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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM division of hematology-oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of hematology-oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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Adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 234-235页

作者： Adam S Bodzin Richard S Finn Ronald W Busuttil DepartmentofSurgery Division of Hematology/Oncology (Finn RS) UCLA Department of Medicine Division of Hematology/OncologyUCLA

In this issue, Lin et al presented a well-written meta- analysis regarding the use of adjuvant chemotherapy in orthotopic liver transplant （OLT） recipients withhepatoceUular carcinoma （HCC）. They highlighted the need for further investigation about the post-OLT management of HCC. The treatment of advanced HCC remains a difficult challenge as there is limited response to chemotherapeutics even after resection and limited literature is available to support the use of chemotherapy after OLT for HCC. This study delves into the impor- tance of preventing HCC recurrence and prolonging survival after transplantation. The conclusions claim that chemotherapy may be useful in increasing survival and prolonging disease-free survival; however the findings that it does not prevent recurrence remain troublesome. Perhaps one of the greatest limitations is that cytotoxic agents have never been shown to improve survival in ad- vanced disease and therefore it is difficult to see a role in the early/adjuvant setting.

关键词： HCC Adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma OLT

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Novel therapy for advanced gastric cancer

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World Journal of Gastrointestinal oncology 2015年第11期7卷 263-270页

作者： Yue Zhang Shenhong Wu division of hematology and oncology Stony Brook University

Gastric cancer(GC) is a common lethal *** junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United *** chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive *** median overall survival(OS) is less than one year for advanced GC patients; thus,there is an urgent unmet need to develop novel therapy for *** multiple targeted agents were studied,only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit(5.2 mo vs 3.8 mo,P = 0.047) as a single agent; 2.2 mo improvement of survival(9.6 mo vs 7.4 mo,P = 0.017) when combined with paclitaxel in previously treated advanced GC *** is the first single agent approved for previously treated GC and the second biologic agent after *** with limited success,targeted therapy may be improved by developing new *** therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical *** evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities.

关键词： Gastric cancer Novel therapy Targeted therapy Immu

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Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2015年第14期21卷 4268-4274页

作者： Min-Young Lee Ki Sun Jung Hae Su Kim Ji Yun Lee Sung Hee Lim Moonjin Kim Hyun Ae Jung Sung Min Kim Jong Mu Sun Myung-Ju Ahn Jeeyun Lee Se Hoon Park Seong Yoon Yi In Gyu Hwang Sang-Cheol Lee Hee Kyung Ahn Do Hyoung Lim Soon Il Lee Keon Woo Park division of hematology-oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of Medicine division of hematology-oncology Department of Internal MedicineInje University Ilsan-Paik Hospital division of hematology-oncology Department of Internal MedicineChung-Ang University Hospital division of hematology-oncology Department of Internal MedicineSoonchunhyang University Hospital division of hematology-oncology Department of Internal MedicineGachon University Gil Hospital division of hematology-oncology Department of Internal MedicineDankook University College of Medicine

AIM: To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate(FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma(SCC).METHODS: A multi-center, open-label, prospective phase Ⅱ study was ***-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m2 and gemcitabine 1000 mg/m2 iv at a FDR(10 mg/m2 per minute) on days 1 and *** was repeatedevery twenty-one days until disease progression, unacceptable toxicity, or consent *** primary endpoint was response rate(RR), and secondary endpoints were safety, progression-free survival(PFS) and overall survival(OS).RESULTS: Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia(97%), fatigue(64%) and neutropenia(55%).One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely *** control(objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30%(95%CI: 15%-46%).The median PFS and OS were 4.0(95%CI: 3.4-4.6) and 8.8 mo(95%CI: 7.8-9.8 mo), ***: A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.

关键词： Clinical trial Phase Ⅱ Chemotherapy Carcinoma,Esop

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Total estimated effective doses from radiologic imaging modalities of children with cancer:a single center experience

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World Journal of Pediatrics 2017年第3期13卷 242-247页

作者： Derya Ozyorük Suna Emir HacιAhmet Demir Gülsah Bayram Kabacam Bahattin Tunc division of Pediatric oncology Ankara Children's Hematology and Oncology Education and Research HospitalAnkaraTurkey division of Radiology Ankara Children's Hematology and Oncology Education and Research HospitalAnkaraTurkey

Background:Recently,awareness of the cumulative radiation exposure for pediatric oncology patients has been increasing,together with increased survival rates and longer life *** aim of our study was to quantify the amount of ionising radiation from imaging modalities of pediatric oncology ***:Eighty-eight patients who were diagnosed with childhood cancer and followed up for 5 years between 2004-2014 in our center were included in the ***' medical files were reviewed retrospectively for imaging history in the first 5 years after *** estimated effective doses from radiologic imaging modalities were ***,the basic demographic data,histologic type,stage,and outcomes of disease were collected for all ***:The individual total estimated effective doses ranged from 8.73 to 167 mSv,with a median of 62.92 *** tomography was the greatest contributor of total effective *** doses ranged 21.45-113.20 mSv (median:62.92 mSv) in Hodgkin lymphoma,12.53-167.10 mSv (median:52 mSv) in non-Hodgkin lymphoma,4.13-172.98 mSv (median:52 mSv) in neuroblastoma,31-149.89 mSv (median:63.10 mSv) in Wilms' tumor,11.50-73.72 mSv (median:36.90 mSv) in germ cell tumor,26.46-125.86 mSv (median:80.90 mSv) in other solid tumor and 0.02-13.31 mSv (5.25 mSv) in brain tumor ***-two children (25%) died with progressive disease during the 5-year follow-up ***:Similar to previous studies,the total estimated effective doses in children with cancer have been found various according to diagnosis,stage and clinical *** clarify the harmfull effects of radiation burden,prospective studies should be conducted in children with cancer.

关键词： children effective dose ionizing radiation

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Hypoxia inducible factor in hepatocellular carcinoma:A therapeutic target

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World Journal of Gastroenterology 2015年第42期21卷 12171-12178页

作者： Daniel Lin Jennifer Wu Fellow hematology and Medical oncology Program NYU School of Medicine Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology NYU School of Medicine Subdivision of GI Oncology Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology

Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.

关键词： Hypoxia Hypoxia-inducible factor alpha Hepatocellu

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Tegafur-uracil-induced rapid development of advanced hepatic fibrosis

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World Journal of Gastroenterology 2017年第31期23卷 5823-5828页

作者： shuya honda koji sawada takumu hasebe shunsuke nakajima mikihiro fujiya toshikatsu okumura division of gastroenterology and hematology/oncology department of medicine asahikawa medical university

Tegafur-uracil has been reported to have only minor adverse effects and is associated with liver injury in 1.79% of Japanese patients. The development of tegafur-uracil-induced hepatic fibrosis with portal hypertension is rare. Here, we report a case of a 74-year-old woman with rapidly developing tegafururacil-induced hepatic fibrosis. The patient had no history of liver disease and had been treated with tegafur-uracil for 8 mo after breast cancer surgery. The patient was admitted to our hospital for abdominal distension and leg edema associated with liver dysfunction. Computed tomography imaging revealed massive ascites and splenomegaly, and a non-invasive assessment of liver fibrosis indicated advanced fibrosis. The histopathological findings revealed periportal fibrosis and bridging fibrosis with septation. The massive ascites resolved after discontinuing tegafururacil. These findings suggest that advanced hepatic fibrosis can develop from a relatively short-term administration of tegafur-uracil and that non-invasive assessment is useful for predicting hepatic fibrosis.

关键词： Tegafur-uracil Drug-induced liver injury Hepatic fibrosis Portal hypertension Non-invasive assessment

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Retrospective analysis of extra-gastrointestinal stromal tumors

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World Journal of Gastroenterology 2015年第6期21卷 1845-1850页

作者： Jun Ho Yi Byeong-Bae Park Jung Hun Kang In Gyu Hwang Dong Bok Shin Sun Jin Sym Hee Kyung Ahn Soon Il Lee Do Hyoung Lim Keon Woo Park Young-Woong Won Sung Hee Lim Se Hoon Park division of hematology-oncology Department of Internal Medicine Hanyang University Seoul Hospital division of hematology-oncology Department of Internal Medicine Gyeongsang National University School of Medicine division of hematology-oncology Department of Internal Medicine Chung-Ang University Hospital ChungAng University College of Medicine division of hematology-oncology Department of Internal MedicineGachon University Gil Hospital Department of hematology-oncology Dankook University School of Medicine division of hematology and oncology Department of Internal Medicine Hanyang University Guri Hospital Hanyang University College of Medicine division of hematologyoncology Department of Medicine Sungkyunkwan University Samsung Medical Center Cancer hospital

AIM:To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors(EGISTs)in South ***:A total of 51 patients with an EGIST were *** clinicopathologic features,including sex,age,location,tumor size,histology,mitotic rate,immunohistochemical features,genetic status and survival data,were ***:The median age was 55 years(range:29-80years),and male:female ratio was 1:*** most common site was in the mesentery(n=15)followed by the retroperitoneum(n=13)and omentum(n=8).The median tumor size was 9.0 cm(range:2.6-30.0cm)and the median mitotic rate was 5.0/50HPF.(1/50-185/50).KIT was analyzed in 16,which revealed 10cases with wild-type KIT and 6 cases with an exon *** 51 patients,31 patients had undergone surgery,and 10 had unresectable disease and had taken palliative imatinib,which resulted in 22.7 mo of progression-free *** the patients who had undergone surgery,18 did not take adjuvant imatinib,and 8 of these were categorized as"high risk"according to the risk ***,the relapse-free survival was not different(P=0.157)between two ***:Because the biologic behaviors of GISTs differ according to the location of the tumor,a more stratified strategy is required for managing EGISTs including incorporation of molecular features.

关键词： Gastrointestinal stromal tumor Survival Imatinib R

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Sustained complete response to erlotinib in squamous cell carcinoma of the head and neck:A case report

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World Journal of Clinical Cases 2019年第5期7卷 616-622页

作者： Mie Mie Thinn Chung-Tzu Hsueh Chung-Tsen Hsueh division of hematology and Medical oncology Loma Linda Veterans Administration Medical Center Department of Dentistry Cathay General Hospital division of Medical oncology and hematology Department of MedicineLoma Linda University

BACKGROUND Squamous cell carcinoma of head and neck(SCCHN) is the fifth most common cancer worldwide. Inhibition of epidermal growth factor receptor signaling has been shown to be a critical component of therapeutic option. Herein, we report a case of durable complete response to *** SUMMARY An 81-year-old Caucasian male who presented with metastatic poorly differentiated squamous cell carcinoma of right cervical lymph nodes(levels 2 and 3). Imaging studies including(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(CT) and contrast-enhanced CT scan of neck and chest did not reveal any other disease elsewhere. Panendoscopic examination with random biopsy did not reveal malignant lesion in nasopharynx,oropharynx, and larynx. He underwent modified neck dissection and postoperative radiation. Within 2 mo after completion of radiation, he developed local recurrence at right neck, which was surgically removed. Two mo after the salvage surgery, he developed a second recurrence at right neck. Due to suboptimal performance status and his preference, he started erlotinib *** achieved partial response after first 2 mo of erlotinib treatment, then complete response after total 6 mo of erlotinib treatment. He developed sever skin rash and diarrhea including Clostridium difficile infection during the course of erlotinib treatment requiring dose reduction and eventual discontinuation. He remained in complete remission for more than two years after discontinuation of *** We report a case of metastatic SCCHN achieving durable complete response from erlotinib. Patient experienced skin rash and diarrhea toxicities which were likely predictors of his treatment response.

关键词： Squamous cell carcinoma of head and neck Epidermal growth factor receptor Erlotinib Complete response Skin rash Tyrosine kinase inhibitor Case report

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Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 341-347页

作者： Philip J Saylor division of hematology-oncology Massachusetts General Hospital Cancer Center Boston Massachusetts USA.

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-K-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

关键词： denosumab osteoporosis osteopenia osteoclast RANK (receptor activator of nuclear factor-kappa B) skeletal-relatedevents

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