• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1719-1723
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• 2014

Background: The current study was aimed to elucidate the association of thymidylate synthase (TYMS) 5'-UTR 28bp tandem repeat and cytosolic serine hydroxymethyltransferase (cSHMT) C1420T polymorphisms with acute leukemia in South Indian subjects. A total of 812 subjects [523 healthy controls, 148 acute lymphoblastic leukemia (ALL) cases and 141 acute myeloid leukemia (AML) cases] were screened for TYMS 5'-UTR 28bp tandem repeat and cSHMT C1420T using PCR-AFLP and PCR-with confronting two-pair primers (CTPP) approaches. TYMS 5'-UTR 2R allele frequencies of controls, ALL and AML cases were 35.3%, 28.0% and 30.1% respectively. This polymorphism conferred protection against ALL (OR: 0.71, 95%CI: 0.53-0.96) while showing no statistically significant association with AML (OR: 0.79, 95%CI: 0.58, 1.07). The cSHMT variant allele (T-) frequencies of ALL and AML cases (6.42% and 5.68% respectively) were significantly lower compared to controls (58.3%). This polymorphism conferred protection against ALL (OR: 0.049, 95%CI: 0.029-0.081) and AML (OR: 0.043, 95%CI: 0.025-0.074). The TYMS 5'-UTR 2R2R genotype was associated with a lower total leukocyte count, smaller percentage of blasts, and more adequate platelet count compared to 2R3R and 3R3R genotypes in ALL cases. No such genotype-dependent differences were observed in AML cases. ALL cases carrying the cSHMT C1420T polymorphism showed higher disease free survival compared to those with the wild genotype. To conclude, the TYMS 5'-UTR 28bp tandem repeat reduces risk for ALL while cSHMT C1420T reduces risk for both ALL and AML. Both also influence disease progression in ALL.

• 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.13 no.7
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• pp.3281-3285
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• 2012

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

• Gut and Liver
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• v.12 no.6
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• pp.728-735
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• 2018

Background/Aims: The combination of nab-paclitaxel and gemcitabine (nab-P/Gem) is widely used for treating metastatic pancreatic cancer (MPC). We aimed to evaluate the therapeutic outcomes and prognostic role of treatment-related peripheral neuropathy in patients with MPC treated with nab-P/Gem in clinical practice. Methods: MPC patients treated with nab-P/Gem as the first-line chemotherapy were included. All 88 Korean patients underwent at least two cycles of nab-P/Gem combination chemotherapy (125 and $1,000mg/m^2$, respectively). Treatment-related adverse events were monitored through periodic follow-ups. Overall survival and progression-free survival were estimated by the Kaplan-Meier method, and the Cox proportional hazards regression linear model was applied to assess prognostic factors. To evaluate the prognostic value of treatment-related peripheral neuropathy, the landmark point analysis was used. Results: Patients underwent a mean of $6.7{\pm}4.2$ cycles during $6.3{\pm}4.4$ months. The median overall survival and progression-free survival rates were 14.2 months (95% confidence interval [CI], 11.8 to 20.3 months) and 8.4 months (95% CI, 7.1 to 13.2 months), respectively. The disease control rate was 84.1%; a partial response and stable disease were achieved in 30 (34.1%) and 44 (50.0%) patients, respectively. Treatment-related peripheral neuropathy developed in 52 patients (59.1%), and 13 (14.8%) and 16 (18.2%) patients experienced grades 2 and 3 neuropathy, respectively. In the landmark model, at 6 months, treatment-related peripheral neuropathy did not have a significant correlation with survival (p=0.089). Conclusions: Nab-P/Gem is a reasonable choice for treating MPC, as it shows a considerable disease control rate while the treatment-related peripheral neuropathy was tolerable. The prognostic role of treatment-related neuropathy was limited.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.531-543
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• 2007

Backgrounds : Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric cancer patients frequently exhibit distant metastasis at the time of diagnosis and at present, there is no standard regimen after operation or chemotherapy to prevent metastasis and recurrences. Aims : The objective of the study was to compare the overall survival and disease free survival in patients treated with wheel balance therapy (WBT) with patients treated with WBT alone or the combination of WBT and conventional therapy and see if there were any significant improvements in survival between the two groups. Setting & Design : East-West Cancer Center at Daejeon University: retrospective study. Materials & Methods : We retrospectively analyzed 62 patients with stage III (40 patients) and stage IV (22 patients) gastric cancer who have received operation or chemotherapy 2 months prior to beginning WBT. The patients followed the WBT protocol which includes herbal medicine such as PSM capsules, OnePlus syrup, or HAD capsules which prevent metastasis and recurrences. Overall survival and disease free survival were analyzed and the patients were treated for 89.55 weeks and 49.27 weeks (median value) for stages III and IV, respectively. Statistical analysis used : Overall survival and disease free survival were estimated using the Kaplan-Meier method and the WBT and combination treatment arms were compared using the log rank test. Results : For stage III, the 3 year overall survival was 78.5% and disease free survival was 78.3%. Metastasis and recurrence occurred in 13 of 40 patients (32.5%). For stage IV, the 2 year overall survival was 18.2% and disease free survival was also 18.2%. Metastasis and recurrence occurred in 19 of 22 patients (86.4%). No significant difference was found statistically between the WBT alone and combination treatment arms though the combination regimen showed superiority (overall survival p=0.5093, disease free survival p=0.5175). Conclusions : WBT yielded satisfactory results in prolonging survival and preventing metastasis and recurrence in gastric cancer patients. The major treatment unit of WBT is composed of herbal medications (HAD, PSM capsules, OnePlus syrup) and a randomized, prospective study should be carried out using only this treatment unit in the future.

• Journal of Life Science
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• v.26 no.9
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• pp.1056-1062
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• 2016

Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.344-351
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• 2005

Background : Both gemcitabine and vinorelbine are effective anticancer drugs with mild toxicity on non-small cell lung cancer, and monotherapy of these drugs are effective as a second-line chemotherapy. The aim of this trial was to assess the response and toxicity of a combination of gemcitabine and vinorelbine in patients of previously treated for non-small cell lung cancer. Materials and Methods : 24 patients, initial stage III A/B,IV and previously treated with platinium and taxane based regimens, were enrolled from June 2000 to March 2004. The regimens consisted of vinorelbine $25mg/m^2$ followed by an infusion of gemcitabine $1000mg/m^2$ on day 1 and day 8 every three weeks. This course was repeated more than twice. Results : Twenty-four patients were analyzed for the response, survival rate, and toxicities. The overall response was 17% with a complete remission rate of 4%. The median time-to progression (TTP) was 3.1 months (95%, CI 1-10months), and the survival time was 8.2 months (95%, CI 1-23 months). The grade 3/4 toxicities encountered were neutropenia (12.5%), anemia (0%), thrombocytopenia (0%). Non-hematological 3/4 toxicities were not observed. Conclusion : A combination of gemcitabine and vinorelbine in patients previously treated for non-small cell lung cancer provides a relatively good response rate, and a low toxicity profile. However, further study will be needed to confirm its effectiveness.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.64-70
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• 2009

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. Materials and Methods: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/$m^2$). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/$m^2$) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Results: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. Conclusion: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.156-163
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• 1998

Background & Objectives: Frameless fractionated stereotactic radiotherapy(FFSRT) is a modification of stereotactic radiosurgery(SRS) with radiobiologic advantage of fractionation without losing mechanical accuracy of SRS. Local recurrence of head and neck cancer at or near skull base benefit from reirradiation. Main barrier to successful palliation is dose limitation secondary to normal tissue tolerance. We try to evaluate the efficacy and safety of FFSRT as a new modality of reirradaton in these challenging patients. Materials & Methods: Seven patients with recurrent head & neck cancer involving at or near skull base received FFSRT from September 1995 to November 1997. Six patients with nasopharyngeal cancer had received induction chemotherapy and curative radiation therapy. One patient with maxillary sinus cancer had received total maxillectomy and postoperative radiation therapy as a initial treatment. Follow-up ranged from 11 to 32 months with median of 24 months. Three of 7 patients received hyperfractionated radiation therapy(1.1-1.2Gy/fraction, bid, total 19.8-24Gy) just before FFSRT. All patients received FFSRT(3-5Gy/fraction, total 15-30Gy/5-10fractions). Chemotherapy(cis-platin $100mg/m^2$) were given concurrently with FFSRT in four patients. Second course of FFSRT were given in 4 patients with progression or recurrence after initial FFSRT. Because IF(irregularity factor; ratio of surface area of target to the surface area of sphere with same volume as a target) is too big to use conventional stereotactic RT using multiple arc method for protection of radiation damage to critical normal tissue, all patients received FFSRT with conformal method using irregular static ports. Results: Five of 7 patients showed complete remission in follow-up CT &/or MRI. Three of these five patients who developed marginal, in-field, and out-field recurrences, respectively. Another one of complete responders has been dead of G-I bleeding without evidence of local recurrence. One partial responder who showed progressive disease 15 months after initial FFSRT has received additional FFSRT, and then he is well-being with symptomatic improvement. One minmal responder who showed progression of locoregional disease 9 months after $1^{st}$ FFSRT has received 2nd FFSRT, and then he is alive with stable disease. Five of 7 case had showed direct invasion to skull base and had complaint headache and various symptoms of cranial nerve involvement. Four of these five case showed improvement of neurologic symptoms after FFSRT. No significant neurologic complicaltion related to FFSRT was observed during follow-up periods. Tumor volumes were ranged from 3.9 to 50.7 cc and surface area ranged from 16.1 to $114.9cm^2$. IF ranged from 1.21 to 1.74. The average ratio of volume of prescription isodose shell to target volume was 1.02 that indicated the improvement of target coverage and dose distribution with FFSRT with conformal method compared to target coverage with FFSRT with multiple arc method. Conclusion: Our initial experience suggests that FFSRT with conformal method was relatively effective and safe modality in the treatment of recurrent head and neck cancer involving at or near skull base. Treatment benefit included good palliation of symptoms and reasonable radiographic response. However, more experience and additional follow-up are needed to better assess its ultimate role in treating these challenging patients.