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Volume 48(4); October 2016
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Special Article
Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor
Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang
Cancer Res Treat. 2016;48(4):1155-1166.   Published online June 24, 2016
DOI: https://doi.org/10.4143/crt.2016.187
AbstractAbstract PDFPubReaderePub
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

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Original Articles
Predictors of Distant Metastasis after Radical Surgery Followed by Postoperative Radiotherapy with or without Chemotherapy for Oropharyngeal Cancer
Mi Joo Chung, Yeon Sil Kim, Ji Yoon Kim, Yun Hee Lee, Ji Hyun Jang, Jin Hyoung Kang, Ie Ryung Yoo, Youn Soo Lee
Cancer Res Treat. 2016;48(4):1167-1176.   Published online March 3, 2016
DOI: https://doi.org/10.4143/crt.2015.379
AbstractAbstract PDFPubReaderePub
Purpose
We investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy.
Materials and Methods
Eighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography scan (18F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed.
Results
Median follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate.
Conclusion
Lower neck LN involvement, high SUVmax in pretreatment 18F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.

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East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL)
Keunchil Park, Joo-Hang Kim, Eun Kyung Cho, Jin-Hyoung Kang, Jin-Yuan Shih, Annamaria Hayden Zimmermann, Pablo Lee, Ekaterine Alexandris, Tarun Puri, Mauro Orlando
Cancer Res Treat. 2016;48(4):1177-1186.   Published online February 22, 2016
DOI: https://doi.org/10.4143/crt.2015.401
AbstractAbstract PDFPubReaderePub
Purpose
REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.
Materials and Methods
Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.
Results
In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).
Conclusion

Results
of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

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Radiation Therapy Alone in cT1-3N0 Non-small Cell Lung Cancer Patients Who Are Unfit for Surgical Resection or Stereotactic Radiation Therapy: Comparison of Risk-Adaptive Dose Schedules
Won Kyung Cho, Jae Myoung Noh, Yong Chan Ahn, Dongryul Oh, Hongryull Pyo
Cancer Res Treat. 2016;48(4):1187-1195.   Published online March 9, 2016
DOI: https://doi.org/10.4143/crt.2015.391
AbstractAbstract PDFPubReaderePub
Purpose
High dose definitive radiation therapy (RT) alone is recommended to patients with cT1-3N0 non-small cell lung cancer, who are unfit for surgery or stereotactic RT. This study was conducted to evaluate the clinical outcomes and cost-effectiveness following RT alone using two different modest hypofractionation dose schemes. Materials and Methods Between 2001 and 2014, 124 patients underwent RT alone. From 2001 till 2010, 60 Gy in 20 fractions was delivered to 79 patients (group 1). Since 2011, 60 Gy in 20 fractions (group 2, 20 patients), and 60 Gy in 15 fractions (group 3, 25 patients) were selectively chosen depending on estimated risk of esophagitis.
Results
At follow-up of 16.7 months, 2-year rates of local control, progression-free survival, and overall survival were 62.6%, 39.1%, and 59.1%, respectively. Overall survival was significantly better in group 3 (p=0.002). In multivariate analyses, cT3 was the most powerful adverse factor affecting clinical outcomes. Incidence and severity of radiation pneumonitis were not different among groups, while no patients developed grade 2 esophagitis in group 3 (p=0.003). Under current Korean Health Insurance Policy, RT cost per person was 22.5% less in group 3 compared with others. Conclusion The current study demonstrated that 60 Gy in 15 fractions instead of 60 Gy in 20 fractions resulted in comparable clinical outcomes with excellent safety, direct cost saving, and improved convenience to the patients with tumors located at ≥ 1.5 cm from the esophagus.

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Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer
So-Young Seol, Chul Kim, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Cancer Res Treat. 2016;48(4):1196-1209.   Published online February 26, 2016
DOI: https://doi.org/10.4143/crt.2015.189
AbstractAbstract PDFPubReaderePub
Purpose
Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer.
Materials and Methods
For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated.
Results
Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated.
Conclusion
High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.

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Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Surrogate Biomarker for Bevacizumab in Colorectal Cancer Liver Metastasis: A Single-Arm, Exploratory Trial
Yeo-Eun Kim, Bio Joo, Mi-Suk Park, Sang Joon Shin, Joong Bae Ahn, Myeong-Jin Kim
Cancer Res Treat. 2016;48(4):1210-1221.   Published online March 17, 2016
DOI: https://doi.org/10.4143/crt.2015.374
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM). Materials and Methods From July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (Ktransand IAUC60) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests.
Results
The median PFS period was 11.2 months. Ktrans, IAUC60, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in Ktrans from baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time. Conclusion DCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in Ktrans at 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.

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Venous Invasion in Colorectal Cancer: Impact of Morphologic Findings on Detection Rate
Chungsu Hwang, Sojeong Lee, Ahrong Kim, Young-Geum Kim, Sang-Jeong Ahn, Do Youn Park
Cancer Res Treat. 2016;48(4):1222-1228.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.429
AbstractAbstract PDFPubReaderePub
Purpose
Venous invasion (VI) is widely accepted as a poor prognostic factor in colorectal cancer (CRC), and is indicated as a high-risk factor determining the use of adjuvant chemotherapy in CRC. However, there is marked interobserver and intraobserver variability in VI identification and marked variability in the real prevalence of VI in CRC.
Materials and Methods
We investigated the detection rate of VI in 93 consecutive cases of T3 or T4 CRC based on the following: original pathology report, review of hematoxylin and eosin (H&E) slides with attention to the “protruding tongue” and “orphan arteriole” signs, and elastic stain as the gold standard.
Results
Overall, the detection rate of VI was significantly increased as follows: 14/93 (15.1%) in the original pathology report, 38/93 (40.9%) in review of H&E slides with attention to the “protruding tongue” and “orphan arteriole” signs, and 45/93 (48.4%) using elastic stain. VI detection based on morphologic features showed 77.8% sensitivity and 91.1% specificity and showed a linear correlation (Spearman correlation coefficient, 0.727; p < 0.001) with VI detected by elastic stain. In addition, improved agreement between detection methods (detection on the basis of morphologic features, κ=0.719 vs. original pathology report, κ=0.318) was observed using kappa statistics.
Conclusion
Slide review with special attention to the “protruding tongue” and “orphan arteriole” signs could be used for better identification of VI in CRC in routine surgical practice.

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A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park
Cancer Res Treat. 2016;48(4):1229-1242.   Published online March 30, 2016
DOI: https://doi.org/10.4143/crt.2015.500
AbstractAbstract PDFPubReaderePub
Purpose
We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis.
Materials and Methods
Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1.
Results
The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients.
Conclusion
This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.

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Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data
Do Young Kim, Hye Jin Kim, Kwang-Hyub Han, Sang Young Han, Jeong Heo, Hyun Young Woo, Soon Ho Um, Yeul Hong Kim, Young Oh Kweon, Ho Yeong Lim, Jung Hwan Yoon, Wan Sik Lee, Byung Seok Lee, Han Chu Lee, Baek-Yeol Ryoo, Seung Kew Yoon
Cancer Res Treat. 2016;48(4):1243-1252.   Published online February 24, 2016
DOI: https://doi.org/10.4143/crt.2015.278
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study).
Materials and Methods
Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients.
Results
More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients.
Conclusion
Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).

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Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma
Hyung Soon Park, Hye Sun Lee, Ji Soo Park, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Min Goo Lee, Hei-Cheul Jeung
Cancer Res Treat. 2016;48(4):1253-1263.   Published online February 3, 2016
DOI: https://doi.org/10.4143/crt.2015.400
AbstractAbstract PDFPubReaderePub
Purpose
This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients.
Materials and Methods
Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox’s proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis.
Results
Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively).
Conclusion
We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

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Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy
Inkeun Park, Seung Joon Choi, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Yong Ju Shin, Dong Bok Shin
Cancer Res Treat. 2016;48(4):1264-1273.   Published online March 23, 2016
DOI: https://doi.org/10.4143/crt.2015.250
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed.
Results
A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

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Is There a Role for Adjuvant Therapy in R0 Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis
Se-Il Go, Young Saing Kim, In Gyu Hwang, Eun Young Kim, Sung Yong Oh, Jun Ho Ji, Haa-Na Song, Se Hoon Park, Joon Oh Park, Jung Hun Kang
Cancer Res Treat. 2016;48(4):1274-1285.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.502
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection.
Materials and Methods
Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors.
Results
In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups.
Conclusion
The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.

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Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08
Ki Hyang Kim, Joo Hoon Kim, Ji Young Lee, Hyo Song Kim, Su Jin Heo, Ji Hyung Kim, Ho Young Kim, Sun Young Rha
Cancer Res Treat. 2016;48(4):1286-1292.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2016.018
AbstractAbstract PDFPubReaderePub
Purpose
We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. Materials and Methods Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment.
Results
Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. Conclusion Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.

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    Manuel Eros Rodríguez-Fuentes, Mario Pérez-Sayáns, Carmen Martín Carreras-Presas, Xabier Marichalar-Mendia, Leticia Bagán-Debón, Rafael López-López
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    Łukasz Mielczarek, Anna Brodziak, Paweł Sobczuk, Maciej Kawecki, Agnieszka Cudnoch-Jędrzejewska, Anna M. Czarnecka
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    Cristina Masini, Maria Giuseppa Vitale, Marco Maruzzo, Giuseppe Procopio, Ugo de Giorgi, Sebastiano Buti, Sabrina Rossetti, Roberto Iacovelli, Francesco Atzori, Laura Cosmai, Francesca Vignani, Giuseppe Prati, Sarah Scagliarini, Annalisa Guida, Annalisa B
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    Ravi K. Paluri, Guru Sonpavde, Charity Morgan, Jacob Rojymon, Anastasia Hartzes Mar, Radhika Gangaraju
    Oncology Reviews.2019;[Epub]     CrossRef
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Poor Preoperative Glycemic Control Is Associated with Dismal Prognosis after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Korean Multicenter Study
Sung Gu Kang, Eu Chang Hwang, Seung Il Jung, Ho Song Yu, Ho Seok Chung, Taek Won Kang, Dong Deuk Kwon, Jun Eul Hwang, Jun Seok Kim, Joon Hwa Noh, Jae Hyung You, Myung Ki Kim, Tae Hoon Oh, Ill Young Seo, Seung Baik, Chul-Sung Kim, Seok Ho Kang, Jun Cheon
Cancer Res Treat. 2016;48(4):1293-1301.   Published online March 23, 2016
DOI: https://doi.org/10.4143/crt.2016.021
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to evaluate the effect of diabetes mellitus (DM) and preoperative glycemic control on prognosis in Korean patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). Materials and Methods A total of 566 patients who underwent RNU at six institutions between 2004 and 2014 were reviewed retrospectively. Kaplan-Meier and Cox regression analyses were performed to assess the association between DM, preoperative glycemic control, and recurrence-free, cancer-specific, and overall survival.
Results
The median follow-up period was 33.8 months (interquartile range, 41.4 months). A total of 135 patients (23.8%) had DM and 67 patients (11.8%) had poor preoperative glycemic control. Patients with poor preoperative glycemic control had significantly shorter median recurrence-free, cancer-specific, and overall survival than patients with good preoperative glycemic control and non-diabetics (all, p=0.001). In multivariable Cox regression analysis, DM with poor preoperative glycemic control showed association with worse recurrence-free survival (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.31 to 3.90; p=0.003), cancer-specific survival (HR, 2.96; 95% CI, 1.80 to 4.87; p=0.001), and overall survival (HR, 2.13; 95% CI, 1.40 to 3.22; p=0.001). Conclusion Diabetic UTUC patients with poor preoperative glycemic control had significantly worse oncologic outcomes than diabetic UTUC patients with good preoperative glycemic control and non-diabetics. Further investigation is needed to elucidate the exact mechanism underlying the impact of glycemic control on UTUC treatment outcome.

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TRIM29 Overexpression Promotes Proliferation and Survival of Bladder Cancer Cells through NF-κB Signaling
Shu-Tao Tan, Sheng-Ye Liu, Bin Wu
Cancer Res Treat. 2016;48(4):1302-1312.   Published online March 11, 2016
DOI: https://doi.org/10.4143/crt.2015.381
AbstractAbstract PDFPubReaderePub
Purpose
TRIM29 overexpression has been reported in several human malignancies and showed correlation with cancer cell malignancy. The aim of the current study is to examine its clinical significance and biological roles in human bladder cancer tissues and cell lines. Materials and Methods A total of 102 cases of bladder cancer tissues were examined for TRIM29 expression by immunohistochemistry. siRNA and plasmid transfection were performed in 5637 and BIU- 87 cell lines. Cell Counting Kit-8, flow cytometry, western blot, and real-time polymerase chain reaction were performed to examine its biological roles and mechanism in bladder cancer cells.
Results
We found that TRIM29 overexpression showed correlation with invading depth (p=0.0087). Knockdown of TRIM29 expression in bladder cancer cell line 5637 inhibited cell growth rate and cell cycle transition while its overexpression in BIU-87 cells accelerated cell proliferation and cell cycle progression. TRIM29 overexpression also inhibited cell apoptosis induced by cisplatin. In addition, we demonstrated that TRIM29 depletion decreased while its overexpression led to upregulated expression of cyclin D1, cyclin E, and Bcl-2. We also showed that TRIM29 knockdown inhibited protein kinase C (PKC) and nuclear factor κB (NF-κB) signaling while its overexpression stimulated the PKC and NF-κB pathways. BAY 11-7082 (NF-κB inhibitor) partly attenuated the effect of TRIM29 on expression of cyclin and Bcl-2. Treatment with PKC inhibitor staurosporine resulted in ameliorated TRIM29 induced activation of NF-κB. Conclusion The current study demonstrated that TRIM29 upregulates cyclin and Bcl family proteins level to facilitate malignant cell growth and inhibit drug-induced apoptosis in bladder cancer, possibly through PKC–NF-κB signaling pathways.

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The Impact of High-Risk HPV Genotypes Other Than HPV 16/18 on the Natural Course of Abnormal Cervical Cytology: A Korean HPV Cohort Study
Kyeong A So, Mi Jung Kim, Ki-Heon Lee, In-Ho Lee, Mi Kyung Kim, Yoo Kyung Lee, Chang-Sun Hwang, Mi Seon Jeong, Mee-Kyung Kee, Chun Kang, Chi Heum Cho, Seok Mo Kim, Sung Ran Hong, Ki Tae Kim, Won-Chul Lee, Jong Sup Park, Tae Jin Kim
Cancer Res Treat. 2016;48(4):1313-1320.   Published online March 9, 2016
DOI: https://doi.org/10.4143/crt.2016.013
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to evaluate the impact of high-risk human papillomaviruses (HPVs) other than HPV 16/18 on the natural course of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods
The study population was derived from the Korean HPV cohort (2010-2014). Women aged 20 to 60 who satisfied the criteria of having both HPV infection and abnormal cervical cytology of either ASC-US or LSIL were recruited from five institutions nationwide. Enrolled patients underwent cervical cytology and HPV DNA testing every 6 months.
Results
A total of 1,158 patients were enrolled. The 10 most common HPV types were HPV 16 (12.3%), 58 (10.0%), 56 (8.8%), 53 (8.4%), 52 (7.7%), 39 (6.2%), 18 (6.0%), 51 (5.7%), 68 (5.1%), and 66 (4.6%). Among these patients, 636 women were positive for high-risk HPVs other than HPV 16 or 18, and 429 women were followed for more than 6 months. Cytology evaluations showed progression in 15.3% of women, no change in 22.6%, and regression in 62.1% of women at 12 months. In cases of HPV 58 single infection, a more highly significant progression rate, compared to other high-risk types, was observed at 6 months (relative risk [RR], 3.3; 95% confidence interval [CI], 2.04 to 5.30; p < 0.001) and 12 months (RR, 5.03; 95% CI, 2.56 to 9.91; p < 0.001).
Conclusion
HPV genotypes numbered in the 50s were frequent in Korean women with ASC-US and LSIL. HPV 58 was the second most common type, with a high progression rate of cervical cytology.

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Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women
Yumi Lee, Myong Cheol Lim, Se Ik Kim, Jungnam Joo, Dong Ock Lee, Sang-Yoon Park
Cancer Res Treat. 2016;48(4):1321-1329.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.425
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women.
Materials and Methods
In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI).
Results
Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ-CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077).
Conclusion
Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding.

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Identification of Prognostic Risk Factors for Transient and Persistent Lymphedema after Multimodal Treatment for Breast Cancer
Myungsoo Kim, Kyung Hwan Shin, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Seung Hyun Chung, Yeon-Joo Kim, Tae Hyun Kim, Kwan Ho Cho
Cancer Res Treat. 2016;48(4):1330-1337.   Published online February 3, 2016
DOI: https://doi.org/10.4143/crt.2015.463
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. Materials and Methods A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next followup; arm swelling that persisted over two consecutive examinations was considered PLE.
Results
At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). Conclusion One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication.

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Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer
Ji-Yeon Kim, Kyunghee Park, Hae Hyun Jung, Eunjin Lee, Eun Yoon Cho, Kwang Hee Lee, Soo Youn Bae, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2016;48(4):1338-1350.   Published online February 18, 2016
DOI: https://doi.org/10.4143/crt.2015.430
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).
Materials and Methods
We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients.
Results
Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57,respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patientswith a TP53 missense mutation (5-year distantrecurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).
Conclusion
Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.

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Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer
Guiyun Sohn, Sei Hyun Ahn, Hee Jeong Kim, Byung-Ho Son, Jong Won Lee, Beom Seok Ko, Yura Lee, Sae Byul Lee, Seunghee Baek
Cancer Res Treat. 2016;48(4):1351-1362.   Published online April 6, 2016
DOI: https://doi.org/10.4143/crt.2015.444
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer.
Materials and Methods
In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups.
Results
A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity=matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting.
Conclusion
GnRHa+T is a reasonable alternative to AC-> T in patients with premenopausal, hormoneresponsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.

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Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment
Eunjin Jwa, Kyung Hwan Shin, Ja Young Kim, Young Hee Park, So-Youn Jung, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, Yeon-Joo Kim, Tae Hyun Kim
Cancer Res Treat. 2016;48(4):1363-1372.   Published online February 18, 2016
DOI: https://doi.org/10.4143/crt.2015.456
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61).
Results
After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.

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Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study
Se Hyun Kim, Kyung Hae Jung, Tae-Yong Kim, Seock-Ah Im, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, Sarah Park, In Hae Park, Keun Seok Lee, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Jee Hyun Kim
Cancer Res Treat. 2016;48(4):1373-1381.   Published online March 23, 2016
DOI: https://doi.org/10.4143/crt.2015.475
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy.
Materials and Methods
This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model.
Results
A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2– subtype.
Conclusion
LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2– patients is notable and worthy of further investigation.

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  • Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System
    Zhe Wang, Wei Chong, Huikun Zhang, Xiaoli Liu, Yawen Zhao, Zhifang Guo, Li Fu, Yongjie Ma, Feng Gu
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
  • The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: A dose-response meta-analysis
    Jinzhao Liu, Yifei Li, Weifang Zhang, Chenhui Yang, Chao Yang, Liang Chen, Mingjian Ding, Liang Zhang, Xiaojun Liu, Guozhong Cui, Yunjiang Liu
    Frontiers in Surgery.2022;[Epub]     CrossRef
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    Yul Ri Chung, Ji Won Woo, Soomin Ahn, Eunyoung Kang, Eun-Kyu Kim, Mijung Jang, Sun Mi Kim, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
    Scientific Reports.2021;[Epub]     CrossRef
  • Using a novel T-lymph node ratio model to evaluate the prognosis of nonmetastatic breast cancer patients who received preoperative radiotherapy followed by mastectomy
    Yang Wang, Yuanyuan Zhao, Song Liu, Weifang Tang, Hong Gao, Xucai Zheng, Shikai Hong, Shengying Wang
    Medicine.2017; 96(42): e8203.     CrossRef
  • The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes
    Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
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    Journal of Breast Cancer.2016; 19(4): 394.     CrossRef
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Clinicopathologic Features and Long-Term Outcomes of Elderly Breast Cancer Patients: Experiences at a Single Institution in Korea
Hee Kyung Kim, Jun Soo Ham, Seonggyu Byeon, Kwai Han Yoo, Ki Sun Jung, Haa-Na Song, Jinhyun Cho, Ji Yun Lee, Sung Hee Lim, Hae Su Kim, Ji-Yeon Kim, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Se Kyung Lee, Soo Youn Bae, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2016;48(4):1382-1388.   Published online March 11, 2016
DOI: https://doi.org/10.4143/crt.2015.423
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. Materials and Methods Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables.
Results
Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. Conclusion Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.

Citations

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  • HISTOPATHOLOGICAL AND BIOLOGICAL BEHAVIOR OF BREAST CANCER IN ELDERLY KURDISH WOMEN
    Kamal Saeed, Shewaz Salih
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Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years
Ji Hyung Hong, Kyung Sun Ha, Yun Hwa Jung, Hye Sung Won, Ho Jung An, Guk Jin Lee, Donghoon Kang, Ji Chan Park, Sarah Park, Jae Ho Byun, Young Jin Suh, Jeong Soo Kim, Woo Chan Park, Sang Seol Jung, Il Young Park, Su-Mi Chung, In Sook Woo
Cancer Res Treat. 2016;48(4):1389-1398.   Published online April 11, 2016
DOI: https://doi.org/10.4143/crt.2015.410
AbstractAbstract PDFPubReaderePub
Purpose
Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC.
Materials and Methods
Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively.
Results
Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease.
Conclusion
Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

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Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma
Na Hee Lee, Meong Hi Son, Young Bae Choi, Eunsang Yi, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo
Cancer Res Treat. 2016;48(4):1399-1407.   Published online March 24, 2016
DOI: https://doi.org/10.4143/crt.2015.481
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
Materials and Methods
TH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.
Results
TH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.
Conclusion
The treatment intensity should be tailored according to TH expression in PB at diagnosis.

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Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor
Ki Woong Sung, Do Hoon Lim, Eun Sang Yi, Young Bae Choi, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Ji Hye Kim, Yeon-Lim Suh, Yoo Sook Joung, Hyung Jin Shin
Cancer Res Treat. 2016;48(4):1408-1419.   Published online April 1, 2016
DOI: https://doi.org/10.4143/crt.2015.347
AbstractAbstract PDFPubReaderePub
Purpose
We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT).
Materials and Methods
For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy.
Results
A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable.
Conclusion
The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients.

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Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study
Myung Ah Lee, Eun Kyung Cho, Sung Yong Oh, Joong Bae Ahn, Ji Yun Lee, Burke Thomas, Hun Jung, Jong Gwang Kim
Cancer Res Treat. 2016;48(4):1420-1428.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.309
AbstractAbstract PDFPubReaderePub
Purpose
This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study. Materials and Methods This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acutephase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]).
Results
In South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI-1). Triple regimen (corticosteroid–5HT3-RA–neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid–5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2). Conclusion Active management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen.

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A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients
Yusook Jeong, Hye Sook Han, Hyo Duk Lee, Jiyoul Yang, Jiwon Jeong, Moon Ki Choi, Jihyun Kwon, Hyun-Jung Jeon, Tae-Keun Oh, Ki Hyeong Lee, Seung Taik Kim
Cancer Res Treat. 2016;48(4):1429-1437.   Published online February 29, 2016
DOI: https://doi.org/10.4143/crt.2015.464
AbstractAbstract PDFPubReaderePub
Purpose
Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic.
Materials and Methods
Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5.
Results
Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049).
Conclusion
We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.

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Case Reports
Coexistence of VHL Disease and CPT2 Deficiency: A Case Report
Alfonso Massimiliano Ferrara, Monica Sciacco, Stefania Zovato, Silvia Rizzati, Irene Colombo, Francesca Boaretto, Maurizio Moggio, Giuseppe Opocher
Cancer Res Treat. 2016;48(4):1438-1442.   Published online March 25, 2016
DOI: https://doi.org/10.4143/crt.2015.450
AbstractAbstract PDFPubReaderePub
von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations.

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  • A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives
    Zhongyu Han, Yuanke Luo, Haoran Chen, Guochen Zhang, Luling You, Meiqi Zhang, Yumeng Lin, Lan Yuan, Shiyi Zhou
    Kidney Diseases.2024; 10(3): 224.     CrossRef
  • Genotype–phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions
    Kenan Zhang, Wuping Yang, Kaifang Ma, Jianhui Qiu, Lei Li, Yawei Xu, Zedan Zhang, Chaojian Yu, Jingcheng Zhou, Yanqing Gong, Lin Cai, Kan Gong
    Journal of Medical Genetics.2023; 60(5): 477.     CrossRef
  • Idiopathic interstitial pneumonia in a patient with von Hippel–Lindau syndrome: a first case
    Letizia Corinna Morlacchi, Umberto Zanini, Andrea Gramegna, Paola Faverio, Francesco Blasi, Fabrizio Luppi
    ERJ Open Research.2023; 9(6): 00504-2023.     CrossRef
  • The Cross‐Link between Ferroptosis and Kidney Diseases
    Jingyu Wang, Yi Liu, Yaqing Wang, Li Sun, Ana Cipak Gasparovic
    Oxidative Medicine and Cellular Longevity.2021;[Epub]     CrossRef
  • Prioritization of differentially expressed genes through integrating public expression data
    W. Xu, S. Li, Z. Zhang, J. Hu, Y. Zhao
    Animal Genetics.2019; 50(6): 726.     CrossRef
  • 14,169 View
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  • 6 Web of Science
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Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide
Aery Choi, Young Kyung Kang, Sewon Lim, Dong Ho Kim, Jung Sub Lim, Jun Ah Lee
Cancer Res Treat. 2016;48(4):1443-1447.   Published online March 30, 2016
DOI: https://doi.org/10.4143/crt.2016.096
AbstractAbstract PDFPubReaderePub
Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

Citations

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  • Cyclophosphamide/dactinomycin/vincristine

    Reactions Weekly.2017; 1637(1): 75.     CrossRef
  • 10,923 View
  • 207 Download
  • 7 Web of Science
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