Cancer treatment with biosimilar drugs:A review

Biosimilars are biological drugs created from living organisms or that contain living components.They share an identical amino-acid sequence and immunogenicity.These drugs are considered to be cost-effective and are utilized in the treatment of cancer and other endocrine disorders.The primary aim of biosimilars is to predict biosimilarity,efficacy,and treatment costs;they are approved by the Food and Drug Administration(FDA)and have no clinical implications.They involve analytical studies to understand the similarities and dissimilarities.A biosimilar manufacturer sets up FDA-approved reference products to evaluate biosimilarity.The contribution of next-generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations.The study shall help to understand the future perspectives of biosimilars for use in gastro-entero-logic diseases,colorectal cancer,and thyroid cancer.They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy,cell treatment,gene therapy,recombinant therapeutic proteins,and personalized medications.Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy.Escherichia coli produces more than six antibodies or antibody-derived proteins to treat cancer such as filgrastim,epoetin alfa,and so on.

Accelerated partial breast irradiation:Current evidence and future developments

Whole breast irradiation after breast-conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery.Accelerated partial breast irradiation(APBI)as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research.APBI is characterised by simple high-dose local irradiation of the tumour bed in a short time,thus improving convenience for patients and saving costs.The implementation methods of APBI mainly include brachytherapy,external beam radiation therapy,and intraoperative radiotherapy.This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires

Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast cancers.However,approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.Methods:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints.Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized mice.The human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and cytokines.To fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 days.Then,human T cells were processed for TCRβ-chain(TRB)sequencing analysis.After the repertoires had been constructed,features such as the fraction,diversity,and immune signature were investigated.Results:The results demonstrated an increase in diversity and clonality of T cells after treatment.The preferential usage and features of TRBV,TRBJ,and the V–J combination were also changed.The stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 expansion.Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.Conclusions:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools.Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.It therefore has the potential to greatly benefit cancer treatment.

Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the lung.Histone deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi effects.To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture conditions.Methods:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective inhibitor.SN38 was concomitantly used as an ameliorant drug with romidepsin treatment.Cytostasis,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug efficacy.In addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.Results:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell line.In the apoptotic inducible cells,co-treatment with SN38 enhanced cell death.In nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction further.As a novel efficacy of SN38,we revealed TWIST1 suppression in SS cells.In the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive cells.We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the reaction.Conclusions:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evidence that concomitant treatment with SN38 can overcome drug resistance to HDACi by suppressing TWIST1 expression.

A comprehensive review of 3D cancer models for drug screening and translational research

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research.In addition to cancer cells,a range of other factors include the stroma,density and composition of extracellular matrix,cancer-associated immune cells(e.g.,cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions,and a number of other factors(e.g.,tumor vasculature and tumor-like microenvironment in vivo)has been widely ignored in the 2D concept of culture.Despite this knowledge,the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials.This review discusses the immense importance of tumor microenvironment(TME)recapitulation in cancer research,prioritizing the individual roles of TME elements in cancer histopathology.The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement,components,and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials,some of which are discussed here.Furthermore,it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors.Furthermore,this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.

Clinical significance,molecular characterization,and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma

Background:Numerous studies have revealed a tight connection between tumor development and the coagulation system.However,the effects of coagulation on the prognosis and tumor microenvironment(TME)of clear cell renal cell carcinoma(ccRCC)remain poorly understood.Methods:We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns.Subsequently,we examined variations in the overall survival(OS),genomic profiles,and TME characteristics between these subtypes.To develop a prognostic coagulation-related risk score(CRRS)model,we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses.We also created a nomogram to aid in the clinical application of the risk score,evaluating the relationships between the CRRS and the immune microenvironment,responsiveness to immunotherapy,and targeted treatment.The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.Results:There were significant differences in clinical features,prognostic stratification,genomic variation,and TME characteristics between the two coagulation-related subtypes.We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients.Significant variations in survival outcomes were observed between the high-and low-risk groups.The nomogram was proficient in predicting the 1-,3-,and 5-year OS.Additionally,the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC.Moreover,we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis.PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.Conclusion:Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.

Organoid co-culture models of the tumor microenvironment promote precision medicine

In recent years,the three-dimensional(3D)culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo.This system offers several advantages,including high throughput,efficiency,and retention of tumor heterogeneity.Traditional Matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial cells.One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types,either in dual,triple or even multiple combinations.Another solution is a holistic approach including patient-derived tumor fragments,air-liquid interface,suspension 3D culture,and microfluidic tumor-on-chip models.Organoid co-culture models have also gained popularity for studying the tumor microenvironment,evaluating tumor immunotherapy,identifying predictive biomarkers,screening for effective drugs,and modeling infections.By leveraging these 3D culture systems,it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.

Comprehensive treatment of von Hippel-Lindau disease:A case report

von Hippel-Lindau(VHL)disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular,as well as cysts in other organs.A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease.Herein,we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma(HB)and clear cell renal cell carcinoma(ccRCC).Four years after the resection of the right kidney,a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed.This patient was started on sorafenib(800 mg,daily)and tislelizumab(200 mg per 3 weeks).After 6 months of treatment,the size of renal cell carcinoma was dramatically reduced and renal function improved.More importantly,she achieved partial response during the whole treatment.Microscopically,intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed.Neurologic symptoms such as numbness and pain were remarkably alleviated.Additionally,tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine,respectively.In short,comprehensive treatment strategies may benefit patients with VHL disease,especially with HB and ccRCC.

Cardiovascular disease burden in patients with urological cancers:The new discipline of uro-cardio-oncology

Cancer remains a major cause of mortality worldwide,and urological cancers are the most common cancers among men.Several therapeutic agents have been used to treat urological cancer,leading to improved survival for patients.However,this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications.Here,we propose the novel discipline of uro-cardio-oncology,an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer.In this comprehensive review,we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers,including androgen deprivation therapy,vascular endothelial growth factor receptor tyrosine kinase inhibitors,immune checkpoint inhibitors,and chemotherapeutics.In addition,we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance,diagnosis,and effective management of cardiovascular complications.Finally,we provide an analysis of future perspectives in this emerging specialty,identifying areas in need of further research.

Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.

MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer

Background:Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer(NSCLC).The atypical mitogen-activated protein kinase 4(MAPK4)has been shown to be involved in the pathogenesis of various diseases.However,the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear.Methods:Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group,respectively.The cell proliferation was analyzed with flow cytometry and immunofluorescence staining.The vascular density in tumor mass was analyzed by immuno-fluorescence staining.The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining,and so on.Results:We found that the expression of MAPK4,which was dominantly expressed in local endothelial cells(ECs),was correlated with tumor angiogenesis of NSCLC.Furthermore,MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs(HUVECs).QKHZC-2020-4Y156,QKH-JC-2018-1428,QKH-RC-2019-5612;Collaborative Innovation Center of Chinese Ministry of Education,Grant/Award Number:2020-39;Program for Science and Technology Joint Fund Project in Zunyi Science and Technology Bureau and Zunyi Medical University,Grant/Award Numbers:ZSKH-RPT-2020-6,ZSKH-HZ-2021-193;Graduate Research Fund of Zunyi Medical University,Grant/Award Number:2023-ZYK-171 Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways,and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2(ERK1/2)pathway but not Akt and c-Jun n-terminal kinase pathways.Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant,which was accompanied with increased transduction of the ERK1/2 pathway.Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC.Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo.Conclusion:Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC.MAPK4 may thus represent a new target for NSCLC.

Advances in the role of circulating tumor cell heterogeneity in metastatic small cell lung cancer

Small cell lung cancer(SCLC),a highly aggressive malignancy,is rapidly at an extensive stage once diagnosed and is one of the leading causes of death from malignancy.In the past decade,the treatment of SCLC has largely remained unchanged,and chemotherapy remains the cornerstone of SCLC treatment.The therapeutic value of adding immune checkpoint inhibitors to chemotherapy for SCLC is low,and only a few SCLC patients have shown a response to immune checkpoint inhibitors.Circulating tumor cells(CTCs)are tumor cells shed from solid tumor masses into the peripheral circulation and are key to tumor metastasis.Single-cell sequencing has revealed that the genetic profiles of individual CTCs are highly heterogeneous and contribute to the poor outcome and prognosis of SCLC patients.Theoretically,phenotypic analysis of CTCs may be able to predict the diagnostic significance of new potential targets for metastatic tumors.In this paper,we will discuss in depth the heterogeneity of CTCs in SCLC and the value of CTCs for the diagnosis and prognosis of SCLC and as relevant tumor markers in metastatic SCLC.

Targeting colorectal cancer using dietary flavonols

Colorectal cancer is among the well-known forms of cancer and a prominent cause of cancer demises worldwide.In vitro experiments reinforced by animal studies,as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects.Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances.The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development.Flavonols are one of the most widespread dietary nutrients of the polyphenols-flavonoids and major constituent of Allium and Brassicaceae vegetables.Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol,myricetin,quercetin,and isorhamnetin.These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer.The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer.

Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo

Background:Since RNA sequencing has shown that induced pluripotent stem cells(iPSCs)share a common antigen profile with tumor cells,cancer vaccines that focus on iPSCs have made promising progress in recent years.Previously,we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia(T-ALL)have a gene expression profile similar to that of T-ALL cell lines.Methods:Mice with T-ALL were treated with dendritic and T(DC-T)cells loaded with intact and complete antigens from T-ALL-derived iPSCs(T-ALL-iPSCs).We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry,cytokine release assay,acute toxicity experiments,long-term toxicity experiments,and other methods.Results:Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity.Conclusion:T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

Clinical practice guidelines for full-cycle standardized management of bone health in breast cancer patients

Bone health management for breast cancer spans the entire cycle of patient care,including the prevention and treatment of bone loss caused by early breast cancer treatment,the adjuvant application of bone-modifying agents to improve prognosis,and the diagnosis and treatment of advanced bone metastases.Making good bone health management means formulating appropriate treatment strategies and dealing with adverse drug reactions,and will help to improve patients'quality of life and survival rates.The Breast Cancer Expert Committee of the National Cancer Center for Quality Control organized relevant experts to conduct an in-depth discussion on the full-cycle management of breast cancer bone health based on evidence-based medicine,and put forward reasonable suggestions to guide clinicians to better deal with health issues in bone health clinics.

Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

Background:Pulmonary sarcomatoid carcinoma(PSC)is a rare and aggressive subtype of non-small cell lung cancer(NSCLC),characterized by the presence of epithelial and sarcoma-like components.The molecular and immune landscape of PSC has not been well defined.Methods:Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel,whole-exome,and RNA sequencing.We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.Results:In total,27 canonical cancer gene mutations were identified,with TP53 the most frequently mutated gene,followed by KRAS.Interestingly,most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors,suggesting branching evolution in most PSC tumors.We identified two distinct molecular subtypes of PSC,driven primarily by immune infiltration and signaling.The Immune High(IM-H)subtype was associated with superior survival,highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.Conclusions:We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis.IM-H tumors were associated with favorable recurrence-free survival and overall survival,highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning

Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommending surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis:A systematic review and meta-analysis

Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province

Background:Neuroblastoma is one of the most common extracranial malignant solid tumors in children.AlkB homolog 5(ALKBH5)is an RNA N6-methyladenosine(m6A)demethylase that plays a critical role in tumorigenesis and development.We assessed the association between single nucleotide polymorphisms(SNPs)in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer controls.Methods:Genotyping was determined by the TaqMan method.The association between ALKBH5 polymorphisms(rs1378602 and rs8400)and the risk of neuroblastoma was evaluated using the odds ratio(OR)and 95%confidence interval(CI).Results:We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma risk.Further stratification analysis by age,sex,primary site,and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males(adjusted OR=0.58,95%CI=0.35–0.97,p=0.036)and children with retroperitoneal neuroblastoma(adjusted OR=0.58,95%CI=0.34–0.98,p=0.040).Conclusions:ALKBH5 SNPs do not seem to be associated with neuroblastoma risk.More studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma.

^(18)F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma

Rhabdomyosarcoma(RMS)originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood.^(18)F-fluoro-deoxyglucose(^(18)F-FDG)positron emission tomography(PET)/computed tomography(CT)has been reported to be valuable in RMS staging and risk stratification.Paratesticular RMS is a relatively uncommon form of RMS,most of which are of the embryonal histologic type.Paratesticular alveolar RMS is associated with aggressive behavior,high metastatic potential,and poor outcomes.To the best of our knowledge,^(18)F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been described.Here,we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on^(18)F-FDG PET/CT.This case also demonstrates the potential value of^(18)F-FDG PET/CT in RMS staging and treatment decisions,and may aid in the differential diagnosis.