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Volume 49(2); April 2017
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Special Articles
Symposium: “Oncology Leadership in Asia”
Dong-Young Noh, Jae Kyung Roh, Yeul Hong Kim, Kazuhiro Yoshida, Hideo Baba, Marie Cherry Lynn Samson-Fernando, Sanjeev Misra, Zeba Aziz, Rainy Umbas, Yogendra P. Singh, Tony Shu Kam Mok, Han-Kwang Yang, Hideyuki Akaza
Cancer Res Treat. 2017;49(2):283-291.   Published online March 9, 2017
DOI: https://doi.org/10.4143/crt.2017.090
AbstractAbstract PDFPubReaderePub
The symposium on “Oncology Leadership in Asia” was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future.

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  • The levels, prevalence and related factors of compassion fatigue among oncology nurses: a systematic review and meta‐analysis
    Wanqing Xie, Jialin Wang, Yonggang Zhang, Min Zuo, Hua Kang, Ping Tang, Li Zeng, Man Jin, Wanying Ni, Chun Ma
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  • A Novel Prediction Model for Bloodstream Infections in Hepatobiliary–Pancreatic Surgery Patients
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    World Journal of Surgery.2019; 43(5): 1294.     CrossRef
  • Global Survey of Clinical Oncology Workforce
    Aju Mathew
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  • 9,132 View
  • 175 Download
  • 3 Web of Science
  • 3 Crossref
Close layer
Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2014
Kyu-Won Jung, Young-Joo Won, Chang-Mo Oh, Hyun-Joo Kong, Duk Hyoung Lee, Kang Hyun Lee, The Community of Population-Based Regional Cancer Registries
Cancer Res Treat. 2017;49(2):292-305.   Published online March 9, 2017
DOI: https://doi.org/10.4143/crt.2017.118
AbstractAbstract PDFPubReaderePub
Purpose
This study presents the 2014 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality.
Materials and Methods
Cancer incidence data from 1999 to 2014 was obtained from the Korea National Cancer Incidence Database and followed until December 31, 2015. Mortality data from 1983 to 2014 were obtained from Statistics Korea. The prevalence was defined as the number of cancer patients alive on January 1, 2015, among all cancer patients diagnosed since 1999. Crude and age-standardized rates (ASRs) for incidence, mortality, prevalence, and 5-year relative survivals were also calculated.
Results
In 2014, 217,057 and 76,611 Koreans were newly diagnosed and died from cancer respectively. The ASRs for cancer incidence and mortality in 2014 were 270.7 and 85.1 per 100,000, respectively. The all-cancer incidence rate has increased significantly by 3.4% annually from 1999 to 2012, and started to decrease after 2012 (2012-2014; annual percent change, –6.6%). However, overall cancer mortality has decreased 2.7% annually since 2002. The 5-year relative survival rate for patients diagnosed with cancer between 2010 and 2014 was 70.3%, an improvement from the 41.2% for patients diagnosed between 1993 and 1995.
Conclusion
Age-standardized cancer incidence rates have decreased since 2012 and mortality rates have also declined since 2002, while 5-year survival rates have improved remarkably from 1993-1995 to 2010-2014 in Korea.

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Prediction of Cancer Incidence and Mortality in Korea, 2017
Kyu-Won Jung, Young-Joo Won, Chang-Mo Oh, Hyun-Joo Kong, Duk Hyoung Lee, Kang Hyun Lee
Cancer Res Treat. 2017;49(2):306-312.   Published online March 17, 2017
DOI: https://doi.org/10.4143/crt.2017.130
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report on cancer incidence and mortality for the year 2017 in Korea in order to estimate the nation’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2014 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2015 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observe age-specific cancer rates against observed years, and then multiplying the projected age-specific rates by the age-specific population. The Joinpoint regression model was used to determine at which year the linear trend changed significantly; we only used data of the latest trend.
Results
A total of 221,143 new cancer cases and 80,268 cancer deaths are expected to occur in Korea in 2017. The most common cancer sites are the colorectum, stomach, lung, thyroid, and breast. These five cancers represent half of the overall burden of cancer in Korea. For mortality, the most common sites are the lung, liver, colorectal, stomach, and pancreas.
Conclusion
The incidence rate of all cancers in Korea appears to have decreased mainly because of a decrease in thyroid cancer. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluation of cancer-control programs.

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Original Articles
Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers
So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim
Cancer Res Treat. 2017;49(2):313-321.   Published online July 7, 2016
DOI: https://doi.org/10.4143/crt.2016.098
AbstractAbstract PDFPubReaderePub
Purpose
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers.
Materials and Methods
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.
Results
MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor.
Conclusion
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

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Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation
Abjal Pasha Shaik, Asma Sultana Shaik, Ali Al Majwal, Achraf Al Faraj
Cancer Res Treat. 2017;49(2):322-329.   Published online July 12, 2016
DOI: https://doi.org/10.4143/crt.2016.091
AbstractAbstract PDFPubReaderePub
Purpose
The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, the in vitro efficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells.
Materials and Methods
Cell viability, reactive oxygen species generation, and apoptosis frequency were assessed in vitro in 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells.
Results
Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells.
Conclusion
These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasis in vivo.

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Current Trends of Lung Cancer Surgery and Demographic and Social Factors Related to Changes in the Trends of Lung Cancer Surgery: An Analysis of the National Database from 2010 to 2014
Samina Park, In Kyu Park, Eung Re Kim, Yoohwa Hwang, Hyun Joo Lee, Chang Hyun Kang, Young Tae Kim
Cancer Res Treat. 2017;49(2):330-337.   Published online July 18, 2016
DOI: https://doi.org/10.4143/crt.2016.196
AbstractAbstract PDFPubReaderePub
Purpose
We investigated current trends in lung cancer surgery and identified demographic and social factors related to changes in these trends.
Materials and Methods
We estimated the incidence of lung cancer surgery using a procedure code-based approach provided by the Health Insurance Review and Assessment Service (http://opendata.hira.or.kr). The population data were obtained every year from 2010 to 2014 from the Korean Statistical Information Service (http://kosis.kr/). The annual percent change (APC) and statistical significance were calculated using the Joinpoint software.
Results
From January 2010 to December 2014, 25,687 patients underwent 25,921 lung cancer surgeries, which increased by 45.1% from 2010 to 2014. The crude incidence rate of lung cancer surgery in each year increased significantly (APC, 9.5; p < 0.05). The male-to-female ratio decreased from 2.1 to 1.6 (APC, −6.3; p < 0.05). The incidence increased in the age group of ≥ 70 years for both sexes (male: APC, 3.7; p < 0.05; female: APC, 5.96; p < 0.05). Furthermore, the proportion of female patients aged ≥ 65 years increased (APC, 7.2; p < 0.05), while that of male patients aged < 65 years decreased (APC, −3.9; p < 0.05). The proportions of segmentectomies (APC, 17.8; p < 0.05) and lobectomies (APC, 7.5; p < 0.05) increased, while the proportion of pneumonectomies decreased (APC, −6.3; p < 0.05). Finally, the proportion of patients undergoing surgery in Seoul increased (APC, 1.1; p < 0.05), while the proportion in other areas decreased (APC, −1.5; p < 0.05).
Conclusion
An increase in the use of lung cancer surgery in elderly patients and female patients, and a decrease in the proportion of patients requiring extensive pulmonary resection were identified. Furthermore, centralization of lung cancer surgery was noted.

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Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway
Boyun Kim, Hee Seung Kim, Soochi Kim, Guy Haegeman, Benjamin K. Tsang, Danny N. Dhanasekaran, Yong Sang Song
Cancer Res Treat. 2017;49(2):338-349.   Published online July 18, 2016
DOI: https://doi.org/10.4143/crt.2016.175
AbstractAbstract PDFPubReaderePub
Purpose
Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells.
Materials and Methods
CD45– and CD31– double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively.
Results
CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients.
Conclusion
ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.

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Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program
Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Tae-Yong Kim, Su Jin Lee, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang
Cancer Res Treat. 2017;49(2):350-357.   Published online July 19, 2016
DOI: https://doi.org/10.4143/crt.2016.067
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
Materials and Methods
Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off).
Results
None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31).
Conclusion
This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

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Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells
Jinxiang Huang, Fenglin Zhang, Lei Jiang, Guohan Hu, Wei Sun, Chenran Zhang, Xuehua Ding
Cancer Res Treat. 2017;49(2):358-373.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.017
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project.
Materials and Methods
Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells.
Results
Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells.
Conclusion
These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

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    Jonahunnatha Nesson George William, Ruby Dhar, Rohit Gundamaraju, Om Saswat Sahoo, Karthikeyan Pethusamy, A. F. P. Allwin Mabes Raj, Subbiah Ramasamy, Mohammed S. Alqahtani, Mohamed Abbas, Subhradip Karmakar
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Induction of Apoptosis in Intestinal Toxicity to a Histone Deacetylase Inhibitor in a Phase I Study with Pelvic Radiotherapy
Erta Kalanxhi, Karianne Risberg, Imon S. Barua, Svein Dueland, Stein Waagene, Solveig Norheim Andersen, Solveig J. Pettersen, Jessica M. Lindvall, Kathrine Røe Redalen, Kjersti Flatmark, Anne Hansen Ree
Cancer Res Treat. 2017;49(2):374-386.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.080
AbstractAbstract PDFPubReaderePub
Purpose
When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) when administered as a potential radiosensitiser.
Materials and Methods
This phase I study for advanced gastrointestinal carcinoma was conducted in sequential patient cohorts exposed to escalating doses of vorinostat combined with standard-fractionated palliative radiotherapy to pelvic target volumes. Gene expression microarray analysis of the study patient peripheral blood mononuclear cells (PBMC) was followed by functional validation in cultured cell lines and mice treated with SAHA.
Results
PBMC transcriptional responses to vorinostat, including induction of apoptosis, were confined to the patient cohort reporting dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic features (annexin V staining and caspase 3/7 activation, but not poly-(ADP-ribose)-polymerase cleavage) were observed in cultured intestinal epithelial cells. Moreover, SAHA-treated mice displayed significant weight loss.
Conclusion
The PRAVO study design implemented a strategy to explore treatment toxicity caused by an HDAC inhibitor when combined with radiotherapy and enabled the identification of apoptosis as a potential mechanism responsible for the dose-limiting effects of vorinostat. To the best of our knowledge, this is the first report deciphering mechanisms of normal tissue adverse effects in response to an HDAC inhibitor within a combined-modality treatment regimen.

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Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma
Young-Bem Se, Seung Hyun Kim, Ji Young Kim, Ja Eun Kim, Yun-Sik Dho, Jin Wook Kim, Yong Hwy Kim, Hyun Goo Woo, Se-Hyuk Kim, Shin-Hyuk Kang, Hak Jae Kim, Tae Min Kim, Soon-Tae Lee, Seung Hong Choi, Sung-Hye Park, Il Han Kim, Dong Gyu Kim, Chul-Kee Park
Cancer Res Treat. 2017;49(2):387-398.   Published online July 19, 2016
DOI: https://doi.org/10.4143/crt.2016.106
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.
Materials and Methods
The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.
Results
The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith lowHOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.
Conclusion
The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

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Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer
In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee
Cancer Res Treat. 2017;49(2):399-407.   Published online July 27, 2016
DOI: https://doi.org/10.4143/crt.2016.215
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined.
Materials and Methods
A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13 mRNA expression levels using a NanoString assay (NanoString Technologies).
Results
The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate.
Conclusion
MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients
Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2017;49(2):408-415.   Published online July 27, 2016
DOI: https://doi.org/10.4143/crt.2016.135
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer
Miso Kim, Bhumsuk Keam, Tae-Min Kim, Hoon-Gu Kim, Jin-Soo Kim, Sung Sook Lee, Seong Hoon Shin, Min Kyoung Kim, Keon Uk Park, Dong-Wan Kim, Hwan Jung Yun, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2017;49(2):416-422.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.121
AbstractAbstract PDFPubReaderePub
Purpose
The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer.
Materials and Methods
Patients were treated with irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity.
Results
A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%).
Conclusion
Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

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Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results
Yeon Hee Park, Tae Yong Kim, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soo-Hyeon Lee, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung
Cancer Res Treat. 2017;49(2):423-429.   Published online August 3, 2016
DOI: https://doi.org/10.4143/crt.2016.191
AbstractAbstract PDFPubReaderePub
Purpose
Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC),who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.
Materials and Methods
In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease.
Results
A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.
Conclusion
This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

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The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome
Marcin R. Lener, Aniruddh Kashyap, Wojciech Kluźniak, Cezary Cybulski, Agnieszka Soluch, Sandra Pietrzak, Tomasz Huzarski, Jacek Gronwald, Jan Lubiński
Cancer Res Treat. 2017;49(2):430-436.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.217
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible associationwith the familial pancreatic cancer (FPC) risk in Poland.
Materials and Methods
In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes.
Results
A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026).
Conclusion
The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome.

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    Marek Szwiec, Joanna Tomiczek-Szwiec, Wojciech Kluźniak, Dominika Wokołorczyk, Karolina Osowiecka, Robert Sibilski, Małgorzata Wachowiak, Jacek Gronwald, Helena Gronwald, Jan Lubiński, Cezary Cybulski, Steven A. Narod, Tomasz Huzarski
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Do Korean Doctors Think a Palliative Consultation Team Would Be Helpful to Their Terminal Cancer Patients?
Hye-Young Shim, Yoon Jung Chang, Kiu-Sang Kawk, Tran Thi Xuan Mai, Jin Young Choi, Eun Mi Ahn, Hyun Jung Jho, So-Jung Park
Cancer Res Treat. 2017;49(2):437-445.   Published online August 10, 2016
DOI: https://doi.org/10.4143/crt.2015.495
AbstractAbstract PDFPubReaderePub
Purpose
Hospice and palliative care services (HPC) are not commonly utilized in Korea; however, palliative care teams (PCTs) have been found to be effective at addressing the shortcomings in HPC. In this study, we attempted to outline unmet palliative care needs of terminal cancer patients and the potential benefits of PCTs as perceived by doctors in Korea.
Materials and Methods
We surveyed 474 doctors at 10 cancer-related academic conferences from June to November 2014 with a self-report questionnaire to assess their perceptions of end-of-life care needs and the expected effects of PCTs on caring for terminal cancer patients. Among those surveyed, 440 respondents who completed the entire questionnaire were analyzed.
Results
In all domains, fewer participants reported satisfaction with palliative care services than those reporting needs (p < 0.001). The surveyed participants also reported difficulties with a shortage of time for treatment, psychological burden, lack of knowledge regarding hospice care, lengths of stay, and palliative ward availability. Multivariate logistic regression analysis revealed that female doctors (odds ratio [OR], 2.672; 95% confidence interval [CI], 1.035 to 6.892), doctors who agreed that referring my patients to a HPC means I must give up on my patient (OR, 3.075; 95% CI, 1.324 to 7.127), and doctors who had no experience with HPC education (OR, 3.337; 95% CI, 1.600 to 7.125) were associated with higher expected effectiveness of PCT activities.
Conclusion
The PCT activities were expected to fill the doctor’s perceived unmet HPC needs of terminal cancer patients and difficulties in communications.

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  • Effects of tertiary palliative care on the pattern of end‐of‐life care in patients with hematologic malignancies in Korea
    Dong Hyun Kim, Jeonghwan Youk, Ja Min Byun, Youngil Koh, Junshik Hong, Tae Min Kim, Inho Kim, Sung‐Soo Yoon, Shin Hye Yoo, Dong‐Yeop Shin
    European Journal of Haematology.2024; 112(5): 743.     CrossRef
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    Abdulrahman Abdulaziz Abdullah, Wafaa Mostafa Abd-El-Gawad, Sobhi Mostafa AboSerea, Fatma AbdelShakor Ali, Saima Ali
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    Antonia M. Willemsen, Stephen Mason, Silja Zhang, Frank Elsner
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    Eunmi Ahn, In Gyu Song, Jin Young Choi, Hyun Jung Jho, Ilyeon Park, Suah Sung, Seohyun Shin, So Jung Park, Eun Jung Nam, Sung Hoon Jeong, Yoon Jung Chang
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Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea
Jae Wook Lee, Seong-koo Kim, Pil-Sang Jang, Nack-Gyun Chung, Dae-Chul Jeong, Myungshin Kim, Bin Cho, Hack-Ki Kim
Cancer Res Treat. 2017;49(2):446-453.   Published online August 10, 2016
DOI: https://doi.org/10.4143/crt.2016.211
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables.
Materials and Methods
Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities.
Results
The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%.
Conclusion
ETV6/RUNX1 ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

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  • Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives
    Laras Pratiwi, Fawzia Hanum Mashudi, Mukti Citra Ningtyas, Henry Sutanto, Pradana Zaky Romadhon
    Hematology Reports.2025; 17(2): 18.     CrossRef
  • Outcome and Prognostic Factors of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Relapsed or Refractory ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia
    Guan-hua Hu, Xiao-hui Zhang, Kai-yan Liu, Lan-ping Xu, Yu Wang, Yi-fei Cheng, Xiao-jun Huang
    Acta Haematologica.2024; 147(5): 534.     CrossRef
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    Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho
    Cancer Research and Treatment.2021; 53(2): 567.     CrossRef
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    Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
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    Yu Wang, Hui-min Zeng, Le-ping Zhang
    Italian Journal of Pediatrics.2018;[Epub]     CrossRef
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    Jae Wook Lee, Bin Cho
    Korean Journal of Pediatrics.2017; 60(5): 129.     CrossRef
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    Parisa Rasighaemi, Alister C. Ward
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    Congcong Sun, Lixian Chang, Xiaofan Zhu
    Oncotarget.2017; 8(21): 35445.     CrossRef
  • 13,795 View
  • 292 Download
  • 6 Web of Science
  • 8 Crossref
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Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea
Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im
Cancer Res Treat. 2017;49(2):454-463.   Published online August 23, 2016
DOI: https://doi.org/10.4143/crt.2016.259
AbstractAbstract PDFPubReaderePub
Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

Citations

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    Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
    Gynecologic Oncology.2017; 147(1): 158.     CrossRef
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DNA Methyltransferase Gene Polymorphisms for Prediction of Radiation-Induced Skin Fibrosis after Treatment of Breast Cancer: A Multifactorial Genetic Approach
Salvatore Terrazzino, Letizia Deantonio, Sarah Cargnin, Laura Donis, Carla Pisani, Laura Masini, Giuseppina Gambaro, Pier Luigi Canonico, Armando A. Genazzani, Marco Krengli
Cancer Res Treat. 2017;49(2):464-472.   Published online August 23, 2016
DOI: https://doi.org/10.4143/crt.2016.256
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis.
Materials and Methods
DNMT1 rs2228611,DNMT3A rs1550117,DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue–Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC).
Results
Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade ≥ 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710).
Conclusion
DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.

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    Xiaxia Man, Qi Li, Baogang Wang, He Zhang, Songling Zhang, Ziyi Li
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
  • DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1


    Chunlin Zhang, Jiaoping Mi, Yuan Deng, Zeyi Deng, Dan Long, Zhaohui Liu
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    Nádia M. Garcês de Couto, Júlia B. Willig, Thaís C. Ruaro, Diogo Losch de Oliveira, Andréia Buffon, Diogo A. Pilger, Mara S.P. Arruda, Diogo Miron, Aline R. Zimmer, Simone C.B. Gnoatto
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    Shashank Shrishrimal, Elizabeth A. Kosmacek, Rebecca E. Oberley-Deegan
    Oxidative Medicine and Cellular Longevity.2019; 2019: 1.     CrossRef
  • Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis
    Salvatore Terrazzino, Sarah Cargnin, Letizia Deantonio, Carla Pisani, Laura Masini, Pier Luigi Canonico, Armando A. Genazzani, Marco Krengli, Christophe Badie
    PLOS ONE.2019; 14(11): e0225685.     CrossRef
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    Jennifer J. Hu, James J. Urbanic, L. Doug Case, Cristiane Takita, Jean L. Wright, Doris R. Brown, Carl D. Langefeld, Mark O. Lively, Sandra E. Mitchell, Anu Thakrar, David Bryant, Kathy Baglan, Jon Strasser, Luis Baez-Diaz, Glenn J. Lesser, Edward G. Shaw
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Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution
Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jeanny Kwon, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2017;49(2):473-483.   Published online August 23, 2016
DOI: https://doi.org/10.4143/crt.2016.166
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors.
Materials and Methods
A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months).
Results
The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%).
Conclusion
Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches.

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  • Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study
    Peter LZ. Labib, Thomas B. Russell, Jemimah L. Denson, Mark A. Puckett, Fabio Ausania, Elizabeth Pando, Keith J. Roberts, Ambareen Kausar, Vasileios K. Mavroeidis, Ricky H. Bhogal, Gabriele Marangoni, Sarah C. Thomasset, Adam E. Frampton, Duncan R. Spaldi
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    Nadine Soliman, Ashton A. Connor, Sudha Kodali, Rafik Mark Ghobrial
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Young Age Is Associated with Increased Locoregional Recurrence in Node-Positive Breast Cancer with Luminal Subtypes
Sang-Won Kim, Mison Chun, Sehwan Han, Yong Sik Jung, Jin Hyuk Choi, Seok Yun Kang, Hyunee Yim, Seung Hee Kang
Cancer Res Treat. 2017;49(2):484-493.   Published online August 23, 2016
DOI: https://doi.org/10.4143/crt.2016.246
AbstractAbstract PDFPubReaderePub
Purpose
The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes.
Materials and Methods
Medicalrecords of 524 breast cancer patientswith positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapywas administered to 413 patientswith positive hormone receptors according to their menstrual status.
Results
During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01).
Conclusion
Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.

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Nationwide Population-Based Incidence and Survival Rates of Malignant Central Nervous System Germ Cell Tumors in Korea, 2005-2012
Seung Hoon Lee, Kyu-Won Jung, Johyun Ha, Chang-Mo Oh, Hyeseon Kim, Hyeon Jin Park, Heon Yoo, Young-Joo Won
Cancer Res Treat. 2017;49(2):494-501.   Published online August 24, 2016
DOI: https://doi.org/10.4143/crt.2016.129
AbstractAbstract PDFPubReaderePub
Purpose
Malignant central nervous system (CNS) germ cell tumors (GCTs), although rare, are thought to occur more frequently among Asians. However, a recent population-based study revealed no differences in GCT incidence between Asians and Caucasians. Therefore, this study was conducted to determine the incidence and survival rates of CNS GCTs using the national cancer incidence database, and to compare these rates to those in the United States and Japan.
Materials and Methods
We extracted CNS GCT patients diagnosed between 2005 and 2012 from the Korea Central Cancer Registry database. Age-standardized rates (ASRs), annual percentage change, and the male-female incidence rate ratios (IRRs) were calculated. To estimate the survival rate, we used data for patients diagnosed between 2005 and 2010 and followed their cases until December 31, 2013.
Results
The ASR for CNS GCT between 2005 and 2012 was 0.179 per 100,000 (95% confidence interval, 0.166 to 0.193), with an overall male-to-female (M:F) IRR of 2.95:1. However, when stratified by site, the M:F IRR was 13.62:1 for tumors of the pineal region and 1.87:1 for those located in nonpineal regions. The most frequent histologic type was germinoma (76.0%), and the most frequent location was the suprasellar region (48.5%). The 5-year survival rate of germinoma patients was 95.3%.
Conclusion
The incidence rate of CNS GCTs in Korea during 2005-2012 was 0.179 per 100,000, which was similar to that of the Asian/Pacific Islander subpopulation in the United States. Moreover, the CNS GCT survival rate in Korea was similar to rates in Japan and the United States.

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The Association between End-of-Life Care and the Time Interval between Provision of a Do-Not-Resuscitate Consent and Death in Cancer Patients in Korea
Sun Kyung Baek, Hye Jung Chang, Ja Min Byun, Jae Joon Han, Dae Seog Heo
Cancer Res Treat. 2017;49(2):502-508.   Published online September 1, 2016
DOI: https://doi.org/10.4143/crt.2016.073
AbstractAbstract PDFPubReaderePub
Purpose
We explored the relationship between the use of each medical intervention and the length of time between do-not-resuscitate (DNR) consent and death in Korea.
Materials and Methods
A total of 295 terminal cancer patients participated in this retrospective study. Invasive interventions (e.g., cardiopulmonary resuscitation, intubation, and hemodialysis), less invasive interventions (e.g., transfusion, antibiotic use, inotropic use, and laboratory tests), and the time interval between the DNR order and death were evaluated. The subjects were divided into three groups based on the amount of time between DNR consent and death (G1, time interval ≤ 1 day; G2, time interval > 1 day to ≤ 3 days; and G3, time interval > 3 days).
Results
In general, there were fewer transfusions and laboratory tests near death. Invasive interventions tended to be implemented only in the G1 group. There was also less inotrope use and fewerlaboratory tests in the G3 group than G1 and G2. Moreover, the G3 group received fewer less invasive interventions than those in G1 (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03 to 0.84; 3 days before death, and OR, 0.16; 95% CI, 0.04 to 0.59; the day before death). The frequency of less invasive interventions both 1 and 3 days before death was significantly lower for the G3 group than the G1 (p ≤ 0.001) and G2 group compared to G1 (p=0.001).
Conclusion
Earlier attainment of DNR permission was associated with reduced use of medical intervention. Thus, physicians should discuss death with terminal cancer patients at the earliest practical time to prevent unnecessary and uncomfortable procedures and reduce health care costs.

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The Role of Notch1 Signaling in Anaplastic Thyroid Carcinoma
Hyeon Jin Kim, Min-Jung Kim, Areumnuri Kim, Chang Won Jung, Sunhoo Park, Jae Soo Koh, Jae Kyung Myung
Cancer Res Treat. 2017;49(2):509-517.   Published online September 1, 2016
DOI: https://doi.org/10.4143/crt.2016.214
AbstractAbstract PDFPubReaderePub
Purpose
The Notch signaling pathway is widely expressed in normal, reactive, and neoplastic tissues; however, its role in thyroid tissues has not been fully elucidated. Therefore, this study was conducted to characterize the expression of the Notch signaling pathway in papillary thyroid cancer (PTC) cells and anaplastic thyroid cancer (ATC) cells.
Materials and Methods
Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA techniquewas employed to knock down Notch1 expression in ATC and PTC cell lines.
Results
The expression of activated Notch1 was higher in ATC cases than in PTC cases. Inhibition of Notch1 significantly reduced proliferation and migration of ATC cells, but not PTC cells. In addition, inhibition of Notch1 in ATC cells significantly reduced the expression of key markers of epithelial-mesenchymal transition and cancer stem cells. Conversely, changes in the expression of these proteins were not observed in PTC cells.
Conclusion
The results of this study suggest that Notch1 expression plays different roles in tumor progression in ATC and PTC cells. We also found that Notch1 expression was significantly related to the highly invasive or proliferative activity of ATC cells.

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Magnetic Resonance Imaging–Detected Intracranial Extension in the T4 Classification Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy
Caineng Cao, Jingwei Luo, Li Gao, Junlin Yi, Xiaodong Huang, Suyan Li, Jianping Xiao, Zhong Zhang, Guozhen Xu
Cancer Res Treat. 2017;49(2):518-525.   Published online August 24, 2016
DOI: https://doi.org/10.4143/crt.2016.299
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted is to identify the prognostic value and staging categories of magnetic resonance imaging (MRI)–detected intracranial extension in nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT) to determine whether it is necessary to subclassify the T4 classification NPC.
Materials and Methods
A total of 335 nonmetastatic T4 classificationNPC patientswith MRI treated between March 2004 and June 2011 by radical IMRTwere included. The T4 classification patientswere subclassified into two grades (T4a, without intracranial extension vs. T4b, with intracranial extension) according to the site of invasion.
Results
The frequency of intracranial extensionwas 40.9% (137 of 335 patients). Multivariate analysis identified subclassification (T4a vs. T4b) as an independent prognostic factor for local failure-free survival (p=0.049; hazard ratio [HR], 0.498) and overall survival (p=0.004; HR, 0.572); however, it had no effect on regional failure-free survival or distant failure-free survival (p > 0.050).
Conclusion
For patients with T4 classification NPC, those with MRI-detected intracranial extension are more likely to experience local failure and death afterIMRT than patientswithout intracranial extension. According to the site of invasion, subclassification of T4 patients as T4a or T4b has prognostic value in NPC.

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    Wenjie Huang, Shuqi Li, Chao Luo, Zhiying Liang, Shumin Zhou, Haojiang Li, Yi Cai, Shaobo Liang, Guangying Ruan, Peiqiang Cai, Lizhi Liu
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Trends and Age-Period-Cohort Effects on the Incidence and Mortality Rate of Cervical Cancer in Korea
Eun-Kyeong Moon, Chang-Mo Oh, Young-Joo Won, Jong-Keun Lee, Kyu-Won Jung, Hyunsoon Cho, Jae Kwan Jun, Myong Cheol Lim, Moran Ki
Cancer Res Treat. 2017;49(2):526-533.   Published online September 1, 2016
DOI: https://doi.org/10.4143/crt.2016.316
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to describe the trends and age-period-cohort effects on the incidence and mortality rate of cervical cancer in Korea.
Materials and Methods
The incidence and mortality rate of cervical cancer among ≥ 20-year-old women from 1993 to 2012 were obtained from the Korea Central Cancer Registry and the Korean Statistical Information Service. Age-standardized rates were calculated and Joinpoint regression was used to evaluate the trends in the incidence and mortality rate. Age-period-cohort analysis was performed to investigate the independent effects of age, period and cohort.
Results
The incidence of cervical cancer decreased from 32.8 per 100,000 in 1993 to 15.9 per 100,000 in 2012 (annual percent change [APC], –3.9%; 95% confidence interval [CI], –4.2% to –3.6%). The mortality rate decreased from 5.2 per 100,000 in 1993 to 2.1 per 100,000 in 2012 (APC, –4.8%; 95% CI, –5.1% to –4.4%); however, the incidence and mortality rates among young women (< 30 years old) increased. An age-period-cohort model of the incidence and mortality rate showed decreasing period effects between 1993 and 2008 and decreasing cohort effects between 1928 and 1973, while birth cohorts after 1973 exhibited slight increases in the incidence and mortality rate of cervical cancer.
Conclusion
Recent decreases in the incidence and mortality rate of cervical cancer were due to decreases in the period and cohort effects, which reflect the implementation of a cancer screening program and changes in lifestyle. However, our findings also highlighted an increase in cohort effects on the incidence and mortality rate among young women born after 1973.

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Meta-Analysis
Alcohol Intake and Risk of Thyroid Cancer: A Meta-Analysis of Observational Studies
Seung-Hee Hong, Seung-Kwon Myung, Hyeon Suk Kim, The Korean Meta-Analysis (KORMA) Study Group
Cancer Res Treat. 2017;49(2):534-547.   Published online July 7, 2016
DOI: https://doi.org/10.4143/crt.2016.161
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to assess whether alcohol intake is associated with the risk of thyroid cancer by a meta-analysis of observational studies.
Materials and Methods
We searched PubMed and EMBASE in June of 2015 to locate eligible studies. We included observational studies such as cross-sectional studies, case-control studies, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) with 95% confidence intervals (CIs).
Results
We included 33 observational studies with two cross-sectional studies, 20 case-controls studies, and 11 cohort studies, which involved a total of 7,725 thyroid cancer patients and 3,113,679 participants without thyroid cancer in the final analysis. In the fixed-effect model meta-analysis of all 33 studies, we found that alcohol intake was consistently associated with a decreased risk of thyroid cancer (OR or RR, 0.74; 95% CI, 0.67 to 0.83; I2=38.6%). In the subgroup meta-analysis by type of study, alcohol intake also decreased the risk of thyroid cancer in both case-control studies (OR, 0.77; 95% CI, 0.65 to 0.92; I2=29.5%; n=20) and cohort studies (RR, 0.70; 95% CI, 0.60 to 0.82; I2=0%; n=11). Moreover, subgroup meta-analyses by type of thyroid cancer, gender, amount of alcohol consumed, and methodological quality of study showed that alcohol intake was significantly associated with a decreased risk of thyroid cancer.
Conclusion
The current meta-analysis of observational studies found that, unlike most of other types of cancer, alcohol intake decreased the risk of thyroid cancer.

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Case Reports
Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia
Mathias Lutz, Arik B. Schulze, Elisabeth Rebber, Stefanie Wiebe, Tarek Zoubi, Oliver M. Grauer, Torsten Keßler, Andrea Kerkhoff, Georg Lenz, Wolfgang E. Berdel
Cancer Res Treat. 2017;49(2):548-552.   Published online July 12, 2016
DOI: https://doi.org/10.4143/crt.2016.110
AbstractAbstract PDFPubReaderePub
Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.

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Erdheim-Chester Disease with Emperipolesis: A Unique Case Involving the Heart
Pengcheng Zhu, Naping Li, Lu Yu, Mariajose Navia Miranda, Guoping Wang, Yaqi Duan
Cancer Res Treat. 2017;49(2):553-558.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.078
AbstractAbstract PDFPubReaderePub
Histiocytosis is an uncommon disease characterized by excessive accumulation of histiocytes. Here, we report a rare case of non-Langerhans-cell histiocytosis in a 51- year-old woman who presented with severe symptoms of pericardial effusion. Radiologic investigation also detected multiple bone (lower limbs, vertebrae, ribs, and ilium) lesions. Resected pericardium showed abundant mono- or multi-nucleated non-foamy histiocytes (CD68+/CD163+/S-100+/CD1α/langerin) in a fibroinflammatory background. The histiocytes demonstrated emperipolesis of lymphocytes, a hallmark feature of Rosai-Dorfman disease (RDD). However, molecular analysis revealed a BRAF V600E mutation of the proliferating histiocytes, highlighting the neoplastic features frequently observed in another non-Langerhans-cell histiocytosis known as Erdheim-Chester Disease (ECD). We consider this case to be a unique presentation of ECD harboring some RDD-like cells with emperipolesis, but not a case of RDD with a BRAF mutation concerning its clinical manifestation (involvement of the heart and bones) and neoplastic features.

Citations

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