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
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-therapy of stageⅣNSCLC.展开更多
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,li...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.展开更多
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 to...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.展开更多
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 inves...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.展开更多
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 pretreat...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.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 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 factor...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.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
BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection follo...BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection following diagnosis.Radiofrequency ablation(RFA)is an accepted alternative therapy for CRLM patients who are not suitable for resection.However,the relatively high rate of local tumor progression(LTP)is an obstacle to the more widespread use of RFA.AIM To determine the oncological outcomes and predictors of RFA in CRLM patients.METHODS A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases,who had received percutaneous RFA treatment at our institution from January 2013 to December 2018.Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations.The Kaplan-Meier method was used to calculate overall survival(OS)and LTP-free survival(LTPFS).The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes.RESULTS There were no RFA procedure-related deaths,and the technique effectiveness of the treatment was 89.1%(123/138).The median follow-up time was 30 mo.The LTP rate was 32.6%(45/138),and the median OS was 36 mo.The 1-,3-,and 5-year OS rates were 90.6%,45.6%,and 22.9%,respectively.Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS,while extrahepatic disease(EHD),tumor number,and tumor size were the factors influencing OS.Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS,while tumor number greater than 1,size larger than 3 cm,and presence of EHD were the independent predictors of shorter OS.CONCLUSION RFA is a safe and effective treatment method for CRLM.Tumor size and ablative margin are the important factors affecting LTPFS.Tumor number,tumor size,and EHD are also critical factors for OS.展开更多
Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)w...Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)with locally advanced or metastatic soft tissue sarcoma were eligible.Each treatment cycle lasted for 3 weeks,and included liposomal doxorubicin(40-50 mg/m^(2))on day 1 and anlotinib(12 mg)on days 8-21.Starting from the 9th cycle,treatment consisted of only anlotinib.Treatment continued until disease progression or intolerable toxicities.The primary efficacy end point was progression-free survival(PFS).Results:Eight patients were enrolled between July 25,2019 and January 8,2020.The median number of treatment cycles was 5.5.Within 5.9 months median follow-up,PFS events occurred in 4(4/8,50%)patients.The median PFS was 11.3 months and the 6-month PFS rate was 56%.No patients attained complete response and 2 patients(fibrosarcoma,1 patient and undifferentiated pleomorphic sarcoma,1 patient)achieved partial response.Three patients(fibrosarcoma,2 patients and synovial sarcoma,1 patient)had stable disease.The objective response rate was 25%(2/8)for the study population,and the disease control rate was 75%(6/8).No new safety concerns emerged.Conclusions:Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas.Due to the small sample size,further investigations with a larger population should be undertaken to confirm the study findings.展开更多
Objective:To analyze the efficacy and safety o f apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm,prospective,and open clinical phase II study.Methods:Informatio...Objective:To analyze the efficacy and safety o f apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm,prospective,and open clinical phase II study.Methods:Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure o f chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed.The participants included 23 males and 11 females,with an average age of 35.24 years(11-73 years).The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),PFS rate(PFR),and overall survival(OS)were evaluated.The treatmentrelated adverse events(AEs)and safety of apatinib were also evaluated.Results:O f the 34 patients,33 were able to be evaluated for efficacy.One patient received apatinib treatment for less than one cycle;therefore,only safety analysis was performed.The 12-week clinical evaluation showed that 2 patients had a partial response(PR),24 patients had stable disease(SD),and 7 patients had progressive disease(PD).The ORR,DCR,and PFR at 12 weeks were 6.06%(2/33),78.79%(26/33),and 82%,respectively.By the end of the follow-up,6 patients had SD(18.18%,6/33),27 patients had PD(81.82%,27/33),and 15 patients died because of disease progression(45.45%,15/33).The ORR was 0(0/33),the DCR was 18.18%(6/33),and the median PFS(mPFS)was 7.89 months(95%Cl:4.56-11.21).The median OS(mOS)was 17.61 months(95%Cl:10.85-24.37).The most common treatment-related AEs were hand-foot syndrome(35.29%,12/34),proteinuria(32.35%,11/34),and hypertension(32.35%,11/34).展开更多
Objective:To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer(EOC).Methods:All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Ho...Objective:To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer(EOC).Methods:All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included.Patient characteristics,tumor features,surgical types,and chemotherapeutic treatments were collected.Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival(PFS)and overall survival(OS).展开更多
BACKGROUND Primary intracranial alveolar soft-part sarcoma(PIASPS)is a rare malignancy.We aimed to investigate the clinical profiles and outcomes for PIASPS.CASE SUMMARY We firstly reported five consecutive cases from...BACKGROUND Primary intracranial alveolar soft-part sarcoma(PIASPS)is a rare malignancy.We aimed to investigate the clinical profiles and outcomes for PIASPS.CASE SUMMARY We firstly reported five consecutive cases from our institute.Then,the cases from previous studies were pooled and analyzed to delineate the characteristics of this disease.Our cohort included two males and three females.The median age was 21-years-old(range:8-54-years-old).All the patients received surgical treatment.Gross total resection(GTR),radiotherapy,and chemotherapy were administered in 3 patients,4 patients,and 1 patient,respectively.After a median follow-up of 36 mo,tumor progression was noticed in 4 patients;and 3 patients died of the disease.Pooled data(n=14)contained 5 males and 9 females with a median age of 19 years.The log-rank tests showed that GTR(P=0.011)could prolong progression-free survival,and radiotherapy(P<0.001)resulted in longer overall survival.CONCLUSION Patients with PIASPS suffer from poor outcomes.Surgical treatment is the first choice,and GTR should be achieved when the tumor is feasible.Patients with PIASPS benefit from radiotherapy,which should be considered as a part of treatment therapies.展开更多
BACKGROUND The effectiveness of regorafenib plus programmed cell death-1(PD-1)inhibitor in treating microsatellite stable(MSS)metastatic colorectal cancer(mCRC)remains controversial.AIM To investigate the benefits of ...BACKGROUND The effectiveness of regorafenib plus programmed cell death-1(PD-1)inhibitor in treating microsatellite stable(MSS)metastatic colorectal cancer(mCRC)remains controversial.AIM To investigate the benefits of regorafenib combined with PD-1 inhibitor in treating MSS mCRC and explore indicators predicting response.METHODS This retrospective study included a total of 30 patients with microsatellite stable metastatic colorectal cancer treated with regorafenib combined with programmed cell death-1 inhibitor at Henan Provincial People’s Hospital between December 2018 and December 2020.During a 4-wk treatment cycle,regorafenib was performed for 3 continuous weeks.PD-1 inhibitor was intravenously injected starting on the first day of the oral intake of regorafenib.We reviewed tumor response,progression-free survival(PFS),overall survival,and treatment-related adverse events(TRAEs)and evaluated association between platelet-tolymphocyte ratio(PLR)and outcomes in this retrospective study.RESULTS Stable disease and progressive disease were found in 18(60.0%)and 12(40.0%)patients,respectively.The disease control rate was 60.0%.The median follow-up time was 12.0 mo,and median PFS was 3.4 mo[95%confidence interval(CI):2.2-4.6 mo].Of the 12 patients with progressive disease,10(83.3%)had liver metastasis before starting the combined treatment.Among the 18 patients with SD,10(55.6%)did not have liver metastases.One patient without liver metastases at baseline was found with a substantially prolonged PFS of 11.2 mo.The liver metastasis,the choice of programmed cell death-1 inhibitor other than nivolumab or pembrolizumab and previous exposure to regorafenib was’t associated with treatment outcome.The median PFS in the low-PLR group was 4.2 mo(95%CI:3.5-4.9 mo),compared with 2.8 mo(95%CI:1.4-4.2 mo)in the high-PLR group(P=0.005).The major TRAEs included hand-foot syndrome(33.3%),hypertension(23.3%),malaise(20.0%),and gastrointestinal reaction(16.7%).The incidence of grade 3 TRAEs was 13.3%(4/30),which comprised abnormal capillary proliferation(n=1),transaminase elevation(n=1),and hand-foot syndrome(n=2).No grade 4 or higher toxicity was observed.CONCLUSION Regorafenib combined with PD-1 inhibitor could lead to a longer PFS in some patients with MSS mCRC.The PLR might be a prediction of the patient response to this therapy.展开更多
BACKGROUND There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma(ESCC) who are not eligible to undergo surgical treatment.AIM To introduce ...BACKGROUND There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma(ESCC) who are not eligible to undergo surgical treatment.AIM To introduce a novel therapy called endoscopic debulking resection(Ed R) followed by additive chemoradiotherapy(CRT) and evaluate its efficacy and safety.METHODS Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received Ed R followed by CRT were deemed the Ed R + CRT group and those without CRT were deemed the Ed R group. Overall survival(OS), progression-free survival(PFS), and adverse events were evaluated.RESULTS A total of 41 patients were enrolled. At a median follow-up of 36 mo(range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent Ed R plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent Ed R alone(1-year OS, 83.3%;2-year OS, 58.3%;3-year OS, 50%;P = 0.05). The estimated 2-year cumulative PFS rate after Ed R + CRT was 85.7%, while it was 61.5% after Ed R(P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage(stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the Ed R procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after Ed R.CONCLUSION Ed R plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.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 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.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.clinicaltrials.gov/,OMESIA,NCT05129202.展开更多
Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after t...Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)展开更多
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 recurrent or metastatic ESCC.展开更多
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.
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-therapy of stageⅣNSCLC.
基金This work was supported by grants from the National Key Technology R&D Program(Grant No.2018YFC1313400)National Natural Science Foundation of China(Grant No.81974246)+1 种基金Scientific Research Program of Tianjin Education Commission(Grant No.2019KJ185)Tianjin Research Innovation Project(Grant No.2020YJSB164)for postgraduate students.
文摘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.
基金the Training Plan for Outstanding Young Teachers of Jilin University(No.419080500356).
文摘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.
基金supported by a grant from Natural Science Foundation of Zhejiang Province(LQ21H160031)。
文摘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.
文摘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.
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 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.
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.
基金Supported by National Natural Science Foundation of China,No.81470086 and No.81871465.
文摘BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection following diagnosis.Radiofrequency ablation(RFA)is an accepted alternative therapy for CRLM patients who are not suitable for resection.However,the relatively high rate of local tumor progression(LTP)is an obstacle to the more widespread use of RFA.AIM To determine the oncological outcomes and predictors of RFA in CRLM patients.METHODS A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases,who had received percutaneous RFA treatment at our institution from January 2013 to December 2018.Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations.The Kaplan-Meier method was used to calculate overall survival(OS)and LTP-free survival(LTPFS).The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes.RESULTS There were no RFA procedure-related deaths,and the technique effectiveness of the treatment was 89.1%(123/138).The median follow-up time was 30 mo.The LTP rate was 32.6%(45/138),and the median OS was 36 mo.The 1-,3-,and 5-year OS rates were 90.6%,45.6%,and 22.9%,respectively.Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS,while extrahepatic disease(EHD),tumor number,and tumor size were the factors influencing OS.Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS,while tumor number greater than 1,size larger than 3 cm,and presence of EHD were the independent predictors of shorter OS.CONCLUSION RFA is a safe and effective treatment method for CRLM.Tumor size and ablative margin are the important factors affecting LTPFS.Tumor number,tumor size,and EHD are also critical factors for OS.
文摘Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)with locally advanced or metastatic soft tissue sarcoma were eligible.Each treatment cycle lasted for 3 weeks,and included liposomal doxorubicin(40-50 mg/m^(2))on day 1 and anlotinib(12 mg)on days 8-21.Starting from the 9th cycle,treatment consisted of only anlotinib.Treatment continued until disease progression or intolerable toxicities.The primary efficacy end point was progression-free survival(PFS).Results:Eight patients were enrolled between July 25,2019 and January 8,2020.The median number of treatment cycles was 5.5.Within 5.9 months median follow-up,PFS events occurred in 4(4/8,50%)patients.The median PFS was 11.3 months and the 6-month PFS rate was 56%.No patients attained complete response and 2 patients(fibrosarcoma,1 patient and undifferentiated pleomorphic sarcoma,1 patient)achieved partial response.Three patients(fibrosarcoma,2 patients and synovial sarcoma,1 patient)had stable disease.The objective response rate was 25%(2/8)for the study population,and the disease control rate was 75%(6/8).No new safety concerns emerged.Conclusions:Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas.Due to the small sample size,further investigations with a larger population should be undertaken to confirm the study findings.
基金partly supported by the Natural Science Foundation of Tianjin(Grant Nos.16JCYBJC24100 and 18YFZCSY00550).
文摘Objective:To analyze the efficacy and safety o f apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm,prospective,and open clinical phase II study.Methods:Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure o f chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed.The participants included 23 males and 11 females,with an average age of 35.24 years(11-73 years).The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),PFS rate(PFR),and overall survival(OS)were evaluated.The treatmentrelated adverse events(AEs)and safety of apatinib were also evaluated.Results:O f the 34 patients,33 were able to be evaluated for efficacy.One patient received apatinib treatment for less than one cycle;therefore,only safety analysis was performed.The 12-week clinical evaluation showed that 2 patients had a partial response(PR),24 patients had stable disease(SD),and 7 patients had progressive disease(PD).The ORR,DCR,and PFR at 12 weeks were 6.06%(2/33),78.79%(26/33),and 82%,respectively.By the end of the follow-up,6 patients had SD(18.18%,6/33),27 patients had PD(81.82%,27/33),and 15 patients died because of disease progression(45.45%,15/33).The ORR was 0(0/33),the DCR was 18.18%(6/33),and the median PFS(mPFS)was 7.89 months(95%Cl:4.56-11.21).The median OS(mOS)was 17.61 months(95%Cl:10.85-24.37).The most common treatment-related AEs were hand-foot syndrome(35.29%,12/34),proteinuria(32.35%,11/34),and hypertension(32.35%,11/34).
基金This study was supported by grants from the National Key Technology R&D Program of China(No.2019YFC1005200,No.2019YFC1005202 and2018YFC1002103)。
文摘Objective:To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer(EOC).Methods:All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included.Patient characteristics,tumor features,surgical types,and chemotherapeutic treatments were collected.Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival(PFS)and overall survival(OS).
文摘BACKGROUND Primary intracranial alveolar soft-part sarcoma(PIASPS)is a rare malignancy.We aimed to investigate the clinical profiles and outcomes for PIASPS.CASE SUMMARY We firstly reported five consecutive cases from our institute.Then,the cases from previous studies were pooled and analyzed to delineate the characteristics of this disease.Our cohort included two males and three females.The median age was 21-years-old(range:8-54-years-old).All the patients received surgical treatment.Gross total resection(GTR),radiotherapy,and chemotherapy were administered in 3 patients,4 patients,and 1 patient,respectively.After a median follow-up of 36 mo,tumor progression was noticed in 4 patients;and 3 patients died of the disease.Pooled data(n=14)contained 5 males and 9 females with a median age of 19 years.The log-rank tests showed that GTR(P=0.011)could prolong progression-free survival,and radiotherapy(P<0.001)resulted in longer overall survival.CONCLUSION Patients with PIASPS suffer from poor outcomes.Surgical treatment is the first choice,and GTR should be achieved when the tumor is feasible.Patients with PIASPS benefit from radiotherapy,which should be considered as a part of treatment therapies.
基金Supported by the Henan Provincial Department of Science and Technology,No. 212102310047
文摘BACKGROUND The effectiveness of regorafenib plus programmed cell death-1(PD-1)inhibitor in treating microsatellite stable(MSS)metastatic colorectal cancer(mCRC)remains controversial.AIM To investigate the benefits of regorafenib combined with PD-1 inhibitor in treating MSS mCRC and explore indicators predicting response.METHODS This retrospective study included a total of 30 patients with microsatellite stable metastatic colorectal cancer treated with regorafenib combined with programmed cell death-1 inhibitor at Henan Provincial People’s Hospital between December 2018 and December 2020.During a 4-wk treatment cycle,regorafenib was performed for 3 continuous weeks.PD-1 inhibitor was intravenously injected starting on the first day of the oral intake of regorafenib.We reviewed tumor response,progression-free survival(PFS),overall survival,and treatment-related adverse events(TRAEs)and evaluated association between platelet-tolymphocyte ratio(PLR)and outcomes in this retrospective study.RESULTS Stable disease and progressive disease were found in 18(60.0%)and 12(40.0%)patients,respectively.The disease control rate was 60.0%.The median follow-up time was 12.0 mo,and median PFS was 3.4 mo[95%confidence interval(CI):2.2-4.6 mo].Of the 12 patients with progressive disease,10(83.3%)had liver metastasis before starting the combined treatment.Among the 18 patients with SD,10(55.6%)did not have liver metastases.One patient without liver metastases at baseline was found with a substantially prolonged PFS of 11.2 mo.The liver metastasis,the choice of programmed cell death-1 inhibitor other than nivolumab or pembrolizumab and previous exposure to regorafenib was’t associated with treatment outcome.The median PFS in the low-PLR group was 4.2 mo(95%CI:3.5-4.9 mo),compared with 2.8 mo(95%CI:1.4-4.2 mo)in the high-PLR group(P=0.005).The major TRAEs included hand-foot syndrome(33.3%),hypertension(23.3%),malaise(20.0%),and gastrointestinal reaction(16.7%).The incidence of grade 3 TRAEs was 13.3%(4/30),which comprised abnormal capillary proliferation(n=1),transaminase elevation(n=1),and hand-foot syndrome(n=2).No grade 4 or higher toxicity was observed.CONCLUSION Regorafenib combined with PD-1 inhibitor could lead to a longer PFS in some patients with MSS mCRC.The PLR might be a prediction of the patient response to this therapy.
基金Supported by Fundamental Research Funds for the Central UniversitiesPostgraduate Research and Practice Innovation Program of Jiangsu Province,No. KYCX19_0118+2 种基金Jiangsu Science and Technology ProjectInnovative Team Project of Esophagus,No. 2017ZXK7QW08National Natural Science Foundation of China,No. 81570503。
文摘BACKGROUND There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma(ESCC) who are not eligible to undergo surgical treatment.AIM To introduce a novel therapy called endoscopic debulking resection(Ed R) followed by additive chemoradiotherapy(CRT) and evaluate its efficacy and safety.METHODS Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received Ed R followed by CRT were deemed the Ed R + CRT group and those without CRT were deemed the Ed R group. Overall survival(OS), progression-free survival(PFS), and adverse events were evaluated.RESULTS A total of 41 patients were enrolled. At a median follow-up of 36 mo(range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent Ed R plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent Ed R alone(1-year OS, 83.3%;2-year OS, 58.3%;3-year OS, 50%;P = 0.05). The estimated 2-year cumulative PFS rate after Ed R + CRT was 85.7%, while it was 61.5% after Ed R(P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage(stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the Ed R procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after Ed R.CONCLUSION Ed R plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.
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 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.
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.clinicaltrials.gov/,OMESIA,NCT05129202.
基金the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences(No.CI2021A01808)the Natural Science Foundation of Beijing(No.7212189)the Outstanding Young Scientific and Technological Talents(Innovation)Training Program of China Academy of Chinese Medical Sciences(No.ZZ15-YQ-026)。
文摘Objective: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival(PFS) and overall survival(OS) of limited-stage small-cell lung cancer(LS-SCLC) patients after the first-line chemoradiotherapy. Methods: The data of 67 LS-SCLC patients who received combined treatment of Chinese medicine(CM) and Western medicine(WM) between January 2013 and May 2020 at the outpatient clinic of Guang’anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method(Kaplan–Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. Results: The median PFS in the CM and WM combination treatment group and the WM group were 19 months(95% CI: 12.36–25.64) vs. 9 months(95% CI: 5.96–12.04), respectively, HR=0.43(95% CI: 0.27–0.69, P <0.001). The median OS in the CM and WM combination group and the WM group were 34.00 months(95% CI could not be calculated) vs. 18.63 months(95% CI: 16.43–20.84), respectively, HR=0.40(95% CI: 0.24–0.66, P<0.001). Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months(P<0.001). Conclusion: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone.(Registration No. Chi CTR2200056616)
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 recurrent or metastatic ESCC.
