Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

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.

Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival:A case report

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.

A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

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-therapy of stageⅣNSCLC.

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Somatic copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung cancer.However,little is known about whether they are predictive of radiotherapy outcomes.We aimed to understand the prognostic value and biological functions of SCNAs.Methods:We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy.Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response.Our results were validated in 20 patients with lung adenocarcinoma(LUAD)receiving radiotherapy.Results:SCNAs were a better predictor of progression-free survival(PFS)in LUAD(P=0.024)than in lung squamous carcinoma(P=0.18)in patients treated with radiotherapy.Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD.Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels(P=0.022).Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS.Additionally,high SCNA may activate the cell cycle pathway and induce tumorigenesis.Conclusions:SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy,in combination with TNM,with the aim of predicting long-term PFS.Therefore,SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.

Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials

BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.DATA SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.

Impact of Real-Time Contrast-Enhanced Ultrasound-Guided Radiofrequency Ablation on Progression-Free Survival in Patients with Hepatocellular Carcinoma:a Retrospective Case-Control Study

Objective To compare the value of contrast-enhanced ultrasound(CEUS)and conventional ultrasound(US)during radiofrequency ablation(RFA)for the treatment of hepatocellular carcinoma(HCC)≥3.0 cm in diameter.Methods A total of 149 HCC patients treated with RFA guided by either CEUS or conventional US between January 2012 and June 2013 were retrospectively analyzed.Patients were divided into different groups based on the type of ultrasound guidance(CEUS or conventional US)and tumor volume(diameter<3.0 or≥3.0 cm).The progressionfree survival(PFS)and complete ablation rates were compared between groups,and risk factors for the PFS were investigated.Results Seventy four patients received CEUS-guided RFA,and conventional US was performed in 75 patients.Among patients with a tumor<3.0 cm,the PFS and complete ablation rates were similar.However,for patients with a tumor≥3.0 cm,those treated with CEUS had a significantly longer PFS(17.3 vs.3.1 months,HR=2.73;95%CI,1.28~5.81;P=0.007)and higher complete ablation rates at 6-and 12-month post-treatment(87.5%vs.57.7%,P=0.042;75.0%vs.38.5%,P=0.009,respectively)than those treated with conventional US-guided RFA.The type of treatment(P=0.024)and maximum tumour size(P=0.011)were both found to be independent factors associated with the PFS.Conclusion Compared with conventional US,CEUS is more effective for guiding RFA in patients with HCC≥3.0 cm.CEUS-guided RFA could target HCC more accurately,and its ability to immediately detect any residual tumor during RFA might contribute to an increase in complete ablation rates and reduced progression.

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

Background:ATP-binding cassette transporter G1(ABCG1)regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity.But,for hepatocellular carcinoma(HCC),the role of ABCG1 has not been investigated.Thus,the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.Methods:One hundred and four adult patients with HCC were enrolled,and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry.All these patients were stratified by ABCG1 expression,Kaplan-Meier analysis was used to compare the overall survival(OS)and recurrence-free survival(RFS),and Cox regression analysis was used to determine independent predictors of tumor recurrence.Results:Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues.Patients with high nuclear ABCG1 expression had lower OS and RFS(P=0.012 and P=0.020,respectively).High nuclear ABCG1 expression was related to larger tumor size(P=0.004)and tumor recurrence(P=0.027).Although ABCG1 was expressed in the cytoplasm,cytosolic expression could not predict the outcome in patients with HCC.A new stratification pattern was established based on the heterogenous ABCG1 expression pattern:high risk(High^(nucleus)/Low^(cytosol)),moderate risk(High^(nucleus)/High^(cytosol) or Low^(nucleus)/Low^(cytosol)),and low risk(Low^(nucleus)/High^(cytosol)).This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC.Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS(P=0.015).Conclusions:High nuclear ABCG1 expression indicates poor prognosis in patients with HCC.Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

Pretreatment serum albumin-to-alkaline phosphatase ratio is an independent prognosticator of survival in patients with metastatic gastric cancer

BACKGROUND Previous studies have suggested that a low albumin-to-alkaline phosphatase ratio(AAPR)is associated with a lower survival rate in patients with various malignancies.However,the relationship between pretreatment AAPR and the prognosis of patients with gastric cancer(GC)remains unclear.AIM To investigate the prognostic value of AAPR in distant metastatic GC.METHODS A total of 191 patients with distant metastatic cancer from a single institute were enrolled in this study.Pretreatment clinical data,including serum albumin and alkaline phosphatase levels,were collected.A chi-square test or Fisher’s exact test was applied to evaluate the correlations between AAPR and various clinical parameters in GC patients.The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic efficacy of AAPR in metastatic GC patients.A two-sided P value lower than 0.05 was considered statistically significant.RESULTS A receiver operating characteristic curve indicated that 0.48 was the optimal threshold value for AAPR.AAPR≤0.48 was significantly associated with bone(P<0.05)and liver metastasis(P<0.05).Patients with high levels of AAPR had better survival in terms of overall survival(OS)and progression-free survival(PFS),regardless of the presence of liver/bone metastasis.Pretreatment AAPR was found to be a favorable predictor of OS and PFS based on a multivariate cox regression model.AAPR-M system,constructed based on AAPR and number of metastatic sites,showed superior predictive ability relative to the number of metastatic sites for predicting survival.CONCLUSION Pretreatment AAPR may serve as an independent prognostic factor for predicting PFS and OS in patients with metastatic GC.Furthermore,AAPR may assist clinicians with individualizing treatment.

Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography Predict Survival in Classical Hodgkin Lymphoma

Interim Positron-Emission Tomography (int-PET) and the peripheral blood absolute lymphocyte/monocyte ratio at di- agnosis (ALC/AMC-DX) have been shown to be predictors for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (cHL). Therefore, we studied if the combination of ALC/AMC-DX and the (int-PET) can further stratified PFS and TTP in cHL patients. Patients were required to be diagnosed, treated, and followed with int-PET at Mayo Clinic, Rochester, Minnesota. From 2000 until 2008, 111 cHL patients qualified for the study. The median follow-up was 2.8 years (range: 0.3 - 10.4 years). Patients with a negative int-PET (N = 98) pre- sented with a higher ALC/AMC-DX (median of 2.32, range: 0.26 - 37.5) compared with patients with a positive int-PET (N = 13) (median of 0.9, range: 0.29 - 3.10), p 1.1. Group 1 experienced superior PFS and TTP in comparison with the other groups. In conclusion, the combination of ALC/AMC-DX and the int-PET provides a simple model to assess clinical outcomes in cHL.

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival(PFS) and overall survival(OS) between extensive-stage small-cell lung cancer(ES-SCLC) patients who acquired partial response(PR) or complete remission(CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin(EP) regimen and those who acquired PR or CR after four or six cycles.Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region(China) between November 2004 and May 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows.Results After a median follow-up of 293 days(range, 62–1531 days), all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months(95% CI, 5.1–6.9), and the median OS was 10.5 months(95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months(95% CI, 4.4–5.2), and the median OS was 7.5 months(95% CI, 6.8–8.2). Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

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.

The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

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.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

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 combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

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 patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

Prolonged progression-free survival and overall survival are associated with diabetes mellitus but inversely associated with levels of blood glucose in patients with lung cancer

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 in lung cancer patients with DM was 37.0 months(95%CI,29.0-46.6)vs.12.0 months in those without DM(95%CI,10.9-13.1).For the other two groups of patients without DM,there was a trend toward a shorter PFS and OS in patients with elevated blood glucose compared with those without elevated blood glucose.Cox regression showed that PFS in lung cancer patients was favorably associated with the usage of anti-DM drugs,BMI,clinical stage of cancer,and chemotherapy regimen(all P<0.05)but was inversely associated with the level of blood glucose(P<0.05).Conclusions:Lung cancer patients with DM have prolonged PFS and OS compared with those without DM,and the level of blood glucose was inversely associated with PFS.The current results indicate that PFS may be a meaningful intermediate endpoint for OS and that the levels of blood glucose hopefully represent a prognostic factor in lung cancer patients.

Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma

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.

Effect of Feitai Capsule(肺泰胶囊) on Quality of Life and Progression-Free Survival of Patients with Unresectable Non-Small Cell Lung Cancer

Objective： To examine the effect of a Chinese medicinal herbal formula （Feitai Capsule, 肺泰胶囊） on the quality of life （QOL） and progression-free survival （PFS） of patients with unresectable non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients were randomly divided into the treatment group （31 cases） and the control group （31 cases）. For the treatment group, 4 capsules （1.2 g/capsule） of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles （12 weeks totally）. If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive dJsease （PD）. For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance （ANOVA）, a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan- Meier analysis was used to compare the two-group PFS. Results： Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different （P〉0.05）. The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant （Z=-2.632, P=0.008）. The control group had a 26.7% improvement in the Karnofsky performance status （KPS）, while the treatment group had a 53.4% improvement. This was also significantly different （Z=-2.182, P=0.029）. A comparative analysis indicated a positive correlation （r=0.917, P〈0.001）. Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively （P=0.048）. Conclusion： Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.

经肝动脉化疗栓塞联合系统治疗对不可切肝细胞癌的疗效分析

目的:探索经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)为基础的不同方案治疗不可切除肝细胞癌(unresectable hepatocellular carcinoma,uHCC)患者的疗效和安全性,以及TACE联合酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)和免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的最佳时机。方法:回顾性分析2016年4月至2021年12月期间在南方医科大学南方医院接受基于TACE治疗的555例uHCC患者资料。根据不同治疗方案分为:TACE组(n=317)、TACE+TKIs组(n=66)、TACE+ICIs组(n=33)、TACE+TKIs+ICIs组(n=139)。在亚组分析中,根据不同的联合时间将TACE+TKIs+ICIs组分为“TACE前”和“TACE后”组。采用单因素、多因素Cox回归分析影响OS的预后因素。结果:TACE+TKIs+ICIs组获得最长的OS(21.9个月,95%CI:17.2~26.6,P=0.030)和PFS(8.3个月,95%CI:7.3~9.3,P=0.004)。在亚组分析中,“TACE后”组比“TACE前”组获得更长的OS(26.8个月vs.19.2个月,P=0.011)。TACE组、TACE+TKIs组、TACE+ICIs组、TACE+TKIs+ICIs组的ORR分别为32.8%、41.1%、42.4%、52.5%(P=0.001),DCR分别为59.6%、71.2%、69.7%、82.7%(P<0.001)。不良反应事件与既往研究相似。Cox回归分析提示肿瘤数量、肝外转移及治疗方案是患者OS的独立预后因素(均P<0.05)。结论:TKIs或ICIs可以提高TACE治疗uHCC患者的OS和PFS,TKIs+ICIs联合TACE生存获益更佳。首次TACE术后3个月内联合“TKIs+ICIs”治疗方案的总生存期获益更显著。

晚期胃癌一线免疫检查点抑制剂联合化疗预后因素及对二线化疗的影响

目的:探索免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)联合化疗一线治疗晚期胃癌中肝转移状态、中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)、体质量指数(body mass index,BMI)等因素与患者预后的关系,以及一线应用ICIs对二线化疗疗效的影响。方法:收集解放军总医院2018年1月至2022年4月收治的胃癌患者临床资料,通过随访获得生存数据。采用Kaplan-Meier法进行生存分析,Log-rank检验比较胃癌一线程序性细胞死亡受体1(programmed cell death receptor-1,PD-1)/程序性细胞死亡配体1(programmed cell death-ligand 1,PD-L1)抑制剂联合化疗中不同NLR、BMI和肝转移状态对预后的影响,以及一线应用PD-1/PD-L1抑制剂对二线化疗的影响。应用Cox回归模型确定影响患者生存的预后因素。结果:共纳入晚期胃癌患者268例,在一线PD-1/PD-L1抑制剂联合化疗组中,总体客观缓解率(objective response rate,ORR)为46.5%,疾病控制率(disease control rate,DCR)为87.7%,中位无进展生存期1(median progression-free survival 1,mPFS1)为6.9(95%CI:6.0~7.8)个月。各亚组中,仅NLR<3组与NLR≥3组的中位PFS1有显著性差异(7.4 vs.6.7个月,P=0.044)。多因素分析显示,基线NLR<3的患者在PD-1/PD-L1抑制剂联合化疗中能够获得更长的无进展生存期(HR=0.57,95%CI:0.36~0.90;P=0.015),而BMI、肝转移状态与患者预后无明显相关(均P>0.05)。二线治疗中,一线PD-1/PD-L1抑制剂联合化疗进展后仅接受化疗患者的ORR(34.6%vs.14.6%,P=0.025)和mPFS2(4.4 vs.2.9个月,HR=0.54,95%CI:0.35~0.82;P=0.004)优于一、二线均仅应用化疗的患者,而DCR及中位总生存期(median overall survival,mOS)比较差异无统计学意义(均P>0.05)。结论:在一线接受PD-1/PD-L1抑制剂联合化疗的晚期胃癌中,基线NLR<3的患者更易从免疫治疗中获益,而肝转移状态、BMI与患者的预后无明显相关。另外,一线应用含免疫治疗的方案可提高胃癌患者二线化疗的疗效,使其获得更长的无进展生存期。

Reduction rate of monoclonal protein as a useful prognostic factor in standard-risk group of newly diagnosed multiple myeloma

BACKGROUND Multiple myeloma(MM)is a common hematologic malignancy that originates from a malignant clone of plasma cells.Solitary plasmacytoma,history of diabetes,and platelet count are considered as prognostic factors for MM.But some patients are still associated with much worse outcomes without any prognostic predictors.This study aimed to observe the reduction rate of monoclonal protein(M protein)after the first and fourth chemotherapy cycles,which is considered as a new prognostic factor for progression-free survival(PFS)in standard-risk group of newly diagnosed MM patients.AIM To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor.METHODS A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included.All patients were diagnosed according to the National Comprehensive Cancer Network(NCCN)2020.V1 diagnostic criteria.The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines.After diagnosis,164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy.The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria.The following baseline data from the patients were collected:Gender,age at diagnosis,Durie-Salmon stage,glutamicpyruvic transaminase,glutamic-oxaloacetic transaminase,catabolite activator protein,albumin/globulin ratio,lactate dehydrogenase,translocation(t)(6;14),t(11;14),maintenance regimen,total cholesterol(TC),triglyceride,and phosphorous.All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis.The factors influencing the overall survival and PFS were then assessed by multivariate analysis.We found the first cycle(C1)reduction rate and the fourth cycle(C4)reduction rate as predictors of PFS.Then,PFS was compared between patients with a C1 reduction rate of M protein of≥25%vs<25%and≥50%vs<50%,and between patients with a C4 reduction rate of≥25%vs<25%,≥50%vs<50%,and≥75%vs<75%.RESULTS Multivariate analysis revealed age[hazard ratio(HR):1.059,95%confidence interval(95%CI):1.033-1.085,P≤0.001],International Staging System stage(HR:2.136,95%CI:1.500-3.041,P≤0.001),autotransplantion(HR:0.201,95%CI:0.069-0.583,P=0.019),TC(HR:0.689,95%CI:0.533-0.891,P=0.019),C1 reduction rate(HR:0474,95%CI:0.293-0.767,P=0.019),and C4 reduction rate(HR:0.254,95%CI:0.139-0.463,P=0.019)as predictors of PFS.The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle(≥50%)and fourth cycle(≥75%)chemotherapy was associated with a longer PFS than the lower one.CONCLUSION Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.