Cancer Medicine

Background Neutrophils interact with tumor cells, potentially exacerbating cancer progression. Additionally, decreased albumin levels are a marker of poor cancer prognosis. The neutrophil‐percentage‐to‐albumin ratio (NPAR) has been used for prognostic assessment in non‐cancerous diseases, but its relationship with mortality risk in cancer patients has not been explored. Therefore, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to investigate the correlation between NPAR and the risks of all‐cause mortality and cancer‐related mortality among cancer patients. Methods This study leveraged comprehensive NHANES data spanning 2005–2016. We analyzed the relationship between NPAR and the risks of cancer incidence, all‐cause mortality, and cancer‐related mortality using weighted Logistic and Cox regression models, as well as trend tests. Restricted cubic spline analysis was employed to investigate NPAR's nonlinear relationship with mortality risk. Furthermore, Kaplan–Meier survival analysis was utilized to assess patient prognoses across varying NPAR levels. Results Elevated NPAR was associated with an increased risk of all‐cause mortality and cancer‐related mortality in cancer patients (p < 0.05), with higher NPAR values correlating with greater risk (p‐trend < 0.05). However, no significant association between NPAR and cancer incidence was observed (p > 0.05). Our analysis further identified a non‐linear relationship between NPAR and all‐cause mortality risk (p‐nonlinear < 0.05), while no non‐linear relationship was found with cancer‐related mortality risk. The relationship is characterized by an optimal NPAR value, correlating with the lowest hazard ratio (HR). Deviations from this optimal NPAR result in increased all‐cause mortality risk (p < 0.05). Kaplan–Meier analysis indicated superior survival rates in patients with lower NPAR values compared to those with higher NPAR values (p < 0.05). Conclusions According to our study, higher NPAR was associated with an increased risk of all‐cause mortality and cancer‐related mortality in cancer patients.

Introduction Small cell neuroendocrine carcinoma of the urinary tract (SCNEC‐URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery. Materials and Methods We identified a definitive‐surgery cohort (n = 224) from an institutional database of patients with cT1‐T4NxM0 SCNEC‐URO treated in 1985–2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time‐to‐event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine‐Gray distribution models assessed covariate associations. Results Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) patients had relapse with 77 (83.7%) having distant organs as first metastatic sites, including 10 (10.9%) with exclusive central nervous system (CNS) metastases, mostly (9/10) within 1 year of surgery. Patients with pathologic complete response (pCR) after neoCTx had the lowest 5‐year CIF (16.5% [95% CI 9.3%–25.6%]). Patients with remaining exclusively small cell (SC) histology had the highest CIF (85.7% [95% CI 46.6–96.9]). Patients with eradicated SCNEC but remaining UC components had an intermediate‐risk CIF (32.5% [95% CI 18.6–47.2]). Multivariable analysis adjusting for neoCTx, clinical stage at diagnosis (T3/4, N0/N+ vs. T1/T2, N0), and pathologic stage (pN+ vs. pN0) demonstrated that any SCNEC histology at resection (vs. pCR) was associated with relapse risk (hazard ratio = 3.69 [95% CI 1.91–7.13], p = 0.0001). Conclusions SCNEC‐URO is a systemic disease with high risk of distant relapse including CNS. Our findings highlight unmet needs for neoadjuvant/adjuvant approaches targeting the rare SCNEC subtype and suggest adding CNS surveillance within the first year after definitive surgery to high‐risk patients. Précis (Condensed Abstract) Alongside neoadjuvant chemotherapy and cancer stage, histology at resection strongly impacts relapse risk in small cell neuroendocrine carcinomas of the urinary tract. The incidence of brain metastasis is notably higher than in “traditional” urothelial cancer within the first year after surgery, especially if small cell cancer persists, thus necessitating close neurological monitoring during this period.

Background Gastric cancer (GC) is an important cause of death. Molecular targeted therapy and immunotherapy are progressing rapidly. It is very important to explore the pathogenesis pathways of GC and provide strong support for its treatment. However, the mechanism of occurrence and development of GC is still unclear. Methods Online databases and immunohistochemistry (IHC) of clinical samples were used to analyze the differential expression of YTHDF1 in the GC and nearby tissues, and its effect on survival prognosis. In vitro experimental study of GC, other mechanisms and functional analyses were specifically designed and performed too. Results Online data and clinical samples analysis showed that the expression of YTHDF1 in GC was markedly elevated compared to surrounding tissues. Higher YTHDF1 levels were correlated with worse survival outcomes. Analysis of correlation with clinical parameters showed that the expression level of YTHDF1 exhibited a favorable correlation with lymphatic metastases, as well as with PD‐1 and PD‐L1 levels. In vitro studies of YTHDF1 overexpression have demonstrated its ability to enhance GC cell growth and migration while inhibiting apoptosis. Based on our results, RELA is a downstream target of YTHDF1, and YTHDF1 triggers the NF‐κB signaling pathway by regulating RELA translation. Conclusion In comparison to adjacent tissues, GC exhibits significantly elevated YTHDF1 expression. Increased YTHDF1 expression in the GC is correlated with decreased patient survival. Lymph node metastasis and the expression of PD‐1 and PD‐L1 are positively correlated with YTHDF1 levels. YTHDF1 inhibits apoptosis while promoting the migration and proliferation of GC. Additionally, it stimulates the NF‐κB pathway and controls the translation of RELA.

Purpose Despite rigorous evidence of improved quality of life and longer survival, disparities in the utilization of palliative and hospice care persist for racial and ethnic minority patients with cancer. This study evaluated the impact of psychosocial factors on utilization of these services. Methods Patients with advanced lung cancer were recruited at a large academic urban hospital. Patients were surveyed about their knowledge of palliative care and hospice and their beliefs regarding medical mistrust, lung cancer care, palliative care and hospice. We used univariate and multivariable logistic regression analyses to examine the association between mistrust, knowledge and beliefs among the entire cohort and minority (Black and Hispanic) and non‐minority patients on utilization of palliative care consultation and hospice care use. Results Ninety‐nine of the enrolled participants had a mean age of 64 years. Minority patients were more likely to receive a palliative care referral (p < 0.001) and attend a consult (p = 0.003). Similarly, they were more likely to receive a hospice referral (p = 0.04), however there was no difference in hospice care use based on minority status (p = 0.102). In our adjusted model, older patients and those reporting negative lung cancer beliefs were more likely to receive hospice care (OR: 1.06, 95% CI: 1.004–1.138; OR: 1.04, 95% CI: 1.002–1.093, respectively). Conclusion Minority patients with advanced lung cancer were more likely to receive a palliative care referral and specialty level consultation when compared to non‐minority patients. Our work highlights the importance of proactive referral processes in facilitating access to palliative and hospice services, particularly among younger patients.

Background To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC). Methods Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR. The secondary outcomes compared the impact of centralisation and surgical approach on PSM and BCR; and margin length and location on BCR. Propensity score matching and Cox regression models were performed using R. Results A total of, 907 patients were included; 662 robot assisted radical prostatectomy (RARP), 245 open RP. PSM rate was 17.7% (161/907), similar in RARP and open cohorts. Patients with PSM had higher rates of BCR; 26.7%, compared to 8.7% in patients with no PSM. Patients with margins of ≥ 1 mm had higher risk of developing BCR. Patients who underwent open RP had increased incidence of PSM ≥ 1 mm; 40/43 (93%) compared to 83/117 (71%) in robotic approach (p = 0.003). Limitations include the study being retrospective, introduction of centralisation and robot concurrently, and evolution of practice. Discussion PSMs in pT2 PC are associated with higher rates of BCR. Introduction of centralisation via the robot had no impact on PSM occurrence or BCR, although did demonstrate a reduction in PSM length.

Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and lethal malignancies worldwide. Despite progress in immunotherapy for cancer treatment, its application and efficacy in ESCC remain limited. Therefore, there is an ongoing need to explore potential molecules and therapeutic strategies related to tumor immunity in ESCC. Methods In this study, we integrated high‐throughput sequencing data, gene chip data, single‐cell sequencing data, and various bioinformatics analysis methods along with experimental approaches to identify key genes involved in immune infiltration in ESCC and investigate their relationship with immune cell development, as well as the potential of these key genes in immunotherapy. Results We discovered and validated a positive correlation between macrophage infiltration and ITGB2 expression in ESCC. ITGB2 is overexpressed in ESCC and has potential as a prognostic biomarker for the disease. We present for the first time the finding that the expression of ITGB2 in infiltrating macrophages increases as these macrophages polarize toward a tumor‐promoting phenotype in ESCC. Moreover, during the progression of ESCC, ITGB2 expression in infiltrating macrophages is upregulated. The higher the expression of ITGB2, the more feasible it is to target macrophages. Additionally, we found that evaluating immune therapy responses in ESCC patients through ITGB2 expression is a viable approach. Furthermore, we identified three miRNAs associated with abnormal ITGB2 expression, providing insights into the upstream molecular interactions of ITGB2. Conclusions Macrophage infiltration in ESCC is closely associated with ITGB2, which holds significant potential for immunotherapy applications in ESCC. Based on our findings and prior studies, we propose a novel hypothesis: inducing M1 macrophages in vitro, knocking out ITGB2, and then reinfusing these ITGB2‐knockout M1 macrophages into ESCC patients may represent a promising new immunotherapy strategy, providing a new avenue for ESCC immunotherapy.

Purpose This study aimed to identify prognostic factors and develop a nomogram for survival in patients with brainstem ependymoma. Methods Data of 652 patients diagnosed with brainstem ependymoma extracted from the Surveillance, Epidemiology, and End Results (SEER) registry from 2000 to 2020 were analyzed. Univariate and multivariable Cox regression analyses were performed to examine factors influencing overall survival (OS). Receiver operating characteristic curve (ROC) and calibration curves were used to verify the nomogram. The Kaplan–Meier method was used to analyze OS based on treatment methods stratification or different age patterns. Results Six independent prognostic factors of patients with brainstem ependymoma were identified, including age, race, marital status, radiation, gross total resection (GTR), and histology. A comprehensive nomogram model was developed utilizing these predictors identified through multivariable Cox regression analysis. Furthermore, we found that patients with GTR have improved overall survival than patient with no surgery and biopsy only or with partial resection (GTR vs. no: p = 0.0004, GTR vs. partial resection: p = 0.022). Patients with radiation have improved overall survival than patient without radiation (p = 0.00013). Patients with GTR combined radiation therapy have improved overall survival than patient without or with GTR or radiation therapy only (p < 0.0001). Different treatment methods have no significant difference in the overall survival probability of the elderly group. Conclusions Individuals who are Black and anaplastic ependymomas were negative risk factors for brainstem ependymoma associated with an increased risk of mortality. Patients aged < 50 years with GTR and radiation always had better survival.

Background Lung adenocarcinoma (LUAD) exhibits molecular heterogeneity, with mitochondrial damage affecting progression. The relationship between mitochondrial damage and immune infiltration, and Weighted Gene Co‐expression Network Analysis (WGCNA)‐derived biomarkers for LUAD classification and prognosis, remains unexplored. Aims The objective of our research is to identify gene modules closely related to the clinical stages of LUAD using the WGCNA method. Based on the genes within these modules, we constructed machine learning (ML) models for classification and prognosis prediction, thereby facilitating precise diagnosis and personalized treatment of LUAD. Materials & Methods Using GeneCards and The Cancer Genome Atlas (TCGA) databases, we screened differentially expressed mitochondrial damage‐related genes in LUAD. Immune cell infiltration patterns were assessed using Single‐Sample Gene Set Enrichment Analysis (SSGSEA) method. Functional enrichment analyses were conducted to explore biological functions and signaling pathways. Gene modules related to clinical stages of LUAD were identified by WGCNA. ML models were constructed for classification and prognosis prediction, and validated in an independent Gene Expression Omnibus (GEO) dataset. Results The study revealed a significant relationship between mitochondrial damage and immune infiltration in LUAD. We identified a gene module closely associated with the clinical stages of LUAD. The ML models for classification and prognosis that were constructed demonstrated good effectiveness and generalization capabilities. Discussion Mitochondrial damage‐related genes are crucial in LUAD progression and linked to immune infiltration. The gene module and models identified have potential applications in LUAD classification and prognosis, offering novel markers for precision medicine. Conclusion This study uncovers the relationship between mitochondrial damage and immune infiltration in LUAD, paving the way for molecular classification, prognosis prediction, and personalized treatment strategies.

Background This study aims to elucidate the expression pattern of SERPINE1, assess its prognostic significance, and explore potential therapeutic drugs targeting this molecule. Methods and Results In this study, we delved into the variations in gene mutation, methylation patterns, and expression levels of SERPINE1 in head and neck squamous cell carcinoma (HNSCC) and normal tissues, leveraging comprehensive analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The connection between the biological function of the gene and prognosis was scrutinized through immune infiltration and enrichment analyses. Concurrently, we assessed the potential therapeutic value of SERPINE1 through drug sensitivity analysis. It was observed that, particularly in human papillomavirus (HPV) negative HNSCC, SERPINE1 exhibited elevated expression levels, correlating with poorer prognosis. The infiltration levels of eight cell types, such as eosinophils, Tgd, and macrophages, showed a positive correlation with SERPINE1 expression, whereas infiltration levels of four cell types, including cytotoxic cells, B cells, and pDCs, displayed a negative correlation. Furthermore, copy number variations of SERPINE1 were primarily characterized by homologous amplification, positively correlating with its expression, while methylation showed an inverse correlation. The outcomes of drug sensitivity analysis underscored the potential of SERPINE1 as a therapeutic target. Conclusion Elevated expression of SERPINE1 in HNSCC is intricately linked with adverse prognostic outcomes and has the potential to influence the immune microenvironment. Subsequent investigations are imperative to fully elucidate the prognostic implications of SERPINE1 as a biomarker and to unlock its therapeutic promise as a target for intervention.

Background The use of digital health strategies for cancer care increased dramatically in the United States over the past 4 years. However, a dearth of knowledge remains about the use of digital health for cancer prevention for some populations with heath disparities. Therefore, the purpose of the present scoping review was to identify digital health interventions for cancer prevention designed for people with disabilities. Methods This scoping review was guided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for scoping reviews and the Arksey and O'Malley methodological framework. The Embase, PubMed, Ovid MEDLINE, and CINAHL/EBSCO databases were searched for peer‐reviewed articles published from database inception to February 5, 2024. Reports published in English of studies that employed digital health strategies for cancer prevention, were conducted among people with disabilities regardless of age, and were conducted in the United States were included. Findings Following screening for eligibility, seven articles were identified. The types of disabilities were cancer (n = 4), bipolar I or II disorder (n = 1), obesity (n = 1), and deafness (n = 1). Interventions focused on education (n = 4), screening (n = 3), smoking cessation (n = 3), physical activity (n = 1), and cessation support (n = 1). Digital health strategies consisted of educational content delivered online, text messaging, interactive educational games, and downloadable informational applications. The common outcome of interest across all manuscripts was intervention efficacy. Interpretation Overall, limited research is available to evaluate the use of digital health for cancer prevention among people with disabilities. This review identified gaps in knowledge that, if addressed, may help guide continued innovation in the use of digital health strategies for cancer prevention among people with disabilities.

Background Gamma‐glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers. Methods Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random‐effect meta‐analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence. Results A total of 26 studies were included in the final review, 12 of which underwent meta‐analysis that investigated 11 million patients. Based on the meta‐analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41–2.02, p‐value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15–1.30, p‐value < 0.001) and Q2 (HR 1.10, 95% CI 1.05–1.16, p‐value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence. Conclusion Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.

Background Chronic and excessive alcohol consumption is the leading cause of death due to chronic liver disease. Alcohol‐related liver disease (ALD) encompasses a broad spectrum of clinical and pathological features, ranging from asymptomatic and reversible pathologies to hepatocellular carcinoma (HCC), a highly prevalent and deadly liver cancer. Indeed, alcohol consumption is one of the main worldwide etiologies of HCC. However, the impact of alcohol consumption on HCC pathophysiology and the associated mechanisms remains unclear. Thus, in vitro alcohol‐related HCC models are essential for addressing this issue and for assessing new molecular markers of this disease. In this review, we discuss the current in vitro models of alcohol‐related HCC. Our global overview demonstrates the lack of uniformity regarding HCC cell lines, alcohol concentration, and duration of alcohol exposure among existing models. Despite efforts to model alcohol exposure effectively that demonstrate enhancement of cancer cell transformation markers and HCC aggressiveness following, respectively, short‐term and long‐term alcohol exposure, current in vitro models possess numerous limitations. Aim This review highlights future challenges in the development of more integrated and representative models of the complex pathophysiology of alcohol‐related HCC.

Background Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis. Methods The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT‐PCR validation. Both in vitro and in vivo functional studies revealed that MIR181A2HG facilitates lymphangiogenesis and lymphatic metastasis. Techniques such as immunofluorescence, immunohistochemistry, qRT‐PCR, ELISA, CHIP, RNA‐pulldown, luciferase reporter assay, and Co‐IP were employed to investigate the mechanism of MIR181A2HG in LNs metastasis of GC. Results MIR181A2HG overexpressed in GC signifies an unfavorable prognosis and drives M2 polarization of TAMs enhancing lymphangiogenesis. Mechanistically, MIR181A2HG/miR‐5680 axis as a novel ceRNA regulatory axis to upregulate versican (VCAN). On one hand, VCAN interacts with CD44 receptors on the surface of TAMs through paracrine secretion, promoting M2 macrophage polarization and subsequently enhancing the secretion of VEGF‐C, ultimately facilitating lymphangiogenesis. On the other hand, VCAN binds to CD44 receptors on the surface of GC cells through autocrine secretion, activating the Hippo pathway and upregulating SP1, thereby promoting the transcription of MIR181A2HG and establishing a feedback loop driving lymphatic metastasis. Conclusion This study highlights the pivotal role of MIR181A2HG in GC progression and LNs metastasis. MIR181A2HG‐based targeted therapy would represent a novel strategy for GC.

Background 7‐Hydroxymethotrexate (7‐OHMTX) is the main metabolite in plasma following high‐dose MTX (HD‐MTX), which may result in activity and toxicity of the MTX. Moreover, 7‐OHMTX could produce crystalline‐like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure–safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity. Method A total of 280 plasma concentration data (140 for MTX and 140 for 7‐OHMTX) for 60 pediatric patients with non‐Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7‐OHMTX concentrations were determined using a high‐performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (Cmax) and area under the curve within the initial 48 h (AUC0‐48h) of the patients after drug administration by Bayesian feedback. The receiver operating characteristic (ROC) curves were generated to identify an exposure threshold associated with nephrotoxicity. Results A three‐compartment chain model (central and peripheral compartments for MTX and central compartment 7‐OHMTX) with the first‐order elimination adequately characterized the in vivo process of MTX and 7‐OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the Cmax of MTX and 7‐OHMTX showed significant differences (p < 0.0001, p = 0.0472, respectively) among patients with or without nephrotoxicity. Similarly, individuals with nephrotoxicity also exhibited substantially higher ratio of 7‐OHMTX to MTX peak concentration and the sum of MTX + 2.25 times the concentration of 7‐OHMTX (p < 0.0001, p = 0.0426, respectively). By ROC analysis, the Cmax of MTX and 7‐OHMTX had the greatest area under the curve (AUC) values (0.769 and 0.771, respectively). A Cmax threshold of 9.26 μmol/L for MTX or a Cmax threshold of 0.66 μmol/L for 7‐OHMTX was associated with the best sensitivity/specificity for toxicity events (MTX: sensitivity = 0.886; specificity = 0.70; 7‐OHMTX: sensitivity = 0.886; specificity = 0.70). Conclusions We demonstrated that the Cmax of MTX and 7‐OHMTX were the most reliable markers associated with nephrotoxicity and proposed a Cmax threshold of 9.26 μmol/L for MTX and 0.66 μmol/L for 7‐OHMTX as the point with a high risk of nephrotoxicity. Altogether, this study may contribute to crucial insights for ensuring the safe administration of drugs in pediatric clinical practice.

Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes of this study were to identify the prognostic mitochondria‐related genes (MRGs) in DLBCL, and to develop a risk model based on MRGs and machine learning algorithms. Methods Transcriptome profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database. The risk model was defined using Least Absolute Shrinkage and Selection Operator (Lasso) regression algorithm, and its prognostic value was further examined in independent datasets. Patients were stratified into two clusters based on the risk scores, additionally a nomogram was generated based on the risk score and clinical characteristics. Gene pathway level, microenvironment, expression of targeted therapy‐associated genes, response to immunotherapy, drug sensitivity, and somatic mutation status were compared between clusters. Results Eighteen prognostic MRGs (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) were identified to construct the risk model. Remarkable discrepancies were observed between groups. The high‐risk group had shorter overall survival, less immune infiltration, lower CD20 and higher PD‐L1 expression than the low‐risk group. Distinct immune microenvironment, responses to immunotherapy and predictive drug IC50 values were found between groups. Conclusions We established a novel prognostic mitochondria‐related signature by machine learning algorithm, which also demonstrated outstanding predictive value in tumor microenvironment and responses to therapies.

Background Medical images play an important role in diagnosis and treatment of pediatric solid tumors. The field of radiology, pathology, and other image‐based diagnostics are getting increasingly important and advanced. This indicates a need for advanced image processing technology such as Deep Learning (DL). Aim Our review focused on the use of DL in multidisciplinary imaging in pediatric surgical oncology. Methods A search was conducted within three databases (Pubmed, Embase, and Scopus), and 2056 articles were identified. Three separate screenings were performed for each identified subfield. Results In total, we identified 36 articles, divided between radiology (n = 22), pathology (n = 9), and other image‐based diagnostics (n = 5). Four types of tasks were identified in our review: classification, prediction, segmentation, and synthesis. General statements about the studies'’ performance could not be made due to the inhomogeneity of the included studies. To implement DL in pediatric clinical practice, both technical validation and clinical validation are of uttermost importance. Conclusion In conclusion, our review provided an overview of all DL research in the field of pediatric surgical oncology. The more advanced status of DL in adults should be used as guide to move the field of DL in pediatric oncology further, to keep improving the outcomes of children with cancer.

Background This study investigated and compared the impact of financial toxicity (FT) on the health‐related quality of life (HRQoL) and financial well‐being of cancer patients and survivors in the United Kingdom (UK) and United States (US). Methods UK & US participants (n = 600) completed an online questionnaire that consisted of a validated FT instrument (COmprehensive Score for financial Toxicity‐COST), a standardised HRQoL instrument (EQ‐5D‐5L) and questions related to their financial well‐being. Tobit regression models and descriptive statistics plus χ² tests were used to analyse the association between FT and (i) HRQoL whilst controlling for sociodemographic characteristics; and (ii) financial well‐being. Results In the UK, health utilities of participants with no assessed experience of FT, mild FT, and moderate/severe FT were 0.81, 0.66, and 0.41, respectively, compared to 0.88, 0.71, and 0.53 in the US. Among those with moderate/severe FT, US participants had significantly higher health utilities compared to their peers in the UK (Mann Whitney test, p = 0.0369). In a pooled analysis of UK and US and after controlling for sociodemographic and clinical characteristics, mild and moderate/severe FT was negatively associated with health utilities (β coff = −0.13, 95% CI: −0.18, −0.08 and β coff = −0.28, 95% CI: −0.34, −0.21, respectively). Over half (54%) of US participants with FT were in debt with median (IQR) debt at I$11,500 (23,000), compared to 32$ 7200 (12,960). US participants with FT were 2.48 times more likely to be in debt than UK participants with FT (OR = 2.48, 95% CI: 1.46–4.21). Conclusions FT is associated with poorer financial well‐being and HRQoL among cancer patients/survivors in the US and UK. The impact of FT on financial well‐being is larger in the US while the impact on HRQoL is worse in the UK. Further studies using prospective data are required to investigate the nature and extent of these relationships.

Background Early‐stage pancreatic ductal adenocarcinoma (PDAC) is frequently misdiagnosed, contributing to its high mortality rate. Exosomal microRNAs (miRNAs) have emerged as potential biomarkers for the early detection of PDAC. Aims This study aimed to evaluate the feasibility of using exosomal miRNAs from PDAC tissues and serum as biomarkers for early detection and prognosis. Materials & Methods Exosomes were isolated from healthy individuals and PDAC patients via tissue and serum samples, then identified by analyzing their particle size and protein content. PDAC‐specific exosomal miRNAs were identified using a microRNA array. A large cohort was subsequently recruited to validate these findings. The diagnostic capacity of the identified miRNAs was assessed using the Brier score and area under the curve (AUC). Verified miRNAs were also used to confirm intracellular mRNA change patterns. Results The combination of miR142‐3p, miR148a‐3p, and CA199 showed a higher AUC (0.747) compared to CA199 alone (0.716) in ROC curve analysis. Gene Ontology (GO) annotations revealed that the two‐miRNA panel was associated with multiple oncogenic pathways. Discussion 142‐3p and miR148a‐3p were identified as specific to PDAC and, when combined with CA199, improved diagnostic accuracy. Their involvement in oncogenic pathways underscores their relevance as diagnostic and prognostic biomarkers. Conclusion MiR142‐3p and miR148a‐3p, alongside CA199, show promise as non‐invasive biomarkers for early detection and prognosis of PDAC, improving diagnostic accuracy.

Background In the UK's National Health Service (NHS), there is specific psychosocial care offered to people with genetic cancer risk conditions but not morphological cancer risk conditions. As researchers develop new ways to diagnose morphological risk conditions, including precancers and in situ cancers, it is important to consider the psychosocial care that those diagnosed might require. Objectives This study compares the National Institute for Health and Care Excellence's guidelines for BRCA1/2, which are genetic risk conditions, and Barrett's oesophagus (BO), a morphological risk condition. It then theorises reasons for the similarities and differences made visible by this comparative work. Methods The author completed an in‐depth analysis of two sets of NICE guidelines, before carrying out a review of historical and social scientific literature on cancer risk to offer potential explanations for the disparities identified. Results The ‘right not to know’ is protected in the case of BRCA1/2 diagnoses, but not BO. Additionally, specialist counselling is required for people receiving diagnoses of genetic risk but not offered for those diagnosed with morphological risk conditions. The paper offers four possible reasons for these disparities, concluding that they appear to be in large part due to historic genetic exceptionalism, rather than differences in patients' needs. Conclusion There may be a need to consider offering further psychosocial care to people with morphological risk conditions like BO. Lessons might be learnt from the field of genetic counselling.

Background The 2021 WHO Classification of Central Nervous System Tumors introduces more molecular markers for glioma reclassification, including TERT promoter (TERTp) mutation as a key feature in glioblastoma diagnosis. Aims Given the changes in the entities included in each subtype under the new classification, this research investigated the distribution, prognostic value, and correlations with other molecular alterations of TERTp mutation in different subgroups under this latest classification. Methods All glioma patients admitted to Peking Union Medical College Hospital for surgical resection or biopsy from 2011 to 2022 were included. Samples were analyzed for TERTp mutation and 59 other gene alterations and chromosome copy number variations. Results A total of 207 patients were included. The occurrence of TERTp mutations varied with percentages of 4.55%, 100%, and 77.92% in astrocytoma, oligodendroglioma, and glioblastoma, respectively. 65% of all adult‐type glioma patients and 42.6% of IDH‐wildtype histology grade 2 or 3 patients were TERTp‐mutant. Survival analysis showed that TERTp mutation was a predictor of better prognosis in IDH‐mutant grade 2 gliomas (median OS (mOS): not reached (NA) (95% CI: NA–NA) vs. 75.9 (95% CI: 55.4–NA) months, HR = 0.077 (95% CI: 0.01–0.64), p = 0.003), while poor OS was associated with all Grade 4 gliomas (mOS: 17.5 (95% CI: 12.6–24.2) vs. 40.5 (95% CI: 24.4–83.8) months, HR = 2.014 (95% CI: 1.17–3.47), p = 0.01) and all IDH‐wildtype histology grade 2 or 3 gliomas (median OS: 12.6 (95% CI: 11–24.2) vs. 83.8 (95% CI: 35.2–NA) months, HR = 3.768 (95% CI: 1.83–7.78), p < 0.001). Moreover, TERTp mutation tended to co‐occur with EGFR, KRAS, and MET in glioblastoma. In the IDH‐mutant subgroup, it tended to co‐occur with CIC and FUBP1 alterations, while being mutually exclusive with ATRX and TP53 alterations. These correlations may further refine prognostic predictions.

Background We explored the interaction between the oral microbiome and the development of radiation‐induced mucositis in patients with head and neck squamous cell cancer (HNSCC) undergoing chemoradiotherapy (CRT). We prospectively studied the oral microbiome and compared it to healthy controls. Additionally, we compared patients with low‐grade (LGM) vs. high‐grade mucositis (HGM). Methods Ten HNSCC patients scheduled for CRT were included. Saliva samples were characterized prior to, during, and nine months after CRT using metagenomic sequencing. We similarly characterized samples from seven healthy controls. We assessed alpha and beta diversity and examined abundances at different taxonomic levels between (sub)groups. Results Patients exhibited significantly reduced alpha diversity compared to controls at all times (p ⟨ 0.05). Differential abundance of taxa between patients and controls was observed at baseline. In patients, the relative abundance of Staphylococcus aureus and Escherichia coli increased significantly during CRT. Capnocytophaga spp. was associated with the definitive CRT patients' subgroup. At baseline, two fungal families (Melampsoraceae and Herpotrichiellaceaea) were more abundant in patients who later developed HGM. No differentially abundant taxa were found between LGM vs. HGM during irradiation. Conclusion Our findings support the hypothesis that CRT, as well as HNSCC itself, influences the composition of the oral microbiome. Microbial markers found in patients who later developed HGM should be evaluated using independent cohorts to qualify their specific biomarker potential.

Purpose Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1‐antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1‐antihistamine use in cancer patients during immunotherapy. Methods All patients who had received at least one dose of immune checkpoint inhibitors (ICIs) from July 1, 2014 to October 31, 2019 were identified from Hong Kong's territory‐wide database, with this date defined as the baseline. A 1‐month landmark analysis was conducted with follow–for up to 6 months, including an exposure period of 1 month before and after the baseline date. Patients were grouped according to the types of primary cancer and the percentages of daily H1‐antihistamine usage within the exposure period. The primary outcome was overall survival. Results A total of 1740 (65.1% male, mean age 61.9 years) were included in the landmark analysis, of which 529 (30.4%) and 307 (17.6%) had primary lung and liver malignancies. The multivariable Cox regression model estimated statistically significant improvement in overall survival of intermediate use in patients with primary lung malignancies (adjusted hazard ratio [aHR] 0.223, 95% confidence interval [CI] 0.052–0.958, p = 0.044), but not with primary liver maligancies. Similar frequency‐dependent effects were identified in Kaplan–Meier analysis. Conclusion The benefits of adjunctive use of H1‐antihistamines may be generation‐ and tumor‐dependent. Further clinical and mechanistic studies are required to confirm the findings.

Background CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti‐tumor effects have previously been demonstrated for GSK‐J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers. Methods To characterize the effect of GSK‐J4, drug response profiling, CRISPR‐Dropout Screening, BH3 profiling and immunoblotting were carried out in ALL cell lines or patient derived samples. Results Here we provide evidence that GSK‐J4 downregulates cyclic AMP‐responsive element‐binding protein (CREB) and CREBBP in B‐cell precursor‐ALL cell lines and patient samples. High CREBBP expression in BCP‐ALL cell lines correlated with high GSK‐J4 sensitivity and low dexamethasone sensitivity. GSK‐J4 treatment also induced Bcl‐2 and Bcl‐XL dependency and apoptosis. Conclusions This study proposes H3K27 demethylase inhibition as a potential treatment strategy for patients with treatment‐resistant ALL, using CREBBP as a biomarker for drug response and combining GSK‐J4 with venetoclax and navitoclax as synergistic partners.

Background Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B‐cell‐specific Moloney murine leukemia virus insertion site‐1 (Bmi‐1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation. We hereby aim to explore the specific involvement of Bmi‐1 in glioma pathogenesis. Methods A comprehensive narrative review was employed using “PubMed”. Articles were screened for relevance specific keywords and medical subject headings (MeSH) terms related to the topic combined with Boolean operators (AND, OR). Keywords and MeSH terms included the following: “glioma”, “polycomb repressive complex 1”, and “Bmi1”. Results In GBMs, several reports have shown that Bmi‐1 is overexpressed and might serve as a prognostic biomarker. We find that Bmi‐1 participates in regulating the gene expression and chromatin structure of several tumor suppressor genes or cell cycle inhibitors. Bmi‐1 has a critical role in modulating the tumor microenvironment to support the plasticity of GBM stem cells.We explore Bmi‐1's involvement in maintaining glioma stem cell (GSC) proliferation and senescence evasion upon regulating the chromatin structure of several tumor suppressor genes, cell cycle inhibitors, or stem cell genes in tumor cells. Additionally, we analyze Bmi‐1's involvement in modulating the DNA repair machinery or activating anti‐apoptotic pathways to confer therapy resistance. Importantly, our research discusses the importance of targeting Bmi‐1 that could be a promising therapeutic target for GBM treatment. Bmi‐1 activates and interacts with NF‐κB to promote angiogenesis and invasion, regulates the INK4a‐ARF locus, and interacts with various microRNAs to influence tumor progression and proliferation. In addition, Bmi‐1 confers radioresistance and chemotherapy by promoting cell senescence evasion and DNA repair. Conclusion Bmi‐1 regulates self‐renewal, proliferation, and differentiation of GBM cells, promoting stemness and therapy resistance. Targeting Bmi‐1 could be a promising novel therapeutic strategy for GBM treatment.

Background Immune checkpoint inhibitors (ICIs) have achieved great success; however, a subset of patients exhibits no response. Consequently, there is a critical need for reliable predictive biomarkers. Our focus is on CDC42, which stimulates multiple signaling pathways promoting tumor growth. We hypothesize that an impaired function of CDC42 may serve as an indicator of a patient's response to ICI therapy. Methods We consider CDC42 and its downstream binding and effector proteins as a gene set, as mutations in these components could lead to defective CDC42 function. To elucidate the biomarker function of mutations within the CDC42 gene set, we curated a comprehensive discovery dataset that included seven ICI treatment cohorts. And we curated two ICI treatment cohorts for validation. We explored the mechanism based on The Cancer Genome Atlas database. We also examined whether combining a CDC42 inhibitor with ICI could enhance ICI's efficacy. Results Mutations in the CDC42 gene set were associated with improved overall survival and progression‐free survival. Furthermore, our analysis of immune response landscapes among different statuses of the CDC42 gene set supports its role as a biomarker. Animal experiments also revealed that the combination of the CDC42 inhibitor (ML141) with anti‐PD‐1 blockade can additively reduce tumor growth. Conclusions Our study suggests that the CDC42 gene set mutations could potentially serve as a novel biomarker for the clinical response to ICI treatment. This finding also provides insights into the potential of combining ICI and CDC42 inhibitor use for more efficient patient treatment.