Introduction: Immune checkpoint inhibitors targeting programmed death protein-1 and cytotoxic-T-lymphocyte-antigen-4 have revolutionized the treatment of various cancers. Despite their effectiveness, these therapies c...Introduction: Immune checkpoint inhibitors targeting programmed death protein-1 and cytotoxic-T-lymphocyte-antigen-4 have revolutionized the treatment of various cancers. Despite their effectiveness, these therapies can lead to immune related adverse events. Observation: We reported a case of a 43- year-old white woman who was referred to our department for a management of acute polyarthritis. She was followed for a relapsing metastatic melanoma (stage IIIb) by surgery and Pembrolizumab, an immune checkpoint inhibitor targeting programmed death protein-1. After receiving her 4th cycle of this therapy she developed arthritis of the knees and the ankles, tenosynovitis and dry eyes with keratitis. After exclusion of other causes of polyarthritis such as connective-tissue disease, the diagnosis of rheumatologic immunerelated adverse events was retained. She was treated by 20 mg of prednisone daily, Pembrolizumab was discontinued. The evolution was favorable. Conclusion: Rheumatologic manifestations secondary to immune checkpoint inhibitors have been less well described in the literature. Their management requires the collaboration of oncologists and rheumatologists to limit the diagnostic delay and for an appropriate therapeutic choice according to their severity.展开更多
BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of a...BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key cl...Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.展开更多
Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhanc...Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhance their efficacy in clinical settings2.Addressing this challenge is critical for advancing the impact of immunotherapy in oncology.展开更多
Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatme...Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.展开更多
Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of adv...Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.展开更多
BACKGROUND Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma(HCC).In recent years,several studies have explored the clinical efficacy and safety of the combination ther...BACKGROUND Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma(HCC).In recent years,several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization(TACE)with tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs).AIM To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC.METHODS All eligible cohort,non-randomized controlled,and randomized controlled trial studies from the PubMed,Web of Science,Embase,Cochrane Library,and MedLine databases up to March 20,2024 were screened for the present metaanalysis.The study endpoints included complete response(CR),objective response rate(ORR),disease control rate(DCR),overall survival(OS),progressionfree survival(PFS),and adverse events(AEs).Stata 16/18 software was used for this meta-analysis,and a P value of<0.05 was considered statistically significant.RESULTS A total of 29 studies with 1754 patients were included.Among the patients who received the TACE therapy with TKIs and ICIs,the tumor response results revealed a pooled CR,ORR,and DCR of 14%[95%CI(0.11–0.18)],61%[95%CI(0.55–0.66)],and 85%[95%CI(0.83–0.87)],respectively.In terms of the survival outcomes,the pooled median PFS and OS were 10.25 months[95%CI(9.31–11.18)]and 20.47 months[95%CI(18.98–21.97)],respectively.The pooled prevalence of all-grade AEs during the triple treatment was 90%[95%CI(0.84–0.94)]and that of grade≥3 AEs was 32%[95%CI(0.24–0.42)].CONCLUSION The combination therapy of TACE,TKIs,and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.展开更多
The combination of transcatheter arterial chemoembolization(TACE)and tyrosine kinase inhibitors(TKIs)has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma(HCC).TACE and TKIs ca...The combination of transcatheter arterial chemoembolization(TACE)and tyrosine kinase inhibitors(TKIs)has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma(HCC).TACE and TKIs can affect the immune microenvironment in patients with HCC.AIM To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.METHODS Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib,lenvatinib,sorafenib,or donafenib before and after 3 wk of treatment were collected.Monocytes were co-cultured with LM3 liver cancer cells,and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment.Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model,and the immune response of tumor tissues was analyzed using immunohistochemistry.RESULTS Compared to before combination therapy,the proportion of programmed cell death protein 1(PD-1)+mononuclear cells and the number of CD4+T cells decreased in the TACE+apatinib group,while the number of absolute count of CD4+and CD8+T cells increased in the TACE+lenvatinib group.Furthermore,the number of regulatory cells decreased in the TACE+donafenib group,whereas the number of CD8+T and natural killer cells increased.Additionally,monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups.Combining TACE with donafenib or lenvatinib increased CD8+T cell infiltration into the tumor tissue.In addition,the proportion of PD-1+in CD8+cells,absolute CD8+T lymphocyte count,and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.CONCLUSION TACE,in combination with different TKIs,produces different immune responses.Specifically,TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influe...The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various factors.This manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ICIs.Additionally,this study introduced a visual predictive model to estimate the prognosis of GC patients.If confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.展开更多
In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite...In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.展开更多
BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to al...BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to all patients with advanced GC.AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models.METHODS Data from 273 patients diagnosed with GC and distant metastasis,who un-derwent≥1 cycle(s)of ICIs therapy were included in this study.Patients were randomly divided into training and test sets at a ratio of 7:3.Training set data were used to develop the machine learning models,and the test set was used to validate their predictive ability.Shapley additive explanations were used to provide insights into the best model.RESULTS Among the 273 patients with GC treated with ICIs in this study,112 died within 1 year,and 129 progressed within the same timeframe.Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting(XGBoost),logistic regression,and decision tree.After comprehensive evaluation,XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival.CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy.Patient nutritional status may,to some extent,reflect prognosis.展开更多
Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-ba...Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.展开更多
In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expresse...In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.展开更多
Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irA...Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.展开更多
Hepatocellular carcinoma cells are relatively prone to metastasis and have a high degree of heterogeneity, making a successful cure rather difficult. In recent years, an increasing number of immune checkpoint inhibito...Hepatocellular carcinoma cells are relatively prone to metastasis and have a high degree of heterogeneity, making a successful cure rather difficult. In recent years, an increasing number of immune checkpoint inhibitors have been approved for listing. Due to their strong targeting and relatively low toxic and side effects, the application of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma has become more widespread. Currently, the research on immune checkpoint inhibitors mainly concentrates on PD-1/PDL1, CTLA-4, TIM-3, LAG-3, and TIGIT. Although they have certain advantages, the occurrence of drug resistance has also been frequently observed in clinical practice, presenting certain limitations. This study examined the structural features of key immune checkpoints, and explored the clinical implementation of their inhibitors and drug resistance mechanisms, aiming to offer insights for improved use of immune checkpoint inhibitors in clinical settings.展开更多
BACKGROUND Accurate data on the prognosis of bone metastases are necessary for appropriate treatment.Immune checkpoint inhibitors(ICIs)are widely used in the treatment of gene mutation-negative non-small cell lung can...BACKGROUND Accurate data on the prognosis of bone metastases are necessary for appropriate treatment.Immune checkpoint inhibitors(ICIs)are widely used in the treatment of gene mutation-negative non-small cell lung cancer(GMN-NSCLC).AIM To investigate the prognostic factors in patients with bone metastases from GMNNSCLC following ICI use.METHODS This retrospective cohort study included 45 patients with GMN-NSCLC who were treated for bone metastases from 2017 to 2022 and received chemotherapy after diagnosis.Using Kaplan–Meier curves and Cox proportional hazards models,we evaluated the association between overall survival(OS)and clinical parameters,including serum biochemical concentrations and blood cell count.RESULTS Univariate analysis showed that Eastern Cooperative Oncology Group performance status≤1 and the use of ICIs and bone-modifying agents after bone metastasis diagnosis were significantly associated with a favorable OS.Multivariate analysis revealed that ICI use after bone metastasis diagnosis was signicantly associated with a favorable OS.CONCLUSION ICI use after bone metastasis diagnosis may be a favorable prognostic factor in patients with bone metastases of GMN-NSCLC.Consideration of ICI treatment for bone metastasis and GMN-NSCLC is warranted to establish a more accurate predictive nomogram for patients with bone metastasis.展开更多
Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectivenes...Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.展开更多
Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Al...Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.展开更多
文摘Introduction: Immune checkpoint inhibitors targeting programmed death protein-1 and cytotoxic-T-lymphocyte-antigen-4 have revolutionized the treatment of various cancers. Despite their effectiveness, these therapies can lead to immune related adverse events. Observation: We reported a case of a 43- year-old white woman who was referred to our department for a management of acute polyarthritis. She was followed for a relapsing metastatic melanoma (stage IIIb) by surgery and Pembrolizumab, an immune checkpoint inhibitor targeting programmed death protein-1. After receiving her 4th cycle of this therapy she developed arthritis of the knees and the ankles, tenosynovitis and dry eyes with keratitis. After exclusion of other causes of polyarthritis such as connective-tissue disease, the diagnosis of rheumatologic immunerelated adverse events was retained. She was treated by 20 mg of prednisone daily, Pembrolizumab was discontinued. The evolution was favorable. Conclusion: Rheumatologic manifestations secondary to immune checkpoint inhibitors have been less well described in the literature. Their management requires the collaboration of oncologists and rheumatologists to limit the diagnostic delay and for an appropriate therapeutic choice according to their severity.
基金Supported by the Key Research and Development Projects of Anhui Province,No.202104j07020048National Key Research and Development Program of China,No.2022YFA1304500.
文摘BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
基金supported by Shandong Provincial Natural Science Foundation(ZR2023LZL005)Jinan Science and Technology Development Foundation.
文摘Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.
基金supported by grants from the National Key R&D Program of China(2022YFA1206100 and 2021YFA1201100)the National Natural Science Foundation of China(32271449)+1 种基金CAS Project for Young Scientists in Basic Research(YSBR-036,China)Beijing Natural Science Foundation(Z230008,China).
文摘Immunotherapy remains one of the most promising strategies for cancer treatment,with ICIs at the forefront of this innovation1.However,patient response to ICIs is highly variable,highlighting the urgent need to enhance their efficacy in clinical settings2.Addressing this challenge is critical for advancing the impact of immunotherapy in oncology.
文摘Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.
基金Supported by IU Simon Comprehensive Cancer Center grant,No.5P30CA082709-24.
文摘Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.
基金Supported by Jiaxing Public Welfare Research Project,No.2022AD30046.
文摘BACKGROUND Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma(HCC).In recent years,several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization(TACE)with tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs).AIM To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC.METHODS All eligible cohort,non-randomized controlled,and randomized controlled trial studies from the PubMed,Web of Science,Embase,Cochrane Library,and MedLine databases up to March 20,2024 were screened for the present metaanalysis.The study endpoints included complete response(CR),objective response rate(ORR),disease control rate(DCR),overall survival(OS),progressionfree survival(PFS),and adverse events(AEs).Stata 16/18 software was used for this meta-analysis,and a P value of<0.05 was considered statistically significant.RESULTS A total of 29 studies with 1754 patients were included.Among the patients who received the TACE therapy with TKIs and ICIs,the tumor response results revealed a pooled CR,ORR,and DCR of 14%[95%CI(0.11–0.18)],61%[95%CI(0.55–0.66)],and 85%[95%CI(0.83–0.87)],respectively.In terms of the survival outcomes,the pooled median PFS and OS were 10.25 months[95%CI(9.31–11.18)]and 20.47 months[95%CI(18.98–21.97)],respectively.The pooled prevalence of all-grade AEs during the triple treatment was 90%[95%CI(0.84–0.94)]and that of grade≥3 AEs was 32%[95%CI(0.24–0.42)].CONCLUSION The combination therapy of TACE,TKIs,and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.
基金Supported by Henan Province Natural Science Foundation,No.212300410403Medical Education Research Project of Henan Province,No.Wjlx2021334。
文摘The combination of transcatheter arterial chemoembolization(TACE)and tyrosine kinase inhibitors(TKIs)has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma(HCC).TACE and TKIs can affect the immune microenvironment in patients with HCC.AIM To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.METHODS Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib,lenvatinib,sorafenib,or donafenib before and after 3 wk of treatment were collected.Monocytes were co-cultured with LM3 liver cancer cells,and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment.Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model,and the immune response of tumor tissues was analyzed using immunohistochemistry.RESULTS Compared to before combination therapy,the proportion of programmed cell death protein 1(PD-1)+mononuclear cells and the number of CD4+T cells decreased in the TACE+apatinib group,while the number of absolute count of CD4+and CD8+T cells increased in the TACE+lenvatinib group.Furthermore,the number of regulatory cells decreased in the TACE+donafenib group,whereas the number of CD8+T and natural killer cells increased.Additionally,monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups.Combining TACE with donafenib or lenvatinib increased CD8+T cell infiltration into the tumor tissue.In addition,the proportion of PD-1+in CD8+cells,absolute CD8+T lymphocyte count,and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.CONCLUSION TACE,in combination with different TKIs,produces different immune responses.Specifically,TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金Supported by National Nature Science Foundation of China,No.82320108022Shanghai Rising-Star Program,No.21QA1409000Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory Cancer Transformation,No.2021KJ03-12.
文摘The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various factors.This manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ICIs.Additionally,this study introduced a visual predictive model to estimate the prognosis of GC patients.If confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.
文摘In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.
基金Supported by the Nn10 Program of Harbin Medical University Cancer Hospital,China,No.Nn10 PY 2017-03.
文摘BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to all patients with advanced GC.AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models.METHODS Data from 273 patients diagnosed with GC and distant metastasis,who un-derwent≥1 cycle(s)of ICIs therapy were included in this study.Patients were randomly divided into training and test sets at a ratio of 7:3.Training set data were used to develop the machine learning models,and the test set was used to validate their predictive ability.Shapley additive explanations were used to provide insights into the best model.RESULTS Among the 273 patients with GC treated with ICIs in this study,112 died within 1 year,and 129 progressed within the same timeframe.Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting(XGBoost),logistic regression,and decision tree.After comprehensive evaluation,XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival.CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy.Patient nutritional status may,to some extent,reflect prognosis.
文摘Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.
基金Supported by Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz,No.NC23189.0.
文摘In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.
基金Supported by The Fundamental Research Funds for the Central Universities,No.2019CDYGYB024The National Natural Science Foundation of China,No.31300726The Chongqing Primary and Middle School Innovation Talent Training Project,No.CY220113.
文摘Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.
文摘Hepatocellular carcinoma cells are relatively prone to metastasis and have a high degree of heterogeneity, making a successful cure rather difficult. In recent years, an increasing number of immune checkpoint inhibitors have been approved for listing. Due to their strong targeting and relatively low toxic and side effects, the application of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma has become more widespread. Currently, the research on immune checkpoint inhibitors mainly concentrates on PD-1/PDL1, CTLA-4, TIM-3, LAG-3, and TIGIT. Although they have certain advantages, the occurrence of drug resistance has also been frequently observed in clinical practice, presenting certain limitations. This study examined the structural features of key immune checkpoints, and explored the clinical implementation of their inhibitors and drug resistance mechanisms, aiming to offer insights for improved use of immune checkpoint inhibitors in clinical settings.
文摘BACKGROUND Accurate data on the prognosis of bone metastases are necessary for appropriate treatment.Immune checkpoint inhibitors(ICIs)are widely used in the treatment of gene mutation-negative non-small cell lung cancer(GMN-NSCLC).AIM To investigate the prognostic factors in patients with bone metastases from GMNNSCLC following ICI use.METHODS This retrospective cohort study included 45 patients with GMN-NSCLC who were treated for bone metastases from 2017 to 2022 and received chemotherapy after diagnosis.Using Kaplan–Meier curves and Cox proportional hazards models,we evaluated the association between overall survival(OS)and clinical parameters,including serum biochemical concentrations and blood cell count.RESULTS Univariate analysis showed that Eastern Cooperative Oncology Group performance status≤1 and the use of ICIs and bone-modifying agents after bone metastasis diagnosis were significantly associated with a favorable OS.Multivariate analysis revealed that ICI use after bone metastasis diagnosis was signicantly associated with a favorable OS.CONCLUSION ICI use after bone metastasis diagnosis may be a favorable prognostic factor in patients with bone metastases of GMN-NSCLC.Consideration of ICI treatment for bone metastasis and GMN-NSCLC is warranted to establish a more accurate predictive nomogram for patients with bone metastasis.
基金funded by the Science and Technology Plan of Inner Mongolia Autonomous Region(no.2022YFSH0097)the Medical Research Advancement Fund Project(no.TB212014).
文摘Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.
文摘Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.
