• Journal of Korean Neurosurgical Society
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• v.30 no.4
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• pp.472-478
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• 2001

Objectives : The authors present a retrospective analysis of 100 consecutive adult patients harboring craniopharyngiomas who underwent microsurgical resection between 1981 and 1999 to assess the long-term outcome of surgical treatment and to determine the most optimal management strategy. Methods : The extent of surgical removal was divided into four categories ; GTR(gross total removal), RSTR(radical subtotal removal), STR(subtotal removal),and PR(partial removal). The median follow-up period was 50 months(4-198). CT scan and/or MR imaging and hormonal status were evaluated to the last follow-up. Results : Visual disturbance was the most common presentation, which was improved in 42 cases and aggravated in 19 cases following the operation. Hypopituitarism was detected in 56 patients preoperatively, 82 during the immediate postoperative period, and 76 at the last follow-up. Improvement of pituitary function was not observed in any of these patients. Twenty of 100 patients showed recurrence at the mean of 27 months(3 to 196). The median progression-free survival(PFS) time of all patients was 145 months and 5-year PFS rate was 74%. Five-year PFS rate of GTR or RSTR group(71%) was significantly higher than that of STR or PR group(30%)(p=0.01). Postoperative radiation therapy significantly prolonged the PFS from 94 months in non-radiation group to 182 months(p=0.002). However, there was no statistical difference in number of patients who required hormonal replacement therapy between radiation and non-radiation group. Conclusion : Visual disturbance can be improved by early diagnosis and surgical decompression. GTR or RSTR in selected patients is considered a proper surgical strategy. Post-operative radiation therapy for residual tumors must be considered, although the ideal timing of radiation therapy is to be determined.

• Journal of Korean Neurosurgical Society
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• v.44 no.4
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• pp.222-227
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• 2008

Objective : Malignant gliomas are the most common primary cerebral neoplasms in adults. Despite multimodality treatments, the prognosis for patients with malignant glioma remains poor. However, recently, the effectiveness of concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) has been reported. We report for the first time preliminary results of the treatment with CCRT of newly diagnosed malignant gliomas in Korean people. Methods : Thirty-two patients over the age of 17 years with newly diagnosed and histologically confirmed high-grade gliomas (HGG), from June 2004 to August 2007 were the subjects of this study. There were 17 men and 15 women, with a median age of 53.5 years (range, 17-74). Pathologically, glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, and gliomatosis cerebri had been diagnosed in eighteen, eight, four, and two patients, respectively. These 32 patients were treated with CCRT with TMZ. Results : The median follow-up period was 12.5 months (range 3-48). At the time of this analysis, 13 patients died and three patients had been lost to follow-up. There was no mortality caused by drug toxicity. The median progression-free survival (PFS) of these patients was 9.0 months, and the six-month PFS rate was 72.4%. The median overall survival (OS) was 26 months, and the one-year OS rate was 83.6%. The 18 patients with glioblastoma were analyzed separately from the other patients with HGG, and the median OS was 18 months, and the one-year OS rates were 81.8%. The median PFS was seven months, and the six-month PFS rate was 75.0%. Conclusion : Our results are consistent with many other reports, confirming that CCRT with TMZ achieves good clinical outcomes in the treatment of HGG. Therefore, we suggest that CCRT with TMZ as adjuvant chemotherapy be considered as a standard therapy for patients with HGG.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9635-9641
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• 2014

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2915-2921
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• 2015

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6493-6499
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• 2013

Background: Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. Materials and Methods: A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Results: Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. Conclusions: ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4115-4119
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• 2013

Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.

• Journal of Yeungnam Medical Science
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• v.28 no.1
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• pp.31-44
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• 2011

Background: The optimal timing of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI) in NSCLC patients has not yet been determined. Methods: We separated 228 patients with advanced /metastatic NSCLC treated with gefitinib into an early gefitinib group (patients who received gefitinib as first- or second-line treatment) and a delayed gefitinib group (patients who received gefitinib as third or fourth-line treatment) and attempted to determine whether the timing of gefitinib treatment affected clinical outcomes. Results: Median overall survival (OS), progression free survival (PFS), and median OS from first-line treatment of advanced/metastatic disease (OSt) for 111 patients in the early gefitinib group were 6.2 months, 3.3 months, and 11.6 months. However, median OS, PFS, and OSt for 84 patients in the delayed gefitinib group were 7.8 months, 2.3 months, and 22.7 months. No differences in OS and PFS were observed between the 2 groups. However, OSt was significantly longer in the delayed gefitnib group. Timing of gefitinib therapy was one of the independent predictors of OSt. Hb ${\geq}$ 10 g/dl, and having never smoked, and ECOG performance status ${\leq}1$ were independent predictors of better PFS. Conclusion：Deferral of gefitinib therapy in patientswith advanced ormetastatic NSCLC may be preferable if they are able to tolerate chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5691-5696
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• 2014

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

• Molecules and Cells
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• v.39 no.12
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• pp.898-908
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• 2016

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.