB in preoperative positioning, diagnosis, and local treatment, then, discussed the clinical application of ENB in the hybrid operating room.

This study aimed to compare the safety and efficacy of CyberKnife (CK) versus TomoTherapy for the treatment of brain metastases (BMs). Three cases of BM treated at our hospital – two with CK and one with TomoTherapy – were compared and analyzed. Both treatments showed good therapeutic effects, but CK was more effective. No radiation-related adverse reactions were observed in the three patients. It is concluded that both CK and TomoTherapy can effectively control target lesions by allowing a higher dose in a single treatment while minimizing damage to surrounding normal brain tissue. This can reduce the total number of treatments needed, improve the prognosis of patients, and save medical resources.

Abstract Purpose To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients. Patients and methods From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis. Results The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301–23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine. Conclusion In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.

Tumor dormancy continues to be a research hotspot with numerous pressing problems that need to be solved. The goal of this study is to perform a bibliometric analysis of pertinent articles published in the twenty-first century. We concentrate on significant keywords, nations, authors, affiliations, journals, and literature in the field of tumor dormancy, which will help researchers to review the results that have been achieved and better understand the directions of future research. We retrieved research articles on tumor dormancy from the Web of Science Core Collection. This study made use of the visualization tools VOSviewer, CiteSpace, and Scimago Graphica, as visualization helps us to uncover the intrinsic connections between information. Research on tumor dormancy has been growing in the 21st century, especially from 2015 to the present. The United States is a leader in many aspects of this research area, such as in the number of publications, the number of partners, the most productive institutions, and the authors working in this field. Harvard University is the institution with the highest number of publications, and Aguirre-Ghiso, Julio A. is the author with the highest number of publications and citations. The keywords that emerged after 2017 were “early dissemination”, “inhibition”, “mechanism”, “bone metastasis”, and “promotion”. We believe that research on tumor dormancy mechanisms and therapy has been, and will continue to be, a major area of interest. The exploration of the tumor dormancy microenvironment and immunotherapeutic treatments for tumor dormancy is likely to represent the most popular future research topics.

Abstract Purpose Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision‐making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non‐metastatic nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods Conditional overall survival (COS) and progression‐free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event‐free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated. Results A total of 1993 patients were eligible for analysis. The estimated 5‐year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event‐free follow‐up, additional 5‐year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non‐significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I‐III across all conditional time points. After 4 years of follow‐up, progression hazard of stage IVA became relatively steady of approximate 6%. Conclusions Survival prospect of non‐metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision‐making in terms of both clinical management and surveillance counseling. Stage‐dependent and hazard‐adapted clinical management and surveillance are warranted.

Gastrointestinal cancer represents a public health concern that seriously endangers human health. The emerging single-cell sequencing (SCS) technologies are different from the large-scale sequencing technologies which provide inaccurate data. SCS is a powerful tool for deciphering the single-cell resolutions of cellular and molecular landscapes, revealing the features of single-cell genomes, transcriptomes, and epigenomes. Recently, SCS has been applied in the field of gastrointestinal cancer research for clarifying the origin and heterogeneity of gastrointestinal cancer, acquiring micro-environmental information, and improving diagnostic and treatment methods. This review outlines the applications of SCS in gastrointestinal cancer research and summarizes the most recent advances in the field.

ObjectivesTo analyze the incidence and spread of lymph node metastasis (LNM) and the effectiveness of prophylactic neck irradiation in patients with SNSCC.MethodsA total of 255 patients with SNSCC were retrospectively reviewed. The LNM spread pattern was revealed. The clinical parameters related to LNM, and the prognostic value of elective neck irradiation (ENI) were assessed. A 1:1 matching with propensity scores was performed between ENI group and observation (OBS) group.ResultsThe initial LNM rate was 20.8%, and the regional recurrence (RR) rate was 7.5%. Lymphatic spreading in SNSCC followed the common trajectories: a. level Ib ➔ level II ➔ level Va/level III/IV lymph nodes (LNs); b. retropharyngeal lymph nodes (RPLNs) ➔ level II LNs. The most frequently involved site was level II LNs (16.1%), followed by level Ib LNs (10.2%), RPLNs (4.7%), level III LNs (3.2%), level Va LNs (1.6%), level IVa LNs (1.4%) and level VIII LNs (0.8%). The median follow-up time was 105 months. The 5-year overall survival (OS) was 55.7% for N0 patients and 38.5% for patients with initial N+ or N- relapse (p = 0.009). After PSM, the 5-year regional recurrence-free survival was 71.6% and 94.7% (p = 0.046) in OBS and ENI group, respectively. The multivariate analysis showed that ENI (p = 0.013) and absence of nasopharynx involvement (p = 0.026) were associated with a significantly lower RR rate.ConclusionsPatients with LNM had poorer survival than those who never experienced LNM. Lymphatic spread in SNSCC followed predictable patterns. ENI effectively reduced the RR rate in patients at high risk.

Purpose: To characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. Methods: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. Results: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p

In addition to rare incidence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 receptor kinase (ROS1) positive patients, patients with brain metastases of non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) sensitive mutation have no effective systemic therapy at present, and the overall prognosis is poor. Since the low blood-brain barrier permeability of chemotherapy drugs, the local treatment plays an important role in brain metastases. To understand the clinical characteristics and treatment of brain parenchymal metastases in patients with NSCLC and EGFR mutation negative, we reviewed the incidence, onset time, site, numbers, size, symptom, therapeutic effect and disease evolution in them, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.

Background: Early integration of palliative care (PC) for patients with advanced cancer has been recommended to improve quality of care. This study aims to describe prevalence, temporal trend and predictors of PC use in metastatic breast cancer (mBCa) patients receiving critical care therapies (CCT; included invasive mechanic ventilation, percutaneous endoscopic gastrostomy tube, total parenteral nutrition, tracheostomy and dialysis). Methods: The National Inpatient Sample was queried for mBCa patients receiving CCT between 2005 and 2014. Annual percent changes (APC) were calculated for PC prevalence in the overall cohort and subgroups. Multivariable logistic analysis was used to explore predictors of PC use. Results: Of 5833 mBCa patients receiving CCT, 880 (15.09%) received PC. Rate of PC use increased significantly from 2.53% in 2005 to 25.96% in 2014 (APC: 35.75%; p

Abstract Background The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB). Materials and methods Between April 1984 and December 2018, 138 patients with non-metastatic ENB were retrospectively analyzed. The treatment modalities mainly included surgery alone (n = 7), radiotherapy alone (n = 33), concurrent chemoradiotherapy (n = 17), surgery combined with current chemoradiotherapy (n = 32), and surgery plus radiotherapy (n = 49). Results The median follow-up time for the entire cohort was 61 months (range, 4–231 months). The 5-year overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) rate were 69.6, 78.0 and 73.9%, respectively. Surgery combined with radiotherapy elicited superior survival results, and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients, patients with advanced Kadish disease, patients receiving intensity modulated radiation therapy and those with positive surgical margin. Univariate analysis identified orbital invasion and treatment modalities were predictors for OS, LRFFS and DMFS. Lymph node metastasis was associated with OS and DMFS, but not LRFFS. Intracranial invasion, advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS. Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modalities was independent prognostic factors for OS and LRFFS. Conclusion Orbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. Regarding the treatment modality, the optimal strategy remined surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.

Abstract Background Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. However, the contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis. Methods Clinical data of 412 patients with BC and 433 transcription files for normal and cancer tissues were downloaded from The Cancer Genome Atlas. The CIBERSORT algorithm was used to determine the relative abundance of 22 immune cell types in each sample and the ESTIMATE algorithm was used to identify differentially expressed genes within the tumour microenvironment of BC, which were subjected to functional enrichment and protein-protein interaction (PPI) analyses. The association of cell subsets and differentially expressed genes with patient survival and clinical parameters was examined by Cox regression analysis and the Kaplan-Meier method. Results Resting natural killer cells and activated memory CD4+ and CD8+ T cells were associated with favourable patient outcome, whereas resting memory CD4+ T cells were associated with poor outcome. Differential expression analysis revealed 1334 genes influencing both immune and stromal cell scores; of them, 97 were predictive of overall survival in patients with BC. Among the top 10 statistically significant hub genes in the PPI network, CXCL12, FN1, LCK, and CXCR4 were found to be associated with BC prognosis. Conclusion Tumour-infiltrating immune cells and cancer microenvironment-related genes can affect the outcomes of patients and are likely to be important determinants of both prognosis and response to immunotherapy in BC.

Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and European experts regarding subsequent treatment of Patient 2. Continuation of TMZ and bevacizumab was suggested until further deterioration. Whether tumor-treating field therapy should play a role in this patient could not be evaluated. However, some other molecular targeted agents (e.g. vascular endothelial growth factor receptor tyrosine kinase inhibitors such as regorafenib or apatinib) after bevacizumab failure, the effectiveness of these drugs remains unclear. Conclusion: In clinical practice, although we should follow established guidelines, the final treatment regimen requires informed consent from the patient. Thus, some real-world cases may deviate from the established guidelines. When patients reach end-stage disease with a marked decrease in their performance status and no standard treatment options, active antitumor treatment might be more likely to be attempted in China, while symptomatic treatment is more frequently performed in Europe. Although treatment philosophies for patients with glioma are slightly different between Eastern and Western medical experts, any treatment strategies should satisfy these patients.

Abstract In the fight against cancer, early detection is a key factor for successful treatment. However, the detection of cancer in the early stage has been hindered by the intrinsic limits of conventional cancer diagnostic methods. Nanotechnology provides high sensitivity, specificity, and multiplexed measurement capacity and has therefore been investigated for the detection of extracellular cancer biomarkers and cancer cells, as well as for in vivo imaging. This review summarizes the latest developments in nanotechnology applications for cancer diagnosis. In addition, the challenges in the translation of nanotechnology-based diagnostic methods into clinical applications are discussed.

Abstract Background Lymph node (LN) metastasis status is the decision‐making basis for the surgical procedure and adjuvant therapy modalities. Fewer studies have previously focused on LN metastasis in N1 station, especially on peripheral lymph node (PLN) metastasis in N1 station. This study aimed to reveal the metastasis status of PLN of non‐small cell lung cancer (NSCLC), and investigate its effects on N staging. Methods We retrospectively evaluated a consecutive series of patients who underwent curative resection for histologically confirmed N1 NSCLC. Propensity score matching (PSM) was used to analyze the effects of PLN on N staging. Results A total of 105 patients with confirmed pathological N1 (pN1) stage NSCLC with solitary nodule and without neoadjuvant therapy were enrolled into the study: 55 patients had intraperipheral LN metastasis (IPLNM), and 50 patients had extra‐peripheral LN metastasis (EPLNM). Before PSM analysis, type of location (P = 0.002), surgical procedure (P = 0.008), number of positive LNs (P = 0.029), number of LNs removed (P = 0.010), lobe of lung cancer (P = 0.031), and vascular invasion (P = 0.049) showed significant differences between the two groups. After PSM analysis, statistically there were differences in type of location (P = 0.034), number of positive LNs (P = 0.008) and vascular invasion (P = 0.049) between them. Conclusion PLN metastasis was a quite common pattern of LN metastasis in N1 station of NSCLC. IPLNM occurred more frequently in central NSCLC and NSCLC with vascular invasion, and thoracotomy was likely to secure more accurate PLN staging. Clinicians should pay great attention to PLN dissection. Follow‐up data will be needed in order to detect the prognosis of IPLNM patients.

Abstract Background Increased attention has been focused on cancer immunity gene signature. However, the threshold of immune scores to predict disease‐free survival (DFS) and overall survival (OS) in breast cancer has not yet been defined. This study aimed to explore the association of immune scores with prognosis and build a clinical nomogram to predict the survival of patients with breast cancer. Methods A total of 986 subjects were analyzed, and clinicopathological characteristics and immune scores were obtained from the TCGA database. Cox proportional hazards regression model was used to estimate the adjusted hazard ratios (HRs). Based on results of multivariate analysis, nomograms were built. The models were subjected to bootstrap internal validation. The predictive accuracy and discriminative ability were measured by concordance index (C‐index) and the calibration curve. Results The patients were divided into three subgroups according to their immune scores. We found that compared with patients with low immune scores, those with intermediate and high immune scores had significantly improved DFS (HR and 95% confidence interval [CI]: 0.439 [0.242‐0.799], 0.541 [0.343‐0.855], respectively), whereas only intermediate immune scores significantly indicated better OS (HR and 95% CI: 0.385 [0.163‐0.910]). The C‐index for DFS and OS prediction was 0.723 (95% CI, 0.661‐0.785) and 0.800 (95% CI, 0.724‐0.877), respectively. The calibration curves for probability of 3‐ and 5‐year DFS showed significant agreement between nomogram predictions and the actual observations. Conclusions High and/or intermediate immune scores are significantly correlated with better DFS and OS in patients with breast cancer. Moreover, the nomograms for predicting prognosis may help to estimate the survival of patients.

PurposeThe high intracranial efficacy of targeted therapeutic agents poses a challenge in determining the optimal sequence of local radiation therapy (RT) and systemic treatment with tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). Therefore, we conducted a cohort study to elucidate the appropriate treatment strategy, either upfront RT or deferred RT including a toxicity assessment, in these patients.Patients and MethodsWe retrospectively evaluated patients with gene-driven BMs from a single institution and divided them into deferred and upfront RT groups. Survival was estimated using a log-rank test. Intracranial progression was estimated using Fine-Gray competing risks model. Cox proportional hazards regression was performed for multivariable analysis in the entire group and subgroups.ResultsAmong the 198 eligible patients, 94 and 104 patients received deferred and upfront RT, respectively. The upfront RT group showed a lower intracranial progression risk with an adjusted sub-distribution hazard ratios of 0.41 (95% CI, 0.30–0.57) than did the deferred RT group (median intracranial progression-free survival [iPFS], 19.9 months vs. 11.1 months; p < 0.001). The median overall survival (OS; 43.2 months vs. 49.1 months, p = 0.377) and BM-specific survival (92.1 months vs. 82.9 months, p = 0.810) after salvage therapy were not significantly different between the upfront and deferred groups. Among patients with progressed extracranial disease, the deferred RT group showed significantly better OS than did the upfront RT group (44.0 vs. 28.1 months, p = 0.022). Grade 3–4 treatment-related adverse events were rare, and similar toxicities were observed between the two groups.ConclusionCompared to the deferred RT group, the upfront RT group achieved longer iPFS and similar survival outcomes in most patients with gene-driven NSCLC BM, although patients with progression of extracranial disease might benefit from deferred RT. Both groups showed well-tolerated toxicities.Trial registration IDNCT04832672.

Epithelial ovarian cancer (EOC) has a poor prognosis and high mortality rate; patients are easy to relapse with standard therapies. So, there is an urgent need to develop novel drugs. In this study, differentially expressed genes (DEGs) of EOC were identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Enrichment and protein–protein interaction (PPI) analyses were performed. The drug candidate which has the possibility to treat EOC was predicted by Connectivity Map (CMAP) databases. Moreover, molecular docking was selected to calculate the binding affinity between drug candidate and hub genes. The cytotoxicity of drug candidates was assessed by MTT and colony formation analysis, the proteins coded by hub genes were detected by Western blots, and apoptosis analysis was evaluated by flow cytometry. Finally, 296 overlapping DEGs (|log 2 fold change|>1; q-value

BackgroundMost hypopharyngeal cancers (HPCs) develop lymph node metastasis (LNM) at initial diagnosis. Understanding the pattern of LNM in HPC could help both surgeons and radiologists make decisions in the management of cervical lymph nodes.MethodsA total of 244 newly diagnosed HPC patients between January 2010 and December 2018 were recruited from three specialized cancer hospitals in mainland China. All patients received pre-treatment magnetic resonance imaging (MRI), and definitive radiotherapy with or without concurrent chemotherapy. We reassessed the features of the primary tumor (tumor size, primary location, and extent of invasion) and the involvement of lymph nodes at each level. According to the incidence of LNM, these levels were sequenced and sorted into drainage stations. Univariate and multivariate analyses were used to determine the risk factors for bilateral and regional lymph node metastasis.ResultsThe cohort consisted of 195 piriform sinus cancers (PSC), 47 posterior wall cancers (PWC), and 2 post-cricoid cancers (PCC). A total of 176 patients (72.1%) presented with MRI-detectable LNMs. The overall LNM rates for level II-VI and retropharyngeal lymph nodes (RPLNs) were 59.0%, 52.9%, 14.3%, 1.6%, 2.9%, and 16.4%, respectively. Based on the prevalence of LNM at each level, we hypothesize that the lymphatic drainage of PSC was carried out in sequence along three stations: Level II and III (61.0% and 55.4%), Level IV and RPLN (15.9% and 11.3%), and Level V and VI (1.5% and 3.1%). For PWCs, lymphatic drainage is carried out at two stations: Level II, III, and RPLN (48.9%, 40.4%, and 34.0%) and Level IV-VI (6.4%, 0%, and 2.1%). According to univariate and multivariate analyses, posterior wall invasion was significantly correlated with bilateral LNM (P = 0.030, HR = 2.853 95%CI, 1.110-7.338) and RPLN metastasis (P = 0.017, HR = 2.880 95%CI, 1.209-6.862). However, pyriform sinus invasion was less likely to present with bilateral LNM (P = 0.027, HR = 0.311, 95%CI, 0.111-0.875) and RPLN metastasis (P = 0.028, HR = 0.346, 95%CI, 0.134-0.891).Conclusions and RelevanceThe primary tumor site and extent of invasion are related to the pattern of lymph node metastasis. That is, the metastasis would drainage station by station along different directions.

Background: Sinonasal squamous cell carcinoma (SNSCC) can arise as either inverted papilloma–associated SCC (IP-SCC) or as de novo SCC (DN-SCC). It is controversial as to whether survival differences between IP-SCC and DN-SCC exist. Methods: Between January 2000 and December 2016, 234 patients with SNSCC were analyzed retrospectively, including 68 with IP-SCC and 166 with DN-SCC. Propensity score matching (PSM) was performed to balance baseline characteristics. The Kaplan–Meier method and Cox proportional hazard model were used to determine risk factors on survival outcomes. Results: The median follow-up time was 98.4 months. Before PSM, lymph node metastasis was noted to be lower in patients with IP-SCC. After PSM, the 5-year DFS, DSS and OS between IP-SCC and DN-SCC were 43.0% vs. 44.5% (p = 0.701), 49.2% vs. 56.2% (p = 0.753), and 48.2% vs. 52.9% (p = 0.978). The annual hazards of local failure, respectively, peaked at 28.4% and 27.8% for IP-SCC and DN-SCC within 12 months after treatment. Afterward, the hazards gradually decreased and the hazard for IP-SCC was always higher before approaching null. Conclusions: This study provides novel evidence to support the clinical utility of improved distinction between IP-SCC and DN-SCC. Further studies are necessary to validate these findings before considering escalation of IP-SCC.

UM-164 is a dual inhibitor of c-Src and p38 MAPK, and has been a lead compound for targeting triple-negative breast cancer. UM-164 shows stronger binding to the active sites of Src compared with the conventional Src inhibitor Dasatinib. While Dasatinib has displayed some inhibitory effects on glioma growth in clinical trials, whether UM-164 can suppress glioma growth has not been reported. Here we show that UM-164 suppressed the proliferation, migration and spheroid formation of glioma cells, and induced cell cycle arrest in the G1 phase. Moreover, UM-164 triggered YAP translocation to the cytoplasm and reduced the activity of YAP, as evidenced by a luciferase assay. Accordingly, UM-164 markedly decreased the expression levels of YAP target genes CYR61 and AXL. Importantly, ectopic expression of wild-type YAP or YAP-5SA (YAP constitutively active mutant) could rescue the anti-proliferative effect induced by UM-164. Intriguingly, p38 MAPK appears to play a greater role than Src in UM-164-mediated inhibition of YAP activity. Furthermore, the in vitro anti-glioma effect mediated by UM-164 was confirmed in a xenograft glioma model. Together, these findings reveal a mechanism by which UM-164 suppresses the malignant phenotypes of glioma cells and might provide a rationale for UM-164-based anti-glioma clinical trials.

BackgroundInflammation-related gene polymorphisms are some of the most important determinants for cancer susceptibility, clinical phenotype diversity, and the response to radiotherapy and chemotherapy. However, the relationship between these polymorphisms and head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study was to investigate the role of inflammation-related gene polymorphisms in the developmental risk and radiotherapy sensitivity of HNSCC.MethodsThe Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) genotyping system was used to genotype 612 individuals from a Chinese population for 28 inflammation-related gene polymorphisms.ResultsThe protein kinase B (AKT1) rs1130233 TT, dominance model (CT+TT vs. CC), recessive model (TT vs. CT+CC), and rs2494732 CC genotypes were associated with reduced risk of HNSCC (P=0.014; P=0.041; P=0.043). The polymeric immunoglobulin receptor (PIGR) rs291097 GA, dominance model (GA+AA vs. GG), and rs291102 dominance model (GA+AA vs. GG) were associated with increased risk of HNSCC (P=0.025; P=0.025; P=0.040). The interleukin-4 receptor-α (IL-4RA) rs1801275 AA genotype was significantly correlated with increased radiotherapy sensitivity of HNSCC patients (P=0.030). In addition, age ≤ 60 years, non-smoker status, and normal levels of squamous cell carcinoma antigen (SCC) were found to be associated with increased radiotherapy sensitivity of HNSCC patients (P=0.033; P=0.033; P=0.030).ConclusionThe AKT1 rs1130233, AKT1 rs2494732, PIGR rs291097, and PIGR rs291102 polymorphisms were significantly related to the risk of HNSCC. The IL-4RA rs1801275 polymorphism, age ≤ 60 years, non-smoker status, and normal levels of SCC were significantly associated with increased radiotherapy sensitivity of HNSCC.

BackgroundTo assess the prevalence, risk factors and prognostic significance of retropharyngeal lymph node (RPLN) metastasis diagnosed by magnetic resonance imaging (MRI) in patients with hypopharyngeal squamous cell carcinoma (HPSCC).Methods259 patients from three cancer institutions in China from Jan 2010 to Dec 2018 were analyzed, retrospectively. All the patients had been given pre-treatment magnetic resonance imaging (MRI) of head and neck and were then treated with definitive radiotherapy with or without chemotherapy. Pretreatment diagnostic MRIs were reviewed by a dedicated head and neck radiologist, for the presence or absence of radiographically positive RPLN, cervical LN and tumor invasion.Demographic variables were analysed by descriptive statistics using SPSS 20.0. Predictors of the presence of RPLN and its prognostic significance were examined.ResultsRPLN metastasis was discovered in 44 patients (17%). Logistic analysis showed that posterior pharyngeal wall (PPW) primary tumor; PPW invasion; N2-3; multiple cervical lymph node (LN) involvement (>2 LNs) were associated with RPLN metastasis, with metastasis rates 37%, 30%, 31% and 33% respectively. Patients with RPLN metastasis had a significantly reduced 5-year overall survival (OS) and disease-free survival (DFS) compared to the non-RPLN metastasis group (OS 28% vs. 48%, p=0.001; DFS 25% vs. 41%, p=0.040).ConclusionsRPLN metastasis was not uncommon in HPSCC patients. Risk factors were: PPW primary tumor, PPW invasion and cervical LN status. RPLN metastasis is a poor prognosticator for survival.

BackgroundA large proportion of patients with Lynch syndrome (LS) have MSH2 abnormalities, but genotype-phenotype studies of MSH2 mutations in LS are still lacking. The aim of this study was to comprehensively analyze the clinicopathological characteristics and molecular basis of colorectal cancer (CRC) in patients with uncommon MSH2 cytoplasmic expression.MethodsWe retrospectively reviewed 4195 consecutive cases of CRC patients diagnosed between January 2015 and December 2017 at the Cancer Hospital Chinese Academy of Medical Sciences. Of the 4195 patients with CRC, 69 were indicated to have abnormal MSH2 expression through tumor immunohistochemical staining. Genetic tests, such as next-generation sequencing, large genomic rearrangement (LGR) analysis, microsatellite instability status analysis and genomic breakpoint analysis, were performed. Clinicopathological and molecular characteristics and clinical immunotherapy response were analyzed.ResultsForty-five of 69 patients were identified to have LS with pathogenic germline mutations in MSH2 and/or EPCAM. Of these LS patients, 26.7% were confirmed to harbor large genomic rearrangements (LGRs). Of note, three tumors from two unrelated family pedigrees exhibited a rare cytoplasmic MSH2 staining pattern that was found in LS patients with EPCAM/MSH2 deletions. RNA analysis showed that two novel mRNA fusions of EPCAM and MSH2 resulted in the predicted protein fusion with MSH2 cytoplasmic localization. Analyses of genomic breakpoints indicated that two novel deletions of EPCAM and MSH2 originated from Alu repeat-mediated recombination events. Our study also provides clinical evidence for the beneficial effect of the PD-1 inhibitor pembrolizumab for CRC patients that exhibit cytoplasmic MSH2 staining.ConclusionOur study demonstrates that the rare cytoplasmic MSH2 staining pattern should be fully recognized by pathologists and geneticists. Given the specific genotype-phenotype correlation in LS screening, we advocate that all CRC patients with cytoplasmic MSH2 staining in histology should be screened for LGRs of EPCAM and MSH2.