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Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3521-3528页

作者： Shin Woo Kang Sung Hee Lim Min-Ji Kim jeeyun lee Young Suk Park Ho Yeong Lim Won Ki Kang Seung Tae Kim Division of Hematology Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Samsung Biomedical Research Institute Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor *** VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab *** cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and *** To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of *** This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with *** A total of 124 patients was included in this *** all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line *** 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line *** numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),*** results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

关键词： Bevacizumab Colorectal cancer Programmed cell death ligand 1 expression First-line chemotherapy Metastatic colorectal cancer

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Pulmonary metastasectomy for colorectal cancer: How many nodules, how many times?

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World Journal of Gastroenterology 2014年第20期20卷 6133-6145页

作者： Hong Kwan Kim Jong Ho Cho Ho Yun lee jeeyun lee Jhingook Kim Department of Thoracic and Cardiovascular Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 South Korea Department of Radiology and Center for Imaging Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 South Korea Department of Hematology and Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135-710 South Korea

Colorectal cancer(CRC)is one of the most common cancers worldwide,with 5%-15%of CRC patients eventually developing lung metastasis(LM).Despite doubts about the role of locoregional therapy in the management of systemic disease,many surgeons have performed pulmonary metastasectomy(PM)for CRC in properly selected ***,the use of pulmonary metastasectomy remains controversial due to the lack of randomized controlled *** article reviews the results of surgical treatment of pulmonary metastases for CRC,focusing on(1)current treatment guidelines and surgical techniques of PM in patients with LM from CRC;(2)outcomes of PM and its prognostic factors;and(3)controversial issues in PM,focusing on repeated metastasectomy,bilateral multiple metas-tases,and combined liver and lung metastasectomy.

关键词： Colorectal cancer Pulmonary metastasectomy Surgery Metastases

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Gastric leptomeningeal carcinomatosis: Multi-center retrospective analysis of 54 cases

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World Journal of Gastroenterology 2009年第40期15卷 5086-5090页

作者： Sung Yong Oh Su-Jin lee jeeyun lee Suee lee Sung-Hyun Kim Hyuk-Chan Kwon Gyeong-Won lee Jung Hun Kang In Gyu Hwang Joung-Soon Jang Ho Yeong Lim Young Suk Park Won Ki Kang Hyo-Jin Kim Department of Internal Medicine and Medical Research Center for Cancer Molecular Therapy Dong-A University College of Medicine Division of Hematology/Oncology Department of MedicineSamsung Medical Center Department of InternalMedicine Gyeongsang National University School of Medicine Department of Internal Medicine College of MedicineChung-Ang University

AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric ***： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to ***： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer sur

关键词： Carcinomatosis Gastric cancer Intrathecal chemotherapy Leptomeningeal

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Comprehensive molecular analysis to predict the efficacy ofchemotherapy containing bevacizumab in patients with metastaticcolorectal cancer

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肿瘤学研究(英文) 2023年第6期31卷 855-866页

作者： SUNG HEE LIM HEE JIN CHO KYOUNG-MEE KIM HO YEONG LIM WON KI KANG jeeyun lee YOUNG SUK PARK HEE CHEOL KIM SEUNG TAE KIM Division of Hematology/Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea Precision Medicine Research Institute Samsung Medical CenterGangnam-guSeoul06351Korea Department of Biomedical Convergence Science and Technology Kyungpook National UniversityDaegu41566Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul06351Korea Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea

Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been ***:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing *** molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient ***:Genomic and molecularcharacterization was successfully conducted in 103 *** of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite *** those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to *** the four SRCCs,two were CMS1,one was CMS4,and the other was *** status was a significantly enriched factor in responders to bevacizumab *** growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in ***,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX ***),thesignificance of the molecular pathways varied according to the backbone ***:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing *** need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic oppor

关键词： Bevacizumab Whole-exome sequencing Ribonucleic acid sequencing Methylation array Colorectal cancer

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Tumor Response to Temsirolimus for Epithelioid Angiomyolipoma and Novel Mutation of <i>SMARCB1/INI1</i>Tumor Suppressor Gene

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Journal of Cancer Therapy 2014年第13期5卷 1215-1222页

作者： Jung Yong Hong jeeyun lee Kyoung-Mee Kim Sung Joo Kim Department of Internal Medicine Chung-Ang University College of Medicine Seoul South Korea Department of Medicine Division of Hematology-Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea Department of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea Department of Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

Epithelioid angiomyolipoma (EAML) is a rare morphologic variant of classic angiomyolipoma (AML), showing potentially malignant phenotype. AML is a benign mesenchymal tumor, which shows frequent inactivating mutations of?TSC1 (encodes harmartin) or?TSC2 (encodes tuberin) genes. Disruption of harmatin-tuberin complex and subsequent inappropriate activation of mTOR pathway is a distinct feature of AML. Thus, mTOR pathway inhibitors have shown significant clinical response in AML. Compared to the great success of mTOR inhibitors in AML, there is no standard therapy for EAML yet. Here, we present a patient with EAML who responded well to mTOR inhibitor (temsirolimus) but suffered rapid disease progression after cessation of temsirolimus. In addition, we performed Cancer Hotspot Panel (Ion AmpliSeqTM) analysis to identify novel tumorigenic properties of EAML. Of note, Cancer Hotspot Panel analysis revealed novel missense mutation in?SMARCB1 (c.1119-41G > A) tumor suppressor gene and subsequent immunohistochemistry analysis also revealed weak and partial losses ofSMARCB1/INI1 protein in nuclei of tumor cells. In this study, we suggest that mTOR inhibitors also can be effective against EAML. However, the long-term efficacy of mTOR inhibitors in EAML needs to be supported in further studies. Furthermore, we speculate that the newly found missense mutation ofSMARCB1/INI1 gene can be the possible novel tumorigenic properties of EAML and highlights the possibility of further novel targeted therapy beyond mTOR inhibitors in EAML.

关键词： Epithelioid Angiomyolipoma Temsirolimus SMARCB1/INI1

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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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