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Volume 52(1); January 2020
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Original Articles
The Effect of Disability on the Diagnosis and Treatment of Multiple Myeloma in Korea: A National Cohort Study
Jihyun Kwon, So Young Kim, Kyoung Eun Yeob, Hye Sook Han, Ki Hyeong Lee, Dong Wook Shin, Yeon-Yong Kim, Jong Heon Park, Jong Hyock Park
Cancer Res Treat. 2020;52(1):1-9.   Published online April 22, 2019
DOI: https://doi.org/10.4143/crt.2018.702
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to determine whether the diagnosis, treatment approach, and prognosis of multiple myeloma (MM) vary according to the presence and type of disability.
Materials and Methods
Demographic, socioeconomic, and medical data were obtained from the National Disability Database, the Korean Central Cancer Registry, and the Korean National Health Insurance claims database. An age- and sex-matched cohort was established using a 1:3 ratio constituted with 2,776,450 people with disabilities and 8,329,350 people without disabilities. Adult patients diagnosed with MM were subsequently selected from this cohort. Disabilities were categorized as physical, communication, intellectual or psychological, and affecting the major internal organs.
Results
The cohort included 4,090 patients with MM, with a significantly lower rate per 100,000 persons among people with disabilities than among people without disabilities (29.1 vs. 39.4, p < 0.001). People with disabilities were more likely to undergo dialysis treatment at the time of diagnosis (16.3% vs. 10.0%, p < 0.001), but were less likely to undergo autologous stem cell transplantation (37.5% vs. 43.7%, p=0.072). This trend was more evident among patients with intellectual or psychological disabilities. The median overall survival among patients with disabilities was significantly shorter than that among patients without disabilities (36.8 months vs. 51.2 months, p < 0.001).
Conclusion
In Korea, people with disabilities generally have a lower rate of MM diagnosis, receive less intensive treatment, and have a lower survival rate than people without disabilities.

Citations

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  • Disparities in prostate cancer diagnosis, treatment, and survival among men with disabilities: Retrospective cohort study in South Korea
    Dong Wook Shin, Jinsung Park, Kyoung Eun Yeob, Seok Jung Yoon, Soong-nang Jang, So Young Kim, Jong Heon Park, Jong Hyock Park, Ichiro Kawachi
    Disability and Health Journal.2021; 14(4): 101125.     CrossRef
  • Disparities in the Diagnosis, Treatment, and Survival Rate of Cervical Cancer among Women with and without Disabilities
    Jin Young Choi, Kyoung Eun Yeob, Seung Hwa Hong, So Young Kim, Eun-Hwan Jeong, Dong Wook Shin, Jong Heon Park, Gil-won Kang, Hak Soon Kim, Jong Hyock Park, Ichiro Kawachi
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  • Disparities in the Diagnosis and Treatment of Gastric Cancer in Relation to Disabilities
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    Clinical and Translational Gastroenterology.2020; 11(10): e00242.     CrossRef
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Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma
Guo-Pei Zhang, Xiao Yue, Shao-Qiang Li
Cancer Res Treat. 2020;52(1):10-23.   Published online April 26, 2019
DOI: https://doi.org/10.4143/crt.2019.145
AbstractAbstract PDFPubReaderePub
Purpose
Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC.
Materials and Methods
HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools.
Results
By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor α (TNF-α)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-α could activate CTSC expression in a concentration- dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-α/MAPK (p38) signaling.
Conclusion
Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

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Comparison of the Efficacy of Two Microsphere Embolic Agents for Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients
Shao-Hua Lee, Chia-Ying Lin, Ya-Chun Hsu, Yi-Sheng Liu, Ming-Tsung Chuang, Ming-Ching Ou
Cancer Res Treat. 2020;52(1):24-30.   Published online April 29, 2019
DOI: https://doi.org/10.4143/crt.2019.018
AbstractAbstract PDFPubReaderePub
Purpose
Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma.
Materials and Methods
This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics.
Results
The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene.
Conclusion
These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

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Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities
Nai-Bin Chen, Bo Qiu, Jun Zhang, Meng-Yun Qiang, Yu-Jia Zhu, Bin Wang, Jin-Yu Guo, Ling-Zhi Cai, Shao-Min Huang, Meng-Zhong Liu, Qun Li, Yong-Hong Hu, Qi-Wen Li, Hui Liu
Cancer Res Treat. 2020;52(1):31-40.   Published online April 30, 2019
DOI: https://doi.org/10.4143/crt.2018.624
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques.
Materials and Methods
A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test.
Results
With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence.
Conclusion
No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

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Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas
Hyemi Shin, Jason K. Sa, Joon Seol Bae, Harim Koo, Seonwhee Jin, Hee Jin Cho, Seung Won Choi, Jong Min Kyoung, Ja Yeon Kim, Yun Jee Seo, Je-Gun Joung, Nayoung K. D. Kim, Dae-Soon Son, Jongsuk Chung, Taeseob Lee, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Yeon-Lim Suh, Woong-Yang Park, Do-Hyun Nam
Cancer Res Treat. 2020;52(1):41-50.   Published online May 7, 2019
DOI: https://doi.org/10.4143/crt.2019.036
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.
Materials and Methods
To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization.
Results
Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene.
Conclusion
We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

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  • Comparative genomic landscape of lower-grade glioma and glioblastoma
    Xinxin Sun, Qingbin Jia, Kun Li, Conghui Tian, Lili Yi, Lili Yan, Juan Zheng, Xiaodong Jia, Mingliang Gu, Michael C. Burger
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Magnetic Resonance-Based Texture Analysis Differentiating KRAS Mutation Status in Rectal Cancer
Ji Eun Oh, Min Ju Kim, Joohyung Lee, Bo Yun Hur, Bun Kim, Dae Yong Kim, Ji Yeon Baek, Hee Jin Chang, Sung Chan Park, Jae Hwan Oh, Sun Ah Cho, Dae Kyung Sohn
Cancer Res Treat. 2020;52(1):51-59.   Published online May 7, 2019
DOI: https://doi.org/10.4143/crt.2019.050
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mutation of the Kirsten Ras (KRAS) oncogene is present in 30%-40% of colorectal cancers and has prognostic significance in rectal cancer. In this study, we examined the ability of radiomics features extracted from T2-weighted magnetic resonance (MR) images to differentiate between tumors with mutant KRAS and wild-type KRAS.
Materials and Methods
Sixty patients with primary rectal cancer (25 with mutant KRAS, 35 with wild-type KRAS) were retrospectively enrolled. Texture analysis was performed in all regions of interest on MR images, which were manually segmented by two independent radiologists. We identified potentially useful imaging features using the two-tailed t test and used them to build a discriminant model with a decision tree to estimate whether KRAS mutation had occurred.
Results
Three radiomic features were significantly associated with KRASmutational status (p < 0.05). The mean (and standard deviation) skewness with gradient filter value was significantly higher in the mutant KRAS group than in the wild-type group (2.04±0.94 vs. 1.59±0.69). Higher standard deviations for medium texture (SSF3 and SSF4) were able to differentiate mutant KRAS (139.81±44.19 and 267.12±89.75, respectively) and wild-type KRAS (114.55±29.30 and 224.78±62.20). The final decision tree comprised three decision nodes and four terminal nodes, two of which designated KRAS mutation. The sensitivity, specificity, and accuracy of the decision tree was 84%, 80%, and 81.7%, respectively.
Conclusion
Using MR-based texture analysis, we identified three imaging features that could differentiate mutant from wild-type KRAS. T2-weighted images could be used to predict KRAS mutation status preoperatively in patients with rectal cancer.

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    J. Gao, Q. Zhang, C. Zhang, M. Chen, D. Li, Y. Fu, X. Lv, B. Zhang, H. Guo
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  • Ability of Radiomics in Differentiation of Anaplastic Oligodendroglioma From Atypical Low-Grade Oligodendroglioma Using Machine-Learning Approach
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  • The Diagnostic Value of Radiomics-Based Machine Learning in Predicting the Grade of Meningiomas Using Conventional Magnetic Resonance Imaging: A Preliminary Study
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Disparities in the Participation Rate of Colorectal Cancer Screening by Fecal Occult Blood Test among People with Disabilities: A National Database Study in South Korea
Dong Wook Shin, Dongkyung Chang, Jin Hyung Jung, Kyungdo Han, So Young Kim, Kui Son Choi, Won Chul Lee, Jong Heon Park, Jong Hyock Park
Cancer Res Treat. 2020;52(1):60-73.   Published online May 7, 2019
DOI: https://doi.org/10.4143/crt.2018.660
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Implementation of screening program may lead to increased health disparity within the population if participation differs by socioeconomic status. In Korea, colorectal cancer screening is provided at no or minimal cost to all people over 50 by National Cancer Screening Program. We investigated colorectal cancer screening participation rate and its trend over the last 10 years in relation to disabilities.
Materials and Methods
We linked national disability registration data with National Cancer Screening Program data. Age, sex-standardized participation rates were analyzed by type and severity of disability for each year, and factors associated with colorectal cancer screening participation were examined by multivariate logistic regression.
Results
Age, sex-standardized participation rate in people without disability increased from 16.2 to 33.9% (change, +17.7), but it increased from 12.7% to 27.2% (change, +14.5) among people with severe disability. People with severe disabilities showed a markedly lower colorectal cancer screening participation rate than people without disability (adjusted odds ratio [aOR], 0.714; 95% confidence interval, 0.713 to 0.720). People with autism (aOR, 0.468), renal failure (aOR, 0.498), brain injury (aOR, 0.581), ostomy (aOR, 0.602), and intellectual disability (aOR, 0.610) showed the lowest participation rates.
Conclusion
Despite the availability of a National Cancer Screening Program and overall increase of its usage in the Korean population, a significant disparity was found in colorectal cancer screening participation, especially in people with severe disabilities and or several specific types of disabilities. Greater effort is needed to identify the barriers faced by these particularly vulnerable groups and develop targeted interventions to reduce inequality.

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    Gwanwook Bang, Minji Park, Jeong‐yeon Seon, So‐Youn Park
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    Ki Bae Kim, Dong Wook Shin, Kyoung Eun Yeob, So Young Kim, Joung-Ho Han, Seon Mee Park, Jong Heon Park, Jong Hyock Park
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    Benedicte Kirkøen, Paula Berstad, Geir Hoff, Tomm Bernklev, Kristin R. Randel, Øyvind Holme, Thomas de Lange, Kathryn A. Robb, Edoardo Botteri
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    Lisa I Iezzoni
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    Fahrin Ramadan Andiwijaya, Calum Davey, Khaoula Bessame, Abdourahmane Ndong, Hannah Kuper
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    Jae Youn Seo, Dong Wook Shin, Su Jong Yu, Jin Hyung Jung, Kyungdo Han, In Young Cho, So Young Kim, Kui Son Choi, Jong Heon Park, Jong Hyock Park, Ichiro Kawachi
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    Kyu-Tae Han, Seungju Kim, Antonio Palazón-Bru
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    Dong Wook Shin, Jinsung Park, Kyoung Eun Yeob, Seok Jung Yoon, Soong-nang Jang, So Young Kim, Jong Heon Park, Jong Hyock Park, Ichiro Kawachi
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    Jin Young Choi, Kyoung Eun Yeob, Seung Hwa Hong, So Young Kim, Eun-Hwan Jeong, Dong Wook Shin, Jong Heon Park, Gil-won Kang, Hak Soon Kim, Jong Hyock Park, Ichiro Kawachi
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    YoungJee Kim, Dong Wook Shin, Hyoung Woo Kim, Jin Hyung Jung, Kyungdo Han, In Young Cho, So Young Kim, Kui Son Choi, Jong Heon Park, Jong Hyock Park, Ichiro Kawachi
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    Hyoung Woo Kim, Dong Wook Shin, Kyoung Eun Yeob, In Young Cho, So Young Kim, Seon Mee Park, Jong Heon Park, Jong Hyock Park, Ichiro Kawachi
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Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers
Jeong Mo Bae, Xianyu Wen, Tae-Shin Kim, Yoonjin Kwak, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang
Cancer Res Treat. 2020;52(1):74-84.   Published online May 8, 2019
DOI: https://doi.org/10.4143/crt.2019.062
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs).
Materials and Methods
We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs).
Results
CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification.
Conclusion
FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.

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SUVmax Predicts Disease Progression after Stereotactic Ablative Radiotherapy in Stage I Non-small Cell Lung Cancer
Yoo-Kang Kwak, Hee Hyun Park, Kyu Hye Choi, Eun Young Park, Soo Yoon Sung, Sea-Won Lee, Ji Hyun Hong, Hyo Chun Lee, Ie Ryung Yoo, Yeon Sil Kim
Cancer Res Treat. 2020;52(1):85-97.   Published online May 17, 2019
DOI: https://doi.org/10.4143/crt.2019.007
AbstractAbstract PDFPubReaderePub
Purpose
Fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) is gaining evidence as a predictive factor in non-small cell lung cancer (NSCLC). Stereotactic ablative radiotherapy (SABR) is the standard treatment in early-stage NSCLC when a patient is unsuitable for surgery. We performed a study to assess the prognostic clinical significance of PET-CT after SABR in early-stage NSCLC.
Materials and Methods
Seventy-six patients with stage I NSCLC treated with SABR were investigated. Total radiation dose ranged from 36 to 63 Gy in three to eight fractions depending on tumor location and size. Respiratory motion control was implemented at simulation and during treatment. PET-CT prior to SABR was performed in 66 patients (86.8%).
Results
Median follow-up time was 32 months (range, 5 to 142 months). Local control rate at 1, 2, and 5 years were 95.9%, 92.8%, and 86.7%, respectively. Overall survival (OS) at 1, 2, and 5 years were 91.0%, 71.3%, and 52.1% respectively. Cause-specific survival at 1, 2, and 5 years were 98.6%, 93.1%, and 84.3% respectively. Tumor size and pre-SABR maximal standardized uptake value (SUVmax) demonstrated statistical significance in the Kaplan-Meier survival analyses with log-rank test. In multivariate analyses pre-SABR SUVmax remained statistically significant in correlation to OS (p=0.024; hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.2 to 8.8) and with marginal significance in regards to regional progression-free survival (p=0.059; HR, 32.5; 95% CI, 2.6 to 402.5).
Conclusion
Pre-SABR SUVmax demonstrated a predictive power in statistical analyses. Tumors with SUVmax above 6 at diagnosis were associated with inferior outcomes.

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  • Invasive Nodal Staging via Endobronchial Ultrasound and Outcome in Patients Treated with Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer – Results from a Single Institution Study
    Benjamin George, Atallah Baydoun, Samar Bhat, Lauryn Bailey, Theodore Arsenault, Yilun Sun, Yuxia Zhang, Yiran Zheng, Prashant Vempati, Tarun Podder, Tithi Biswas
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  • Parámetros cuantitativos de la PET/TC con 18F-FDG como factores pronósticos en el cáncer de pulmón localizado e inoperable
    J.R. Infante, J. Cabrera, J.I. Rayo, C. Cruz, J. Serrano, M. Moreno, A. Martínez, P. Jiménez, A. Cobo
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    J.R. Infante, J. Cabrera, J.I. Rayo, C. Cruz, J. Serrano, M Moreno, A. Martínez, P. Jiménez, A. Cobo
    Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2020; 39(6): 353.     CrossRef
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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment
Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim
Cancer Res Treat. 2020;52(1):98-108.   Published online May 27, 2019
DOI: https://doi.org/10.4143/crt.2019.195
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

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    Journal of NeuroInterventional Surgery.2024; 16(4): 352.     CrossRef
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    Lei Jiang, Xingwang Zhao, Yilin Li, Yajie Hu, Yu Sun, Shengde Liu, Zizhen Zhang, Yanyan Li, Xujiao Feng, Jiajia Yuan, Jian Li, Xiaotian Zhang, Yang Chen, Lin Shen
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    Samuel J. Schulte, Mark E. Fornace, John K. Hall, Grace J. Shin, Niles A. Pierce
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    Pharmaceutics.2023; 15(3): 946.     CrossRef
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    Jiansheng Wang, Xintian Mao, Yan Wang, Xiang Tao, Junhao Chu, Qingli Li
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    Magdalena Kuras
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    Aisling Forder, Greg L. Stewart, Nikita Telkar, Wan L. Lam, Cathie Garnis
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    Rodolfo Montironi, Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Gregor Mikuz
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    Du-Min Go, Seung Hyun Lee, Su-Hyung Lee, Sang-Ho Woo, Kibyeong Kim, Kyeongdae Kim, Kyu Seong Park, Jong-Hwan Park, Sang-Jun Ha, Woo Ho Kim, Jae-Hoon Choi, Dae-Yong Kim
    Cellular and Molecular Gastroenterology and Hepatology.2021; 12(2): 715.     CrossRef
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    Yujun Park, An Na Seo, Jiwon Koh, Soo Kyoung Nam, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
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Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma
Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang
Cancer Res Treat. 2020;52(1):109-116.   Published online May 30, 2019
DOI: https://doi.org/10.4143/crt.2019.202
AbstractAbstract PDFPubReaderePub
Purpose
The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design.
Materials and Methods
Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method.
Results
Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS.
Conclusion
NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

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    Mohammed Badwelan, Hasan Muaddi, Abeer Ahmed, Kyungjun T. Lee, Simon D. Tran
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    Aleksandra Janowiak-Majeranowska, Jakub Osowski, Bogusław Mikaszewski, Alan Majeranowski
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    Qigen Fang, Junhui Yuan, Wei Du, Liyuan Dai, Xu Zhang, Ruihua Luo
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  • Survival Significance of Number of Positive Lymph Nodes in Oral Squamous Cell Carcinoma Stratified by p16
    Peng Li, Qigen Fang, Yanjie Yang, Defeng Chen, Wei Du, Fei Liu, Ruihua Luo
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Chunmiao Xu, Junhui Yuan, Liuqing Kang, Xiaoxian Zhang, Lifeng Wang, Xuejun Chen, Qi Yao, Hailiang Li
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    Chunmiao Xu, Hailiang Li, Dongjie Seng, Fei Liu
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  • Lingual Lymph Node Metastasis in cT1-2N0 Tongue Squamous Cell Carcinoma: Is It an Indicator for Elective Neck Dissection
    Wenli Yang, Minglei Sun, Qiaoyan Jie, Haixia Zhou, Peng Zhang, Juanfang Zhu
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    Guo Zhao, Jianli Sun, Kai Ba, Yunxiang Zhang
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    Wei Du, Qigen Fang, Shanting Liu, Defeng Chen, Ruihua Luo, Xu Zhang
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    BMC Cancer.2020;[Epub]     CrossRef
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Pediatric Adenocarcinoma in Korea: A Multicenter Study
Hee-Beom Yang, Jung-Man Namgoong, Ki Hoon Kim, Dae Yeon Kim, Jinyoung Park, Hyun Beak Shin, Joong Kee Youn, Sanghoon Lee, Ji Won Lee, Sung Eun Jung, Jae Hee Chung, Yun-Mee Choe, Tae Gil Heo, In Geol Ho, Hyun-Young Kim
Cancer Res Treat. 2020;52(1):117-127.   Published online June 3, 2019
DOI: https://doi.org/10.4143/crt.2019.092
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea.
Materials and Methods
Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval.
Results
Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001).
Conclusion
In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.

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    Xing Lei, Yongfei Zheng, Guohua Zhang, Hailan Zheng
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Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray
Sung Han Kim, Weon Seo Park, Boram Park, Jinsoo Chung, Jae Young Joung, Kang Hyun Lee, Ho Kyung Seo
Cancer Res Treat. 2020;52(1):128-138.   Published online June 19, 2019
DOI: https://doi.org/10.4143/crt.2019.119
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to identify prognostic tissue markers for several survival outcomes after radical nephroureterectomy among patients with upper urinary tract urothelial carcinoma using tissue microarray and immunohistochemistry.
Materials and Methods
Retrospectively, data of 162 non-metastatic patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy between 2004 and 2016 were reviewed to determine intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS). The expression of 27 tissue markers on a tissue microarray of radical nephroureterectomy samples and prognostic values of clinicopathological parameters were evaluated using immunohistochemistry and Cox proportional hazard models after adjusting for significant prognostic clinicopathological variables. The expression of all tissue markers was categorized into a binary group with continuous H-scores (0-300).
Results
Median follow-up was 53.4 months (range, 3.6 to 176.5 months); and, 58 (35.8%), 48 (29.6%), and 19 (11.7%) bladder recurrence, disease progression, and all cause death, respectively, were identified. After adjusting for significant clinicopathological factors including intravesical instillation for bladder recurrence-free survival, pathologic T category and intravesical instillation for disease progression-free survival , and pathologic T category for OS (p < 0.05), IVRFS was associated with epithelial cadherin (hazard ratio [HR], 0.49), epidermal growth factor receptor/erythroblastosis oncogene B (c-erb) (HR, 2.59), and retinoblastoma protein loss (HR, 1.85); DFS was associated with cyclin D1 (HR, 2.16) and high-molecular-weight cytokeratin (HR, 0.42); OS was associated with E-cadherin (HR, 0.34) and programmed cell death 1 ligand (HR, 13.42) (p < 0.05).
Conclusion
Several significant tissue markers were associated with survival outcomes in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy.

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  • A multi‐institutional retrospective study of open versus laparoscopic nephroureterectomy focused on the intravesical recurrence
    Soichiro Shimura, Kazumasa Matsumoto, Masaomi Ikeda, Shigenori Moroo, Dai Koguchi, Yoshinori Taoka, Takahiro Hirayama, Yasukiyo Murakami, Takuji Utsunomiya, Daisuke Matsuda, Norihiko Okuno, Akira Irie, Masatsugu Iwamura
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    Giulia Mazzaschi, Giulia Claire Giudice, Matilde Corianò, Davide Campobasso, Fabiana Perrone, Michele Maffezzoli, Irene Testi, Luca Isella, Umberto Maestroni, Sebastiano Buti
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    Frontiers in Oncology.2020;[Epub]     CrossRef
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  • 140 Download
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Prevalence and Predictors of Sustained Smoking after a Cancer Diagnosis in Korean Men
Hye Yeon Koo, Kiheon Lee, Sang Min Park, Jooyoung Chang, Kyuwoong Kim, Seulggie Choi, Mi Hee Cho, Jihye Jun, Sung Min Kim
Cancer Res Treat. 2020;52(1):139-148.   Published online June 25, 2019
DOI: https://doi.org/10.4143/crt.2018.609
AbstractAbstract PDFPubReaderePub
Purpose
Although smoking has a significant impact on mortality and morbidity of cancer patients, many patients continue to smoke post-diagnosis. The purpose of this study was to investigate prevalence and predictors of sustained smoking among male cancer survivors.
Materials and Methods
The Korean National Health Insurance Service-National Health Screening Cohort database was used for this population-based, retrospective study. Study subjects were 15,141 men who were diagnosed with their first incident cancer between 2004 and 2011. Changes in smoking status before and after a cancer diagnosis were investigated. For patients who were current smokers pre-diagnosis, association between post-diagnosis sustained smoking and demographic, socioeconomic, and clinical variables were examined.
Results
Of the 4,657 pre-diagnosis smokers, 2,255 (48%) had quit after cancer diagnosis, while 2,402 (51.6%) continued to smoke. In a multivariate logistic regression analysis, younger age at cancer diagnosis (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.21 to 1.55; p < 0.001), low socioeconomic status (aOR, 1.29; 95% CI, 1.15 to 1.45; p ≤ 0.001), pre-diagnosis heavy smoking (aOR, 1.24; 95% CI, 1.09 to 1.41; p=0.001), diagnosis of non-smoking– related cancer (aOR, 1.67; 95% CI, 1.42 to 1.96; p < 0.001), and high serum glucose level (aOR, 1.23; 95% CI, 1.03 to 1.46; p=0.019) were associated with sustained smoking after a cancer diagnosis.
Conclusion
Almost half of the male smokers continue to smoke after a cancer diagnosis. Targeted interventions for smoking cessation should be considered for patients with younger age, low socioeconomic status, heavy smoking history, non-smoking–related cancer, and high blood glucose levels.

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    Liza M. González Ruiz, Lía I. Mondragón Márquez, Daniela L. Domínguez Bueso, Jason J. Liu
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    Patricia Fox, Nancy Bhardwaj, Ailsa Lyons, Vikram Niranjan, Kate Frazer, Shiraz Syed, Amanda McCann, Sinead Brennan, Donal Brennan, Catherine Kelly, Michael Keane, Patricia Fitzpatrick
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    Youngmee Kim, Won-Kyung Cho
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    Saverio Caini, Marco Del Riccio, Virginia Vettori, Vieri Scotti, Chiara Martinoli, Sara Raimondi, Giulio Cammarata, Domenico Palli, Marco Banini, Giovanna Masala, Sara Gandini
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    Feras I. Hawari, Minas A. Abu Alhalawa, Rasha H. Alshrideh, Ahmad M. Al Nawaiseh, Alia Khamis, Yasmeen I. Dodin, Nour A. Obeidat
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    Kathleen Gali, Frederike Bokemeyer, Sabine Behrens, Annika Möhl, Nadia Obi, Heiko Becher, Jenny Chang-Claude
    Cancer Epidemiology.2022; 81: 102282.     CrossRef
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    Feras I. Hawari, Minas A. Abu Alhalawa, Rasha H. Alshraiedeh, Ahmad M. Al Nawaiseh, Alia Khamis, Yasmeen I. Dodin, Nour A. Obeidat
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Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Cancer Res Treat. 2020;52(1):149-166.   Published online June 25, 2019
DOI: https://doi.org/10.4143/crt.2019.183
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.
Materials and Methods
We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings.
Results
In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
Conclusion
Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

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    Hanfeng Wang, Yang Fan, Weihao Chen, Zheng Lv, Shengpan Wu, Yundong Xuan, Chenfeng Wang, Yongliang Lu, Tao Guo, Donglai Shen, Fan Zhang, Qingbo Huang, Yu Gao, Hongzhao Li, Xin Ma, Baojun Wang, Yan Huang, Xu Zhang
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    Nitasha Gupta, Tzu-Ting Huang, Sachi Horibata, Jung-Min Lee
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    Tianen Chen, Suparat Tongpeng, Ziyi Lu, Win Topatana, Sarun Juengpanich, Shijie Li, Jiahao Hu, Jiasheng Cao, Cheeshin Lee, Yitong Tian, Mingyu Chen, Xiujun Cai
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    Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani
    Clinical and Translational Oncology.2022; 24(8): 1478.     CrossRef
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    Giulia Petroni, Aitziber Buqué, Lisa M. Coussens, Lorenzo Galluzzi
    Nature Reviews Drug Discovery.2022; 21(6): 440.     CrossRef
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    Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani
    Cancer Immunology, Immunotherapy.2022; 71(10): 2325.     CrossRef
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    Zhengkun Zhang, Lang Bu, Junhang Luo, Jianping Guo
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    Tong Zhang, Haixiang Yu, Xiangpeng Dai, Xiaoling Zhang
    Frontiers in Immunology.2022;[Epub]     CrossRef
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    Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
    Journal of Experimental & Clinical Cancer Research.2022;[Epub]     CrossRef
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    Xiaoting Huang, Wei Liu, Chunshan Liu, Jijie Hu, Baiyao Wang, Anbang Ren, Xiaona Huang, Yawei Yuan, Jinquan Liu, Mingyi Li
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
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    Larissa Costa de Almeida, Felipe Antunes Calil, João Agostinho Machado-Neto, Leticia Veras Costa-Lotufo
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    Giulia Petroni, Aitziber Buqué, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
    Cancer Cell.2021; 39(3): 310.     CrossRef
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    Jian Chen, Xing Jia, Zequn Li, Wenfeng Song, Cheng Jin, Mengqiao Zhou, Haiyang Xie, Shusen Zheng, Penghong Song
    Biochemical Pharmacology.2021; 188: 114494.     CrossRef
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    Mei-Hua Jin, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
    Gastric Cancer.2021; 24(5): 1003.     CrossRef
  • ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer
    Ah-Rong Nam, Jeesun Yoon, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Jae-Min Kim, Tae-Yong Kim, Do-Youn Oh
    Cancer Letters.2021; 516: 38.     CrossRef
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    Timothy A. Yap, Eileen E. Parkes, Weiyi Peng, Justin T. Moyers, Michael A. Curran, Hussein A. Tawbi
    Cancer Discovery.2021; 11(6): 1368.     CrossRef
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    Aditi Jain, Vikas Bhardwaj
    World Journal of Gastroenterology.2021; 27(39): 6527.     CrossRef
  • A steroidal saponin isolated from Allium chinense simultaneously induces apoptosis and autophagy by modulating the PI3K/Akt/mTOR signaling pathway in human gastric adenocarcinoma
    Jingwen Xu, Mingmei Zhang, Xiaoying Lin, Yihai Wang, Xiangjiu He
    Steroids.2020; : 108672.     CrossRef
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Clinical Outcomes of Postoperative Radiotherapy Following Radical Prostatectomy in Patients with Localized Prostate Cancer: A Multicenter Retrospective Study (KROG 18-01) of a Korean Population
Sung Uk Lee, Kwan Ho Cho, Won Park, Won Kyung Cho, Jae-Sung Kim, Chan Woo Wee, Young Seok Kim, Jin Ho Kim, Taek-Keun Nam, Jaeho Cho, Song Mi Jeong, Youngkyong Kim, Su Jung Shim, Youngmin Choi, Jun-Sang Kim
Cancer Res Treat. 2020;52(1):167-180.   Published online June 25, 2019
DOI: https://doi.org/10.4143/crt.2019.126
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the clinical outcomes of postoperative radiotherapy (PORT) patients who underwent radical prostatectomy for localized prostate cancer.
Materials and Methods
Localized prostate cancer patients who received PORT after radical prostatectomy between 2001 and 2012 were identified retrospectively in a multi-institutional database. In total, 1,117 patients in 19 institutions were included. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥ nadir+2 after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA regardless of its value.
Results
Ten-year biochemical failure-free survival, clinical failure-free survival, distant metastasisfree survival, overall survival (OS), and cause-specific survival were 60.5%, 76.2%, 84.4%, 91.1%, and 96.6%, respectively, at a median of 84 months after PORT. Pre-PORT PSA ≤ 0.5 ng/ml and Gleason’s score ≤ 7 predicted favorable clinical outcomes, with 10-year OS rates of 92.5% and 94.1%, respectively. The 10-year OS rate was 82.7% for patients with a PSA > 1.0 ng/mL and 86.0% for patients with a Gleason score of 8-10. The addition of longterm ADT (≥ 12 months) to PORT improved OS, particularly in those with a Gleason score of 8-10 or ≥ T3b.
Conclusion
Clinical outcomes of PORT in a Korean prostate cancer population were very similar to those in Western countries. Lower Gleason score and serum PSA level at the time of PORT were significantly associated with favorable outcomes. Addition of long-term ADT (≥ 12 months) to PORT should be considered, particularly in unfavorable risk patients with Gleason scores of 8-10 or ≥ T3b.

Citations

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  • Optimal Definition of Biochemical Recurrence in Patients Who Receive Salvage Radiotherapy Following Radical Prostatectomy for Prostate Cancer
    Sung Uk Lee, Jae-Sung Kim, Young Seok Kim, Jaeho Cho, Seo Hee Choi, Taek-Keun Nam, Song Mi Jeong, Youngkyong Kim, Youngmin Choi, Dong Eun Lee, Won Park, Kwan Ho Cho
    Cancer Research and Treatment.2022; 54(4): 1191.     CrossRef
  • A discussion on controversies and ethical dilemmas in prostate cancer screening
    Satish Chandra Mishra
    Journal of Medical Ethics.2021; 47(3): 152.     CrossRef
  • Clinical Outcome of Salvage Radiotherapy for Locoregional Clinical Recurrence After Radical Prostatectomy
    Sung Uk Lee, Kwan Ho Cho, Jin Ho Kim, Young Seok Kim, Taek-Keun Nam, Jae-Sung Kim, Jaeho Cho, Seo Hee Choi, Su Jung Shim, Jin Hee Kim, Ah Ram Chang
    Technology in Cancer Research & Treatment.2021;[Epub]     CrossRef
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Factors Influencing Imatinib-Induced Hepatotoxicity
Ji Min Han, Jeong Yee, Yoon Sook Cho, Hye Sun Gwak
Cancer Res Treat. 2020;52(1):181-188.   Published online June 26, 2019
DOI: https://doi.org/10.4143/crt.2019.131
AbstractAbstract PDFPubReaderePub
Purpose
Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity.
Materials and Methods
We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs.
Results
The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg.
Conclusion
The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

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  • Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes
    Rongrong Fu, Rui Chang, Andong Peng, Changshun Feng, Weifan Zhu, Yi Chen, Xue Tian, Rui Wang, Hui Yan, Dianlong Jia, Jun Li
    Pharmaceutical Development and Technology.2024; : 1.     CrossRef
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    Mansour Tobaiqy, Nawal Helmi, Katie MacLure, Sylvia Saade
    International Journal of Clinical Pharmacy.2024; 46(2): 368.     CrossRef
  • Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis
    Emilia Neuwirt, Giovanni Magnani, Tamara Ćiković, Svenja Wöhrle, Larissa Fischer, Anna Kostina, Stephan Flemming, Nora J. Fischenich, Benedikt S. Saller, Oliver Gorka, Steffen Renner, Claudia Agarinis, Christian N. Parker, Andreas Boettcher, Christopher J
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    Isak W. Tengesdal, Charles A. Dinarello, Carlo Marchetti
    Pharmacology & Therapeutics.2023; 251: 108545.     CrossRef
  • Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms
    Shubhrat Purwar, Anam Fatima, Himashree Bhattacharyya, Lakshmi Venkata Simhachalam Kutikuppala, Matei-Alexandru Cozma, Bahadar Singh Srichawla, Leah Komer, Khulud Mahmood Nurani, Mihnea-Alexandru Găman
    World Journal of Hepatology.2023; 15(9): 1021.     CrossRef
  • Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study
    Feng-Ru Huang, Wen-Tong Fang, Zi-Ping Cheng, Ye Shen, Dun-Jian Wang, Yong-Qing Wang, Lu-Ning Sun
    Archives of Toxicology.2022; 96(4): 1075.     CrossRef
  • A Risk Scoring System Utilizing Machine Learning Methods for Hepatotoxicity Prediction One Year After the Initiation of Tyrosine Kinase Inhibitors
    Ji Min Han, Jeong Yee, Soyeon Cho, Min Kyoung Kim, Jin Young Moon, Dasom Jung, Jung Sun Kim, Hye Sun Gwak
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Drug‐Drug Interactions and Disease Status Are Associated With Irinotecan‐Induced Hepatotoxicity: A Cross‐Sectional Study in Shanghai
    Juan Li, Bing Chen, Wen‐qi Xi, Wan Jia, Wei‐xia Zhang, Xiao‐lan Bian
    The Journal of Clinical Pharmacology.2022; 62(9): 1160.     CrossRef
  • A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity
    Sitong Sun, Manshu Wang, Yu Yuan, Shuo Wang, Haoran Ding, Chenrui Liang, Xiaomeng Li, Simiao Fan, Yubo Li
    Toxicology Letters.2022; 363: 11.     CrossRef
  • Effects of High-Dose of Copper Amino Acid Complex on Laying Performance, Hematological and Biochemical Parameters, Organ Index, and Histopathology in Laying Hens
    Qin Zhou, Jiaming Zhu, Bing Liu, Jialing Qiu, Xintao Lu, Brian Curtin, Fei Ji, Dongyou Yu
    Biological Trace Element Research.2021; 199(8): 3045.     CrossRef
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    Debasish Basak, Scott Arrighi, Yasenya Darwiche, Subrata Deb
    Life.2021; 12(1): 48.     CrossRef
  • Factors affecting high-grade hepatotoxicity of tyrosine kinase inhibitors in cancer patients: a multi-center observational study
    Ji Min Han, Hye Won Han, Jeong Yee, Min Kyoung Kim, Jin Young Moon, Soyeon Cho, Dasom Jung, Yoon Sook Cho, Inyoung Seo, Jae Youn Kim, Hye Sun Gwak
    European Journal of Clinical Pharmacology.2020; 76(8): 1183.     CrossRef
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Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis
Rui Gao, Tian-Shuo Man, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Wei Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu
Cancer Res Treat. 2020;52(1):189-206.   Published online July 1, 2019
DOI: https://doi.org/10.4143/crt.2019.122
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL).
Materials and Methods
Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM.
Results
The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI.
Conclusion
Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

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  • Causal associations between site-specific cancer and diabetes risk: A two-sample Mendelian randomization study
    Rong Xu, Tingjin Zheng, Chaoqun Ouyang, Xiaoming Ding, Chenjin Ge
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Association between diabetes and acute lymphocytic leukemia, acute myeloid leukemia, non-Hopkin lymphoma, and multiple myeloma
    Ji Zhong Zhao, Yu Cheng Lu, Yan Min Wang, Bo Lian Xiao, Hong Yan Li, Shao Chin Lee, Li Juan Wang
    International Journal of Diabetes in Developing Countries.2022; 42(4): 694.     CrossRef
  • Increased serum level of alpha-2 macroglobulin and its production by B-lymphocytes in chronic lymphocytic leukemia
    Regina Michelis, Lama Milhem, Evleen Galouk, Galia Stemer, Ariel Aviv, Tamar Tadmor, Mona Shehadeh, Lev Shvidel, Masad Barhoum, Andrei Braester
    Frontiers in Immunology.2022;[Epub]     CrossRef
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  • 177 Download
  • 3 Web of Science
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Inequalities in Awareness and Attitude towards HPV and Its Vaccine between Local and Migrant Residents Who Participated in Cervical Cancer Screening in Shenzhen, China
Wei Lin, Yueyun Wang, Zhihua Liu, Bin Chen, Shixin Yuan, Bo Wu, Lin Gong
Cancer Res Treat. 2020;52(1):207-217.   Published online July 1, 2019
DOI: https://doi.org/10.4143/crt.2019.053
AbstractAbstract PDFPubReaderePub
Purpose
A cross-sectional survey was conducted to evaluate the differences on awareness and attitude towards human papillomavirus (HPV) and its vaccine between local and migrant residents who participated in cervical cancer screening in Shenzhen, China.
Materials and Methods
A total of 9,855 females sampled from healthcare institutions in 20 street blocks through the Cervical Cancer Prevention Network were surveyed in this study by a self-administered questionnaire. Multivariate logistic regression was conducted to explore the role of the hukou and resident status in the willingness to receive HPV vaccination.
Results
Local residents had a relatively higher awareness of HPV (62.0% vs. 35.6% vs. 29.9%, p < 0.001) and its vaccine (35.3% vs. 15.4% vs. 14.8%, p < 0.001), as well as a higher willingness to receive HPV vaccination (68.5% vs. 62.5% vs. 56.2%, p < 0.001) than non-permanent residents and floating population. Except for age, education level, marital status, monthly income, having daughter(s), and heard of HPV and its vaccine, the hukou and resident status significantly associated with the willingness to receive HPV vaccination (local residents vs. floating population: odds ratio, 1.216; 95% confidence interval, 1.057 to 1.398). None significant difference on the associated factors was found between local residents and internal migrants (p for interactions > 0.05).
Conclusion
Inequalities in awareness and attitude towards HPV and its vaccine existed between local and migrant residents in Shenzhen. The hukou and resident status did impact on the willingness to receive HPV vaccination, therefore, it is critical to implement effective health education campaigns on HPV and its vaccine among internal migrants.

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  • Parental willingness of HPV vaccination in Mainland China: A meta-analysis
    Sensen Tan, Sumeng Wang, Xunwen Zou, Xinhua Jia, Chenyunhao Tong, Jian Yin, Xuemei Lian, Youlin Qiao
    Human Vaccines & Immunotherapeutics.2024;[Epub]     CrossRef
  • Barriers to and Facilitators for Accessing HPV Vaccination in Migrant and Refugee Populations: A Systematic Review
    Davide Graci, Nicolò Piazza, Salvatore Ardagna, Alessandra Casuccio, Anton Drobov, Federica Geraci, Angelo Immordino, Alessandra Pirrello, Vincenzo Restivo, Riccardo Rumbo, Rosalba Stefano, Roberta Virone, Elena Zarcone, Palmira Immordino
    Vaccines.2024; 12(3): 256.     CrossRef
  • Public awareness, specific knowledge, and worry about mpox (monkeypox): A preliminary community-based study in Shenzhen, China
    Fangmei Ren, Junchao Liu, Jianping Miao, Yucheng Xu, Ruiyin Zhang, Jingjie Fan, Wei Lin
    Frontiers in Public Health.2023;[Epub]     CrossRef
  • Knowledge of Cervical Cancer and HPV, and Willingness to Receive HPV Vaccination Among 20–45-Year-Old Women — Six Provinces, China, 2018
    Di Gao, Gengli Zhao, Jiangli Di, Xiaosong Zhang, Linhong Wang
    China CDC Weekly.2023; 5(9): 201.     CrossRef
  • Willingness to receive and recommend hypothetical mpox vaccination and associated factors in Chinese adults: a community-based survey in Shenzhen, China
    F. Ren, J. Miao, J. Liu, B. Xia, Z. Chen, Y. Xu, R. Zhang, J. Fan, W. Lin
    Public Health.2023; 225: 267.     CrossRef
  • Cognition of the warning symptoms and risk factors for cancer among Chinese college students: a cross-sectional study based on a summer social practice activity
    Lin-sen Feng, Qing-li Li, Qing Yang, Yu-lu Zhu, Fu-lin Yin, Qi-yao Wang, Wen-jue Zhong, Xiao-qian Wu, Ruo-yu Yan, Zheng-jiao Dong
    Annals of Medicine.2023;[Epub]     CrossRef
  • Awareness, Acceptance, and Associated Factors of Human Papillomavirus Vaccine among Parents of Daughters in Hadiya Zone, Southern Ethiopia: A Cross-Sectional Study
    Yilma Markos Larebo, Legesse Tesfaye Elilo, Desta Erkalo Abame, Denebo Ersulo Akiso, Solomon Gebre Bawore, Abebe Alemu Anshebo, Natarajan Gopalan
    Vaccines.2022; 10(12): 1988.     CrossRef
  • Prevalence and genotype distribution of human papillomavirus among women with cervical lesions in Shenzhen city, China
    Qingfeng Mai, Xiaohan Yang, Huan Cheng, Genghang Wu, Zikun Wu
    Human Vaccines & Immunotherapeutics.2021; 17(4): 965.     CrossRef
  • Cervical Cancer Screening Rate and Willingness among Female Migrants in Shenzhen, China: Three-Year Changes in Citywide Surveys
    Wei Lin, Bin Chen, Bo Wu, Shixin Yuan, Chuyan Zhong, Weikang Huang, Haiyan Hu, Zhihua Liu, Yueyun Wang
    Cancer Research and Treatment.2021; 53(1): 212.     CrossRef
  • Inequalities in Cervical Cancer Screening Uptake Between Chinese Migrant Women and Local Women: A Cross-Sectional Study
    Hunter K. Holt, Xi Zhang, Shang-Ying Hu, Fang-Hui Zhao, Jennifer S. Smith, You-Lin Qiao
    Cancer Control.2021;[Epub]     CrossRef
  • Access to Vaccination Information and Confidence/Hesitancy towards Childhood Vaccination: A Cross-Sectional Survey in China
    Fanxing Du, Tracey Chantler, Mark R. Francis, Fiona Yueqian Sun, Xuan Zhang, Kaiyi Han, Lance Rodewald, Hongjie Yu, Shiyi Tu, Heidi Larson, Zhiyuan Hou
    Vaccines.2021; 9(3): 201.     CrossRef
  • The Impact of Video-Based Educational Interventions on Cervical Cancer, Pap Smear and HPV Vaccines
    Emmanuel Kwateng Drokow, Clement Yaw Effah, Clement Agboyibor, Evans Sasu, Cecilia Amponsem-Boateng, Gloria Selorm Akpabla, Hafiz Abdul Waqas Ahmed, Kai Sun
    Frontiers in Public Health.2021;[Epub]     CrossRef
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    Qiao Gu, Wenjie Hou, Huan Liu, Lijuan Shi, Zonghao Zhu, Wenfeng Ye, Xiaoyuan Ni
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    Emmanuel Kwateng Drokow, Liu Zi, Qian Han, Clement Yaw Effah, Clement Agboyibor, Evans Sasu, Gloria Selorm Akpabla, Francis Foli, Kai Sun
    Frontiers in Oncology.2020;[Epub]     CrossRef
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Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response
Qiao Xu, Ying Shao, Jinman Zhang, Huikun Zhang, Yawen Zhao, Xiaoli Liu, Zhifang Guo, Wei Chong, Feng Gu, Yongjie Ma
Cancer Res Treat. 2020;52(1):218-245.   Published online July 8, 2019
DOI: https://doi.org/10.4143/crt.2019.217
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.
Materials and Methods
AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.
Results
AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.
Conclusion
AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

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  • Modulation of Protein Disulfide Isomerase Functions by Localization: The Example of the Anterior Gradient Family
    Arvin S. Pierre, Noa Gavriel, Marianne Guilbard, Eric Ogier-Denis, Eric Chevet, Frederic Delom, Aeid Igbaria
    Antioxidants & Redox Signaling.2024; 41(10-12): 675.     CrossRef
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    Minghe Li, Huike Guo, Keao Wang, Chuanze Kang, Yanbin Yin, Han Zhang
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    Chun-Yan Yan, Meng-Lu Zhao, Ya-Nan Wei, Xi-He Zhao
    Molecular Therapy - Oncolytics.2023; 28: 212.     CrossRef
  • Prognostic Impact of AGR3 Protein Expression in Breast Cancer: A Systematic Review and Meta-analysis
    Carolina Leão de Moraes, Carolina Rodrigues Mendonça, Natália Cruz e Melo, Fernanda Sardinha de Abreu Tacon, Jair Pereira de Melo Junior, Waldemar Naves do Amaral
    Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics.2023; 45(10): e609.     CrossRef
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    Thilde Terkelsen, Maria Pernemalm, Pavel Gromov, Anna‐Lise Børresen‐Dale, Anders Krogh, Vilde D. Haakensen, Janne Lethiö, Elena Papaleo, Irina Gromova
    Molecular Oncology.2021; 15(2): 429.     CrossRef
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Immunogenicity and Optimal Timing of 13-Valent Pneumococcal Conjugate Vaccination during Adjuvant Chemotherapy in Gastric and Colorectal Cancer: A Randomized Controlled Trial
Wonyoung Choi, Jong Gwang Kim, Seung-Hoon Beom, Jun-Eul Hwang, Hyun-Jung Shim, Sang-Hee Cho, Min-Ho Shin, Sin-Ho Jung, Ik-Joo Chung, Joon Young Song, Woo Kyun Bae
Cancer Res Treat. 2020;52(1):246-253.   Published online July 9, 2019
DOI: https://doi.org/10.4143/crt.2019.189
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies.
Materials and Methods
We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killing assay.
Results
Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments.
Conclusion
The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

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Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Kyoungmin Lee, Kyunghye Bang, Changhoon Yoo, Inhwan Hwang, Jae Ho Jeong, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Do Hyun Park, Sang Soo Lee, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Kyu-pyo Kim, Baek-Yeol Ryoo
Cancer Res Treat. 2020;52(1):254-262.   Published online July 9, 2019
DOI: https://doi.org/10.4143/crt.2019.190
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM.
Materials and Methods
Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors.
Results
Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy.
Conclusion
2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

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Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study
Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn, Youn Wha Kim, Seung-Mo Hong, on behalf of the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists
Cancer Res Treat. 2020;52(1):263-276.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.192
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice.
Materials and Methods
Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs.
Results
Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity.
Conclusion
Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

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Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea
Hee Yeon Lee, Ji Hyung Hong, Jae Ho Byun, Hee-Jun Kim, Sun Kyung Baek, Jin Young Kim, Ki Hyang Kim, Jina Yun, Jung A Kim, Kwonoh Park, Hyo Jin Lee, Jung Lim Lee, Young-Woong Won, Il Hwan Kim, Woo Kyun Bae, Kyong Hwa Park, Der-Sheng Sun, Suee Lee, Min-Young Lee, Guk Jin Lee, Sook Hee Hong, Yun Hwa Jung, Ho Jung An
Cancer Res Treat. 2020;52(1):277-283.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.292
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage.
Materials and Methods
Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.
Results
Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.
Conclusion
Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

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    Caner ÇAKIR, Fatih KILIÇ, Çiğdem KILIÇ, Dilek YÜKSEL, Vakkas KORKMAZ, Günsu KİMYON CÖMERT, Osman TÜRKMEN, Taner TURAN
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Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies
Myung-Ju Ahn, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, Jong Seok Lee
Cancer Res Treat. 2020;52(1):284-291.   Published online July 23, 2019
DOI: https://doi.org/10.4143/crt.2019.200
AbstractAbstract PDFPubReaderePub
Purpose
Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261).
Materials and Methods
Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR).
Results
In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%).
Conclusion
Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

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    Valerio Nardone, Caterina Romeo, Emma D’Ippolito, Pierpaolo Pastina, Maria D’Apolito, Luigi Pirtoli, Michele Caraglia, Luciano Mutti, Giovanna Bianco, Antonella Consuelo Falzea, Rocco Giannicola, Antonio Giordano, Pierosandro Tagliaferri, Claudia Vincigue
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Clinical Characteristics and Outcomes of Non-small Cell Lung Cancer Patients with HER2 Alterations in Korea
Kangkook Lee, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(1):292-300.   Published online July 26, 2019
DOI: https://doi.org/10.4143/crt.2019.186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Human epidermal growth factor receptor 2 (HER2) alterations are found in approximately 1%-3% of non-small cell lung cancers (NSCLCs). We evaluated the clinical features and outcomes of NSCLC harboring HER2 alteration detected by next-generation sequencing (NGS) in Korea.
Materials and Methods
A total of 1,108 patients who were diagnosed with NSCLC between December 2015 and December 2017 were screened and analyzed by NGS. Medical records were reviewed retrospectively to analyze the clinical characteristics and outcomes from various treatments.
Results
HER2 alterations were identified in 36 NSCLC patients. Of the patients, 22 (61.1%) had an exon 20 in-frame insertion mutation, 15 (41.7%) had HER2 amplification, and one had both. The median patient age was 58 years, 55.6% were male, and 50.0% were never-smokers. Adenocarcinoma was predominant (88.9%). The most common metastatic site was bone (58.3%), and 66.7% of patients were stage IV at initial diagnosis. Six patients (16.7%) had a coexistent sensitizing epidermal growth factor receptor (EGFR) mutation, and two patients (5.6%) had anaplastic lymphoma kinase (ALK) rearrangement. With a median 14 months of follow-up, the median progression-free survival of first-line treatment was 6 months (95% confidence interval, 4.172 to 7.828), and median overall survival was not reached. The proportions of adenocarcinoma, never-smokers, and metastasis to the liver were higher in the exon 20 in-frame insertion mutation group, whereas coexistence of EGFR mutation was more frequently found in the HER2 amplification group.
Conclusion
HER2-altered NSCLC showed distinct clinical features. Moreover, different characteristics were identified between the HER2 in-frame insertion mutation group and the HER2 amplification group.

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Time Trends for Prostate Cancer Incidence from 2003 to 2013 in South Korea: An Age-Period-Cohort Analysis
Hyun Young Lee, Do Kyoung Kim, Seung Whan Doo, Won Jae Yang, Yun Seob Song, Bora Lee, Jae Heon Kim
Cancer Res Treat. 2020;52(1):301-308.   Published online August 1, 2019
DOI: https://doi.org/10.4143/crt.2019.194
AbstractAbstract PDFPubReaderePub
Purpose
Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis.
Materials and Methods
Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence.
Results
Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort.
Conclusion
PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

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Characterization of Oncolytic Vaccinia Virus Harboring the Human IFNB1 and CES2 Transgenes
Euna Cho, S M Bakhtiar Ul Islam, Fen Jiang, Ju-Eun Park, Bora Lee, Nam Deuk Kim, Tae-Ho Hwang
Cancer Res Treat. 2020;52(1):309-319.   Published online August 6, 2019
DOI: https://doi.org/10.4143/crt.2019.161
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to assess characteristics of SJ-815, a novel oncolytic vaccinia virus lacking a functional thymidine kinase-encoding TK gene, and instead, having two human transgenes: the IFNB1 that encodes interferon β1, and the CES2 that encodes carboxylesterase 2, which metabolizes the prodrug, irinotecan, into cytotoxic SN-38.
Materials and Methods
Viral replication and dissemination of SJ-815 were measured by plaque assay and comet assay, respectively, and compared to the backbone of SJ-815, a modified Western Reserve virus named WI. Tumor cytotoxicity of SJ-815 (or mSJ-815, which has the murine IFNB1 transgene for mouse cancers) was evaluated using human and mouse cancer cells. Antitumor effects of SJ-815, with/without irinotecan, were evaluated using a human pancreatic cancer-bearing mouse model and a syngeneic melanoma-bearing mouse model. The SN-38/ irinotecan ratios in mouse melanoma tissue 4 days post irinotecan treatment were compared between groups with and without SJ-815 intravenous injection.
Results
SJ-815 demonstrated significantly lower viral replication and dissemination, but considerably stronger in vitro tumor cytotoxicity than WI. The combination use of SJ-815 plus irinotecan generated substantial tumor regression in the human pancreatic cancer model, and significantly prolonged survival in the melanoma model (hazard ratio, 0.11; 95% confidence interval, 0.02 to 0.50; p=0.013). The tumor SN-38/irinotecan ratios were over 3-fold higher in the group with SJ-815 than those without (p < 0.001).
Conclusion
SJ-815 demonstrates distinct characteristics gained from the inserted IFNB1 and CES2 transgenes. The potent antitumor effects of SJ-815, particularly when combined with irinotecan, against multiple solid tumors make SJ-815 an attractive candidate for further preclinical and clinical studies.

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Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028)
E Sun Paik, Myong Cheol Lim, Moon-Hong Kim, Yun Hwan Kim, Eun Seop Song, Seok Ju Seong, Dong Hoon Suh, Jong-Min Lee, Chulmin Lee, Chel Hun Choi
Cancer Res Treat. 2020;52(1):320-333.   Published online August 5, 2019
DOI: https://doi.org/10.4143/crt.2019.124
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy.
Materials and Methods
We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors.
Results
Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group.
Conclusion
We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

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