Showing papers in "Cancer Research and Treatment in 2016"

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2013.

Abstract: Purpose: This study described the 2013 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality.

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor.

Abstract: 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.

Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.

Abstract: Purpose Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.

What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy

Abstract: PURPOSE Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. MATERIALS AND METHODS This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. RESULTS All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. CONCLUSION The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone.

Incidence and Survival of Childhood Cancer in Korea.

Abstract: Purpose An epidemiologic study of childhood cancer would provide useful information on cancer etiology and development of management guidelines.

BRAF-Activated Long Noncoding RNA Modulates Papillary Thyroid Carcinoma Cell Proliferation through Regulating Thyroid Stimulating Hormone Receptor

Abstract: Purpose The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. Materials and methods Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. Results Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. Conclusion These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.

Prediction of Cancer Incidence and Mortality in Korea, 2016

Abstract: Purpose: To estimate of Korea’s current cancer burden, this study aimed to report on projected cancer incidence and mortality rates for the year 2016.

Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer

Abstract: 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 patients with a TP53 missense mutation (5-year distant recurrence-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.

Serum Concentrations of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer

Abstract: Purpose Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associations between concentrations of selenium (Se) and copper (Cu) in the serum of PaCa patients. Materials and methods The study included 100 PaCa patients and 100 control subjects from the same geographical region in Poland. To determine the average concentration of Se, Cu, and ratio Cu:Se in the Polish population, assay for Se and Cu was performed in 480 healthy individuals. Serum levels of Se and Cu were measured using inductively coupled plasma mass spectrometry. Results In the control group, the average Se level was 76 µg/L and Cu 1,098 µg/L. The average Se level among PaCa patients was 60 µg/L and the mean Cu level was 1,432 µg/L. The threshold point at which any decrease in Se concentration was associated with PaCa was 67.45 µg/L. The threshold point of Cu level above which there was an increase in the prevalence of PaCa was 1,214.58 µg/L. In addition, a positive relationship was observed between increasing survival time and Se plasma level. Conclusion This retrospective study suggests that low levels of Se and high levels of Cu might influence development of PaCa and that higher levels of Se are associated with longer survival in patients with PaCa. The results suggest that determining the level of Se and Cu could be incorporated into a risk stratification scheme for the selection and surveillance control examination to complement existing screening and diagnostic procedures.

Chronological Changes of Quality of Life in Long-Term Survivors after Gastrectomy for Gastric Cancer.

Abstract: Purpose A few studies have prospectively evaluated changes in quality of life (QoL) after surgery in short-term survivors; however, no prospective study has evaluated the longitudinal changes in QoL in long-terms survivors. We prospectively evaluated the chronological changes in QoL after a gastrectomy over a 5-year postoperative period in a large group of patients.

Identification of Prognostic Risk Factors for Transient and Persistent Lymphedema after Multimodal Treatment for Breast Cancer.

Abstract: Purpose The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer.

A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients

Abstract: 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.

The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.

Abstract: Purpose The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.

Surgery Alone Versus Surgery Followed by Chemotherapy and Radiotherapy in Resected Extrahepatic Bile Duct Cancer: Treatment Outcome Analysis of 336 Patients

Abstract: PURPOSE This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients. MATERIALS AND METHODS A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49). RESULTS The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05). CONCLUSION Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.

Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy.

Abstract: 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.

Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment.

Abstract: 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).

Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women.

Abstract: 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.

Oncologic and Functional Outcomes after Partial Nephrectomy Versus Radical Nephrectomy in T1b Renal Cell Carcinoma: A Multicenter, Matched Case-Control Study in Korean Patients

Abstract: Purpose The study was to compare the oncologic and functional outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for pathologically proven T1b renal cell carcinoma using pair-matched groups. Materials and methods We reviewed our prospectively maintained database for RN and PN in T1b renal tumors surgically treated between 1999 and 2011 at five institutions in Korea. Of 611 patients treated with PN or RN for a solitary and NX/N0 M0 renal mass (4-7 cm), 577 (PN, 100; RN, 477) patients with pathologically confirmed pT1b remained for analysis. Study subjects were grouped by PN or RN, then matched by age, sex, comorbidities, body mass index, tumor size and depth, histologic type, and preoperative estimated glomerular filtration rate (eGFR) using propensities score. To evaluate oncologic outcomes, overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were analyzed. The functional outcomes were evaluated by postoperative eGFR. Results The median follow-up in the RN group was 48.1 and 42.6 months in the PN group. The estimated 10-year CSS rate (PN 85.7% vs. RN 84.4%, p=0.52) and 5- and estimated 10-year PFS rates (PN: 86.4% and 79.2% vs. RN: 86.0% and 66.1%, p=0.66) did not differ significantly between groups. The estimated 10-year OS rate was significantly higher in the PN group (85.7%) compared to the RN group (73.3%) (p=0.003). PN was less likely to induce new-onset chronic kidney disease (CKD) and end-stage CKD compared with RN. Conclusion Our study suggests that patients treated with PN demonstrate a superior OS rate and postoperative renal function with analogous CSS and PFS rates compared with pair-matched patients treated with RN.

Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years

Abstract: 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.

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

Abstract: Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

TRIM29 Overexpression Promotes Proliferation and Survival of Bladder Cancer Cells through NF-κB Signaling.

Abstract: 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.

Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide Cohort Study.

Abstract: Purpose The aim of this study was to investigate whether aspirin use can reduce the incidence of gastric cancer in patients with hypertension or type 2 diabetes. Materials and methods A total of 200,000 patients with hypertension or type 2 diabetes were randomly selected from the Korean National Health Insurance claim database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non-users) were selected at a frequency of 1:2, matched by age, sex, comorbid illnesses (type 2 diabetes and hypertension), and observation periods. The incidence of gastric cancer in this cohort was then assessed during the observation period of 2004 to 2010. Results In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1% (86/7,808) for aspirin non-users, but the cumulative incidence rates were not significantly different between groups (p=0.116, log-rank test). However, in multivariate analysis, regular aspirin users had a reduced risk of gastric cancer (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08; p=0.107). Duration of aspirin use showed significant association with reduction of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to 0.99; p=0.044), particularly in patients who used aspirin for more than 3 years (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045). Conclusion Long-term low-dose aspirin use was associated with reduced gastric cancer risk in patients with hypertension or type 2 diabetes.

Appendiceal Neuroendocrine, Goblet and Signet-Ring Cell Tumors: A Spectrum of Diseases with Different Patterns of Presentation and Outcome

Abstract: Purpose Appendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (TNET), goblet cell carcinoids (GCC), and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC, and SRCC patients.

Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors.

Abstract: PURPOSE The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.

Radiation-Induced Sarcoma: A 15-Year Experience in a Single Large Tertiary Referral Center

Abstract: Purpose The purpose of this study is to report on the incidence and the experience in management of radiation-induced sarcoma (RIS) at a large single center in Korea for 15 years. Materials and methods We retrospectively reviewed the sarcoma registry of a large institution from January 2000 to April 2014. Results Out of the 3,674 patients listed in the registry, 33 patients (0.9%) diagnosed with RIS were identified. The median latency of RIS was 12.1 years. The number of cases of RIS increased from four cases in the years 2000-2003 to 14 cases in the years 2012-2014. The most common histology was osteosarcoma (36.4%). The median follow-up period was 23.1 months, the median overall survival (OS) of all patients was 2.9 years, and their 5-year survival rate was 44.7%. Univariate and multivariate analyses showed association of the age at diagnosis (p=0.01) and the treatment aim (p=0.001) with the OS. The median OS and the 5-year survival rate of patients treated with curative surgery (n=19) were 9.6 years and 65%, respectively, and of the conservatively treated patients, 0.7 years and 0% (n=14). Re-irradiation was delivered to nine patients, and radiation toxicity was observed in five patients. Conclusion In this study, RIS accounted for 0.9% of the cases of sarcoma, with increasing incidence. Despite the association of curative resection with increased survival, it could be applied to only 58% of the patients. Considering the limited treatment options for RIS, conduct of a genetic study to identify the underlying mechanism of RIS is needed.

Dexamethasone Inhibits TGF-β1-Induced Cell Migration by Regulating the ERK and AKT Pathways in Human Colon Cancer Cells Via CYR61.

Abstract: Purpose One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy. Materials and methods We used colorectal cancer cells, HCT116, co-treated with transforming growth factor β1 (TGF-β1) and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF-β1 and dexamethasone. Results We report that dexamethasone significantly inhibited TGF-β1-induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the epithelial-mesenchymal transition process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1-induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment. Conclusion These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1-induced migration.

Dental Anomalies as Late Adverse Effect among Young Children Treated for Cancer.

Abstract: Purpose The aim of this study was to compare the incidence of dental complications in childhood cancer survivors with that of healthy control subjects, and to determine the possible influence of various factors associated with patient and treatment.

Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer.

Abstract: 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.

Objective Measurement of Cosmetic Outcomes of Breast Conserving Therapy Using BCCT.core

Abstract: Purpose The purpose of this study is to evaluate objective cosmetic outcomes and factors related to breast-conserving therapy (BCT) using the BCCT.core software. Materials and methods Fifty-one patients who received BCT with informed consent were evaluated using the BCCT.core software. Patients were divided into two groups based on the BCCT score: excellent or good (n=42) vs. fair or poor (n=9). Analysis of clinical factors was performed to determine factors affecting cosmetic outcomes. Results The objective cosmetic outcome of BCT measured using the BCCT.core software was excellent in 10% of patients, good in 72%, and fair in 18%. None of the patients were classified as poor outcome. Tumor characteristics, systemic adjuvant therapy (chemotherapy and hormonal therapy), and radiation dose or energy of electron boost did not show correlation with the score measured by the BCCT.core program (p > 0.05). In univariate analysis, maximum dose within the breast (Dmax), width of tangential field, and excised tumor volume were smaller in patients with excellent or good by the BCCT.core compared to those with fair or poor (Dmax, 110.2 ± 1.5% vs. 111.6 ± 1.7%, p=0.019; width of tangential field, 8.0 ± 1.1 cm vs. 8.6 ± 0.7 cm, p=0.034; excised tumor volume, 64.0 ± 35.8 cm(3) vs. 95.3 ± 54.4 cm(3), p=0.067). In multivariate analysis, only Dmax was a significant factor for breast cosmetic outcome with a risk ratio of 1.697 (95% confidence interval, 1.006 to 2.863; p=0.047). Conclusion Objective measurement of cosmetic outcome of BCT using the BCCT.core software was feasible. The cosmetic outcome of BCT may be affected by the maximum dose within the breast.

VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.

Abstract: Purpose The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). Materials and methods A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). Results In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. Conclusion High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.