Cancer Research and Treatment

Baek-Yeol Ryoo

21 Articles

Gastrointestinal cancer

Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma: Se Jin Choi, Sung Won Chung, Jonggi Choi, Kang Mo Kim, Hyung-Don Kim, Changhoon Yoo, Baek-Yeol Ryoo, Seung Soo Lee, Won-Mook Choi, Sang Hyun Choi; Cancer Res Treat. 2024;56(4):1219-1230. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.283

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Purpose
This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC).
Materials and Methods
This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, ver. 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test.
Results
Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19 to 14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05 to 8.93; p=0.04), and the absence of arterial-phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18 to 18.47; p < 0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors.
Conclusion
In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.

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Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence
María Martínez Burgos, Rocío González Grande, Susana López Ortega, Inmaculada Santaella Leiva, Jesús de la Cruz Lombardo, Julio Santoyo Santoyo, Miguel Jiménez Pérez
Biomedicines.2024; 12(6): 1302. CrossRef

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Clinical Outcomes of Surgery after Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma: Yoo Na Lee, Min Kyu Sung, Dae Wook Hwang, Yejong Park, Bong Jun Kwak, Woohyung Lee, Ki Byung Song, Jae Hoon Lee, Changhoon Yoo, Kyu-Pyo Kim, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim; Cancer Res Treat. 2024;56(4):1240-1251. Published online June 19, 2024; DOI: https://doi.org/10.4143/crt.2023.977

Abstract PDF PubReader ePub: Purpose
Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods
We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results
Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion
Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

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General

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors: Yoon-Koo Kang, Min-Hee Ryu, Yong Sang Hong, Chang-Min Choi, Tae Won Kim, Baek-Yeol Ryoo, Jeong Eun Kim, John R. Weis, Rachel Kingsford, Cheol Hee Park, Seong Jang, Arlo McGinn, Theresa L. Werner, Sunil Sharma; Cancer Res Treat. 2024;56(3):743-750. Published online January 18, 2024; DOI: https://doi.org/10.4143/crt.2023.980

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors.
Materials and Methods
In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer.
Results
A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%.
Conclusion
The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

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Gastrointestinal cancer

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection: Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo; Cancer Res Treat. 2023;55(4):1313-1320. Published online May 4, 2023; DOI: https://doi.org/10.4143/crt.2023.452

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Purpose
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

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A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers
Zexi Allan, David S Liu, Margaret M Lee, Jeanne Tie, Nicholas J Clemons
Clinical Chemistry.2024; 70(1): 49. CrossRef
High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study
Lei Huang, Yao Lv, Shasha Guan, Huan Yan, Lu Han, Zhikuan Wang, Quanli Han, Guanghai Dai, Yan Shi
Journal of Translational Medicine.2024;[Epub] CrossRef
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Khadija Turabi, Kelsey Klute, Prakash Radhakrishnan
Cancers.2024; 16(13): 2432. CrossRef
Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma
Ibone Labiano, Ana E. Huerta, Maria Alsina, Hugo Arasanz, Natalia Castro, Saioa Mendaza, Arturo Lecumberri, Iranzu Gonzalez-Borja, David Guerrero-Setas, Ana Patiño-Garcia, Gorka Alkorta-Aranburu, Irene Hernández-Garcia, Virginia Arrazubi, Elena Mata, Davi
Scientific Reports.2024;[Epub] CrossRef
Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer
Wei Guo, Peiyao Ying, Ruiyang Ma, Zuoqian Jing, Gang Ma, Jin Long, Guichen Li, Zhe Liu
Cytokine & Growth Factor Reviews.2023; 73: 69. CrossRef

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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX: So Heun Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Sora Kang, Jae Ho Jeong, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Yejong Park, Bong Jun Kwak, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim; Cancer Res Treat. 2023;55(3):956-968. Published online February 27, 2023; DOI: https://doi.org/10.4143/crt.2022.409

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Purpose
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

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The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database
Hao Hu, Yang Xu, Qiang Zhang, Yuan Gao, Zhenyu Wu
Expert Review of Anticancer Therapy.2024; 24(6): 467. CrossRef
Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how
Nebojsa Manojlovic, Goran Savic, Stevan Manojlovic
World Journal of Gastrointestinal Surgery.2024; 16(5): 1223. CrossRef
Case Study on Analysing the Early Disease Detection of Pancreatic Ductal Adenocarcinoma in Korean Association for Clinical Oncology
Sijithra Ponnarassery Chandran, N. Santhi
American Journal of Clinical Oncology.2024; 47(10): 475. CrossRef
Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis
Jiahao Wu, Yike Zhang, Haodong Wang, Wenyi Guo, Chengqing Li, Yichen Yu, Han Liu, Feng Li, Lei Wang, Jianwei Xu
Frontiers in Oncology.2024;[Epub] CrossRef

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Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients: Jwa Hoon Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Kyu-pyo Kim, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Yejong Park, Jae Woo Kwon, Dae Wook Hwang, Jae Hoon Lee, Woohyung Lee, Song Cheol Kim, Changhoon Yoo, Ki Byung Song; Cancer Res Treat. 2021;53(2):424-435. Published online November 9, 2020; DOI: https://doi.org/10.4143/crt.2020.953

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.
Materials and Methods
Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.
Results
The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).
Conclusion
AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

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Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer
Chae Hwa Kwon, Hyung Il Seo, Dong Uk Kim, Sung Yong Han, Suk Kim, Nam Kyung Lee, Seung Baek Hong, Ji Hyun Ahn, Young Mok Park, Byeong Gwan Noh
World Journal of Clinical Cases.2024; 12(2): 267. CrossRef
Prognostic efficacy of lymph node parameters in resected ampullary adenocarcinoma based on long-term follow-up data after adjuvant treatment
Namyoung Park, In Rae Cho, Sang Hyub Lee, Joo Seong Kim, Jin Ho Choi, Min Woo Lee, Woo Hyun Paik, Kwang Ro Joo, Ji Kon Ryu, Yong-Tae Kim
World Journal of Surgical Oncology.2024;[Epub] CrossRef
Adjuvant Chemotherapy and Effect on Long-Term Survival in Ampullary Adenocarcinoma: A Multicenter Cohort Study
Dong Woo Shin, Jae Min Lee, Jong-chan Lee, Hee Seung Lee, Seung Bae Yoon, Dong Kee Jang, Joo Kyung Park, Min Kyu Jung, Yoon Suk Lee, Jin-Hyeok Hwang
Journal of the American College of Surgeons.2023; 237(3): 501. CrossRef
Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma
Se Jun Park, Kabsoo Shin, In-Ho Kim, Tae Ho Hong, Younghoon Kim, Myung-ah Lee
World Journal of Gastrointestinal Oncology.2023; 15(4): 677. CrossRef
Remission from the 5-Fu-Based Chemotherapy to Gemcitabine-Based Chemotherapy-Based on the Pathological Classification of Periampullary Carcinoma: A Case Report and Literature Review
Wei Hu, Zhiqing Duan, Yinuo Zhang, Jing Liu, Jing Bao, Ruqing Gao, Yajie Tang, Tiande Liu, Hu Xiong, Wen Li, Xiaowei Fu, Shousheng Liao, Lu Fang, Bo Liang
OncoTargets and Therapy.2022; Volume 15: 891. CrossRef

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Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion: Changhoon Yoo, Chung Ryul Oh, Seung-Tae Kim, Woo Kyun Bae, Hye-Jin Choi, Do-Youn Oh, Myung-Ah Lee, Baek-Yeol Ryoo; Cancer Res Treat. 2021;53(2):291-300. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1233

Abstract PDF PubReader ePub

Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

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Efficacy and Safety of Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Unresectable or Metastatic Neuroendocrine Tumors in Korea
Yeokyeong Shin, Bo Hyun Moon, Baek-Yeol Ryoo, Heung-Moon Chang, Kyu-pyo Kim, Yong Sang Hong, Tae Won Kim, Jin-Sook Ryu, Yong-il Kim, Changhoon Yoo
Targeted Oncology.2024; 19(1): 41. CrossRef
Effectiveness and Safety of Retreatment with177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States
Ebrahim S. Delpassand, Soheil M. Yazdi, Shashank Ghantoji, Antonio Nakasato, Corinne Strickland, Rodolfo Nunez, Afshin Shafie, Susan Cork, Clare Byrne, Jackson Tang, Jeetvan Patel
Journal of Nuclear Medicine.2024; 65(5): 746. CrossRef
Advances in hydrogel materials applied to pancreatic-related diseases
Yuan Zhou, Maoen Pan, Ronggui Lin, Heguang Huang
Journal of Pancreatology.2024; 7(3): 222. CrossRef
Prognostic value of interim [68Ga]Ga-DOTA-TOC PET/CT in patients with neuroendocrine tumour who underwent peptide receptor radionuclide therapy
Eonwoo Shin, Yong-il Kim, Changhoon Yoo, Yeokyeong Shin, Baek-Yeol Ryoo, Dong Yun Lee, Jin-Sook Ryu
European Radiology.2024;[Epub] CrossRef
Consideration of quality of life in the treatment decision-making for patients with advanced gastroenteropancreatic neuroendocrine tumors
Boris G. Naraev, Josh Mailman, Thorvardur R. Halfdanarson, Heloisa P. Soares, Erik S. Mittra, Julie Hallet
Expert Review of Anticancer Therapy.2023; 23(6): 601. CrossRef
KSNM60 in Nuclear Endocrinology: from the Beginning to the Future
Chae Moon Hong, Young Jin Jeong, Hae Won Kim, Byeong-Cheol Ahn
Nuclear Medicine and Molecular Imaging.2022; 56(1): 17. CrossRef
Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis
Eun-Joo Park, Hyo-Jung Park, Kyung-Won Kim, Chong-Hyun Suh, Changhoon Yoo, Young-Kwang Chae, Sree Harsha Tirumani, Nikhil H. Ramaiya
Cancers.2022; 14(3): 794. CrossRef
Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs)
Krzysztof Kaliszewski, Maksymilian Ludwig, Maria Greniuk, Agnieszka Mikuła, Karol Zagórski, Jerzy Rudnicki
Cancers.2022; 14(8): 2028. CrossRef
Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index <55%: single-arm phase II study
H. Jeong, J. Shin, J.H. Jeong, K.-p. Kim, S.-M. Hong, Y.-i. Kim, J.-S. Ryu, B.-Y. Ryoo, C. Yoo
ESMO Open.2021; 6(3): 100119. CrossRef

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Gastrointestinal cancer

Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3^- CD4⁺ T Cells in Biliary Tract Cancer: Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo; Cancer Res Treat. 2021;53(1):162-171. Published online August 31, 2020; DOI: https://doi.org/10.4143/crt.2020.704

Abstract PDF Supplementary Material PubReader ePub

Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8⁺ T cells, FoxP3^- CD4⁺ helper T cells, and FoxP3⁺ CD4⁺ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8⁺ T cell and FoxP3^- CD4⁺ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3^-CD4⁺ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3^- CD4⁺ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3^-CD4⁺ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

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Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
Molecular Cancer.2024;[Epub] CrossRef
Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma
Sijia Hua, Xinyi Gu, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang
Biomedicine & Pharmacotherapy.2024; 177: 117080. CrossRef
Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer
Luohang Ni, Jianing Xu, Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao
Cancer Management and Research.2024; Volume 16: 941. CrossRef
Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as a Potential Biomarker for Immune Checkpoint Inhibitors in Patients with Biliary Tract Cancer
Yeong Hak Bang, Choong-kun Lee, Kyunghye Bang, Hyung-Don Kim, Kyu-pyo Kim, Jae Ho Jeong, Inkeun Park, Baek-Yeol Ryoo, Dong Ki Lee, Hye Jin Choi, Taek Chung, Seung Hyuck Jeon, Eui-Cheol Shin, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chang Ho Ahn, T
Clinical Cancer Research.2024; 30(20): 4635. CrossRef
Prognostic value of tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma
S.-Y. Jun, S. An, S.-M. Hong, J.-Y. Kim, K.-P. Kim
ESMO Open.2024; 9(11): 103969. CrossRef
Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)
Siqi Yang, Ruiqi Zou, Yushi Dai, Yafei Hu, Fuyu Li, Haijie Hu
International Journal of Oncology.2023;[Epub] CrossRef
Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes
Chaoqun Li, Lei Bie, Muhua Chen, Jieer Ying
Exploration of Targeted Anti-tumor Therapy.2023; 4(6): 1310. CrossRef
Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
Hyung-Don Kim, Sun Young Kim, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Buhm Han, Eunyoung Tak, Yeon-Mi Ryu, Sang-Yeob Kim, Tae Won Kim
Scientific Reports.2022;[Epub] CrossRef
Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma
Taek Chung, Young Nyun Park
Frontiers in Medicine.2022;[Epub] CrossRef
The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Dong Liu, Lara Rosaline Heij, Zoltan Czigany, Edgar Dahl, Sven Arke Lang, Tom Florian Ulmer, Tom Luedde, Ulf Peter Neumann, Jan Bednarsch
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
Jwa Hoon Kim, Gi Hwan Kim, Yeon-Mi Ryu, Sang-Yeob Kim, Hyung-Don Kim, Shin Kyo Yoon, Yong Mee Cho, Jae Lyun Lee
Frontiers in Oncology.2022;[Epub] CrossRef
Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
Journal of Hematology & Oncology.2021;[Epub] CrossRef

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Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response: Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-hong Park, Seung-Mo Hong, Kyu-pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo; Cancer Res Treat. 2020;52(2):594-603. Published online December 18, 2019; DOI: https://doi.org/10.4143/crt.2019.493

Abstract PDF PubReader ePub

Purpose
The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.
Materials and Methods
In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.
Results
Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).
Conclusion
Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

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Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Kyoungmin Lee, Kyunghye Bang, Changhoon Yoo, Inhwan Hwang, Jae Ho Jeong, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Do Hyun Park, Sang Soo Lee, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Kyu-pyo Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2020;52(1):254-262. Published online July 9, 2019; DOI: https://doi.org/10.4143/crt.2019.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM.
Materials and Methods
Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors.
Results
Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy.
Conclusion
2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

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Brandon M. Huffman, Atrayee Basu Mallick, Nora K. Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A. Morse, Muhammad Shaalan Beg, Janet E. Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L. Schlechter, Hanna Sanoff, Christopher Manz, Brian M. Wolp
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Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG)
H.S. Park, B. Kang, H.J. Chon, H.-S. Im, C.-K. Lee, I. Kim, M.J. Kang, J.E. Hwang, W.K. Bae, J. Cheon, J.O. Park, J.Y. Hong, J.H. Kang, J.H. Kim, S.H. Lim, J.W. Kim, J.-W. Kim, C. Yoo, H.J. Choi
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Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin: Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(3):901-909. Published online October 4, 2018; DOI: https://doi.org/10.4143/crt.2018.326

Abstract PDF Supplementary Material PubReader ePub

Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma: Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(2):510-518. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.226

Abstract PDF Supplementary Material PubReader ePub

Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

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Cell Proliferation.2023;[Epub] CrossRef
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Discovery of a Highly Potent and Orally Bioavailable STAT3 Dual Phosphorylation Inhibitor for Pancreatic Cancer Treatment
Peng He, Aiwu Bian, Ying Miao, Wangrui Jin, Huang Chen, Jia He, Liting Li, Yue Sun, Jiangnan Ye, Mingyao Liu, Zhengfang Yi, Wenbo Zhou, Yihua Chen
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Han‐Qi Wang, Qi‐Wen Man, Fang‐Yi Huo, Xin Gao, Hao Lin, Su‐Ran Li, Jing Wang, Fu‐Chuan Su, Lulu Cai,, Yi Shi, Bing Liu,, Lin‐Lin Bu
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Yinjie Fan, Hang Xue, Huachuan Zheng
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Joaquín Martínez‑López, Pau Montesinos, Nieves López‑Muñoz, Rosa Ayala, Pilar Martínez‑Sánchez, Julian Gorrochategui, José Rojas‑Rudilla, Daniel Primo, Juan-Miguel Bergua‑Burgues, María Calbacho, Evelyn Acuña‑Cruz, José Pérez‑Simón, Adolfo De La Fuente, J
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Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment
Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Huang Chen, Jiangnan Ye, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
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Mitochondrial Plasticity Promotes Resistance to Sorafenib and Vulnerability to STAT3 Inhibition in Human Hepatocellular Carcinoma
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Prognosis of Pancreatic Cancer Patients with Synchronous or Metachronous Malignancies from Other Organs Is Better than Those with Pancreatic Cancer Only: Su-Jin Shin, Hosub Park, You-Na Sung, Changhoon Yoo, Dae Wook Hwang, Jin-hong Park, Kyu-pyo Kim, Sang Soo Lee, Baek-Yeol Ryoo, Dong-Wan Seo, Song Cheol Kim, Seung-Mo Hong; Cancer Res Treat. 2018;50(4):1175-1185. Published online December 20, 2017; DOI: https://doi.org/10.4143/crt.2017.494

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic cancer associated double primary tumors are rare and their clinicopathologic characteristics are not well elucidated.
Materials and Methods
Clinicopathologic factors of 1,352 primary pancreatic cancers with or without associated double primary tumors were evaluated.
Results
Of resected primary pancreatic cancers, 113 (8.4%) had associated double primary tumors, including 26 stomach, 25 colorectal, 18 lung, and 13 thyroid cancers. The median interval between the diagnoses of pancreatic cancer and associated double primary tumors was 0.5 months. Overall survival (OS) of pancreatic cancer patients with associated double primary tumors was longer than those with pancreatic cancer only (median, 23.1 months vs. 17.0 months, p=0.002). Patients whose pancreatic cancers were resected before the diagnosis of metachronous tumors had a better OS than patients whose pancreatic cancer resected after the diagnosis of metachronous tumors (48.9 months and 13.5 months, p=0.001) or those whose pancreatic cancers were resected synchronously with non-pancreas tumors (19.1 months, p=0.043). The OS of pancreatic cancer patients with stomach (33.9 months, p=0.032) and thyroid (117.8 months, p=0.049) cancers was significantly better than those with pancreas cancer only (17.0 months).
Conclusion
About 8% of resected pancreatic cancers had associated double primary tumors, and those from the colorectum, stomach, lung, and thyroid were common. Patients whose pancreatic cancer was resected before the diagnosis of metachronous tumors had better OS than those resected after the diagnosis of metachronous tumors or those resected synchronously.

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Motoki Ebihara, Kentoku Fujisawa, Shusuke Haruta, Hironori Uruga, Masaki Ueno
Cureus.2024;[Epub] CrossRef
Synchronous primary multiple cancer: distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail
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Lei Zhang, Xin Long, Zheng-Nan Hu, Yu Wu, Jia Song, Bi-Xiang Zhang, Wei-Xun Chen
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Min Ji Kim, Han-Sang Baek, Sung Hak Lee, Dong-Jun Lim
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Qing Han, Junhe Li, Jianping Xiong, Zhiwang Song
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Oronzo Brunetti, Giuseppe Badalamenti, Simona De Summa, Angela Calabrese, Antonella Argentiero, Livia Fucci, Vito Longo, Domenico Galetta, Pia Maria Soccorsa Perrotti, Rosamaria Pinto, Daniela Petriella, Katia Danza, Stefania Tommasi, Francesco Leonetti,
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241 Download
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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer: Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang; Cancer Res Treat. 2018;50(4):1324-1330. Published online January 8, 2018; DOI: https://doi.org/10.4143/crt.2017.526

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m² oxaliplatin (day 1), 135 mg/m² irinotecan (day 1), and 40 mg/m² S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

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Phase II Study of Induction Chemotherapy with Docetaxel, Capecitabine, and Cisplatin Plus Bevacizumab for Initially Unresectable Gastric Cancer with Invasion of Adjacent Organs or Paraaortic Lymph Node Metastasis: Jwa Hoon Kim, Sook Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo, Kyu-pyo Kim, Beom Su Kim, Moon-Won Yoo, Jeong Hwan Yook, Byung Sik Kim, Jihun Kim, Sun-Ju Byeon, Yoon-Koo Kang; Cancer Res Treat. 2018;50(2):518-529. Published online May 24, 2017; DOI: https://doi.org/10.4143/crt.2017.005

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC).
Materials and Methods
Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m² docetaxel intravenously on day 1, 937.5 mg/m² capecitabine orally twice daily on days 1-14, 60 mg/m² cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate.
Results
Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively.
Conclusion
Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.

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Clinical Efficacy and Safety of Bevacizumab, Apatinib, and Recombinant Human Endothelial Inhibitor in the Treatment of Advanced Gastric Cancer
Liang Wang, Wei Li, Ya-Gang Liu, Cui Zhang, Wei-Na Gao, Li-Fei Gao, Wei long Zhong
Journal of Oncology.2022; 2022: 1. CrossRef
Neoadjuvant Bevacizumab Plus Docetaxel/Cisplatin/Capecitabine Chemotherapy in Locally Advanced Gastric Cancer Patients: A Pilot Study
Deguo Yu, Zhenfeng Wang, Tingbang He, Lijun Yang
Frontiers in Surgery.2022;[Epub] CrossRef
Research progress in targeted therapy and immunotherapy for gastric cancer
Xuewei Li, Jun Xu, Jun Xie, Wenhui Yang
Chinese Medical Journal.2022; 135(11): 1299. CrossRef
Novel Drug Delivery Method Targeting Para-Aortic Lymph Nodes by Retrograde Infusion of Paclitaxel into Pigs’ Thoracic Duct
Akira Saito, Natsuka Kimura, Yuji Kaneda, Hideyuki Ohzawa, Hideyo Miyato, Hironori Yamaguchi, Alan Kawarai Lefor, Ryozo Nagai, Naohiro Sata, Joji Kitayama, Kenichi Aizawa
Cancers.2022; 14(15): 3753. CrossRef
New therapeutic options opened by the molecular classification of gastric cancer
Mihaela Chivu-Economescu, Lilia Matei, Laura G Necula, Denisa L Dragu, Coralia Bleotu, Carmen C Diaconu
World Journal of Gastroenterology.2018; 24(18): 1942. CrossRef
Gastric cancer: Basic aspects
Henrique O. Duarte, Joana Gomes, José C. Machado, Celso A. Reis
Helicobacter.2018;[Epub] CrossRef

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Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen: Changhoon Yoo, Bum Jun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Tae Won Kim, Baek-Yeol Ryoo, Heung-Moon Chang; Cancer Res Treat. 2017;49(3):759-765. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.371

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy.
Materials and Methods
Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea.
Results
The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second- line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029).
Conclusion
Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.

Citations

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Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program: Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Tae-Yong Kim, Su Jin Lee, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang; Cancer Res Treat. 2017;49(2):350-357. Published online July 19, 2016; DOI: https://doi.org/10.4143/crt.2016.067

Abstract PDF PubReader ePub

Purpose
The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
Materials and Methods
Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off).
Results
None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31).
Conclusion
This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

Citations

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Seiichi Hirota, Ukihide Tateishi, Yuji Nakamoto, Hidetaka Yamamoto, Shinji Sakurai, Hirotoshi Kikuchi, Tatsuo Kanda, Yukinori Kurokawa, Haruhiko Cho, Toshirou Nishida, Akira Sawaki, Masato Ozaka, Yoshito Komatsu, Yoichi Naito, Yoshitaka Honma, Fumiaki Tak
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Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
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Charlotte Margareta Brinch, Ninna Aggerholm-Pedersen, Estrid Hogdall, Anders Krarup-Hansen
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Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
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Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib
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Oncotarget.2017; 8(55): 93813. CrossRef

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Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data: Do Young Kim, Hye Jin Kim, Kwang-Hyub Han, Sang Young Han, Jeong Heo, Hyun Young Woo, Soon Ho Um, Yeul Hong Kim, Young Oh Kweon, Ho Yeong Lim, Jung Hwan Yoon, Wan Sik Lee, Byung Seok Lee, Han Chu Lee, Baek-Yeol Ryoo, Seung Kew Yoon; Cancer Res Treat. 2016;48(4):1243-1252. Published online February 24, 2016; DOI: https://doi.org/10.4143/crt.2015.278

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study).
Materials and Methods
Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients.
Results
More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients.
Conclusion
Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).

Citations

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Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea
Sojung Han, Do Young Kim, Ho Yeong Lim, Jung-Hwan Yoon, Baek-Yeol Ryoo, Yujeong Kim, Kookhee Kim, Bo Yeon Kim, So Young Yi, Dong-Sook Kim, Do-Yeon Cho, Jina Yu, Suhyun Kim, Joong-Won Park
Gut and Liver.2024; 18(1): 116. CrossRef
Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor
Po-Ting Lin
American Journal of Cancer Research.2024; 14(3): 1306. CrossRef
Advances in Pharmacotherapy of Hepatocellular Carcinoma: A State-of-the-Art Review
Florian P. Reiter, Najib Ben Khaled, Liangtao Ye, Changhua Zhang, Max Seidensticker, Mark op den Winkel, Gerald Denk, Andreas Geier, Enrico N. De Toni
Digestive Diseases.2022; 40(5): 565. CrossRef
Treatment efficacy by hepatic arterial infusion chemotherapy vs. sorafenib after liver-directed concurrent chemoradiotherapy for advanced hepatocellular carcinoma
Sojung Han, Hye Jin Choi, Seung-Hoon Beom, Hye Rim Kim, Hyein Lee, Jae Seung Lee, Hye Won Lee, Jun Yong Park, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Jinsil Seong, Jong Yun Won, Beom Kyung Kim
Journal of Cancer Research and Clinical Oncology.2021; 147(10): 3123. CrossRef
Hepatocellular cancer therapy in patients with HIV infection: Disparities in cancer care, trials enrolment, and cancer-related research
Francesca Negri, Gabriele Missale, Anna Degli Antoni, Camillo Porta
Translational Oncology.2021; 14(9): 101153. CrossRef
Efficacy and Safety of Liver-Directed Concurrent Chemoradiotherapy and Sequential Sorafenib for Advanced Hepatocellular Carcinoma: A Prospective Phase 2 Trial
Beom Kyung Kim, Do Young Kim, Hwa Kyung Byun, Hye Jin Choi, Seung-Hoon Beom, Hye Won Lee, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Jinsil Seong, Kwang-Hyub Han
International Journal of Radiation Oncology*Biology*Physics.2020; 107(1): 106. CrossRef
Transarterial Infusion of Epirubicin and Cisplatin Combined With Systemic Infusion of 5-Flurouracil Versus Sorafenib for Hepatocellular Carcinoma With Refractoriness of Transarterial Chemoembolization Using Doxorubicin
Sun Hong Yoo, Jung Hyun Kwon, Soon Woo Nam, Jong Yul Lee, Young Woon Kim, Dong Jae Shim, Sung Won Lee, Jeong Won Jang
Cancer Control.2020;[Epub] CrossRef
Hepatocellular Carcinoma in Korea between 2012 and 2014: an Analysis of Data from the Korean Nationwide Cancer Registry
Young Eun Chon, Han Ah Lee, Jun Sik Yoon, Jun Yong Park, Bo Hyun Kim, In Joon Lee, Suk Kyun Hong, Dong Hyeon Lee, Hyun-Joo Kong, Eunyang Kim, Young-Joo Won, Jeong-Hoon Lee
Journal of Liver Cancer.2020; 20(2): 135. CrossRef
Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion

Sojung Han, Hye Won Lee, Jun Yong Park, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Jinsil Seong, Jong Yun Won, Dai Hoon Han, Beom Kyung Kim
Journal of Hepatocellular Carcinoma.2020; Volume 7: 403. CrossRef
Sorafenib: key lessons from over 10 years of experience
Bernard Escudier, Francis Worden, Masatoshi Kudo
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Liver Transplantation after Successful Downstaging with Hepatic Arterial Infusion Chemotherapy in a Patient with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
Hee Chul Nam, Pil Soo Sung, Ho Jong Chun, Dong Goo Kim, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon
Journal of Liver Cancer.2019; 19(1): 64. CrossRef
18F–fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment
Pil Soo Sung, Hye Lim Park, Keungmo Yang, Seawon Hwang, Myeong Jun Song, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Ie Ryung Yoo, Si Hyun Bae
European Journal of Nuclear Medicine and Molecular Imaging.2018; 45(3): 384. CrossRef
Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC Phase 3 Randomized Controlled Trial
Nikhil Chauhan, Janet Bukovcan, Eveline Boucher, David Cosgrove, Julien Edeline, Bonnie Hamilton, Laura Kulik, Fayaz Master, Riad Salem
JMIR Research Protocols.2018; 7(8): e11234. CrossRef
Sorafenib: A Review in Hepatocellular Carcinoma
Gillian M. Keating
Targeted Oncology.2017; 12(2): 243. CrossRef
Treatment options after sorafenib failure in patients with hepatocellular carcinoma
Imane El Dika, Ghassan K. Abou-Alfa
Clinical and Molecular Hepatology.2017; 23(4): 273. CrossRef
Dickkopf-1 induces angiogenesis via VEGF receptor 2 regulation independent of the Wnt signaling pathway
Sung Hoon Choi, Hyemi Kim, Hyun Gyu Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
Oncotarget.2017; 8(35): 58974. CrossRef

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Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha–Mutated Gastrointestinal Stromal Tumors: Changhoon Yoo, Min-Hee Ryu, Jungmin Jo, Inkeun Park, Baek-Yeol Ryoo, Yoon-Koo Kang; Cancer Res Treat. 2016;48(2):546-552. Published online June 22, 2015; DOI: https://doi.org/10.4143/crt.2015.015

Abstract PDF PubReader ePub

Purpose
The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed.
Materials and Methods
Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea.
Results
KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02).
Conclusion
Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.

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Severe Imatinib-Associated Skin Rash in Gastrointestinal Stromal Tumor Patients: Management and Clinical Implications: Sook Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo, Mo Youl Beck, In Soon Lee, Mi Jung Choi, Mi Woo Lee, Yoon-Koo Kang; Cancer Res Treat. 2016;48(1):162-170. Published online September 1, 2015; DOI: https://doi.org/10.4143/crt.2015.017

Abstract PDF PubReader ePub

Purpose
This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients.
Materials and Methods
A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use.
Results
Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinibassociated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326).
Conclusion
By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions.

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Albina N. Khlebnikova, Valentina E. Shikina, Gayane E. Bagramova
Almanac of Clinical Medicine.2024; 51(7): 417. CrossRef
Untargeted metabolomics analysis reveals the potential mechanism of imatinib-induced skin rash in patients with gastrointestinal stromal tumor
Xiao Huang, Linhua Chen, Li Liu, Hefen Chen, Zhujun Gong, Jianbo Lyu, Yao Li, Qi Jiang, Xiangyu Zeng, Peng Zhang, Hong Zhou
International Immunopharmacology.2024; 140: 112728. CrossRef
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Fangyao Hu, Sara F. Santagostino, Dimitry M. Danilenko, Min Tseng, Jochen Brumm, Philip Zehnder, Kai Connie Wu
The American Journal of Pathology.2022; 192(4): 687. CrossRef
Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature
Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
Cancers.2022; 14(7): 1832. CrossRef
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Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-Analysis Based on Individual Patient-Level Data of Randomized Trials: Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo; Received July 16, 2024 Accepted October 15, 2024 Published online October 17, 2024; DOI: https://doi.org/10.4143/crt.2024.652 [Accepted]

Abstract PDF: Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p =0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs nal-IRI plus 5-FU/LV, 95% CI 0.93-2.07, p=0.11) and 1.36 (mFOLFIRI vs nal-IRI plus 5-FU/LV, 95% CI 0.92-2.03, p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

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