Cancer Research and Treatment

Original Articles

General

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations: Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim; Cancer Res Treat. 2022;54(1):30-39. Published online May 20, 2021; DOI: https://doi.org/10.4143/crt.2021.218

Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Citations

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Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
BMC Cancer.2024;[Epub] CrossRef
Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator
Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
The Oncologist.2023; 28(5): e242. CrossRef
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Scientific Reports.2023;[Epub] CrossRef
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
Cancer Research and Treatment.2022; 54(1): 1. CrossRef

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Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis: Jun Ho Ji, Young Saing Kim, Inkeun Park, Soon Il Lee, Rock Bum Kim, Joon Oh Park, Sung Yong Oh, In Gyu Hwang, Joung-Soon Jang, Haa-Na Song, Jung-Hun Kang; Cancer Res Treat. 2018;50(3):791-800. Published online August 23, 2017; DOI: https://doi.org/10.4143/crt.2017.044

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Purpose
Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients.
Materials and Methods
Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis.
Results
In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052).
Conclusion
Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

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National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma
Faisal Saud Dar, Zaigham Abbas, Irfan Ahmed, Muhammad Atique, Usman Iqbal Aujla, Muhammad Azeemuddin, Zeba Aziz, Abu Bakar Hafeez Bhatti, Tariq Ali Bangash, Amna Subhan Butt, Osama Tariq Butt, Abdul Wahab Dogar, Javed Iqbal Farooqi, Faisal Hanif, Jahanzai
World Journal of Gastroenterology.2024; 30(9): 1018. CrossRef
Treatment patterns and survival in older adults with unresected nonmetastatic biliary tract cancers
Ali Belkouz, Elise de Savornin Lohman, Jyothi R. Thumma, Bas Groot Koerkamp, Philip R. de Reuver, Martijn G.H. van Oijen, Cornelis J.A. Punt, Hari Nathan, Heinz-Josef Klümpen
Journal of Geriatric Oncology.2023; 14(3): 101447. CrossRef
Main causes of death in advanced biliary tract cancer
Kana Kimura‐Seto, Yasushi Kojima, Shiori Komori, Yuya Hisada, Yuki Otake, Yuka Yanai, Akiko Saito, Naoki Akazawa, Yasuo Tanaka, Chizu Yokoi, Mikio Yanase, Junichi Akiyama, Natsuyo Yamamoto, Kazuhiko Yamada
Cancer Medicine.2023; 12(9): 10889. CrossRef
A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
Targeted Oncology.2023; 18(6): 837. CrossRef
Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018
Van Nghiem, Sarah Wood, Rekha Ramachandran, Grant Williams, Darryl Outlaw, Ravikumar Paluri, Young-il Kim, Olumide Gbolahan
Cancer Control.2023;[Epub] CrossRef
Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map
Carolina Requeijo, Javier Bracchiglione, Nicolás Meza, Roberto Acosta-Dighero, Josefina Salazar, Marilina Santero, Adriana-G Meade, María Jesús Quintana, Gerardo Rodríguez-Grijalva, Anna Selva, Ivan Solà, Gerard Urrútia, Xavier Bonfill Cosp
Clinical Epidemiology.2023; Volume 15: 1069. CrossRef

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Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy: Inkeun Park, Seung Joon Choi, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Yong Ju Shin, Dong Bok Shin; Cancer Res Treat. 2016;48(4):1264-1273. Published online March 23, 2016; DOI: https://doi.org/10.4143/crt.2015.250

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Purpose
The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed.
Results
A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

Citations

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Academic Radiology.2023; 30(8): 1552. CrossRef
Pre-Therapeutic Sarcopenia among Cancer Patients: An Up-to-Date Meta-Analysis of Prevalence and Predictive Value during Cancer Treatment
Anne-Laure Couderc, Evelyne Liuu, Pascaline Boudou-Rouquette, Johanne Poisson, Maxime Frelaut, Coline Montégut, Soraya Mebarki, Romain Geiss, Zoé ap Thomas, Aurélien Noret, Monica Pierro, Capucine Baldini, Elena Paillaud, Frédéric Pamoukdjian
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Association of myosteatosis with treatment response and survival in patients with hepatocellular carcinoma undergoing chemoembolization: a retrospective cohort study
Kittipitch Bannangkoon, Keerati Hongsakul, Teeravut Tubtawee, Natee Ina, Ply Chichareon
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Li Yang, Xianghui Liao, Zhong Xie, Haiwen Li
Medicine.2023; 102(19): e33663. CrossRef
Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients?
Marco Cefalì, Isabel Scala, Giuliana Pavone, Daniel Helbling, Saskia Hussung, Ralph Fritsch, Cäcilia Reiner, Soleen Stocker, Dieter Koeberle, Marc Kissling, Vito Chianca, Filippo Del Grande, Sara De Dosso, Stefania Rizzo
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Johanna Mandl, Sebastian Baumer, Bernadette Holtzem, Rainer Theurer, Niels Zorger, Oliver Pech
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Is There a Role for Adjuvant Therapy in R0 Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis: Se-Il Go, Young Saing Kim, In Gyu Hwang, Eun Young Kim, Sung Yong Oh, Jun Ho Ji, Haa-Na Song, Se Hoon Park, Joon Oh Park, Jung Hun Kang; Cancer Res Treat. 2016;48(4):1274-1285. Published online February 12, 2016; DOI: https://doi.org/10.4143/crt.2015.502

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection.
Materials and Methods
Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors.
Results
In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups.
Conclusion
The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.

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Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection
Sundeep Singh Saluja, Phani Kumar Nekarakanti, Pramod Kumar Mishra, Anurita Srivastava, Kishore Singh
Journal of Gastrointestinal Surgery.2022; 26(2): 398. CrossRef
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Xiuqiong Chen, Fanqiao Meng, Hua Xiong, Yanmei Zou
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Angela Lamarca, Julien Edeline, Mairéad G McNamara, Richard A Hubner, Masato Nagino, John Bridgewater, John Primrose, Juan W Valle
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Jung Ho Im, Woo Jung Lee, Chang Moo Kang, Ho Kyoung Hwang, Jinsil Seong
HPB.2020; 22(8): 1168. CrossRef
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Bala Basak Oven Ustaalioglu, Ahmet Bilici, Mesut Seker, Umut Kefeli, Dincer Aydin, Serkan Celik, Tarik Demir, Burcak Erkol
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Abhay K. Kattepur, Shraddha Patkar, Mahesh Goel, Anant Ramaswamy, Vikas Ostwal
Journal of Gastrointestinal Surgery.2019; 23(11): 2232. CrossRef
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Carlos Manterola, Galo Duque, Luis Grande, Xabier de Aretxabala, Roque Conejeros, Tamara Otzen, Nayely García
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Byoung Hyuck Kim, Jeanny Kwon, Eui Kyu Chie, Kyubo Kim, Young Hoon Kim, Dong Wan Seo, Amol K. Narang, Joseph M. Herman
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Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer
T Ebata, S Hirano, M Konishi, K Uesaka, Y Tsuchiya, M Ohtsuka, Y Kaneoka, M Yamamoto, Y Ambo, Y Shimizu, F Ozawa, A Fukutomi, M Ando, Y Nimura, M Nagino, S Nakamori, T Ajiki, H Baba, R Yamaguchi, M Kawai, H Nagano, F Miura, T Arai, Y Nishiwaki, S Kawasaki
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Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer: Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin; Cancer Res Treat. 2016;48(1):80-87. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.307

Abstract PDF PubReader ePub

Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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Himani Aggarwal, Kerigo Ndirangu, Katherine B Winfree, Catherine Elizabeth Muehlenbein, Emily Zhu, Vanita Tongbram, Howard Thom
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Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis
Yi Zhao, Bo Cheng, Zisheng Chen, Jianfu Li, Hengrui Liang, Ying Chen, Feng Zhu, Caichen Li, Ke Xu, Shan Xiong, Weixiang Lu, Zhuxing Chen, Ran Zhong, Shen Zhao, Zhanhong Xie, Jun Liu, Wenhua Liang, Jianxing He
Critical Reviews in Oncology/Hematology.2021; 160: 103305. CrossRef
Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis
Zhihao Zhang, Xiyong Wang, Huaiqing Xiao, Dongqiang Wu, Dongliang Zhang, Qun Yu, Linna Yuan, Tao Huang
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Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
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Case Report

Oxaliplatin-Induced Immune-Mediated Thrombocytopenia: A Case Report: Hyun Sun Woo, Kyoung Hwa Lee, Phill Hoon Yoon, Su Ji Kim, Inkeun Park, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Dong Bok Shin, Sun Jin Sym; Cancer Res Treat. 2015;47(4):949-953. Published online October 28, 2014; DOI: https://doi.org/10.4143/crt.2014.052

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Oxaliplatin is a third-generation platinum derivative used for metastatic or advanced colorectal cancer treatment. Although myelosuppression is the most common cause of oxaliplatin-induced thrombocytopenia, rare cases of oxaliplatin-induced immunemediated thrombocytopenia are reported. We report a case of a 57-year-old woman with colon cancer who developed gum bleeding and petechiae after oxaliplatin infusion. Laboratory tests revealed grade 4 thrombocytopenia and grade 4 neutropenia. She recovered from the thrombocytopenia and accompanying neutropenia within 4 days with no recurrence following discontinuation of oxaliplatin. Physicians need to be aware of the risk of severe acute thrombocytopenia following oxaliplatin administration.

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Ju Li, Wanqing Wang, Kaipeng Jiang, Jiuwei Cui, Chang Wang, Tingting Liang, Yizhuo Wang, Shuhan Liu, Wenshuo Zhou
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Khin Pyai, David I LeRoy, Joseph Attallah, Hosam Hakim, Zyad Kafri
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Marek Kos, Piotr Tomaka, Paulina Mertowska, Sebastian Mertowski, Julia Wojnicka, Anna Błażewicz, Ewelina Grywalska, Krzysztof Bojarski
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Benjamin K. Gersten, Tracy S. Fitzgerald, Katharine A. Fernandez, Lisa L. Cunningham
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Haider Ghazanfar, Iqra Nawaz, Nisha Ali
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Vanesa Stojanovska, Monica Prakash, Rachel McQuade, Sarah Fraser, Vasso Apostolopoulos, Samy Sakkal, Kulmira Nurgali
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Original Article

Oxaliplatin, 5-fluorouracil and Leucovorin (FOLFOX-4) Combination Chemotherapy as a Salvage Treatment in Advanced Gastric Cancer: Young Saing Kim, Junshik Hong, Sun Jin Sym, Se Hoon Park, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Dong Bok Shin; Cancer Res Treat. 2010;42(1):24-29. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.24

Abstract PDF PubReader ePub

Purpose

This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC).

Materials and Methods

The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m² on day 1), leucovorin (200 mg/m² on days 1 and 2) and 5-fluorouracil (400 mg/m² as a bolus and 600 mg/m² as a 22-hour infusion on days 1 and 2) every 2 weeks.

Results

For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable.

Conclusion

Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.

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