BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate...BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting angiogenesis.Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove efficacy.Lenvatinib,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE.However,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been investigated.AIM To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced HCC.METHODS A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022.Baseline characteristics were compared,and propensity score matching was applied.Overall survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were analyzed.RESULTS The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L group.The TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were reported.CONCLUSION TACE+SL demonstrated superior outcomes in terms of OS and PFS,compared to TACE+L.These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and adva...In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular carcinoma.The triple therapy,which integrates interventional therapy,targeted therapy,and immunotherapy,has emerged as a promising research focus in the treatment of liver cancer.Consequently,it is of utmost significance to select an appropriate combination of interventional therapy,targeted therapy,and immunotherapy for patients suffering from intermediate and advanced liver cancer.展开更多
BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of cu...BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of curative treatment,outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy.In recent years,immune checkpoint inhibitors,especially anti-PD-1 antibodies like sintilimab,have shown promise in improving survival when combined with chemotherapy.However,the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.AIM To compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab(SOX+PD-1),albumin-bound paclitaxel plus oxaliplatin and S-1(P-SOX),and SOX—in patients with advanced GC.METHODS A retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy.Among them,81 patients received SOX plus sintilimab,118 received the P-SOX regimen,and 100 received the SOX regimen.All patients were randomly assigned to training(70%)or validation(30%)cohorts using the R software sample function.Short-term efficacy,long-term survival outcomes,and adverse events were assessed across the three groups.Additionally,clinical factors associated with progression-free survival(PFS)were further investigated.RESULTS In terms of short-term efficacy,the SOX+sintilimab group had higher objective response rates[91.4%and 70.4%according to the tumor regression grade(TRG)and Response Evaluation Criteria in Solid Tumors(RECIST)1.1 criteria,respectively]than did the P-SOX(88.1%and 59.3%)and SOX groups(84.0%and 55.0%),although the intergroup differences were not statistically significant(P=0.167).For long-term outcomes,the SOX+sintilimab group demonstrated significantly better OS rates at 1 year(98.8%),18 months(92.6%),2 years(84.0%),and 3 years(48.1%)than did the P-SOX(93.2%,86.4%,71.2%,30.5%)and SOX(91.0%,84.0%,72.0%,29.0%)groups,with the 3-year overall survival(OS)difference being statistically significant(P=0.007).Similarly,PFS rates in the SOX+sintilimab group(1 year:92.6%;18 months:77.8%;2 years:65.4%;3 years:35.8%)were significantly greater than those in the P-SOX(82.2%,68.6%,53.4%,26.3%)and SOX(77.0%,66.0%,43.0%,27.0%)groups,with significant differences at 1 year(P=0.021)and 2 years(P=0.011).In terms of safety,grade 1-2 gastrointestinal reactions,peripheral neuropathy,and alopecia were the main TRAEs across groups.The P-SOX group had a significantly greater incidence of alopecia(54.2%vs 53.0%vs 23.5%,P=0.009)and more cases of grade 2 alopecia(6.8%vs 1.2%),potentially due to the accumulation of triple-agent toxicity.No significant intergroup differences were observed in hematologic toxicity or liver dysfunction(all P>0.05).CONCLUSION Compared with the SOX and P-SOX regimens,the SOX plus sintilimab combination demonstrated significantly improved short-and long-term efficacy with favorable safety,with superior advantages in terms of 2-and 3-year OS and early PFS,suggesting that this combination is a more promising therapeutic option for patients with advanced GC.Patients who achieved good perioperative chemotherapy responses(meeting the TRG and RECIST 1.1 criteria)and had tumor diameters≤2 cm,well-differentiated histology,earlier cTNM stages,and no lymph node metastasis had a better prognosis.展开更多
BACKGROUND Gallbladder cancer is a highly malignant and aggressive tumor,often diagnosed at an advanced stage.The prognosis for advanced gallbladder cancer remains poor,with limited options for effective treatment.CAS...BACKGROUND Gallbladder cancer is a highly malignant and aggressive tumor,often diagnosed at an advanced stage.The prognosis for advanced gallbladder cancer remains poor,with limited options for effective treatment.CASE SUMMARY A 65-year-old male patient presented with a soft tissue mass in the gallbladder.Following laparoscopic exploration,he underwent radical surgery for gallbladder cancer,with the tumor staged as pT2N1M0(stage III).Post-surgery,the patient received four cycles of adjuvant chemotherapy.However,one month later,over 60 metastatic lesions were detected in the liver,lungs,and lymph nodes.In response to the widespread metastasis,he underwent six cycles of combination therapy consisting of sintilimab,albumin-bound paclitaxel,and cisplatin.After two cycles,a partial response was achieved.Maintenance therapy was initiated with a combination of sintilimab and albumin-bound paclitaxel for four cycles.Monotherapy with sintilimab was continued thereafter until October 2023.Complete remission was confirmed in September 2021.The patient sustained this complete response for more than three years,including an eleven-month period without disease progression following the discontinuation of sintilimab.Genetic analysis revealed a tumor mutational burden of 15.4 mutations/megabase,which indicates a potentially favorable response to immunotherapy.CONCLUSION This case demonstrates the potential of combining immunotherapy(sintilimab)with chemotherapy to achieve durable remission in metastatic gallbladder cancer,even in a patient with extensive metastasis.In addition,it indicated the importance of tumor mutational burden as a predictive biomarker of immunotherapy.展开更多
BACKGROUND This article discusses a case involving a 63-year-old man with non-small cell lung cancer,who was treated with a combination of chemotherapy and immunothe-rapy.The patient was treated with five cycles of ch...BACKGROUND This article discusses a case involving a 63-year-old man with non-small cell lung cancer,who was treated with a combination of chemotherapy and immunothe-rapy.The patient was treated with five cycles of chemotherapy(pemetrexed and carboplatin)combined with sintilimab,a programmed death 1 inhibitor.CASE SUMMARY After the fifth cycle of treatment,the patient developed skin itching and a vitiligo-like rash,which are known side effects of immunotherapy.Despite dermatologi-cal consultation and treatment with topical corticosteroids,the rash worsened while the itching subsided.The patient continued with the treatment,and after 15 cycles,the tumor showed a response with a reduction in size.The vitiligo-like rash increased,but the antitumor treatment remained effective.CONCLUSION The case highlights the use of immunotherapy in patients with non-small cell lung cancer and the potential side effect of vitiligo-like rash.The patient’s tumor res-ponded well to the treatment,and despite the skin reaction,the treatment was not discontinued due to its effectiveness.The article suggests that further studies are needed to understand the mechanism behind vitiligo in patients with lung cancer receiving immune checkpoint inhibitors and whether the development of vitiligo-like rash after immune checkpoint inhibitor therapy is associated with improved prognosis.The case also underscores the importance of managing immune-related adverse events in the context of effective antitumor treatment.展开更多
Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced live...Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced liver cancer who visited from January 2022 to January 2025 were selected as samples and randomly divided into two groups.Group A received interventional therapy combined with lenvatinib and sintilimab,while Group B received interventional therapy combined with lenvatinib.Disease remission rate,adverse reactions,liver function indicators,and tumor marker indicators were compared between the two groups.Results:The disease control rate(DCR)in Group A was higher than that in Group B(P<0.05).There was no difference in adverse reaction rates between Group A and Group B(P>0.05).Total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in Group A were lower than those in Group B(P<0.05).Carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),and alpha-L-fucosidase(AFU)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:Intermediate and advanced liver cancer patients receiving interventional therapy combined with lenvatinib and sintilimab showed reduced tumor marker levels,lessened liver function damage,and a high disease control rate and treatment safety.展开更多
BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therap...BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.展开更多
BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the t...BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.展开更多
BACKGROUND Stereotactic body radiotherapy(SBRT)and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma(HCC)in retrospective studies.AIM To evaluate the efficacy of combining SB...BACKGROUND Stereotactic body radiotherapy(SBRT)and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma(HCC)in retrospective studies.AIM To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC.METHODS This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression.The primary endpoint was progression-free survival(PFS).RESULTS Twenty-five patients were enrolled from August 14,2019,to August 23,2021.The median treatment duration was 10.2(range,0.7-14.6)months.SBRT was delivered at a median dose of 54(range,48-60)Gy in 6(range,6-10)fractions.The median follow-up time was 21.9(range,10.3-39.7)mo,and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1.The median PFS was 19.7 mo[95%confidence interval(CI):16.9-NA],with PFS rates of 68%(95%CI:52-89)and 45.3%(95%CI:28-73.4)at 12 and 24 mo,respectively.The median overall survival(OS)was not reached,with OS rates of 91.5%(95%CI:80.8-100.0)and 83.2%(95%CI:66.5-100.0)at 12 and 24 mo,respectively.The 1-and 2-year local control rate were 100%and 90.9%(95%CI:75.4%-100.0%),respectively.The confirmed objective response rate and disease control rate was 96%,and 96%,respectively.Most adverse events were graded as 1 or 2,and grade 3 adverse events were observed in three patients.CONCLUSION SBRT plus sintilimab is an effective,well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.展开更多
BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ...BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.展开更多
BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the ...BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.METHODS During the period spanning from April 2019 to April 2022,Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study,the observation group and the control group.The control group was administered anlotinib hy-drochloride as their designated therapy,whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group.The administration of treatment occurred in cycles consisting of a duration of 3 wk,and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups.A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period.Changes in the levels of carcinoembryonic Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy.Finally,a 1-year follow-up was conducted for both groups of patients,and the survival status was recorded and analyzed.RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group,with a statistically significant discrepancy(76.09%vs 50.00%),reaching a significance level denoted as P<0.05.Following the administration of treatment,the observation group manifested a considerable reduction in numerous serum indicators,which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group(P<0.05).Post-treatment,the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration,surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group(P<0.05).Subsequent to the therapeutic intervention,the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality.These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group(P<0.05).The safety levels of drug use in the two group were comparable(19.57%vs 13.04%),and no distinct difference was observed upon comparison(P>0.05).After the completion of treatment,both groups of patients underwent a 1-year follow-up outside the hospital.Throughout this period,1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up.During the follow-up period of the observation group,12 patients died,resulting in a survival rate of 73.33%(33/45),while in the control group,21 patients died,resulting in a survival rate of 52.27%(23/44).The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups(log-rank=4.710,P=0.030).CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients,leading to improvements in patient immunity and prognosis.Additionally,it exerted inhibitory effects on the expression of carcinoembryonic antigen,CA199,and CA125.展开更多
BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carbo...BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.展开更多
BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of ...BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.展开更多
The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabin...The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabine plus tegafur with best response of partial response.Second-line treatment was 4 cycles of nab-paclitaxel monotherapy ended up with disease progression.Third-line treatment was sintilimab with anlotinib for 10 cycles.The patient's condition has achieved clinical complete remission so far.展开更多
Background:The prognosis for non-small cell lung cancer(NSCLC)patients treatedwith standard platinum-based chemotherapywas suboptimal,with safety concerns.Following encouraging results from a preliminary phase I study...Background:The prognosis for non-small cell lung cancer(NSCLC)patients treatedwith standard platinum-based chemotherapywas suboptimal,with safety concerns.Following encouraging results from a preliminary phase I study,this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.Methods:In this open-label,randomized controlled trial(NCT04124731),metastatic NSCLC without epithelial growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),or proto-oncogene tyrosine-protein kinase ROS(ROS1)mutations,and previous treatments for metastatic disease were enrolled.Participants were randomly assigned in a 1:1 ratio to either sintilimab(200 mg every 3 weeks)plus anlotinib(12 mg D1-14 every 3 weeks)or a standard platinum-based chemotherapy regimen.Patients in the chemotherapy group were permitted to switch to sintilimab after disease progression.The primary endpoint was the objective response rate(ORR).Results:From November 2019 to March 2023,99 patients were randomized into the sintilimab plus anlotinib group(n=49)and the chemotherapy group(n=50).The ORR was significantly higher in the sintilimab plus anlotinib group(44.9%;95%confidence interval[CI]=30.7%-59.8%)compared to the chemotherapy group(18.0%;95%CI=8.6%-31.4%,P=0.003).Progression-free survival(PFS)was also notably longer(median:14.4 vs.5.6 months;hazard ratio[HR]=0.39;95%CI=0.23-0.67;P<0.001).The 24-month overall survival rate was 58.4%(95%CI=40.4%-72.6%)and 43.2%(95%CI=26.0%-59.2%),respectively.The rate of grade 3 or higher treatment-related adverse events was lower in the sintilimab plus anlotinib group(28.0%)than in the chemotherapy group(49.0%),especially for the hematological toxicities.Conclusion:First-line sintilimab plus anlotinib showed improved ORR and PFS,alongside a superior safety profile,compared to the standard platinumbased chemotherapy for metastatic NSCLC patients.展开更多
We aimed to evaluate the efficacy and safety of adding apatinib,to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer(TNBC).In the phase 2 NeoSAC trial,patients with early ...We aimed to evaluate the efficacy and safety of adding apatinib,to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer(TNBC).In the phase 2 NeoSAC trial,patients with early TNBC received six cycles of apatinib,sintilimab,nab-paclitaxel,and carboplatin followed by surgery.The primary endpoint was pathological complete response(pCR)rate.Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment.Among 34 enrolled patients,24 achieved pCR(70.6%;95%confidence interval(CI),53.0-85.3),and 79.4%(95%CI,65.1-93.7)had residual cancer burden 0-I.Imaging evaluation showed 21 complete responses(61.8%)and 13 partial responses(38.2%).The most common grade 3-4 adverse events were leukopenia(47%),neutropenia(36%),and thrombocytopenia(24%).The 36-month disease-free survival rate stood at 94.1%with a median follow-up of 39.1 months.Notably,baseline high ImmuneScore,immune cell infiltration,and enrichment of interferon-related pathways correlated with pCR.Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets,thereby activating the tumor microenvironment.Moreover,higher oxeiptosis scores were associated with an increased likelihood of achieving pCR.Following neoadjuvant therapy,the pCR group showed a decrease in oxeiptosis score,whereas the non-pCR group exhibited an increase.Our study suggests that apatinib,sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study.ClinicalTrials.gov registration:NCT04722718.展开更多
Background and aims:Hepatocellular carcinoma(HCC)presents a significant challenge in tumor management because of its low resection rates.Conversion therapy aims to transform unresectable tumors into resectable ones th...Background and aims:Hepatocellular carcinoma(HCC)presents a significant challenge in tumor management because of its low resection rates.Conversion therapy aims to transform unresectable tumors into resectable ones through local treatments,thereby providing surgical options for some patients with HCC.However,the overall strategies and efficacy of conversion therapy for HCC remain inadequately defined.This study was performed to evaluate the efficacy of hepatic arterial infusion chemotherapy(HAIC)combined with sintilimab and bevacizumab in patients with unresectable liver cancer.Methods:We conducted a retrospective analysis of patients with initially unresectable HCC who received HAIC in conjunction with sintilimab and bevacizumab.Preoperative demographic data,tumor markers,tumor size,tumor count,conversion outcomes,and surgery-related clinical data were collected and analyzed before and after treatment.Results:Twelve patients were included in this study.All patients exhibited satisfactory antitumor effects.Ten patients underwent one or two treatment cycles,while two completed four cycles.The mean alpha-fetoprotein level decreased from 73,471±138,239 to 2374±6325 ng/mL,and the mean tumor size decreased from 11.4±2.2 to 7.6±1.0 cm.Following evaluation,10 patients were successfully converted,with 6 ultimately undergoing curative liver cancer resection;of these 6 patients,4 achieved a pathological complete response.Conclusion:The combination of HAIC with sintilimab and bevacizumab represents a safe and effective strategy for tumor conversion.This approach can achieve significant tumor reduction and favorable effects on portal vein tumor thrombus within a short timeframe,facilitating curative resection of liver cancer.展开更多
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting angiogenesis.Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove efficacy.Lenvatinib,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE.However,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been investigated.AIM To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced HCC.METHODS A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022.Baseline characteristics were compared,and propensity score matching was applied.Overall survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were analyzed.RESULTS The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L group.The TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were reported.CONCLUSION TACE+SL demonstrated superior outcomes in terms of OS and PFS,compared to TACE+L.These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
文摘In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular carcinoma.The triple therapy,which integrates interventional therapy,targeted therapy,and immunotherapy,has emerged as a promising research focus in the treatment of liver cancer.Consequently,it is of utmost significance to select an appropriate combination of interventional therapy,targeted therapy,and immunotherapy for patients suffering from intermediate and advanced liver cancer.
基金Supported by Qinghai Provincial Science and Technology Plan,No.2023-ZJ-787.
文摘BACKGROUND Gastric cancer(GC)remains a major global health burden,particularly in East Asia,due to its high incidence,aggressive progression,and poor prognosis in advanced stages.Although surgery is the mainstay of curative treatment,outcomes for locally advanced cases remain unsatisfactory despite perioperative chemotherapy.In recent years,immune checkpoint inhibitors,especially anti-PD-1 antibodies like sintilimab,have shown promise in improving survival when combined with chemotherapy.However,the comparative efficacy and safety of SOX plus sintilimab vs established regimens such as P-SOX and SOX alone in the neoadjuvant setting have not been fully explored.AIM To compare the efficacy and safety of three neoadjuvant chemotherapy regimens—SOX combined with sintilimab(SOX+PD-1),albumin-bound paclitaxel plus oxaliplatin and S-1(P-SOX),and SOX—in patients with advanced GC.METHODS A retrospective analysis was conducted on 299 patients with advanced GC who received both neoadjuvant and adjuvant chemotherapy along with standard D2 radical gastrectomy.Among them,81 patients received SOX plus sintilimab,118 received the P-SOX regimen,and 100 received the SOX regimen.All patients were randomly assigned to training(70%)or validation(30%)cohorts using the R software sample function.Short-term efficacy,long-term survival outcomes,and adverse events were assessed across the three groups.Additionally,clinical factors associated with progression-free survival(PFS)were further investigated.RESULTS In terms of short-term efficacy,the SOX+sintilimab group had higher objective response rates[91.4%and 70.4%according to the tumor regression grade(TRG)and Response Evaluation Criteria in Solid Tumors(RECIST)1.1 criteria,respectively]than did the P-SOX(88.1%and 59.3%)and SOX groups(84.0%and 55.0%),although the intergroup differences were not statistically significant(P=0.167).For long-term outcomes,the SOX+sintilimab group demonstrated significantly better OS rates at 1 year(98.8%),18 months(92.6%),2 years(84.0%),and 3 years(48.1%)than did the P-SOX(93.2%,86.4%,71.2%,30.5%)and SOX(91.0%,84.0%,72.0%,29.0%)groups,with the 3-year overall survival(OS)difference being statistically significant(P=0.007).Similarly,PFS rates in the SOX+sintilimab group(1 year:92.6%;18 months:77.8%;2 years:65.4%;3 years:35.8%)were significantly greater than those in the P-SOX(82.2%,68.6%,53.4%,26.3%)and SOX(77.0%,66.0%,43.0%,27.0%)groups,with significant differences at 1 year(P=0.021)and 2 years(P=0.011).In terms of safety,grade 1-2 gastrointestinal reactions,peripheral neuropathy,and alopecia were the main TRAEs across groups.The P-SOX group had a significantly greater incidence of alopecia(54.2%vs 53.0%vs 23.5%,P=0.009)and more cases of grade 2 alopecia(6.8%vs 1.2%),potentially due to the accumulation of triple-agent toxicity.No significant intergroup differences were observed in hematologic toxicity or liver dysfunction(all P>0.05).CONCLUSION Compared with the SOX and P-SOX regimens,the SOX plus sintilimab combination demonstrated significantly improved short-and long-term efficacy with favorable safety,with superior advantages in terms of 2-and 3-year OS and early PFS,suggesting that this combination is a more promising therapeutic option for patients with advanced GC.Patients who achieved good perioperative chemotherapy responses(meeting the TRG and RECIST 1.1 criteria)and had tumor diameters≤2 cm,well-differentiated histology,earlier cTNM stages,and no lymph node metastasis had a better prognosis.
文摘BACKGROUND Gallbladder cancer is a highly malignant and aggressive tumor,often diagnosed at an advanced stage.The prognosis for advanced gallbladder cancer remains poor,with limited options for effective treatment.CASE SUMMARY A 65-year-old male patient presented with a soft tissue mass in the gallbladder.Following laparoscopic exploration,he underwent radical surgery for gallbladder cancer,with the tumor staged as pT2N1M0(stage III).Post-surgery,the patient received four cycles of adjuvant chemotherapy.However,one month later,over 60 metastatic lesions were detected in the liver,lungs,and lymph nodes.In response to the widespread metastasis,he underwent six cycles of combination therapy consisting of sintilimab,albumin-bound paclitaxel,and cisplatin.After two cycles,a partial response was achieved.Maintenance therapy was initiated with a combination of sintilimab and albumin-bound paclitaxel for four cycles.Monotherapy with sintilimab was continued thereafter until October 2023.Complete remission was confirmed in September 2021.The patient sustained this complete response for more than three years,including an eleven-month period without disease progression following the discontinuation of sintilimab.Genetic analysis revealed a tumor mutational burden of 15.4 mutations/megabase,which indicates a potentially favorable response to immunotherapy.CONCLUSION This case demonstrates the potential of combining immunotherapy(sintilimab)with chemotherapy to achieve durable remission in metastatic gallbladder cancer,even in a patient with extensive metastasis.In addition,it indicated the importance of tumor mutational burden as a predictive biomarker of immunotherapy.
文摘BACKGROUND This article discusses a case involving a 63-year-old man with non-small cell lung cancer,who was treated with a combination of chemotherapy and immunothe-rapy.The patient was treated with five cycles of chemotherapy(pemetrexed and carboplatin)combined with sintilimab,a programmed death 1 inhibitor.CASE SUMMARY After the fifth cycle of treatment,the patient developed skin itching and a vitiligo-like rash,which are known side effects of immunotherapy.Despite dermatologi-cal consultation and treatment with topical corticosteroids,the rash worsened while the itching subsided.The patient continued with the treatment,and after 15 cycles,the tumor showed a response with a reduction in size.The vitiligo-like rash increased,but the antitumor treatment remained effective.CONCLUSION The case highlights the use of immunotherapy in patients with non-small cell lung cancer and the potential side effect of vitiligo-like rash.The patient’s tumor res-ponded well to the treatment,and despite the skin reaction,the treatment was not discontinued due to its effectiveness.The article suggests that further studies are needed to understand the mechanism behind vitiligo in patients with lung cancer receiving immune checkpoint inhibitors and whether the development of vitiligo-like rash after immune checkpoint inhibitor therapy is associated with improved prognosis.The case also underscores the importance of managing immune-related adverse events in the context of effective antitumor treatment.
文摘Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced liver cancer who visited from January 2022 to January 2025 were selected as samples and randomly divided into two groups.Group A received interventional therapy combined with lenvatinib and sintilimab,while Group B received interventional therapy combined with lenvatinib.Disease remission rate,adverse reactions,liver function indicators,and tumor marker indicators were compared between the two groups.Results:The disease control rate(DCR)in Group A was higher than that in Group B(P<0.05).There was no difference in adverse reaction rates between Group A and Group B(P>0.05).Total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in Group A were lower than those in Group B(P<0.05).Carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),and alpha-L-fucosidase(AFU)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:Intermediate and advanced liver cancer patients receiving interventional therapy combined with lenvatinib and sintilimab showed reduced tumor marker levels,lessened liver function damage,and a high disease control rate and treatment safety.
基金Capital Health Development and Scientific Research Special Project,No.2022-2-2175.
文摘BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
文摘BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.
基金The Ministry of Science and Technology of The People's Republic of China,No.2022YFC2503700,and No.2022YFC2503704.
文摘BACKGROUND Stereotactic body radiotherapy(SBRT)and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma(HCC)in retrospective studies.AIM To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC.METHODS This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression.The primary endpoint was progression-free survival(PFS).RESULTS Twenty-five patients were enrolled from August 14,2019,to August 23,2021.The median treatment duration was 10.2(range,0.7-14.6)months.SBRT was delivered at a median dose of 54(range,48-60)Gy in 6(range,6-10)fractions.The median follow-up time was 21.9(range,10.3-39.7)mo,and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1.The median PFS was 19.7 mo[95%confidence interval(CI):16.9-NA],with PFS rates of 68%(95%CI:52-89)and 45.3%(95%CI:28-73.4)at 12 and 24 mo,respectively.The median overall survival(OS)was not reached,with OS rates of 91.5%(95%CI:80.8-100.0)and 83.2%(95%CI:66.5-100.0)at 12 and 24 mo,respectively.The 1-and 2-year local control rate were 100%and 90.9%(95%CI:75.4%-100.0%),respectively.The confirmed objective response rate and disease control rate was 96%,and 96%,respectively.Most adverse events were graded as 1 or 2,and grade 3 adverse events were observed in three patients.CONCLUSION SBRT plus sintilimab is an effective,well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.
基金Supported by Key Research and Development Project of Science and Technology Department of Zhejiang Province,No.2019C03038.
文摘BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.
文摘BACKGROUND Microsatellite stable(MSS)colorectal cancer(CRC)is a common type of tumor with limited treatment options.Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs.AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment.METHODS During the period spanning from April 2019 to April 2022,Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study,the observation group and the control group.The control group was administered anlotinib hy-drochloride as their designated therapy,whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group.The administration of treatment occurred in cycles consisting of a duration of 3 wk,and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups.A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period.Changes in the levels of carcinoembryonic Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy.Finally,a 1-year follow-up was conducted for both groups of patients,and the survival status was recorded and analyzed.RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group,with a statistically significant discrepancy(76.09%vs 50.00%),reaching a significance level denoted as P<0.05.Following the administration of treatment,the observation group manifested a considerable reduction in numerous serum indicators,which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group(P<0.05).Post-treatment,the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration,surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group(P<0.05).Subsequent to the therapeutic intervention,the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality.These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group(P<0.05).The safety levels of drug use in the two group were comparable(19.57%vs 13.04%),and no distinct difference was observed upon comparison(P>0.05).After the completion of treatment,both groups of patients underwent a 1-year follow-up outside the hospital.Throughout this period,1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up.During the follow-up period of the observation group,12 patients died,resulting in a survival rate of 73.33%(33/45),while in the control group,21 patients died,resulting in a survival rate of 52.27%(23/44).The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups(log-rank=4.710,P=0.030).CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients,leading to improvements in patient immunity and prognosis.Additionally,it exerted inhibitory effects on the expression of carcinoembryonic antigen,CA199,and CA125.
文摘BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.
文摘BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.
文摘The patient was a 63-year-old female,who was diagnosed with advanced pancreatic cancer with mediastinal lymph node and lung metastases and pleural effusion in June 2019.First-line treatment with 6 cycles of gemcitabine plus tegafur with best response of partial response.Second-line treatment was 4 cycles of nab-paclitaxel monotherapy ended up with disease progression.Third-line treatment was sintilimab with anlotinib for 10 cycles.The patient's condition has achieved clinical complete remission so far.
基金Science and Technology Innovation Action PlanMedical Innovation Research Special Project of Shanghai,Grant/Award Number:21Y11913500Medical and Health Technology Development Research Center of the National Health Commission,Grant/Award Number:WKZX2023CX030003。
文摘Background:The prognosis for non-small cell lung cancer(NSCLC)patients treatedwith standard platinum-based chemotherapywas suboptimal,with safety concerns.Following encouraging results from a preliminary phase I study,this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.Methods:In this open-label,randomized controlled trial(NCT04124731),metastatic NSCLC without epithelial growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),or proto-oncogene tyrosine-protein kinase ROS(ROS1)mutations,and previous treatments for metastatic disease were enrolled.Participants were randomly assigned in a 1:1 ratio to either sintilimab(200 mg every 3 weeks)plus anlotinib(12 mg D1-14 every 3 weeks)or a standard platinum-based chemotherapy regimen.Patients in the chemotherapy group were permitted to switch to sintilimab after disease progression.The primary endpoint was the objective response rate(ORR).Results:From November 2019 to March 2023,99 patients were randomized into the sintilimab plus anlotinib group(n=49)and the chemotherapy group(n=50).The ORR was significantly higher in the sintilimab plus anlotinib group(44.9%;95%confidence interval[CI]=30.7%-59.8%)compared to the chemotherapy group(18.0%;95%CI=8.6%-31.4%,P=0.003).Progression-free survival(PFS)was also notably longer(median:14.4 vs.5.6 months;hazard ratio[HR]=0.39;95%CI=0.23-0.67;P<0.001).The 24-month overall survival rate was 58.4%(95%CI=40.4%-72.6%)and 43.2%(95%CI=26.0%-59.2%),respectively.The rate of grade 3 or higher treatment-related adverse events was lower in the sintilimab plus anlotinib group(28.0%)than in the chemotherapy group(49.0%),especially for the hematological toxicities.Conclusion:First-line sintilimab plus anlotinib showed improved ORR and PFS,alongside a superior safety profile,compared to the standard platinumbased chemotherapy for metastatic NSCLC patients.
基金funded by the Provincial-Level Clinical Key Specialty Construction in Qinghai Province in China.
文摘We aimed to evaluate the efficacy and safety of adding apatinib,to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer(TNBC).In the phase 2 NeoSAC trial,patients with early TNBC received six cycles of apatinib,sintilimab,nab-paclitaxel,and carboplatin followed by surgery.The primary endpoint was pathological complete response(pCR)rate.Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment.Among 34 enrolled patients,24 achieved pCR(70.6%;95%confidence interval(CI),53.0-85.3),and 79.4%(95%CI,65.1-93.7)had residual cancer burden 0-I.Imaging evaluation showed 21 complete responses(61.8%)and 13 partial responses(38.2%).The most common grade 3-4 adverse events were leukopenia(47%),neutropenia(36%),and thrombocytopenia(24%).The 36-month disease-free survival rate stood at 94.1%with a median follow-up of 39.1 months.Notably,baseline high ImmuneScore,immune cell infiltration,and enrichment of interferon-related pathways correlated with pCR.Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets,thereby activating the tumor microenvironment.Moreover,higher oxeiptosis scores were associated with an increased likelihood of achieving pCR.Following neoadjuvant therapy,the pCR group showed a decrease in oxeiptosis score,whereas the non-pCR group exhibited an increase.Our study suggests that apatinib,sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study.ClinicalTrials.gov registration:NCT04722718.
基金funded by the General Project of the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0604)the Chongqing Doctoral“Through Train”Research Program(CSTB2022BSXM-JCX0045).
文摘Background and aims:Hepatocellular carcinoma(HCC)presents a significant challenge in tumor management because of its low resection rates.Conversion therapy aims to transform unresectable tumors into resectable ones through local treatments,thereby providing surgical options for some patients with HCC.However,the overall strategies and efficacy of conversion therapy for HCC remain inadequately defined.This study was performed to evaluate the efficacy of hepatic arterial infusion chemotherapy(HAIC)combined with sintilimab and bevacizumab in patients with unresectable liver cancer.Methods:We conducted a retrospective analysis of patients with initially unresectable HCC who received HAIC in conjunction with sintilimab and bevacizumab.Preoperative demographic data,tumor markers,tumor size,tumor count,conversion outcomes,and surgery-related clinical data were collected and analyzed before and after treatment.Results:Twelve patients were included in this study.All patients exhibited satisfactory antitumor effects.Ten patients underwent one or two treatment cycles,while two completed four cycles.The mean alpha-fetoprotein level decreased from 73,471±138,239 to 2374±6325 ng/mL,and the mean tumor size decreased from 11.4±2.2 to 7.6±1.0 cm.Following evaluation,10 patients were successfully converted,with 6 ultimately undergoing curative liver cancer resection;of these 6 patients,4 achieved a pathological complete response.Conclusion:The combination of HAIC with sintilimab and bevacizumab represents a safe and effective strategy for tumor conversion.This approach can achieve significant tumor reduction and favorable effects on portal vein tumor thrombus within a short timeframe,facilitating curative resection of liver cancer.
