Cancer Research and Treatment

Original Articles

Long-Term Clinical Efficacy of Radiotherapy for Patients with Stage I-II Gastric Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A Retrospective Multi-Institutional Study: Jae Uk Jeong, Hyo Chun Lee, Jin Ho Song, Keun Yong Eom, Jin Hee Kim, Yoo Kang Kwak, Woo Chul Kim, Sun Young Lee, Jin Hwa Choi, Kang Kyu Lee, Jong Hoon Lee; Received July 16, 2024 Accepted October 1, 2024 Published online October 4, 2024; DOI: https://doi.org/10.4143/crt.2024.651 [Accepted]

Abstract PDF: Purpose
To evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiation therapy (RT).
Materials and Methods
A total of 229 patients who received RT in ten tertiary hospitals between 2010 and 2019 were included in this multi-center analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS) were evaluated.
Results
After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 (99.6%) patients achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a prognostic factor for LRFS [hazard ratio (HR) of 3.72 and confidence interval (CI), 1.38-10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 (30.1%) patients. Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 (4.8%) patients after RT.
Conclusion
Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for radiotherapy to the stomach is not high.

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Lung and Thoracic cancer

Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non–Small Cell Lung Cancer: A Retrospective Analysis of a 10-Year Bi-institutional Experience: Myungsoo Kim, Jihye Cha, Hun Jung Kim, Woo Chul Kim, Jeongshim Lee; Cancer Res Treat. 2025;57(1):47-56. Published online July 3, 2024; DOI: https://doi.org/10.4143/crt.2024.223

Abstract PDF PubReader ePub: Purpose
Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥ 65 years who had 1-10 BM from non–small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC.
Results
During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8% and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9% and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT.
Conclusion
SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

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Gastrointestinal cancer

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814): Younghee Park, Tae Hyun Kim, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Jinsil Seong, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie; Cancer Res Treat. 2024;56(1):272-279. Published online July 31, 2023; DOI: https://doi.org/10.4143/crt.2023.616

Abstract PDF PubReader ePub: Purpose
Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
Materials and Methods
Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
Results
After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
Conclusion
Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

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Hematologic malignancy

Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis: Jinchul Kim, Jinhyun Cho, Sang Eun Yoon, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2023;55(3):1031-1047. Published online March 13, 2023; DOI: https://doi.org/10.4143/crt.2022.1658

Abstract PDF Supplementary Material PubReader ePub

Purpose
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
Materials and Methods
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
Results
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
Conclusion
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.

Citations

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Efficacy and safety of polatuzumab-vedotin plus bendamustine and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: A systematic review and meta-analysis
Hanzala Ahmed Farooqi, Muhammad Saffi Ullah, Ahmed Raza, Zain Sadiq, Wardah Ali Shaikh, Rahmah Muhammad, Muhammad Shoaib Hussain
Critical Reviews in Oncology/Hematology.2025; 207: 104611. CrossRef
Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol
Mohammadreza Eslami, Mahdi Mehrabi, Mehrdad Payandeh, Fakhredin Saba, Chen Li
PLOS ONE.2024; 19(8): e0308247. CrossRef
Real-world effectiveness of chemoimmunotherapy and novel therapies for patients with relapsed/refractory aggressive large B-cell lymphoma
Loretta J. Nastoupil, Clark R. Andersen, Amy Ayers, Yucai Wang, Thomas M. Habermann, Dai Chihara, Brad S. Kahl, Brian K. Link, Jean L. Koff, Jonathon B. Cohen, Peter Martin, Izidore S. Lossos, Michele Stanchina, Sara Haddadi, Carla Casulo, Sabarish Ayyapp
Clinical Lymphoma Myeloma and Leukemia.2024;[Epub] CrossRef
Clinical scoring systems, molecular subtypes and baseline [18F]FDG PET/CT image analysis for prognosis of diffuse large B-cell lymphoma
Zhuxu Sun, Tianshuo Yang, Chongyang Ding, Yuye Shi, Luyi Cheng, Qingshen Jia, Weijing Tao
Cancer Imaging.2024;[Epub] CrossRef
Targeting CD22 for B-cell hematologic malignancies
Jia Xu, Wenjing Luo, Chenggong Li, Heng Mei
Experimental Hematology & Oncology.2023;[Epub] CrossRef

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Breast cancer

Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer: Young-Gon Kim, In Hye Song, Seung Yeon Cho, Sungchul Kim, Milim Kim, Soomin Ahn, Hyunna Lee, Dong Hyun Yang, Namkug Kim, Sungwan Kim, Taewoo Kim, Daeyoung Kim, Jonghyeon Choi, Ki-Sun Lee, Minuk Ma, Minki Jo, So Yeon Park, Gyungyub Gong; Cancer Res Treat. 2023;55(2):513-522. Published online September 6, 2022; DOI: https://doi.org/10.4143/crt.2022.055

Abstract PDF Supplementary Material PubReader ePub

Purpose
Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients.
Materials and Methods
A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study.
Results
The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis.
Conclusion
In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Citations

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Comparing the diagnostic efficacy of optical coherence tomography and frozen section for margin assessment in breast-conserving surgery: a meta-analysis
Shishun Fan, Huirui Zhang, Zhenyu Meng, Ang Li, Yuqing Luo, Yueping Liu
Journal of Clinical Pathology.2024; 77(8): 517. CrossRef
Intraoperative Margin Assessment in Breast Conservation Surgery: A Necessity or a Luxury?
Srijan Shukla, Nisha Hariharan
Annals of Surgical Oncology.2023; 30(9): 5314. CrossRef

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Lung cancer

A Phase II Trial of Osimertinib as the First-Line Treatment of Non–Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1: Cheol-Kyu Park, Hyun-Ju Cho, Yoo-Duk Choi, In-Jae Oh, Young-Chul Kim; Cancer Res Treat. 2021;53(1):93-103. Published online September 21, 2020; DOI: https://doi.org/10.4143/crt.2020.459

Abstract PDF Supplementary Material PubReader ePub

Purpose
Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non–small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA.
Materials and Methods
Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety.
Results
Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis.
Conclusion
Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

Citations

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Non-small cell lung cancer: an update on emerging EGFR-targeted therapies
Valentina Favorito, Ilaria Ricciotti, Andrea De Giglio, Laura Fabbri, Renata Seminerio, Alessandro Di Federico, Eleonora Gariazzo, Silvia Costabile, Giulio Metro
Expert Opinion on Emerging Drugs.2024; 29(2): 139. CrossRef
Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review
Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, Yamil Liscano
Cancers.2024; 16(13): 2338. CrossRef
ctDNA SNORD3F Hypermethylation is a Prognostic Indicator in EGFR-TKI-Treated Advanced Non-Small Cell Lung Cancer
Bin Liu, Bingtian Zhao, Yan Yin, Yan Jiang, Xue Feng, Lei Wang, Liang Zhai, Guangxin Liu, Dongsheng Shi, Jianwen Qin
Cancer Management and Research.2024; Volume 16: 1405. CrossRef
Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?
Yi-Ze Li, Sheng-Nan Kong, Yun-Peng Liu, Yue Yang, Hong-Mei Zhang
Journal of Clinical Medicine.2023; 12(4): 1438. CrossRef
Effect of Osimertinib on CTCs and ctDNA in EGFR Mutant Non-Small Cell Lung Cancer Patients: The Prognostic Relevance of Liquid Biopsy
Galatea Kallergi, Emmanouil Kontopodis, Aliki Ntzifa, Núria Jordana-Ariza, Niki Karachaliou, Evangelia Pantazaka, Haris A. Charalambous, Amanda Psyrri, Emily Tsaroucha, Ioannis Boukovinas, Anna Koumarianou, Dora Hatzidaki, Evi Lianidou, Vassilis Georgouli
Cancers.2022; 14(6): 1574. CrossRef

8,231 View
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5 Web of Science
5 Crossref

Breast cancer

Challenge for Diagnostic Assessment of Deep Learning Algorithm for Metastases Classification in Sentinel Lymph Nodes on Frozen Tissue Section Digital Slides in Women with Breast Cancer: Young-Gon Kim, In Hye Song, Hyunna Lee, Sungchul Kim, Dong Hyun Yang, Namkug Kim, Dongho Shin, Yeonsoo Yoo, Kyowoon Lee, Dahye Kim, Hwejin Jung, Hyunbin Cho, Hyungyu Lee, Taeu Kim, Jong Hyun Choi, Changwon Seo, Seong il Han, Young Je Lee, Young Seo Lee, Hyung-Ryun Yoo, Yongju Lee, Jeong Hwan Park, Sohee Oh, Gyungyub Gong; Cancer Res Treat. 2020;52(4):1103-1111. Published online June 30, 2020; DOI: https://doi.org/10.4143/crt.2020.337

Abstract PDF PubReader ePub

Purpose
Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients.
Materials and Methods
A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve).
Results
The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy.
Conclusion
In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting

Citations

Citations to this article as recorded by

Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer
Young-Gon Kim, In Hye Song, Seung Yeon Cho, Sungchul Kim, Milim Kim, Soomin Ahn, Hyunna Lee, Dong Hyun Yang, Namkug Kim, Sungwan Kim, Taewoo Kim, Daeyoung Kim, Jonghyeon Choi, Ki-Sun Lee, Minuk Ma, Minki Jo, So Yeon Park, Gyungyub Gong
Cancer Research and Treatment.2023; 55(2): 513. CrossRef
Artificial intelligence and frozen section histopathology: A systematic review
Benjamin G. Gorman, Mark A. Lifson, Nahid Y. Vidal
Journal of Cutaneous Pathology.2023; 50(9): 852. CrossRef
Effectiveness of transfer learning for enhancing tumor classification with a convolutional neural network on frozen sections
Young-Gon Kim, Sungchul Kim, Cristina Eunbee Cho, In Hye Song, Hee Jin Lee, Soomin Ahn, So Yeon Park, Gyungyub Gong, Namkug Kim
Scientific Reports.2020;[Epub] CrossRef

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Lung cancer

Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea: Sun Min Lim, Sang-We Kim, Byoung Chul Cho, Jin Hyung Kang, Myung-Ju Ahn, Dong-Wan Kim, Young-Chul Kim, Jin Soo Lee, Jong-Seok Lee, Sung Yong Lee, Keon Uk Park, Ho Jung An, Eun Kyung Cho, Tae Won Jang, Bong-Seog Kim, Joo-Hang Kim, Sung Sook Lee, Im-II Na, Seung Soo Yoo, Ki Hyeong Lee; Cancer Res Treat. 2020;52(4):1112-1119. Published online May 15, 2020; DOI: https://doi.org/10.4143/crt.2020.245

Abstract PDF Supplementary Material PubReader ePub

Purpose
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Citations

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Advances in reprogramming of energy metabolism in tumor T cells
Liu Xuekai, Song Yan, Chu Jian, Song Yifei, Wu Xinyue, Zhang Wenyuan, Han Shuwen, Yang Xi
Frontiers in Immunology.2024;[Epub] CrossRef
Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study
Ning Wan, Yongbang Chen, Liqing Lu, Bing Wang, Liuliu He, Hongyi Liang, Fei Xie, Xiaoshun Jian, Bo Ji, Jianping Zhang, Hammoda Abu-Odah
European Journal of Cancer Care.2024; 2024: 1. CrossRef
Optimization of treatment strategies for elderly patients with advanced non-small cell lung cancer
Qiang Chen, Shuo Ying, Jianwen Qin, Li Zhang
Frontiers in Oncology.2024;[Epub] CrossRef
Real-World Data on Pembrolizumab for Pretreated Non-Small-Cell Lung Cancer: Clinical Outcome and Relevance of the Lung Immune Prognostic Index
Ana Ortega-Franco, Clare Hodgson, Haseem Raja, Mathew Carter, Colin Lindsay, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Yvonne Summers, Fiona Blackhall, Raffaele Califano
Targeted Oncology.2022; 17(4): 453. CrossRef
Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
Frontiers in Oncology.2022;[Epub] CrossRef
Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis
Donghui Wang, Cen Chen, Yanli Gu, Wanjun Lu, Ping Zhan, Hongbing Liu, Tangfeng Lv, Yong Song, Fang Zhang
Frontiers in Oncology.2021;[Epub] CrossRef
Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer
Min Jung Geum, Chungsoo Kim, Ji Eun Kang, Jae Hee Choi, Jae Song Kim, Eun Sun Son, Sun Min Lim, Sandy Jeong Rhie
Pharmaceuticals.2021; 14(5): 445. CrossRef
Nivolumab

Reactions Weekly.2021; 1855(1): 269. CrossRef
Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis
Zhe Zhao, Xinfeng Wang, Jinghan Qu, Wei Zuo, Yan Tang, Huijuan Zhu, Xiaoguang Chen
Frontiers in Oncology.2021;[Epub] CrossRef

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Report of the Korean Association of Lung Cancer Registry (KALC-R), 2014: Chang-Min Choi, Ho Cheol Kim, Chi Young Jung, Deog Gon Cho, Jae Hyun Jeon, Jeong Eun Lee, Jin Seok Ahn, Seung Joon Kim, Yeongdae Kim, Yoo-Duk Choi, Yang-Gun Suh, Jung-Eun Kim, Boram Lee, Young-Joo Won, Young-Chul Kim; Cancer Res Treat. 2019;51(4):1400-1410. Published online February 25, 2019; DOI: https://doi.org/10.4143/crt.2018.704

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study was to investigate epidemiology, clinical characteristics and sex differences of patients with lung cancer using nationwide registry in Korea.
Materials and Methods
The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry, and surveyed about 10% of lung cancer cases. For this first survey of cases diagnosed in 2014, cases were selected through a systematic sampling method.
Results
Total 2,621 lung cancer patients were surveyed, and the median patient age was 70 years. During the study period, adenocarcinoma was the most frequent histologic type, the proportion of female patients was 28.4%, and women had a better prognosis (median survival, not reached vs. 13 months; p<0.001) than did men for non-small cell lung cancer. The proportion of never-smokers was 36.4%, and never-smoking was more prevalent in women than in men (87.5 vs. 16.0%, p<0.001). Epidermal growth factor receptor (EGFR) mutations were found in 36.8% of stage IV adenocarcinoma patients, and higher in female compared to male patients (51.2 vs. 26.6%, p<0.001). In addition, patients with EGFR mutation showed better survival (median survival, 18 vs. 8 months; p<0.001) than patients without EGFR mutation in these patients.
Conclusion
This is the first survey to gather unbiased nationwide lung cancer statistics in Korea. More than one-third of lung cancer patients had no smoking history. Female had a high proportion of non-smoker, more adenocarcinoma with EGFR mutation and generally better prognosis than male.

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Prognostic value of electronic health records-based frailty measures for all-cause mortality in older patients with non-small cell lung cancer
Minh-Thao Tu, Thi-Ngoc Tran, Hoejun Kwon, Yoon-Jung Choi, Youngjoo Lee, Hyunsoon Cho
Journal of Geriatric Oncology.2025; 16(1): 102130. CrossRef
Study Protocol of the Korean EGFR Registry: A Multicenter Prospective and Retrospective Cohort Study in Nonsmall Cell Lung Cancer Patients With EGFR Mutation
Chang Dong Yeo, Dong Won Park, Seong Hoon Yoon, Eun Young Kim, Jeong Eun Lee, Shin Yup Lee, Chang‐Min Choi, In‐Jae Oh, Do Jin Kim, Jeong Seon Ryu, Jae Cheol Lee, Young‐Chul Kim, Tae Won Jang, Kye Young Lee, Seung Hun Jang, Seung Joon Kim
The Clinical Respiratory Journal.2025;[Epub] CrossRef
Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data
Kyu Yean Kim, Ho Cheol Kim, Tae Jung Kim, Hong Kwan Kim, Mi Hyung Moon, Kyongmin Sarah Beck, Yang Gun Suh, Chang Hoon Song, Jin Seok Ahn, Jeong Eun Lee, Jae Hyun Jeon, Chi Young Jung, Jeong Su Cho, Yoo Duk Choi, Seung Sik Hwang, Chang Min Choi, Seung Hun
Cancer Research and Treatment.2025; 57(1): 83. CrossRef
Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel
Fuyumi Nishihara-Kato, Hisao Imai, Takeshi Tsuda, Satoshi Wasamoto, Yoshiaki Nagai, Takayuki Kishikawa, Yosuke Miura, Akihiro Ono, Yutaka Yamada, Ken Masubuchi, Takashi Osaki, Junichi Nakagawa, Yukihiro Umeda, Hiroyuki Minemura, Yuki Kozu, Hirokazu Tanigu
Oncology.2024; 102(1): 30. CrossRef
Diagnostic challenge and survival analysis of pulmonary oligometastases and primary lung cancer in breast cancer patients
Siyao Mai, Haiqing Liu, Hong Zeng, Ziliang Cheng, Jingwen Huang, Guangzi Shi, Yong Li, Zhuo Wu
Thoracic Cancer.2024; 15(12): 1017. CrossRef
Real‐world treatment patterns and clinical outcomes in patients with stage III NSCLC in Korea: The KINDLE study
Jiyun Lee, Hee Kyung Ahn, Sang‐We Kim, Ji‐Youn Han, Sung Sook Lee, Hyung Soon Park, Hyun Woo Lee, Joo‐Hang Kim, Eunhan Cho, Reto Huggenberger, Byoung Chul Cho
Cancer Medicine.2024;[Epub] CrossRef
Sex differences in prognosis factors in patients with lung cancer: A nationwide retrospective cohort study in Korea
Youn Huh, Yeo Ju Sohn, Hae-Rim Kim, Hyejin Chun, Hwa Jung Kim, Ki Young Son, Dong Keon Yon
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A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA: LiquidLung-O-Cohort 2: Cheol-Kyu Park, Hyun-Ju Cho, Yoo-Duk Choi, In-Jae Oh, Young-Chul Kim; Cancer Res Treat. 2019;51(2):777-787. Published online September 7, 2018; DOI: https://doi.org/10.4143/crt.2018.387

Abstract PDF Supplementary Material PubReader ePub

Purpose
Administering the best treatment after failure of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy requires knowledge of resistance status. In this trial, treatment efficacy of osimertinib was assessed in patients with non-small cell lung carcinoma (NSCLC) harboring the T790M resistance mutation, detected from circulating tumor DNA (ctDNA) with unknown tumor mutation status.
Materials and Methods
To extract ctDNA from plasma, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas ver. 2 and PANA Mutyper were used for ctDNA genotyping. Patients with T790M, detected from ctDNA, were enrolled and they received a oncedaily administration of osimertinib 80 mg. The primary endpoint was objective response rate (ORR), and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety.
Results
Eighty patients with acquired resistance to prior EGFR-TKI therapies were screened. ctDNA of 21 patients showed T790M positivity, and 19 patients were enrolled. In the responseevaluable population (n=15), ORR was 66.7% (10/15). Median PFS was 8.3 months (95% confidence interval [CI], 7.9 to 8.7) and median DoR was 6.8 months (95% CI, 5.3 to 8.3) in the intent-to-treat population (n=19). No subject experienced drug-related adverse event of grades ≥ 3 or required dose reduction. The sensitivity of the ctDNA tests was 56.8% using both methods and 45.9% with either method from the estimated T790M-positive cases.
Conclusion
Osimertinib has favorable efficacy in patients with NSCLC harboring T790M, detected from ctDNA with unknown tumor mutation status, in whom disease had progressed during prior EGFR-TKI therapy.

Citations

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Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma: Hae Il Jung, Dongjun Jeong, Sanghee Ji, Tae Sung Ahn, Sang Ho Bae, Susie Chin, Jun Chul Chung, Hyung Chul Kim, Moon Soo Lee, Moo-Jun Baek; Cancer Res Treat. 2017;49(1):246-254. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.066

Abstract PDF PubReader ePub

Purpose
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.
Materials and Methods
Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.
Results
The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).
Conclusion
The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

Citations

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Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer: So-Young Seol, Chul Kim, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho; Cancer Res Treat. 2016;48(4):1196-1209. Published online February 26, 2016; DOI: https://doi.org/10.4143/crt.2015.189

Abstract PDF PubReader ePub

Purpose
Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer.
Materials and Methods
For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated.
Results
Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated.
Conclusion
High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.

Citations

Citations to this article as recorded by

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Biomeditsinskaya Khimiya.2017; 63(3): 181. CrossRef
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Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry.2017; 11(4): 309. CrossRef
Expression of ERO1L in gastric cancer and its association with patient prognosis
Bo Zhou, Gongping Wang, Shegan Gao, Ye Chen, Canhui Jin, Zengfang Wang, Yantong Yang, Zhikun Ma, Wei Zhang, Xiaoshan Feng
Experimental and Therapeutic Medicine.2017; 14(3): 2298. CrossRef
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Hongzhe Li, Xinjing Wang, Yuan Fang, Zhen Huo, Xiongxiong Lu, Xi Zhan, Xiaxin Deng, Chenghong Peng, Baiyong Shen
Oncotarget.2017; 8(32): 52571. CrossRef

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Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer: Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Hayoung Choi, Jinsun Chang, Hong-Joon Shin, Cheol-Kyu Park, Young-Chul Kim; Cancer Res Treat. 2015;47(4):661-669. Published online February 23, 2015; DOI: https://doi.org/10.4143/crt.2014.282

Abstract PDF PubReader ePub

Purpose
Direct sequencing (DS) is the standard method for detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC); however, low detection sensitivity is a problem. The aim of this study is to demonstrate higher detection rate of EGFR gene mutation with peptide nucleic acid (PNA) clamping compared with DS. Materials and Methods This is a single arm, prospective study for patients with stage IIIB/IV or relapsed NSCLC. Using tumor DNA from 138 patients, both DS and PNA clamping for EGFR gene in exon 18, 19, 20, and 21 were performed. Discrepant results between the two methods were verified using Cobas and a mutant enrichment based next generation sequencing (NGS). Patients with activating mutations were treated with EGFR tyrosine kinase inhibitor (EGFR-TKI, gefitinib, or erlotinib) as first line treatment.
Results
Of 138 paired test sets, 24 (17.4%) and 45 (32.6%) cases with activating mutations were detected by DS and PNA clamping, respectively. The difference of detection rate between the two methods was 15.2% (95% confidence interval, 8.7% to 17.8%; p < 0.001). Between the two methods, 25 cases showed discrepant results (n=23, PNA+/DS–; n=2, PNA–/DS+). Mutations were confirmed by Cobas or NGS in 22 of 23 PNA+/DS– cases. The response rates to EGFR-TKI were 72.2% in the PNA+/DS+ group and 85.0% in the PNA+/DS– group. Conclusion PNA clamping showed a significantly higher detection rate of EGFR gene mutation compared with DS. Higher sensitivity of PNA clamping was not compromised by the loss of predictive power of response to EGFR-TKI.

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Highly Sensitive Enrichment of Low-Frequency Variants by Hairpin Competition Amplification
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Bronchial brushing cytology is comparable to bronchial biopsy for epidermal growth factor receptor mutation test in non-small cell lung cancer
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Xiao-Dong Ren, Ding-Yuan Liu, Hai-Qin Guo, Liu Wang, Na Zhao, Ning Su, Kun Wei, Sai Ren, Xue-Mei Qu, Xiao-Tian Dai, Qing Huang
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Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9-mediated genome editing
Mi-Young Park, Min Hee Jung, Eun Young Eo, Seokjoong Kim, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young Jae Cho, Jin Haeng Chung, Cheol Hyeon Kim, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
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Application of Peptide Nucleic Acid-based Assays Toward Detection of Somatic Mosaicism
Christopher S Hong, Chunzhang Yang, Zhengping Zhuang
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Quantification of epidermal growth factor receptor (EGFR) mutation may be a predictor of EGFR‐tyrosine kinase inhibitor treatment response
Ha Young Park, Hyung Joo Oh, Ki‐Hyun Kim, Tae‐Ok Kim, Cheol‐Kyu Park, Hong‐Jun Shin, Jung‐Hwan Lim, Yong‐Soo Kwon, In‐Jae Oh, Yu‐Il Kim, Sung‐Chul Lim, Young‐Chul Kim, Yoo‐Duk Choi
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Association between GWAS-identified lung adenocarcinoma susceptibility loci andEGFRmutations in never-smoking Asian women, and comparison with findings from Western populations
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Human Molecular Genetics.2016; : ddw414. CrossRef

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Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis: Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2015;47(4):718-726. Published online February 2, 2015; DOI: https://doi.org/10.4143/crt.2014.064

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.
Materials and Methods
Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse- transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue- microarray (TMA) comprising 47 AGC patients.
Results
CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI- 1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).
Conclusion
DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

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A Survey of Stereotactic Body Radiotherapy in Korea: Sun Hyun Bae, Mi-Sook Kim, Won Il Jang, Chul-Seung Kay, Woochul Kim, Eun Seog Kim, Jin Ho Kim, Jin Hee Kim, Kwang Mo Yang, Kyu Chan Lee, A Ram Chang, Sunmi Jo; Cancer Res Treat. 2015;47(3):379-386. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2014.021

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the current status of stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology (KROG 13-13).
Materials and Methods
SBRT was defined as radiotherapy with delivery of a high dose of radiation to an extracranial lesion in ≤ 4 fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation oncology at 85 institutions in June 2013.
Results
All institutions (100%) responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47 institutions (55%) have not used SBRT. Regarding the treatment site, the lung (92%) and liver (76%) were the two most common sites. The most common schedules were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography (CT) was the most common method for planning CT (74%). During planning CT, the most common method of immobilization was the use of an alpha cradle/vacuum-lock (42%).
Conclusion
Based on this survey, conduct of further prospective studies will be needed in order to determine the appropriate prescribed doses and to standardize the practice of SBRT.

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Stereotactic radiotherapy for hepatocellular carcinoma: Expanding the multidisciplinary armamentarium
Mihir D Shanker, Howard Y Liu, Yoo Young Lee, Katherine A Stuart, Elizabeth E Powell, Alan Wigg, David I Pryor
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A national survey on technology and quality assurance for stereotactic body radiation therapy
Carmelo Marino, Cristina Garibaldi, Ivan Veronese, Claudia Carbonini, Serenella Russo, Michele Stasi, Pietro Mancosu
Physica Medica.2019; 65: 6. CrossRef
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Hyejung Cha, Hee Chul Park, Jeong Il Yu, Tae Hyun Kim, Taek-Keun Nam, Sang Min Yoon, Won Sup Yoon, Jun Won Kim, Mi Sook Kim, Hong Seok Jang, Youngmin Choi, Jin Hee Kim, Chul Seung Kay, Inkyung Jung, Jinsil Seong
Cancer Research and Treatment.2017; 49(1): 61. CrossRef
Application of stereotactic body radiation therapy to cancer liver metastasis
Si-Yuan Zhang, Guang-Ying Zhu, Gong Li, Yi-Bao Zhang, Jian-Hao Geng
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Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group
Sun Hyun Bae, Mi-Sook Kim, Won Il Jang, Chul-Seung Kay, Woochul Kim, Eun Seog Kim, Jin Ho Kim, Jin Hee Kim, Kwang Mo Yang, Kyu Chan Lee, A Ram Chang, Sunmi Jo
Japanese Journal of Clinical Oncology.2016; 46(4): 363. CrossRef
Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology
Francesco Dionisi, Alessia Guarneri, Veronica Dell’Acqua, Mariacristina Leonardi, Rita Niespolo, Gabriella Macchia, Tiziana Comito, Maurizio Amichetti, Pierfrancesco Franco, Savino Cilla, Luciana Caravatta, Filippo Alongi, Giovanna Mantello
La radiologia medica.2016; 121(9): 735. CrossRef

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Case Report

MET-Amplified Intramucosal Gastric Cancer Widely Metastatic after Complete Endoscopic Submucosal Dissection: Dakeun Lee, Young Chul Kim, Kee Myung Lee, Joon-Kee Yoon, Young-Bae Kim; Cancer Res Treat. 2015;47(1):120-125. Published online August 25, 2014; DOI: https://doi.org/10.4143/crt.2013.137

Abstract PDF PubReader ePub

Intramucosal gastric cancer (IGC) is associated with a very low risk of lymph node metastasis; thus it is the main candidate for minimally invasive surgical procedures, such as endoscopic submucosal dissection (ESD). Herein, we document an extraordinary case of IGC, which showed a very aggressive clinical course. A 66-year-old female underwent ESD for early gastric cancer. Histologically, the tumor consisted mainly of moderately differentiated adenocarcinoma measuring 1.6 cm in diameter, and the tumor was confined to the mucosa. Despite annual esophagogastroduodenoscopic follow-up, the tumor recurred, with wide metastasis to multiple lymph nodes and bones throughout the body after three years. Fluorescence in situ hybridization study demonstrated MET gene amplification as well as low grade polysomy 7 in both original and recurrent tumors. The clinical characteristics of metastatic IGCs and the implication of MET amplification are discussed.

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MicroRNA signatures associated with lymph node metastasis in intramucosal gastric cancer
Seokhwi Kim, Won Jung Bae, Ji Mi Ahn, Jin-Hyung Heo, Kyoung-Mee Kim, Kyeong Woon Choi, Chang Ohk Sung, Dakeun Lee
Modern Pathology.2021; 34(3): 672. CrossRef

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Original Article

A Nationwide Survey of Knowledge of and Compliance with Cancer Pain Management Guidelines by Korean Physicians: Do Yeun Kim, Jin Seok Ahn, Kyung Hee Lee, Young Chul Kim, Juneyoung Lee, Si-Young Kim; Cancer Res Treat. 2014;46(2):131-140. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.131

Abstract PDF PubReader ePub

Purpose

Although cancer pain is prevalent, under-treatment still remains a problem. Knowledge of and compliance with guidelines for management of cancer pain were analyzed for exploration of physician-related barriers to cancer pain management. In addition, physicians' knowledge and its correlation with cancer pain control were audited.

Materials and Methods

From July 8 to December 2, 2010, a nationwide survey of house staff enquired about their knowledge of cancer pain control guidelines, and the medical records of patients under their care were analyzed.

Results

In total, 180 physicians participated in the study. Their average score for knowledge was 14.6 (range, 7 to 19; maximum possible, 20). When the knowledge score was divided into low, medium, and high scores, patients receiving care from physicians with high levels of knowledge tended to have better cancer pain control (p<0.001). Of the total patients with severe pain, 19.5% were not prescribed strong opioids, and 40% were not prescribed any medication for breakthrough pain.

Conclusion

Physicians' knowledge of guidelines for control of cancer pain showed an association with improvement of pain management. Overall adherence to the guidelines was lacking. Continuous interventions such as education and audits regarding cancer pain control guidelines for physician are needed.

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Paolo Bossi, Tatiana Pietrzyńska, César Margarit Ferri, Irene Mansilla, Valeria Tellone, Sara Fioravanti, Giorgio Di Loreto, Alessandro Comandini
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A Survey of Knowledge and Barriers of Healthcare Professionals toward Opioid Analgesics in Cancer Pain Management
Nehad M. Ayoub, Malak Jibreel, Khawla Nuseir, Ghaith M. Al-Taani, Manish Gupta
International Journal of Clinical Practice.2022; 2022: 1. CrossRef
Rapid-Onset Opioids for Management of Breakthrough Cancer Pain: Considerations for Daily Practice
Paolo Bossi, Yolanda Escobar, Federico Pea
Frontiers in Pain Research.2022;[Epub] CrossRef
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Marcos Edgar Fernández Cuadros, María Jesús Albaladejo Florin, Sandra Alava Rabasa, Daiana Peña Lora, Olga Susana Pérez Moro
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Michael A. Smith, Kyle C. Quirk, D'Anna C. Saul, Phillip E. Rodgers, Maria J. Silveira
Journal of Pain and Symptom Management.2020; 59(1): 116. CrossRef
Physician’s Attitude toward Treating Breakthrough Cancer Pain in Korea
Min Seok Seo, Jae Yong Shim, Youn Seon Choi, Do Yeun Kim, In Gyu Hwang, Sun Kyung Baek, Jin Young Shin, Juneyoung Lee, Chang Geol Lee
The Korean Journal of Hospice and Palliative Care.2017; 20(1): 18. CrossRef
Commentary on “A Nationwide Survey of Knowledge of and Compliance with Cancer Pain Management Guidelines by Korean Physicians”
Kieran Walsh
Cancer Research and Treatment.2014; 46(4): 425. CrossRef

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Review Article

Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor: Jae Cheol Lee, Seung Hun Jang, Kye Young Lee, Young-Chul Kim; Cancer Res Treat. 2013;45(2):79-85. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.79

Abstract PDF PubReader ePub

Since the first description of non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity, studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of treatment. The median response duration of TKIs as a first-line treatment for EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL), transformation to mesenchymal cell or small cell features, and tumor heterogeneity. Until development of a successful treatment strategy to overcome such acquired resistance, few options are currently available. Here we provide a summary of the therapeutic options after failure of first line EGFR-TKI treatment for NSCLC.

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Andrés F. Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E. Pino
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Integrating Models to Quantify Environment-Mediated Drug Resistance
Noemi Picco, Erik Sahai, Philip K. Maini, Alexander R.A. Anderson
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Histological transformation from non‐small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor‐tyrosine kinase inhibitor
Woo‐Jin Kim, Sunmin Kim, Hayoung Choi, Jinsun Chang, Hong‐Joon Shin, Cheol‐Kyu Park, In‐Jae Oh, Kyu‐Sik Kim, Young‐Chul Kim, Yoo‐Duk Choi
Thoracic Cancer.2015; 6(6): 800. CrossRef
Clinically beneficial continued treatment with gefitinib after asymptomatic progression of lung adenocarcinoma
Hayoung Choi, Jinsun Chang, Hong‐Joon Shin, Cheol‐Kyu Park, In‐Jae Oh, Kyu‐Sik Kim, Young‐Chul Kim
Thoracic Cancer.2015; 6(2): 224. CrossRef
The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study
Kwai Han Yoo, Seung Tae Kim, Ki Sun Jung, Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Hae Soo Kim, Hee Jin Kwon, In Young Kim, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Hanyang Medical Reviews.2015; 35(3): 180. CrossRef
Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer
Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Hayoung Choi, Jinsun Chang, Hong-Joon Shin, Cheol-Kyu Park, Young-Chul Kim
Cancer Research and Treatment.2015; 47(4): 661. CrossRef
Long Term Therapeutic Plan for Patients with Non-Small Cell Lung Cancer HarboringEGFRMutation
Seung Hun Jang
Tuberculosis and Respiratory Diseases.2014; 76(1): 8. CrossRef
Multiplexed immunohistochemistry, imaging, and quantitation: A review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis
Edward C. Stack, Chichung Wang, Kristin A. Roman, Clifford C. Hoyt
Methods.2014; 70(1): 46. CrossRef
Comparison of pemetrexed and docetaxel as salvage chemotherapy for the treatment for nonsmall-cell lung cancer after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors
Lei Dong, Zhao-feng Han, Zi-hui Feng, Zhi-yang Jia
Journal of International Medical Research.2014; 42(1): 191. CrossRef
Heterogeneity of epidermal growth factor receptor mutations in lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangements: A case report
QIONG SUN, JIAN-YU WU, SHUN-CHANG JIAO
Oncology Letters.2014; 8(5): 2093. CrossRef
Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib
Hyojeong Kim, Tak Yun, Young Joo Lee, Ji-Youn Han, Heung Tae Kim, Geon Kook Lee
Journal of Korean Medical Science.2013; 28(11): 1595. CrossRef

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Original Articles

Analysis of Cellular Changes Resulting from Forced Expression of Dickkopf-1 in Hepatocellular Carcinoma Cells: Mi Hee Kwack, Sun Young Hwang, In Seok Jang, Sang Uk Im, Jin Oh Kim, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung; Cancer Res Treat. 2007;39(1):30-36. Published online March 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.1.30

Abstract PDF PubReader ePub

Purpose

Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied.

Materials and Methods

The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed.

Results

RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK-1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line.

Conclusion

Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells.

Citations

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Non-invasive biomarkers for the detection of hepatocellular carcinoma
Daniela Campion, Alessandra Tucci, Paola Ponzo, Gian Paolo Caviglia
Minerva Biotecnologica.2019;[Epub] CrossRef
DKK1 promotes hepatocellular carcinoma inflammation, migration and invasion: Implication of TGF-β1
Maha Fezza, Mayssam Moussa, Rita Aoun, Rita Haber, George Hilal, Masaru Katoh
PLOS ONE.2019; 14(9): e0223252. CrossRef
MicroRNA-320a downregulation mediates human liver cancer cell proliferation through the Wnt/β-catenin signaling pathway
Caicheng Lu, Zengwei Liao, Minxian Cai, Guirong Zhang
Oncology Letters.2017; 13(2): 573. CrossRef
Musashi1 regulates survival of hepatoma cell lines by activation of Wnt signalling pathway
Kunlun Chen, Qing Gao, Wei Zhang, Zhongwei Liu, Jiangyi Cai, Ying Liu, Jinkai Xu, Jie Li, Yi Yang, Xin Xu
Liver International.2015; 35(3): 986. CrossRef
Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma
Seung Up Kim, Jeon Han Park, Hyon-Suk Kim, Jae Myun Lee, Hyun Gyu Lee, Hyemi Kim, Sung Hoon Choi, Shinhwa Baek, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Jong Doo Lee, Kwang-Hyub Han
Yonsei Medical Journal.2015; 56(5): 1296. CrossRef
Serum level of DKK-1 and its prognostic potential in non–small cell lung cancer
Liang-liang Dong, Lu-yun Qu, Li-yan Chu, Xiao-hui Zhang, Ying-hui Liu
Diagnostic Pathology.2014;[Epub] CrossRef

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Pattern of Apoptosis by NS398, a Selective COX-2 Inhibitor, in Hepatocellular Carcinoma Cell Lines: Mi Kyung Park, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung; Cancer Res Treat. 2005;37(5):313-317. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.313

Abstract PDF PubReader ePub

Purpose

NS398, a selective COX-2 inhibitor, is known to inhibit the growth of COX-2 expressing hepatocellular carcinoma cells. The present study investigated whether the cytotoxic effect of NS398 was COX-2 dependent and whether caspases were involved in NS398-induced apoptosis in hepatocellular carcinoma cells.

Materials and Methods

The expressions of COX-2 in SNU 423 and SNU 449 hepatocellular carcinoma cell lines were examined using RT-PCR and Western blot. The cytotoxic effect of NS398 was measured using MTT in the presence or absence of caspase inhibitors. The distribution of the cell cycle and extent of apoptosis were analyzed using flow cytometry and a Cell Death Elisa kit, respectively.

Results

The expression of COX-2 was observed in SNU423 cells, but not in SNU 449 cells. NS398 treatment resulted in both dose-and time-dependent growth inhibitions, with increases in apoptotic cells in both cell lines. Treatment with the pan-caspase inhibitor, z-VAD- fmk, or the caspase-3 inhibitor, Ac-DMQD-CHO, showed no attenuation of the cytotoxic effect of NS398 in either cell line.

Conclusion

This study demonstrated that the cytotoxic effect of NS398 was independent of COX-2 expression. Caspases were also shown not to be involved in NS398-induced apoptosis in either SNU 423 or SNU 449 Korean HCC cell lines. Our data suggests the feasibility of preventing hepatocellular carcinoma with the use of COX-2 inhibitors needs to be carefully evaluated.

Citations

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First study on the immunohistochemical expression of cyclooxygenase-2 and clinicopathological association in canine hepatoid gland neoplasms
Pinkarn Chantawong, Thanongsak Mamom, Sahatchai Tangtrongsup, Setthakit Chitsanoor, Hassadin Boonsriroj
Veterinary World.2022; : 2432. CrossRef
Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line
Bahram Daraei, Gholamreza Karimi, Pouran Makhdoumi, Afshin Zarghi
Journal of Pharmacopuncture.2017; 20(3): 207. CrossRef
RETRACTED ARTICLE: Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells
Xinyan Wang, Yu Liang, Jun Wang, Min Wang
Tumor Biology.2013; 34(3): 1517. CrossRef
Gene Expression Profile of Coronary Artery Cells Treated With Nonsteroidal Anti-inflammatory Drugs Reveals Off-target Effects
Sanjeewani T. Palayoor, Molykutty J-Aryankalayil, Adeola Y. Makinde, David Cerna, Michael T. Falduto, Scott R. Magnuson, C. Norman Coleman
Journal of Cardiovascular Pharmacology.2012; 59(6): 487. CrossRef

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Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer: Yoon Mi Shin, Hae Suk Han, Seong Woo Lim, Byung Chul Kim, Kyung Suck Cheoi, Young Ook Eum, Seung Taek Kim, Ki Hyeong Lee; Cancer Res Treat. 2005;37(5):284-289. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.284

Abstract PDF PubReader ePub

Purpose

The aim of this study was to evaluate the efficacy and tolerability of the oxaliplatin, 5-fluorouracil (5-FU) and low dose leucovorin (LV) combination in patients with advanced colorectal cancer.

Materials and Methods

Patients with unresectable or recurrent colorectal carcinomas were prospectively accrued. Up to one prior chemotherapy regimen was allowed. Patients received oxaliplatin, 85 mg/m², administered as a 2-hour infusion on day 1, followed by LV, 20 mg/m², as a bolus and 5-FU, 1,500 mg/m², via continuous infusion for 24 hours on days 1 and 2. Treatment was repeated every 2 weeks until disease progression or adverse effects prohibited further therapy.

Results

Between August 1999 and May 2004, 31 patients were enrolled in this study. Of the patients enrolled, 24 and 31 were evaluable for tumor response and survival analysis, respectively. The patients' characteristics included a median age of 59, with 6 (19%) having had prior chemotherapy. No patient achieved a complete response, but nine (38%) attained a partial response. Seven (29%) patients maintained a stable disease and 8 (33%) experienced increasing disease. The median duration of the response was 6 months. After a median follow-up of 9.6 months, the median time to progression was 3.8 months, with a median survival of 10.7 months. The hematological toxicities were mild to moderate, with no treatment-related mortality or infection. The major non-hematological toxicity was gastrointestinal toxicity.

Conclusion

The combination chemotherapy of oxaliplatin, low dose LV and continuous infusion of 5-FU is safe and has a cost-benefit, but is a moderately effective regimen in advanced colorectal cancer. A randomized trial comparing low and high dosages of leucovorin in the FOLFOX regimen is warranted.

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Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells
JaeJin An, Eun-Mi Ha
Journal of Microbiology.2022; 60(7): 735. CrossRef
Prognostic and Predictive Role of Excision Repair Cross-complementation Group 1 and Thymidylate Synthase in Colorectal Carcinoma Patients Received FOLFOX Chemotherapy: An Immunohistochemical Study
Dalia M. Badary, Mai M. Elkabsh, Hussam H. Mady, Adel Gabr, Sana S. Kroosh
Applied Immunohistochemistry & Molecular Morphology.2020; 28(10): 741. CrossRef
Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer
Joon Ho Moon, Jong Gwang Kim, Sang Kyun Sohn, Jin Ho Baek, Yoon Young Cho, Yee Soo Chae, Byung Min Ahn, Shi Nae Kim, Soo Jung Lee, In Taek Lee, Gyu Seog Choi, Soo Han Jun
Journal of Korean Medical Science.2007; 22(3): 400. CrossRef

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Results of Curative Radiation Therapy with or without Chemotherapy for Stage III Unresectable Non-Small Cell Lung Cancer: Sung-Ja Ahn, Young-Chul Kim, Kyu-Sik Kim, Kyung-Ok Park, Woong-Ki Chung, Taek-Keun Nam, Byung-Sik Nah, Ju-Young Song, Mi-Sun Yoon; Cancer Res Treat. 2005;37(5):268-272. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.268

Abstract PDF PubReader ePub

Purpose

We retrospectively analyzed the patients who received curative radiotherapy for unresectable stage III NSCLC to investigate the impact of chemotherapy.

Materials and Methods

From 1998 to 2001, the records of 224 patients who completed curative radiotherapy for NSCLC were reviewed. There were 210 males and 14 females, and their median age was 64 years (range 38~83). 54 patients had stage IIIA disease and 170 patients had stage IIIB disease. Conventional radiotherapy was given and the radiation dose ranged from 50~70 Gy with a median of 60 Gy, and chemotherapy was combined for 116 patients (52%).

Results

The median survival, the 2-year, and 5-year actuarial survival rates of all 224 patients were 15 months, 30%, and 7%, respectively. The median survival of the patients with stage IIIA and IIIB disease were 21 months and 13 months, respectively (p=0.14). The median survival of patients who received chemoradiation was 18 months compared to 14 months for the patients who received RT alone (p=0.02). Among the chemoradiation group of patients, the median survival time of the patients who received 1 to 3 cycles of chemotherapy was 16 months and that for the patients who received more than 3 cycles was 22 months (p=0.07). We evaluated the effects of the timing of chemoradiation in 57 patients who received more than 3 cycles of chemotherapy. The median survival of the patients with the concurrent sequence was 25 months and that for the patients with the sequential chemotherapy was 19 months (p=0.81).

Conclusions

For advanced stage III non-small cell lung cancer patients who completed the curative radiotherapy, the addition of chemotherapy improved the survival compared to the patients who received radiotherapy alone.

Citations

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Treatment for Non-Small-Cell Lung Cancer and Circulating Tumor Cells
Joel Mason, Benjamin Blyth, Michael P MacManus, Olga A Martin
Lung Cancer Management.2017; 6(4): 129. CrossRef
Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer
Dong-Soo Lee, Yeon-Sil Kim, Jin-Hyoung Kang, Sang-Nam Lee, Young-Kyoun Kim, Myung-Im Ahn, Dae-Hee Han, Ie-Ryung Yoo, Young-Pil Wang, Jae-Gil Park, Sei-Chul Yoon, Hong-Seok Jang, Byung-Oak Choi
Cancer Research and Treatment.2011; 43(1): 32. CrossRef

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The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer: Yong Tai Kim, Chul Kim, Joo Hyuk Sohn, So Young Park, Soo Young Park, Nae Choon Yu, Young Sam Kim, Se Kyu Kim, Joon Chang, Kil Dong Kim, Kyung Young Chung, Joo Hang Kim; Cancer Res Treat. 2003;35(6):502-506. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.502

Abstract PDF

PURPOSE
The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty-five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events.
CONCLUSION
The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens.

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Serum Carcinoembryonic Antigen as an Index of the Therapeutic Effect of EGFR-TKIs in Patients with Advanced Non-Small Cell Lung Cancer
Jin Hee Park, Sung Bin Kim, Sung Jin Nam, Su Hyeon Jeong, Chul Ho Oak, Tae Won Jang, Maan Hong Jung
Journal of Lung Cancer.2010; 9(2): 97. CrossRef
A review of the benefit–risk profile of gefitinib in Asian patients with advanced non‐small‐cell lung cancer
Keunchil Park, Koichi Goto
Current Medical Research and Opinion.2006; 22(3): 561. CrossRef

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Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Lung Cancer Susceptibility of Korean Population: Jun Hwa Hwang, Kyu Sik Kim, Yu Il Kim, Eun Joung Kim, Kyung Hwa Park, Gye Jung Cho, Jin Young Ju, Sung Chul Lim, Young Chul Kim, Kyung Ok Park, Jong Tae Park, Sung Ja Ahn; Cancer Res Treat. 2003;35(6):483-488. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.483

Abstract PDF: PURPOSE
Although 80~90% of patients with lung cancer are smokers, only 11% of smokers develop lung cancer. Genetic susceptibility according to the polymorphism of the epoxide hydrolase (mEPHX) gene and homozygous deletion of GSTM1 (M1 subunit of Glutathione S transferase) was studied in this case control study. MATERIALS AND METHODS: Genomic DNA from 76 subjects with lung cancer (40 squamous cell carcinoma, 13 adenocarcinoma, 10 subtype undetermined non-small cell lung cancer, and 13 small cell lung carcinoma) and 62 age- matched controls were extracted from peripheral white blood cells. PCR and RFLP (restriction fragments length polymorphism) with restriction enzyme (RsaI) and automatic sequencing were used for mEPHX genotyping (T-->C, Tyr113His) in exon 3 and (A-->G, His139Arg) in exon 4. Looking for homozygous deletions of GSTM1, multiplex PCR with primers for the GSTM1 gene and coagulation factor V gene (as positive control) were performed. RESULTS: The age distribution between the cancer and control groups were similar (63.6 7.2 vs. 61.1 7.9 years). The lung cancer group, however, had more smokers (73.3%, 44/60) than the control group (21/54, 38.9%, p<0.001). The rate of homozygous deletion of the GSTM1 gene was significantly higher in the lung cancer group (65.8%, 50/76) than in the control group (46.8%, 29/62, p<0.05), causing the relative risk of GSTM1 deletion for lung cancer as 2.19 (95% CI: 1.10~4.35, p=0.02). Among 118 subjects whose mEPHX gene polymorphisms were studied, 62 (52.5%) subjects showed genotypes with slow enzyme activity while 45 (38.1%) showed normal enzyme activity and 11 (9.3%) showed fast enzyme activity. There was no significant difference in the distribution of mEPHX gene polymorphisms between the two groups. CONCLUSION: The homozygous deletion of the GSTM1 gene was associated with high lung cancer susceptibility, whereas the mEPHX genotype showed no significant connection with risk of lung cancer in a sample Korean population.

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Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer: Yoon Jae Kim, Joo Hyuk Sohn, Chul Kim, Yong Tai Kim, Hai Jin Kim, Joong Bae Ahn, Se Kyu Kim, Joon Chang, Nae Choon Yoo, Joo Hang Kim, Jae Yong Cho; Cancer Res Treat. 2003;35(4):294-298. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.294

Abstract PDF: PURPOSE
With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies.
MATERIALS AND METHODS
Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks.
RESULTS
Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed.
CONCLUSION
The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.

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Infusional 5-Fluorouracil, Leucovorin and Docetaxel in Advanced Gastric Cancer: Yong Tai Kim, Joo Hyuk Sohn, So Hun Kim, Sun Young Rha, Chul Kim, Jae Kyung Roh, Byung Soo Kim, Woo Ick Jang, Hyun Cheol Chung; Cancer Res Treat. 2003;35(2):123-129. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.123

Abstract PDF

PURPOSE
This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. RESULTS: The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. CONCLUSION: This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients.

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The Efficacy of Docetaxel and Cisplatin Combination Chemotherapy for the Treatment of Advanced Gastric Cancer after Failing to 5-Fluorouracil Based Chemotherapy
Sang-Joon Shin, Min-Kyoung Kim, Kyung-Hee Lee, Myung-Soo Hyun, Sang Woon Kim, Sun Kyo Song, Sung-Hwa Bae, Hun-Mo Ryoo
Cancer Research and Treatment.2004; 36(6): 367. CrossRef

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High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Persistent/Relapsed Ovarian Cancer: So Eun Kim, Jong Ho Won, Hyun Soo Kim, Joon Sung Park, Chan Kyu Kim, Kyu Taeg Lee, Sung Kyu Park, Seung Ho Baick, Dae Sik Hong, Hee Sook Park, Hugh Chul Kim; Cancer Res Treat. 2002;34(6):439-443. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.439

Abstract PDF

PURPOSE
High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report.
MATERIALS AND METHODS
We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals.
RESULTS
Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths.
CONCLUSION
HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders.

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Analysis of chromosomal changes in serous ovarian carcinoma using high‐resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant disease
Sang Wun Kim, Jae Wook Kim, Young Tae Kim, Jae Hoon Kim, Sunghoon Kim, Bo Sung Yoon, Eun Ji Nam, Hye Yeon Kim
Genes, Chromosomes and Cancer.2007; 46(1): 1. CrossRef

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Effect of Vinorelbine, Ifosfamide and Cisplatin Combination Chemotherapy in Stage III-IV Non-Small-Cell Lung Cancer: Young Chul Kim, So Young Lee, Hong Joo Cho, Jung A Kim, So Hyang Song, Chi Hong Kim, Hoon Kyo Kim, Meyung Im Ahn, Jin Young You, Sung Whan Kim, Deng Gon Cho, Kyu Do Cho, Jin Hyung Kang; Cancer Res Treat. 2002;34(5):352-356. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.352

Abstract PDF: PURPOSE
To evaluate the response rates, toxicitiesy, and survival rates, to vinorelbine (Navelbine(R)), cisplatin and ifosfamide combination chemotherapy, of the patients with inoperable NSCLC (stage III and IV), who received vinorelbine (Navelbine(R)), cisplatin, ifosfamide combinationthe mentioned chemotherapy every 4 weeks.
MATERIALS AND METHODS
This study included 26 patients with inoperable NSCLC (stage III and IV), who attended St. Vincent's Hospital Bbetween April 1999 and December 2001, 26 patients were included at St.Vincent's Hospital. The chemotherapy regimen consisted of vinorelbine (25 mg/m2 on days 1 and 8), ifosfamide (1,500 mg/m2 on days 1- and 2 with mesna), and cisplatin (30 mg/m2 on days 1- to 3). The cycles were administered every 4 weeks. A 25% reduction in the doses reduction was applied into subsequent courses if there werewas grade 3~4 neutropenia.
RESULTS
The median age was 63 (range, 44~73) years and the male : to female ratio was 19 : 7. One patient had stage IIIa, 6 had stage IIIb and 19 had stage IV. Twenty two patients had an ECOG performance status of 0 or 1, andwith 4 hadhave one of 2. Eighteen of the patients had adenocarcinoma, 7 had squamous cell carcinomas, and 1 had an undifferentiated NSCLC. Two patients were innot able to be evaluatedble due to follow-up loss. Among Of the 24 patients able to be evaluatedble patients, 1 patient had a complete response and 9 patients hada partial responses, and thewith an overall response rate wasof 41.7%. During a total of 104 cycles, grade 3 neutropenia occurred in 29%, grade 4 neutropenia in 12%, grade 3~4 thrombocytopenia in 4%, grade 3 anemia in 11%, and grade 3~4 mucositis in 2%. The mean time to progression was 6.4 months (range 1~13) and the median overall survival was 10 months (range 1.5~32).
CONCLUSION
The combination of vinorelbine, ifosfamide and cisplatin, in the dose and schedule employed in this study, shows an response rate of 41.7%, but, because grade 3- or 4 neutropenia occurred in 41%, a careful investigation is needed.

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Phase II Study of Topotecan and Etoposide as Second-line Treatment in Chemotherapy-refractory Small-cell Lung Cancer: Chul Kim, Joo Hyuk Sohn, Joo Hang Kim, Se Kyu Kim, Young Sam Kim, Joon Chang, Jae Yong Cho; Cancer Res Treat. 2002;34(5):334-338. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.334

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PURPOSE
Refractory small-cell lung cancer (SCLC) has a poor prognosis, and current salvage chemotherapy for refractory SCLC, such as CAV (cyclophosphamide, adriamycin, vincristine) or topotecan, has an unsatisfactory outcome, with a response rate and overall survival of less than 10% and 6 months, respectively. This phase II study evaluated the role of topotecan combined with etoposide in SCLC patients that have progressed, or relapsed, within 3 months following completion of the initial chemotherapy.
MATERIALS AND METHODS
Twenty-seven patients were entered into this study. Eligible patients had an ECOG performance status of less than, or equal to, 2, at least one bidimensionally measurable lesion and adequate end organ function. IV topotecan, 1.0 mg/m2/d for 5 consecutive days, and etoposide, 100 mg/m2/d through days 1 to 3, were administered every 3 weeks until disease progression or undue toxicity.
RESULTS
The major toxicity was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocy-topenia occurred in 14.2, 34.8, and 27.3% of cycles, respectively. There was no treatment-related death, and other non-hematologic toxicities were generally mild. Four patients achieved partial responses, with a response rate RR of 14.8%. The progression-free survival PFS ranged from 1 to 7 months, with a median of 2.0 months (95% confidence interval 1.22~2.78 months). Twenty-five patients died, with a median overall survival of 5.5 months (ranging from 1 to 21 months, 95% CI 4.32~6.68 months), and the 6-month survival rate was 32.1% (95% confidence interval 14.4~49.8%).
CONCLUSION
The combination of topotecan and etoposide chemotherapy showed a modest response rate, but failed to prolong survival of refractory SCLC patients compared to topotecan monotherapy.

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Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea
Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Lung Cancer: Targets and Therapy.2024; Volume 15: 149. CrossRef

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A Phase II Study of Gemcitabine Monotherapy in Breast Cancer Patients Refractory to Anthracycline and Taxane: Jun Yong Park, Chul Kim, Joo Hyuk Sohn, Yong Tae Kim, Sun Young Rha, Woo Ick Jang, Gwi Eon Kim, Hyun Cheol Chung; Cancer Res Treat. 2002;34(4):274-279. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.274

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We performed a phase II trial to evaluate the efficacy and the safety of gemcitabine monotherapy, a pyrimidine antimetabolite, in patients, who had previously failed anthracycline and taxane-based chemotherapy for the treatment of metastatic breast cancer.
MATERIALS AND METHODS
Twenty-one patients with metastatic breast cancer, which was unresponsive to previous chemotherapy, were entered into this study. Gemcitabine was administered at 850 mg/m2, as a 60- minute intravenous infusion on days 1, 8 and 15. This regimen was repeated every 28 days with G-CSF support, but without dose reduction.
RESULTS
Objective responses were seen in 6 of the 20 patients who were able to be evaluated (1 complete response and 5 partial responses), with an objective response rate of 30%. The median time to progression was 5 (1~20) months, and the median overall survival duration was 11 (2~21) months. The actual dose intensity was 566.7 mg/m2/wk (range; 340~637.5 mg/m2/wk) and the relative dose intensity was 0.89 (range; 0.40~1.00). Toxicity was mainly hematological. Toxicities included: grade 3 neutropenia in 20% and anemia in 5%. Grades 3 and 4 thrombocytopenia occurred in 15% of the patients.
CONCLUSION
Gemcitabine monotherapy is an effective and safe treatment for refractory breast cancer patients heavily treated with the anthracycline and taxane- based regimen.

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A phase II study of tipifarnib and gemcitabine in metastatic breast cancer
Clinton Yam, Rashmi K. Murthy, Vicente Valero, Janio Szklaruk, Girish S. Shroff, Carol J. Stalzer, Aman U. Buzdar, James L. Murray, Wei Yang, Gabriel N. Hortobagyi, Stacy L. Moulder, Banu Arun
Investigational New Drugs.2018; 36(2): 299. CrossRef
Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines
Woo Sun Kwon, Sun Young Rha, Yeon Ho Choi, Jung Ok Lee, Kyu Hyun Park, Jae Joon Jung, Tae Soo Kim, Hei-Cheul Jeung, Hyun Cheol Chung
Pharmacogenetics and Genomics.2006; 16(6): 429. CrossRef
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 Research and Treatment.2006; 38(4): 206. CrossRef
Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer
Sun Young Rha, Yong Hwa Moon, Hei Chul Jeung, Yong Tae Kim, Joo Hyuk Sohn, Woo Ick Yang, Chang Ok Suh, Gwi Eon Kim, Jae Kyung Roh, Hyun Cheol Chung
Breast Cancer Research and Treatment.2005; 90(3): 215. CrossRef

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