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Volume 49(3); July 2017
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Special Article
Development of a Community-Based Palliative Care Model for Advance Cancer Patients in Public Health Centers in Busan, Korea
Sook-Nam Kim, Soon-Ock Choi, Seong Hoon Shin, Ji-Sun Ryu, Jeong-Won Baik
Cancer Res Treat. 2017;49(3):559-568.   Published online October 18, 2016
DOI: https://doi.org/10.4143/crt.2016.276
AbstractAbstract PDFPubReaderePub
Purpose
A feasible palliative care model for advance cancer patients is needed in Korea with its rapidly aging population and corresponding increase in cancer prevalence. This study describes the process involved in the development of a community-based palliative care (CBPC) model implemented originally in a Busan pilot project.
Materials and Methods
The model development included steps I and II of the pilot project, identification of the service types, a survey exploring the community demand for palliative care, construction of an operational infrastructure, and the establishment of a service delivery system. Public health centers (including Busan regional cancer centers, palliative care centers, and social welfare centers) served as the regional hubs in the development of a palliative care model.
Results
The palliative care project included the provision of palliative care, establishment of a support system for the operations, improvement of personnel capacity, development of an educational and promotional program, and the establishment of an assessment system to improve quality. The operational infrastructure included a service management team, provision teams, and a support team. The Busan Metropolitan City CBPC model was based on the principles of palliative care as well as the characteristics of public health centers that implemented the community health projects.
Conclusion
The potential use of the Busan CBPC model in Korea should be explored further through service evaluations.

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Original Articles
An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer
In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro
Cancer Res Treat. 2017;49(3):569-577.   Published online September 12, 2016
DOI: https://doi.org/10.4143/crt.2016.289
AbstractAbstract PDFPubReaderePub
Purpose
Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).
Materials and Methods
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).
Results
The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.
Conclusion
Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

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    Xin-shuai Wang, De-jiu Kong, Tzu-yin Lin, Xiao-cen Li, Yoshihiro Izumiya, Xue-zhen Ding, Li Zhang, Xiao-chen Hu, Jun-qiang Yang, She-gan Gao, Kit S Lam, Yuan-pei Li
    Acta Pharmacologica Sinica.2017; 38(6): 931.     CrossRef
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Real-World Treatment Patterns among Patients with Advanced Gastric Cancer in South Korea
Gebra Cuyun Carter, Anna Kaltenboeck, Jasmina Ivanova, Astra M. Liepa, Alexandra San Roman, Maria Koh, Narayan Rajan, Rebecca Cheng, Howard G. Birnbaum, Jong Seok Kim, Yung-Jue Bang
Cancer Res Treat. 2017;49(3):578-587.   Published online September 12, 2016
DOI: https://doi.org/10.4143/crt.2016.001
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to understand patient treatment patterns, outcomes, and healthcare resource use in cases of metastatic and/orlocally recurrent, unresectable gastric cancer (MGC) in South Korea.
Materials and Methods
Thirty physicians reviewed charts of eligible patients to collect de-identified data. Patients must have received platinum/fluoropyrimidine first-line therapy followed by second-line therapy or best supportive care, had no other primary cancer, and not participated in a clinical trial following MGC diagnosis. Data were summarized using descriptive statistics. Kaplan-Meier analysis was used to describe survival.
Results
Of 198 patients, 73.7% were male, 78.3% were diagnosed with MGC after age 55 (mean, 61.3 years), and 47.0% were current orformer smokers. The majority of tumorswere located in the antrum/pylorus (51.5%). Metastatic sites most often occurred in the peritoneum (53.5%), lymph nodes (47.5%), and liver (38.9%). At diagnosis, the mean Charlson comorbidity indexwas 0.4 (standard deviation, 0.6). The most common comorbiditieswere chronic gastritis (22.7%) and cardiovascular disease (18.7%). Most patients (80.3%) received second-line treatment. Single-agent fluoropyrimidine was reported for 22.0% of patients, while 19.5% were treated with irinotecan and a fluoropyrimidine or platinum agent. The most common physician-reported symptoms during second-line treatment were nausea/vomiting (44.7%) and pain (11.3%), with antiemetics (44.7%), analgesics (36.5%), and nutritional support (11.3%) most often used as supportive care. Two-thirds of inpatient hospitalizations were for chemotherapy infusion. Outpatient hospitalization (31.6%) and visits to the oncologist (58.8%) were common among second-line patients.
Conclusion
Most patients received second-line treatment, although regimens varied. Understanding MGC patient characteristics and treatment patterns in South Korea will help address unmet needs.

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    Jingdong Zhang, Guangyu Wang, Xianhe Xie, Wensheng Pan, Qian Dong, Nianhai Zhang, Jie Dong, Li Zhou, Chan Zhou, Jinnan Li, Grace Segall, Yanqiao Zhang
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    Sylvain Manfredi, Marie Dior, Olivier Bouche, Emilie Barbier, Vincent Hautefeuille, Marielle Guillet, Justine Turpin, Vincent Bourgeois, Dall Osto Helene, Romain Desgrippes, Franck Audemar, Yann Molin, Christophe Locher, Thierry Chatellier, Thierry Lecomt
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Survey of Medical Oncology Status in Korea (SOMOS-K): A National Survey of Medical Oncologists in the Korean Association for Clinical Oncology (KACO)
Do Yeun Kim, Yun Gyoo Lee, Bong-Seog Kim
Cancer Res Treat. 2017;49(3):588-594.   Published online September 23, 2016
DOI: https://doi.org/10.4143/crt.2016.313
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to investigate the current role of medical oncologists in cancer care with a focus on increasing the recognition of medical oncology as an independent specialty.
Materials and Methods
Questionnaires modified from the Medical Oncology Status in Europe Survey dealing with oncology structure, resources, research, and patterns of care given by medical oncologists were selected. Several modifications were made to the questionnaire after feedback from the insurance and policy committee of the Korean Association for Clinical Oncology (KACO). The online survey was then sent to KACO members.
Results
A total of 214 medical oncologists (45.8% of the total inquiries), including 71 directors of medical oncology institutions, took the survey. Most institutions had various resources, including a medical oncology department (94.1%) and a department of radiation oncology (82.4%). There was an average of four medical oncologists at each institution. Medical oncologists were involved in various treatments from diagnosis to end-of-life care. They were also chemotherapy providers from a wide range of institutions that treated many types of solid cancers. In addition, 86.2% of the institutions conducted research.
Conclusion
This is the first national survey in Korea to show that medical oncologists are involved in a wide range of cancer treatments and care. This survey emphasizes the contributions and proper roles of medical oncologists in the evolving health care environment in Korea.

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  • Current status of medical oncology in Japan and changes over the most recent 7-year period: results of a questionnaire sent to designated cancer care hospitals
    Makoto Arai, Izumi Ohno, Koji Takahashi, Meng Meng Fan, Akinobu Tawada, Chikashi Ishioka, Yuichi Takiguchi
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    The Korean Journal of Internal Medicine.2019; 34(3): 626.     CrossRef
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Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer
Taejong Song, Hye-Kyung Jeon, Ji Eun Hong, Jung-Joo Choi, Tae-Joong Kim, Chel Hun Choi, Duk-Soo Bae, Byoung-Gie Kim, Jeong-Won Lee
Cancer Res Treat. 2017;49(3):595-606.   Published online September 27, 2016
DOI: https://doi.org/10.4143/crt.2016.034
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer.
Materials and Methods
The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively.
Results
Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05).
Conclusion
V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.

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Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea
Jae Young Joung, Jiwon Lim, Chang-Mo Oh, Kyu-Won Jung, Hyunsoon Cho, Sung Han Kim, Ho Kyung Seo, Weon Seo Park, Jinsoo Chung, Kang Hyun Lee, Young-Joo Won
Cancer Res Treat. 2017;49(3):607-615.   Published online September 23, 2016
DOI: https://doi.org/10.4143/crt.2016.139
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea.
Materials and Methods
In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data.
Results
Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, –2.01%; p=0.05) and bladder (APC, –0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (–7.20%).
Conclusion
The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.

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Lung Cancer Epidemiology in Korea
Aesun Shin, Chang-Mo Oh, Byung-Woo Kim, Hyeongtaek Woo, Young-Joo Won, Jin-Soo Lee
Cancer Res Treat. 2017;49(3):616-626.   Published online September 23, 2016
DOI: https://doi.org/10.4143/crt.2016.178
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea.
Materials and Methods
Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated.
Results
Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups.
Conclusion
The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.

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Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes among Korean Breast Cancer Patients
Kyong-Ah Yoon, Boyoung Park, Byung Il Lee, Moon Jung Yang, Sun-Young Kong, Eun Sook Lee
Cancer Res Treat. 2017;49(3):627-634.   Published online September 13, 2016
DOI: https://doi.org/10.4143/crt.2016.292
AbstractAbstract PDFPubReaderePub
Purpose
Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls.
Materials and Methods
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast CancerInformation Core databasewere selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico.
Results
Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function.
Conclusion
This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.

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  • Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
    Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
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    Jee-Soo Lee, Sohee Oh, Sue Kyung Park, Min-Hyuk Lee, Jong Won Lee, Sung-Won Kim, Byung Ho Son, Dong-Young Noh, Jeong Eon Lee, Hai-Lin Park, Man Jin Kim, Sung Im Cho, Young Kyung Lee, Sung Sup Park, Moon-Woo Seong
    Journal of Medical Genetics.2018; 55(12): 794.     CrossRef
  • Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from ‘unknown significance’ to ‘Likely pathogenic’ based on clinical evidence in Korea
    Jai Min Ryu, Goeun Kang, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Se Kyung Lee, Soo Youn Bae, Sungmin Park, Hyun-June Paik, Jong-Won Kim, Sung-Shin Park, Jeong Eon Lee, Sung-Won Kim
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Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer
E Sun Paik, Insuk Sohn, Sun-Young Baek, Minhee Shim, Hyun Jin Choi, Tae-Joong Kim, Chel Hun Choi, Jeong-Won Lee, Byoung-Gie Kim, Yoo-Young Lee, Duk-Soo Bae
Cancer Res Treat. 2017;49(3):635-642.   Published online September 27, 2016
DOI: https://doi.org/10.4143/crt.2016.282
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS).
Materials and Methods
We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV).
Results
In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively.
Conclusion
Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

Citations

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    Xianglin Nie, Ting Xu, Lin Zhang, Wenjun Cheng
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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis
Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2017;49(3):643-655.   Published online October 6, 2016
DOI: https://doi.org/10.4143/crt.2016.168
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

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Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer
Ga Won Yim, Hee Jung Kim, Lee Kyung Kim, Sang Wun Kim, Sunghoon Kim, Eun Ji Nam, Young Tae Kim
Cancer Res Treat. 2017;49(3):656-668.   Published online October 11, 2016
DOI: https://doi.org/10.4143/crt.2016.263
AbstractAbstract PDFPubReaderePub
Purpose
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC).
Materials and Methods
HOXA11as expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference.
Results
HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that HOXA11as was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression.
Conclusion
These findings highlight the clinical significance of HOXA11as to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.

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Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy
Hyun Ju Kim, Yang-Gun Suh, Yong Chan Lee, Sang Kil Lee, Sung Kwan Shin, Byung Chul Cho, Chang Geol Lee
Cancer Res Treat. 2017;49(3):669-677.   Published online October 6, 2016
DOI: https://doi.org/10.4143/crt.2016.354
AbstractAbstract PDFPubReaderePub
Purpose
The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT).
Materials and Methods
Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients.
Results
There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups.
Conclusion
A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

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ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer
Ji-Youn Han, Geon Kook Lee, Kun Young Lim, Young Ju Lee, Byung Ho Nam, Jin Soo Lee
Cancer Res Treat. 2017;49(3):678-687.   Published online October 11, 2016
DOI: https://doi.org/10.4143/crt.2016.365
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).
Materials and Methods
Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1 every 3 weeks) or IP (irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level.
Results
A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; p=0.082), median progression-free survival (PFS; 4.5 months vs. 3.9 months, respectively; p=0.117), and overall survival (OS; 16.5 months vs. 16.7 months, respectively; p=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, p=0.509; IP, 30.2% vs. 21.6%, respectively, p=0.536), median PFS (GP, 4.6 months vs. 5.0 months, respectively, p=0.506; IP, 3.9 months vs. 3.7 months, respectively, p=0.748), or median OS (GP, 18.6 months vs. 11.9 months, respectively, p=0.070; IP, 17.5 months vs. 14.0 months, respectively, p=0.821).
Conclusion
Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC.

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  • Meta‐Analysis of ERCC1 Protein Expression and Platinum Chemosensitivity in Non‐Small‐Cell Lung Cancer
    Guoping Li, Dan Cheng, Jamal A. Mahajna
    Evidence-Based Complementary and Alternative Medicine.2020;[Epub]     CrossRef
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    Yu-Liang Huang, Jun-Rong Wu, Min Fang, Hui-Liu Zhao, Zhi-Min Liu, Jian Ye, Ling-Sha Huang, Bo Zhu
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  • 196 Download
  • 5 Web of Science
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Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea
Sanghyuk Song, Ji Hyun Chang, Hak Jae Kim, Yeon Sil Kim, Jin Hee Kim, Yong Chan Ahn, Jae-Sung Kim, Si Yeol Song, Sung Ho Moon, Moon June Cho, Seon Min Youn
Cancer Res Treat. 2017;49(3):688-694.   Published online October 31, 2016
DOI: https://doi.org/10.4143/crt.2016.219
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea.
Materials and Methods
We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants’ opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey.
Results
SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule.
Conclusion
The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

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  • Guidelines for safe practice of stereotactic body (ablative) radiation therapy: RANZCR 2023 update
    Howard Yu‐hao Liu, Nicholas Hardcastle, Michael Bailey, Shankar Siva, Anna Seeley, Tamara Barry, Jeremy Booth, Louis Lao, Michelle Roach, Stacey Buxton, David Thwaites, Matthew Foote
    Journal of Medical Imaging and Radiation Oncology.2024; 68(2): 217.     CrossRef
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    Sophia C. Kamran, David Palma, Matthew S. Katz, Anthony L. Zietman
    Seminars in Radiation Oncology.2021; 31(3): 200.     CrossRef
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    Shufang Li, Yuping Feng, Yuxia Huang, Yu Liu, Yanxi Wang, Yan Liang, Hui Zeng, Hong Qu, Ling Wei
    Open Life Sciences.2020; 15(1): 389.     CrossRef
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  • 3 Crossref
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Clinicopathologic Characteristics and Prognosis of Tongue Squamous Cell Carcinoma in Patients with and without a History of Radiation for Nasopharyngeal Carcinoma: A Matched Case-Control Study
Peng Zhang, Li Zhang, Hui Liu, Lei Zhao, Yong Li, Jing-Xian Shen, Qing Liu, Meng-Zhong Liu, Mian Xi
Cancer Res Treat. 2017;49(3):695-705.   Published online October 11, 2016
DOI: https://doi.org/10.4143/crt.2016.317
AbstractAbstract PDFPubReaderePub
Purpose
Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC.
Materials and Methods
From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival.
Results
The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray’s test, p=0.001).
Conclusion
TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

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    Li Wang, Siyu Wang, Jiayu Zhang, Jianmin Peng, Bin Cheng, Huan Li, Qinchao Hu
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    James C. H. Chow, Wah Cheuk, William C. S. Cho, Chi-Fai Wong, Dennis W. Y. Au, Anthony H. P. Tam, Rachel C. W. Wong, Jeffrey C. H. Chan, Simon C. C. Law, Roger K. C. Ngan, Kam-Hung Wong, Ka-Man Cheung
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    Sybil T. Sha, Edward Christopher Dee, Matthew Mossanen, Brandon A. Mahal, Cierra Zaslowe-Dude, Trevor J. Royce, Michelle S. Hirsch, Guru Sonpavde, Mark A. Preston, Paul L. Nguyen, Kent W. Mouw, Vinayak Muralidhar
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    Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang
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    Chuanjun Chen, Huiguo Shan
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    Alhadi Almangush, Matti Pirinen, Ilkka Heikkinen, Antti A Mäkitie, Tuula Salo, Ilmo Leivo
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    Qinchao Hu, Tong Wu, Xiaobing Chen, Huan Li, Zhicheng Du, Yuantao Hao, Jianmin Peng, Shanshan Tai, Ming Song, Bin Cheng
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    Xiaoyan Fu, Shuwei Chen, Weichao Chen, Zhongyuan Yang, Ming Song, Hao Li, Huayong Zhang, Fan Yao, Xuan Su, Tianrun Liu, An-Kui Yang
    Oral Oncology.2018; 84: 20.     CrossRef
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A Multicenter Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-Line Chemotherapy in Metastatic Gastric Cancer Patients Who Had Progressed after Cisplatin Plus Either S-1 or Capecitabine
Keun-Wook Lee, Bum Jun Kim, Mi-Jung Kim, Hye Sook Han, Jin Won Kim, Young Iee Park, Sook Ryun Park
Cancer Res Treat. 2017;49(3):706-716.   Published online October 18, 2016
DOI: https://doi.org/10.4143/crt.2016.216
AbstractAbstract PDFPubReaderePub
Purpose
This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen.
Materials and Methods
Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m2 intravenously (IV) on D1 (D), docetaxel 60 mg/m2 IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m2 IV D1 plus oral S-1 30 mg/m2 twice a day on D1-14 (DS).
Results
Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035).
Conclusion
A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.

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Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1
In Kyung Hwang, Seung Min Hahn, Hyo Sun Kim, Sang Kyum Kim, Hyo Song Kim, Kyoo‑Ho Shin, Chang Ok Suh, Chuhl Joo Lyu, Jung Woo Han
Cancer Res Treat. 2017;49(3):717-726.   Published online December 1, 2016
DOI: https://doi.org/10.4143/crt.2016.271
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs.
Materials and Methods
The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared.
Results
Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS.
Conclusion
NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.

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Why Do Some People Choose Opportunistic Rather Than Organized Cancer Screening? The Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012
Myung-Il Hahm, Hsueh-Fen Chen, Thaddeus Miller, Liam O’Neill, Hoo-Yeon Lee
Cancer Res Treat. 2017;49(3):727-738.   Published online October 31, 2016
DOI: https://doi.org/10.4143/crt.2016.243
AbstractAbstract PDFPubReaderePub
Purpose
Although the Korean government has implemented a universal screening program for common cancers, some individuals choose to participate in opportunistic screening programs. Therefore, this study was conducted to identify factors contributing to the selection of organized versus opportunistic screening by the Korean general population.
Materials and Methods
Data from 11,189 participants aged ≥ 40 yearswho participated in the fifth KoreanNational Health and Nutrition Examination Survey (2010-2012) were analyzed in this study.
Results
A total of 6,843 of the participants (58.6%) underwent cancer screening, of which 6,019 (51.1%) participated in organized and 824 (7.5%) participated in opportunistic screening programs. Being female, older, highly educated, in the upper quartile of income, an ex-smoker, and a light drinker as well as having supplementary private health insurance and more comorbid conditions and engaging in moderate physical activity 1-4 days per week were related to participation in both types of screening programs. Being at least a high school graduate, in the upper quartile for income, and a light drinker, as well as having more comorbid conditions and engaging in moderate physical activities 1-4 days per week had a stronger effect on those undergoing opportunistic than organized screening.
Conclusion
The results of this study suggest that socioeconomic factors such as education and income, aswell as health status factors such as health-related quality of life and number of comorbid conditions and health behaviors such as drinking and engaging in moderate physical activity 1-4 days per week had a stronger influence on participation in an opportunistic than in an organized screening program for cancer.

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Incorporating Risk Factors to Identify the Indication of Post-mastectomy Radiotherapy in N1 Breast Cancer Treated with Optimal Systemic Therapy: A Multicenter Analysis in Korea (KROG 14-23)
Hae Jin Park, Kyung Hwan Shin, Jin Ho Kim, Seung Do Ahn, Ja Young Kim, Won Park, Yong Bae Kim, Yeon-joo Kim, Jin Hee Kim, Kyubo Kim, Kyung Ran Park, Hyun Soo Shin, Bae Kwon Jeong, Sun Young Lee, Suzy Kim
Cancer Res Treat. 2017;49(3):739-747.   Published online October 19, 2016
DOI: https://doi.org/10.4143/crt.2016.405
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT.
Materials and Methods
One thousand three hundred eighty-two pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy.
Results
After a median follow-up of 5.9 years, there were 173 AFR (53 loco-regional recurrence [LRR] without distant metastases [DM], 38 LRR with DM, and 82 DM without LRR). The 5-year LRR and AFR rates were 6.1% and 12.0%, respectively. Multivariate analysis revealed that close resection margin (p=0.001) was the only independent risk factor for LRR. Multivariate analysis for AFR revealed that age < 35 years (p=0.025), T2 stage (p=0.004), high tumor grade (p=0.032), close resection margin (p=0.035), and triple-negative biological subtype (p=0.031) were independent risk factors. Two or three positive lymph nodes (p=0.078) were considered a marginally significant factor. When stratified by these six factors, the 5-year LRR rates were 3.6% with 0-1 (n=606), 7.5% with 2-3 (n=655), and 12.7% with 4-6 (n=93) risk factors. The 5-year AFR rates were 7.1% with 0-1, 15.0% with 2-3, and 24.5% with 4-6 risk factors.
Conclusion
Patients with pT1-2N1M0 breast cancer who underwent mastectomy and optimal systemic therapy showed excellent loco-regional control and disease control. The patients with four or more risk factors may benefit from PMRT, and those with two or three risk factors merit consideration of PMRT.

Citations

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  • Clinical treatment score Post-5 Years (CTS5) predicts the benefit of postmastectomy radiotherapy in patients with T1-2N1 luminal breast cancer
    Ke Liu, Guan-Qiao Li, Si-Qi Li, Xue-Qin Chen, San-Gang Wu
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Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients
Boram Ha, Seung Yeun Chung, Yeon-Joo Kim, Ho-Shin Gwak, Jong Hee Chang, Sang Hyun Lee, In Hae Park, Keun Seok Lee, Seeyoun Lee, Tae Hyun Kim, Dae Yong Kim, Seok-Gu Kang, Chang-Ok Suh
Cancer Res Treat. 2017;49(3):748-758.   Published online October 31, 2016
DOI: https://doi.org/10.4143/crt.2016.303
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer.
Materials and Methods
Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not.
Results
With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM.
Conclusion
WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

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Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen
Changhoon Yoo, Bum Jun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Tae Won Kim, Baek-Yeol Ryoo, Heung-Moon Chang
Cancer Res Treat. 2017;49(3):759-765.   Published online November 9, 2016
DOI: https://doi.org/10.4143/crt.2016.371
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy.
Materials and Methods
Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea.
Results
The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second- line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029).
Conclusion
Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.

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FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition
Sang Hee Cho, Chang Soo Hong, Hee Nam Kim, Min Ho Shin, Ka Rham Kim, Hyun Jeong Shim, Jun Eul Hwang, Woo Kyun Bae, Ik Joo Chung
Cancer Res Treat. 2017;49(3):766-777.   Published online November 9, 2016
DOI: https://doi.org/10.4143/crt.2016.457
AbstractAbstract PDFPubReaderePub
Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patientswith resected colon cancer, including the underlying mechanism.
Materials and Methods
FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Results
Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
Conclusion
The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

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  • FGFR4 promotes CAF activation through the CXCL10-CXCR3 axis in colon cancer
    Eun-Gene Sun, Ji-Na Choi, Mi-Ra Park, Dae-Hwan Kim, MinJeong Sung, Hyun-Jeong Shim, Jun-Eul Hwang, Woo-Kyun Bae, Chaeyong Jung, Young-Kook Kim, Ik-Joo Chung, Sang-Hee Cho
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    Meli’sa S. Crawford, Tara M. Nordgren, Declan F. McCole
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  • FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
    Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
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  • Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer
    Chang‐Soo Hong, Eun‐Gene Sun, Ji‐Na Choi, Dae‐Hwan Kim, Jo‐Heon Kim, Kyung‐Hyun Ryu, Hyun‐Jeong Shim, Jun‐Eul Hwang, Woo‐Kyun Bae, Hyeong‐Rok Kim, Kyung Keun Kim, Chaeyong Jung, Ik‐Joo Chung, Sang‐Hee Cho
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    Maohua Chen, Xiangqian Yin, Chuan Lu, Xiandong Chen, Huajun Ba, Jianyong Cai, Jun Sun
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    Sabine Heublein, Michael S. Anglesio, Frederik Marmé, Stefan Kommoss
    Journal of Cancer Research and Clinical Oncology.2019; 145(9): 2251.     CrossRef
  • TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma
    Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
    Cancer Letters.2018; 415: 106.     CrossRef
  • The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction
    Álvaro Quintanal-Villalonga, Laura Ojeda-Márquez, Ángela Marrugal, Patricia Yagüe, Santiago Ponce-Aix, Ana Salinas, Amancio Carnero, Irene Ferrer, Sonia Molina-Pinelo, Luis Paz-Ares
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  • Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients
    Lu Chen, Huijie Qi, Liudi Zhang, Haixia Li, Jie Shao, Haifei Chen, Mingkang Zhong, Xiaojin Shi, Ting Ye, Qunyi Li
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Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Cancer Res Treat. 2017;49(3):778-789.   Published online November 11, 2016
DOI: https://doi.org/10.4143/crt.2015.485
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to observe the effects of metformin on human esophageal cancer cell and to investigate its possible mechanisms.
Materials and Methods
Cell viability was detected by using a Cell Counting Kit-8, while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo. Immunohistochemistry was determined based on the expression of PKM2 and Bim in tumor tissues. Tunnel was used to assess tumor cell apoptosis.
Results
Esophageal cancer cells viability was reduced after metformin treatment. The cell cycle was arrested in the G0/G1 phase, apoptosis was induced, caspase 3 was activated, caspase 9 was downregulated, and the pro-apoptotic protein Bim increased. Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Insulin-like growth factor 1 partly reversed metfromin-induced apoptosis and attenuated the repression effect of metfomin to PI3K, pAKT, and PKM2. Knockout PKM2 resulted in the activation of caspase 3, down-regulation of caspase 9, and increased expression of Bim. In the Eca109 xenograft model, metformin significantly reduced tumor growth. Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues.
Conclusion
Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.

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p15Ink4b Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients
Shahid M. Baba, Niyaz A. Azad, Zafar A. Shah, Dil-Afroze , Arshad A. Pandith, Aleem Jan, Sheikh A. Aziz
Cancer Res Treat. 2017;49(3):790-797.   Published online December 5, 2016
DOI: https://doi.org/10.4143/crt.2016.108
AbstractAbstract PDFPubReaderePub
Purpose
The p15Ink4b gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir(North India).
Materials and Methods
p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction,while its subsequent expression analysiswas carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).
Results
Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA.
Conclusion
Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

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  • Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation
    Miao Zhang, Jia-yi Zhang, Ming-qian Sun, Peng Lu, Jian-xun Liu
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    Liang Xia, Wenzhu Zhang, Li Gao
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    Hye Young Shin, Mina Suh, Kui Son Choi, Sang-Hyun Hwang, Jae Kwan Jun, Dong Soo Han, You Kyoung Lee, Jae Hwan Oh, Chan Wha Lee, Do-Hoon Lee
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    Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
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    Chen Yang, Xiaoxiao Gao, Jing Ye, Jianping Ding, Ya Liu, Hongyu Liu, Xiumei Li, Yunhai Zhang, Jie Zhou, Weiping Huang, Fugui Fang, Yinghui Ling
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Trends in Participation Rates for the National Cancer Screening Program in Korea, 2002-2012
Mina Suh, Seolhee Song, Ha Na Cho, Boyoung Park, Jae Kwan Jun, Eunji Choi, Yeol Kim, Kui Son Choi
Cancer Res Treat. 2017;49(3):798-806.   Published online November 11, 2016
DOI: https://doi.org/10.4143/crt.2016.186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The National Cancer Screening Program (NCSP) in Korea supports cancer screening for stomach, liver, colorectal, breast, and cervical cancer. This study was conducted to assess trends in participation rates among Korean men and women invited to undergo screening via the NCSP as part of an effort to guide future implementation of the program in Korea.
Materials and Methods
Data from the NCSP for 2002 to 2012 were used to calculate annual participation rates with 95% confidence intervals (CI) by sex, insurance status, and age group for stomach, liver, colorectal, breast, and cervical cancer screening.
Results
In 2012, participation rates for stomach, liver, colorectal, breast, and cervical cancer screening were 47.3%, 25.0%, 39.5%, 51.9%, and 40.9%, respectively. The participation rates increased annually by 4.3% (95% CI, 4.0 to 4.6) for stomach cancer, 3.3% (95% CI, 2.5 to 4.1) for liver cancer, 4.1% (95% CI, 3.2 to 5.0) for colorectal cancer, 4.6% (95% CI, 4.1 to 5.0) for breast cancer, and 0.9% (95% CI, –0.7 to 2.5) for cervical cancer from 2002 to 2012.
Conclusion
Participant rates for the NCSP for the five above-mentioned cancers increased annually from 2002 to 2012.

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    Seo Young Kang, Ye-Jee Kim, Sehee Kim, Hye Soon Park
    Journal of Korean Medical Science.2025;[Epub]     CrossRef
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    Ji Young Lee, Jae Myung Cha, Jin Young Yoon, Min Seob Kwak, Hun Hee Lee
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    Kazuhiro Kashiwagi, Toshifumi Yoshida, Satoshi Kinoshita, Hiromasa Nakamizo, Rieko Nakamura, Hiromasa Takaishi, Yasushi Iwao, Takanori Kanai
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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy
Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang
Cancer Res Treat. 2017;49(3):807-815.   Published online January 18, 2017
DOI: https://doi.org/10.4143/crt.2016.326
AbstractAbstract PDFPubReaderePub
Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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A Randomized Phase II Study of Leucovorin/5-Fluorouracil with or without Oxaliplatin (LV5FU2 vs. FOLFOX) for Curatively-Resected, Node-Positive Esophageal Squamous Cell Carcinoma
Sung Hee Lim, Young Mog Shim, Se Hoon Park, Hong Kwan Kim, Young Soo Choi, Myung-Ju Ahn, Keunchil Park, Jae Ill Zo, Jong-Mu Sun
Cancer Res Treat. 2017;49(3):816-823.   Published online November 9, 2016
DOI: https://doi.org/10.4143/crt.2016.417
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The optimal perioperative treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. We evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapies administered adjuvantly for curatively-resected, node-positive ESCC.
Materials and Methods
Patients with pathologically node-positive esophageal cancer after curative R0 resection were enrolled and randomly assigned to receive LV5FU2 or FOLFOX biweekly for up to eight cycles. The primary endpoint was disease-free survival (DFS).
Results
Between 2011 and 2015, 62 patients were randomized into the two treatment groups (32 in the LV5FU2 arm and 30 in the FOLFOX arm). The median age was 60 years and both groups had similar pathologic characteristics in tumor, nodal status, and location. Treatment completion rates were similarly high in both groups. The DFS rate at 12 months was 67% in the LV5FU2 group and 63% in the FOLFOX group with a hazard ratio of 1.3 (95% confidence interval [CI], 0.66 to 2.62). After a median follow-up period of 27 months, the median DFS was 29.6 months (95% CI, 4.9 to 54.2) in the LV5FU2 arm and 16.8 months (95% CI, 7.5 to 26.1) in the FOLFOX arm (p=0.428), respectively, while the median overall survival was not reached in either arm. Grade 3 or 4 neutropenia was more frequent in patients in the FOLFOX arm than the LV5FU2 arm (20.0% vs. 3.1%).
Conclusion
The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.

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Meta-Analysises
Impact of Resection Margin Distance on Survival of Pancreatic Cancer: A Systematic Review and Meta-Analysis
Kyung Su Kim, Jeanny Kwon, Kyubo Kim, Eui Kyu Chie
Cancer Res Treat. 2017;49(3):824-833.   Published online August 26, 2016
DOI: https://doi.org/10.4143/crt.2016.336
AbstractAbstract PDFPubReaderePub
Purpose
While curative resection is the only chance of cure in pancreatic cancer, controversies exist about the impact of surgical margin status on survival. Non-standardized pathologic report and different criteria on the R1 status made it difficult to implicate adjuvant therapy after resection based on the margin status. We evaluated the influence of resection margins on survival by meta-analysis.
Materials and Methods
We thoroughly searched electronic databases of PubMed, EMBASE, and Cochrane Library. We included studies reporting survival outcomeswith different margin status: involved margin (R0 mm), margin clearance with ≤ 1 mm (R0-1 mm), and margin with > 1 mm (R>1 mm). Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis.
Results
A total of eight retrospective studies involving 1,932 patients were included. Pooled HR for overall survival showed that patients with R>1 mm had reduced risk of death than those with R0-1 mm (HR, 0.74; 95% confidence interval [CI], 0.61 to 0.88; p=0.001). In addition, patients with R0-1 mm had reduced risk of death than those with R0 mm (HR, 0.81; 95% CI, 0.72 to 0.91; p < 0.001). There was no heterogeneity between the included studies (I 2 index, 42% and 0%; p=0.10 and p=0.82, respectively).
Conclusion
Our results suggest that stratification of the patients based on margin status is warranted in the clinical trials assessing the role of adjuvant treatment for pancreatic cancer.

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Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis
Chiara Cremolini, Carlotta Antoniotti, Filippo Pietrantonio, Rosa Berenato, Marco Tampellini, Chiara Baratelli, Lisa Salvatore, Federica Marmorino, Beatrice Borelli, Federico Nichetti, Paolo Bironzo, Cristina Sonetto, Maria Di Bartolomeo, Filippo de Braud, Fotios Loupakis, Alfredo Falcone, Massimo Di Maio
Cancer Res Treat. 2017;49(3):834-845.   Published online November 15, 2016
DOI: https://doi.org/10.4143/crt.2016.249
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).
Materials and Methods
A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson’s correlation coefficient (R) and the coefficient of determination (R2).
Results
Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R2=0.539, p < 0.001) and poor correlation (R=0.169, R2=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.
Conclusion
Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

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Case Report
A Rare Case of Phyllodes Tumor Metastasis to the Stomach Presenting as Anemia
Do Il Choi, Ho Seok Chi, Sang Ho Lee, Youngmee Kwon, Seog Yun Park, Sung Hoon Sim, In Hae Park, Keun Seok Lee
Cancer Res Treat. 2017;49(3):846-849.   Published online September 1, 2016
DOI: https://doi.org/10.4143/crt.2016.188
AbstractAbstract PDFPubReaderePub
Metastasis of a phyllodes tumor to the stomach is an extremely rare condition with important clinical implications. A 44-year-old woman was initially diagnosed with a phyllodes tumor in her right breast in 2008, and subsequently presented to an outpatient clinic with dizziness on December 16, 2013. We found that she had severe anemia (hemoglobin levels, 6.7 g/dL), and we quickly performed esophagogastroduodenoscopy to identify the cause. This procedure revealed large ulcerofungating masses with active bleeding in the stomach. Histopathological examination revealed that the masses were consistent with phyllodes tumor metastases. In patients with a metastatic phyllodes tumor presenting as anemia, gastric metastasis should be considered as one of the differential diagnoses because overlooking the possibility might have dire consequences if cytotoxic chemotherapy were administered.

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