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22 "Changhoon Yoo"
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Original Articles
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]
AbstractAbstract 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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Gastrointestinal cancer
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
AbstractAbstract PDFPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • 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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Special Article
Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
Cancer Res Treat. 2024;56(3):721-742.   Published online November 29, 2023
DOI: https://doi.org/10.4143/crt.2023.1043
AbstractAbstract PDFPubReaderePub
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
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Original Article
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • 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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Erratum
ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim
Cancer Res Treat. 2023;55(3):1061-1061.   Published online April 21, 2023
DOI: https://doi.org/10.4143/crt.2021.1115.E
Corrects: Cancer Res Treat 2022;54(1):1
PDFPubReaderePub
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Original Articles
Gastrointestinal cancer
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

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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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Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer
Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo
Cancer Res Treat. 2023;55(1):219-230.   Published online April 6, 2022
DOI: https://doi.org/10.4143/crt.2021.1166
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Citations

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  • Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
    Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
    Journal of Clinical Medicine.2024; 13(9): 2718.     CrossRef
  • 5,673 View
  • 194 Download
  • 1 Web of Science
  • 1 Crossref
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Special Article
Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim
Cancer Res Treat. 2022;54(1):1-9.   Published online December 13, 2021
DOI: https://doi.org/10.4143/crt.2021.1115
Correction in: Cancer Res Treat 2023;55(3):1061
AbstractAbstract PDFPubReaderePub
Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Citations

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  • Expert Consensus on Molecular Tumor Boards in Taiwan: Joint Position Paper by the Taiwan Oncology Society and the Taiwan Society of Pathology
    Ming-Huang Chen, Wan-Shan Li, Bin-Chi Liao, Chiao-En Wu, Chien-Feng Li, Chia-Hsun Hsieh, Feng-Che Kuan, Huey-En Tzeng, Jen-Fan Hang, Nai-Jung Chiang, Tse-Ching Chen, Tom Wei-Wu Chen, John Wen-Cheng Chang, Yao-Yu Hsieh, Yen-Lin Chen, Yi-Chen Yeh, Yi-Hsin L
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  • Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
    Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
    Journal of Pathology and Translational Medicine.2024; 58(4): 147.     CrossRef
  • Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
    Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
    Cancer Research and Treatment.2024; 56(3): 721.     CrossRef
  • Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05
    T.-Y. Kim, S.Y. Kim, J.H. Kim, H.A. Jung, Y.J. Choi, I.G. Hwang, Y. Cha, G.-W. Lee, Y.-G. Lee, T.M. Kim, S.-H. Lee, S. Lee, H. Yun, Y.L. Choi, S. Yoon, S.W. Han, T.-Y. Kim, T.W. Kim, D.Y. Zang, J.H. Kang
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  • Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers
    Yongjun Cha, Sheehyun Kim, Sae-Won Han
    Cancer Research and Treatment.2023; 55(2): 367.     CrossRef
  • Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
    Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
    International Journal of Cancer.2023; 153(3): 571.     CrossRef
  • Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
    Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
    Journal of Pathology and Translational Medicine.2023; 57(5): 265.     CrossRef
  • Implementation of Precision Oncology in the National Healthcare System: A Statement Proposal Endorsed by Italian Scientific Societies
    Gianpiero Fasola, Maria C. Barducci, Valeria D. Tozzi, Luigi Cavanna, Saverio Cinieri, Francesco Perrone, Carmine Pinto, Antonio Russo, Anna Sapino, Francesco Grossi, Giuseppe Aprile
    JCO Precision Oncology.2023;[Epub]     CrossRef
  • Development of two 410-cancer-gene panel tests for solid tumors and liquid biopsy based on genome data of 5,143 Japanese cancer patients
    Yuji SHIMODA, Takeshi NAGASHIMA, Kenichi URAKAMI, Fukumi KAMADA, Sou NAKATANI, Maki MIZUGUCHI, Masakuni SERIZAWA, Keiichi HATAKEYAMA, Keiichi OHSHIMA, Tohru MOCHIZUKI, Sumiko OHNAMI, Shumpei OHNAMI, Takeshi KAWAKAMI, Kentaro YAMAZAKI, Haruyasu MURAKAMI, H
    Biomedical Research.2022; 43(4): 115.     CrossRef
  • Clinical Implication of Molecular Tumor Board
    Soohyeon Lee
    The Korean Journal of Medicine.2022; 97(5): 319.     CrossRef
  • Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study
    Jung Ho Park, Mi Jung Kwon, Jinwon Seo, Ho Young Kim, Soo Kee Min, Lee Su Kim
    Journal of Breast Cancer.2022; 25(5): 379.     CrossRef
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Review Article
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
AbstractAbstract PDFPubReaderePub
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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Original Articles
Gastrointestinal cancer
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFPubReaderePub
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer
Changhoon Yoo, Sung-Bae Kim, Jungsil Ro, Seock-Ah Im, Young-Hyuck Im, Jee Hyun Kim, Jin-Hee Ahn, Kyung Hae Jung, Hong Suk Song, Seok Yun Kang, Hee Sook Park, Hyun-Cheol Chung
Cancer Res Treat. 2016;48(2):499-507.   Published online July 14, 2015
DOI: https://doi.org/10.4143/crt.2015.089
AbstractAbstract PDFPubReaderePub
Purpose
This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
Materials and Methods
A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)- AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
Results
In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
Conclusion
Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.
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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
AbstractAbstract PDFPubReaderePub
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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A Randomized Phase II Trial of Capecitabine Plus Vinorelbine Followed by Docetaxel Versus Adriamycin Plus Cyclophosphamide Followed by Docetaxel as Neoadjuvant Chemotherapy for Breast Cancer
Changhoon Yoo, Sung-Bae Kim, Jin-Hee Ahn, Jeong Eun Kim, Kyung Hae Jung, Gyung-Yub Gong, Byung-Ho Son, Sei-Hyun Ahn, Seung Do Ahn, Hak-Hee Kim, Hee Jung Shin, Woo Kun Kim
Cancer Res Treat. 2015;47(3):406-415.   Published online November 27, 2014
DOI: https://doi.org/10.4143/crt.2014.073
AbstractAbstract PDFPubReaderePub
Purpose
Given the promising activity of capecitabine and vinorelbine in metastatic breast cancer, this randomized phase II trial evaluated the efficacy and safety of this combination as neoadjuvant chemotherapy in breast cancer. Materials and Methods Patients with operable breast cancer (n=75) were randomly assigned to receive either four cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of docetaxel 75 mg/m2 every 3 weeks (AC-D) or four cycles of capecitabine 2,000 mg/m2 (day 1-14) plus vinorelbine 25 mg/m2 (days 1 and 8) every 3 weeks followed by four cycles of docetaxel 75 mg/m2 (CV-D). The primary endpoint was pathologic complete response (pCR) in the primary breast (ypT0/is). Results Most patients (84%) had locally advanced (n=41) or inflammatory breast cancer (n=22). pCR rates in the primary breast were 15% (95% confidence interval [CI], 7% to 30%) and 11% (95% CI, 4% to 26%) in the AC-D and CV-D groups, respectively. The overall response rates and 5-year progression-free survival rates in the AC-D and CV-D groups were 62% and 64%, and 51.3% (95% CI, 34.6% to 68.0%) and 30.2% (95% CI, 13.3% to 47.1%), respectively. Although both regimens were well tolerated, CV-D showed less frequent grade 3-4 neutropenia and vomiting than AC-D, whereas manageable diarrhea and hand-foot syndrome were more common in the CV-D group. Conclusion CV-D is a feasible and active non-anthracycline–based neoadjuvant chemotherapy regimen for breast cancer.

Citations

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  • Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials
    Ze-Chun Zhang, Qi-Ni Xu, Sui-Ling Lin, Xu-Yuan Li, Hemant Kumar Bid
    PLOS ONE.2016; 11(10): e0164663.     CrossRef
  • 12,023 View
  • 101 Download
  • 6 Web of Science
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