Cancer Research and Treatment

Original Article

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer: Seong-Eun Kim, Hyehyun Jeong, Sun Young Kim, Jeong Eun Kim, Yong Sang Hong, Deokhoon Kim, Jihun Kim, Ji Sung Lee, Tae-Won Kim; Received June 17, 2024 Accepted January 7, 2025 Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.569 [Accepted]

Abstract PDF: Purpose
To compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on EGFR amplification status.
Materials and Methods
Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least 5 copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp-).
Results
Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp- patients (median OS 76 vs. 37 months, p=0.15). Among 572 patients who received anti-EGFR antibody-based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp- patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp- patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).
Conclusion
This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

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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

Abstract PDF PubReader ePub: 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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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

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Original Articles

General

Interlaboratory Comparison Study (Ring Test) of Next-Generation Sequencing–Based NTRK Fusion Detection in South Korea: Seung Eun Lee, Mi-Sook Lee, Yoon Kyung Jeon, Hyo Sup Shim, Jun Kang, Jihun Kim, Yoon-La Choi; Cancer Res Treat. 2023;55(1):28-40. Published online February 10, 2022; DOI: https://doi.org/10.4143/crt.2021.1572

Abstract PDF Supplementary Material PubReader ePub

Purpose
Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)–based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea.
Materials and Methods
A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions.
Results
NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples.
Conclusion
This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

Citations

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International Journal of Thyroidology.2024; 17(1): 168. CrossRef
CANTRK
Tracy L. Stockley, Bryan Lo, Adrian Box, Andrea Gomez Corredor, John DeCoteau, Patrice Desmeules, Harriet Feilotter, Daria Grafodatskaya, Wenda Greer, Cynthia Hawkins, Weei Yuarn Huang, Iyare Izevbaye, Guylaine Lépine, Sebastiao N. Martins Filho, Andreas
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NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas
Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
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Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors
Moonsik Kim, Changseon Lee, Juyeon Hong, Juhee Kim, Ji Yun Jeong, Nora Jee-Young Park, Ji-Eun Kim, Ji Young Park
Cancer Research and Treatment.2023; 55(2): 429. CrossRef

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Gastrointestinal cancer

Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer: Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim; Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022; DOI: https://doi.org/10.4143/crt.2021.1133

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification.

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Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
Small.2023;[Epub] 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

Abstract PDF PubReader ePub

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.

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Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II
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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
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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
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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
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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
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Clinical Implication of Molecular Tumor Board
Soohyeon Lee
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Erratum

ERRATUM: Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location: Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2021;53(3):893-893. Published online June 8, 2021; DOI: https://doi.org/10.4143/crt.2018.392.E; Corrects: Cancer Res Treat 2019;51(3):1135

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Original Articles

Gastrointestinal cancer

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer: Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim; Cancer Res Treat. 2020;52(4):1135-1144. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2020.218

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

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Hassan Abushukair, Obada Ababneh, Ayah Al-Bzour, Ibrahim Halil Sahin, Anwaar Saeed
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Daniele Fanale, Lidia Rita Corsini, Raimondo Scalia, Chiara Brando, Alessandra Cucinella, Giorgio Madonia, Alessandra Dimino, Clarissa Filorizzo, Nadia Barraco, Marco Bono, Alessia Fiorino, Luigi Magrin, Roberta Sciacchitano, Alessandro Perez, Tancredi Di
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Japanese Journal of Clinical Oncology.2020;[Epub] CrossRef

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Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location: Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim; Cancer Res Treat. 2019;51(3):1135-1143. Published online November 29, 2018; DOI: https://doi.org/10.4143/crt.2018.392; Correction in: Cancer Res Treat 2021;53(3):893

Abstract PDF PubReader ePub

Purpose
Extranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers.
Materials and Methods
The medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed.
Results
ENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients.
Conclusion
ENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.

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Nelleke P M Brouwer, Shannon van Vliet, Joanna IntHout, Johannes H W De Wilt, Femke Simmer, Niek Hugen, Iris D Nagtegaal
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Assessment of prognostic indicators and KRAS mutations in rectal cancer using a fractional-order calculus MR diffusion model: whole tumor histogram analysis
Mi Zhou, Hongyun Huang, Deying Bao, Meining Chen, Fulin Lu
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Xuefei Zhang, Lanxin Hu, Junfeng Du, Chen Su, Xiang Xu
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MRI-based multiregional radiomics for predicting lymph nodes status and prognosis in patients with resectable rectal cancer
Hang Li, Xiao-li Chen, Huan Liu, Tao Lu, Zhen-lin Li
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Prognostic significance of extranodal extension of nodal metastasis in adenocarcinoma of the ampulla of Vater
Jihyun Chun, Yeon Wook Kim, Seo-rin Jeong, Hyung Jun Cho, Kyu-Pyo Kim, Dae Wook Hwang, Seung-Mo Hong
Human Pathology.2023; 137: 36. CrossRef
Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail
Zheng Li, Xiao-Jie Zhang, Chong-Yuan Sun, Ze-Feng Li, He Fei, Dong-Bing Zhao
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Effect of visceral fat area on the accuracy of preoperative CT-N staging of colorectal cancer
Meizhen Xie, Gangyi Liu, Yan Dong, Lan Yu, Rui Song, Wei Zhang, Ying Zhang, Shafei Huang, Jiaqian He, Yunping Xiao, Liling Long
European Journal of Radiology.2023; 168: 111131. CrossRef
Prognostic Value of the N1c in Stage III and IV Colorectal Cancer: A Propensity Score Matching Study Based on the Surveillance, Epidemiology, and End Results (SEER) Database
Chongshun Liu, Mengxiang Tian, Haiping Pei, Fengbo Tan, Yuqiang Li
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Tumor Deposits and Perineural Invasion had Comparable Impacts on the Survival of Patients With Non-metastatic Colorectal Adenocarcinoma: A Population-Based Propensity Score Matching and Competing Risk Analysis
Bin Luo, Xianzhe Chen, Guanfu Cai, Weixian Hu, Yong Li, Junjiang Wang
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The application of apparent diffusion coefficients derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer
Yi Yuan, Xiao-li Chen, Zhen-lin Li, Guang-wen Chen, Hao Liu, Yi-Sha Liu, Ming-hui Pang, Si-yun Liu, Hong Pu, Hang Li
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Beyond N staging in colorectal cancer: Current approaches and future perspectives
Gianluca Arrichiello, Mario Pirozzi, Bianca Arianna Facchini, Sergio Facchini, Fernando Paragliola, Valeria Nacca, Antonella Nicastro, Maria Anna Canciello, Adele Orlando, Marianna Caterino, Davide Ciardiello, Carminia Maria Della Corte, Morena Fasano, St
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Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy
Young Il Kim, Chan Wook Kim, Jong Hoon Kim, Jihun Kim, Jun-Soo Ro, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
Diseases of the Colon & Rectum.2022; 65(11): 1325. CrossRef
Prognostic Impact of Extranodal Extension in Rectal Cancer Patients Undergoing Radical Resection After Preoperative Chemoradiotherapy
Young Il Kim, Haeyon Cho, Chan Wook Kim, Yangsoon Park, Jihun Kim, Jun-Soo Ro, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
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Yichao Liang, Xinling Cai, Xu Zheng, Hongzhuan Yin
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Xia Yang, XiaoXi Ma, Wentao Yang, Ruohong Shui
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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Jin Won Kim, Hee Young Na, Sejoon Lee, Ji-Won Kim, Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jaihwan Kim, Jin-Hyeok Hwang, Kihwan Hwang, Chae-Yong Kim, Yong Beom Kim, Soomin Ahn, Kyu Sang Lee, Hyojin Kim, Hye Seung Lee, So Yeo
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Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients
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Yuki Okawa, Nobutaka Ebata, Nayoung K.D. Kim, Masashi Fujita, Kazuhiro Maejima, Shota Sasagawa, Toru Nakamura, Woong-Yang Park, Satoshi Hirano, Hidewaki Nakagawa
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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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Deguo Yu, Zhenfeng Wang, Tingbang He, Lijun Yang
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Xuewei Li, Jun Xu, Jun Xie, Wenhui Yang
Chinese Medical Journal.2022; 135(11): 1299. CrossRef
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Akira Saito, Natsuka Kimura, Yuji Kaneda, Hideyuki Ohzawa, Hideyo Miyato, Hironori Yamaguchi, Alan Kawarai Lefor, Ryozo Nagai, Naohiro Sata, Joji Kitayama, Kenichi Aizawa
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Mihaela Chivu-Economescu, Lilia Matei, Laura G Necula, Denisa L Dragu, Coralia Bleotu, Carmen C Diaconu
World Journal of Gastroenterology.2018; 24(18): 1942. CrossRef
Gastric cancer: Basic aspects
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Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer: Dalyong Kim, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Sung-Min Chun, Jihun Kim, Se Jin Jang, Tae Won Kim; Cancer Res Treat. 2017;49(1):37-43. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.069

Abstract PDF PubReader ePub

Purpose
Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods
Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results
The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion
Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.

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Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri
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Uludağ Üniversitesi Tıp Fakültesi Dergisi.2019; 45(2): 131. CrossRef
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Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Cancer Research and Treatment.2018; 50(4): 1351. CrossRef
Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer
Dalyong Kim, Sun Young Kim, Ji Sung Lee, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jihun Kim, Se Jin Jang, Young-Kwang Yoon, Tae Won Kim
BMC Gastroenterology.2017;[Epub] CrossRef

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