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Volume 50(1); January 2018
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Review Article
The Generation and Application of Patient-Derived Xenograft Model for Cancer Research
Jaeyun Jung, Hyang Sook Seol, Suhwan Chang
Cancer Res Treat. 2018;50(1):1-10.   Published online September 13, 2017
DOI: https://doi.org/10.4143/crt.2017.307
AbstractAbstract PDFPubReaderePub
Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics. In attempt to avoid these discrepancies between xenograft model and patients’ tumor, a patient-derived xenograft (PDX) model has been actively generated and applied. The PDX model can be developed by the implantation of cancerous tissue from a patient’s tumor into an immune-deficient mouse directly, thereby it preserves both cell-cell interactions and tumor microenvironment. In addition, the PDX model has shown advantages as a preclinical model in drug screening, biomarker development and co-clinical trial. In this review, we will summarize the methodology and applications of PDX in detail, and cover critical issues for the development of this model for preclinical research.

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Original Articles
Evaluation of Diagnostic Performance of Screening Thyroid Ultrasonography and Imaging Findings of Screening-Detected Thyroid Cancer
Jeongin Yoo, Hye Shin Ahn, Soo Jin Kim, Sung Hee Park, Mirinae Seo, Semin Chong
Cancer Res Treat. 2018;50(1):11-18.   Published online February 24, 2017
DOI: https://doi.org/10.4143/crt.2016.600
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate the diagnostic performance and cost of screening thyroid ultrasonography (US) in an asymptomatic population and determine the US features of screening-detected thyroid cancer.
Materials and Methods
This study included 1,845 asymptomatic participants who underwent screening thyroid US between March and August 2012 at the screening center in our hospital. We evaluated the diagnostic performance of screening thyroid US for thyroid cancer and the average cost of diagnosis for each patient. We also determined the characteristic US features of screening-detected thyroid cancer.
Results
Of the 1,845 subjects, 661 showed no abnormalities, 1,155 exhibited benign thyroid nodules, and 29 exhibited thyroid cancer. Imaging features such as solid composition, hypoechogenicity, taller-than-wide axis, and ill-defined or spiculated margins of nodules were suggestive of malignancy. The rate of detection of cancer was 1.6% (29/1,845), and the sensitivity, specificity, and positive and negative predictive values were 100% (18/18), 98.7% (1,051/1,065), 56.3% (18/32), and 100% (1,051/1,051), respectively. Of 18 patients who underwent thyroidectomy, three (16.7%) had a pathological tumor staging of T3, and four (22.2%) had a pathological nodal staging of N1a. The average cost of diagnosis for each patient with cancer was $7,319.
Conclusion
Screening thyroid US exhibited a good diagnostic performance, with a feasible social cost of use. This modality demonstrated significant differences in sonographic features between screening-detected cancer and benign nodules.

Citations

Citations to this article as recorded by  
  • Temporal Trends in Thyroid Nodule Size on Ultrasonography
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The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients
Li-Ting Liu, Qiu-Yan Chen, Lin-Quan Tang, Shan-Shan Guo, Ling Guo, Hao-Yuan Mo, Ming-Yuan Chen, Chong Zhao, Xiang Guo, Chao-Nan Qian, Mu-Sheng Zeng, Jin-Xin Bei, Jing Tan, Shuai Chen, Ming-Huang Hong, Jian-Yong Shao, Ying Sun, Jun Ma, Hai-Qiang Mai
Cancer Res Treat. 2018;50(1):19-29.   Published online April 5, 2017
DOI: https://doi.org/10.4143/crt.2016.595
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test.
Results
A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ≥ 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ≥ 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ≥ 390 cells/μL and post3m-ALC ≥ 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006).
Conclusion
Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

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    Pim J.J. Damen, Tiuri E. Kroese, Richard van Hillegersberg, Ewoud Schuit, Max Peters, Joost J.C. Verhoeff, Steven H. Lin, Peter S.N. van Rossum
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    De-Song Shen, Chang Yan, Yu Liang, Kai-Hua Chen, Xiao-Dong Zhu
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    Olsi Gjyshi, Zhongxing Liao
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    Qianqian Zhao, Tingting Li, Gang Chen, Zhaochong Zeng, Jian He
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    Yasunori Yoshino, Ayumi Taguchi, Maki Takao, Tomoko Kashiyama, Akiko Furusawa, Masaya Uno, Satoshi Okada, Nao Kino, Toshiharu Yasugi
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    Hwa Kyung Byun, Nalee Kim, Sangjoon Park, Jinsil Seong
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    Aleksei N. Shoutko
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    Sangjoon Park, Hwa Kyung Byun, Jinsil Seong
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    Cheng Xu, Shi-Ping Yang, Yuan Zhang, Ling-Long Tang, Guan-Qun Zhou, Xu Liu, Yan-Ping Mao, Rui Guo, Wen-Fei Li, Lei Chen, Ai-Hua Lin, Ying Sun, Jun Ma
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    Susannah G. Ellsworth
    Advances in Radiation Oncology.2018; 3(4): 512.     CrossRef
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    Anne Rodallec, Guillaume Sicard, Raphaelle Fanciullino, Sébastien Benzekry, Bruno Lacarelle, Gerard Milano, Joseph Ciccolini
    Expert Opinion on Drug Metabolism & Toxicology.2018; : 1.     CrossRef
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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study
Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee
Cancer Res Treat. 2018;50(1):30-39.   Published online February 27, 2017
DOI: https://doi.org/10.4143/crt.2016.569
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

Citations

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  • Ocular complication induced by anticancer drug S-1: association with drug concentrations in tears
    Masakazu Yamada, Tomoyuki Kamao, Atsushi Shiraishi, Jo Sakai, Yuichi Ohashi, Masashi Mimura, Yoshitsugu Inoue, Kazuyoshi Ohtomo, Tai-ichiro Chikama, Chika Miyazaki, Yuka Hosotani
    Japanese Journal of Ophthalmology.2025;[Epub]     CrossRef
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    Transboundary and Emerging Diseases.2024;[Epub]     CrossRef
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    Vasily D. Yartsev, Eugenia L. Atkova
    International Ophthalmology Clinics.2023; 63(3): 137.     CrossRef
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    Camilla Duarte Silva, Fabricio Lopes da Fonseca, Juliana Mika Kato, Suzana Matayoshi
    Revista Brasileira de Oftalmologia.2022;[Epub]     CrossRef
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    Hisataka Ominato, Michihisa Kono, Hidekiyo Yamaki, Takumi Kumai, Miki Takahara, Akihiro Katada, Tatsuya Hayashi
    Practica Oto-Rhino-Laryngologica.2022; 115(6): 503.     CrossRef
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    Jeremy Chung Bo Chiang, David Goldstein, Susanna B. Park, Arun V. Krishnan, Maria Markoulli
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  • Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
    Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
    International Journal of Clinical Oncology.2019; 24(6): 660.     CrossRef
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Development and Validation of the Korean Version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Non-muscle Invasive Bladder Cancer: EORTC QLQ-NMIBC24
Jinsung Park, Dong Wook Shin, Tae-Hwan Kim, Seung Il Jung, Jong Kil Nam, Seung Chol Park, Sungwoo Hong, Jae Hung Jung, Hongwook Kim, Won Tae Kim
Cancer Res Treat. 2018;50(1):40-49.   Published online March 10, 2017
DOI: https://doi.org/10.4143/crt.2016.594
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to evaluate psychometric properties of the Korean version of the EORTC QLQ-NMIBC24 when applied to Korean non-muscle invasive bladder cancer (NMIBC) patients.
Materials and Methods
A total of 249 patients who underwent curative transurethral resection of bladder tumor (TURBT) for primary orrecurrentNMIBCwere asked to complete theKorean version of EORTC QLQ-C30 and -NMIBC24 questionnaires three times (preoperative, post-TURBT 3 months and 6 months). Linguistic validation and psychometric evaluation of the questionnaire was conducted.
Results
Multitrait scaling analysis confirmed satisfactory construct validity in five scales except the malaise scale. Internal consistency was good (Cronbach’s alpha ≥ 0.70) for the five scales except the malaise scale at the all three time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status as expected, and better sexual function in men than women (p < 0.05). Most of the scales had low correlations (< 0.40) with the scales in QLQ-C30 showing divergent validity, except for malaise scale which showed higher correlations (0.42 to 0.60). Responsiveness to change was consistent with clinical implications over time after TURBT.
Conclusion
The Korean version of the EORTC QLQ-NMIBC24 has good reliability and cross-cultural validity for measuring various QOL aspects that can be self-administered to Korean NMIBC patients undergoing TURBT.

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  • Health-related Quality of Life During the First 4 Years After Non–Muscle-invasive Bladder Cancer Diagnosis: Results of a Large Multicentre Prospective Cohort
    Ivy Beeren, Nena E. Klerks, Katja K. Aben, Jorg R. Oddens, J. Alfred Witjes, Lambertus A. Kiemeney, Alina Vrieling
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    An Xu
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    E. Rammant, L. Fox, K. Beyer, N. K. Aaronson, R. Chaloner, S. De Padova, F. Liedberg, L. M. Wintner, K. Decaestecker, V. Fonteyne, N. Perdek, H. Wylie, J. W. F. Catto, T. M. Ripping, B. Holzner, M. Van Leeuwen, M. Van Hemelrijck
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    Sima Rafiei, Golnaz Kheradkhah, Grigorios Kotronoulas, Maryam Doustmehraban, Farnoosh Shafiei, Maryam Masoumi, Elaheh Parnian, Elmira Nosrati Sanjabad, Ahmad Ghashghaee
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    Jeongok Park, Young Deuk Choi, Kyoungjin Lee, Miae Seo, Ahyoung Cho, Sejeong Lee, Keum-hee Nam
    Asia-Pacific Journal of Oncology Nursing.2022; 9(6): 100063.     CrossRef
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    Theodora M. Ripping, Ellen Westhoff, Neil K. Aaronson, Mieke Van Hemelrijck, Elke Rammant, J. Alfred Witjes, Lambertus. A. Kiemeney, Katja K. H. Aben, Alina Vrieling
    Journal of Patient-Reported Outcomes.2021;[Epub]     CrossRef
  • Humanistic and Economic Burden of Non-Muscle Invasive Bladder Cancer: Results of Two Systematic Literature Reviews


    Lauren J Lee, Christina S Kwon, Anna Forsythe, Carla M Mamolo, Elizabeth T Masters, Ira A Jacobs
    ClinicoEconomics and Outcomes Research.2020; Volume 12: 693.     CrossRef
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    Zhonghui Li, Dan Wei, Chenxi Zhu, Qing Zhang
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Risk and Characteristics of Postcolonoscopy Interval Colorectal Cancer after a Positive Fecal Test: A Nationwide Population-Based Study in Korea
Chang Kyun Lee, Kui Son Choi, Chang Soo Eun, Dong-Il Park, Dong Soo Han, Minjoo Yoon, Mina Suh, Jae Kwan Jun
Cancer Res Treat. 2018;50(1):50-59.   Published online February 24, 2017
DOI: https://doi.org/10.4143/crt.2017.027
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Fecal tests remain a mainstay of population-based colorectal cancer (CRC) screening programs worldwide. However, data on interval CRC (iCRC) arising after follow-up colonoscopy of a positive fecal test are scarce. We conducted a nationwide population-based study to reveal the risk and characteristics of iCRC in this setting.
Materials and Methods
We searched the National Cancer Screening Program for CRC database in Korea (2005-2010). Incidence of iCRC within the program was estimated, then Cox proportional-hazards regression analysis was performed to determine the independent predictors of iCRC. The clinical characteristics of iCRC were compared with screen-detected CRC (sCRC).
Results
We identified 280 iCRC among 150,660 negative colonoscopies as a follow-up exam to a positive fecal immunochemical test (FIT), and 2,427 sCRC. The overall incidence of iCRC was 0.49/1,000 person-years (95% confidence interval [CI], 0.48 to 0.51). iCRC was more likely to occur in men (adjusted hazard ratio [aHR], 1.79; 95% CI, 1.39 to 2.30) and elderly patients (aHR, 1.77; 95% CI, 1.38 to 2.28 in 65-74 years; aHR, 3.13, 95% CI, 2.13-4.60 in ≥ 75 years). The National Quality Improvement Program for colonoscopy reduced a short-term risk of iCRC (aHR, 0.48; 95% CI, 0.27 to 0.87). Compared with sCRC, iCRC was more likely to occur in the proximal colon, be diagnosed at the localized stage, and have a lower CRC mortality (32.7 vs. 17.4%, 56.8 vs. 34.1%, 12.5 vs. 17.7%, respectively; all p < 0.05).
Conclusion
In a population-based CRC screening program with FIT, the burden of iCRC after follow-up colonoscopy was substantial. Men and elderly patients possess a significantly higher risk of iCRC.

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    Jeffrey K. Lee, James H-E. Kang, Sophie A. Merchant, Christopher D. Jensen, Nicholas E. Burr, Douglas A. Corley
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    Bernard Denis, Alice Bertolaso, Isabelle Gendre, Philippe Perrin, Karima Hammas
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    Pieter H. A. Wisse, Sybrand Y. de Boer, Marco Oudkerk Pool, Jochim S Terhaar sive Droste, Claudia Verveer, Gerrit A. Meijer, Evelien Dekker, Manon C. W. Spaander
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    Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Ji Eun Kim, Hooyeon Lee
    Cancer Research and Treatment.2024; 56(4): 1164.     CrossRef
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    Chi Thi-Du Tran, Mai Vu-Tuyet Nguyen, Mo Thi Tran, Thuy Thi-Van Tuong, Quang Hong Tran, Linh Cu Le, Huong Thi-Thu Pham, Nam Chi Bui, Hien Huy Vu, Tu Thi-Cam Nguyen, Phuong Que Ta, Hien Thi-Thu Ha, Dung Tuan Trinh, Hanh Thi-My Bui, Dien Quang Trinh, Khanh
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    James H.‐E. Kang, Nicole Evans, Siddharth Singh, Niloy J. Samadder, Jeffrey K. Lee
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    Efrat L. Amitay, Katarina Cuk, Tobias Niedermaier, Korbinian Weigl, Hermann Brenner
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    Kyeong Ok Kim, Kyu Chan Huh, Sung Pil Hong, Won Hee Kim, Hyuk Yoon, Sang Wook Kim, Yeon Soo Kim, Jong Ha Park, Jun Lee, Bum Jae Lee, Young Sook Park
    Gut and Liver.2018; 12(5): 537.     CrossRef
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Magnetic Resonance Imaging for Colorectal Cancer Metastasis to the Liver: Comparative Effectiveness Research for the Choice of Contrast Agents
Nieun Seo, Mi-Suk Park, Kyunghwa Han, Kyung Ho Lee, Seong Ho Park, Gi Hong Choi, Jin-Young Choi, Yong Eun Chung, Myeong-Jin Kim
Cancer Res Treat. 2018;50(1):60-70.   Published online March 14, 2017
DOI: https://doi.org/10.4143/crt.2016.533
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to compare the diagnostic performance and early recurrence rate between gadoxetic acid–enhanced magnetic resonance imaging (Gd-EOB-MRI) and magnetic resonance imaging (MRI) with extracellular contrast agent (ECA-MRI) for evaluating hepatic lesions in colorectal cancer.
Materials and Methods
Between 2005 and 2010, 418 colorectal cancer patients with both preoperative computed tomography (CT) and liver MRI were retrospectively reviewed. Image analysis was based on initial radiologic reports, and diagnostic performance was assessed based on the area under the receiver operating characteristic curve (AUROC). The early intrahepatic recurrence rate within 6 months was then evaluated.
Results
Overall, 291 and 127 patients underwent Gd-EOB-MRI and ECA-MRI, respectively. The AUROCs were not significantly different between Gd-EOB-MRI (0.990; 95% CI, 0.980 to 0.999) and ECA-MRI (0.985; 95% CI, 0.968 to 1.000; p=0.836). When compared with CT alone, ECA-MRI detected additional 21 lesions in 14 patients (14/127, 11.0%), whereas Gd-EOB-MRI detected 56 lesions in 33 patients (33/291, 11.3%) without a significant difference between two MRI groups (p=0.331). The early recurrence rate in the ECA-MRI (28.6%) was significantly higher than that in the Gd-EOB-MRI (11.6%) for patients who underwent hepatic resection (p=0.031).
Conclusion
Gd-EOB-MRI is potentially better than ECA-MRI for decreasing the early intrahepatic recurrence rate, although the two MRI modalities showed comparable diagnostic performance in colorectal cancer patients.

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  • Clinical performance of a simulated abbreviated liver magnetic resonance imaging in combination with contrast-enhanced computed tomography for the baseline evaluation of the liver in patients with colorectal cancer
    F. Castagnoli, S.J. Withey, M. Konidari, I. Chau, A. Riddell, J. Shur, C. Messiou, D.M. Koh
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    Ya-Wei Xu, Hong Fu
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    Jeong Woo Kim, Chang Hee Lee, Yang Shin Park, Jongmee Lee, Kyeong Ah Kim
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    Serena Langella, Francesco Ardito, Nadia Russolillo, Elena Panettieri, Serena Perotti, Caterina Mele, Felice Giuliante, Alessandro Ferrero
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    M. S. Tlostanova, A. L. Dolbov, A. A. Stanzhevskii
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  • Imagerie par résonance magnétique dans le bilan local préopératoire des cancers du rectum
    M. Djelouah, C. Durot, S. Deguelte-Lardière, J. Cohen, A. Devie, L. Protin-Catteau, C. Hoeffel
    EMC - Radiologie et imagerie médicale - Abdominale - Digestive.2019; 37(2): 1.     CrossRef
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Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18
Xiaohui Xu, Cheng Song, Zhihua Chen, Chenxiao Yu, Yi Wang, Yiting Tang, Judong Luo
Cancer Res Treat. 2018;50(1):71-87.   Published online February 24, 2017
DOI: https://doi.org/10.4143/crt.2017.013
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC).
Materials and Methods
In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used.
Results
In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay.
Conclusion
HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

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Re-stratification of Patients with High-Risk Prostate Cancer According to the NCCN Guidelines among Patients Who Underwent Radical Prostatectomy: An Analysis Based on the K-CaP Registry
Kwang Suk Lee, Kyo Chul Koo, In Young Choi, Ji Youl Lee, Jun Hyuk Hong, Choung-Soo Kim, Hyun Moo Lee, Sung Kyu Hong, Seok-Soo Byun, Koon Ho Rha, Byung Ha Chung
Cancer Res Treat. 2018;50(1):88-94.   Published online March 7, 2017
DOI: https://doi.org/10.4143/crt.2016.494
AbstractAbstract PDFPubReaderePub
Purpose
The present study aimed to re-stratify patients with high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines among patients who underwent radical prostatectomy (RP).
Materials and Methods
This study used the Korean Prostate Cancer Database registry and identified 1,060 patients with high-risk prostate cancer who underwent RP between May 2001 and April 2013. All patients were categorized into risk groups, and subgroups were identified according to the type and number of high-risk factors.
Results
Of the 1,060 high-risk patients, 599 (56.5%), 408 (38.5%), and 53 (5.0%) had 1, 2, and 3 risk factors, respectively. In multivariate analysis, the Gleason score, percentage of positive biopsy cores, and number of risk factors present were identified as independent predictors of biochemical recurrence. There were significant differences in the 5-year postoperative biochemical failure-free survival (BCFFS) rate among the different high-risk factor subgroups (log-rank p < 0.001). There were no significant differences in the BCFFS rate between the subgroup of high-risk patients with a prostate-specific antigen level > 20 ng/mL alone and the intermediate-risk group with all factors (log-rank p=0.919 and p=0.781, respectively). Additionally, no significant differencewas noted in the BCFFS rate between high-risk patients having all factors and those in the very-high-risk group (p=0.566).
Conclusion
We successfully re-stratified patients with high-risk prostate cancer and identified the combinations of high-risk criteria that will help in the selection of patients for RP.

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    Cheng-Kuang Yang, Chi-Rei Yang, Yen-Chuan Ou, Chen-Li Cheng, Hao-Chung Ho, Kun-Yuan Chiu, Shian-Shiang Wang, Jian-Ri Li, Chuan-Shu Chen, Chi-Feng Hung, Cheng-Che Chen, Shu-Chi Wang, Chia-Yen Lin, Sheng-Chun Hung
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Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer
Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim
Cancer Res Treat. 2018;50(1):95-102.   Published online March 17, 2017
DOI: https://doi.org/10.4143/crt.2016.591
AbstractAbstract PDFPubReaderePub
Purpose
Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis.
Results
All patients had ≥ 1 EGFR mutation—54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1–positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1–positive groups (TPS ≥ 1%) compared with the PD-L1–negative group (median, 35 months).
Conclusion
PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR-mutant NSCLC.

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    Yidan Zhang, Yingqi Xu, Hongping Jin, Tengfei Liu, Hua Zhong, Jianlin Xu, Yuqing Lou, Runbo Zhong
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Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model
Pawel Chrom, Rafal Stec, Lubomir Bodnar, Cezary Szczylik
Cancer Res Treat. 2018;50(1):103-110.   Published online March 3, 2017
DOI: https://doi.org/10.4143/crt.2017.033
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.
Materials and Methods
This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R2, Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.
Results
Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R2, 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R2, 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).
Conclusion
Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

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Proteomic Biomarkers for Bisphenol A–Early Exposure and Women’s Thyroid Cancer
Ho-Sun Lee, Yunkyeong Kang, Kyung Tae, Gyu-Un Bae, Jong Y. Park, Yoon Hee Cho, Mihi Yang
Cancer Res Treat. 2018;50(1):111-117.   Published online March 8, 2017
DOI: https://doi.org/10.4143/crt.2017.001
AbstractAbstract PDFPubReaderePub
Purpose
For the target treatment and prevention of women’s increased thyroid cancer, we focused on risks of environmental exposure to endocrine disrupting chemicals, particularly bisphenol A (BPA), and its high susceptible exposure-timing, particularly early exposure in lives.
Materials and Methods
Female ICR mice were exposed to BPA in utero and in early life (15, 75, and 300 mg/L of drinking water via pregnant mice and lactation). We identified BPA-responsive proteins in mice thyroid by two-dimensional gel electrophoresis, image analyses, and electrospray ionization quadrupole time-of-flight mass spectrometry. We further analyzed expression of the BPA-responsive proteins in women thyroid cancer patients (n=28).
Results
We found the altered 17 proteins in BPA dose-dependent manner among the thyroid tissues of offspring mice and identified nine proteins of them, including Anxa6, Atp5b, Hspa5, and Vcp, etc. In addition, we observed the positive association between blood BPA levels and mRNA expression of the ANXA6 and VCP not in normal but thyroid cancer tissues.
Conclusion
Our study provides ANXA6 and VCP as proteomic biomarkers for BPA–early life exposure and their potential for women’s thyroid cancer.

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    Ylenia Della Rocca, Enrico Matteo Traini, Francesca Diomede, Luigia Fonticoli, Oriana Trubiani, Alessia Paganelli, Jacopo Pizzicannella, Guya Diletta Marconi
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    Susan Costantini, Francesca Capone, Andrea Polo, Palmina Bagnara, Alfredo Budillon
    International Journal of Molecular Sciences.2021; 22(18): 10177.     CrossRef
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    Mark L. Sowers, Hui Tang, Bing Tian, Randall Goldblum, Terumi Midoro-Horiuti, Kangling Zhang
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Patterns of Care for Radiotherapy in the Neoadjuvant and Adjuvant Treatment of Gastric Cancer: A Twelve-Year Nationwide Cohort Study in Korea
Jee Suk Chang, Young Choi, Jaeyong Shin, Kyung Hwan Kim, Ki Chang Keum, Hyo Song Kim, Woong Sub Koom, Eun-Cheol Park
Cancer Res Treat. 2018;50(1):118-128.   Published online March 8, 2017
DOI: https://doi.org/10.4143/crt.2016.575
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although Korea has the highest incidence of gastric cancer worldwide and D2-lymphadenectomies are routinely performed, radiotherapy (RT) practice patterns have not been well studied. Therefore, we examined RT usage trends for neoadjuvant/adjuvant patients and identified factors associated with RT. We also examined survival benefits and net medical cost advantages of adding RT.
Materials and Methods
Patients diagnosed with gastric cancer who underwent gastrectomy from 2002-2013 were identified using National Health Insurance Service-National Sample Cohort.
Results
Annually, 30.9 cases per 100,000 population in crude rate underwent gastrectomy in 230 hospitals and 49.8% received neoadjuvant/adjuvant therapy in 182 hospitals. For neoadjuvant/adjuvant patients, postoperative chemo-RT was administered in 4% of cases in 26 hospitals. No significant trends regarding treatment type were observed over time. Having undergone RT was inversely associated with being ≥ 60 years old and having a low income. Having undergone RT was positively related to having a Charlson comorbidity index ≥ 4, hospital location and hospital volume (≥ 2,000 beds). Significant portions of patients treated with RT in this nation (52%) were concentrated in one large-volume hospital. Use of RT linked to increased cost of primary treatment, yet not to reduced overall medical expense. RT did not influence both on overall and disease-specific survivals after adjusting for potential confounders (p > 0.05).
Conclusion
RT was uncommonly utilized as adjuvant or neoadjuvant treatment by physicians in Korea. Despite intrinsic drawback in this data, we did not find either survival benefit or net medical cost advantage by adding RT in adjuvant treatment.

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    Yung-Sung Yeh, Ming-Yii Huang, Cheng-Jen Ma, Ching-Wen Huang, Hsiang-Lin Tsai, Yen-Cheng Chen, Ching-Chun Li, Fang-Jung Yu, Hsiang-Yao Shih, Jaw-Yuan Wang
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    Weipeng Gong, Hongwei Zhao, Shanshan Liu, Jie Guan, Xin Liu, Qingsheng Hou, Zhenyu Zhu, Hongliang Guo
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Cancer-Specific Mortality Among Korean Men with Localized or Locally Advanced Prostate Cancer Treated with Radical Prostatectomy Versus Radiotherapy: A Multi-Center Study Using Propensity Scoring and Competing Risk Regression Analyses
Kyo Chul Koo, Jin Seon Cho, Woo Jin Bang, Seung Hwan Lee, Sung Yong Cho, Sun Il Kim, Se Joong Kim, Koon Ho Rha, Sung Joon Hong, Byung Ha Chung
Cancer Res Treat. 2018;50(1):129-137.   Published online March 8, 2017
DOI: https://doi.org/10.4143/crt.2017.004
AbstractAbstract PDFPubReaderePub
Purpose
Studies comparing radical prostatectomy (RP) outcomes with those of radiotherapy with or without androgen deprivation therapy (RT±ADT) for prostate cancer (PCa) have yielded conflicting results. Therefore, we used propensity score-matched analysis and competing risk regression analysis to compare cancer-specific mortality (CSM) and other-cause mortality (OCM) between these two treatments.
Materials and Methods
The multi-center, Severance Urological Oncology Group registry was utilized to identify 3,028 patients with clinically localized or locally advanced PCa treated by RP (n=2,521) or RT±ADT (n=507) between 2000 and 2016. RT±ADT cases (n=339) were matched with an equal number of RP cases by propensity scoring based on age, preoperative prostate-specific antigen, clinical tumor stage, biopsy Gleason score, and Charlson Comorbidity Index (CCI). CSM and OCM were co-primary endpoints.
Results
Median follow-up was 65.0 months. Five-year overall survival rates for patients treated with RP and RT±ADT were 94.7% and 92.0%, respectively (p=0.105). Cumulative incidence estimates revealed comparable CSM rates following both treatments within all National Comprehensive Cancer Network risk groups. Gleason score ≥ 8 was associated with higher risk of CSM (p=0.009). OCM rates were comparable between both groups in the low- and intermediate-risk categories (p=0.354 and p=0.643, respectively). For high-risk patients, RT±ADT resulted in higher OCM rates than RP (p=0.011). Predictors of OCM were age ≥ 75 years (p=0.002) and CCI ≥ 2 (p < 0.001).
Conclusion
RP and RT±ADT provide comparable CSM outcomes in patients with localized or locally advanced PCa. The risk of OCM may be higher for older high-risk patients with significant comorbidities.

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    Caroline M. van der Starre, Chris H. Bangma, Maarten J. Bijlsma, Alfons C.M. van den Bergh, Lambertus A.L.M. Kiemeney, Wietske Kievit, Kees Vos, Diederik M. Somford, Sally M. Wildeman, Katja K.H. Aben, Igle J. de Jong, Floris J. Pos, Berdine L. Heesterman
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    Yasuo Kohjimoto, Hiroji Uemura, Masahiro Yoshida, Shiro Hinotsu, Satoru Takahashi, Tsutomu Takeuchi, Kazuhiro Suzuki, Hiroshi Shinmoto, Tsutomu Tamada, Takahiro Inoue, Mikio Sugimoto, Atsushi Takenaka, Tomonori Habuchi, Hitoshi Ishikawa, Takashi Mizowaki,
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    Berdine L. Heesterman, Katja K. H. Aben, Igle Jan de Jong, Floris J. Pos, Olga L. van der Hel
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    Jun Seop Kim, Jae Hoon Chung, Wan Song, Minyong Kang, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Change Jeong, Seong Il Seo, Hyun Moo Lee, Seong Soo Jeon
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Ruthenium-106 Brachytherapy with or without Additional Local Therapy Shows Favorable Outcome for Variable-Sized Choroidal Melanomas in Korean Patients
Yeona Cho, Jee Suk Chang, Jin Sook Yoon, Sung Chul Lee, Yong Bae Kim, Joo Ho Kim, Ki Chang Keum
Cancer Res Treat. 2018;50(1):138-147.   Published online March 24, 2017
DOI: https://doi.org/10.4143/crt.2016.391
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to report clinical outcomes of ruthenium-106 (106Ru) brachytherapy with or without additional local therapy for choroidal melanomas in Korean patients.
Materials and Methods
A total of 88 patients diagnosed with choroidal melanomas were treated with 106Ru brachytherapy between 2006 and 2012. Patients were divided into two groups according to their tumor height: a large group (≥ 6 mm, n=50) and a small group (< 6 mm, n=38). Most patients in the large group received combined therapy with local excision and/or transpupillary thermotherapy. In general, 85-95 Gy was administered to the apex of the tumor, while 100 Gy was administered to the point 2-6 mm from the outer surface of the sclera for patients undergoing combined therapy.
Results
The median follow-up duration was 30 months. The 3-year local control rate was significantly higher in the small group than in the large group (94% vs. 70%, p=0.047). The free from distant metastasis (FFDM) rate and the overall survival (OS) rate were also higher in patients in the small group (3-year FFDM, 97% vs. 76%; p=0.031 and 3-year OS, 97% vs. 72%; p=0.036). A total of 13 patients underwent enucleation. The eye-preservation rate was also higher in the small group (3-year eye-preservation rate, 94% vs. 70%; p=0.050), and tumor height was a significant prognostic factor for eye-preservation.
Conclusion
106Ru brachytherapy showed favorable outcomes in small choroidal melanomas in Korean patients. Although additional local treatment could improve eye-preservation rate for large tumors, other strategies should be considered for disease control.

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    Viktor T. Gill, Gustav Stålhammar
    Heliyon.2024; 10(1): e23447.     CrossRef
  • Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma
    Gustav Stålhammar
    International Journal of Radiation Oncology*Biology*Physics.2023; 117(5): 1125.     CrossRef
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    Fátima Virgínia Gama Justi, Gabriella Araújo Matos, Juan de Sá Roriz Caminha, Cássia Rodrigues Roque, Edinilton Muniz Carvalho, Márcio Wilker Soares Campelo, Ludmila Belayev, Luiz Gonzaga de França Lopes, Reinaldo Barreto Oriá
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    Gilda Cennamo, Daniela Montorio, Luca D’ Andrea, Antonio Farella, Elide Matano, Mario Giuliano, Raffaele Liuzzi, Maria Angelica Breve, Sabino De Placido, Giovanni Cennamo
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Yong Joon Kim, Christopher Seungkyu Lee, Sung Chul Lee
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    Daniel Lorenzo, María Ochoa, Josep Maria Piulats, Cristina Gutiérrez, Luis Arias, Jaume Català, María Grau, Judith Peñafiel, Estefanía Cobos, Pere Garcia-Bru, Marcos Javier Rubio, Noel Padrón-Pérez, Bruno Dias, Joan Pera, Josep Maria Caminal
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Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study
Loredana Amoroso, Giovanni Erminio, Guy Makin, Andrew D. J. Pearson, Penelope Brock, Dominique Valteau-Couanet, Victoria Castel, Marlène Pasquet, Genevieve Laureys, Caroline Thomas, Roberto Luksch, Ruth Ladenstein, Riccardo Haupt, Alberto Garaventa, SIOPEN Group
Cancer Res Treat. 2018;50(1):148-155.   Published online March 21, 2017
DOI: https://doi.org/10.4143/crt.2016.511
AbstractAbstract PDFPubReaderePub
Purpose
Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.
Materials and Methods
Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.
Results
Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).
Conclusion
TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

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    Marcus Borenäs, Ganesh Umapathy, Dan E. Lind, Wei-Yun Lai, Jikui Guan, Joel Johansson, Eva Jennische, Alexander Schmidt, Yeshwant Kurhe, Jonatan L. Gabre, Agata Aniszewska, Anneli Strömberg, Mats Bemark, Michael N. Hall, Jimmy Van den Eynden, Bengt Hallbe
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Radiotherapy Versus Cordectomy in the Management of Early Glottic Cancer
Seung Yeun Chung, Kyung Hwan Kim, Ki Chang Keum, Yoon Woo Koh, Se-Heon Kim, Eun Chang Choi, Chang Geol Lee
Cancer Res Treat. 2018;50(1):156-163.   Published online March 17, 2017
DOI: https://doi.org/10.4143/crt.2016.503
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare the treatment outcomes of definitive radiotherapy (RT) with cordectomy in patients with early glottic cancer.
Materials and Methods
A total of 165 patientswhowere diagnosedwith T1/2 squamous cell carcinoma of the glottic larynx between January 2006 and December 2012 were retrospectively analyzed. A total of 112 patients received RT and 53 patients received cordectomy. Local control (LC), disease-free survival (DFS), overall survival (OS), and larynx preservation rates after RT and cordectomy were investigated.
Results
The median follow-up period was 77.7 months (range, 10.7 to 127.0 months). The 3- and 5-year LC rates were 91.9% and 89.9%, respectively, for the RT group, and 82.8% and 73.2%, respectively, for the cordectomy group (p=0.006). The 3- and 5-year DFS rates were 87.5% and 83.7%, respectively, for the RT group and 79.2% and 68.0%, respectively, for the cordectomy group (p=0.046). No significant differences were identified in the 5-year OS (92.8% vs. 90.6%, p=0.713) or larynx preservation rates (98.2% vs. 97.2%, p=0.831) between groups. The major failure pattern was local failure (n=26), followed by regional (n=3) and distant failure (n=2). Multivariate analysis of LC showed that T2 stage (p=0.012) and receiving cordectomy as initial treatment (p=0.001) were significantly associated with poorer LC.
Conclusion
RT resulted in higher rates of LC and DFS compared to cordectomy for early glottic cancer. Treatment with radiotherapy is feasible and should be encouraged for both T1 and T2 glottic cancer.

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Epidemiology of Intracranial Metastases in Korea: A National Cohort Investigation
Tackeun Kim, Changhoon Song, Jung Ho Han, In-Ah Kim, Yu Jung Kim, Se Hyun Kim, Jee Hyun Kim, Chae-Yong Kim
Cancer Res Treat. 2018;50(1):164-174.   Published online March 21, 2017
DOI: https://doi.org/10.4143/crt.2017.072
AbstractAbstract PDFPubReaderePub
Purpose
To investigate the epidemiologic features of intracranial metastases (ICMET) in Korea, we performed a cohort study using the National Health Insurance Service–National Sample Cohort database, which comprised healthcare usage information of approximately 1 million Korean individuals over 12 years.
Materials and Methods
We enrolled 998,602 subjects, after excluding 18,218 subjects diagnosed with any cancer during the washout period (2002-2004). The observation period was 9 years (2005-2013; 8,725,438 person-years). The initial diagnosis date of ICMET and the primary cancer was recorded. The incidence was determined based on the number of incident cases and observation size, whereas survival was estimated using death statistics from the database.
Results
Through observation period, a total 776 subjects developed ICMET. The age-standardized incidence of ICMET was 8.2 per 100,000 person-years. The mean interval between the initial diagnosis date of the primary cancer and ICMET was 13.1 months. Patients with ICMET had shorter survival than those without ICMET (30.9 months vs. 81.4 months, p < 0.001). The ICMET incidence among the cancer patients was 5.0 per 1,000 personyears; it was highest in lung cancer cases, followed by breast and liver cancer cases. Moreover, ICMET from lung cancer was the most common metastasis type, followed by ICMET from liver and breast cancer.
Conclusion
The incidence of ICMET was 8.2 per 100,000 person-years among the Korean population and 5.0 per 1,000 person-years among cancer patients. Most of the ICMET cases arose from lung cancer. ICMET also critically influenced survival in cancer patients.

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Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study
Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim
Cancer Res Treat. 2018;50(1):175-182.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2016.535
AbstractAbstract PDFPubReaderePub
Purpose
This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence.
Materials and Methods
A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients.
Results
A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes.
Conclusion
GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

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  • Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma
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    Tae Hun Kim, Ki Hyuk Sung, So Hak Chung
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    Lilamani Rajthala, Sagar Gyawali, Sabin Banmala, Surendra Shah
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The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study
Malek B. Hannouf, Eric Winquist, Salaheddin M. Mahmud, Muriel Brackstone, Sisira Sarma, George Rodrigues, Peter K. Rogan, Jeffrey S. Hoch, Gregory S. Zaric
Cancer Res Treat. 2018;50(1):183-194.   Published online March 21, 2017
DOI: https://doi.org/10.4143/crt.2016.532
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS).
Materials and Methods
We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have “occult” primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as “obvious.” We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment.
Results
Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences.
Conclusion
GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

Citations

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  • Relationship between metastasis and second primary cancers in women with breast cancer
    Chaofan Li, Mengjie Liu, Jia Li, Xixi Zhao, Yusheng Wang, Xi Chen, Weiwei Wang, Shiyu Sun, Cong Feng, Yifan Cai, Fei Wu, Chong Du, Yinbin Zhang, Shuqun Zhang, Jingkun Qu
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    Malek B. Hannouf, Eric Winquist, Salaheddin M. Mahmud, Muriel Brackstone, Sisira Sarma, George Rodrigues, Peter K. Rogan, Jeffrey S. Hoch, Gregory S. Zaric
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An Open-Label, Randomized, Parallel, Phase II Trial to Evaluate the Efficacy and Safety of a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel as First-Line Treatment for Ovarian Cancer: A Korean Gynecologic Oncology Group Study (KGOG-3021)
Shin-Wha Lee, Yong-Man Kim, Chi Heum Cho, Young Tae Kim, Seok Mo Kim, Soo Young Hur, Jae-Hoon Kim, Byoung-Gie Kim, Seung-Cheol Kim, Hee-Sug Ryu, Soon Beom Kang
Cancer Res Treat. 2018;50(1):195-203.   Published online March 21, 2017
DOI: https://doi.org/10.4143/crt.2016.376
AbstractAbstract PDFPubReaderePub
Purpose
Genexol-PM is a biodegradable cremophor EL–free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment.
Materials and Methods
In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR).
Results
Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m2 Genexol-PM or 174.24±3.81 mg/m2 Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable.
Conclusion
Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

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    Small.2018;[Epub]     CrossRef
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Validation of the Korean Version of the Quality of Life–Cancer Survivors (QOL-CS-K) Questionnaire in Lymphoma Survivors
Juhee Cho, Danbee Kang, Im Ryung Kim, Won Seog Kim, Betty Ferrell, Seok Jin Kim
Cancer Res Treat. 2018;50(1):204-211.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2017.091
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The objective of this study was to validate the Korean version of the Quality of Life–Cancer Survivors (QOL-CS-K) in a sample of lymphoma survivors.
Materials and Methods
We conducted a cross-sectional survey of lymphoma survivors who had survived for at least 24 months since diagnosis. Participants were recruited at the outpatient clinics and at a hospital event in a tertiary hospital in Seoul, Korea. Survivors were asked to complete the QOLCS-K and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) questionnaires. To determine test-retest reliability, a second questionnaire was sent to participants who completed the first questionnaire adequately. Exploratory factor analysis and Pearson’s correlations were used for evaluating reliability and validity of the QOL-CS-K.
Results
Among 257 survivors, 245 (95.3%) completed all questionnaires and had no missing data. The mean age of study participants was 52.2 years, 54.9% were men, and the mean time since diagnosis was 4.0±1.6 years. The Cronbach’s α for the overall QOL-CS-K was 0.90, and the α coefficients for each subscale ranged from 0.73 to 0.83. The test and retest reliability was 0.88. Moderate correlations were found between comparable subscales of the QOL-CS-K and subscales of the EORTC QLQ-C30 (r=0.51-0.55) except for the spiritual well-being subscale of the QOL-CS-K, which did not correlate with any of the EORTC QLQ-C30 subscales (–0.08 to 0.16).
Conclusion
The QOL-CS-K is a reliable and valid scale for measuring the QOL in long-term lymphoma survivors.

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  • Korean patients with hereditary cancer: a prospective multicentre cohort study protocol exploring psychosocial and health outcomes
    Jun-Kyu Kim, Mi-Ae Jang, Jong Eun Park, Dongju Won, Jung-Sook Ha, Kyoung-Bo Kim, Boyoung Park, Sun-Young Kong
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  • Measuring patient‐reported distress from breast magnetic resonance imaging: Development and validation of the MRI‐related distress scale (MRI‐DS)
    Danbee Kang, Sooyeon Kim, Jiyoon Han, Youngha Kim, Juhee Cho, Jeong Eon Lee, Eun Sook Ko
    Cancer Medicine.2024;[Epub]     CrossRef
  • Quality of life patient/cancer survivor version in Chinese cancer survivors: A validation study
    Hai-Ying Wang, Stephen Wai Hang Kwok, Xian-Liang Liu, Tao Wang, Daniel Bressington, Yushan Shen, Qing Zhang, Hou-Qiang Huang, Jing-Yu Tan
    Asia-Pacific Journal of Oncology Nursing.2023; 10(8): 100255.     CrossRef
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    Tânia Alteniza Leandro, Viviane Martins da Silva, Marcos Venícios de Oliveira Lopes, Nayana Maria Gomes de Souza, Kiarelle Lourenço Penaforte, Emanuela Aparecida Teixeira Gueiros, Marisa Nascimento de Oliveira
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  • Prediction Model for Postoperative Quality of Life Among Breast Cancer Survivors Along the Survivorship Trajectory From Pretreatment to 5 Years: Machine Learning–Based Analysis
    Danbee Kang, Hyunsoo Kim, Juhee Cho, Zero Kim, Myungjin Chung, Jeong Eon Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Jai Min Ryu, Se Kyung Lee
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    Yi-Cheng Hu, Shih-Ying Chen, Wen-Chi Chou, Jen-Shi Chen, Li-Chueh Weng, Pei-Kwei Tsay, Woung-Ru Tang, Chong-Chi Chiu
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    Danbee Kang, Ka Ryeong Bae, Jihyun Lim, Nayeon Kim, Sungkeun Shim, Sun Seog Kweon, Hwa Jeong Seo, Juhee Cho
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    Danbee Kang, Juhee Cho, Im Ryung Kim, Mi Kyung Kim, Won Seog Kim, Seok Jin Kim
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Strategic Distributional Cost-Effectiveness Analysis for Improving National Cancer Screening Uptake in Cervical Cancer: A Focus on Regional Inequality in South Korea
Tae-Hoon Lee, Woorim Kim, Jaeyong Shin, Eun-Cheol Park, Sohee Park, Tae Hyun Kim
Cancer Res Treat. 2018;50(1):212-221.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2016.525
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to conduct a cost effectiveness analysis of strategies designed to improve national cervical cancer screening rates, along with a distributional cost effectiveness analysis that considers regional disparities.
Materials and Methods
Cost effectiveness analysis was conducted using a Markov cohort simulation model, with quality adjusted life years as the unit of effectiveness. The strategies considered were current (biennial Papanicolaou smear cytology of females aged 20 or above), strong screening recommendation by mail to target regions (effect, 12% increase in screening uptake; cost, 1,000 Korean won per person), regular universal screening recommendation by mail (effect, 6% increase in screening uptake; cost, 500 Korean won per person), and strong universal screening recommendation by mail (effect, 12% increase in screening uptake; cost, 1,000 Korean won per person). Distributional cost effectiveness analysis was conducted by calculating the cost effectiveness of strategies using the Atkinson incremental cost effectiveness ratio.
Results
All strategies were under the threshold value, which was set as the Korean gross domestic product of $25,990. In particular, the ‘strong screening recommendation to target regions’ strategy was found to be the most cost effective (incremental cost effectiveness ratio, 7,361,145 Korean won). This was also true when societal inequality aversion increased in the distributional cost effectiveness analysis.
Conclusion
The ‘strong screening recommendation to target regions’ strategy was the most cost effective approach, even when adjusting for inequality. As efficiency and equity are objectives concurrently sought in healthcare, these findings imply a need to develop appropriate economic evaluation methodologies to assess healthcare policies.

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  • 276 Download
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Nationwide Statistical Analysis of Lymphoid Malignancies in Korea
Hyewon Lee, Hyeon Jin Park, Eun-Hye Park, Hee Young Ju, Chang-Mo Oh, Hyun-Joo Kong, Kyu-Won Jung, Byung-Kiu Park, Eunyoung Lee, Hyeon-Seok Eom, Young-Joo Won
Cancer Res Treat. 2018;50(1):222-238.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2017.093
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Regional differences in the incidence of lymphoid malignancies have been reported worldwide, but there has been no large-scale epidemiologic analysis in Korea. The aim of this study was to provide a nationwide population-based statistical analysis of Korean patients with lymphoid malignancies.
Materials and Methods
The Korea Central Cancer Registry analyzed the incidence and survival of patients with lymphoid malignancies from the Korean National Cancer Incidence Database. Diseases were grouped by clinically relevant categories based on the 2008 World Health Organization classification.
Results
Overall 65,948 lymphoid diseases were identified between 1999 and 2012. The incidence of most subtypes increased with age, except for precursor cell neoplasms. Male predominance (male:female ratio=1.28:1) was observed. In 2012, annual age-standardized incidence rates per 100,000 persons of Hodgkin’s lymphoma, mature B-cell neoplasm, mature T/natural killer (NK)–cell neoplasm, and precursor cell neoplasm were 0.46, 6.60, 0.95, and 1.50, respectively, and they increased yearly from 1999. Composite Hodgkin’s and non-Hodgkin’s lymphomas were extremely rare. Survival improvement estimated using 5-year relative survival rate was observed in patients with Hodgkin’s lymphoma (71.1%- 83.0%), diffuse large B-cell lymphoma (49.5%-61.5%), plasma cell neoplasms (20.2%- 36.9%), and lymphoblastic lymphoma/leukemia (41.5%-56.3%) between 1993 and 2012. However, survival rates of T/NK-cell lymphoma (excluding cutaneous T-cell lymphoma) ranged from 40.5%-43.5% during the study period. Survival rates decreased with age in most subtypes.
Conclusion
This report presented the subtype-specific statistical analysis of lymphoid malignancies in the Korean population, showing increasing incidences and survival rates in most subtypes.

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FOXO1 Suppression is a Determinant of Acquired Lapatinib-Resistance in HER2-Positive Gastric Cancer Cells Through MET Upregulation
Jinju Park, Yiseul Choi, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Jong-Wan Park, Byung Lan Lee
Cancer Res Treat. 2018;50(1):239-254.   Published online March 24, 2017
DOI: https://doi.org/10.4143/crt.2016.580
AbstractAbstract PDFPubReaderePub
Purpose
Lapatinib is a candidate drug for treatment of trastuzumab-resistant, human epidermal growth factor receptor 2 (HER2)–positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells.
Materials and Methods
Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib. SNU-216 LR cells with FOXO1 overexpression were generated by stable transfection of a constitutively active FOXO1 mutant (FOXO1A3). HER2 and MET in SNU-216 LR cells were downregulated using RNA interference. The sensitivity of GC cells to lapatinib and/or cisplatin was determined by crystal violet assay. In addition, Western blot analysis, luciferase reporter assay and reverse transcription–polymerase chain reaction were performed.
Results
SNU-216 LR cells showed upregulations of HER2 and MET, but downregulation of FOXO1 compared to parental SNU-216 cells. FOXO1 overexpression in SNU-216 LR cells significantly suppressed resistance to lapatinib and/or cisplatin. In addition, FOXO1 negatively controlled HER2 and MET at the transcriptional level and was negatively controlled by these molecules at the post-transcriptional level. A positive crosstalk was shown between HER2 and MET, each of which increased resistance to lapatinib and/or cisplatin.
Conclusion
FOXO1 serves as an important linker between HER2 and MET signaling pathways through negative crosstalks and is a key regulator of the acquired lapatinib resistance in HER2-positive GC cells. These findings provide a rationale for establishing a novel treatment strategy to overcome lapatinib resistance in a subtype of GC patients.

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Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2
Sang Mee Hwang, Ki Chan Lee, Min Seob Lee, Kyoung Un Park
Cancer Res Treat. 2018;50(1):255-264.   Published online April 7, 2017
DOI: https://doi.org/10.4143/crt.2017.062
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Transition to next generation sequencing (NGS) for BRCA1/BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1/2.
Materials and Methods
The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1/BRCA2. Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite.
Results
Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both falsepositive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant.
Conclusion
Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

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Selection Criteria for Active Surveillance of Patients with Prostate Cancer in Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy
Chang Wook Jeong, Sung Kyu Hong, Seok Soo Byun, Seong Soo Jeon, Seong Il Seo, Hyun Moo Lee, Hanjong Ahn, Dong Deuk Kwon, Hong Koo Ha, Tae Gyun Kwon, Jae Seung Chung, Cheol Kwak, Hyung Jin Kim
Cancer Res Treat. 2018;50(1):265-274.   Published online April 14, 2017
DOI: https://doi.org/10.4143/crt.2016.477
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Korean patients with prostate cancer (PC) typically present with a more aggressive disease than patients in Western populations. Consequently, it is unclear if the current criteria for active surveillance (AS) can safely be applied to Korean patients. Therefore, this study was conducted to define appropriate selection criteria for AS for patients with PC in Korea.
Materials and Methods
We conducted a multicenter retrospective study of 2,126 patients with low risk PC who actually underwent radical prostatectomy. The primary outcome was an unfavorable disease, which was defined by non-organ confined disease or an upgrading of the Gleason score to ≥ 7 (4+3). Predictive variables of an unfavorable outcome were identified by multivariate analysis using randomly selected training samples (n=1,623, 76.3%). We compared our selected criteria to various Western criteria for the primary outcome and validated our criteria using the remaining validation sample (n=503, 23.7%).
Results
A non-organ confined disease rate of 14.9% was identified, with an increase in Gleason score ≥ 7 (4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following criteria were selected: Gleason score ≤ 6, clinical stage T1-T2a, prostate-specific antigen (PSA) ≤ 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of positive cores ≤ 2, and maximum cancer involvement in any one core ≤ 20%. These criteria provided the lowest unfavorable disease rate (11.7%) when compared to Western criteria (13.3%-20.7%), and their validity was confirmed using the validation sample (5.9%).
Conclusion
We developed AS criteria which are appropriate for Korean patients with PC. Prospective studies using these criteria are now warranted.

Citations

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No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery
Tae In Yoon, Jong Won Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Il Young Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Gyungyub Gong, Sung-Bae Kim, Su Ssan Kim, Seung Do Ahn, Minsung Chung, Sei Hyun Ahn
Cancer Res Treat. 2018;50(1):275-282.   Published online April 14, 2017
DOI: https://doi.org/10.4143/crt.2017.041
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy.
Materials and Methods
In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed.
Results
Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57).
Conclusion
Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

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    Scientific Reports.2020;[Epub]     CrossRef
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    Jasmin Zeindler, Fabienne Schwab
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    George Boundouki, Joseph Ryan Wong Sik Hee, Natalie Croghan, Katie Stocking, Andrew Pieri, Adam Critchley, Cliona C. Kirwan, James R. Harvey
    Breast Cancer Research and Treatment.2019; 176(2): 311.     CrossRef
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    Archives of Gynecology and Obstetrics.2019; 300(2): 365.     CrossRef
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Clinical Significance of Discordance between Carcinoembryonic Antigen Levels and RECIST in Metastatic Colorectal Cancer
In-Ho Kim, Ji Eun Lee, Ji Hyun Yang, Joon Won Jeong, Sangmi Ro, Seong Taek Oh, Jun-Gi Kim, Moon Hyung Choi, Myung Ah Lee
Cancer Res Treat. 2018;50(1):283-292.   Published online May 8, 2017
DOI: https://doi.org/10.4143/crt.2016.537
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the prognostic implications of carcinoembryonic antigen (CEA) levels that are inconsistent with Response Evaluation Criteria in Solid Tumor (RECIST) responses in metastatic colorectal cancer patients.
Materials and Methods
We retrospectively evaluated 360 patients with at least one measurable lesion who received first-line palliative chemotherapy. CEA-response was defined as CEA-complete response (CR; CEA normalization), CEA-partial response (PR; ≥ 50% decrease in CEA levels), CEA-progressive disease (PD; ≥ 50% increase in CEA levels), and CEA-stable disease (SD; non-CR/PR/PD). Overall survival (OS) and progression-free survival (PFS) were evaluated according to CEA-response.
Results
In RECIST-PR patients, poorer CEA-response was associated with disease progression at the subsequent evaluation. In RECIST-SD patients, CEA-CR and -PR were associated with lower disease progression rates than CEA-PD at the subsequent evaluation. Correlations between survival outcome and CEA-response in same-category RECIST patients were assessed. In RECIST-PR patients, discordant CEA-response (CEA-PD/SD) was associated with poorer survival than CEA-CR/PR (median OS and PFS, 44.0 and 15.4 [CEA-CR], 28.9 and 12.5 [CEA-PR], 21.0 and 9.8 [CEA-SD], and 13.0 and 7.0 [CEA-PD] months, respectively; all p < 0.001). In RECIST-SD patients, favorable CEA-response produced better survival (median OS and PFS, 26.8 and 21.0 [CEA-CR], 21.0 and 11.0 [CEA-PR], 16.1 and 8.2 [CEA-SD], and 12.2 and 6.0 [CEA-PD] months, respectively; all p < 0.001). RECIST-PD patients with CEA-CR showed longer OS than those with CEA-PD. Multivariate analysis demonstrated that discordant CEA-response is a powerful prognostic factor for RECIST-PR and RECIST-SD patients.
Conclusion
Among patients of the same RECIST-response categories, CEA-response patterns are significantly prognostic and strongly predictive of subsequent evaluation outcomes.

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    Katsuji Sawai, Takanori Goi, Youhei Kimura, Kenji Koneri
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Second Primary Cancer Risk among Kidney Cancer Patients in Korea: A Population-Based Cohort Study
Jae Young Joung, Whi-An Kwon, Jiwon Lim, Chang-Mo Oh, Kyu-Won Jung, Sung Han Kim, Ho Kyung Seo, Weon Seo Park, Jinsoo Chung, Kang Hyun Lee, Young-Joo Won
Cancer Res Treat. 2018;50(1):293-301.   Published online April 19, 2017
DOI: https://doi.org/10.4143/crt.2016.543
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Secondary primary cancers (SPCs) commonly arise in patients with renal cell carcinoma (RCC). We designed the present study to estimate the SPC incidence in Korean patients with RCC.
Materials and Methods
The study cohort was population-based and consisted of 40,347 individuals from the Korean Central Cancer Registry who were diagnosed with primary renal cancer between 1993 and 2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different ages at diagnosis, latencies, diagnostic periods, and treatments.
Results
For patients with primary RCC, the risk of developing a SPC was higher than the risk of developing cancer in the general population (SIR, 1.13; 95% confidence interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients with RCC than in the general population. However, the relative incidence of gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in young patients (< 30 years) with RCC, but reduced in older (≥ 30) patients with RCC. Patients with advanced RCC died prematurely, regardless of SPC development. In contrast, those with early-stage RCC survived for longer periods, although SPC development affected their post-RCC survival. After SPC development, women had better survival than men.
Conclusion
In Korean patients with primary RCC, the incidence of SPC was 13% higher than the incidence of cancer in the general population. These findings may play important roles in the conduct of follow-up evaluations and education for patients with RCC.

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