Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

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

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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

Citations to this article as recorded by

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
British Journal of Cancer.2024; 131(2): 299. CrossRef
Two Decades of Gastrointestinal Stromal Tumor Management With First-Line Treatment: A Case Report
Maria M Pereira, Elisabete Couto, Ali Shamseddine, Teresa Macedo
Cureus.2024;[Epub] CrossRef
Imatinib

Reactions Weekly.2023; 1960(1): 224. CrossRef
Clinical importance of tumor rupture in gastrointestinal stromal tumor
Toshirou Nishida, Naoto Gotouda, Tsuyoshi Takahashi, Hui Cao
Journal of Digestive Diseases.2023;[Epub] CrossRef
Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours
Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
Cancers.2023; 15(16): 4081. CrossRef
Impact of tumour rupture risk on the oncological rationale for the surgical treatment choice of gastrointestinal stromal tumours
Nadia Peparini
World Journal of Gastrointestinal Surgery.2023; 15(8): 1559. CrossRef
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
La radiologia medica.2022; 127(10): 1085. CrossRef
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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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

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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
International Journal of Clinical Oncology.2024; 29(6): 647. CrossRef
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
Frontiers in Oncology.2023;[Epub] CrossRef
Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours
Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
Cancers.2023; 15(16): 4081. CrossRef
Medical oncological treatment for patients with Gastrointestinal Stromal Tumor (GIST) – A systematic review
Charlotte Margareta Brinch, Ninna Aggerholm-Pedersen, Estrid Hogdall, Anders Krarup-Hansen
Critical Reviews in Oncology/Hematology.2022; 172: 103650. CrossRef
Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature
Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
Cancers.2022; 14(7): 1832. CrossRef
Efficacy and safety of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors
Ryugo Teranishi, Tsuyoshi Takahashi, Toshirou Nishida, Seiichi Hirota, Yukinori Kurokawa, Takuro Saito, Kazuyoshi Yamamoto, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Masaaki Motoori, Takeshi Omori, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki
International Journal of Clinical Oncology.2022; 27(7): 1164. CrossRef
The Role of Regorafenib in the Management of Advanced Gastrointestinal Stromal Tumors: A Systematic Review
Vahe Khachatryan, Asmaa Muazzam, Chandani Hamal, Lakshmi Sai Deepak Reddy Velugoti, Godfrey Tabowei, Greeshma N Gaddipati, Maria Mukhtar, Mohammed J Alzubaidee, Raga Sruthi Dwarampudi, Sheena Mathew, Sumahitha Bichenapally, Lubna Mohammed
Cureus.2022;[Epub] CrossRef
CT Image Examination Based on Virtual Reality Analysis in Clinical Diagnosis of Gastrointestinal Stromal Tumors
Zhiying Wang, Qiaoyan Qu, Ke Cai, Ting Xu, Zhihan Lv
Journal of Healthcare Engineering.2021; 2021: 1. CrossRef
The Use of Inhibitors of Tyrosine Kinase in Paediatric Haemato-Oncology—When and Why?
Agnieszka Kaczmarska, Patrycja Śliwa, Monika Lejman, Joanna Zawitkowska
International Journal of Molecular Sciences.2021; 22(21): 12089. CrossRef
Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors
Seketoulie Keretsu, Suparna Ghosh, Seung Joo Cho
International Journal of Molecular Sciences.2020; 21(21): 8232. CrossRef
Regorafenib treatment outcome for Taiwanese patients with metastatic gastrointestinal stromal tumors after failure of imatinib and sunitinib: A prospective, non‑randomized, single‑center study
Chia‑Hsiang Hu, Chun‑Nan Yeh, Jen‑Shi Chen, Chun‑Yi Tsai, Shang‑Yu Wang, Chi‑Tung Cheng, Ta‑Sen Yeh
Oncology Letters.2020; 20(3): 2131. CrossRef
Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers
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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
The Oncologist.2019; 24(11): e1212. CrossRef
Growing Role of Regorafenib in the Treatment of Patients with Sarcoma
Mark Agulnik, Steven Attia
Targeted Oncology.2018; 13(4): 417. CrossRef
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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22 Web of Science
17 Crossref

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

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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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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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Original Article

Clinicopathological and Immunohistochemical Features of Gastointestinal Stromal Tumors: Yu Na Kang, Hye Ra Jung, Ilseon Hwang; Cancer Res Treat. 2010;42(3):135-143. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.135

Abstract PDF PubReader ePub

Purpose

The purpose of this study was to evaluate the clinicopathological features and immunohistochemical features of gastrointestinal stromal tumor (GIST), and specifically the expressions of platelet derived growth factor receptor A (PDGFRA), protein kinase C theta (PKC theta), discovered on GIST-1 (DOG-1), p16 and p27.

Materials and Methods

Total 118 patients who underwent surgical resection for GIST at our institution between Jan 1997 and Dec 2007 were retrospectively studied. Immunohistochemical staining for c-kit, PDGFRA, PKC-theta, DOG-1, p16 and p27 was performed on a tissue microarray of the 118 GIST. The clinicopathologic parameters, the disease-free survival (DFS) and the overall survival rate were analyzed along with immunohistochemistry.

Results

The immunohistochemical stains for c-kit, CD34, PKC-theta, PDGFRA, DOG-1, p16 and p27 were positive in 89.8%, 72.0%, 56.8%, 94.9%, 90.7%, 69.5% and 44.1% of the tumor samples, respectively. The immunohistochemical expression of c-kit was strongly correlated with PKC-theta (p=0.000), DOG-1 (p=0.000) and CD34 (p=0.002). The DFS rate was significantly decreased for the patients with peritoneal GIST, high risk GIST, ≥10 cm-sized GIST, ≥10 mitoses/50 high power fields (HPFs) and p16 positivity (p=0.001, p=0.004, p=0.001, p=0.003 and p=0.028). GISTs ≥10 cm, epithelioid tumor cell type, and c-kit, and DOG-1 negativity were significantly associated with shorter period of overall survival (p=0.048, p=0.006, p=0.000 and p=0.000).

Conclusion

The expression of p16 and no expression of c-kit and DOG-1 in GISTs, as well as peritoneal tumor site, high risk group, large tumor size, epithelioid tumor cell type and numerous mitoses, may be potentially prognostic factors for predicting worse outcome for patients who suffer from GIST.

Citations

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Case Reports

Primary Epithelial Ovarian Carcinoma with Gastric Metastasis Mimic Gastrointestinal Stromal Tumor: Woo Dae Kang, Cheol Hong Kim, Moon Kyoung Cho, Jong Woon Kim, Ji Shin Lee, Seong Yeob Ryu, Yoon Ha Kim, Ho Sun Choi, Seok Mo Kim; Cancer Res Treat. 2008;40(2):93-96. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.93

Abstract PDF PubReader ePub

Epithelial ovarian carcinoma rarely metastasizes to the parenchyma of the stomach. A 55-years-old woman presented with epigastric pain and a feeling of fullness for one month. A subsequent contrast-enhanced CT scan demonstrated a 4.5×4 cm submucosal mass with focal ulceration in the gastric antrum, and this finding was suggestive of GIST. After gastric antrectomy, the final pathology showed metastatic gastric tumor from a primary ovarian serous carcinoma. Because epithelial ovarian carcinoma is usually spread along the peritoneal surface, stomach involvement is rare. Furthermore, transmural gastric metastasis is very rare in a patient with primary ovarian carcinoma. Until now, there has been no reported case of stomach involvement at presentation in a patient with primary ovarian carcinoma. We present here a case of ovarian carcinoma with gastric metastasis that mimicked GIST.

Citations

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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

Abstract PDF PubReader ePub

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

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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
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Cancer Research and Treatment.2012; 44(2): 85. CrossRef
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Kyu Jong Yoon, Nam Kyu Kim, Kang Young Lee, Byung Soh Min, Hyuk Hur, Jeonghyun Kang, Sarah Lee
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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
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