Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been es...Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurren展开更多
BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging ...BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System(ISS), Durie-Salmon(DS)staging and related indicators is affected by the renal function of patients,resulting in poor performance. This study assesses the relationship between interleukin-32(IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIM To investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODS This was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups.The variables under consideration included age, blood β2-microglobulin,albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease(MRD) after induction treatment. The main outcomes were progression-free survival(PFS) and overall survival(OS).RESULTS IL-32 was an important factor affecting PFS and OS in patients with MM.Compared with patients with IL-32 levels ≥ 856.4 pg/m L, patients with IL-32 levels < 856.4 pg/m L had longer PFS(P = 0.0387) and OS(P = 0.0379);Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS(P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/m L and MRD positive were still independent risk factors for OS and PFS(P < 0.05).CONCLUSION IL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.展开更多
AIM:To investigate tumor response and survival in patients with postembolization fever(PEF) and to determine the risk factors for PEF.METHODS:Four hundred forty-three hepatocellular carcinoma(HCC) patients who underwe...AIM:To investigate tumor response and survival in patients with postembolization fever(PEF) and to determine the risk factors for PEF.METHODS:Four hundred forty-three hepatocellular carcinoma(HCC) patients who underwent the first session of transcatheter arterial chemoembolization(TACE) between January 2005 and December 2009 were analyzed retrospectively.PEF was defined as a body temperature greater than 38.0 ℃ that developed within 3 d of TACE without evidence of infection.The tumor progression-free interval was defined as the interval from the first TACE to the second TACE based on mRECIST criteria.Clinical staging was based on the American Joint Committee on Cancer tumor,node,metastases(TNM) classification of malignant tumors.All patients were admitted before their 1 st TACE treatment,and blood samples were obtained from all patients before and after treatment.Clinicoradiological variables and host-related variables were compared between two groups:patients with PEF vs patients without PEF.Additionally,variables related to 20-mo mortality and tumor progression-free survival were analyzed.RESULTS:The study population comprised 370(85.4%) men and 73(14.6%) women with a mean age of 62.29 ± 10.35 years.A total of 1836 TACE sessions were conducted in 443 patients,and each patient received between 1 and 27(mean:4.14 ± 3.57) TACE sessions.The mean follow-up duration was 22.23 ± 19.6 mo(range:0-81 mo).PEF developed in 117 patients(26.41%) at the time of the first TACE session.PEF was not associated with 20-mo survival(P = 0.524) or computed tomography(CT) response(P = 0.413) in a univariate analysis.A univariate analysis further indicated that diffuse-type HCC(P = 0.021),large tumor size(≥ 5 cm)(P = 0.046),lipiodol dose(≥ 7 mL,P = 0.001),poor blood glucose control(P = 0.034),alanine aminotransferase(ALT) value after TACE(P = 0.004) and C-reactive protein(CRP) value after TACE(P = 0.036) served as possible risk factors correlated with PEF.The ALT value after TACE(P = 0.021) and lipiodol dose over 7 mL(P = 0.01展开更多
BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex ...BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN： This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles Progression-free survival （PFS） is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life （EORTC QLQ-LC43, and TCM syndrome score） Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION： Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.展开更多
In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survi...In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus.展开更多
Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-ther...Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results p展开更多
Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicente...Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.展开更多
BACKGROUND Enhanced magnetic resonance imaging(MRI)is widely used in the diagnosis,treatment and prognosis of hepatocellular carcinoma(HCC),but it can not effectively reflect the heterogeneity within the tumor and eva...BACKGROUND Enhanced magnetic resonance imaging(MRI)is widely used in the diagnosis,treatment and prognosis of hepatocellular carcinoma(HCC),but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment.Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival(PFS).AIM To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images.METHODS Delineate the regions of interest(ROI)in arterial phase,portal venous phase and delayed phase of enhanced MRI.After extracting the combinatorial features of ROI,the features are fused to obtain deep learning radiomics(DLR)_Sig.DeLong's test was used to evaluate the diagnostic performance of different typological features.K-M analysis was applied to assess PFS in different risk groups,and the discriminative ability of the model was evaluated using the Cindex.RESULTS Tumor diameter and diolame were independent factors influencing the prognosis of PFS.Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases(P<0.05).In deep transfer learning(DTL)and DLR,significant differences were observed between the multi-phase and individual phases feature sets(P<0.05).K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months,respectively,and the predicted probabilities of 6 months,1 year and 2 years were 92%,60%,40%and 98%,90%,73%,respectively.The C-index was 0.764,indicating relatively good consistency between the predicted and observed results.DTL and DLR have higher predictive value for 2-year PFS in nomogram.CONCLUSION Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph,it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the展开更多
Background:Previous studies have provided conflicting evidence about the increased overall survival(OS)in lung cancer patients with diabetes mellitus(DM)compared with those without DM.This study assessed progression-f...Background:Previous studies have provided conflicting evidence about the increased overall survival(OS)in lung cancer patients with diabetes mellitus(DM)compared with those without DM.This study assessed progression-free survival(PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients.Methods:Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,Shanghai.The data included patient sex,age,body mass index(BMI),smoking status,history of DM,level of blood glucose,pathological type,clinical stage of cancer,chemotherapy regimen,and history of anti-DM drugs.The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS.For comparison of PFS/OS in lung cancer with or without DM,patients were divided into three groups:lung cancer with DM,lung cancer without DM but with elevated level of blood glucose,lung cancer without DM or elevated level of blood glucose.Results:In total,the data from 200 lung cancer patients(138 males/62 females,aged 29.0 to 78.0 years,mean 60.0±8.6 years)were collected.For the comparison of PFS/OS in lung cancer patients with or without DM,patients were divided into three groups:lung cancer with DM(n=31);lung cancer without DM but with elevated levels of blood glucose(n=40);and lung cancer without both DM and elevated levels of blood glucose(n=128),whereas 1 patient dropped out of the study.All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months.Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM(log-rank,P<0.05,P<0.01);the median PFS in lung cancer with DM was 12.0 months(95%confidence interval[CI],4.0-16.0)vs.6.0 months in those without DM(95%CI,5.8-6.3);and the median OS i展开更多
Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism betwee...Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.展开更多
BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)usi...BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.展开更多
BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for h...BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in p展开更多
Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms ...Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.展开更多
BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sar...BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.展开更多
Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma （MM）.The exact expression pattern and prognostic valu...Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma （MM）.The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma （PRAME） in MM are unknown and were explored in this study.Methods The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction,and the prognostic value of PRAME was determined through retrospective survival analysis.PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME （＋）.Results Sixty-two patients （62.0％） overexpressed PRAME.PRAME overexpression showed no prognostic significance to either overall survival （n=100） or progression-free survival （PFS,n=96,all P ＞0.05） of patients.The patients were also categorized according to regimens with or without bortezomib.PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens （53.5％ vs.76.9％,P=0.071）.By contrast,it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens （77.5％ vs.63.9％,P ＞0.05）.When the patients were categorized into PRAME （＋） and PRAME （-） groups,treatment with bortezomib-containing regimens predicted a higher two-year PFS rate in PRAME （＋） patients （77.5％ vs.53.5％,P=0.027） but showed no significant effect on two-year PFS rate in PRAME （-） patients （63.9％ vs.76.9％,P ＞0.05）.Conclusion PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens.Bortezomib improves PFS in patients overexpressing PRAME.展开更多
Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy amo...Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clini展开更多
Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemothe...Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-thera展开更多
BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated dru...BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.展开更多
基金This study was supported by the National Key Basic Research Program of China(973 Program No.2015CB553902)
文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurren
基金Supported by Foundation for Excellent Young Medical Talents from the Quzhou People’s Hospital
文摘BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System(ISS), Durie-Salmon(DS)staging and related indicators is affected by the renal function of patients,resulting in poor performance. This study assesses the relationship between interleukin-32(IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIM To investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODS This was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups.The variables under consideration included age, blood β2-microglobulin,albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease(MRD) after induction treatment. The main outcomes were progression-free survival(PFS) and overall survival(OS).RESULTS IL-32 was an important factor affecting PFS and OS in patients with MM.Compared with patients with IL-32 levels ≥ 856.4 pg/m L, patients with IL-32 levels < 856.4 pg/m L had longer PFS(P = 0.0387) and OS(P = 0.0379);Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS(P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/m L and MRD positive were still independent risk factors for OS and PFS(P < 0.05).CONCLUSION IL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.
文摘AIM:To investigate tumor response and survival in patients with postembolization fever(PEF) and to determine the risk factors for PEF.METHODS:Four hundred forty-three hepatocellular carcinoma(HCC) patients who underwent the first session of transcatheter arterial chemoembolization(TACE) between January 2005 and December 2009 were analyzed retrospectively.PEF was defined as a body temperature greater than 38.0 ℃ that developed within 3 d of TACE without evidence of infection.The tumor progression-free interval was defined as the interval from the first TACE to the second TACE based on mRECIST criteria.Clinical staging was based on the American Joint Committee on Cancer tumor,node,metastases(TNM) classification of malignant tumors.All patients were admitted before their 1 st TACE treatment,and blood samples were obtained from all patients before and after treatment.Clinicoradiological variables and host-related variables were compared between two groups:patients with PEF vs patients without PEF.Additionally,variables related to 20-mo mortality and tumor progression-free survival were analyzed.RESULTS:The study population comprised 370(85.4%) men and 73(14.6%) women with a mean age of 62.29 ± 10.35 years.A total of 1836 TACE sessions were conducted in 443 patients,and each patient received between 1 and 27(mean:4.14 ± 3.57) TACE sessions.The mean follow-up duration was 22.23 ± 19.6 mo(range:0-81 mo).PEF developed in 117 patients(26.41%) at the time of the first TACE session.PEF was not associated with 20-mo survival(P = 0.524) or computed tomography(CT) response(P = 0.413) in a univariate analysis.A univariate analysis further indicated that diffuse-type HCC(P = 0.021),large tumor size(≥ 5 cm)(P = 0.046),lipiodol dose(≥ 7 mL,P = 0.001),poor blood glucose control(P = 0.034),alanine aminotransferase(ALT) value after TACE(P = 0.004) and C-reactive protein(CRP) value after TACE(P = 0.036) served as possible risk factors correlated with PEF.The ALT value after TACE(P = 0.021) and lipiodol dose over 7 mL(P = 0.01
基金supported by the Longhua Medicial Project (D-11)The Science and Technology Commission of Shanghai Municipality (No.12401905700)
文摘BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN： This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles Progression-free survival （PFS） is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life （EORTC QLQ-LC43, and TCM syndrome score） Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION： Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.
文摘In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus.
基金This post hoc analysis was sponsored by Shanghai Roche Pharmaceuticals Ltd.,China.Shanghai Roche Pharmaceuticals Ltd.,China was involved in the data interpretation and writing of the report.F.Hoffmann-La Roche Ltd.was involved in the study design,data collection,and data analysis
文摘Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results p
基金supported by the National Natural Science Foundation of China(Grant No.82272744)Natural Science Foundation of Guangdong Province(Grant No.2022A1515010814)Sun Yat-sen University Clinical Research 5010 Program(Grant No.2022008).
文摘Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.
文摘BACKGROUND Enhanced magnetic resonance imaging(MRI)is widely used in the diagnosis,treatment and prognosis of hepatocellular carcinoma(HCC),but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment.Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival(PFS).AIM To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images.METHODS Delineate the regions of interest(ROI)in arterial phase,portal venous phase and delayed phase of enhanced MRI.After extracting the combinatorial features of ROI,the features are fused to obtain deep learning radiomics(DLR)_Sig.DeLong's test was used to evaluate the diagnostic performance of different typological features.K-M analysis was applied to assess PFS in different risk groups,and the discriminative ability of the model was evaluated using the Cindex.RESULTS Tumor diameter and diolame were independent factors influencing the prognosis of PFS.Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases(P<0.05).In deep transfer learning(DTL)and DLR,significant differences were observed between the multi-phase and individual phases feature sets(P<0.05).K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months,respectively,and the predicted probabilities of 6 months,1 year and 2 years were 92%,60%,40%and 98%,90%,73%,respectively.The C-index was 0.764,indicating relatively good consistency between the predicted and observed results.DTL and DLR have higher predictive value for 2-year PFS in nomogram.CONCLUSION Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph,it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the
基金supported by a grant from the National Natural Science Foundation of China(No.81172219).
文摘Background:Previous studies have provided conflicting evidence about the increased overall survival(OS)in lung cancer patients with diabetes mellitus(DM)compared with those without DM.This study assessed progression-free survival(PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients.Methods:Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,Shanghai.The data included patient sex,age,body mass index(BMI),smoking status,history of DM,level of blood glucose,pathological type,clinical stage of cancer,chemotherapy regimen,and history of anti-DM drugs.The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS.For comparison of PFS/OS in lung cancer with or without DM,patients were divided into three groups:lung cancer with DM,lung cancer without DM but with elevated level of blood glucose,lung cancer without DM or elevated level of blood glucose.Results:In total,the data from 200 lung cancer patients(138 males/62 females,aged 29.0 to 78.0 years,mean 60.0±8.6 years)were collected.For the comparison of PFS/OS in lung cancer patients with or without DM,patients were divided into three groups:lung cancer with DM(n=31);lung cancer without DM but with elevated levels of blood glucose(n=40);and lung cancer without both DM and elevated levels of blood glucose(n=128),whereas 1 patient dropped out of the study.All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months.Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM(log-rank,P<0.05,P<0.01);the median PFS in lung cancer with DM was 12.0 months(95%confidence interval[CI],4.0-16.0)vs.6.0 months in those without DM(95%CI,5.8-6.3);and the median OS i
文摘Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.
基金Supported by National Natural Science Foundation of China,No.82072736 and No.81874184the Key Project of Hubei Health Commission,No.WJ2019Q030.
文摘BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.
基金Supported by Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0314。
文摘BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in p
文摘Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.
基金This study was approved by the Ethics Committee of Harbin Medical University Cancer Hospital.
文摘BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.
文摘Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma （MM）.The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma （PRAME） in MM are unknown and were explored in this study.Methods The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction,and the prognostic value of PRAME was determined through retrospective survival analysis.PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME （＋）.Results Sixty-two patients （62.0％） overexpressed PRAME.PRAME overexpression showed no prognostic significance to either overall survival （n=100） or progression-free survival （PFS,n=96,all P ＞0.05） of patients.The patients were also categorized according to regimens with or without bortezomib.PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens （53.5％ vs.76.9％,P=0.071）.By contrast,it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens （77.5％ vs.63.9％,P ＞0.05）.When the patients were categorized into PRAME （＋） and PRAME （-） groups,treatment with bortezomib-containing regimens predicted a higher two-year PFS rate in PRAME （＋） patients （77.5％ vs.53.5％,P=0.027） but showed no significant effect on two-year PFS rate in PRAME （-） patients （63.9％ vs.76.9％,P ＞0.05）.Conclusion PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens.Bortezomib improves PFS in patients overexpressing PRAME.
基金support from the National Natural Science Foundation of China(Nos.82003206 and 82173338)Natural Science Foundation of Hunan Province(Nos.2020SK2031,2020SK2030,2021RC4040,and 2020JJ3025).
文摘Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clini
基金supported by the National Key Research and Development Plan of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Scientific Foundation of China(No.81771912,81901910,82072090,and 82001986)。
文摘Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-thera
文摘BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.
