Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenva...Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.展开更多
Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tu...Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.展开更多
BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established...BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.展开更多
BACKGROUND Immunotherapy,specifically the use of checkpoint inhibitors such as pembrolizumab,has become an important tool in personalized cancer therapy.These inhibitors target proteins on T-cells that regulate the im...BACKGROUND Immunotherapy,specifically the use of checkpoint inhibitors such as pembrolizumab,has become an important tool in personalized cancer therapy.These inhibitors target proteins on T-cells that regulate the immune response against tumor cells.Pembrolizumab,which targets the programmed cell death 1 receptor on T-cells,has been approved for the treatment of metastatic melanoma and nonsmall cell lung cancer.However,it can also lead to immune-related side effects,including pneumonitis,colitis,thyroid abnormalities,and rare cases of type 1 diabetes.CASE SUMMARY The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment.The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes.The patient had a history of hypothyroidism and a family history of breast cancer.Treatment for diabetic ketoacidosis was initiated,and the patient was discharged for close follow-up with an endocrinologist.CONCLUSION This literature review highlights the occurrence of diabetic ketoacidosis and newonset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer.Overall,the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment,particularly pembrolizumab,while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients.Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.展开更多
BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as firstline therapy in patients with advanced esophageal cancer.Few trials have assessed the safety and efficacy of this treatment in pati...BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as firstline therapy in patients with advanced esophageal cancer.Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease.AIM To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma(ESCC)in the real world.METHODS Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study.Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system.The patients received different treatments based on clinical stage.In brief,patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery.For those who were not candidates for resection,radical concurrent chemoradiotherapy plus pembrolizumab was more preferable.Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab.Long-term survival outcomes such as overall survival(OS),progression-free survival,disease-free survival,long-term adverse effects(AEs),immune maintenance therapy and predictors of immune checkpoint inhibitors(ICIs)efficacy were evaluated.RESULTS A total of 55 patients with advanced ESCC were enrolled in this retrospective,observational study.The median age was 61 years(range 44-74),with 47.3%(26/55)of the patients in stage IV and 45.5%of the patients had the tumor(25/55)located in the middle third of the esophagus.The median OS in all patients was not reached.The 12-mo OS rate among all patients was 78.8%and the 18-mo OS rate was 72.7%.9 patients died due to tumor progression and 7 patients died due to treatment-related complications.The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome.Patients with complete response or partial response in all patients(P=0.005)and in the chemoradiotherapy plus pembrolizumab group(P=0.007)obtained a better prognosis than non-responders.A total of 20 patients(20/55,36%)received immune maintenance therapy.Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and neutrophil-to-(leukocyte-neutrophil)ratio did not predict the efficacy of ICIs.CONCLUSION Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC,with safe and manageable long-term AEs.展开更多
BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we rep...BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we report a case involving the discovery of a pancreatic mass detected during a routine physical examination.Subsequent imaging and pathological tests of the patient led to the diagnosis of LGMS of the pancreas.Following surgical intervention,the patient experienced recurrence and metastasis.Conventional treatment is not effective for postoperative recurrent pancreatic LGMS with multiple metastases.After communicating with the patients and their families,informed consent was obtained for the treatment of anlotinib combined with pembrolizumab.Evaluation of imaging and clinical symptoms post-treatment revealed a relatively favorable response to the combination of anlotinib and pembrolizumab.CONCLUSION Based on the comprehensive literature review,our report aimed to provide evidence for a better understanding of the disease characteristics,diagnostic criteria,imaging findings,and identification of LGMS.And explore novel treatment strategies for this disease.展开更多
BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal ...BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.展开更多
BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship...BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.展开更多
3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺...3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺癌亚型，通常具有更高的病理分级，易进展且侵袭性强，因为缺少治疗靶点导致治疗策略单一，只能选择毒副作用大的全身性化疗。目前研究表明程序性死亡受体1（programmed death receptor1，PD-1）单克隆抗体Pembrolizumab通过阻断PD-1/PD-L1信号通路，激发人体自身免疫系统对抗肿瘤细胞及避免肿瘤逃逸，对TNBC、黑色素瘤、胃癌、泌尿道上皮细胞癌及头颈部癌症等多种晚期进展性PD-L1阳性恶性肿瘤具有治疗潜力。展开更多
1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 s...1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 study[J].Lancet Oncol,2016,17（11）：1497-1508.2证据水平1b。3背景·在以往的临床试验中,单药PD-1抑制剂Pembrolizumab在晚期非小细胞肺癌（non-smallcell lung cancer,NSCLC）的治疗中已显示可喜的疗效。展开更多
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.
文摘Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.
文摘BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.
文摘BACKGROUND Immunotherapy,specifically the use of checkpoint inhibitors such as pembrolizumab,has become an important tool in personalized cancer therapy.These inhibitors target proteins on T-cells that regulate the immune response against tumor cells.Pembrolizumab,which targets the programmed cell death 1 receptor on T-cells,has been approved for the treatment of metastatic melanoma and nonsmall cell lung cancer.However,it can also lead to immune-related side effects,including pneumonitis,colitis,thyroid abnormalities,and rare cases of type 1 diabetes.CASE SUMMARY The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment.The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes.The patient had a history of hypothyroidism and a family history of breast cancer.Treatment for diabetic ketoacidosis was initiated,and the patient was discharged for close follow-up with an endocrinologist.CONCLUSION This literature review highlights the occurrence of diabetic ketoacidosis and newonset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer.Overall,the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment,particularly pembrolizumab,while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients.Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.
基金The study was reviewed and approved by the Medical Ethics Committee of the General Hospital of the Chinese People’s Liberation Army,No.S2021-265-01.
文摘BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as firstline therapy in patients with advanced esophageal cancer.Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease.AIM To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma(ESCC)in the real world.METHODS Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study.Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system.The patients received different treatments based on clinical stage.In brief,patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery.For those who were not candidates for resection,radical concurrent chemoradiotherapy plus pembrolizumab was more preferable.Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab.Long-term survival outcomes such as overall survival(OS),progression-free survival,disease-free survival,long-term adverse effects(AEs),immune maintenance therapy and predictors of immune checkpoint inhibitors(ICIs)efficacy were evaluated.RESULTS A total of 55 patients with advanced ESCC were enrolled in this retrospective,observational study.The median age was 61 years(range 44-74),with 47.3%(26/55)of the patients in stage IV and 45.5%of the patients had the tumor(25/55)located in the middle third of the esophagus.The median OS in all patients was not reached.The 12-mo OS rate among all patients was 78.8%and the 18-mo OS rate was 72.7%.9 patients died due to tumor progression and 7 patients died due to treatment-related complications.The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome.Patients with complete response or partial response in all patients(P=0.005)and in the chemoradiotherapy plus pembrolizumab group(P=0.007)obtained a better prognosis than non-responders.A total of 20 patients(20/55,36%)received immune maintenance therapy.Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and neutrophil-to-(leukocyte-neutrophil)ratio did not predict the efficacy of ICIs.CONCLUSION Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC,with safe and manageable long-term AEs.
文摘BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we report a case involving the discovery of a pancreatic mass detected during a routine physical examination.Subsequent imaging and pathological tests of the patient led to the diagnosis of LGMS of the pancreas.Following surgical intervention,the patient experienced recurrence and metastasis.Conventional treatment is not effective for postoperative recurrent pancreatic LGMS with multiple metastases.After communicating with the patients and their families,informed consent was obtained for the treatment of anlotinib combined with pembrolizumab.Evaluation of imaging and clinical symptoms post-treatment revealed a relatively favorable response to the combination of anlotinib and pembrolizumab.CONCLUSION Based on the comprehensive literature review,our report aimed to provide evidence for a better understanding of the disease characteristics,diagnostic criteria,imaging findings,and identification of LGMS.And explore novel treatment strategies for this disease.
基金Supported by the National Natural Science Foundation of China,No.81803160.
文摘BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.
文摘BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.
文摘3背景三阴性乳腺癌（triple negative breast cancer，TNBC）即激素受体（hormone receptor，HR）阴性、人表皮生长因子受体2（humanepid ermal receptor2，HER2）阴性的亚型，占乳腺癌总发病率的20%。该亚型相较于激素受体阳性的乳腺癌亚型，通常具有更高的病理分级，易进展且侵袭性强，因为缺少治疗靶点导致治疗策略单一，只能选择毒副作用大的全身性化疗。目前研究表明程序性死亡受体1（programmed death receptor1，PD-1）单克隆抗体Pembrolizumab通过阻断PD-1/PD-L1信号通路，激发人体自身免疫系统对抗肿瘤细胞及避免肿瘤逃逸，对TNBC、黑色素瘤、胃癌、泌尿道上皮细胞癌及头颈部癌症等多种晚期进展性PD-L1阳性恶性肿瘤具有治疗潜力。
文摘1文献来源Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and Pemetrexed with or without Pembrolizumab for advanced,non-squamous non-small-cell lung cancer：A randomised,phase 2 cohort of the open-label KEYNOTE-021 study[J].Lancet Oncol,2016,17（11）：1497-1508.2证据水平1b。3背景·在以往的临床试验中,单药PD-1抑制剂Pembrolizumab在晚期非小细胞肺癌（non-smallcell lung cancer,NSCLC）的治疗中已显示可喜的疗效。
