Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely int...Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.展开更多
Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the ...Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.展开更多
Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole...Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data.Our findings reveal a unique mutational profile in East Asian acral melanoma,characterized by fewer point mutations and structural variations,a higher prevalence of NRAS mutations,and a lower frequency of BRAF mutations compared to patients of European descent.Notably,we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations.Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors.We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis.The structural variations and amplifications in EP300,TERT,RAC1,and LZTR1 point to potential therapeutic targets tailored to East Asian populations.The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation.In summary,our study provides important insights into the genetic underpinnings of acral melanoma in East Asians,creating opportunities for targeted therapies.展开更多
BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcino...BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.展开更多
BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or...BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or other conditions).Idiopathic retroperitoneal fibrosis(IRPF)typically affects the abdominal aorta and iliac arteries along with the surrounding retroperitoneal area.This case review aims to summarize the imaging characteristics of IRPF arising from the peritoneal space.CASE SUMMARY An abdominal mass was discovered in a 52-year-old man during a routine physical examination,he had not complained of abdominal pain,distension,nausea,vomiting,diarrhea,fever,and had no significant past medical or family history.Abdominal magnetic resonance imaging revealed a soft tissue mass with poorly defined margins surrounding the duodenum,exhibiting slight to moderate high signal intensity on both T1-weighted and T2-weighted images.Diffusionweighted imaging with aβvalue of 800 mm²/second demonstrated slightly to moderate high signal intensity.Dynamic contrast enhanced images showed uneven enhancement on the arterial phase,with significant enhancement observed on the delayed phase.The mass infiltrated adjacent structures,including the head of the pancreas,the hepatic flexure of the colon,and part of the intestine,raising suspicion for malignant tumors such as sarcoma or lymphoma.However,surgery confirmed the diagnosis of IRPF.The patient underwent routine followup for one year,with no recurrence.CONCLUSION IRPF is a rare condition that presents considerable diagnostic challenges when lesions arise from the peritoneal space.In cases where imaging findings are atypical,a further puncture biopsy may be necessary to confirm the diagnosis.展开更多
Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and pro...Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.展开更多
Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesio...Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.展开更多
Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT045...Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT04550949).Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phaseⅢtrial.Patients were randomized(1:1)to receive either three cycles of QL1206 or denosumab(120 mg subcutaneously every 4 weeks).Subsequently,they received 10 cycles of QL1206(120 mg)over 40 weeks,followed by a 20-week safety follow-up.The primary endpoint was the percentage changes from baseline to week 13 in urinary Ntelopeptide corrected for creatinine(u NTx/Cr).Results:The breast cancer cohort consisted of 311 patients.Vertebral involvement(66.4%)was the most prevalent BM site at enrollment,while 27.7%of patients presented with≥3 metastatic bone lesions.At week 13,QL1206 demonstrated a median u NTx/Cr reduction of-69.9%(range:-98.1%-568.0%)vs.-74.3%(range:-97.7%-386.3%)for denosumab.The analysis of covariance revealed comparable least-square means for log-transformed changes:-1.416[95%confidence interval(95%CI):-1.736 to-1.096]vs.-1.501(95%CI:-1.824 to-1.178),yielding an between-group difference of 0.085(90%CI:-0.062-0.232;P=0.343).After a 53-week treatment period,83.6%achieved bone density improvement/disease stabilization.Safety profiles were comparable between groups.Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer,supporting QL1206 as a new option for management of BM from breast cancer.展开更多
Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/...Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/2 genes,increase the risk of BC and other cancers(ovarian and pancreatic cancer)^(2,3).Recent studies have demonstrated substantial benefits of poly(adenosine diphosphate ribose)polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs^(4).展开更多
In recmt years,depresion has emerged ss a significant gbbal health cotcern,prompting many individuals to seek pharmacoogical interventions.The identification of inflammatory changes in the hippocampns of depressed pat...In recmt years,depresion has emerged ss a significant gbbal health cotcern,prompting many individuals to seek pharmacoogical interventions.The identification of inflammatory changes in the hippocampns of depressed patients has highlighted a potential therapeutic target.Never-thelo,the effectiveness of medicntions targeting these specific alterntions has yrt to be fully substantinted.Prediminary remrch has suggusted the potentisl bemefits of photobiomodulation(PBM)as a trestment fot deptession,with no significant adetse eflects reported.This study utiliæd nesr-infrared light at intensities of 50 mW/cmend 300 mW/cm"to illuminate mice with chronic mild strea(CMS)-induced depresion model,aiming to explorethe therapeutik effects of PBM an depresion.The findings revealed that when exposedto a power denstty af 300 m W/cm?,the mice exhibited enhanæd behavioral outcomes,aскоmpanied by deressed levels of inflam-matory eytokines such as Il-1a,11-13,11-5,and'I-6 in the hippocampus.A notewarthy ae-socistion was observed between behavioral manifestations and inflammatory cytokine kvels.This study poits that PBM at an intensity of 300mW/cm is a viable nonpharmacological intervention for depression,as it demonstrntes a notable enhanoment in deprasive symptoms and the regulation of inflammatory medistors within the hippocятpal region of the brain.However,this study is constrained by the particular PBM parameters employed;therefore,additional resesrch is neceary to investigate a broader spectrum af doees and trestment durations in order to enhan the therapeutic application and deepen the understanding of the underlying mechanisma.展开更多
Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across d...Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings.This study aimed to assess the outcomes of LDG vs.open distal gastrectomy(ODG)in patients with LAGC despite differences in clinical trial populations and treatment environments.Methods:The KLASS-02 and CLASS-01 trials are multicenter,non-inferiority,open-label,randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China,respectively.Some 1,050 patients were enrolled in KLASS-02,and 1,056 patients were enrolled in CLASS-01.Individual patient data(IPD)from KLASS-02 and CLASS-01 were pooled and analyzed.Results:There were 900 patients in the LDG group and 920 in the ODG group.Baseline characteristics were well balanced between groups.The LDG group had better short-term and recovery outcomes than the ODG group,although anastomotic leakage was more frequent.For patients who underwent LDG vs.ODG,5-year overall survival(OS)was 82.7%[95%confidence interval(95%CI),80.2%-85.2%]vs.83.3%(95%CI,80.9%-85.8%)(P=0.706)and 5-year recurrence-free survival(RFS)was 76.9%(95%CI,74.1%-79.7%)vs.77.9%(95%CI,75.2%-80.6%)(P=0.666),respectively,with a median follow-up of 70 months.In the multivariable prognostic IPD meta-analysis,the operative approach was not independently associated with OS[hazard ratio(HR)=1.045,95%CI,0.833-1.311;P=0.706]or RFS(HR=1.044,95%CI,0.859-1.269;P=0.667)for LDG vs.ODG.In the subgroup analysis,LDG demonstrated a significant association with poorer RFS in the p T4 subgroup(HR=1.377,95%CI,1.022-1.760;P=0.034).Conclusions:Despite differences in patient populations,surgical practices,and postoperative treatments between trials,LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC,except for the p T4 patients.Therefore,LDG could be a good treatment alternative for patients with LAGC;however,caution should be warranted in its application for patients classified as T4.展开更多
BACKGROUND Accurate target volume delineation is the premise for the implementation of precise radiotherapy.Inadequate target volume delineation may diminish tumor control or increase toxicity.Although several clinica...BACKGROUND Accurate target volume delineation is the premise for the implementation of precise radiotherapy.Inadequate target volume delineation may diminish tumor control or increase toxicity.Although several clinical target volume(CTV)delineation guidelines for rectal cancer have been published in recent years,significant interobserver variation(IOV)in CTV delineation still exists among radiation oncologists.However,proper education may serve as a bridge that connects complex guidelines with clinical practice.AIM To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer.METHODS The study consisted of a baseline target volume delineation,a 150-min education intervention,and a follow-up evaluation.A 42-year-old man diagnosed with stage IIIC(T3N2bM0)rectal adenocarcinoma was selected for target volume delineation.CTVs obtained before and after the program were compared.Dice similarity coefficient(DSC),inclusiveness index(IncI),conformal index(CI),and relative volume difference[ΔV(%)]were analyzed to quantitatively evaluate the disparities between the participants’delineation and the standard CTV.Maximum volume ratio(MVR)and coefficient of variation(CV)were calculated to assess the IOV.Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume,external iliac area,groin area,and ischiorectal fossa.RESULTS Of the 18 radiation oncologists from 10 provinces in China,13 completed two sets of CTVs.In quantitative analysis,the average CTV volume decreased from 809.82 cm3 to 705.21 cm3(P=0.001)after the education program.Regarding the indices for geometric comparison,the mean DSC,IncI,and CI increased significantly,whileΔV(%)decreased remarkably,indicating improved agreement between participants’delineation and the standard CTV.Moreover,an 11.80%reduction in MVR and 18.19%reduction in CV were noted,demonstrating a smaller IOV in delineation after the education program.Regarding qualitative analysis,the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa;61.54%(8/13)and 53.85%(7/13)of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa,respectively.However,the education program reduced these variations.CONCLUSION Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in China's Mainland.A well-structured education program could improve delineation accuracy and reduce IOVs.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase in...Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.展开更多
Objective： In this study,we aimed to estimate the updated incidence and mortality rate of stomach cancer based on the cancer registration data in 2014,collected by the National Central Cancer Registry of China（NCCRC...Objective： In this study,we aimed to estimate the updated incidence and mortality rate of stomach cancer based on the cancer registration data in 2014,collected by the National Central Cancer Registry of China（NCCRC）.Methods： In 2017,339 registries＇ data were qualified based on the criteria of data quality control of the NCCRC.Cases of stomach cancer were retrieved from the national database.We estimated numbers of stomach cancer cases and deaths in China using age-specific rates and corresponding national population stratified by area,sex,agegroup（0,1–4,5–9,10–14,…,85＋）.Chinese standard population in 2000 and Segi＇s world population were applied for age-standardized incidence and mortality rates.Results： In 2014,410,400 new stomach cancer cases and 293,800 cancer-associated deaths were estimated to have occurred in China.The crude incidence rate of stomach cancer was 30.00/100,000,age-standardized incidence rates by Chinese standard population（ASIRC） and by world standard population（ASIRW） were 19.62/100,000 and19.51/100,000,respectively.The crude mortality rate of stomach cancer was 21.48/100,000,age-standardized mortality rates by Chinese（ASMRC） and by world standard population（ASMRW） were 13.44/100,000 and13.30/100,000,respectively.Incidence and mortality rates in rural areas were both higher than that in urban areas.Stomach cancer has a strong relationship with gender and age.The disease has occurred more frequently among men than women with a male to female ratio of 2.4 for ASIRC.After age group of 40-44 years,incidence rates are substantially higher in men than in women,same pattern was seen for age-specific mortality rates.Conclusions： There is still a heavy burden of stomach cancer in China.The incidence and mortality patterns of stomach cancer show substantial gender and regional disparities.Great effort is needed to provide more accessible health services,sufficient financial resources,and adequate cancer-care infrastructure for the Chinese population,especially for people living in rural areas.展开更多
In China, colorectal cancer(CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first wor...In China, colorectal cancer(CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, sex, lifestyle, genetic factors, obesity, diabetes, gut microbiota status, and precancerous lesions. Furthermore, incidence and mortality rates of CRC are closely related to socioeconomic development levels, varying according to regional and population characteristics. Prevention is the main strategy to reduce incidence and mortality rates of CRC. This can be achieved through strategies stimulating lifestyle changes, healthy diet habits, and early screening for high-risk individuals. To reduce the burden of CRC, public health officials should promote prevention and management of modifiable risk factors through national policies. The rising incidence and mortality rates of CRC in China may be timely curbed by clarifying specific epidemiological characteristics, optimizing early screening strategies, and strictly implementing diagnosis and treatment guidelines. Thus, this study aimed to collect and report the current research status on epidemiology and risk factors of CRC in China.展开更多
Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association betwee...Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.展开更多
Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current...Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.展开更多
Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric...Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.展开更多
基金support by grants from Capital’s Funds for Health Improvement and Research(Grant No.2024-2-1024)Beijing Natural Science Foundation(Grant No.7232018).
文摘Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
文摘Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.
基金supported by the National Key Research and Development Program(2023YFC2506404)the Natural Science Foundation of China(82272848,82425047,82272676)+2 种基金Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20220901)Beijing Natural Science Foundation(7242021,L248021)Sichuan Provincial Science and Technology Department Key Research and Development Program(2024YFHZ0004)。
文摘Acral melanoma,the most common melanoma subtype in East Asia,is associated with a poor prognosis.This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians.We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data.Our findings reveal a unique mutational profile in East Asian acral melanoma,characterized by fewer point mutations and structural variations,a higher prevalence of NRAS mutations,and a lower frequency of BRAF mutations compared to patients of European descent.Notably,we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations.Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors.We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis.The structural variations and amplifications in EP300,TERT,RAC1,and LZTR1 point to potential therapeutic targets tailored to East Asian populations.The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation.In summary,our study provides important insights into the genetic underpinnings of acral melanoma in East Asians,creating opportunities for targeted therapies.
基金Supported by the National Key Research and Development Program of China,No.2023YFF1204702the National Natural Science Foundation of China,No.82173151+2 种基金Capital’s Funds for Health Improvement and Research,No.CFH 2022-4-1025Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.XMLX202119Science Foundation of Peking University Cancer Hospital,No.PY202329.
文摘BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.
文摘BACKGROUND Retroperitoneal fibrosis is a rare fibro-inflammatory condition which can be classified into idiopathic(accounting for over 75%)and secondary types(due to malignancies,infections,medications,radiotherapy or other conditions).Idiopathic retroperitoneal fibrosis(IRPF)typically affects the abdominal aorta and iliac arteries along with the surrounding retroperitoneal area.This case review aims to summarize the imaging characteristics of IRPF arising from the peritoneal space.CASE SUMMARY An abdominal mass was discovered in a 52-year-old man during a routine physical examination,he had not complained of abdominal pain,distension,nausea,vomiting,diarrhea,fever,and had no significant past medical or family history.Abdominal magnetic resonance imaging revealed a soft tissue mass with poorly defined margins surrounding the duodenum,exhibiting slight to moderate high signal intensity on both T1-weighted and T2-weighted images.Diffusionweighted imaging with aβvalue of 800 mm²/second demonstrated slightly to moderate high signal intensity.Dynamic contrast enhanced images showed uneven enhancement on the arterial phase,with significant enhancement observed on the delayed phase.The mass infiltrated adjacent structures,including the head of the pancreas,the hepatic flexure of the colon,and part of the intestine,raising suspicion for malignant tumors such as sarcoma or lymphoma.However,surgery confirmed the diagnosis of IRPF.The patient underwent routine followup for one year,with no recurrence.CONCLUSION IRPF is a rare condition that presents considerable diagnostic challenges when lesions arise from the peritoneal space.In cases where imaging findings are atypical,a further puncture biopsy may be necessary to confirm the diagnosis.
基金supported by the National Natural Science Foundation of China(No.82372001,82171973,82171980)the Youth Talent Support Program(No.A002863)Scientific Research Foundation of Peking University Cancer Hospital(No.BJCH2024CZ02)。
文摘Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.
基金funded by the National Natural Science Foundation of China(Grant No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant Nos.2023ZD0501400-2023ZD0501402)+3 种基金Beijing Hospitals Authority’s Ascent Plan(Grant No.DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(Grant No.ZLRK202325)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(Grant No.BMU2022XKQ004)the Science Foundation of Peking University Cancer Hospital(Grant Nos.BJCH2024BJ02,XKFZ2410,and 2022-27).
文摘Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
文摘Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT04550949).Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phaseⅢtrial.Patients were randomized(1:1)to receive either three cycles of QL1206 or denosumab(120 mg subcutaneously every 4 weeks).Subsequently,they received 10 cycles of QL1206(120 mg)over 40 weeks,followed by a 20-week safety follow-up.The primary endpoint was the percentage changes from baseline to week 13 in urinary Ntelopeptide corrected for creatinine(u NTx/Cr).Results:The breast cancer cohort consisted of 311 patients.Vertebral involvement(66.4%)was the most prevalent BM site at enrollment,while 27.7%of patients presented with≥3 metastatic bone lesions.At week 13,QL1206 demonstrated a median u NTx/Cr reduction of-69.9%(range:-98.1%-568.0%)vs.-74.3%(range:-97.7%-386.3%)for denosumab.The analysis of covariance revealed comparable least-square means for log-transformed changes:-1.416[95%confidence interval(95%CI):-1.736 to-1.096]vs.-1.501(95%CI:-1.824 to-1.178),yielding an between-group difference of 0.085(90%CI:-0.062-0.232;P=0.343).After a 53-week treatment period,83.6%achieved bone density improvement/disease stabilization.Safety profiles were comparable between groups.Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer,supporting QL1206 as a new option for management of BM from breast cancer.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82272932,81974422,and 92359201).
文摘Breast cancer(BC)is now the most common cancer and the fifth leading cause of cancer-associated mortality among women in China1.Germline pathogenic variants(PVs)of BC susceptibility genes,such as the well-known BRCA1/2 genes,increase the risk of BC and other cancers(ovarian and pancreatic cancer)^(2,3).Recent studies have demonstrated substantial benefits of poly(adenosine diphosphate ribose)polymerase inhibitors in the treatment of BC patients who carry BRCA1/2 PVs^(4).
基金supported by the National Natural Science Foundation of China(Grant No.81927804),horizontal projects ofthe integration between industry and education(Nos.KH54429301,KH54392701)supported by the Research Funding of Hangzhou International Innovation Institute of Beihang University(Grant No.2024KQ098)+2 种基金the China Disabled Persons,Federation special topic(Grant No.CDPF2023KF00001)the National Natural Science Foundation of China(Grant No.8246140544)the National Key Research and Development Plan(Grant Nos.2021YFF0501600,and 2022YFC3601200).
文摘In recmt years,depresion has emerged ss a significant gbbal health cotcern,prompting many individuals to seek pharmacoogical interventions.The identification of inflammatory changes in the hippocampns of depressed patients has highlighted a potential therapeutic target.Never-thelo,the effectiveness of medicntions targeting these specific alterntions has yrt to be fully substantinted.Prediminary remrch has suggusted the potentisl bemefits of photobiomodulation(PBM)as a trestment fot deptession,with no significant adetse eflects reported.This study utiliæd nesr-infrared light at intensities of 50 mW/cmend 300 mW/cm"to illuminate mice with chronic mild strea(CMS)-induced depresion model,aiming to explorethe therapeutik effects of PBM an depresion.The findings revealed that when exposedto a power denstty af 300 m W/cm?,the mice exhibited enhanæd behavioral outcomes,aскоmpanied by deressed levels of inflam-matory eytokines such as Il-1a,11-13,11-5,and'I-6 in the hippocampus.A notewarthy ae-socistion was observed between behavioral manifestations and inflammatory cytokine kvels.This study poits that PBM at an intensity of 300mW/cm is a viable nonpharmacological intervention for depression,as it demonstrntes a notable enhanoment in deprasive symptoms and the regulation of inflammatory medistors within the hippocятpal region of the brain.However,this study is constrained by the particular PBM parameters employed;therefore,additional resesrch is neceary to investigate a broader spectrum af doees and trestment durations in order to enhan the therapeutic application and deepen the understanding of the underlying mechanisma.
基金supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health&Welfare,Republic of Korea(No.RS-2023-KH140183)the 2024 intramural research fund of Ajou University Medical Center(No.M-2024-C0460-00083)+3 种基金an Investigator-Initiated Study granted from Ethicon,Inc-Johnson and Johnson Med Tech(No.ENG-2021-04)the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(No.2020B121201004)Guangdong Provincial Major Talents Project(No.2019JC05Y361)Major Clinical Technology Project in Guangzhou(No.2023P-ZD01)。
文摘Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings.This study aimed to assess the outcomes of LDG vs.open distal gastrectomy(ODG)in patients with LAGC despite differences in clinical trial populations and treatment environments.Methods:The KLASS-02 and CLASS-01 trials are multicenter,non-inferiority,open-label,randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China,respectively.Some 1,050 patients were enrolled in KLASS-02,and 1,056 patients were enrolled in CLASS-01.Individual patient data(IPD)from KLASS-02 and CLASS-01 were pooled and analyzed.Results:There were 900 patients in the LDG group and 920 in the ODG group.Baseline characteristics were well balanced between groups.The LDG group had better short-term and recovery outcomes than the ODG group,although anastomotic leakage was more frequent.For patients who underwent LDG vs.ODG,5-year overall survival(OS)was 82.7%[95%confidence interval(95%CI),80.2%-85.2%]vs.83.3%(95%CI,80.9%-85.8%)(P=0.706)and 5-year recurrence-free survival(RFS)was 76.9%(95%CI,74.1%-79.7%)vs.77.9%(95%CI,75.2%-80.6%)(P=0.666),respectively,with a median follow-up of 70 months.In the multivariable prognostic IPD meta-analysis,the operative approach was not independently associated with OS[hazard ratio(HR)=1.045,95%CI,0.833-1.311;P=0.706]or RFS(HR=1.044,95%CI,0.859-1.269;P=0.667)for LDG vs.ODG.In the subgroup analysis,LDG demonstrated a significant association with poorer RFS in the p T4 subgroup(HR=1.377,95%CI,1.022-1.760;P=0.034).Conclusions:Despite differences in patient populations,surgical practices,and postoperative treatments between trials,LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC,except for the p T4 patients.Therefore,LDG could be a good treatment alternative for patients with LAGC;however,caution should be warranted in its application for patients classified as T4.
基金Supported by the Beijing Municipal Science&Technology Commission,No.Z181100001718192the Capital’s Funds for Health Improvement and Research,No.2020-2-1027 and No.2020-1-4021+1 种基金the National Natural Science Foundation,No.82073333the Beijing Natural Science Foundation,No.1212011.
文摘BACKGROUND Accurate target volume delineation is the premise for the implementation of precise radiotherapy.Inadequate target volume delineation may diminish tumor control or increase toxicity.Although several clinical target volume(CTV)delineation guidelines for rectal cancer have been published in recent years,significant interobserver variation(IOV)in CTV delineation still exists among radiation oncologists.However,proper education may serve as a bridge that connects complex guidelines with clinical practice.AIM To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer.METHODS The study consisted of a baseline target volume delineation,a 150-min education intervention,and a follow-up evaluation.A 42-year-old man diagnosed with stage IIIC(T3N2bM0)rectal adenocarcinoma was selected for target volume delineation.CTVs obtained before and after the program were compared.Dice similarity coefficient(DSC),inclusiveness index(IncI),conformal index(CI),and relative volume difference[ΔV(%)]were analyzed to quantitatively evaluate the disparities between the participants’delineation and the standard CTV.Maximum volume ratio(MVR)and coefficient of variation(CV)were calculated to assess the IOV.Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume,external iliac area,groin area,and ischiorectal fossa.RESULTS Of the 18 radiation oncologists from 10 provinces in China,13 completed two sets of CTVs.In quantitative analysis,the average CTV volume decreased from 809.82 cm3 to 705.21 cm3(P=0.001)after the education program.Regarding the indices for geometric comparison,the mean DSC,IncI,and CI increased significantly,whileΔV(%)decreased remarkably,indicating improved agreement between participants’delineation and the standard CTV.Moreover,an 11.80%reduction in MVR and 18.19%reduction in CV were noted,demonstrating a smaller IOV in delineation after the education program.Regarding qualitative analysis,the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa;61.54%(8/13)and 53.85%(7/13)of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa,respectively.However,the education program reduced these variations.CONCLUSION Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in China's Mainland.A well-structured education program could improve delineation accuracy and reduce IOVs.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by grants from the National Natural Sciences Foundation Key Program(No.81330062)Education Ministry Innovative Research Team Program(No.IRT13003)+1 种基金Peking University-Tsinghua University Joint Center for Life Sciences Clinical Investigator,National High Technology Research and Development Program 863(No.SS2015AA020403)Beijing Technology Project(No.Z141100000214013)
文摘Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.
基金supported by grants from the Beijing Young Talent Program (No.2016000021469 G189)Special Fund for Health Research in the Public Interest (No.201502001)CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2016-12M-2-004)
文摘Objective： In this study,we aimed to estimate the updated incidence and mortality rate of stomach cancer based on the cancer registration data in 2014,collected by the National Central Cancer Registry of China（NCCRC）.Methods： In 2017,339 registries＇ data were qualified based on the criteria of data quality control of the NCCRC.Cases of stomach cancer were retrieved from the national database.We estimated numbers of stomach cancer cases and deaths in China using age-specific rates and corresponding national population stratified by area,sex,agegroup（0,1–4,5–9,10–14,…,85＋）.Chinese standard population in 2000 and Segi＇s world population were applied for age-standardized incidence and mortality rates.Results： In 2014,410,400 new stomach cancer cases and 293,800 cancer-associated deaths were estimated to have occurred in China.The crude incidence rate of stomach cancer was 30.00/100,000,age-standardized incidence rates by Chinese standard population（ASIRC） and by world standard population（ASIRW） were 19.62/100,000 and19.51/100,000,respectively.The crude mortality rate of stomach cancer was 21.48/100,000,age-standardized mortality rates by Chinese（ASMRC） and by world standard population（ASMRW） were 13.44/100,000 and13.30/100,000,respectively.Incidence and mortality rates in rural areas were both higher than that in urban areas.Stomach cancer has a strong relationship with gender and age.The disease has occurred more frequently among men than women with a male to female ratio of 2.4 for ASIRC.After age group of 40-44 years,incidence rates are substantially higher in men than in women,same pattern was seen for age-specific mortality rates.Conclusions： There is still a heavy burden of stomach cancer in China.The incidence and mortality patterns of stomach cancer show substantial gender and regional disparities.Great effort is needed to provide more accessible health services,sufficient financial resources,and adequate cancer-care infrastructure for the Chinese population,especially for people living in rural areas.
基金the Beijing Municipal Science&Technology Commission,Clinical Application and Development of Capital Characteristic(No.Z171100001017087)。
文摘In China, colorectal cancer(CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, sex, lifestyle, genetic factors, obesity, diabetes, gut microbiota status, and precancerous lesions. Furthermore, incidence and mortality rates of CRC are closely related to socioeconomic development levels, varying according to regional and population characteristics. Prevention is the main strategy to reduce incidence and mortality rates of CRC. This can be achieved through strategies stimulating lifestyle changes, healthy diet habits, and early screening for high-risk individuals. To reduce the burden of CRC, public health officials should promote prevention and management of modifiable risk factors through national policies. The rising incidence and mortality rates of CRC in China may be timely curbed by clarifying specific epidemiological characteristics, optimizing early screening strategies, and strictly implementing diagnosis and treatment guidelines. Thus, this study aimed to collect and report the current research status on epidemiology and risk factors of CRC in China.
文摘Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.
基金supported by MSD Holding Co.,Ltd.The funding was only for the payment of using CHIRA database
文摘Background： Few studies have attempted to evaluate the use of antiemetic therapy for chemotherapyinduced nausea and vomiting （CINV） at a national level in China or to assess how treatment regimens adhere to current guidelines. Methods： We searched the China Health Insurance Research Association （CHIRA） Database to identify patients with cancer who were 〉 18 years old and received either moderately or highly emetogenie chemotherapy （MEC and HEC, respectively） between 2008 and 2012. Patients＇ characteristics as well as usage of specific antiemetic regimens were analyzed using descriptive statistics. Results： Of the 14,548 patients included in the study, 6,477 received HEC while 8,071 were treated with MEC. Approximately 89.9% used antiemetics prophylactically to prevent acute CINV and 71.5% for delayed CINV while 9.0% were prescribed antiemetics as rescue therapy. A significantly lower proportion of patients treated with HEC received prophylactic antiemetic therapy for delayed CINV as compared to those treated with MEC （59.4% vs. 81.3 %; P〈0.001）. The HEC group had a slightly lower proportion of patients using a mixed regimen containing a 5-HT3 antagonist to prevent both acute and delayed CINV than the MEC group （P〈0.012）; however, a higher proportion received a mixed regimen containing eorticosteroids （P≤0.007）. Although more than half of the patients in the HEC group took three antiemeties to prevent acute and delayed CINV, these rates were significantly lower than those of the MEC group （both P〈0.001）. Finally, analysis of the regimens used revealed that there is over-utilization of drugs within the same class of antiemetic. Conclusions： These findings indicate that more attention is needed for treatment of delayed CINV, in terms of both overall use and the components of a typical treatment regimen.
基金supported by the National "863" High‐Tech Res & Dev Program of China (No. 2006AA02A402)Beijing Municipal Science & Technology Commission Program "Optimization of pharmacotherapy and individual selection in gastric cancer" (No D101100050010023)
文摘Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.
