Cancer Research and Treatment

Original Articles

General

The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group: Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang; Cancer Res Treat. 2025;57(1):39-46. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.421

Abstract PDF PubReader ePub: Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

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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

GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment: Jaewon Hyung, Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Meesun Moon, Yoon-Koo Kang; Cancer Res Treat. 2024;56(1):199-207. Published online June 20, 2023; DOI: https://doi.org/10.4143/crt.2023.490

Abstract PDF Supplementary Material PubReader ePub: Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

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Adjuvant Imatinib Treatment for 5 Years versus 3 Years in Patients with Ruptured Localized Gastrointestinal Stromal Tumor: A Retrospective Analysis: Sora Kang, Min-Hee Ryu, Yeong Hak Bang, Hyung-Don Kim, Hyung Eun Lee, Yoon-Koo Kang; Cancer Res Treat. 2022;54(4):1167-1174. Published online December 6, 2021; DOI: https://doi.org/10.4143/crt.2021.1040

Abstract PDF Supplementary Material PubReader ePub

Purpose
Three years of adjuvant imatinib is the standard treatment for resected gastrointestinal stromal tumors (GISTs) with rupture, but the recurrence rate is prominently high. We aimed to investigate the efficacy and safety of 5-year adjuvant imatinib compared with 3-year treatment in patients with a ruptured GIST following surgical resection.
Materials and Methods
A total of 51 patients were included in the analysis. The assessment of GIST rupture was based on Nishida’s classification. Twenty patients who were diagnosed before November 2013 were treated with 5 years of imatinib, and 31 patients who were diagnosed after November 2013 were treated with 3 years of imatinib. We retrospectively compared the clinical outcomes of the two groups.
Results
Baseline characteristics and the incidence of the adverse events were generally comparable between the two groups. During a median follow-up duration of 43.8 months and 104.2 months in the 3- and 5-year group, 8 and 9 patients had a disease recurrence, respectively. The 5-year group showed better recurrence-free survival (RFS) than the 3-year group. In multivariate analysis, low mitotic index was a significant independent favorable prognostic factor for RFS, while 5-year imatinib treatment was marginally associated with a favorable RFS.
Conclusion
Five years of adjuvant imatinib treatment in patients with ruptured GIST was associated with favorable survival outcomes with manageable toxicity profiles. Our findings warrant validation and confirmation in future studies.

Citations

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Survival of patients with ruptured gastrointestinal stromal tumour treated with adjuvant imatinib in a randomised trial
Heikki Joensuu, Annette Reichardt, Mikael Eriksson, Peter Hohenberger, Kjetil Boye, Silke Cameron, Lars H. Lindner, Philipp J. Jost, Sebastian Bauer, Jochen Schütte, Stefan Lindskog, Raija Kallio, Panu M. Jaakkola, Dorota Goplen, Eva Wardelmann, Peter Rei
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Imatinib

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Toshirou Nishida, Naoto Gotouda, Tsuyoshi Takahashi, Hui Cao
Journal of Digestive Diseases.2023;[Epub] CrossRef
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Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
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Clinical outcomes and prognostic factors for patients with high‐risk gastrointestinal stromal tumors treated with 3‐year adjuvant imatinib
Yeong Hak Bang, Min‐Hee Ryu, Hyung‐Don Kim, Hyung Eun Lee, Yoon‐Koo Kang
International Journal of Cancer.2022; 151(10): 1770. CrossRef
Prediction of recurrence-free survival and adjuvant therapy benefit in patients with gastrointestinal stromal tumors based on radiomics features
Fu-Hai Wang, Hua-Long Zheng, Jin-Tao Li, Ping Li, Chao-Hui Zheng, Qi-Yue Chen, Chang-Ming Huang, Jian-Wei Xie
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Development and validation of a prognostic model to predict the prognosis of patients with colorectal gastrointestinal stromal tumor: A large international population-based cohort study
Yiding Li, Yujie Zhang, Yang Fu, Wanli Yang, Xiaoqian Wang, Lili Duan, Liaoran Niu, Junfeng Chen, Wei Zhou, Jinqiang Liu, Jing Wang, Daiming Fan, Liu Hong
Frontiers in Oncology.2022;[Epub] CrossRef

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Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting: Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Heejung Chae, Eo Jin Kim, Mee-Sun Moon, Yoon-Koo Kang; Cancer Res Treat. 2021;53(2):436-444. Published online October 6, 2020; DOI: https://doi.org/10.4143/crt.2020.725

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns.
Materials and Methods
A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4).
Results
There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6).
Conclusion
The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Citations

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Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair
Young-Gyu Park, Hyung-Don Kim, Jaewon Hyung, Young Soo Park, Min-Hee Ryu
Gastric Cancer.2024; 27(4): 840. CrossRef
Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha
Cancer Research and Treatment.2024; 56(4): 1136. CrossRef
Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination
Sun Young Rha, Hyun Cheol Chung
Journal of Gastric Cancer.2023;[Epub] CrossRef
Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab
Kyunghye Bang, Jaekyung Cheon, Young Soo Park, Hyung-Don Kim, Min-Hee Ryu, Yangsoon Park, Meesun Moon, Hyungeun Lee, Yoon-Koo Kang
Gastric Cancer.2022; 25(4): 794. CrossRef
Clinicopathological features and CT findings of papillary gastric adenocarcinoma
Mengying Xu, Song Liu, Xiangmei Qiao, Lin Li, Changfeng Ji, Zhengyang Zhou
Abdominal Radiology.2022; 47(11): 3698. CrossRef
New prognostic model for patients with advanced gastric cancer: Fluoropyrimidine/platinum doublet for first-line chemotherapy
Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Mee-Sun Moon, Yoon-Koo Kang
World Journal of Gastroenterology.2021; 27(48): 8357. CrossRef

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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
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Xuewei Li, Jun Xu, Jun Xie, Wenhui Yang
Chinese Medical Journal.2022; 135(11): 1299. CrossRef
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Review Article

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review: Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang; Cancer Res Treat. 2017;49(4):851-868. Published online January 3, 2017; DOI: https://doi.org/10.4143/crt.2016.176

Abstract PDF Supplementary Material PubReader ePub

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

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Original Article

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

Citations to this article as recorded by

English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology
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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A randomised phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumours
Hyung-Don Kim, Changhoon Yoo, Min-Hee Ryu, Yoon-Koo Kang
British Journal of Cancer.2023; 129(2): 275. CrossRef
Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule
Maria Susanna Grimaudo, Alice Laffi, Nicolò Gennaro, Roberta Fazio, Federico D’Orazio, Laura Samà, Licia Vanessa Siracusano, Federico Sicoli, Salvatore Lorenzo Renne, Armando Santoro, Alexia Francesca Bertuzzi
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Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib
Jae-Joon Kim, Min-Hee Ryu, Changhoon Yoo, Mo Youl Beck, Jung Eun Ma, Yoon-Koo Kang
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Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients
Gustavo Schvartsman, Michael J. Wagner, Behrang Amini, Chrystia M. Zobniw, Van Anh Trinh, Andrea G. Barbo, Heather Y. Lin, Wei-Lien Wang, Anthony Paul Conley, Vinod Ravi, Dejka M. Araujo, Maria Alejandra Zarzour, Robert S. Benjamin, Shreyaskumar Patel, Ne
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Special Article

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor: Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang; Cancer Res Treat. 2016;48(4):1155-1166. Published online June 24, 2016; DOI: https://doi.org/10.4143/crt.2016.187

Abstract PDF PubReader ePub

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

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Original Articles

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.

Citations

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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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Current Status and Challenges of Cancer Clinical Trials in Korea: Byoung Yong Shim, Se Hoon Park, Soonil Lee, Jin-Soo Kim, Kyoung Eun Lee, Yoon-Koo Kang, Myung-Ju Ahn; Cancer Res Treat. 2016;48(1):20-27. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.317

Abstract PDF PubReader ePub

Purpose
Cancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems. Materials and Methods We analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers in 56 academic hospitals.
Results
The number of cancer clinical trials approved by the KFDA increased almost twofold from 2007 to 2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and investigator-initiated clinical trials (IITs) increased by almost 640%. Three hundred and fortyfour clinical trials were approved by the KFDA between 2012 and 2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were ongoing in all hospitals. Six high volume hospitals were each conducting more than 50 clinical trials, including both SITs and IITs. Fifty-six investigators (31%) complained of the difficulties in raising funds to conduct clinical trials. Conclusion The number of cancer clinical trials in Korea rapidly increased from 2007 to 2013, as has the number of multicenter clinical trials and IITs run by cooperative study groups. Limited funding for IIT is a serious problem, and more financial support is needed both from government agencies and public donations from non-profit organizations.

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Review Article

Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea: Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2012;44(2):85-96. Published online June 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.2.85

Abstract PDF PubReader ePub

Despite their rarity in incidence and prevalence, gastrointestinal stromal tumors (GISTs) have emerged as a distinct and noteworthy pathogenetic entity. The clinical management of GISTs has rapidly evolved due to the recent elucidation of their oncogenic signal transduction pathway and the introduction of molecular-targeted therapies. Successful management of GISTs requires a multidisciplinary approach firmly based on an accurate histopathologic diagnosis. In 2007, the Korean GIST study group published the first guideline for optimal diagnosis and treatment of GISTs in Korea. The second version of the guideline was published in 2010. Herein, we provide the results of relevant clinical studies for the purpose of further revision to the guideline. We expect this new guideline will enhance the accuracy of diagnosis, as performed by members of the Korean associate of physicians involved in GIST patient care, thus improving the efficacy of treatment.

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Toshihide Komatsubara, Toru Zuiki, Alan Kawarai Lefor, Norio Hirota, Jun Oki
International Journal of Surgery Open.2016; 5: 33. CrossRef
Rechallenge with imatinib in advanced gastrointestinal stromal tumors: clinical implications of the RIGHT trial
Changhoon Yoo, Yoon-Koo Kang
Clinical Investigation.2015; 5(7): 665. CrossRef
The Role of Surgical Resection Following Imatinib Treatment in Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses
Seong Joon Park, Min-Hee Ryu, Baek-Yeol Ryoo, Young Soo Park, Byeong Seok Sohn, Hwa Jung Kim, Chan Wook Kim, Ki-Hun Kim, Chang Sik Yu, Jeong Hwan Yook, Byung Sik Kim, Yoon-Koo Kang
Annals of Surgical Oncology.2014; 21(13): 4211. CrossRef
Minimally invasive surgery for submucosal (subepithelial) tumors of the stomach
Chang Min Lee
World Journal of Gastroenterology.2014; 20(36): 13035. CrossRef
Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib
Y-K Kang, C Yoo, B-Y Ryoo, J J Lee, E Tan, I Park, J H Park, Y J Choi, J Jo, J-S Ryu, M-H Ryu
British Journal of Cancer.2013; 109(9): 2309. CrossRef
Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial
Yoon-Koo Kang, Min-Hee Ryu, Changhoon Yoo, Baek-Yeol Ryoo, Hyun Jin Kim, Jong Jin Lee, Byung-Ho Nam, Nikhil Ramaiya, Jyothi Jagannathan, George D Demetri
The Lancet Oncology.2013; 14(12): 1175. CrossRef
Surgeon's role for gastric gastrointestinal stromal tumor in imatinib era
Ji Yeon Park, Young-Woo Kim
Korean Journal of Clinical Oncology.2013; 9(1): 5. CrossRef
Diagnosis and Treatment of Gastrointestinal Stromal Tumor
Yoon-Koo Kang, Dong Hoe Koo
Korean Journal of Medicine.2013; 85(4): 341. CrossRef
Surgical Treatment of Gastric Gastrointestinal Stromal Tumor
Seong-Ho Kong, Han-Kwang Yang
Journal of Gastric Cancer.2013; 13(1): 3. CrossRef
Clinical practice guidelines for patients with gastrointestinal stromal tumor in Taiwan
Chun-Nan Yeh, Tsann-Long Hwang, Ching-Shui Huang, Po-Huang Lee, Chew-Wun Wu, Ker Chen-Guo, Yi-Yin Jan, Miin-Fu Chen
World Journal of Surgical Oncology.2012;[Epub] CrossRef

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Original Article

Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients: Min Kyoung Kim, Sung-Bae Kim, Jin Hee Ahn, Soon Im Lee, Sei-Hyun Ahn, Byung Ho Son, Gyungyub Gong, Hak-Hee Kim, Jung-Shin Lee, Yoon-Koo Kang, Woo Kun Kim; Cancer Res Treat. 2006;38(4):206-213. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.206

Abstract PDF PubReader ePub

Purpose

To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2^nd-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX).

Materials and Methods

Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively.

Results

The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), com - bination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival.

Conclusions

The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2^nd-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

Citations

Citations to this article as recorded by

A Systematic Review of Vinorelbine for the Treatment of Breast Cancer
Ying-Chun Xu, Hong-Xia Wang, Lei Tang, Yue Ma, Feng-Chun Zhang
The Breast Journal.2013; 19(2): 180. CrossRef

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Case Report

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases: Ji Seon Oh, Jae-Lyun Lee, Mi-Jung Kim, Min-Hee Ryu, Heung Moon Chang, Tae Won Kim, Se Jin Jang, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Yoon-Koo Kang; Cancer Res Treat. 2006;38(3):178-183. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.178

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Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

Citations

Citations to this article as recorded by

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor
Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang
Cancer Research and Treatment.2016; 48(4): 1155. CrossRef
Correlation between Computed Tomography and Pathological Findings of Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate
Ki Choon Sim, Beom Jin Park, Na Yeon Han, Deuk Jae Sung, Min Ju Kim, Sung Bum Cho, Hyun Kwon Ha, Hyoung Rae Kim
Journal of the Korean Society of Radiology.2014; 71(5): 239. CrossRef
Diagnosis and Treatment of Gastrointestinal Stromal Tumor
Yoon-Koo Kang, Dong Hoe Koo
Korean Journal of Medicine.2013; 85(4): 341. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Cancer Research and Treatment.2012; 44(2): 85. CrossRef
Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor
Kyu Jong Yoon, Nam Kyu Kim, Kang Young Lee, Byung Soh Min, Hyuk Hur, Jeonghyun Kang, Sarah Lee
Journal of the Korean Society of Coloproctology.2011; 27(3): 147. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Hye Jin Kang, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Journal of Korean Medical Science.2010; 25(11): 1543. CrossRef
Clinical Practice Guideline for Adequate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang
Journal of the Korean Medical Association.2007; 50(9): 830. CrossRef

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Original Articles

Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy: Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Jung Shin Lee, Yoon-Koo Kang; Cancer Res Treat. 2005;37(4):201-207. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.201

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Purpose

Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.

Materials and Methods

A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m² IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.

Results

A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.

Conclusion

Docetaxel, 75 mg/m², is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Citations

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Comparison of adverse events following injection of original or generic docetaxel for the treatment of breast cancer
Nao Tagawa, Erika Sugiyama, Masataka Tajima, Yasutsuna Sasaki, Seigo Nakamura, Hiromi Okuyama, Hisanori Shimizu, Vilasinee Hirunpanich Sato, Tadanori Sasaki, Hitoshi Sato
Cancer Chemotherapy and Pharmacology.2017; 80(4): 841. CrossRef
Efficacy and Safety of Trastuzumab-based Therapy in Combination with Different Chemotherapeutic Regimens in Advanced Esophagogastric Cancer – a Single Cancer-center Experience
Georg-Martin Haag, Leonidas Apostolidis, Dirk Jaeger
Tumori Journal.2014; 100(3): 237. CrossRef
Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors
Nicolas Isambert, Gilles Freyer, Sylvie Zanetta, Benoît You, Pierre Fumoleau, Claire Falandry, Laure Favier, Sylvie Assadourian, Karen Soussan-Lazard, Samira Ziti-Ljajic, Veronique Trillet-Lenoir
Clinical Cancer Research.2012; 18(6): 1743. CrossRef
A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy
Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Minsun Kim, Young Joo Chun, Jung Shin Lee, Yoon-Koo Kang
Cancer Chemotherapy and Pharmacology.2008; 61(4): 631. CrossRef

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Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer: Jin-hong Park, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Yoon-Koo Kang, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Eun Kyung Choi; Cancer Res Treat. 2004;36(6):354-359. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.354

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Purpose

Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.

Materials and Methods

A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m² capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.

Results

Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.

Conclusion

Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.

Citations

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MRI for Rectal Cancer: Staging, mrCRM, EMVI, Lymph Node Staging and Post-Treatment Response
David D.B. Bates, Maria El Homsi, Kevin J. Chang, Neeraj Lalwani, Natally Horvat, Shannon P. Sheedy
Clinical Colorectal Cancer.2022; 21(1): 10. CrossRef
MRI of Rectal Cancer: An Overview and Update on Recent Advances
Kartik S. Jhaveri, Hooman Hosseini-Nik
American Journal of Roentgenology.2015; 205(1): W42. CrossRef
Current Controversies in Neoadjuvant Chemoradiation of Rectal Cancer
P. Terry Phang, Xiaodong Wang
Surgical Oncology Clinics of North America.2014; 23(1): 79. CrossRef
Tailored rectal cancer treatment – a time for implementing contemporary prognostic factors?
A. Wibe, W. L. Law, V. Fazio, C. P. Delaney
Colorectal Disease.2013; 15(11): 1333. CrossRef
Oncologic Outcome After Preoperative Chemoradiotherapy in Patients With Pathologic T0 (ypT0) Rectal Cancer
Tae Young Jang, Chang Sik Yu, Yong Sik Yoon, Seok-Byung Lim, Seung-Mo Hong, Tae Won Kim, Jong Hoon Kim, Jin Cheon Kim
Diseases of the Colon & Rectum.2012; 55(10): 1024. CrossRef
Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
J G Kim, S K Sohn, D H Kim, J H Baek, S B Jeon, Y S Chae, K B Lee, J S Park, J H Sohn, J C Kim, I K Park
British Journal of Cancer.2005; 93(10): 1117. CrossRef
Preoperative Concurrent Chemoradiotherapy with Oral Fluoropyrimidine in Locally Advanced Rectal Cancer: How Good Is Good Enough?
Hyun Cheol Chung
Cancer Research and Treatment.2004; 36(6): 341. CrossRef

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Clinical Value of Cyclooxygenase-2 Expression in Human Breast Carcinoma: Jin-Hee Ahn, Sung-Bae Kim, Sei-Hyun Ahn, Gyung-Yub Gong, Myung-Ju Ahn, Yoon-Koo Kang, Jung-Shin Lee, Woo Kun Kim; Cancer Res Treat. 2004;36(3):192-198. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.192

Abstract PDF PubReader ePub

Purpose

To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease-free survival of patients with operable breast cancer.

Materials and Methods

Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed-up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34.

Results

COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3±8.0 vs. 6.6±7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axil lary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527).

Conclusion

Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.

Citations

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The Role of Immunohistochemical Biomarkers as Prognostic Factors by the Use of a Tissue Microarray in Breast Cancer Patients Under 45-years-old
Eun Seog Kim, Doo Ho Choi, So Young Jin, Dong Wha Lee, Hee Sook Park, Min Hyuk Lee, Jong Ho Won, Yong Ho Kim, Kyu Taek Lee, Sung Yong Kim
The Journal of the Korean Society for Therapeutic Radiology and Oncology.2008; 26(1): 45. CrossRef
Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors
Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung
Cancer Research and Treatment.2005; 37(3): 165. CrossRef
Cyclooxygenase-2: A Potential Target in Human Cancer
Jong-Ho Won
Cancer Research and Treatment.2004; 36(3): 161. CrossRef

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