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( Kyunghye Bang ),( Kyu-pyo Kim ),( Baek-yeol Ryoo ),( Changhoon Yoo ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Nivolumab showed promising anti-tumor efficacy in advanced HCC in prior phase I/II CheckMate-040 trial. We analyzed clinical outcomes of HCC patients enrolled in our biomarker prospective cohort and treated with nivolumab after failure of sorafenib. Methods: Single-center, prospective cohort study. 46 patients with unresectable or metastatic HCC who received nivolumab after failure of sorafenib in Asan Medical Center, Seoul, Korea, between May 2018 and March 2020, were included. Nivolumab was given at 3mg/kg intravenously, every 2 weeks. Results: Median age was 59 years and 82.6% (n=38) were male. 76.1% (n=35) had HBV infection and 67.4% (n=31) were Child-Pugh A. All patients were BCLC stage C, and extrahepatic metastasis and major vascular invasion were detected in 44 (95.7%) and 23 (50.0%), respectively. Median time-to-progression (TTP) on prior sorafenib was 2.6 months (95% CI, 1.4-3.8). Nivolumab was administered as 2nd-, 3rdand 4th-line treatment in 28 (60.9%), 14 (30.4%) and 4 (8.7%), respectively. The number of treatment cycle was median 4 (range, 1-35). Objective response rate (ORR) was 15.2% (1 CR, 6 PR) and median time-to-response (TTR) was 1.7 months (range, 1.3-4.0). Median duration of response (DOR) was 6.0 months (range, 3.6-15.6) and 2 patients are ongoing (10.18+ to 18.92+ months) at data cut-off. Median progression-free survival (PFS) was 1.7 months (95% CI, 1.6-1.8) and overall survival (OS) was 5.4 months (95% CI, 2.8-7.9). 6-month PFS and OS rates were 26.8% and 49.2%, respectively. AEs were anorexia (13.0%), fatigue (6.5%), diarrhea (4.3%), and thyroid dysfunction (2.2%). Conclusions: Nivolumab showed modest efficacy in this study. In patients who achieved objective response (15.2%), median DOR was promising as 6 months. Although CheckMate-459, a randomized phase 3 study evaluating nivolumab vs sorafenib as 1<sup>st</sup>-line treatment, failed to meet the primary endpoint, our findings indicate that nivolumab may have therapeutic implications in sorafenib-progressed HCC patients.
Progressive Dehazing and Depth Estimation from a Single Hazy Image
Jeonghoon Kim,Sungyoon Kim,Changhoon Pyo,Hyeongmyeon Kim,Changhoon Yim 대한전자공학회 2022 IEIE Transactions on Smart Processing & Computing Vol.11 No.5
We propose a progressive dehazing and depth estimation (PDDE) method with optimal estimation of the attenuation coefficient. We investigated the characteristics of dehazing operations related to the depth and attenuation coefficient for PDDE. Entropy was used as a non-reference image quality metric for optimality assessment of dehazed images. The proposed PDDE method provides an optimal dehazed image and depth estimation from a single hazy image. Experimental results show that the proposed method provides clearer and subjectively better results for single image dehazing than previous image dehazing methods. It also results in a significant improvement in the accuracy of depth estimation from a single hazy image compared with previous depth estimation methods.
Kim, Bum Jun,Yoo, Changhoon,Kim, Kyu-pyo,Hyung, Jaewon,Park, Seong Joon,Ryoo, Baek-Yeol,Chang, Heung-Moon Nature Publishing Group 2017 The British journal of cancer Vol. No.
<P><B>Background:</B></P><P>We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS).</P><P><B>Methods:</B></P><P>We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy.</P><P><B>Results:</B></P><P>Fluoropyrimidine monotherapy and fluoropyrimidine–platinum combination were used in 255 and 66 patients, respectively. In patients with measurable disease, the overall response rate (ORR) was 3% and disease control rate was 47%. After a median follow-up of 27.6 months (range, 0.9–70.4 months), the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval (CI), 1.6–2.2) and 6.5 months (95% CI, 5.9–7.0), respectively. The ORR was significantly higher in patients who received fluoropyrimidine–platinum combination compared with those who received fluoropyrimidine alone (8 <I>vs</I> 1%, <I>P</I>=0.009), although the PFS (<I>P</I>=0.43) and OS (<I>P</I>=0.88) did not significantly differ between these groups.</P><P><B>Conclusions:</B></P><P>Fluoropyrimidine-based chemotherapy was modestly effective as a second-line chemotherapy for advanced BTC patients after failure of GEMCIS. Fluoropyrimidine–platinum combination therapy was not associated with improved survival outcomes, as compared with fluoropyrimidine monotherapy.</P>
Chae, Heejung,Kim, Deokhoon,Yoo, Changhoon,Kim, Kyu-pyo,Jeong, Jae Ho,Chang, Heung-Moon,Lee, Sang Soo,Park, Do Hyun,Song, Tae Jun,Hwang, Shin,Kim, Ki-Hun,Song, Gi-Won,Ahn, Chul Soo,Lee, Jae Hoon,Hwang Elsevier 2019 European journal of cancer Vol.120 No.-
<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers.</P> <P><B>Methods</B></P> <P>Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease.</P> <P><B>Results</B></P> <P>Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were <I>TP53</I> (44.4%), <I>KRAS</I> (29.0%), <I>ARID1A</I> (12.1%) and <I>IDH1</I> (9.7%). <I>IDH1/2</I> mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while <I>ERBB2</I>/<I>3</I> mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring <I>TP53</I> mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, <I>P</I> = 0.018), while <I>IDH1</I> mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, <I>P</I> = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, <I>P</I> = 0.013) and OS (21.0 vs. 13.3 months, <I>P</I> = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88).</P> <P><B>Conclusions</B></P> <P>A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We examined genetic landscape of biliary tract cancer with targeted sequencing. </LI> <LI> Certain genetic mutations were associated with clinical outcomes. </LI> <LI> More than half of patients harboured at least one potentially actionable alteration. </LI> <LI> DNA damage repair gene alterations were associated with a better response to platinum-based treatment. </LI> </UL> </P>