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
Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is co...Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.展开更多
Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,...Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.展开更多
Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrenc...Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.展开更多
Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to p...Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease.Methods:A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts.Multivariate logistic regression analysis was used to construct the nomogram.Model performance was evaluated by discrimination,calibration,and clinical usefulness.An independent multicenter cohort consisting of 250 patients was used for external validation.Results:A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9),CA125,CA50,and CA242.A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis:risk score of the four-marker signature,computed tomography-reported LN status,and clinical tumor stage.The prediction model exhibited good discrimination ability,with C-indexes of 0.806,0.742 and 0.763 for the development,internal validation,and external validation cohorts,respectively.The model also showed good calibration and clinical usefulness.A cut-off value(0.72)for the probability of LN metastasis was determined to separate low-risk and high-risk patients.Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status.Conclusions:This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.展开更多
To evaluate whether prostate volume(PV)would provide additional predictive utility to the prostate health index(phi)for predicting prostate cancer(PCa)or clinically significant prostate cancer,we designed a prospectiv...To evaluate whether prostate volume(PV)would provide additional predictive utility to the prostate health index(phi)for predicting prostate cancer(PCa)or clinically significant prostate cancer,we designed a prospective,observational multicenter study in two prostate biopsy cohorts.Cohort 1 included 595 patients from three medical centers from 2012 to 2013,and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014.Area under the receiver operating characteristic curves(AUC)and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models.Linear regression analysis showed that both total prostate-specific antigen(tPSA)and free PSA(fPSA)were significantly correlated with PV(all P<0.05).[-2]proPSA(p2PSA)was significantly correlated with PV in Cohort 2(P<0.001)but not in Cohort 1(P=0.309),while no significant association was observed between phi and PV.When combining phi with PV,phi density(PHID)and another phi derivative(PHIV,calculated as phi/PV°5)did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort 2.Logistic regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa(all P<0.05);however,PV did not provide additional predictive value to phi when combining these derivatives in a regression model(all models vs phi were not statistically significant,all P>0.05).In conclusion,PV-based derivatives(both PHIV and PHID)and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.展开更多
Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had ...Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.展开更多
Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in Chi...Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.展开更多
Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer...Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.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: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
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
Objective:Large-scale CRISPR screens have identified essential genes across cancer cell lines,but links between tumor functional properties and specific dependencies require investigation to reveal the mechanisms unde...Objective:Large-scale CRISPR screens have identified essential genes across cancer cell lines,but links between tumor functional properties and specific dependencies require investigation to reveal the mechanisms underlying dependencies and broaden understanding of targeted therapy.Methods:We selected 47 breast cancer cell lines from the Cancer Cell Line Encyclopedia(CCLE)with multi-omics data including gene dependency;somatic mutations;copy number alterations;and transcriptomic,proteomic,metabolomic,and methylation data.We established a dependency marker association(DMA)analytic pipeline by using linear regression modeling to assess associations between 3,874 representative gene dependencies and multi-omics markers.Additionally,we conducted non-negative matrix factorization clustering,to stratify breast cancer cell lines according to gene dependency features,and investigated cluster-specific DMAs.Results:We interpreted valuable DMAs according to two primary aspects.First,dependencies associated with gain-of-function alterations revealed addiction to lactate transporter SLC16A3,thus suggesting a promising therapeutic target.Second,dependencies associated with loss-of-function alterations included synthetic lethality(SL),collateral SL,and prioritized metabolic SL,encompassing paralog SL(e.g.,IMPDH1 and IMPDH2),single pathway SL(e.g.,GFPT1 and UAP1),and alternative pathway SL(e.g.,GPI and PGD).DMA analysis of the two clusters with divergent dependency signatures demonstrated that cluster1 cell lines exhibited extensive metabolism with mitochondrial protein dependencies,whereas cluster2 displays enhanced cell signaling,and reliance on DNA replication and membrane organelle regulators.Conclusions:We established a DMA analysis pipeline linking the gene dependencies of breast cancer cell lines to multi-omics characteristics,thus elucidating the underpinnings of tumor dependencies and offering a valuable resource for developing novel precision treatment strategies incorporating relevant markers.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
In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein lig...In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma.Compared with TACE alone,the triple therapy reduced the resistance rate from 38.8%to 9.7%and increased the median progression-free survival and median overall survival by 92.3%and 26.8%,respectively.TACE induces tumor antigen release and upregulates programmed death protein ligand 1,activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration,forming a dynamic synergistic network of embolization-immune activation-vascular inhibition.The maximum tumor diameter,capsule loss,and bilateral distribution were identified as independent predictors.This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment.In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through crossomics strategies,further explore biomarkers,optimize treatment sequences,and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.展开更多
Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and ...Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.展开更多
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 National Natural Science Foundation of China (82072693, 81902417 and 82172884)the Scientific Innovation Project of Shanghai Education Commit-tee (2019-01-07-00-07-E00057)+2 种基金Clinical and Scientific Innovation Project of Shanghai Hospital Development Center (SHDC12018109)Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1006A)National Key Research and Development Program of China (2020YFA0803202)。
文摘Background: Open pancreaticoduodenectomy(OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy(LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. Methods: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. Results: A total of 63 patients underwent pancreaticoduodenectomy(PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss(200 vs. 400 m L, P < 0.001), lower proportion of intraoperative blood transfusion(16.0% vs. 39.5%, P = 0.047), longer operation time(390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay(11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively( P = 0.927). Conclusions: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.
文摘Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.
文摘Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.
基金supported by grants from the National Natural Science Foundation of China(81772555,81802352 and 81902428)the National Science Foundation for Distinguished Young Scholars of China(81625016)+4 种基金the Shanghai Sailing Program(19YF1409400 and 20YF1409000)the Shanghai Rising-Star Program(20QA1402100)the Shanghai Anticancer Association Young Eagle Program(SACA-CY19A06)the Clinical and Scientific Innovation Project of Shanghai Hospital Development Center(SHDC12018109 and SHDC12019109)the Scientific Innovation Project of Shanghai Education Committee(2019-01-07-00-07-E00057)。
文摘Background:Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer.This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease.Methods:A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts.Multivariate logistic regression analysis was used to construct the nomogram.Model performance was evaluated by discrimination,calibration,and clinical usefulness.An independent multicenter cohort consisting of 250 patients was used for external validation.Results:A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9),CA125,CA50,and CA242.A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis:risk score of the four-marker signature,computed tomography-reported LN status,and clinical tumor stage.The prediction model exhibited good discrimination ability,with C-indexes of 0.806,0.742 and 0.763 for the development,internal validation,and external validation cohorts,respectively.The model also showed good calibration and clinical usefulness.A cut-off value(0.72)for the probability of LN metastasis was determined to separate low-risk and high-risk patients.Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status.Conclusions:This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.
基金by grants from the innovation grant by Shanghai Hospital Development Center(SHDC12015105)to Jianfeng Xuthe National Natural Science Foundation of China(Grant No.81772741)+3 种基金Shanghai Rising-Star Program(Grant No.18QA1402800)the“Chen Guang”project supported by Shanghai Municipal Education CommissionShanghai Education Development FoundationShanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(Grant No.20181701)to Rong Na.
文摘To evaluate whether prostate volume(PV)would provide additional predictive utility to the prostate health index(phi)for predicting prostate cancer(PCa)or clinically significant prostate cancer,we designed a prospective,observational multicenter study in two prostate biopsy cohorts.Cohort 1 included 595 patients from three medical centers from 2012 to 2013,and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014.Area under the receiver operating characteristic curves(AUC)and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models.Linear regression analysis showed that both total prostate-specific antigen(tPSA)and free PSA(fPSA)were significantly correlated with PV(all P<0.05).[-2]proPSA(p2PSA)was significantly correlated with PV in Cohort 2(P<0.001)but not in Cohort 1(P=0.309),while no significant association was observed between phi and PV.When combining phi with PV,phi density(PHID)and another phi derivative(PHIV,calculated as phi/PV°5)did not outperform phi for predicting PCa or clinically significant PCa in either Cohort 1 or Cohort 2.Logistic regression analysis also showed that phi and PV were independent predictors for both PCa and clinically significant PCa(all P<0.05);however,PV did not provide additional predictive value to phi when combining these derivatives in a regression model(all models vs phi were not statistically significant,all P>0.05).In conclusion,PV-based derivatives(both PHIV and PHID)and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.
文摘Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.
文摘Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.
基金supported by the National Natural Science Foundation of China(Grant No.81825016,81772719,81772728,81572514)the Key Areas Research and Development Program of Guangdong(Grant No.2018B010109006)Medical Scientific Research Foundation of Guangdong Province(Grant No.A2018388).
文摘Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.
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.
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 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 grants from the National Key Research and Development Project of China(Grant No.2020YFA0112304)the National Natural Science Foundation of China(Grant Nos.91959207 and 82202883).
文摘Objective:Large-scale CRISPR screens have identified essential genes across cancer cell lines,but links between tumor functional properties and specific dependencies require investigation to reveal the mechanisms underlying dependencies and broaden understanding of targeted therapy.Methods:We selected 47 breast cancer cell lines from the Cancer Cell Line Encyclopedia(CCLE)with multi-omics data including gene dependency;somatic mutations;copy number alterations;and transcriptomic,proteomic,metabolomic,and methylation data.We established a dependency marker association(DMA)analytic pipeline by using linear regression modeling to assess associations between 3,874 representative gene dependencies and multi-omics markers.Additionally,we conducted non-negative matrix factorization clustering,to stratify breast cancer cell lines according to gene dependency features,and investigated cluster-specific DMAs.Results:We interpreted valuable DMAs according to two primary aspects.First,dependencies associated with gain-of-function alterations revealed addiction to lactate transporter SLC16A3,thus suggesting a promising therapeutic target.Second,dependencies associated with loss-of-function alterations included synthetic lethality(SL),collateral SL,and prioritized metabolic SL,encompassing paralog SL(e.g.,IMPDH1 and IMPDH2),single pathway SL(e.g.,GFPT1 and UAP1),and alternative pathway SL(e.g.,GPI and PGD).DMA analysis of the two clusters with divergent dependency signatures demonstrated that cluster1 cell lines exhibited extensive metabolism with mitochondrial protein dependencies,whereas cluster2 displays enhanced cell signaling,and reliance on DNA replication and membrane organelle regulators.Conclusions:We established a DMA analysis pipeline linking the gene dependencies of breast cancer cell lines to multi-omics characteristics,thus elucidating the underpinnings of tumor dependencies and offering a valuable resource for developing novel precision treatment strategies incorporating relevant markers.
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Supported by the National Natural Science Foundation of China,No.82404058Shanghai Municipal Commission of Health and Family Planning,No.2024ZZ2049Beijing Xisike Clinical Oncology Research Foundation,No.Y-HS202401-0011.
文摘In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma.Compared with TACE alone,the triple therapy reduced the resistance rate from 38.8%to 9.7%and increased the median progression-free survival and median overall survival by 92.3%and 26.8%,respectively.TACE induces tumor antigen release and upregulates programmed death protein ligand 1,activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration,forming a dynamic synergistic network of embolization-immune activation-vascular inhibition.The maximum tumor diameter,capsule loss,and bilateral distribution were identified as independent predictors.This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment.In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through crossomics strategies,further explore biomarkers,optimize treatment sequences,and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.
基金supported by Shanghai Science and Technology Commission,China(No.21S11902100)Shanghai Municipal Health Commission Scientific Research Project(No.202140308)+3 种基金Clinical Research Project of Tongji Hospital of Tongji University[No.ITJ(ZD)2209]Shanghai Tongji Hospital National Natural Science Foundation Cultivation Project(No.GJPY2216)Shanghai Medical Innovation Research Special Foundation(No.23Y11908800)CSCO-Haosen Oncology Research Fund(No.Y-HS202301-0096).
文摘Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.
