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Volume 51(3); July 2019
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Review Article
Autoimmune Diseases and Gastric Cancer Risk: A Systematic Review and Meta-Analysis
Minkyo Song, Gonzalo Latorre, Danisa Ivanovic-Zuvic, M. Constanza Camargo, Charles S. Rabkin
Cancer Res Treat. 2019;51(3):841-850.   Published online May 3, 2019
DOI: https://doi.org/10.4143/crt.2019.151
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Autoimmunity is an alternative etiology of gastric inflammation, the initiating event in the gastric carcinogenic cascade. This mechanism may be an increasingly important cause of gastric cancer with the waning prevalence of its primary etiologic factor, chronic Helicobacter pylori infection.
Materials and Methods
PubMed and EMBASE were searched up to September 2018. Autoimmunity and 96 specific manifestations were considered for associations with gastric cancer risk. Random effects analysis was used to calculate pooled relative risk estimates (RR) and 95% confidence intervals (CI).
Results
We found a total of 52 observational studies representing 30 different autoimmune diseases. Overall, the presence of an autoimmune condition was associated with a gastric cancer pooled RR of 1.37 (95% CI, 1.24 to 1.52). Among the 24 autoimmune conditions with two or more independent reports, nine were significantly associated with increased gastric cancer risk: dermatomyositis (RR, 3.69; 95% CI, 1.74 to 7.79), pernicious anemia (RR, 2.84; 95% CI, 2.30 to 3.50), Addison disease (RR, 2.11; 95% CI, 1.26 to 3.53), dermatitis herpetiformis (RR, 1.74; 95% CI, 1.02 to 2.97; n=3), IgG4-related disease (RR, 1.69; 95% CI, 1.00 to 2.87), primary biliary cirrhosis (RR, 1.64; 95% CI, 1.13 to 2.37), diabetes mellitus type 1 (RR, 1.41; 95% CI, 1.20 to 1.67), systemic lupus erythematosus (RR, 1.37; 95% CI, 1.01 to 1.84), and Graves disease (RR, 1.27; 95% CI, 1.06 to 1.52).
Conclusion
Our analysis documents the wide range of autoimmune diseases associated with gastric cancer. These associations may reflect unreported links between these conditions and autoimmune gastritis. Further studies are warranted to investigate potential causal mechanisms.

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    ii ivanov
    Medicine of Extreme Situations.2020;[Epub]     CrossRef
  • Role of heredity, endogenous and exogenous factors in gastric cancer
    PV Ershov
    Medicine of Extreme Situations.2020;[Epub]     CrossRef
  • Editorial: determinants of diagnostic delay in autoimmune atrophic gastritis—a salutary lesson
    Marjorie M. Walker
    Alimentary Pharmacology & Therapeutics.2019; 50(4): 458.     CrossRef
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    Marjorie M. Walker, Nicholas J. Talley
    Current Gastroenterology Reports.2019;[Epub]     CrossRef
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  • 526 Download
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  • 45 Crossref
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Special Article
Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients
Jung Hye Kwon, Sang-Cheol Lee, Myung Ah Lee, Yu Jung Kim, Jung Hun Kang, Jin Young Kim, Hyo Jin Lee, Woo Kyun Bae, Mi-Jung Kim, Eui Kyu Chie, Jin Kim, Yeul Hong Kim, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2019;51(3):851-860.   Published online June 7, 2019
DOI: https://doi.org/10.4143/crt.2019.137
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea.
Materials and Methods
Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution.
Results
In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians.
Conclusion
Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

Citations

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Original Articles
A Phage Display-Identified Peptide Selectively Binds to Kidney Injury Molecule-1 (KIM-1) and Detects KIM-1-Overexpressing Tumors in vivo
Md. Enamul Haque, Fatima Khan, Lianhua Chi, Smriti Gurung, Sri Murugan Poongkavithai Vadevoo, Rang-Woon Park, Dong-Kyu Kim, Sang Kyoon Kim, Byungheon Lee
Cancer Res Treat. 2019;51(3):861-875.   Published online October 1, 2018
DOI: https://doi.org/10.4143/crt.2018.214
AbstractAbstract PDFPubReaderePub
Purpose
This study was carried out to identify a peptide that selectively binds to kidney injury molecule-1 (KIM-1) by screening a phage-displayed peptide library and to use the peptide for the detection of KIM-1overexpressing tumors in vivo.
Materials and Methods
Biopanning of a phage-displayed peptide library was performed on KIM-1–coated plates. The binding of phage clones, peptides, and a peptide multimer to the KIM-1 protein and KIM-1–overexpressing and KIM-1–low expressing cells was examined by enzyme-linked immunosorbent assay, fluorometry, and flow cytometry. A biotin-peptide multimer was generated using NeutrAvidin. In vivo homing of the peptide to KIM-1–overexpressing and KIM1–low expressing tumors in mice was examined by whole-body fluorescence imaging.
Results
A phage clone displaying the CNWMINKEC peptide showed higher binding affinity to KIM-1 and KIM-1–overexpressing 769-P renal tumor cells compared to other phage clones selected after biopanning. The CNWMINKEC peptide and a NeutrAvidin/biotin-CNWMINKEC multimer selectively bound to KIM-1 over albumin and to KIM-1–overexpressing 769-P cells and A549 lung tumor cells compared to KIM-1-low expressing HEK293 normal cells. Co-localization and competition assays using an anti–KIM-1 antibody demonstrated that the binding of the CNWMINKEC peptide to 769-P cells was specifically mediated by KIM-1. The CNWMINKEC peptide was not cytotoxic to cells and was stable for up to 24 hours in the presence of serum. Whole-body fluorescence imaging demonstrated selective homing of the CNWM-INKEC peptide to KIM-1–overexpressing A498 renal tumor compared to KIM1–low expressing HepG2 liver tumor in mice.
Conclusion
The CNWMINKEC peptide is a promising probe for in vivo imaging and detection of KIM-1‒overexpressing tumors.

Citations

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    International Journal of Peptide Research and Therapeutics.2021; 27(3): 1741.     CrossRef
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  • 387 Download
  • 11 Web of Science
  • 8 Crossref
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Comparison of the 7th and the 8th AJCC Staging System for Non-metastatic D2-Resected Lymph Node–Positive Gastric Cancer Treated with Different Adjuvant Protocols
Jeong Il Yu, Do Hoon Lim, Jeeyun Lee, Won Ki Kang, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Seung Tae Kim, Su Jin Lee, Sung Kim, Tae Sung Sohn, Jun Ho Lee, Ji Yeong An, Min Gew Choi, Jae Moon Bae, Heejin Yoo, Kyunga Kim
Cancer Res Treat. 2019;51(3):876-885.   Published online October 1, 2018
DOI: https://doi.org/10.4143/crt.2018.401
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Commission on Cancer (AJCC) staging system for gastric cancer (GC) patients.
Materials and Methods
A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability.
Results
In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT.
Conclusion
Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.

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Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer
Ah-Rong Nam, Ji-Won Kim, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2019;51(3):886-900.   Published online October 1, 2018
DOI: https://doi.org/10.4143/crt.2018.375
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.
Materials and Methods
We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.
Results
Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.
Conclusion
Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

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  • COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma
    Jiahui Liu, Dexing Han, Junfeng Xuan, Jinye Xie, Weijia Wang, Quan Zhou, Kang Chen
    Aging.2024; 16(6): 5264.     CrossRef
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    Liping Wang, Xiaojiao Zeng, Gui Yang, Guohong Liu, Yunbao Pan
    Heliyon.2022; 8(12): e12553.     CrossRef
  • Jab1/Cops5: a promising target for cancer diagnosis and therapy
    Chunjue Yuan, Dong Wang, Guohong Liu, Yunbao Pan
    International Journal of Clinical Oncology.2021; 26(7): 1159.     CrossRef
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Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin
Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(3):901-909.   Published online October 4, 2018
DOI: https://doi.org/10.4143/crt.2018.326
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

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    Gael S. Roth, Loic Verlingue, Matthieu Sarabi, Jean-Frédéric Blanc, Emmanuel Boleslawski, Karim Boudjema, Anne-Laure Bretagne-Bignon, Marine Camus-Duboc, Romain Coriat, Gilles Créhange, Thierry De Baere, Christelle de la Fouchardière, Clarisse Dromain, Ju
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    Do-Youn Oh, Aiwu Ruth He, Mohamed Bouattour, Takuji Okusaka, Shukui Qin, Li-Tzong Chen, Masayuki Kitano, Choong-kun Lee, Jin Won Kim, Ming-Huang Chen, Thatthan Suksombooncharoen, Masafumi Ikeda, Myung Ah Lee, Jen-Shi Chen, Piotr Potemski, Howard A Burris,
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Retrospective Study of the Significant Predictive Role of Inflammatory Degree in Initial and Repeat Prostate Biopsy Specimens for Detecting Prostate Cancer
Sung Han Kim, Boram Park, Jae Young Joung, Jinsoo Chung, Ho Kyung Seo, Kang Hyun Lee, Weon Seo Park
Cancer Res Treat. 2019;51(3):910-918.   Published online October 2, 2018
DOI: https://doi.org/10.4143/crt.2018.314
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to determine whether histologic inflammation (HI) in initial and repeat prostate biopsy specimens was significantly associated with the detection of prostate cancer.
Materials and Methods
Between 2005 and 2017, the clinicopathological records of patients with high prostatespecific antigen (PSA) levels who underwent initial and repeat prostate biopsies were retrospectively reviewed. The presence of HI and its degree in each biopsied specimen were interpreted by one uropathologist with 20 years of experience. The association between HI and cancer diagnosis was statistically assessed, with p < 0.05 considered significant, and the cancer and non-cancer groups were compared.
Results
Among the 522 patients with a median PSA levels of 6.5 ng/dL, including 258 (49.4%) whose cancer was diagnosed following repeat biopsy, the median degrees of HI in the initial and repeat biopsies were 25.0% and 41.7%, respectively. Furthermore, 211 (40.4%) and 247 (47.3%) patients had HI (> 0%) on biopsied specimens, respectively. Comparison of the cancer and noncancer groups revealed that a greater rate of HI specimens in the initial biopsy was associated with fewer prostate cancer diagnoses following repeat biopsy (p < 0.001). Other comparisons between the cancer and non-cancer groups showed that the cancer group had a significantly higher rate of hypertension, whereas those non-cancer group had a significantly higher rate of benign prostatic hyperplasia and prostatitis (p < 0.05).
Conclusion
A finding of a lesser degree of HI in the initial and a greater degree of HI in the repeat biopsied specimens was associated with the higher probability of cancer diagnosis in patients with high PSA levels.

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  • Growth and differentiation factor 15 and NF‐κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection
    Benjamin A. Rybicki, Sudha M. Sadasivan, Yalei Chen, Oleksandr Kravtsov, Watchareepohn Palangmonthip, Kanika Arora, Nilesh S. Gupta, Sean Williamson, Kevin Bobbitt, Dhananjay A. Chitale, Deliang Tang, Andrew G. Rundle, Kenneth A. Iczkowski
    Cancer Medicine.2021; 10(9): 3013.     CrossRef
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  • 144 Download
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Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial
Xueying Li, He Huang, Bing Xu, Hongqiang Guo, Yingcheng Lin, Sheng Ye, Jiqun Yi, Wenyu Li, Xiangyuan Wu, Wei Wang, Hongyu Zhan, Derong Xie, Jiewen Peng, Yabing Cao, Xingxiang Pu, Chengcheng Guo, Huangming Hong, Zhao Wang, Xiaojie Fang, Yong Zhou, Suxia Lin, Qing Liu, Tongyu Lin
Cancer Res Treat. 2019;51(3):919-932.   Published online October 2, 2018
DOI: https://doi.org/10.4143/crt.2018.230
AbstractAbstract PDFPubReaderePub
Purpose
Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population.
Materials and Methods
Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities.
Results
Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21.
Conclusion
R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

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  • Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival
    Wan‐Ru Zhang, Xin Liu, Qiu‐Zi Zhong, Tao Wu, Yong Yang, Bo Chen, Hao Jing, Yuan Tang, Jing Jin, Yue‐Ping Liu, Yong‐Wen Song, Hui Fang, Ning‐Ning Lu, Ning Li, Yi‐Rui Zhai, Wen‐Wen Zhang, Shu‐Lian Wang, Fan Chen, Lin Yin, Shu‐Nan Qi, Ye‐Xiong Li
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    Yan Qin, Yongping Song, Dong Wang, Ou Bai, Jifeng Feng, Xiuhua Sun, Lihua Qiu, Jianmin Yang, Yu Yang, Zhao Wang, Jianda Hu, Huaqing Wang, Hang Su, Zhengming Jin, Wenbin Qian, Chuan Jin, Mingzhi Zhang, Ding Yu, Li Liu, Guoan Chen, Yarong Li, Tao Sun, Jie J
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    Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong
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    Lorenz Thurner, Marita Ziepert, Christian Berdel, Christian Schmidt, Peter Borchmann, Dominic Kaddu-Mulindwa, Andreas Viardot, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Bernd Metzner, Gerald Wulf, Eva Lengfelder, Ulrich B. Keller, Norbert Fr
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    Aleksander Sergeevich Luchinin
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    Shunfeng Hu, Na Chen, Kang Lu, Changqing Zhen, Xiaohui Sui, Xiaosheng Fang, Ying Li, Yingshu Luo, Xiangxiang Zhou, Xin Wang
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    Ye Zhou, Chao Zhang, Yingying Gong, Linqing Yang, Yunfei Wang
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    Svetlana Valer'evna Samarina, A.S. Luchinin, N.V. Minaeva, I.V. Paramonov, D.A. D'yakonov, E.V. Vaneeva, V.A. Rosin, S.V. Gritsaev
    Clinical oncohematology.2019; 12(4): 25.     CrossRef
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The Health Burden of Cancer Attributable to Obesity in Korea: A Population-Based Cohort Study
Joo Eun Lee, Chung Mo Nam, Sang Gyu Lee, Sohee Park, Tae Hyun Kim, Eun-Cheol Park
Cancer Res Treat. 2019;51(3):933-940.   Published online October 4, 2018
DOI: https://doi.org/10.4143/crt.2018.301
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Considering the health impact of obesity and cancer, it is important to estimate the burden of cancer attributable to high body mass index (BMI). Therefore, the present study attempts to measure the health burden of cancer attributable to excess BMI, according to cancer sites.
Materials and Methods
The present study used nationwide medical check-up sample cohort data (2002-2015). The study subjects were 496,390 individuals (268,944 men and 227,446 women). We first calculated hazard ratio (HR) in order to evaluate the effect of excess BMI on cancer incidence and mortality. Then, the adjusted HR values and the prevalence of excess BMI were used to calculate the population attributable risk. This study also used the Global Burden of Disease method, to examine the health burden of obesity-related cancers attributable to obesity.
Results
The highest disability-adjusted life year (DALY) values attributable to overweight and obesity in men were shown in liver cancer, colorectal cancer, and gallbladder cancer. Among women, colorectal, ovarian, and breast (postmenopausal) cancers had the highest DALYs values attributable to overweight and obesity. Approximately 8.0% and 12.5% of cancer health burden (as measured by DALY values) among obesity-related cancers in men and women, respectively, can be prevented.
Conclusions
Obesity has added to the health burden of cancer. By measuring the proportion of cancer burden attributable to excess BMI, the current findings provide support for the importance of properly allocating healthcare resources and for developing cancer prevention strategies to reduce the future burden of cancer.

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    Matteo Di Maso, Claudio Pelucchi, Giulia Collatuzzo, Gianfranco Alicandro, Matteo Malvezzi, Fabio Parazzini, Eva Negri, Paolo Boffetta, Carlo La Vecchia, Federica Turati
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    Xiaolong Wang, Lin Li, Mingjian Bai, Jiaxin Zhao, Xiaojie Sun, Yu Gao, Haitao Yu, Xia Chen, Chunjing Zhang
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    Zhangjian Zhou, Xuan Wang, Xueting Ren, Linghui Zhou, Nan Wang, Huafeng Kang
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Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review
Byung Su Kwon, Jung Mi Byun, Hyun Joo Lee, Dae Hoon Jeong, Tae Hwa Lee, Kyung-Hwa Shin, Dong Soo Suh, Ki Hyung Kim
Cancer Res Treat. 2019;51(3):941-950.   Published online October 8, 2018
DOI: https://doi.org/10.4143/crt.2018.312
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients.
Materials and Methods
Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review.
Results
Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC).
Conclusion
The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

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Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib
Seulki Kim, Tae Min Kim, Dong-Wan Kim, Soyeon Kim, Miso Kim, Yong-Oon Ahn, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2019;51(3):951-962.   Published online October 10, 2018
DOI: https://doi.org/10.4143/crt.2018.052
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.
Materials and Methods
We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.
Results
We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.
Conclusion
Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.

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Laparoscopy versus Open Nephroureterectomy in Prognostic Outcome of Patients with Advanced Upper Tract Urothelial Cancer: A Retrospective, Multicenter, Propensity-Score Matching Analysis
Sung Han Kim, Mi Kyung Song, Jung Kwon Kim, Bumsik Hong, Seok Ho Kang, Ja Hyeon Ku, Byong Chang Jeong, Ho Kyung Seo, On behalf of Urothelial Cancer-Advanced Research and Treatment (UCART) Study Group
Cancer Res Treat. 2019;51(3):963-972.   Published online October 12, 2018
DOI: https://doi.org/10.4143/crt.2018.465
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare oncologic outcomes between open nephroureterectomy (ONU) and laparoscopic nephroureterectomy (LNU) in patients with upper tract urothelial carcinoma.
Materials and Methods
The medical records of consecutive ONU and LNU cases from five tertiary institutions were retrospectively analyzed between 2000 and 2012. The propensity-score matching methodology was used to compare the two surgical approaches in terms of age, body mass index, American Society of Anesthesiologists score, tumor location, grade, pathologic T and N categories, the presence of lymphovascular invasion, and follow-up duration. The Kaplan-Meier with log-rank tests and clustered Cox regression were used to compare the estimated rates of survival for each surgical approach and to investigate the effect of the surgical approach on each prognostic outcome.
Results
Six hundred thirty-eight propensity-score matching pairs (n=1,276) were compared; LNU was significantly better than ONU in all types of survival, including intravesical recurrencefree survival (IVRFS), disease-free survival, overall survival (OS), and cancer-specific survival (CSS) (p < 0.05). The 3-year OS and CSS rates were significantly higher with LNU than with ONU (p < 0.05). Compared with ONU, LNU had significantly better 3-year OS and CSS rates (82.9% and 86.2% vs. 78.3% and 81.8%); there were no differences at 5 years. In subgroup analysis of the early-staged group, advanced-stage group, lymph node–positive group, and lymph node–negative group, the two approaches did not significantly affect prognostic outcomes, except LNU improved the IVRFS in the lymph node–negative or no history of previous bladder cancer group.
Conclusion
LNU had a significantly better prognostic outcome than ONU after propensity-score matching.

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Improved Survival of Cancer Patients Admitted to the Intensive Care Unit between 2002 and 2011 at a U.S. Teaching Hospital
Christopher Martin Sauer, Jinghui Dong, Leo Anthony Celi, Daniele Ramazzotti
Cancer Res Treat. 2019;51(3):973-981.   Published online October 10, 2018
DOI: https://doi.org/10.4143/crt.2018.360
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Cancer patients are at increased risk of treatment- or disease-related admission to the intensive care unit. Over the past decades, both critical care and cancer care have improved substantially. Due to increased cancer-specific survival, we hypothesized that the number of cancer patients admitted to the intensive care unit (ICU) and survival have increased.
Materials and Methods
MIMIC-III was used to study trends and outcomes of cancer patients admitted to the ICU between 2002 and 2011. Multiple logistic regression analysis was performed to adjust for confounders of mortality.
Results
Among 41,468 patients analyzed, 1,083 were hemato-oncologic, 4,330 were oncologic and 66 patients had both a hematological and solid malignancy. Admission numbers more than doubled and the proportion of cancer patients in the ICU increased steadily from 2002 to 2011. In both the univariate and multivariate analyses, solid cancers and hematologic cancers were strongly associated with 28-day mortality. This association was even stronger for 1-year mortality, with odds ratios of 4.02 (95% confidence interval [CI], 3.69 to 4.38) and 2.25 (95% CI, 1.93 to 2.62), respectively. Over the 10-year study period, both 28-day and 1-year mortality decreased, with hematologic patients showing the strongest annual adjusted decrease in the odds of death. There was considerable heterogeneity among solid cancer types.
Conclusion
Between 2002 and 2011, the number of cancer patients admitted to the ICU more than doubled, while clinical severity scores remained overall unchanged, suggesting improved treatment. Although cancer patients had higher mortality rates, both 28-day and 1-year mortality of hematologic patients decreased faster than that of non-cancer patients, while mortality rates of cancer patients strongly depended on cancer type.

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Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013
Lu-Lu Zhang, Guo-Hong Li, Yi-Yang Li, Zhen-Yu Qi, Ai-Hua Lin, Ying Sun
Cancer Res Treat. 2019;51(3):982-991.   Published online October 11, 2018
DOI: https://doi.org/10.4143/crt.2018.298
AbstractAbstract PDFPubReaderePub
Purpose
The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized.
Methods
and Materials Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival.
Results
Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival.
Conclusion
This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Citations

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    Fen Xue, Xiaoshuang Niu, Chaosu Hu, Xiayun He
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Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan
Muhammad Usman Rashid, Faiz Ali Khan, Noor Muhammad, Asif Loya, Ute Hamann
Cancer Res Treat. 2019;51(3):992-1000.   Published online October 11, 2018
DOI: https://doi.org/10.4143/crt.2018.356
AbstractAbstract PDFPubReaderePub
Purpose
Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan.
Materials and Methods
PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations.
Results
A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated.
Conclusion
Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

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  • Prevalence of FANCM germline variants in BRCA1/2 negative breast and/or ovarian cancer patients from Pakistan
    Muhammad Usman Rashid, Noor Muhammad, Umara Shehzad, Faiz Ali Khan, Asif Loya, Ute Hamann
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    Sadia Ajaz, Sani-e-Zehra Zaidi, Saleema Ali, Aisha Siddiqa, Muhammad Ali Memon
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  • 333 Download
  • 7 Web of Science
  • 8 Crossref
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Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06 Study
Eunah Chung, Jae Myoung Noh, Kyu Chan Lee, Jin Hee Kim, Weon Kuu Chung, Yang-Gun Suh, Jung Ae Lee, Ki Ho Seol, Hong Gyun Wu, Yeon Sil Kim, O Kyu Noh, Jae Won Park, Dong Soo Lee, Jihae Lee, Young Suk Kim, Woo-Yoon Park, Min Kyu Kang, Sunmi Jo, Yong Chan Ahn
Cancer Res Treat. 2019;51(3):1001-1010.   Published online October 15, 2018
DOI: https://doi.org/10.4143/crt.2018.415
AbstractAbstract PDFPubReaderePub
Purpose
Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study.
Materials and Methods
Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated.
Results
In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol.
Conclusion
The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.

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    Chloe Brooks, Elizabeth Miles, Peter J Hoskin
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Axillary Lymph Node Dissection Does Not Improve Post-mastectomy Overall or Disease-Free Survival among Breast Cancer Patients with 1-3 Positive Nodes
Ji Hyeon Joo, Su Ssan Kim, Byung Ho Son, Seung Do Ahn, Jin Hong Jung, Eun Kyung Choi, Sei Hyun Ahn, Jong Won Lee, Hee Jeong Kim, Beom Seok Ko
Cancer Res Treat. 2019;51(3):1011-1021.   Published online October 16, 2018
DOI: https://doi.org/10.4143/crt.2018.438
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Axillary lymph node dissection (ALND) may be avoidable for breast cancer patients with 1-2 positive lymph nodes (LN) after breast-conserving therapy. However, the effects of ALND after mastectomy remain unclear because radiation is not routinely used. Herein, we compared the benefits of post-mastectomy ALND versus sentinel node biopsy (SNB) alone for breast cancer patients with 1-3 metastatic LNs.
Materials and Methods
A total of 1,697 patients with pN1 disease who underwent mastectomy during 2000-2015 were identified from an institutional database. Outcomes were compared using the inverse probability of treatment weighted method.
Results
Patients who underwent SNB tended to have smaller tumors, a lower histology grade, a lower number of positive LNs, and better immunohistochemical findings. After correcting all confounding factors regarding patient, tumor, and adjuvant treatment, the SNB and ALND groups did not differ in terms of overall survival (OS) and disease-free survival (DFS), distant metastasis and locoregional recurrence. The 10-year DFS and OS rates were 83% and 84%, respectively, during a median follow-up period of 93 months.
Conclusion
ALND did not improve post-mastectomy survival outcomes among patients with N1 breast cancer, even after adjusting for all histopathologic and treatment-related factors.

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Dietary Intake of Omega-3 fatty acids and Endocrine-related Gynecological Cancer: A Meta-Analysis of Observational Studies
Tung Hoang, Seung-Kwon Myung, Thu Thi Pham
Cancer Res Treat. 2019;51(3):1022-1032.   Published online October 17, 2018
DOI: https://doi.org/10.4143/crt.2018.473
Retraction in: Cancer Res Treat 2020;52(1):334
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Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer
Young Ae Cho, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
Cancer Res Treat. 2019;51(3):1033-1040.   Published online October 18, 2018
DOI: https://doi.org/10.4143/crt.2018.447
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.
Materials and Methods
In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.
Results
Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.
Conclusion
Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals’ genetic risk.

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Comparison of Breast Conserving Surgery Followed by Radiation Therapy with Mastectomy Alone for Pathologic N1 Breast Cancer Patients in the Era of Anthracycline Plus Taxane-Based Chemotherapy: A Multicenter Retrospective Study (KROG 1418)
Gyu Sang Yoo, Won Park, Jeong Il Yu, Doo Ho Choi, Yeon-Joo Kim, Kyung Hwan Shin, Chan Woo Wee, Kyubo Kim, Kyung Ran Park, Yong Bae Kim, Sung Ja Ahn, Jong Hoon Lee, Jin Hee Kim, Mison Chun, Hyung-Sik Lee, Jung Soo Kim, Jihye Cha
Cancer Res Treat. 2019;51(3):1041-1051.   Published online November 1, 2018
DOI: https://doi.org/10.4143/crt.2018.424
AbstractAbstract PDFPubReaderePub
Purpose
We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy.
Materials and Methods
We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups.
Results
The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly.
Conclusion
There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III.

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    Yu Zhang, Fuxiu Ye, Yun Teng, Jin Zheng, Chunlu Li, Ruilan Ma, Haichen Zhang
    Frontiers in Oncology.2023;[Epub]     CrossRef
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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Res Treat. 2019;51(3):1052-1063.   Published online October 24, 2018
DOI: https://doi.org/10.4143/crt.2018.411
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

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  • NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
    Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
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    Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel E. Johnson
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    Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
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    Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
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    Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
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  • Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
    Daniel E. Gracilla, Praveen Kumar Korla, Ming‐Tsung Lai, An‐Jen Chiang, Wen‐Shiung Liou, Jim Jinn‐Chyuan Sheu
    Molecular Oncology.2020; 14(12): 3065.     CrossRef
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    Eun Kyung Kim, Yoon Ah Cho, Mi-kyoung Seo, Hyunmi Ryu, Byoung Chul Cho, Yoon Woo Koh, Sun Och Yoon
    Scientific Reports.2019;[Epub]     CrossRef
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    Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
    Head & Neck.2019; 41(1): 198.     CrossRef
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Oncologic, Perioperative Outcomes of Female Radical Cystectomy: Results from a Multicenter Study in Korea
Ji Sung Shim, Ho Kyung Seo, Ja Hyeon Ku, Byong Chang Jeong, Bumsik Hong, Seok Ho Kang, UCART (Urothelial Cancer-Advanced Research and Treatment Group in Korea) Group
Cancer Res Treat. 2019;51(3):1064-1072.   Published online October 30, 2018
DOI: https://doi.org/10.4143/crt.2018.515
AbstractAbstract PDFPubReaderePub
Purpose
The lower incidence of bladder cancer among women has led to a lack of information on female radical cystectomy (RC). This study aimed to analyze the characteristics related with female RC in a cohort from multiple academic institutions.
Materials and Methods
This was a retrospective review of 384 female patients who underwent RC for bladder cancer. Epidemiologic, perioperative variables including urologic referral periodwith consequent pathologic stage distributions were assessed. The changes in surgical techniques over time were illustrated. Also, we evaluated recurrence-free survival (RFS) at 2 and 5 years and overall survival (OS) at 5 years with stage-specific analyses using the Kaplan-Meier method.
Results
The mean follow-up time was 35 months (interquartile rage [IQR], 9 to 55). The average time to urologic referral with initial symptoms was 5.5 (IQR, 1 to 6) months and over 20% of patients visited clinics after 6 months. In subsequent stage distributions according to referral period, T2 or higher stage distributions were abruptly increased after 1 year. Overall 2-year/5-year RFS rates were 0.72/0.57 and 5-year OS was 0.61. Notable surgical descriptions were as follows: 91% of patients underwent open RC; 80% of patients underwent an ileal conduit; and 83% of patients received anterior exenteration. However, the proportions of robotic surgery, orthotopic neobladder and organ sparing cystectomy have increased recen-tly.
Conclusion
We identified the general characteristics and changes in pattern of female RC. Our results also suggest that women are susceptible to delays in referral to an urologist and are at greater risk for worse prognosis.

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  • Perioperative, oncological, and survival outcomes of robotic radical cystectomy with urinary diversion in females
    Varun V. Agarwal, B. Yuvaraja Thyavihally, Santosh Subhash Waigankar, Preetham Dev, Abhinav P. Pednekar, Diptiman Roy, Nevitha Athikari, Meenal Hastak, Naresh Badlani, D. Harshwardhan Pokharkar, Nagaraja Sekhar Ayyalasomayajula, Archan Khandekar, Ashish A
    Indian Journal of Urology.2023; 39(1): 27.     CrossRef
  • Safety and Efficacy of Reproductive Organ-Sparing Radical Cystectomy in Women With Variant Histology and Advanced Stage
    Sunil H. Patel, Shirley Wang, Meredith R. Metcalf, Natasha Gupta, Andrew Gabrielson, Esther Lee, Mary Rostom, Phil Pierorazio, Armine Smith, Noah Hahn, Mark Schoenberg, Max Kates, Jean Hoffman-Censits, Trinity J. Bivalacqua
    Clinical Genitourinary Cancer.2022; 20(1): 60.     CrossRef
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    Tae Il Noh, Ji Sung Shim, Sung Gu Kang, Jun Cheon, Jong Hyun Pyun, Seok Ho Kang
    Frontiers in Oncology.2022;[Epub]     CrossRef
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A Nomogram for Predicting the Oncotype DX Recurrence Score in Women with T1-3N0-1miM0 Hormone Receptor‒Positive, Human Epidermal Growth Factor 2 (HER2)‒Negative Breast Cancer
Sae Byul Lee, Junetae Kim, Guiyun Sohn, Jisun Kim, Il Yong Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Sei-Hyun Ahn, Jong Won Lee, Kyung Hae Jung
Cancer Res Treat. 2019;51(3):1073-1085.   Published online November 1, 2018
DOI: https://doi.org/10.4143/crt.2018.357
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients.
Materials and Methods
Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay.
Results
Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95).
Conclusion
The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.

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    Wei Wang, Wenqian Lei, Ziru Fang, Ruiyuan Jiang, Xiaojia Wang
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    Asim Dhungana, Augustin Vannier, Fangyuan Zhao, Jincong Q. Freeman, Poornima Saha, Megan Sullivan, Katharine Yao, Elbio M. Flores, Olufunmilayo I. Olopade, Alexander T. Pearson, Dezheng Huo, Frederick M. Howard
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    Ji Min Kim, Eun Yoon Cho
    Journal of Breast Cancer.2024; 27(3): 201.     CrossRef
  • Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer
    Akio Shibata, Nobuko Tamura, Keiichi Kinowaki, Aya Nishikawa, Kiyo Tanaka, Yoko Kobayashi, Takuya Ogura, Yuko Tanabe, Hidetaka Kawabata
    Breast Cancer.2024; 31(6): 1018.     CrossRef
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    Ji Hyun Youk, Eun Ju Son, Joon Jeong, Hye Mi Gweon, Na Lae Eun, Jeong-Ah Kim
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    Min Chong Kim, Sun Young Kwon, Jung Eun Choi, Su Hwan Kang, Young Kyung Bae
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    Ran Song, Dong-Eun Lee, Eun-Gyeong Lee, Seeyoun Lee, Han-Sung Kang, Jai Hong Han, Keun Seok Lee, Sung Hoon Sim, Heejung Chae, Youngmee Kwon, Jaeyeon Woo, So-Youn Jung
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    Kwang Hyun Yoon, Suk Jun Lee, Yujin Kim, Jee Hyun Ahn, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Seho Park
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    Hongxiao Li, Jigang Wang, Zaibo Li, Melad Dababneh, Fusheng Wang, Peng Zhao, Geoffrey H. Smith, George Teodoro, Meijie Li, Jun Kong, Xiaoxian Li
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©
    Matthew G. Davey, Amirhossein Jalali, Éanna J. Ryan, Ray P. McLaughlin, Karl J. Sweeney, Michael K. Barry, Carmel M. Malone, Maccon M. Keane, Aoife J. Lowery, Nicola Miller, Michael J. Kerin
    Journal of Personalized Medicine.2022; 12(7): 1117.     CrossRef
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    Austin D. Williams, Kate R. Pawloski, Hannah Y. Wen, Varadan Sevilimedu, Donna Thompson, Monica Morrow, Mahmoud El-Tamer
    Breast Cancer Research and Treatment.2022; 196(3): 565.     CrossRef
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    Jaime A. Pardo, Betty Fan, Alessandra Mele, Stephanie Serres, Monica G. Valero, Isha Emhoff, Amulya Alapati, Ted A. James
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    Jing Yu, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen
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    Matthew G. Davey, Éanna J. Ryan, Sami Abd Elwahab, Jessie A. Elliott, Peter F. McAnena, Karl J. Sweeney, Carmel M. Malone, Ray McLaughlin, Michael K. Barry, Maccon M. Keane, Aoife J. Lowery, Michael J. Kerin
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    Bo Bae Choi
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    Minji Koh, Jinhong Jung, Su Ssan Kim, Seung Do Ahn, Eun Kyung Choi, Il Yong Chung, Jong Won Lee, Sung-Bae Kim, Jae Ho Jeong
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    Young Joo Lee, Young Sol Hwang, Junetae Kim, Sei-Hyun Ahn, Byung Ho Son, Hee Jeong Kim, Beom Seok Ko, Jisun Kim, Il Yong Chung, Jong Won Lee, Sae Byul Lee
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    Shin Hye Yoo, Tae-Yong Kim, Miso Kim, Kyung-Hun Lee, Eunshin Lee, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Sae-Won Han, Tae-You Kim, Seock-Ah Im
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    Yanna Zhang, Yidong Zhou, Feng Mao, Ru Yao, Qiang Sun
    Cancer Communications.2020; 40(4): 181.     CrossRef
  • Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update
    Kimberly H. Allison, M. Elizabeth H. Hammond, Mitchell Dowsett, Shannon E. McKernin, Lisa A. Carey, Patrick L. Fitzgibbons, Daniel F. Hayes, Sunil R. Lakhani, Mariana Chavez-MacGregor, Jane Perlmutter, Charles M. Perou, Meredith M. Regan, David L. Rimm, W
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  • Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis
    Fabio Marazzi, Roberto Barone, Valeria Masiello, Valentina Magri, Antonino Mulè, Angela Santoro, Federica Cacciatori, Luca Boldrini, Gianluca Franceschini, Francesca Moschella, Giuseppe Naso, Silverio Tomao, Maria Antonietta Gambacorta, Giovanna Mantini,
    Clinical Breast Cancer.2020; 20(5): e600.     CrossRef
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Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer
Junghoon Shin, Jin-Haeng Chung, Se Hyun Kim, Kyu Sang Lee, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jeong-Ok Lee, Jin-Won Kim, Yu-Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee
Cancer Res Treat. 2019;51(3):1086-1097.   Published online November 5, 2018
DOI: https://doi.org/10.4143/crt.2018.537
AbstractAbstract PDFPubReaderePub
Purpose
Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.
Materials and Methods
We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.
Results
The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.
Conclusion
Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

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Patient and Care Delays of Breast Cancer in China
Yue-Lin Li, Ya-Chao Qin, Lu-Ying Tang, Yu-Huang Liao, Wei Zhang, Xiao-Ming Xie, Qiang Liu, Ying Lin, Ze-Fang Ren
Cancer Res Treat. 2019;51(3):1098-1106.   Published online November 6, 2018
DOI: https://doi.org/10.4143/crt.2018.386
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China.
Methods
A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis.
Results
There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination.
Conclusion
Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.

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Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection
Jieun Jang, Eun-Jung Cho, Yunji Hwang, Elisabete Weiderpass, Choonghyun Ahn, Jeoungbin Choi, Soung-Hoon Chang, Hai-Rim Shin, Min Kyung Lim, Keun-Young Yoo, Sue K. Park
Cancer Res Treat. 2019;51(3):1107-1116.   Published online November 21, 2018
DOI: https://doi.org/10.4143/crt.2018.182
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information.
Materials and Methods
We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model.
Results
Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori.
Conclusion
This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

Citations

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    Sangjun Lee, Sue K. Park
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    C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
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    Jieun Jang, Tianyi Wang, Hui Cai, Fei Ye, Gwen Murphy, Taichi Shimazu, Philip R Taylor, You‐Lin Qiao, Keun‐Young Yoo, Sun Ha Jee, Jeongseon Kim, Sheau‐Chiann Chen, Christian C Abnet, Shoichiro Tsugane, Wei Zheng, Xiao‐Ou Shu, Michael Pawlita, Sue K. Park,
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Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer
Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam
Cancer Res Treat. 2019;51(3):1117-1127.   Published online November 6, 2018
DOI: https://doi.org/10.4143/crt.2018.405
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing.
Materials and Methods
To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA).
Results
Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845).
Conclusion
We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

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A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
Youjin Kim, Tae Won Kim, Sae Won Han, Joong Bae Ahn, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang
Cancer Res Treat. 2019;51(3):1128-1134.   Published online November 21, 2018
DOI: https://doi.org/10.4143/crt.2018.379
AbstractAbstract PDFPubReaderePub
Purpose
Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
Materials and Methods
Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m2 plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m2 twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.
Results
From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.
Conclusion
Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.

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    Fatemeh Zahedipour, Seyede Atefe Hosseini, Željko Reiner, Eugenia Tedeschi-Reiner, Tannaz Jamialahmadi, Amirhossein Sahebkar
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    Kumiko Taniguchi, Kei Sugihara, Takashi Miura, Daisuke Hoshi, Susumu Kohno, Chiaki Takahashi, Eishu Hirata, Etsuko Kiyokawa
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    Rong Jiang, Lian Lou, Wen Shi, Yuxiao Chen, Zhaoming Fu, Shuo Liu, Thida Sok, Zhihang Li, Xuan Zhang, Jian Yang
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Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location
Chan Wook Kim, Jihun Kim, Yangsoon Park, Dong-Hyung Cho, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
Cancer Res Treat. 2019;51(3):1135-1143.   Published online November 29, 2018
DOI: https://doi.org/10.4143/crt.2018.392
Correction in: Cancer Res Treat 2021;53(3):893
AbstractAbstract PDFPubReaderePub
Purpose
Extranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers.
Materials and Methods
The medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed.
Results
ENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients.
Conclusion
ENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.

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    Mi Zhou, Hongyun Huang, Deying Bao, Meining Chen, Fulin Lu
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    Young Il Kim, Chan Wook Kim, Jong Hoon Kim, Jihun Kim, Jun-Soo Ro, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
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Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer
Se Ik Kim, Minsun Song, Suhyun Hwangbo, Sungyoung Lee, Untack Cho, Ju-Hyun Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Dae-Shik Suh, Taesung Park, Yong-Sang Song
Cancer Res Treat. 2019;51(3):1144-1155.   Published online November 20, 2018
DOI: https://doi.org/10.4143/crt.2018.508
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC.
Materials and Methods
We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied.
Results
The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively.
Conclusion
We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

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