Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic cha...Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.展开更多
Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dos...Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.展开更多
Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted the...Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.展开更多
BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple c...BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages.METHODS This was a retrospective study conducted from 2005 to 2014,involving six cancer hospitals and eight general hospitals across seven geographical regions of China(East,South,North,Central,Southwest,Northwest,and Northeast).Stratified sampling was used based on the population distribution of each region.Efficacy assessments were conducted by Cox proportional hazards regression models.When assessing the effectiveness of various chemotherapy regimens,traditional drugs such as gemcitabine used as monotherapy served as the reference.RESULTS A total of 3256 patients were included.The median follow-up time was 407 days,and the median overall survival was 183 days.At diagnosis,56%of patients were already in stage IV.Chemotherapy was administered to 39.73%of patients.In the adjuvant therapy phase,gemcitabine+fluorouracil was superior to gemcitabine monotherapy[hazard ratio(HR)=0.35,95%confidence interval(CI):0.14-0.89].In fluorouracil-based regimens,other combination regimens did not show effectiveness relative to monotherapy.For first-line treatment in patients with advanced disease,tegafur alone(HR=0.20,95%CI:0.06-0.66),gemcitabine plus cisplatin(HR=0.16,95%CI:0.04-0.70),and tegafur,gemcitabine plus platinum-based agents(HR=0.32,95%CI:0.11-0.91)were associated with a lower risk of death compared to gemcitabine alone.In second-line treatment,there were no significant differences in efficacy among various drugs,but FOLFIRINOX(irinotecan+oxaliplatin+leucovorin+5-fluorouracil)had an outstanding point estimate(HR=0.10,95%CI:0.01-1.27).CONCLUSION In China,pancreatic cancer is often diagnosed at advanced stages,emphasizing the need for early diagnosis and treatment.Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy,and FOLFIRINOX might offer more significant benefits in second-line treatment.展开更多
Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for imp...Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.展开更多
Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods...Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods:We analyzed the clinicopathological data of 3,926 gastrointestinal cancer patients from the Prevalence of Abdominal Complications After GastroEnterological surgery(PACAGE)database,covering 20 medical centers from December 2018 to December 2020.The predictive performance was evaluated using receiver operating characteristic(ROC)curves and Brier Score.Results:The patients were divided into gastric(2,271 cases)and colorectal cancer(1,655 cases)groups and further divided into training and external validation sets.The overall postoperative complication rates for gastric and colorectal cancer groups were 18.1%and 14.8%,respectively.The most common complication was the intraabdominal infection in both gastric and colorectal cancer groups.In the training set,the Random Forest(RF)model predicted the highest mean area under the curve(AUC)values for overall complications and different types of complications,in both the gastric cancer group and the colorectal cancer group,with similar results obtained in the external validation set.ROC curve analysis showed good predictive performance of the RF model for overall and infectious complications.An application-based clinical tool was developed for easy application in clinical practice.Conclusions:This model demonstrated good predictive performance for overall and infectious complications based on the multi-center database,supporting clinical decision-making and personalized treatment strategies.展开更多
Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering va...Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.展开更多
BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investig...BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.展开更多
Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is s...Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is still facing many obstacles to eradicate cancer： complexity of a mul- ti-factorial disease with organ-based specificities, high fail- ure rate of many anti-cancer drugs in clinical trials, lack of understanding of the cancer genesis factors.展开更多
This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel(abpaclitaxel)and anlotinib for ovarian cancer.In this study,44 patients diagnosed with platinum-resistant ovarian cancer were ...This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel(abpaclitaxel)and anlotinib for ovarian cancer.In this study,44 patients diagnosed with platinum-resistant ovarian cancer were enrolled.Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity.Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria.The primary endpoint was the investigator-evaluated objective response rate(ORR).44patients were enrolled between January2021 and March 2023 with a median age of 49 years.Twenty-nine had measurable lesions and 15 had non-measurable lesions.Overall,the investigator-evaluated ORRwas 56.8%(25/44;95%CI0.4110.713)in intention-to-treat population and 58.1%(25/43;95%CI 0.4220.726)in per-protocol population.The median progression-free survival was 9.8 months,and the median duration of response was 7.4 months.For safety,grade 3/4 adverse events(AEs)included leukopenia,gum pain,hypertension,and hand-foot syndrome.The response rates were 55.0%(11/20)in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors.The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer.Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.展开更多
Objective:To systematically evaluate the effectiveness of research-oriented integrated nursing interventions on cancer pain management in hospitalized oncology patients in China.Methods:A computerized search of Chines...Objective:To systematically evaluate the effectiveness of research-oriented integrated nursing interventions on cancer pain management in hospitalized oncology patients in China.Methods:A computerized search of Chinese and English databases was conducted to identify relevant studies.Two researchers independently assessed the quality of included literature using the Newcastle-Ottawa Scale(NOS).Data were extracted and analyzed via Stata 14.A random-effects model was applied due to significant heterogeneity(I²>50%).Sensitivity analysis and Egger’s test were performed to assess bias.Results:12 eligible studies(2014-2024)were included.Meta-analysis demonstrated that integrated nursing interventions significantly reduced cancer pain scores compared to routine care(SMD=-1.51,95%CI:-1.90 to-1.12;I²=84.8%),with superior efficacy.Subgroup-analyses revealed enhanced effects for“Nursing modes”(SMD=-2.11)and“cancer pain education”(SMD=-2.30).Conclusion:Research-oriented integrated nursing interventions significantly improve cancer pain management in Chinese hospitalized oncology patients,particularly through synergistic effects of“Nursing modes”and“can-cer pain education.”However,implementation bias from“additive interventions”in teaching hospitals and high heterogeneity warrant attention.Future studies should optimize designs to enhance clinical applicability.展开更多
Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy r...Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.展开更多
Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of ...Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.展开更多
Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological fu...Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological function of OTUB2 in TNBC and uncover the underlying mechanisms.Methods:First,we found that the expression of OTUB2 was upregulated in TNBC by bioinformatics analysis,we then validated its expression in TNBC tissues and cells using immunohistochemistry(IHC)and qPCR and plotted the survival curves by Kaplan-Meier method.Gene set enrichment analysis(GSEA)suggested that OTUB2 may be involved in tumor proliferation and metastasis.Further functional assays,including Cell Counting Kit-8(CCK-8),colony formation,Transwell,and wound healing assays,were performed to assess the effects of OTUB2 overexpression and knockdown on TNBC cell proliferation and migration.Additionally,UbiBrowser 2.0 was used to identify OTUB2 substrate proteins and western blotting was conducted to clarify the molecular mechanisms involved.Results:Our results demonstrated that OTUB2 expression was elevated in TNBC and associated with poor prognosis.Overexpression of OTUB2 enhanced the proliferation and migration of TNBC cells,while its knockdown inhibited these processes.Moreover,OTUB2 stabilized tumor necrosis factor receptor-associated factor 6(TRAF6)by deubiquitinating it,leading to activation of the protein kinase B(AKT)pathway.Conclusions:OTUB2 exerts its promoting effects on the progression of TNBC by activating the TRAF6/AKT pathway.展开更多
Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficient...Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.展开更多
The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and cli...The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and clinically significant prostate cancer(csPCa).Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center(Shanghai,China)between January 2019 and December 2023 were analyzed.Propensity score matching(PSM)was used to balance baseline characteristics,and detection rates were compared before and after PSM.Subgroup analyses based on prostate-specific antigen(PSA)levels and Prostate Imaging-Reporting and Data System(PI-RADS)scores were performed.Primary and secondary outcomes were the detection rates of PCa and csPCa,respectively.Of 2572 men,1778 were included in the PSM analysis.Before PSM,CB had higher detection rates for both PCa(62.9%vs 52.4%,odds ratio[OR]:1.54,P<0.001)and csPCa(54.9%vs 43.3%,OR:1.60,P<0.001)compared to SB.After PSM,CB remained superior in detecting PCa(63.1%vs 47.9%,OR:1.86,P<0.001)and csPCa(55.0%vs 38.2%,OR:1.98,P<0.001).In patients with PSA 4–12 ng ml−1(>4 ng ml-1 and≤12 ng ml-1,which is also applicable to the following text),CB detected more PCa(59.8%vs 40.7%,OR:2.17,P<0.001)and csPCa(48.1%vs 27.7%,OR:2.42,P<0.001).CB also showed superior csPCa detection in those with PI-RADS 3 lesions(32.1%vs 18.0%,OR:2.15,P=0.038).Overall,CB significantly improves PCa and csPCa detection,especially in patients with PSA 4–12 ng ml−1 or PI-RADS 3 lesions.展开更多
Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and...Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.展开更多
Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,H...Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,HR^(+)/HER2^(−)breast cancer relapse patterns are divided into three distinct types:primary resistant,secondary resistant,and endocrine sensitive.However,owing to the lack of cohorts with treatment and follow-up data,the heterogeneity among different recurrence patterns remains uncharted.Current treatments still lack precision.Methods:This analysis included data from a large-scale multiomics study of a HR^(+)/HER2^(−)breast cancer cohort(n=314).Through the analysis of transcriptomics(n=312),proteomics(n=124),whole-exome sequencing(n=290),metabolomics(n=217),and digital pathology(n=228)data,we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.Results:We explored distinct clinicopathological characteristics,biological heterogeneity,and potential therapeutic strategies for recurrence.Based on a shared relapse signature,we stratified patients into high-and lowrecurrence-risk groups.Patients with different relapse patterns presented unique molecular features in primary tumors.Specifically,receptor tyrosine kinase(RTK)pathway activation in the primary resistant group suggested the utility of RTK inhibitors,whereas mammalian target of rapamycin(mTOR)and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors.Interestingly,the endocrine-sensitive group displayed a quiescent state and high genomic instability,suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase(PARP)inhibitors could be effective strategies.Conclusions:These findings illuminate the clinicopathological and molecular landscape of HR^(+)/HER2^(−)breast cancer patients with distinct recurrence patterns,highlighting potential targeted therapies.展开更多
BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease af...BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease after radiofrequency ablation(RFA)treatment.We compared the outcomes of patients with lung oligometa-stases from CRC after RFA plus maintenance capecitabine with RFA alone.AIM To determine whether adding capecitabine to RFA improves prognosis compared with RFA alone.METHODS This multicenter retrospective study included consecutive patients from two tertiary cancer centers treated for pulmonary oligometastases from CRC between 2016 and 2023.Subjects were assigned to RFA plus capecitabine(combined)or RFA alone(only RFA)groups.Primary outcomes included overall survival(OS)and progression-free survival(PFS)survival and the secondary outcome was local tumor progression(LTP).The OS,PFS,and LTP rates were compared between the two groups.In addition,prognostic factors were identified using univariate and multivariate analyses.RESULTS Combination therapy(RFA+capecitabine,n=148)and RFA monotherapy(n=99)were compared in patients with CRC and lung metastases.The median OS was 37.8 months(22.4,50.3),the PFS was 18.7 months(13.0,36.5),and the LTP was 31.5 months(20.0,52.4)in the Only RFA group.The OS increased significantly(P=0.011)and the LTP decreased at all time points(P<0.001)in the combined group.The multivariate cox analysis revealed that combined chemotherapy significantly improved OS,with hazard ratios ranging from 0.29 to 0.35(all P<0.015)after adjusting for demographic,tumor,and treatment-related factors.The risk of death was consistently lower in the combination therapy group compared to RFA monotherapy.CONCLUSION RFA prolongs survival and local control in patients with CRC pulmonary oligometastases.Adjuvant capecitabine increases OS and reduces LTP compared to RFA alone,but PFS did not significantly change.展开更多
The efficacy,safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)for patients with resected EGFR-mutated non-small-cell lung cancer(NSCLC)were not kno...The efficacy,safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)for patients with resected EGFR-mutated non-small-cell lung cancer(NSCLC)were not known until 2014,when this study was initiated.In this phase 3 ICTAN trial(GASTO1002,NCT01996098),patients with completely resected,EGFR-mutated,stage Ⅱ-ⅢA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib(125 mg,three times daily)for 12 months,to receive icotinib for 6 months,or to undergo observation.The primary endpoint was disease-free survival(DFS).This trial was terminated early.A total of 251 patients were randomized.Adjuvant icotinib for 12 months significantly improved DFS(hazard ratio[HR]:0.40,95%confidence interval[CI],0.27–0.61;P<0.001)and overall survival(OS;HR:0.55,95%CI,0.32–0.96;P=0.032)compared with observation.Adjuvant icotinib of 6 months also significantly improved DFS(HR:0.41,95%CI,0.27–0.62;P<0.001)and OS(HR:0.56,95%CI,0.32–0.98;P=0.038)compared with observation.Adjuvant icotinib for 12 months did not improve DFS(HR:0.97;P=0.89)or OS(HR:1.00;P=0.99)compared with 6 months of this drug.Rates of adverse events of grade 3 or higher were 8.3%,6.0%and 2.4%for the 12-month icotinib,6-month icotinib,and observation groups,respectively.Adjuvant icotinib for 12 months or 6 months following adjuvant chemotherapy improved DFS and OS compared with observation in patients with resected EGFR-mutated stage Ⅱ-ⅢA NSCLC with a manageable safety profile,supporting it as a potential treatment option.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81172568)
文摘Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.
基金supported by the National Key Technologies Research and Development Program of China(No.85-914-02)the National Natural Science Foundation of China(No.30770641,31170805)
文摘Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.
基金funded by the medical and health category of the Science and Technology Project of Shantou(No.230509116495542,Wu Haoming)National Natural Science Foundation of China(NSFC)Cultivation Project of the Cancer Hospital of Shantou University Medical College(No.2024GP002,Wu Haoming)National Natural Science Foundation of China(82203130,Ye Feng).
文摘Background:Breast cancer remains a leading cause of morbidity and mortality among women worldwide,with significant geographic disparities in its impact.While human epidermal growth factor receptor 2(HER2)-targeted therapies,such as trastuzumab,have improved outcomes for HER2-positive breast cancer,challenges like therapy resistance persist,highlighting the need for novel treatments.Recent developments in antibody-drug conjugates(ADCs),particularly disitamab vedotin(RC48),show promising efficacy in targeting both HER2-positive and HER2-low expression tumors,warranting further investigation through real-world studies to assess its broader clinical applicability.Method:This retrospective,multicenter observational study evaluated the real-world efficacy and safety of RC48 in patients with HER2-positive or HER2-low breast cancer across three medical centers in China.Patient demographic characteristics,treatment patterns,sequential use of ADCs,and treatment-related adverse events were recorded and analyzed.Result:The median progression-free survival(mPFS)for the overall population(n 96)was=4.31 months,with HER2-positive patients demonstrating significantly longer mPFS(5.26 months)compared to HER2-low patients(3.45 months;p<0.044),while subgroup analyses revealed no significant differences in mPFS based on=estrogen receptor(ER),progesterone receptor(PR),or hormone receptor(HR)status.Safety data indicated that adverse events were consistent with prior reports,with no new safety concerns identified during the study period.Conclusion:This real-world study demonstrates the efficacy of RC48 in both HER2-positive and HER2-low breast cancer.Notably,combination therapy significantly improved outcomes in HER2-low patients.
文摘BACKGROUND The survival rate of pancreatic cancer is low,and there is a lack of effective treatment.AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages.METHODS This was a retrospective study conducted from 2005 to 2014,involving six cancer hospitals and eight general hospitals across seven geographical regions of China(East,South,North,Central,Southwest,Northwest,and Northeast).Stratified sampling was used based on the population distribution of each region.Efficacy assessments were conducted by Cox proportional hazards regression models.When assessing the effectiveness of various chemotherapy regimens,traditional drugs such as gemcitabine used as monotherapy served as the reference.RESULTS A total of 3256 patients were included.The median follow-up time was 407 days,and the median overall survival was 183 days.At diagnosis,56%of patients were already in stage IV.Chemotherapy was administered to 39.73%of patients.In the adjuvant therapy phase,gemcitabine+fluorouracil was superior to gemcitabine monotherapy[hazard ratio(HR)=0.35,95%confidence interval(CI):0.14-0.89].In fluorouracil-based regimens,other combination regimens did not show effectiveness relative to monotherapy.For first-line treatment in patients with advanced disease,tegafur alone(HR=0.20,95%CI:0.06-0.66),gemcitabine plus cisplatin(HR=0.16,95%CI:0.04-0.70),and tegafur,gemcitabine plus platinum-based agents(HR=0.32,95%CI:0.11-0.91)were associated with a lower risk of death compared to gemcitabine alone.In second-line treatment,there were no significant differences in efficacy among various drugs,but FOLFIRINOX(irinotecan+oxaliplatin+leucovorin+5-fluorouracil)had an outstanding point estimate(HR=0.10,95%CI:0.01-1.27).CONCLUSION In China,pancreatic cancer is often diagnosed at advanced stages,emphasizing the need for early diagnosis and treatment.Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy,and FOLFIRINOX might offer more significant benefits in second-line treatment.
基金supported by the Guangdong Province Nature Foundation of China Project (No. 2022A1515012200 to Li Z)Shenzhen Science and Technology Program (No. RCYX20221008093032008 to Li Z)Shenzhen People's Hospital Clinician Scientist Training Program (No. SYWGSJCYJ202405 to Li Z).
文摘Objective The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer(AJCC)anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement.Methods The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups.Kaplan–Meier plots were used to estimate the disease-specific survival(DSS)of the patients.The accuracy of the staging systems was investigated using the Harrell's concordance index(C-index).Results According to the 8th AJCC anatomic and prognostic stage groups,the 5-year DSS rates for patients with stages 0is/a,I,IIA,IIB,IIIA,IIIB,and IV disease were 100%,99%,86%,81%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–IIA)<0.001,p_(IIA–IIB)=0.5,p_(IIB–IIIA)<0.001,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).According to the modified model 1 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,88%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.002,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).Similarly,according to the modified model 2 system,the 5-year DSS rates without survivorship overlap for patients with stages 0is/a,I,II,IIIA,IIIB,and IV disease were 100%,99%,86%,66%,34%,and 23%,respectively(p_(0is/a–I)=0.8,p_(I–II)<0.001,p_(II–IIIA)=0.008,p_(IIIA–IIIB)<0.001,p_(IIIB–IV)=0.004,and p_(Total)<0.001).The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups.These results were confirmed by the bootstrap internal validation.Conclusion There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups.The improved models,which are more concise and convenient,have similar prediction accuracy.
基金supported by the Natural Science Foundation of Fujian Province(No.2022J01755)。
文摘Objective:This study aimed to develop and validate a predictive model for postoperative complications in gastrointestinal cancer patients using a large multicenter database,based on machine learning algorithms.Methods:We analyzed the clinicopathological data of 3,926 gastrointestinal cancer patients from the Prevalence of Abdominal Complications After GastroEnterological surgery(PACAGE)database,covering 20 medical centers from December 2018 to December 2020.The predictive performance was evaluated using receiver operating characteristic(ROC)curves and Brier Score.Results:The patients were divided into gastric(2,271 cases)and colorectal cancer(1,655 cases)groups and further divided into training and external validation sets.The overall postoperative complication rates for gastric and colorectal cancer groups were 18.1%and 14.8%,respectively.The most common complication was the intraabdominal infection in both gastric and colorectal cancer groups.In the training set,the Random Forest(RF)model predicted the highest mean area under the curve(AUC)values for overall complications and different types of complications,in both the gastric cancer group and the colorectal cancer group,with similar results obtained in the external validation set.ROC curve analysis showed good predictive performance of the RF model for overall and infectious complications.An application-based clinical tool was developed for easy application in clinical practice.Conclusions:This model demonstrated good predictive performance for overall and infectious complications based on the multi-center database,supporting clinical decision-making and personalized treatment strategies.
基金supported by grants from the Medical Engineering Jiont Fund of the Fudan University(No.IDH2310117)。
文摘Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.
文摘BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.
文摘Cancer is a leading cause of death in China with an estima- tion of nearly 2 million deaths every year （Chen and Fu, 2011b）. Matter of a public health importance in China and worldwide, the scientific community is still facing many obstacles to eradicate cancer： complexity of a mul- ti-factorial disease with organ-based specificities, high fail- ure rate of many anti-cancer drugs in clinical trials, lack of understanding of the cancer genesis factors.
文摘This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel(abpaclitaxel)and anlotinib for ovarian cancer.In this study,44 patients diagnosed with platinum-resistant ovarian cancer were enrolled.Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity.Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria.The primary endpoint was the investigator-evaluated objective response rate(ORR).44patients were enrolled between January2021 and March 2023 with a median age of 49 years.Twenty-nine had measurable lesions and 15 had non-measurable lesions.Overall,the investigator-evaluated ORRwas 56.8%(25/44;95%CI0.4110.713)in intention-to-treat population and 58.1%(25/43;95%CI 0.4220.726)in per-protocol population.The median progression-free survival was 9.8 months,and the median duration of response was 7.4 months.For safety,grade 3/4 adverse events(AEs)included leukopenia,gum pain,hypertension,and hand-foot syndrome.The response rates were 55.0%(11/20)in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors.The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer.Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.
文摘Objective:To systematically evaluate the effectiveness of research-oriented integrated nursing interventions on cancer pain management in hospitalized oncology patients in China.Methods:A computerized search of Chinese and English databases was conducted to identify relevant studies.Two researchers independently assessed the quality of included literature using the Newcastle-Ottawa Scale(NOS).Data were extracted and analyzed via Stata 14.A random-effects model was applied due to significant heterogeneity(I²>50%).Sensitivity analysis and Egger’s test were performed to assess bias.Results:12 eligible studies(2014-2024)were included.Meta-analysis demonstrated that integrated nursing interventions significantly reduced cancer pain scores compared to routine care(SMD=-1.51,95%CI:-1.90 to-1.12;I²=84.8%),with superior efficacy.Subgroup-analyses revealed enhanced effects for“Nursing modes”(SMD=-2.11)and“cancer pain education”(SMD=-2.30).Conclusion:Research-oriented integrated nursing interventions significantly improve cancer pain management in Chinese hospitalized oncology patients,particularly through synergistic effects of“Nursing modes”and“can-cer pain education.”However,implementation bias from“additive interventions”in teaching hospitals and high heterogeneity warrant attention.Future studies should optimize designs to enhance clinical applicability.
基金supported by grants from the Special Funding of China Postdoctoral Science Foundation(No.2022TQ0389)the National Natural Science Foundation of China(No.82303693)the National Postdoctoral Program for Innovative Talents(No.BX2021386)。
文摘Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.
基金supported by grants from the National Natural Science Foundation of China(No.82172741)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.
基金supported by the National Natural Science Foundation of China(No.82373380,Xinhua Xie).
文摘Objectives:Deubiquitinase OTUB2 plays a critical role in the progression of various tumors.However,its specific role in triple-negative breast cancer(TNBC)remains unclear.This study aims to elucidate the biological function of OTUB2 in TNBC and uncover the underlying mechanisms.Methods:First,we found that the expression of OTUB2 was upregulated in TNBC by bioinformatics analysis,we then validated its expression in TNBC tissues and cells using immunohistochemistry(IHC)and qPCR and plotted the survival curves by Kaplan-Meier method.Gene set enrichment analysis(GSEA)suggested that OTUB2 may be involved in tumor proliferation and metastasis.Further functional assays,including Cell Counting Kit-8(CCK-8),colony formation,Transwell,and wound healing assays,were performed to assess the effects of OTUB2 overexpression and knockdown on TNBC cell proliferation and migration.Additionally,UbiBrowser 2.0 was used to identify OTUB2 substrate proteins and western blotting was conducted to clarify the molecular mechanisms involved.Results:Our results demonstrated that OTUB2 expression was elevated in TNBC and associated with poor prognosis.Overexpression of OTUB2 enhanced the proliferation and migration of TNBC cells,while its knockdown inhibited these processes.Moreover,OTUB2 stabilized tumor necrosis factor receptor-associated factor 6(TRAF6)by deubiquitinating it,leading to activation of the protein kinase B(AKT)pathway.Conclusions:OTUB2 exerts its promoting effects on the progression of TNBC by activating the TRAF6/AKT pathway.
基金supported by grants from the National Natural Science Foundation of China(No.82373303,No.82072922,No.82403750)a grant from the Natural Science Foundation of Shanghai(No.24ZR1412600)。
文摘Objective:Lymphovascular invasion(LVI)is a crucial step in metastasis and is closely associated with poor prognosis in patients with breast cancer.However,its clinical and molecular characteristics remain insufficiently defined.We aimed to identify molecular targets for LVI-positive(LVI+)breast cancer and predict patient prognosis via the analysis of genomic variations using targeted sequencing.Methods:We established a large-scale targeted sequencing cohort of 4,079 breast cancer samples,which included 3,159 early-stage and locally advanced patients with available LVI statuses.Comparisons of somatic mutation frequencies and germline pathogenic/likely pathogenic(P/LP)mutation frequencies,mutational signature analyses,and mutual exclusivity and co-occurrence analyses were performed to identify key genomic features involved in LVI+patients.Additionally,Kaplan-Meier survival analysis was conducted to further explore the prognostic value of co-mutations in LVI+cases.Results:We observed that LVI+patients with the hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and triple-negative breast cancer(TNBC)subtypes exhibited worse disease-free survival.Notably,HR+/HER2-and HER2+breast cancer patients with LVI displayed distinct genomic features compared with LVI-tumors.Specifically,LVI+HR+/HER2-tumors exhibited greater frequencies of somatic mutations in TP53 and ESR1,germline BRCA2 P/LP variations,and an enrichment of clock-like single-base substitution(SBS)1 mutational signatures.In contrast,LVI+HER2+tumors demonstrated a higher incidence of somatic PIK3CA mutations and increased activity of the apolipoprotein B m RNA editing enzyme catalytic polypeptide(APOBEC)-associated SBS2 signature.Furthermore,we revealed that the co-mutation of TP53 and NF1 could serve as a potential prognostic marker for LVI+HR+/HER2-patients.Conclusions:Our findings provide a comprehensive overview of the genomic characteristics of LVI in breast cancer,thereby offering insights that may help in refining precision treatment strategies for LVI+breast cancer patients.
基金supported financially by the National Nature Science Foundation of China(No.82373355,No.82172703,No.82303856,and No.82473505)the Discipline Leader Project of Shanghai Municipal Health Commission(No.2022XD013)the AoXiang Project of Shanghai Anti-Cancer Association(No.SACA-AX202302).
文摘The choice of biopsy method is critical in diagnosing prostate cancer(PCa).This retrospective cohort study compared systematic biopsy(SB)or cognitive fusion-targeted biopsy combined with SB(CB)in detecting PCa and clinically significant prostate cancer(csPCa).Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center(Shanghai,China)between January 2019 and December 2023 were analyzed.Propensity score matching(PSM)was used to balance baseline characteristics,and detection rates were compared before and after PSM.Subgroup analyses based on prostate-specific antigen(PSA)levels and Prostate Imaging-Reporting and Data System(PI-RADS)scores were performed.Primary and secondary outcomes were the detection rates of PCa and csPCa,respectively.Of 2572 men,1778 were included in the PSM analysis.Before PSM,CB had higher detection rates for both PCa(62.9%vs 52.4%,odds ratio[OR]:1.54,P<0.001)and csPCa(54.9%vs 43.3%,OR:1.60,P<0.001)compared to SB.After PSM,CB remained superior in detecting PCa(63.1%vs 47.9%,OR:1.86,P<0.001)and csPCa(55.0%vs 38.2%,OR:1.98,P<0.001).In patients with PSA 4–12 ng ml−1(>4 ng ml-1 and≤12 ng ml-1,which is also applicable to the following text),CB detected more PCa(59.8%vs 40.7%,OR:2.17,P<0.001)and csPCa(48.1%vs 27.7%,OR:2.42,P<0.001).CB also showed superior csPCa detection in those with PI-RADS 3 lesions(32.1%vs 18.0%,OR:2.15,P=0.038).Overall,CB significantly improves PCa and csPCa detection,especially in patients with PSA 4–12 ng ml−1 or PI-RADS 3 lesions.
基金supported by the National Key Research and Development Project of China(Grant No.2021YFF1201300 and 2021YFF1201302)the Shanghai Committee of Science and Technology(Grant No.24DX2800100)the Institutional Projects of SIBPT(Grant No.YZ2024-07)。
文摘Objective:While immunotherapy holds great potential for triple-negative breast cancer(TNBC),the lack of non-invasive biomarkers to identify beneficiaries limits the application.Methods:Paired baseline,on-treatment,and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center(FUSCC)for sequential high-precision proteomic profiling.Results:ARG1,NOS3,and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC.Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment.Furthermore,the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.Conclusions:The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.
基金supported by the National Key Research and Development Program of China (No. 2020YFA0112304)the National Natural Science Foundation of China (No. 82373167, 82341003 and 92159301)+4 种基金the Natural Science Foundation of Shanghai (No. 22ZR1479200)the Shanghai Key Laboratory of Breast Cancer (No. 12DZ2260100)the SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (No. SHDC12 021103)Shanghai Medical Innovation Research Project (No. 22Y11912700)Shanghai Anticancer Association EYAS PROJECT (No. SACA-CY22A05)
文摘Objective:Recurrence continues to be a pivotal challenge among hormone receptor-positive(HR^(+))/human epidermal growth factor receptor 2^(−)negative(HER2^(−))breast cancers.In the international consensus guidelines,HR^(+)/HER2^(−)breast cancer relapse patterns are divided into three distinct types:primary resistant,secondary resistant,and endocrine sensitive.However,owing to the lack of cohorts with treatment and follow-up data,the heterogeneity among different recurrence patterns remains uncharted.Current treatments still lack precision.Methods:This analysis included data from a large-scale multiomics study of a HR^(+)/HER2^(−)breast cancer cohort(n=314).Through the analysis of transcriptomics(n=312),proteomics(n=124),whole-exome sequencing(n=290),metabolomics(n=217),and digital pathology(n=228)data,we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.Results:We explored distinct clinicopathological characteristics,biological heterogeneity,and potential therapeutic strategies for recurrence.Based on a shared relapse signature,we stratified patients into high-and lowrecurrence-risk groups.Patients with different relapse patterns presented unique molecular features in primary tumors.Specifically,receptor tyrosine kinase(RTK)pathway activation in the primary resistant group suggested the utility of RTK inhibitors,whereas mammalian target of rapamycin(mTOR)and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors.Interestingly,the endocrine-sensitive group displayed a quiescent state and high genomic instability,suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase(PARP)inhibitors could be effective strategies.Conclusions:These findings illuminate the clinicopathological and molecular landscape of HR^(+)/HER2^(−)breast cancer patients with distinct recurrence patterns,highlighting potential targeted therapies.
基金Supported by the National Natural Science Foundation of China,No.82072034。
文摘BACKGROUND No clear guidelines for long-term postoperative maintenance therapy have been established for patients with lung oligometastases from colorectal cancer(CRC)who achieve radiological no evidence of disease after radiofrequency ablation(RFA)treatment.We compared the outcomes of patients with lung oligometa-stases from CRC after RFA plus maintenance capecitabine with RFA alone.AIM To determine whether adding capecitabine to RFA improves prognosis compared with RFA alone.METHODS This multicenter retrospective study included consecutive patients from two tertiary cancer centers treated for pulmonary oligometastases from CRC between 2016 and 2023.Subjects were assigned to RFA plus capecitabine(combined)or RFA alone(only RFA)groups.Primary outcomes included overall survival(OS)and progression-free survival(PFS)survival and the secondary outcome was local tumor progression(LTP).The OS,PFS,and LTP rates were compared between the two groups.In addition,prognostic factors were identified using univariate and multivariate analyses.RESULTS Combination therapy(RFA+capecitabine,n=148)and RFA monotherapy(n=99)were compared in patients with CRC and lung metastases.The median OS was 37.8 months(22.4,50.3),the PFS was 18.7 months(13.0,36.5),and the LTP was 31.5 months(20.0,52.4)in the Only RFA group.The OS increased significantly(P=0.011)and the LTP decreased at all time points(P<0.001)in the combined group.The multivariate cox analysis revealed that combined chemotherapy significantly improved OS,with hazard ratios ranging from 0.29 to 0.35(all P<0.015)after adjusting for demographic,tumor,and treatment-related factors.The risk of death was consistently lower in the combination therapy group compared to RFA monotherapy.CONCLUSION RFA prolongs survival and local control in patients with CRC pulmonary oligometastases.Adjuvant capecitabine increases OS and reduces LTP compared to RFA alone,but PFS did not significantly change.
基金sponsored by Betta Pharmaceuticals Co.,Ltdsupported by the Basic and Applied Basic Research Foundation of Guangdong Province(2024A1515030227,Ning Li).
文摘The efficacy,safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)for patients with resected EGFR-mutated non-small-cell lung cancer(NSCLC)were not known until 2014,when this study was initiated.In this phase 3 ICTAN trial(GASTO1002,NCT01996098),patients with completely resected,EGFR-mutated,stage Ⅱ-ⅢA NSCLC after adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib(125 mg,three times daily)for 12 months,to receive icotinib for 6 months,or to undergo observation.The primary endpoint was disease-free survival(DFS).This trial was terminated early.A total of 251 patients were randomized.Adjuvant icotinib for 12 months significantly improved DFS(hazard ratio[HR]:0.40,95%confidence interval[CI],0.27–0.61;P<0.001)and overall survival(OS;HR:0.55,95%CI,0.32–0.96;P=0.032)compared with observation.Adjuvant icotinib of 6 months also significantly improved DFS(HR:0.41,95%CI,0.27–0.62;P<0.001)and OS(HR:0.56,95%CI,0.32–0.98;P=0.038)compared with observation.Adjuvant icotinib for 12 months did not improve DFS(HR:0.97;P=0.89)or OS(HR:1.00;P=0.99)compared with 6 months of this drug.Rates of adverse events of grade 3 or higher were 8.3%,6.0%and 2.4%for the 12-month icotinib,6-month icotinib,and observation groups,respectively.Adjuvant icotinib for 12 months or 6 months following adjuvant chemotherapy improved DFS and OS compared with observation in patients with resected EGFR-mutated stage Ⅱ-ⅢA NSCLC with a manageable safety profile,supporting it as a potential treatment option.
