The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.展开更多
Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application....Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application.Alantolactone(A)was found to augment the anticancer efficacy of paclitaxel(P)at a molar ratio of 1:0.5(P:A)through induction of more potent ICD via modulation of STAT3 signaling pathways.Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents,thereby enhancing multi-drug chemoimmunotherapy.To improve tumor targeting ability and bioavailability of hydrophobic drugs,an amphiphilic prodrug conjugate(HA-PTX)was chemically modified with paclitaxel(PTX)and hyaluronic acid(HA)as a backbone.Based on this concept,CD44-targeted nanodrugs(A@HAP NPs)were developed for co-delivery of A and P in colorectal cancer treatment,aiming to achieve synergistic toxicity-based chemo-immunotherapy.The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting,providing a solid foundation for subsequent synergistic therapy and immunoregulation.In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation,thus offering a novel approach for colorectal cancer chemoimmunotherapy.展开更多
Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteri...Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteristics for event-free survival(EFS),major pathological response(MPR),and pathological complete response(pCR)in patients with NSCLC undergoing neoadjuvant chemoimmunotherapy.Methods:A retrospective analysis was performed on the clinical data of 180 patients with NSCLC who received neoadjuvant chemoimmunotherapy between October 2019 and December 2023.The primary endpoint was EFS,and the secondary endpoint was the pathological response rate.Fisher exact test and the nonparametricMann-Whitney U test were used to compare categorical and continuous data between the pCR/MPR and non-pCR/non-MPR groups.The Kaplan-Meier method was used to estimate EFS curves,and Cox regression analysis was performed to compare the differences in EFS between patients with or without pCR or MPR.Results:Sex(p=0.004),smoking history(p=0.025),and clinical stage(p=0.002)were identified as predictors of pCR and MPR.In our study,pCR was observed in 38.12%and MPR in 44.75%of the patients.Through the multivariate logistic regression model,age and pathological response were found to predict the 1-and 2-year EFS rates,demonstrating satisfactory predictive power(area under the curve,0.866 and 0.736,respectively).Patients with pCR or MPR exhibited longer EFS compared with those without pCR or MPR,as determined by Cox analysis.Conclusions:Sex,smoking history,and clinical stage were identified as predictors of pCR and MPR in patients with NSCLC.Survival analysis revealed that age and pathological response were key prognostic factors for EFS.展开更多
Esophageal squamous cell carcinoma(ESCC)remains a highly aggressive ma-lignancy with limited effective therapeutic options for patients with locally advanced unresectable disease.The study by Wei et al,featured in thi...Esophageal squamous cell carcinoma(ESCC)remains a highly aggressive ma-lignancy with limited effective therapeutic options for patients with locally advanced unresectable disease.The study by Wei et al,featured in this issue,highlights the potential of induction chemoimmunotherapy followed by definitive radiotherapy or concurrent chemoradiotherapy to improve treatment outcomes in this challenging patient population.This retrospective analysis of 132 patients demonstrates promising results,including a median progression-free survival of 14.2 months and overall survival of 19.9 months,alongside an acceptable safety profile.Notably,the study identifies the effectiveness of induction therapy and maintenance immunotherapy as key prognostic factors,emphasizing the syner-gistic potential of integrating immune checkpoint inhibitors with radiotherapy.While these findings are encouraging,they require further validation through prospective trials,along with biomarker-based and immune response studies,to refine patient selection and maximize therapeutic benefits.This editorial explores the implications of this research,its impact on clinical practice,and future di-rections for advancing the treatment landscape of ESCC.展开更多
Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immu...Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.展开更多
AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treat...AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.展开更多
BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However...BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.展开更多
BACKGROUND Primary testicular lymphoma(PTL)is a rare,aggressive malignancy,representing a small fraction of testicular tumors and non-Hodgkin lymphomas,yet it is the most common testicular malignancy in older men.Diff...BACKGROUND Primary testicular lymphoma(PTL)is a rare,aggressive malignancy,representing a small fraction of testicular tumors and non-Hodgkin lymphomas,yet it is the most common testicular malignancy in older men.Diffuse large B-cell lymphoma(DLBCL),which is typically the aggressive subtype,dominates PTL and shows diffuse B-cell infiltration.Venous tumor thrombus,uncommon in lymphomas,is uniquely reported in this case of testicular DLBCL with gonadal vein involvement.CASE SUMMARY A 62-year-old man presented with a two-month history of painless left testicular swelling and stiffness.Diagnostic imaging[ultrasonography,computed tomography(CT),and 18F-fluorodeoxyglucose positron emission tomography/CT(18FFDG-PET/CT)]revealed bilateral testicular masses and a gonadal vein tumor thrombus(SUVmax 16.5).Left orchiectomy confirmed DLBCL with CD20,Bcl-2,and MUM1 positivity(Ki-67:approximately 80%).The disease was staged as Ann Arbor stage IVA(International Prognostic Index score 3,high-intermediate risk).The patient received Rituximab,Polatuzumab Vedotin,Cyclophosphamide,Epirubicin,and Prednisolone chemotherapy,completing the first cycle with good tolerability.No adverse events were reported,and follow-up is ongoing to assess long-term outcomes.This case highlights the diagnostic utility of 18F-FDGPET/CT and the importance of multidisciplinary management in rare PTL presentations with tumor thrombus.CONCLUSION This case demonstrates the diagnostic complexities of PTL with gonadal vein tumor thrombus,underscoring the importance of considering lymphoma in elderly patients with testicular masses and venous involvement.A multi-disciplinary team including urologists,hematologists,and radiation oncologists is needed to ensure appropriate therapy.展开更多
Objective This study aimed to develop an effective predictive tool that combines radiomics and clinical information to predict the survival outcomes of patients with advanced non-small cell lung cancer(NSCLC)undergoin...Objective This study aimed to develop an effective predictive tool that combines radiomics and clinical information to predict the survival outcomes of patients with advanced non-small cell lung cancer(NSCLC)undergoing chemoimmunotherapy.Methods Data were collected from 201 patients with advanced NSCLC who received first-line chemoimmunotherapy across three institutions:those from Centers I&II(n=164)were randomly split in a 7:3 ratio into training(n=115)and validation(n=49)cohorts,and those form Center III(n=37)were designated as the external test cohort.The analysis was conducted using CT images and clinical data obtained before and after induction chemoimmunotherapy.We developed multiple intratumoral and peritumoral radiomics-based models,along with clinical prediction model that integrated patients’baseline clinicopathological characteristics with plasma biomarker profiles,to predict progression-free survival(PFS).Based on expectations derived from prior established models,a stepwise backward elimination approach was utilized to select candidate submodels for the combined model construction.This combined model was internally validated using time-dependent ROC curves in training and validation sets and externally validated in the external test set.Results The combined model was constructed by integrating four candidate sub-models(DeltaSub,Clinical,P4mm,and Habitat)selected through the stepwise regression analysis.The combined model demonstrated superior performance compared to conventional models that utilized only clinical features,as well as Classical-Pre,Classical-Post,delta intratumor feature-based,and peritumor feature-based models.The combined model demonstrated satisfactory predictive performance across all three datasets,achieving a C-index of 0.849(95%CI:0.812–0.885)in the training set,0.744(95%CI:0.664–0.842)in the validation set,and 0.731(95%CI:0.639–0.824)in the external test set for PFS.Conclusions We developed a novel radiomic-clinical model to predict PFS for advanced NSCLC patients treated with first-line chemoimmunotherapy.This model enhanced survival assessment through comprehensive feature integration.展开更多
The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently develop...The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently developed therapeutic strategies against NHL such as chemoimmunotherapy and targeted therapy have drawbacks.Therefore,novel therapeutic approaches for NHL are urgently needed.Maytansine-loaded PLA-TPGS(polyethylene glycol 1000 succinate-polylactide)nanoparticles were synthesized.And then,rituximab targeting NHL was conjugated together by using EDC(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide)as a coupling agent.The in vitro/vivo antitumor activity was evaluated by Raji cell proliferation inhibition and nude mice xenograft tumor models for NHL.Both the rituximab-conjugated and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs(Nanoparticles)-rituximab)and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs)presented significant inhibition effect on Raji cell proliferation in a concentration-dependent manner.Compared with conventional maytansine and maytansine-NPs,maytansine-NPs-rituximab showed significantly enhanced cytotoxicity and increased cell apoptosis in Raji cells.The maytansine-NPs-rituximab described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to CD20+B cell malignancies.展开更多
Objective： The aim of the present study was to investigate the effects of 5-fluorouracil（5-Fu） and oxaliplatin on the function and activation pathways of mouse dendritic cells（DCs）, and to clarify whether 5-Fu/ox...Objective： The aim of the present study was to investigate the effects of 5-fluorouracil（5-Fu） and oxaliplatin on the function and activation pathways of mouse dendritic cells（DCs）, and to clarify whether 5-Fu/oxaliplatin combined with the CD1d-MC38/α-galactosylceramide（α-GC） tumor vaccine exhibits synergistic effects on the treatment of colon cancer in mice.Methods： The combination of the Toll like receptor（TLR） ligands and/or 5-Fu/oxaliplatin was added into myeloid-derived DCs in vitro culture. DC phenotypic changes were detected by flow cytometry, and the secretion of DC cytokines was detected by cytometric bead array（CBA）. A MC38 mouse colon cancer model was constructed and the DCs were isolated from the spleen, tumor tissue and lymph nodes following intraperitoneal injection of 5-Fu/oxaliplatin. The cell phenotypes were detected by flow cytometry. The tumor infiltrating leukocytes,splenocytes and lymph node cells were co-cultured with the dead MC38 tumor cells, and the secretion levels of interferon-γ（IFN-γ） were detected. 5-Fu/oxaliplatin combined with our previously developed CD1d-MC38/α-GC tumor vaccine was used to inhibit the growth of MC38 colon cancer in mice, and the tumor growth rate and survival time were recorded.Results： 5-Fu/oxaliplatin exerted no significant effect on the expression of the stimulating phenotypes of DCs in vitro, while it could reduce the expression of programmed death ligand 1/2（PD-L1/L2） and promote interleukin-12（IL-12） secretion by DCs. Furthermore 5-Fu/oxaliplatin was beneficial to the differentiation of T-helper 1（Th1） cells. 5-Fu/oxaliplatin further enhanced the stimulating phenotypic expression of DCs in tumor bearing mice, decreased PD-L1/L2 expression, and specifically activated the lymphocytes. The CD1d-MC38/α-GC tumor vaccine combined with 5-Fu/oxaliplatin could exert a synergistic role that resulted in a significant delay of the tumor growth rate, and an increase in the survival time of tumor bearing mice.Conclusions： 5-Fu/oxaliplatin decreased the expression of the DC inhibitory phenotypes PD-L1/L2, promoted DC phenotypic maturation in tumor bearing mice, activated the lymphocytes of tumor bearing mice, and exerted synergistic effects with the CD1d-MC38/α-GC colon cancer tumor vaccine.展开更多
Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(...Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(UM-IGHV)and TP53 aberration failed to benefit from it.The emergency of the small molecular targeted agents including Bruton’s tyrosine kinase(BTK)inhibitor(BTKi)leads to a brand-new era,from a CIT to a chemo-free era in CLL.However,the treatment of target agents is not enough to attain a deep remission and high rate of complete remission(CR),especially in patients with high risks.The long duration brought about problems,such as cost,drug resistance and toxicity.To benefit CLL in progression free survival(PFS)and long-term remission,exploration of time-limited therapies,mainly with BTKi plus CIT and BCL2i based combination therapy has become a mainstream in clinical trials.The time-limited combination therapy shed light on the promising potentiality to attain sustainable deep remission and partly overcame the risk factors,although long term follow-up is required to consolidate the conclusion.In this review,we intend to introduce key results of clinical trials with combination therapy,discuss the achievements and limitations and put forward future direction for clinical trial design in this field.展开更多
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
基金supported by Zhejiang Provincial Natural Science Foundation(LYY22H300001,LGF22H150016)Wenzhou Municipal Science and Technology Bureau(Y20210212)+2 种基金Application Basic Research Project of Liaoning Provincial Department of Science and Technology(2023JH2/101700072)Zhejiang Medical Doctor Association(YS2022-2-001)Health innovation talents program(Longfa Kou)from Health Commission of Zhejiang Province.
文摘Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application.Alantolactone(A)was found to augment the anticancer efficacy of paclitaxel(P)at a molar ratio of 1:0.5(P:A)through induction of more potent ICD via modulation of STAT3 signaling pathways.Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents,thereby enhancing multi-drug chemoimmunotherapy.To improve tumor targeting ability and bioavailability of hydrophobic drugs,an amphiphilic prodrug conjugate(HA-PTX)was chemically modified with paclitaxel(PTX)and hyaluronic acid(HA)as a backbone.Based on this concept,CD44-targeted nanodrugs(A@HAP NPs)were developed for co-delivery of A and P in colorectal cancer treatment,aiming to achieve synergistic toxicity-based chemo-immunotherapy.The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting,providing a solid foundation for subsequent synergistic therapy and immunoregulation.In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation,thus offering a novel approach for colorectal cancer chemoimmunotherapy.
基金Supported by a grant from Beijing Municipal PublicWelfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,No.JYY2023-14).
文摘Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteristics for event-free survival(EFS),major pathological response(MPR),and pathological complete response(pCR)in patients with NSCLC undergoing neoadjuvant chemoimmunotherapy.Methods:A retrospective analysis was performed on the clinical data of 180 patients with NSCLC who received neoadjuvant chemoimmunotherapy between October 2019 and December 2023.The primary endpoint was EFS,and the secondary endpoint was the pathological response rate.Fisher exact test and the nonparametricMann-Whitney U test were used to compare categorical and continuous data between the pCR/MPR and non-pCR/non-MPR groups.The Kaplan-Meier method was used to estimate EFS curves,and Cox regression analysis was performed to compare the differences in EFS between patients with or without pCR or MPR.Results:Sex(p=0.004),smoking history(p=0.025),and clinical stage(p=0.002)were identified as predictors of pCR and MPR.In our study,pCR was observed in 38.12%and MPR in 44.75%of the patients.Through the multivariate logistic regression model,age and pathological response were found to predict the 1-and 2-year EFS rates,demonstrating satisfactory predictive power(area under the curve,0.866 and 0.736,respectively).Patients with pCR or MPR exhibited longer EFS compared with those without pCR or MPR,as determined by Cox analysis.Conclusions:Sex,smoking history,and clinical stage were identified as predictors of pCR and MPR in patients with NSCLC.Survival analysis revealed that age and pathological response were key prognostic factors for EFS.
基金Supported by National Science Centre,Poland,No.2021/43/B/NZ5/03345.
文摘Esophageal squamous cell carcinoma(ESCC)remains a highly aggressive ma-lignancy with limited effective therapeutic options for patients with locally advanced unresectable disease.The study by Wei et al,featured in this issue,highlights the potential of induction chemoimmunotherapy followed by definitive radiotherapy or concurrent chemoradiotherapy to improve treatment outcomes in this challenging patient population.This retrospective analysis of 132 patients demonstrates promising results,including a median progression-free survival of 14.2 months and overall survival of 19.9 months,alongside an acceptable safety profile.Notably,the study identifies the effectiveness of induction therapy and maintenance immunotherapy as key prognostic factors,emphasizing the syner-gistic potential of integrating immune checkpoint inhibitors with radiotherapy.While these findings are encouraging,they require further validation through prospective trials,along with biomarker-based and immune response studies,to refine patient selection and maximize therapeutic benefits.This editorial explores the implications of this research,its impact on clinical practice,and future di-rections for advancing the treatment landscape of ESCC.
基金supported by the National Natural Science Foundation of China(No.81974498,No.81773652)。
文摘Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.
基金Grants-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘AIM: To investigate the association of plasma levels of interleukin(IL)-6 and-8 with Wilms' tumor 1(WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma(PDA) treated with dendritic cells(DCs) pulsed with three types of major histocompatibility complex classⅠand Ⅱ-restricted WT1 peptides combined with chemotherapy.METHODS: During the entire treatment period, plasma levels of IL-6 and-8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity(DTH) test.RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival(OS) was significantly longer in PDA patients with low plasma IL-6 levels(< 2 pg/m L) after 5 vaccinations than in patients with high plasma IL-6 levels(≥ 2 pg/m L)(P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS.CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.
基金the National Natural Science Foundation of Hunan Province,No.2023JJ60039Natural Science Foundation of Hunan Province National Health Commission,No.B202303027655+3 种基金Natural Science Foundation of Changsha Science and Technology Bureau,No.Kq2208150Wu Jieping Foundation of China,No.320.6750.2022-22-59,320.6750.2022-17-41Guangdong Association of Clinical Trials(GACT)/Chinese Thoracic Oncology Group(CTONG)and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer,No.2017B030314120.
文摘BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.
文摘BACKGROUND Primary testicular lymphoma(PTL)is a rare,aggressive malignancy,representing a small fraction of testicular tumors and non-Hodgkin lymphomas,yet it is the most common testicular malignancy in older men.Diffuse large B-cell lymphoma(DLBCL),which is typically the aggressive subtype,dominates PTL and shows diffuse B-cell infiltration.Venous tumor thrombus,uncommon in lymphomas,is uniquely reported in this case of testicular DLBCL with gonadal vein involvement.CASE SUMMARY A 62-year-old man presented with a two-month history of painless left testicular swelling and stiffness.Diagnostic imaging[ultrasonography,computed tomography(CT),and 18F-fluorodeoxyglucose positron emission tomography/CT(18FFDG-PET/CT)]revealed bilateral testicular masses and a gonadal vein tumor thrombus(SUVmax 16.5).Left orchiectomy confirmed DLBCL with CD20,Bcl-2,and MUM1 positivity(Ki-67:approximately 80%).The disease was staged as Ann Arbor stage IVA(International Prognostic Index score 3,high-intermediate risk).The patient received Rituximab,Polatuzumab Vedotin,Cyclophosphamide,Epirubicin,and Prednisolone chemotherapy,completing the first cycle with good tolerability.No adverse events were reported,and follow-up is ongoing to assess long-term outcomes.This case highlights the diagnostic utility of 18F-FDGPET/CT and the importance of multidisciplinary management in rare PTL presentations with tumor thrombus.CONCLUSION This case demonstrates the diagnostic complexities of PTL with gonadal vein tumor thrombus,underscoring the importance of considering lymphoma in elderly patients with testicular masses and venous involvement.A multi-disciplinary team including urologists,hematologists,and radiation oncologists is needed to ensure appropriate therapy.
基金supported by the National Natural Science Foundation of China(Nos.82203502,81670144,and 82403850)in addition,it was also funded by the Cross-innovation Talent Project at Renmin Hospital of Wuhan University(No.JCRCGW-2022-002).
文摘Objective This study aimed to develop an effective predictive tool that combines radiomics and clinical information to predict the survival outcomes of patients with advanced non-small cell lung cancer(NSCLC)undergoing chemoimmunotherapy.Methods Data were collected from 201 patients with advanced NSCLC who received first-line chemoimmunotherapy across three institutions:those from Centers I&II(n=164)were randomly split in a 7:3 ratio into training(n=115)and validation(n=49)cohorts,and those form Center III(n=37)were designated as the external test cohort.The analysis was conducted using CT images and clinical data obtained before and after induction chemoimmunotherapy.We developed multiple intratumoral and peritumoral radiomics-based models,along with clinical prediction model that integrated patients’baseline clinicopathological characteristics with plasma biomarker profiles,to predict progression-free survival(PFS).Based on expectations derived from prior established models,a stepwise backward elimination approach was utilized to select candidate submodels for the combined model construction.This combined model was internally validated using time-dependent ROC curves in training and validation sets and externally validated in the external test set.Results The combined model was constructed by integrating four candidate sub-models(DeltaSub,Clinical,P4mm,and Habitat)selected through the stepwise regression analysis.The combined model demonstrated superior performance compared to conventional models that utilized only clinical features,as well as Classical-Pre,Classical-Post,delta intratumor feature-based,and peritumor feature-based models.The combined model demonstrated satisfactory predictive performance across all three datasets,achieving a C-index of 0.849(95%CI:0.812–0.885)in the training set,0.744(95%CI:0.664–0.842)in the validation set,and 0.731(95%CI:0.639–0.824)in the external test set for PFS.Conclusions We developed a novel radiomic-clinical model to predict PFS for advanced NSCLC patients treated with first-line chemoimmunotherapy.This model enhanced survival assessment through comprehensive feature integration.
文摘The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently developed therapeutic strategies against NHL such as chemoimmunotherapy and targeted therapy have drawbacks.Therefore,novel therapeutic approaches for NHL are urgently needed.Maytansine-loaded PLA-TPGS(polyethylene glycol 1000 succinate-polylactide)nanoparticles were synthesized.And then,rituximab targeting NHL was conjugated together by using EDC(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide)as a coupling agent.The in vitro/vivo antitumor activity was evaluated by Raji cell proliferation inhibition and nude mice xenograft tumor models for NHL.Both the rituximab-conjugated and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs(Nanoparticles)-rituximab)and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs)presented significant inhibition effect on Raji cell proliferation in a concentration-dependent manner.Compared with conventional maytansine and maytansine-NPs,maytansine-NPs-rituximab showed significantly enhanced cytotoxicity and increased cell apoptosis in Raji cells.The maytansine-NPs-rituximab described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to CD20+B cell malignancies.
文摘Objective： The aim of the present study was to investigate the effects of 5-fluorouracil（5-Fu） and oxaliplatin on the function and activation pathways of mouse dendritic cells（DCs）, and to clarify whether 5-Fu/oxaliplatin combined with the CD1d-MC38/α-galactosylceramide（α-GC） tumor vaccine exhibits synergistic effects on the treatment of colon cancer in mice.Methods： The combination of the Toll like receptor（TLR） ligands and/or 5-Fu/oxaliplatin was added into myeloid-derived DCs in vitro culture. DC phenotypic changes were detected by flow cytometry, and the secretion of DC cytokines was detected by cytometric bead array（CBA）. A MC38 mouse colon cancer model was constructed and the DCs were isolated from the spleen, tumor tissue and lymph nodes following intraperitoneal injection of 5-Fu/oxaliplatin. The cell phenotypes were detected by flow cytometry. The tumor infiltrating leukocytes,splenocytes and lymph node cells were co-cultured with the dead MC38 tumor cells, and the secretion levels of interferon-γ（IFN-γ） were detected. 5-Fu/oxaliplatin combined with our previously developed CD1d-MC38/α-GC tumor vaccine was used to inhibit the growth of MC38 colon cancer in mice, and the tumor growth rate and survival time were recorded.Results： 5-Fu/oxaliplatin exerted no significant effect on the expression of the stimulating phenotypes of DCs in vitro, while it could reduce the expression of programmed death ligand 1/2（PD-L1/L2） and promote interleukin-12（IL-12） secretion by DCs. Furthermore 5-Fu/oxaliplatin was beneficial to the differentiation of T-helper 1（Th1） cells. 5-Fu/oxaliplatin further enhanced the stimulating phenotypic expression of DCs in tumor bearing mice, decreased PD-L1/L2 expression, and specifically activated the lymphocytes. The CD1d-MC38/α-GC tumor vaccine combined with 5-Fu/oxaliplatin could exert a synergistic role that resulted in a significant delay of the tumor growth rate, and an increase in the survival time of tumor bearing mice.Conclusions： 5-Fu/oxaliplatin decreased the expression of the DC inhibitory phenotypes PD-L1/L2, promoted DC phenotypic maturation in tumor bearing mice, activated the lymphocytes of tumor bearing mice, and exerted synergistic effects with the CD1d-MC38/α-GC colon cancer tumor vaccine.
基金grants from the National Natural Science Foundation of China(No.81970146)National Science Foundation of China International Cooperation and Exchange Program(No.81720108002)+1 种基金National Science and Technology Major Project(No.2018ZX09734007)Six Talent Peaks Project in Jiangsu Province,2019(No.WSN-001).
文摘Chemoimmunotherapy(CIT)is defined as standard first line treatment for chronic lymphocytic leukemia(CLL)patients while patients with unfavorable biological characteristics such as unmutated immunoglobulin heavy chain(UM-IGHV)and TP53 aberration failed to benefit from it.The emergency of the small molecular targeted agents including Bruton’s tyrosine kinase(BTK)inhibitor(BTKi)leads to a brand-new era,from a CIT to a chemo-free era in CLL.However,the treatment of target agents is not enough to attain a deep remission and high rate of complete remission(CR),especially in patients with high risks.The long duration brought about problems,such as cost,drug resistance and toxicity.To benefit CLL in progression free survival(PFS)and long-term remission,exploration of time-limited therapies,mainly with BTKi plus CIT and BCL2i based combination therapy has become a mainstream in clinical trials.The time-limited combination therapy shed light on the promising potentiality to attain sustainable deep remission and partly overcame the risk factors,although long term follow-up is required to consolidate the conclusion.In this review,we intend to introduce key results of clinical trials with combination therapy,discuss the achievements and limitations and put forward future direction for clinical trial design in this field.
