BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper...Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohor...BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.展开更多
Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with near...Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.展开更多
BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up da...BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.展开更多
BACKGROUND Cardiac metastatic tumors(CMTs)are rare yet pose significant medical concerns.Clinical studies on CMT are limited,particularly those involving multicenter data analysis.AIM To systematically analyze the eti...BACKGROUND Cardiac metastatic tumors(CMTs)are rare yet pose significant medical concerns.Clinical studies on CMT are limited,particularly those involving multicenter data analysis.AIM To systematically analyze the etiology,sources,classification,treatment,and prognosis of CMT.METHODS A total of 226 CMT patients from two centers(2013 to 2023)were reviewed,and 153 tumor patients from China Health and Retirement Longitudinal Study were used as controls.The survival rates of 96 CMT patients were tracked through medical records and telephone follow-ups.Logistic regression and survival analyses were conducted to characterize CMT.RESULTS CMTs were predominantly male(67.26%vs 39.47%,P<0.001).Intracardiac metastasis patients had worse heart and coagulation function than pericardial metastasis patients(prothrombin time:13.90 vs 13.30,P=0.002),D-dimer levels(2.16 vs 0.85,P=0.001),B-type natriuretic peptide(BNP)levels(324.00 vs 136.50,P=0.004),and troponin levels(5.35 vs 0.03,P<0.001)).Lung and liver cancers were the predominant primary tumor types in CMT.Patients with lung cancer(76.40%vs 30.77%)and thymoma(7.45%vs 1.54%)exhibited a higher prevalence of pericardial metastasis,while those with liver cancer(35.38%vs 0.62%)showed a higher prevalence of intracardiac metastasis.Overall survival was better for pericardial metastasis than for intracardiac metastasis patients(median survival:419 days vs 129 days,log-rank test P=0.0029).Cox proportional hazards model revealed that advanced age[hazard ratio(HR)=1.034,95%confidence interval(95%CI):1.011-1.057]and higher BNP and troponin levels(HR=1.011,95%CI:1.004-1.018)were associated with worse survival.Surgery significantly improved the survival rate of patients.The median survival time was 275 days for patients who did not undergo surgery and 708 days for those who had surgery(log-rank test P=0.0128)CONCLUSION Clinicians should consider CMT in the male lung or liver cancer patients with cardiac symptoms.Abnormal coagulation,impaired heart function,tumor location,and age are key prognostic factors for CMT.Surgical intervention is the preferred treatment option,as it significantly prolongs median survival.展开更多
BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into fi...BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into first-line standard-of-care(SOC)therapy for metastatic colorectal cancer(mCRC).However,data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.AIM To evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.METHODS Four biomedical databases(PubMed,Embase,Cochrane Library,Web of Science)were systematically interrogated to identify eligible studies published up to October 12,2024.The analysis focused on evaluating the primary outcome of overall survival(OS)in the mCRC population with secondary outcomes of progression-free survival(PFS),overall response rate(ORR),and incidence rate of grade≥3 adverse events.Additionally,we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient(MSS/pMMR)subpopulation,based on a subset of the included studies.Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.RESULTS This pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy.The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations[hazard ratio(HR)=0.8,95%confidence interval(CI):0.65-0.98,P=0.033].Nevertheless,the MSS/pMMR subgroup showed no PFS benefit(HR=0.83,95%CI:0.67-1.03,P=0.091),and no cohort exhibited OS improvement(intention-to-treat:HR=0.84,95%CI:0.66-1.05,P=0.124;MSS/pMMR:HR=0.79,95%CI:0.60-1.03,P=0.083).Comparable outcomes were observed for ORR(risk ratio=1.03,95%CI:0.90-1.17,P=0.711)and incidence rate of grade≥3 adverse events(risk ratio=1.12,95%CI:0.93-1.36,P=0.245)between treatment arms.CONCLUSION The findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR.Existing clinical data remain inadequate to establish OS advantages,particularly in patients with MSS/pMMR,despite exhibiting manageable toxicity profiles.Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available the...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available therapeutic options is typically low.CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2(HER2)gene has shown responsiveness to HER2-targeted therapies.CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability,identified through tumor sequencing,along with HER2 overexpression detected by immunohistochemistry.She exhibited an excellent response to disitamab vedotin-containing therapy.To our knowledge,this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy.CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overex-pressing mCRC,offering patients an additional treatment option.展开更多
BACKGROUND Pseudoachalasia mimics primary achalasia in symptoms and diagnostic findings,as observed in gastroscopy and barium swallow studies.However,pseudoachalasia,often associated with malignancies like metastatic ...BACKGROUND Pseudoachalasia mimics primary achalasia in symptoms and diagnostic findings,as observed in gastroscopy and barium swallow studies.However,pseudoachalasia,often associated with malignancies like metastatic breast cancer,requires prompt differentiation to avoid misdiagnosis and inappropriate treatment.This report highlights a rare case of pseudoachalasia secondary to metastatic breast cancer and highlights the diagnostic value of esophageal motility changes.CASE SUMMARY A 52-year-old woman presented with a one-year history of intermittent dysphagia following breast cancer surgery.Initial examinations suggested achalasia,but the patient’s high-resolution manometry(HRM)results showed a rapid shift from ineffective esophageal motility to type Ⅱ achalasia within four months.Further investigations revealed metastatic adenocarcinoma of the cardia,originating from the breast.CONCLUSION In patients with a history of malignancy,rapidly evolving esophageal motility abnormalities should raise suspicion of pseudoachalasia.HRM plays a crucial role in differentiating between primary and secondary achalasia.Early diagnosis through advanced imaging and pathology is essential for proper management.展开更多
Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medici...Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medicine in treating BRAF mutant mCRC has garnered increasing attention.Recent studies indicate that combining traditional Chinese and modern Western medical approaches not only extend survival but also reduces the risk of mortality in patients with BRAF V600E mutant mCRC.This approach is particularly effective for colorectal cancer patients who have right-sided colon involvement,liver metastasis,or a history of radiotherapy or chemotherapy.In this treatment combination,traditional Chinese medicine may offer symptomatic relief and improve quality of life,while Western medicine targets the disease more aggressively with advanced pharmacological agents.Ongoing research is crucial to further elucidate the mechanisms underlying these benefits and to optimize treatment protocols.展开更多
BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings....BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.展开更多
Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug lo...Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.展开更多
BACKGROUND Colorectal cancer(CRC)represents a major global public health issue,ranking as the third most common cancer worldwide.Given the substantial prevalence of CRC,there is a critical need to identify precise pro...BACKGROUND Colorectal cancer(CRC)represents a major global public health issue,ranking as the third most common cancer worldwide.Given the substantial prevalence of CRC,there is a critical need to identify precise prognostic and predictive biomar-ker tools for better treatment outcomes.Phase angle(PA)has been proposed as a prognostic marker in various non-malignant and malignant clinical conditions.AIM To investigate the relationship between PA and survival outcomes in the first-line treatment of metastatic CRC(mCRC).METHODS In this prospective observational study,we obtained data on patients who started first-line systemic chemotherapy from the beginning of 2020 until the end of 2022.The PA,assessed by the bioelectrical impedance analysis scale,was evaluated as a possible prognostic factor for treatment outcomes,which were measured as pro-gression-free survival(PFS)and objective response rate(ORR).RESULTS Using the cut-point value for PA set at 4.60°,144 patients were divided into two cohorts.The high PA group of patients exhibited a significantly longer median PFS than the low PA group,14.8 vs 10.5 months,respectively.No difference in ORR was observed.However,patients with PA≥4.60°had a higher disease control rate.CONCLUSION PA represents a novel and objective pre-chemotherapy prognostic factor to identify mCRC patients who are at increased risk of a worse survival outcome.展开更多
BACKGROUND Gastric cancer(GC)poses a significant threat to public health.However,the clinicopathological features and tumor biological behaviors vary among the GC patients,leading to individual variations in lymph nod...BACKGROUND Gastric cancer(GC)poses a significant threat to public health.However,the clinicopathological features and tumor biological behaviors vary among the GC patients,leading to individual variations in lymph node metastasis.Consequently,the stratification of lymph node dissection according to the specific type,particularly upper GC,has emerged as a prominent area of research.AIM To investigate the distribution of metastatic lymph nodes in patients with upper and lower GC and to analyze the differences in related pathological elements and prognosis.METHODS Differential analysis between upper and lower GC patients with various clinicopathological factors was performed using the chi-square test and rank-sum regression models were used to analyze risk factors affecting patient prognosis.The Kaplan-Meier method was used to construct survival curves associated with prognostic risk factors for GC.RESULTS Significant differences were observed between the two GC populations regarding tumor diameter,histological grade,pT stage,pN stage,tumor-node-metastasis(pTNM)stage,vascular invasion,and adjuvant chemotherapy usage(all P<0.05).Lymph node metastasis rates were highest for Siewert type II patients in groups Nos.1,3,2 and 7;for Siewert type III patients in groups Nos.3,1,2 and 7;and for other/unclassified patients in groups Nos.1,3,7,2.In the lower GC samples,the sequences were Nos.3,6,7,4.Pathological type,pT stage,pTNM stage,and positive vascular invasion were independent risk factors for development of lymph node metastasis.Age,pathological type,pT stage,pN stage,pTNM stage,vascular invasion,and absence of adjuvant chemotherapy were identified as independent prognostic factors.CONCLUSION Upper GC showed a significantly higher malignancy grade and different lymph node metastasis pattern than lower GC.展开更多
Metastatic urothelial carcinoma(mUC)is a challenging malignancy with historically limited treatment options.Advances in understanding its biology have enabled the development of innovative therapies,including immune c...Metastatic urothelial carcinoma(mUC)is a challenging malignancy with historically limited treatment options.Advances in understanding its biology have enabled the development of innovative therapies,including immune checkpoint inhibitors and antibody-drug conjugates(ADCs).ADCs,such as enfortumab vedotin,sacituzumab govitecan,and trastuzumab deruxtecan,represent transformative advancements,offering targeted delivery of cytotoxic agents.This review highlights the evolving role of ADCs in mUC,examining their mechanisms,clinical efficacy,patient selection criteria,genetic insights,and future directions in personalized treatment strategies.展开更多
BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcino...BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.展开更多
BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in m...BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in microsatellite stable(MSS)metastatic colorectal cancer(mCRC).However,it is still unclear which therapy can bring better prognosis.AIM To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.METHODS This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital.Patients with MSS mCRC who had received at least the second line treatment were eligible.Propensity score(PS)would be calculated to balance the baseline characteristics of two cohorts.Progression-free survival(PFS)was set as the primary endpoint.The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios(HRs)and 95%confidence intervals(CIs).Landmark analysis was performed to create segmented survival curves,studying the impact of treatment regimen on prognosis during different follow-up periods.RESULTS Between July 2019 and March 2025(data cutoff),127 eligible patients were enrolled,with 88 and 39 patients assigned to the TP and TB cohorts,respectively,based on treatment allocation.At a global median follow-up of 9.73 months,the crude median PFS was 3.9 months(95%CI:3.03-5.53)in the TP cohort vs 4.17 months(95%CI:2.87-5.6)in the TB cohort,yielding a nonsignificant HR of 1.43(95%CI:0.94-2.18,P=0.092;TB as reference).Multivariate Cox regression analysis,adjusted for sex,age>60 years,Eastern Cooperative Oncology Group performance status,RAS mutation,primary tumor location(left vs right),number of metastatic organs(liver/lung),and treatment line(≥3rd line),demonstrated an adjusted HR of 1.23(95%CI:0.80-1.88,P=0.348).PS-based analyses using three methodologies:Inverse probability weighting,PS matching(post-matching n=55 vs 30),and PS-adjusted multivariate Cox regression.These analyses revealed consistent nonsignificant trends favoring TB,with HRs for TP of 1.26(95%CI:0.76-2.10,P=0.077),1.42(95%CI:0.87-2.34,P=0.164),and 1.26(95%CI:0.76-2.10,P=0.367),respectively.Notably,landmark PFS analyses at 90,120,and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints(P=0.048,0.031,and 0.035,respectively),suggesting sustained clinical benefits in TP responders.CONCLUSION TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses.However,patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB.Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments,this regimen could provide additional prolonged clinical benefits,which warrants further validation through large-scale cohort investigations.展开更多
BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline ca...BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.展开更多
Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries...Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.展开更多
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
基金Supported by Department of Biotechnology,Government of India,No.RLS/BT/Re-entry/05/2012.
文摘Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
基金Supported by National Natural Science Foundation of China,No.82174461Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0201-22Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01811.
文摘BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.
文摘Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,by the Ministry of Health&Welfare,Republic of Korea,No.RS-2018-KH049509the 2022 Cancer Research Support Project from the Korea Foundation for Cancer Research,No.CB-2022-A-3.
文摘BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.
文摘BACKGROUND Cardiac metastatic tumors(CMTs)are rare yet pose significant medical concerns.Clinical studies on CMT are limited,particularly those involving multicenter data analysis.AIM To systematically analyze the etiology,sources,classification,treatment,and prognosis of CMT.METHODS A total of 226 CMT patients from two centers(2013 to 2023)were reviewed,and 153 tumor patients from China Health and Retirement Longitudinal Study were used as controls.The survival rates of 96 CMT patients were tracked through medical records and telephone follow-ups.Logistic regression and survival analyses were conducted to characterize CMT.RESULTS CMTs were predominantly male(67.26%vs 39.47%,P<0.001).Intracardiac metastasis patients had worse heart and coagulation function than pericardial metastasis patients(prothrombin time:13.90 vs 13.30,P=0.002),D-dimer levels(2.16 vs 0.85,P=0.001),B-type natriuretic peptide(BNP)levels(324.00 vs 136.50,P=0.004),and troponin levels(5.35 vs 0.03,P<0.001)).Lung and liver cancers were the predominant primary tumor types in CMT.Patients with lung cancer(76.40%vs 30.77%)and thymoma(7.45%vs 1.54%)exhibited a higher prevalence of pericardial metastasis,while those with liver cancer(35.38%vs 0.62%)showed a higher prevalence of intracardiac metastasis.Overall survival was better for pericardial metastasis than for intracardiac metastasis patients(median survival:419 days vs 129 days,log-rank test P=0.0029).Cox proportional hazards model revealed that advanced age[hazard ratio(HR)=1.034,95%confidence interval(95%CI):1.011-1.057]and higher BNP and troponin levels(HR=1.011,95%CI:1.004-1.018)were associated with worse survival.Surgery significantly improved the survival rate of patients.The median survival time was 275 days for patients who did not undergo surgery and 708 days for those who had surgery(log-rank test P=0.0128)CONCLUSION Clinicians should consider CMT in the male lung or liver cancer patients with cardiac symptoms.Abnormal coagulation,impaired heart function,tumor location,and age are key prognostic factors for CMT.Surgical intervention is the preferred treatment option,as it significantly prolongs median survival.
文摘BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into first-line standard-of-care(SOC)therapy for metastatic colorectal cancer(mCRC).However,data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.AIM To evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.METHODS Four biomedical databases(PubMed,Embase,Cochrane Library,Web of Science)were systematically interrogated to identify eligible studies published up to October 12,2024.The analysis focused on evaluating the primary outcome of overall survival(OS)in the mCRC population with secondary outcomes of progression-free survival(PFS),overall response rate(ORR),and incidence rate of grade≥3 adverse events.Additionally,we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient(MSS/pMMR)subpopulation,based on a subset of the included studies.Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.RESULTS This pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy.The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations[hazard ratio(HR)=0.8,95%confidence interval(CI):0.65-0.98,P=0.033].Nevertheless,the MSS/pMMR subgroup showed no PFS benefit(HR=0.83,95%CI:0.67-1.03,P=0.091),and no cohort exhibited OS improvement(intention-to-treat:HR=0.84,95%CI:0.66-1.05,P=0.124;MSS/pMMR:HR=0.79,95%CI:0.60-1.03,P=0.083).Comparable outcomes were observed for ORR(risk ratio=1.03,95%CI:0.90-1.17,P=0.711)and incidence rate of grade≥3 adverse events(risk ratio=1.12,95%CI:0.93-1.36,P=0.245)between treatment arms.CONCLUSION The findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR.Existing clinical data remain inadequate to establish OS advantages,particularly in patients with MSS/pMMR,despite exhibiting manageable toxicity profiles.Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes.
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available therapeutic options is typically low.CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2(HER2)gene has shown responsiveness to HER2-targeted therapies.CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability,identified through tumor sequencing,along with HER2 overexpression detected by immunohistochemistry.She exhibited an excellent response to disitamab vedotin-containing therapy.To our knowledge,this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy.CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overex-pressing mCRC,offering patients an additional treatment option.
文摘BACKGROUND Pseudoachalasia mimics primary achalasia in symptoms and diagnostic findings,as observed in gastroscopy and barium swallow studies.However,pseudoachalasia,often associated with malignancies like metastatic breast cancer,requires prompt differentiation to avoid misdiagnosis and inappropriate treatment.This report highlights a rare case of pseudoachalasia secondary to metastatic breast cancer and highlights the diagnostic value of esophageal motility changes.CASE SUMMARY A 52-year-old woman presented with a one-year history of intermittent dysphagia following breast cancer surgery.Initial examinations suggested achalasia,but the patient’s high-resolution manometry(HRM)results showed a rapid shift from ineffective esophageal motility to type Ⅱ achalasia within four months.Further investigations revealed metastatic adenocarcinoma of the cardia,originating from the breast.CONCLUSION In patients with a history of malignancy,rapidly evolving esophageal motility abnormalities should raise suspicion of pseudoachalasia.HRM plays a crucial role in differentiating between primary and secondary achalasia.Early diagnosis through advanced imaging and pathology is essential for proper management.
基金Supported by the Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medicine in treating BRAF mutant mCRC has garnered increasing attention.Recent studies indicate that combining traditional Chinese and modern Western medical approaches not only extend survival but also reduces the risk of mortality in patients with BRAF V600E mutant mCRC.This approach is particularly effective for colorectal cancer patients who have right-sided colon involvement,liver metastasis,or a history of radiotherapy or chemotherapy.In this treatment combination,traditional Chinese medicine may offer symptomatic relief and improve quality of life,while Western medicine targets the disease more aggressively with advanced pharmacological agents.Ongoing research is crucial to further elucidate the mechanisms underlying these benefits and to optimize treatment protocols.
基金Supported by Hebei Provincial Medical Science Research Project Program,No.20240164.
文摘BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.
基金the National Natural Science Foundation of China(32271319 and 32071267)the Science and Technology Department of Jilin Province(YDZJ202301ZYTS537 and 20240402035GH)+1 种基金the Development and Reform Commission of Jilin Province(2023C015)the“Medicine+X”cross-innovation team of Bethune Medical Department of Jilin University“Leading the Charge with Open Competition”construction project(2022JBGS04).
文摘Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
文摘BACKGROUND Colorectal cancer(CRC)represents a major global public health issue,ranking as the third most common cancer worldwide.Given the substantial prevalence of CRC,there is a critical need to identify precise prognostic and predictive biomar-ker tools for better treatment outcomes.Phase angle(PA)has been proposed as a prognostic marker in various non-malignant and malignant clinical conditions.AIM To investigate the relationship between PA and survival outcomes in the first-line treatment of metastatic CRC(mCRC).METHODS In this prospective observational study,we obtained data on patients who started first-line systemic chemotherapy from the beginning of 2020 until the end of 2022.The PA,assessed by the bioelectrical impedance analysis scale,was evaluated as a possible prognostic factor for treatment outcomes,which were measured as pro-gression-free survival(PFS)and objective response rate(ORR).RESULTS Using the cut-point value for PA set at 4.60°,144 patients were divided into two cohorts.The high PA group of patients exhibited a significantly longer median PFS than the low PA group,14.8 vs 10.5 months,respectively.No difference in ORR was observed.However,patients with PA≥4.60°had a higher disease control rate.CONCLUSION PA represents a novel and objective pre-chemotherapy prognostic factor to identify mCRC patients who are at increased risk of a worse survival outcome.
文摘BACKGROUND Gastric cancer(GC)poses a significant threat to public health.However,the clinicopathological features and tumor biological behaviors vary among the GC patients,leading to individual variations in lymph node metastasis.Consequently,the stratification of lymph node dissection according to the specific type,particularly upper GC,has emerged as a prominent area of research.AIM To investigate the distribution of metastatic lymph nodes in patients with upper and lower GC and to analyze the differences in related pathological elements and prognosis.METHODS Differential analysis between upper and lower GC patients with various clinicopathological factors was performed using the chi-square test and rank-sum regression models were used to analyze risk factors affecting patient prognosis.The Kaplan-Meier method was used to construct survival curves associated with prognostic risk factors for GC.RESULTS Significant differences were observed between the two GC populations regarding tumor diameter,histological grade,pT stage,pN stage,tumor-node-metastasis(pTNM)stage,vascular invasion,and adjuvant chemotherapy usage(all P<0.05).Lymph node metastasis rates were highest for Siewert type II patients in groups Nos.1,3,2 and 7;for Siewert type III patients in groups Nos.3,1,2 and 7;and for other/unclassified patients in groups Nos.1,3,7,2.In the lower GC samples,the sequences were Nos.3,6,7,4.Pathological type,pT stage,pTNM stage,and positive vascular invasion were independent risk factors for development of lymph node metastasis.Age,pathological type,pT stage,pN stage,pTNM stage,vascular invasion,and absence of adjuvant chemotherapy were identified as independent prognostic factors.CONCLUSION Upper GC showed a significantly higher malignancy grade and different lymph node metastasis pattern than lower GC.
文摘Metastatic urothelial carcinoma(mUC)is a challenging malignancy with historically limited treatment options.Advances in understanding its biology have enabled the development of innovative therapies,including immune checkpoint inhibitors and antibody-drug conjugates(ADCs).ADCs,such as enfortumab vedotin,sacituzumab govitecan,and trastuzumab deruxtecan,represent transformative advancements,offering targeted delivery of cytotoxic agents.This review highlights the evolving role of ADCs in mUC,examining their mechanisms,clinical efficacy,patient selection criteria,genetic insights,and future directions in personalized treatment strategies.
基金Supported by the National Key Research and Development Program of China,No.2023YFF1204702the National Natural Science Foundation of China,No.82173151+2 种基金Capital’s Funds for Health Improvement and Research,No.CFH 2022-4-1025Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.XMLX202119Science Foundation of Peking University Cancer Hospital,No.PY202329.
文摘BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-Center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘BACKGROUND Targeted therapy combined with anti-programmed cell death 1 immunotherapy(TP)and trifluridine/tipiracil(TAS-102)combined with bevacizumab(TB)are two common therapies for patients with late-line therapy in microsatellite stable(MSS)metastatic colorectal cancer(mCRC).However,it is still unclear which therapy can bring better prognosis.AIM To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.METHODS This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital.Patients with MSS mCRC who had received at least the second line treatment were eligible.Propensity score(PS)would be calculated to balance the baseline characteristics of two cohorts.Progression-free survival(PFS)was set as the primary endpoint.The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios(HRs)and 95%confidence intervals(CIs).Landmark analysis was performed to create segmented survival curves,studying the impact of treatment regimen on prognosis during different follow-up periods.RESULTS Between July 2019 and March 2025(data cutoff),127 eligible patients were enrolled,with 88 and 39 patients assigned to the TP and TB cohorts,respectively,based on treatment allocation.At a global median follow-up of 9.73 months,the crude median PFS was 3.9 months(95%CI:3.03-5.53)in the TP cohort vs 4.17 months(95%CI:2.87-5.6)in the TB cohort,yielding a nonsignificant HR of 1.43(95%CI:0.94-2.18,P=0.092;TB as reference).Multivariate Cox regression analysis,adjusted for sex,age>60 years,Eastern Cooperative Oncology Group performance status,RAS mutation,primary tumor location(left vs right),number of metastatic organs(liver/lung),and treatment line(≥3rd line),demonstrated an adjusted HR of 1.23(95%CI:0.80-1.88,P=0.348).PS-based analyses using three methodologies:Inverse probability weighting,PS matching(post-matching n=55 vs 30),and PS-adjusted multivariate Cox regression.These analyses revealed consistent nonsignificant trends favoring TB,with HRs for TP of 1.26(95%CI:0.76-2.10,P=0.077),1.42(95%CI:0.87-2.34,P=0.164),and 1.26(95%CI:0.76-2.10,P=0.367),respectively.Notably,landmark PFS analyses at 90,120,and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints(P=0.048,0.031,and 0.035,respectively),suggesting sustained clinical benefits in TP responders.CONCLUSION TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses.However,patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB.Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments,this regimen could provide additional prolonged clinical benefits,which warrants further validation through large-scale cohort investigations.
文摘BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.
文摘Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.
