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Volume 51(1); January 2019
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Original Articles
S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial
Choong-kun Lee, Minkyu Jung, Hyo Song Kim, Inkyung Jung, Dong Bok Shin, Seok Yun Kang, Dae Young Zang, Ki Hyang Kim, Moon Hee Lee, Bong-Seog Kim, Kyung Hee Lee, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2019;51(1):1-11.   Published online February 5, 2018
DOI: https://doi.org/10.4143/crt.2018.028
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.
Materials and Methods
Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate.
Results
Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment.
Conclusion
Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
    Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer
    Lili Liu, Li Sun, Ning Zhang, Cheng-gong Liao, Haichuan Su, Jie Min, Yang Song, Xue Yang, Xiaofeng Huang, Dongxu Chen, Yu Chen, Hong-wei Zhang, Helong Zhang
    International Journal of Hyperthermia.2022; 39(1): 239.     CrossRef
  • Comment on “post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial”
    Qiang Hu, Yuanshui Sun
    Clinical Nutrition.2021; 40(3): 1438.     CrossRef
  • THE ROLE OF ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED GASTRIC CANCER
    A. A. Bobryshev, M. M. Davudov, M. N. Narimanov, S. B. Polycarpova, V. Y. Kirsanov, V. N. Blindar
    Siberian journal of oncology.2021; 20(1): 133.     CrossRef
  • Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review
    Kotaro Sugawara, Yoshikuni Kawaguchi, Yasuyuki Seto, Jean-Nicolas Vauthey
    Surgical Oncology.2021; 38: 101599.     CrossRef
  • Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis
    Chih-Chieh Yen, Yan-Shen Shan, Ying-Jui Chao, Ting-Kai Liao, I-Shu Chen, Hsuan-Yi Huang, I-Ting Liu, Chia-Jui Yen
    BMC Cancer.2021;[Epub]     CrossRef
  • Treatment of Locally Advanced Gastric Cancer (LAGC): Back to Lauren’s Classification in Pan–Cancer Analysis Era?
    Ina Valeria Zurlo, Michele Basso, Antonia Strippoli, Maria Alessandra Calegari, Armando Orlandi, Alessandra Cassano, Mariantonietta Di Salvatore, Giovanna Garufi, Emilio Bria, Giampaolo Tortora, Carlo Barone, Carmelo Pozzo
    Cancers.2020; 12(7): 1749.     CrossRef
  • A systematic review and network meta-analysis protocol of adjuvant chemotherapy regimens for resected gastric cancer
    Long Ge, Liangying Hou, Qingxia Yang, Yiting Wu, Xiue Shi, Jiang Li, Kehu Yang
    Medicine.2019; 98(7): e14478.     CrossRef
  • Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
    Tom van den Ende, Emil ter Veer, Rosa M. A. Mali, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
    Cancers.2019; 11(4): 530.     CrossRef
  • COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis
    Tom van den Ende, Frank A. Abe Nijenhuis, Héctor G. van den Boorn, Emil ter Veer, Maarten C. C. M. Hulshof, Suzanne S. Gisbertz, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • Cutting-edge evidence of adjuvant treatments for gastric cancer
    Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera, Junichi Sakamoto
    Expert Review of Gastroenterology & Hepatology.2018; 12(11): 1109.     CrossRef
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The Effect of Hospital Case Volume on Clinical Outcomes in Patients with Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Analysis (KROG-1106)
Boram Ha, Kwan Ho Cho, Sung Ho Moon, Chang-Geol Lee, Ki Chang Keum, Yeon-Sil Kim, Hong-Gyun Wu, Jin Ho Kim, Yong Chan Ahn, Dongryul Oh, Jae Myoung Noh, Jong Hoon Lee, Sung Hwan Kim, Won Taek Kim, Young-Taek Oh, Min Kyu Kang, Jin Hee Kim, Ji-Yoon Kim, Moon-June Cho, Chul Seoung Kay, Jin Hwa Choi
Cancer Res Treat. 2019;51(1):12-23.   Published online February 5, 2018
DOI: https://doi.org/10.4143/crt.2017.273
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS).
Results
At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170).
Conclusion
A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.

Citations

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  • Accumulated Dose Deviation of Rotational and Residual Setup Errors on Nasopharyngeal Carcinoma Using MIM Treated by Helical Tomotherapy
    Wenyan Yao, Jiang Hu, Peixun Xu, Mengxue He, Yongwen Fang, Mingzhi Liu, Zongtai Li, Huilang He, Hui Liu, Wenzhao Sun, Senkui Xu
    Technology in Cancer Research & Treatment.2023;[Epub]     CrossRef
  • Systematic Review and Meta-analysis of the Association Between Radiation Therapy Treatment Volume and Patient Outcomes
    Jerry Ye Aung Kyaw, Alice Rendall, Erin F. Gillespie, Tom Roques, Laurence Court, Yolande Lievens, Alison C. Tree, Chris Frampton, Ajay Aggarwal
    International Journal of Radiation Oncology*Biology*Physics.2023; 117(5): 1063.     CrossRef
  • The Influence of Hospital Volume on the Outcomes of Nasopharyngeal, Sinonasal, and Skull-Base Tumors: A Systematic Review of the Literature
    Stephanie Flukes, Rahul K. Sharma, Shivangi Lohia, Marc A. Cohen
    Journal of Neurological Surgery Part B: Skull Base.2022; 83(03): 270.     CrossRef
  • A Comprehensive Analysis of Treatment Management and Survival Outcomes in Nasopharyngeal Carcinoma
    Khodayar Goshtasbi, Brandon M. Lehrich, Jack L. Birkenbeuel, Arash Abiri, Jeremy P. Harris, Edward C. Kuan
    Otolaryngology–Head and Neck Surgery.2021; 165(1): 93.     CrossRef
  • Hospital volume and physician volume in association with survival in patients with nasopharyngeal cancer after radiation therapy
    Tzu-Yu Lai, Chiu-Mei Yeh, Yu-Wen Hu, Chia-Jen Liu
    Radiotherapy and Oncology.2020; 151: 190.     CrossRef
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  • 5 Web of Science
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Incremental Role of Pancreatic Magnetic Resonance Imaging after Staging Computed Tomography to Evaluate Patients with Pancreatic Ductal Adenocarcinoma
Hye Jin Kim, Mi-Suk Park, Jin Yong Lee, Kyunghwa Han, Yong Eun Chung, Jin-Young Choi, Myeong-Jin Kim, Chang Moo Kang
Cancer Res Treat. 2019;51(1):24-33.   Published online February 5, 2018
DOI: https://doi.org/10.4143/crt.2017.404
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the impact of contrast enhanced pancreatic magnetic resonance imaging (MRI) in resectability and prognosis evaluation after staging computed tomography (CT) in patients with pancreatic ductal adenocarcinoma (PDA).
Materials and Methods
From January 2005 to December 2012, 298 patients were diagnosed to have potentially resectable stage PDA on CT. Patients were divided into CT+MR (patients underwent both CT and MRI; n=216) and CT only groups (n=82). Changes in resectability staging in the CT+MR group were evaluated. The overall survival was compared between the two groups. The recurrence-free survival and median time to liver metastasis after curative surgery were compared between the two groups.
Results
Staging was changed from resectable on CT to unresectable state on MRI in 14.4% of (31 of 216 patients) patients of the CT+MR group. The overall survival and recurrence-free survival rates were not significantly different between the two groups (p=0.162 and p=0.721, respectively). The median time to liver metastases after curative surgery in the CT+MR group (9.9 months) was significantly longer than that in the CT group (4.2 months) (p=0.011).
Conclusion
Additional MRI resulted in changes of resectability and treatment modifications in a significant proportion of patients who have potentially resectable state at CT and in prolonged time to liver metastases in patients after curative surgery. Additional MRI to standard staging CT can be recommended for surgical candidates of PDA.

Citations

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    Felix G. Gassert, Sebastian Ziegelmayer, Johanna Luitjens, Florian T. Gassert, Fabian Tollens, Johann Rink, Marcus R. Makowski, Johannes Rübenthaler, Matthias F. Froelich
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    Hyungjin Rhee, Mi-Suk Park
    Korean Journal of Radiology.2021; 22(1): 23.     CrossRef
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    Journal of the Korean Society of Radiology.2021; 82(3): 638.     CrossRef
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The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era
Ya-Nan Jin, Wang-Jian Zhang, Xiu-Yu Cai, Mei-Su Li, Wayne R. Lawrence, Si-Yang Wang, Dong-Mei Mai, Yu-Yun Du, Dong-Hua Luo, Hao-Yuan Mo
Cancer Res Treat. 2019;51(1):34-42.   Published online February 6, 2018
DOI: https://doi.org/10.4143/crt.2017.551
AbstractAbstract PDFPubReaderePub
Purpose
We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era.
Methods
and Materials From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses.
Results
For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05).
Conclusion
Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

Citations

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    Yu Liang, Kai-hua Chen, Jie Yang, Jing Zhang, Ru-rong Peng, Song Qu, Ling Li, Xiao-dong Zhu
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  • Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain Injury
    Tong-Min Wang, Guo-Ping Shen, Ming-Yuan Chen, Jiang-Bo Zhang, Ying Sun, Jing He, Wen-Qiong Xue, Xi-Zhao Li, Shao-Yi Huang, Xiao-Hui Zheng, Shao-Dan Zhang, Ye-Zhu Hu, Hai-De Qin, Jin-Xin Bei, Jun Ma, Jianbing Mu, Yin Yao Shugart, Wei-Hua Jia
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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01)
In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro
Cancer Res Treat. 2019;51(1):43-52.   Published online February 14, 2018
DOI: https://doi.org/10.4143/crt.2017.562
AbstractAbstract PDFPubReaderePub
Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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Medical Travel among Non-Seoul Residents to Seek Prostate Cancer Treatment in Medical Facilities of Seoul
Jae Heon Kim, So Young Kim, Seok-Joong Yun, Jae Il Chung, Hoon Choi, Ho Song Yu, Yun-Sok Ha, In-Chang Cho, Hyung Joon Kim, Hyun Chul Chung, Jun Sung Koh, Wun-Jae Kim, Jong-Hyock Park, Ji Youl Lee
Cancer Res Treat. 2019;51(1):53-64.   Published online February 20, 2018
DOI: https://doi.org/10.4143/crt.2017.468
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aims to investigate the trend in medical travel by non-Seoul residents to Seoul for treatment of prostate cancer and also to investigate the possible factors affecting the trend.
Materials and Methods
This study represents a retrospective cohort study using data from theKoreanNationalHealth Insurance System from 2002 to 2015. Annual trends were produced for proportions of patients who traveled according to the age group, economic status and types of treatment. Multiple logistic analysiswas used to determine factors affecting surgeries at medical facilities in Seoul among the non-Seoul residents.
Results
A total of 68,543 patients were defined as newly diagnosed prostate cancer cohorts from 2005 to 2014. The proportion of patients who traveled to Seoul for treatment, estimated from cases with prostate cancer-related claims, decreased slightly over 9 years (28.0 at 2005 and 27.0 at 2014, p=0.02). The average proportion of medical travelers seeking radical prostatectomy increased slightly but the increase was not statistically significant (43.1 at 2005 and 45.4 at 2014, p=0.26). Income level and performance ofrobot-assisted radical prostatectomy were significant positive factors for medical travel to medical facilities in Seoul. Combined comorbidity diseases and year undergoing surgery were significant negative factors for medical travel to medical facilities in Seoul.
Conclusion
The general trend of patients travelling from outside Seoul for prostate cancer treatment decreased from 2005 to 2014. However, a large proportion of traveling remained irrespective of direct distance from Seoul.

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Hepatic Resection Provides Survival Benefit for Selected Intermediate-Stage (BCLC-B) Hepatocellular Carcinoma Patients
Zhang Zhaohui, Shen Shunli, Chen Bin, Li Shaoqiang, Hua Yunpeng, Kuang Ming, Liang Lijian, Peng Bao Gang
Cancer Res Treat. 2019;51(1):65-72.   Published online February 26, 2018
DOI: https://doi.org/10.4143/crt.2018.038
AbstractAbstract PDFPubReaderePub
Purpose
The intermediate stage of hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B) comprises a highly heterogeneous population, and the treatment strategy is still controversial. Because of the heterogeneity, a subclassification of intermediate-stage HCCs was put forward by Bolondi according to the ‘beyond Milan and within up-to-7’ criteria and Child-Pugh score. In this study, we aim to analyze the prognosis of BCLC-B stage HCC patients who received hepatic resection according to the Bolondi’s subclassification.
Materials and Methods
One thousand and one hundred three patients diagnosedwith HCC and treatedwith hepatic resectionwere enrolled in our hospital between 2006 and 2012. According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed.
Results
According to Bolondi’s subclassification, the BCLC-B patients were divided into four groups: B1 (n=41, 18.7%), B2 (n=160, 73.1%), B3 (n=11, 5.0%), and B4 (n=7, 3.2%). Significant difference was observed between B1 and other groups (B1 vs. B2, p=0.022; B1 vs. B3, p < 0.001; B1 vs. B4, p < 0.001), but no difference for B2 vs. B4 (p=0.542) and B3 vs. B4 (p=0.542). In addition, no significant differences were observed between BCLC-A and BCLC-B1 group for both RFS (p=0.087) and OS (p=0.643). In multivariate analysis, BCLC-B subclassification was not a risk factor for both OS (p=0.263) and RFS (p=0.892).
Conclusion
In our study, HCC patients at B1 stagewere benefited from hepatic resection and had similar survival to BCLC-A stage patients. Our study provided rationality of hepatic resection for selected BCLC-B stage HCC patients instead of routine transarterial chemoembolization.

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Paranasal Sinus Invasion in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy
Caineng Cao, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Qiaoying Hu, Yuanyuan Chen, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Xiaozhong Chen
Cancer Res Treat. 2019;51(1):73-79.   Published online February 26, 2018
DOI: https://doi.org/10.4143/crt.2017.607
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study is to evaluate the prognostic significance of paranasal sinus invasion for nasopharyngeal carcinoma (NPC) and its suitable position in the T classification.
Materials and Methods
The magnetic resonance imaging (MRI) scans of 695 patients with previously untreated, biopsy-proven, non-metastatic NPC that was treated with intensity-modulated radiotherapy (IMRT) were reviewed retrospectively.
Results
The incidence of paranasal sinus invasion was 39.4% (274 of 695 patients). Multivariate analysis showed that paranasal sinus invasion was an independent negative prognostic factor for local failure-free survival (LFFS) (p < 0.05). According to the eighth American Joint Committee on Cancer (AJCC) staging system, 275 patients were classified as T3 classification. Of these, 78 patients (28.4%) developed paranasal sinus invasion (T3b) and 197 (71.6%) didn’t (T3a). The estimated 5-year LFFS and overall survival (OS) rates for the patients with T3b and T3a classification were 88.6% versus 95.0% (p=0.047), and 84.5% versus 93.3% (p=0.183), respectively. The estimated 5-year LFFS and OS rates for the patientswith T4 classificationwere 89.5% and 83.2%,whichwere similarwith the outcomes of patients with T3b classification.
Conclusion
MRI-determined paranasal sinus invasion is an independent prognostic factor of NPC treated by IMRT. Paranasal sinus invasion is recommended to classify as T4 classification in the 8th AJCC staging system for NPC.

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Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Cancer Res Treat. 2019;51(1):80-89.   Published online February 26, 2018
DOI: https://doi.org/10.4143/crt.2017.500
AbstractAbstract PDFPubReaderePub
Purpose
In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear.
Materials and Methods
We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts.
Results
In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041).
Conclusion
Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.

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A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy: Results of the Korean South West Oncology Group (KSWOG) Study
So-Yeon Jeon, Hye Sook Han, Woo Kyun Bae, Moo-Rim Park, Hyeok Shim, Sang-Cheol Lee, Se-Il Go, Hwan Jung Yun, Yong-Jin Im, Eun-Kee Song
Cancer Res Treat. 2019;51(1):90-97.   Published online February 27, 2018
DOI: https://doi.org/10.4143/crt.2017.577
AbstractAbstract PDFPubReaderePub
Purpose
Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC.
Materials and Methods
We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL.
Results
Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015).
Conclusion
Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

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Validation of the Eighth American Joint Committee on Cancer Staging System for Distal Bile Duct Carcinoma
Sun-Young Jun, You-Na Sung, Jae Hoon Lee, Kwang-Min Park, Young-Joo Lee, Seung-Mo Hong
Cancer Res Treat. 2019;51(1):98-111.   Published online March 2, 2018
DOI: https://doi.org/10.4143/crt.2017.595
AbstractAbstract PDFPubReaderePub
Purpose
T category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes.
Materials and Methods
To validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions.
Results
T categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011; T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001; N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002; II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors.
Conclusion
The T andNcategories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis.

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Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Maria Lee, Yumi Lee, Kidong Kim, Eun Young Park, Myong Cheol Lim, Jung-Sup Kim, Hee Seung Kim, Yong-Beom Kim, Yong-Man Kim, Jungnam Joo, Sang Yoon Park, Chel Hun Choi, Jae-Hoon Kim
Cancer Res Treat. 2019;51(1):112-118.   Published online March 7, 2018
DOI: https://doi.org/10.4143/crt.2017.361
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility.
Materials and Methods
In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated.
Results
Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting.
Conclusion
Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

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Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer
Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo
Cancer Res Treat. 2019;51(1):119-127.   Published online March 12, 2018
DOI: https://doi.org/10.4143/crt.2018.019
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
Materials and Methods
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
Results
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
Conclusion
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

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Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients
Ling Deng, Xuehua Zhu, Yun Sun, Jiemin Wang, Xiaorong Zhong, Jiayuan Li, Min Hu, Hong Zheng
Cancer Res Treat. 2019;51(1):128-140.   Published online March 15, 2018
DOI: https://doi.org/10.4143/crt.2017.598
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis.
Materials and Methods
Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CAwere detected in freshfrozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed.
Results
The AKT1mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival.
Conclusion
A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.

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    Pathology - Research and Practice.2022; 238: 154063.     CrossRef
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    Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
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    A. L. Kornietskaya, L. V. Bolotina, S. F. Evdokimova, V. V. Savchina, Yu. B. Karagodina, A. A. Kachmazov
    Meditsinskiy sovet = Medical Council.2022; (22): 148.     CrossRef
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    Mahboobeh Hodaei, Mehdi Rahimmalek, Mandana Behbahani
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    Dirk Hempel, Florian Ebner, Arun Garg, Zeljka Trepotec, Armin Both, Werner Stein, Andreas Gaumann, Lucia Güttler, Wolfgang Janni, Amelie DeGregorio, Louisa Hempel, Valeria Milani
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    Daniela Miricescu, Alexandra Totan, Iulia-Ioana Stanescu-Spinu, Silviu Constantin Badoiu, Constantin Stefani, Maria Greabu
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What We Talk about When We Talk about Caregiving: The Distribution of Roles in Cancer Patient Caregiving in a Family-Oriented Culture
Ansuk Jeong, Dongwook Shin, Jong Hyock Park, Keeho Park
Cancer Res Treat. 2019;51(1):141-149.   Published online March 21, 2018
DOI: https://doi.org/10.4143/crt.2017.557
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
When it comes to cancer care, the psychological well-being of family caregivers has gotten its deserved attention. However, the specific roles that the family caregivers take have not been examined as much. The current study aimed to investigate the distribution of family caregivers’ roles, particularly in a family-oriented culture, Korea.
Materials and Methods
A sample of 439 participants was recruited from 11 national and regional cancer centers in Korea. The participants who were 60 years old or above went through treatments for their gastric, colorectal, or lung cancer. The individual survey included questions regarding the family type, living arrangement, and the sources of support when it comes to their physical, emotional, financial, and decision-making needs.
Results
The responses from the participants showed that cancer caregiving is shared by multiple family caregivers; the major source of support for elderly cancer patients on diverse domains was their spouse; patients’ reliance on their daughter(s) increased for emotional support; and patients’ reliance on their son(s) stood out for financial support and decision-making support. Also, the older the patients were, the heavier their reliance was on the adult children, including sons, daughters, and daughters-in-law.
Conclusion
Future support programs for elderly cancer patients are suggested to involve multiple family caregivers to encourage effective and efficient intervention. Also, the limitations of the current study and the suggestions for future research are discussed.

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    Araviinthansai Subramaniam, Kalyani Kirtikar Mehta
    International Journal of Environmental Research and Public Health.2024; 21(2): 182.     CrossRef
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    Myung Kyung Lee
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    Laura M.L. Tielemans, Kirsten D. van Heugten, Marije E. Hamaker, Inez C. van Walree
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    Cristina Alfaro-Díaz, Erla Kolbrun Svavarsdottir, Nuria Esandi, Marianne E. Klinke, Ana Canga-Armayor
    Journal of Family Nursing.2022; 28(2): 95.     CrossRef
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    Karen S. Lyons, Jessica R. Gorman, Brandon S. Larkin, Grace Duncan, Brandon Hayes-Lattin
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    Siew Tzuh, Wen-Cheng Chang, Wen-Chi Chou, Chia-Hsun Hsieh, Jen-Shi Chen, Fur-Hsing Wen
    Journal of Palliative Medicine.2021; 24(3): 405.     CrossRef
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    Shradha S. Parsekar, Ajay Bailey, Binu V. S., Suma Nair
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The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH
Jin-Hua Liang, Luo Lu, Hua-Yuan Zhu, Wang Li, Lei Fan, Jian-Yong Li, Wei Xu
Cancer Res Treat. 2019;51(1):150-157.   Published online April 2, 2018
DOI: https://doi.org/10.4143/crt.2017.476
AbstractAbstract PDFPubReaderePub
Purpose
Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens.
Materials and Methods
Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen.
Results
Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response.
Conclusion
Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

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  • Impact of the peripheral blood inflammatory indices and modified nomogram-revised risk index on survival of Extranodal Nasal-Type Natural Killer/T-Cell lymphoma
    Qing Hou, He Li, Yu Liang, Ningning Yao, Xin Cao, Jianting Liu, Bochen Sun, Peixin Feng, Wenjuan Zhang, Jianzhong Cao
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    M. Mathieu, M. de Vicq de Cumptich, A. Kul, B. Richert
    Journal of the European Academy of Dermatology and Venereology.2024;[Epub]     CrossRef
  • Real-world study and prognostic analysis of angioimmunoblastic T-cell lymphoma
    Suxiao Li, Xiaoyan Feng, Yunfei Song, Mengke Fan, Qingjiang Chen, Mingzhi Zhang, Xiaolong Wu, Meng Dong, Jieming Zhang, Lijuan Han, Xudong Zhang
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • The Clinical Significance and Prognostic Role of Whole-Blood Epstein-Barr Virus DNA in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis
    Jing Zhang, Shuchao Qin, Ze Jin, Qingqing Chen, Lingxiao Xing, Tonglu Qiu, Yi Xia, Jinhua Liang, Huayuan Zhu, Li Wang, Lei Fan, Wei Xu, Jianyong Li, Yi Miao
    Journal of Clinical Immunology.2023; 43(6): 1302.     CrossRef
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    Tong-Yao Xing, Zi-Wen Duan, Wei-Ting Wang, Kai-Xin Du, Hao-Rui Shen, Hua Yin, Jia-Zhu Wu, Yue Li, Li Wang, Jian-Yong Li, Jin-Hua Liang, Wei Xu
    Annals of Hematology.2023; 102(9): 2471.     CrossRef
  • Impact of Epstein-Barr Virus on Peripheral T-Cell Lymphoma Not Otherwise Specified and Angioimmunoblastic T-Cell Lymphoma
    Tong-Yoon Kim, Gi-June Min, Young-Woo Jeon, Sung-Soo Park, Silvia Park, Seung-Hawn Shin, Seung-Ah Yahng, Jae-Ho Yoon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Hee-Je Kim, Chang-Ki Min, Jong-Wook Lee, Seok-Goo Cho
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Zheng Cao, Linshu Zeng, Lin Feng, Xiaoli Feng
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    Jia-Qi Qin, Hua Yin, Jia-Zhu Wu, Rui-Ze Chen, Yi Xia, Li Wang, Hua-Yuan Zhu, Lei Fan, Jian-Yong Li, Jin-Hua Liang, Wei Xu
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    Davide Facchinelli, Alice Parisi, Mauro Krampera, Dino Veneri
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    Chen Huang, Huichao Zhang, Yuhuan Gao, Lanping Diao, Lihong Liu
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    Woo Jin Lee, Kwang Hee Won, Jae Won Choi, Chong Hyun Won, Sung Eun Chang, Jee Ho Choi, Mi Woo Lee
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Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma
In Kyoung Hwang, Seung Sook Paik, Seung Hyeun Lee
Cancer Res Treat. 2019;51(1):158-168.   Published online April 2, 2018
DOI: https://doi.org/10.4143/crt.2018.084
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma.
Materials and Methods
We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups.
Results
A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group.
Conclusion
Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.

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    Chuan Wang, Rong-Qi Zou, Guo-Zhong He
    Frontiers in Immunology.2024;[Epub]     CrossRef
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    Lovisa Karlsson, Isabelle Öhrnberg, Shumaila Sayyab, David Martínez-Enguita, Mika Gustafsson, Patricia Espinoza, Melissa Méndez-Aranda, Cesar Ugarte-Gil, Lameck Diero, Ronald Tonui, Jakob Paues, Maria Lerm
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    Giulia Polinário, Laura Maria Duran Gleriani Primo, Maiara Alane Baraldi Cerquetani Rosa, Freddy Humberto Marin Dett, Paula Aboud Barbugli, Cesar Augusto Roque-Borda, Fernando Rogério Pavan
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    Abhay Vashishth, Mohd Shuaib, Tanya Bansal, Shashank Kumar
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    Nadira Putri Nastiti, Laksmi Wulandari, Sulistiawati Sulistiawati, Anna Febriani, Wiwin Is Effendi
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    Soo Young Hwang, Jong Yeob Kim, Hye Sun Lee, Sujee Lee, Dayeong Kim, Subin Kim, Jong Hoon Hyun, Jae Il Shin, Kyoung Hwa Lee, Sang Hoon Han, Young Goo Song
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    Javier Cabrera-Sanchez, Vicente Cuba, Victor Vega, Patrick Van der Stuyft, Larissa Otero
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    Reema Bansal, Mohd M. Khan, Surendra Dasari, Indu Verma, David R. Goodlett, Nathan P. Manes, Aleksandra Nita-Lazar, Surya P. Sharma, Aman Kumar, Nirbhai Singh, Anuradha Chakraborti, Vishali Gupta, M.R. Dogra, Jagat Ram, Amod Gupta
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    Caibao Jin, Bin Yang
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The Risk of Herpes Zoster in Patients with Non-small Cell Lung Cancer according to Chemotherapy Regimens: Tyrosine Kinase Inhibitors versus Cytotoxic Chemotherapy
Ji Young Choi, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Seong Jin Jo
Cancer Res Treat. 2019;51(1):169-177.   Published online April 5, 2018
DOI: https://doi.org/10.4143/crt.2017.491
AbstractAbstract PDFPubReaderePub
Purpose
Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients.
Materials and Methods
We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method.
Results
Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different.
Conclusion
Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.

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  • The effect of food on the pharmacokinetics of Sutetinib maleate capsule, an irreversible EGFR tyrosine kinase inhibitor, in healthy Chinese subjects
    Bei Cao, Tingting Ma, Yuqiang Zhang, Lei Huang, Hui Lin, Huanhuan Jiang, Yu Zhao, Yan Geng, Yuanxun Yang, Sumin Cao, Juan Li
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    Yoshiaki Nagai, Masafumi Sata, Hiromitsu Ohta, Tsugitoshi Onuki, Tatsuya Saito, Ayumi Uchiyama, Ayako Kurosaki, Naoko Yoshizumi, Ayako Takigami, Shoko Nakazawa, Masayuki Nakayama, Hironori Yamaguchi, Koichi Hagiwara
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    Naoya Yasokawa, Yuri Yasuda, Houhi Chin, Koji Kurose, Yumi Aoyama, Toru Oga
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Psychosocial Health of Disease-Free Breast Cancer Survivors Compared with Matched Non-cancer Controls
Boyoung Park, Moo Hyun Lee, Sun-Young Kong, Eun Sook Lee
Cancer Res Treat. 2019;51(1):178-186.   Published online April 5, 2018
DOI: https://doi.org/10.4143/crt.2017.585
AbstractAbstract PDFPubReaderePub
Purpose
The present study investigated the psychosocial health of disease-free breast cancer survivors who receive health examinations compared to matched non-cancer controls in a community setting.
Materials and Methods
We used baseline data from the Health Examinee cohort, which is composed of subjects participating in health. The disease-free breast cancer survivors were defined as those who were ≥ 2 years from initial diagnosis of breast cancer who had completed treatment. Females without a history of cancer were randomly selected at 1:4 ratio by 5-year age groups, education, and household income as a comparison group. We analyzed results from the Psychosocial Well-being Index-Short Form (PWI-SF) as a psychosocial health measurement.
Results
A total of 347 survivors of breast cancer and 1,388 matched controls were included. Total scores on the PWI-SF were lower in breast cancer survivors than matched non-cancer controls (p=0.006), suggesting a lower level of psychosocial stress in breast cancer survivors. In comparison to the control group, prevalence of drinking, smoking and obesity were lower, while exercising for ≥ 150 min/wk was higher in breast cancer survivors (p < 0.05). These findings suggest that breast cancer survivors have better health behaviors than their noncancer controls. After adjusting for other sociodemographic variables, breast cancer survivors were 36% less likely to be included in the stress group (odds ratio, 0.64; 95% confidence interval, 0.42 to 0.98).
Conclusion
The disease-free breast cancer survivors resuming daily life demonstrated better psychosocial health status compared to matched non-cancer controls.

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Long-term Survival in Patients Treated with a Robotic Radiosurgical Device for Liver Metastases
Sebastian Stintzing, Jobst von Einem, Christoph Fueweger, Alfred Haidenberger, Michael Fedorov, Alexander Muavcevic
Cancer Res Treat. 2019;51(1):187-193.   Published online April 16, 2018
DOI: https://doi.org/10.4143/crt.2017.594
AbstractAbstract PDFPubReaderePub
Purpose
The treatment of liver metastases with local procedures is a fast progressing field. For the most, long-term survival data is missing raising questions with regard to the efficacy of such modalities when compared to surgical resection. Radiosurgery using the CyberKnife device enables the treatment of liver lesions with a single-session approach. Here we present long-term survival data to explore the curative potential of this strategy.
Materials and Methods
Patients with oligo-metastatic disease limited to the liver have been treated with single-session or hypo-fractioned radiosurgery in curative intent and prospectively followed until death. Follow-up (FU) was performed using magnetic resonance imaging (MRI) 2 months after radiation and at 3-month intervals for the first 2 years. After that annual computed tomography or MRI scans were performed until 5 years post-treatment. Local recurrence in the radiated volume and recurrence outside the treated volume were used to define local and distant progression. Survival times were censored at the time of the last FU.
Results
One hundred twenty-six patients treated between 2005 and 2015 with 194 lesions were included into this study. Median FU was 30.0 months. According to Response Evaluation Criteria in Solid Tumors, 55.2% had a complete remission and 11.3% a partial remission. Seventy-two point two percent recurred outside the radiated lesion and median overall survival was 35.2 months with a 3-year survival rate of 47.7%.
Conclusion
This is currently the largest cohort of stereotactic body radiation therapy treated liver lesions with a median long-term follow of 30 months. Robotic radiosurgery using a single session approach has a high efficacy to control the radiated lesion with the potential to cure patients.

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  • Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment
    Ilektra Kyrochristou, Ilias Giannakodimos, Maria Tolia, Ioannis Georgakopoulos, Nikolaos Pararas, Francesk Mulita, Nikolaos Machairas, Dimitrios Schizas
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    Colleen M. Garvey, Roy Lau, Alyssa Sanchez, Ren X. Sun, Emma J. Fong, Michael E. Doche, Oscar Chen, Anthony Jusuf, Heinz-Josef Lenz, Brent Larson, Shannon M. Mumenthaler
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Cancer-Associated Fibroblasts Promote the Chemo-resistance in Gastric Cancer through Secreting IL-11 Targeting JAK/STAT3/Bcl2 Pathway
Jun Ma, Xiao Song, Xiaowu Xu, Yiping Mou
Cancer Res Treat. 2019;51(1):194-210.   Published online April 20, 2018
DOI: https://doi.org/10.4143/crt.2018.031
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Our aim was to detect the potential role of interleukin 11 (IL-11) in the development of chemo-resistance in gastric cancer and to reveal the mechanism involved in the process.
Materials and Methods
Here, we used flow cytometry to examine the percentage of cancer-associated-fibroblasts in tumor samples from chemo-resistant and -sensitive gastric cancer patients. Using MTT assay, we detected the cell viability under different conditions. Using quantitative real-time polymerase chain reaction and Western blotting, we determined the target expressions in mRNA and protein levels. We also performed immunohistochemistry and immunofluorescence to detect the target proteins under different conditions. Animal models were constructed to verify the potential role of IL-11 in chemo-resistant develop in vivo.
Results
Herein, we observed enriched cancer associated fibroblasts in drug resistant tumor tissues from gastric patients. Those fibroblasts facilitate the chemotherapeutic drugs resistance development through the secretion of IL-11, which activates the IL-11/IL-11R/gp130/ JAK/STAT3 anti-apoptosis signaling pathway in gastric cancer cells. We found that the combination of chemotherapeutic drugs and JAK inhibitor overcomes the resistance and increases the survival of mice with gastric cancer xenografts.
Conclusion
Ourresults demonstrated that IL-11 contributed to the obtain ofresistance to chemotherapy drugs through gp130/JAK/STAT3/Bcl2 pathway, and targeting the IL-11 signaling pathway induced by fibroblasts might be a promising strategy to overcome the multi-drugs resistant cancer in clinic.

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients
Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park
Cancer Res Treat. 2019;51(1):211-222.   Published online April 23, 2018
DOI: https://doi.org/10.4143/crt.2018.132
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer
Jin Won Kim, Jong Gwang Kim, Byung Woog Kang, Ik-Joo Chung, Young Seon Hong, Tae-You Kim, Hong Suk Song, Kyung Hee Lee, Dae Young Zang, Yoon Ho Ko, Eun-Kee Song, Jin Ho Baek, Dong‐Hoe Koo, So Yeon Oh, Hana Cho, Keun-Wook Lee
Cancer Res Treat. 2019;51(1):223-239.   Published online October 19, 2018
DOI: https://doi.org/10.4143/crt.2018.073
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC).
Materials and Methods
Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians.
Results
Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy.
Conclusion
This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Citations

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  • Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer
    Z.A. Wainberg, P.C. Enzinger, S. Qin, K. Yamaguchi, J. Wang, X. Zhou, A. Gnanasakthy, K. Taylor, A. Yusuf, I. Majer, A. Jamotte, Y.-K. Kang
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    Adán Rodríguez-Gonzalez, Alberto Carmona-Bayonas, Raquel Hernandez San Gil, Patricia Cruz-Castellanos, Mónica Antoñanzas-Basa, David Lorente-Estelles, María Jose Corral, Manuel González-Moya, Oscar Alfredo Castillo-Trujillo, Emilio Esteban, Paula Jiménez-
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    Xing Wu, Weiwei Zhang
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    Eun Mi Lee, Paula Jiménez-Fonseca, Rocio Galán-Moral, Sara Coca-Membribes, Ana Fernández-Montes, Elena Sorribes, Esmeralda García-Torralba, Laura Puntí-Brun, Mireia Gil-Raga, Juana Cano-Cano, Caterina Calderon
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The Comparison of Oncologic Outcomes between Open and Laparoscopic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Korean Multicenter Collaborative Study
Tae Heon Kim, Bumsik Hong, Ho Kyung Seo, Seok Ho Kang, Ja Hyeon Ku, Byong Chang Jeong, on behalf of Urothelial Cancer-Advanced Research and Treatment (UCART) Study Group
Cancer Res Treat. 2019;51(1):240-251.   Published online April 24, 2018
DOI: https://doi.org/10.4143/crt.2017.417
AbstractAbstract PDFPubReaderePub
Purpose
We compared oncologic outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent open nephroureterectomy (ONU) or laparoscopic nephroureterectomy (LNU).
Materials and Methods
Consecutive cases of ONU and LNU between 2000 and 2012 at five participating institutions were included in this retrospective analysis. Clinical characteristics and pathologic outcomes were compared between the two surgical approaches. The influence of the type of surgical approach on intravesical recurrence-free survival (IVRFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using the Kaplan-Meier method and differences were assessed with the log-rank test. Predictors of IVRFS, PFS, CSS, and OS were also analyzed with a multivariable Cox regression model.
Results
A total of 1,521 patients with UTUC were eligible for the present study (ONU, 906; LNU, 615). The estimated 5-year IVRFS (57.8 vs. 51.0%, p=0.010), CSS (80.4 vs. 76.4%, p=0.032), and OS (75.8 vs. 71.4%, p=0.026) rates were significantly different between the two groups in favor of LNU. Moreover, in patients with locally advanced disease (pT3/pT4), the LNU group showed better 5-year IVRFS (62.9 vs. 54.1%, p=0.038), CSS (64.3 vs. 56.9%, p=0.022), and OS (60.4 vs. 53.1%, p=0.018) rates than the ONU group. Multivariable Cox regression analyses showed that type of surgical approach was independently associated with IVRFS, but was not related to PFS, CSS, and OS.
Conclusion
Our findings indicate that LNU provided better oncologic control of IVRFS, CSS, and OS compared with ONU for the management of patients with UTUC.

Citations

Citations to this article as recorded by  
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    Giuseppe Ottone Cirulli, Nicholas Corsi, Ivan Rakic, Alex Stephens, Giuseppe Chiarelli, Marco Finati, Matthew Davis, Shane Tinsley, Akshay Sood, Nicolò Buffi, Giovanni Lughezzani, Giuseppe Carrieri, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Cr
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    Guihong Liu, Zeqin Yao, Guoqiang Chen, Yalang Li, Bing Liang
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    Guihong Liu, Zeqin Yao, Guoqiang Chen, Yalang Li, Bing Liang
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    Tae Heon Kim, Yoon Seok Suh, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Hyun Hwan Sung
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  • 210 Download
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Tumor-Associated Macrophages Derived TGF-β‒Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway
Jianhui Cai, Limin Xia, Jinlei Li, Shichang Ni, Huayu Song, Xiangbin Wu
Cancer Res Treat. 2019;51(1):252-266.   Published online April 25, 2018
DOI: https://doi.org/10.4143/crt.2017.613
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process.
Materials and Methods
In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins.
Results
Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells.
Conclusion
Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.

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Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients
Jung-Hwan Oh, Mun-Gan Rhyu, Suk-Il Kim, Mi-Ri Yun, Jung-Ha Shin, Seung-Jin Hong
Cancer Res Treat. 2019;51(1):267-279.   Published online April 30, 2018
DOI: https://doi.org/10.4143/crt.2018.085
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigenetic period for neoplastic transformation.
Materials and Methods
Normal-appearing gastric mucosa was biopsied from 110 H. pylori–positive controls, 95 H. pylori–negative controls, 99 gastric cancer patients, and 118 gastric dysplasia patients. Gastric atrophy was assessed using endoscopic-atrophic-border score. Methylation-variable sites of eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR (MMP2, CDKN2A, RUNX2, and RUNX3) retroelements and stomach-specific TFF3 gene were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction.
Results
Mean ages of H. pylori–positive controls with mild, moderate, and severe atrophy were 51, 54, and 65 years and those of H. pylori–associated TFF3 overmethylation at the three atrophic levels (51, 58, and 63 years) tended to be periodic. Alu-adjacent overmethylation (50 years) was earlier than TFF3 overmethylation (58 years) in H. pylori–positive controls with moderate atrophy. Cancer patients with moderate atrophy showed late Alu-adjacent (58 years) overmethylation and frequent LTR-adjacent overmethylation. LTR-adjacent overmethylation was frequent in cancer (66 years) and dysplasia (68 years) patients with severe atrophy.
Conclusion
Atrophic progression is associated with gastric cancer at moderate level by impeding the initiation of Alu-adjacent methylation. LTR-adjacent methylation is increased in cancer patients and subsequently in dysplasia patients.

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    Maryam Shirani, Reza Pakzad, Mohammad Hossein Haddadi, Sousan Akrami, Arezoo Asadi, Hossein Kazemian, Melika Moradi, Vahab Hassan Kaviar, Abolfazl Rafati Zomorodi, Saeed Khoshnood, Mahnaz Shafieian, Ronia Tavasolian, Mohsen Heidary, Morteza Saki
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Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers
Eun-Gyeong Lee, Hyok Jo Kang, Myong Cheol Lim, Boyoung Park, Soo Jin Park, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Sang-Yoon Park, Boram Park, Jungnam Joo, Jai Hong Han, Sun-Young Kong, Eun Sook Lee
Cancer Res Treat. 2019;51(1):280-288.   Published online May 4, 2018
DOI: https://doi.org/10.4143/crt.2018.079
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers.
Materials and Methods
The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management.
Results
Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001).
Conclusion
RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.

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    Akiko Abe, Hidetaka Nomura, Atsushi Fusegi, Mayu Yunokawa, Arisa Ueki, Eri Habano, Hiromi Arakawa, Keika Kaneko, Yuko Minoura, Hitoshi Inari, Takayuki Ueno, Hiroyuki Kanao
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    Sung Mi Jung, Jai Min Ryu, Hyung Seok Park, Ji Soo Park, Eunyoung Kang, Seeyoun Lee, Han-Byoel Lee, Hyun Jo Youn, Tae-Kyung Yoo, Jisun Kim, Jeong Eon Lee, Sang Ah Han, Dongwon Kim, Sung-Won Kim
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Health-Related Quality of Life, Perceived Social Support, and Depression in Disease-Free Survivors Who Underwent Curative Surgery Only for Prostate, Kidney and Bladder Cancer: Comparison among Survivors and with the General Population
Dong Wook Shin, Hyun Sik Park, Sang Hyub Lee, Seung Hyun Jeon, Seok Cho, Seok Ho Kang, Seung Chol Park, Jong Hyock Park, Jinsung Park
Cancer Res Treat. 2019;51(1):289-299.   Published online May 4, 2018
DOI: https://doi.org/10.4143/crt.2018.053
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare health-related quality of life (HRQoL) of disease-free prostate (PC), kidney (KC), and bladder cancer (BC) survivors with that of the general population.
Materials and Methods
Our study included 331 urological cancer (UC) survivors (114 PC, 108 KC, and 109 BC) aged ≥ 50 years disease-free for at least 1 year after surgery. The control group included 1,177 subjects without a history of cancer. The HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30, the Duke-UNC Functional Social Support Questionnaire, and the Patient Health Questionnaire-9.
Results
There was no significant difference between the groups in terms of any of the functioning sub-scales and symptoms, except significantly lower social functioning observed in BC survivors than that observed in KC survivors. Although the three groups of UC survivors showed essentially similar functioning sub-scales and symptoms when compared to the general population, PC and BC survivors showed significantly lower social functioning and a lower appetite than that observed in controls. KC survivors showed lower physical functioning, as well as higher pain and dyspnea. Although all three groups of UC survivors reported higher financial difficulties, they also reported higher perceived social support than that reported by the non-cancer control group. No statistically significant difference was observed in terms of depressive symptoms between each group of UC survivors and the general population.
Conclusion
Disease-free survivors of the three major types of UCs showed generally similar HRQoL compared to the general population, as well as compared to each other.

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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma
Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim
Cancer Res Treat. 2019;51(1):300-312.   Published online May 9, 2018
DOI: https://doi.org/10.4143/crt.2018.012
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

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Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same
Vishal Sahu, Lokesh Nigam, Vertica Agnihotri, Abhishek Gupta, Shashank Shekhar, Naidu Subbarao, Suman Bhaskar, Sharmistha Dey
Cancer Res Treat. 2019;51(1):313-325.   Published online May 9, 2018
DOI: https://doi.org/10.4143/crt.2018.105
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same.
Materials and Methods
Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors.
Results
We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket.
Conclusion
In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

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