• Radiation Oncology Journal
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• v.34 no.4
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• pp.250-259
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• 2016

Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4993-4998
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• 2013

Background: A retrospective analysis of all cancer patients attending the radiotherapy outpatient department (OPD) of a single unit during the period of January 2005 till December 2006 was conducted to know the geographical distribution and incidence of the most common cancers, their stage of presentation, treatment compliance among the patients and follow-up. Materials and Methods: A total of 4,484 patients were registered in the Institute of Medical Sciences, Banaras Hindu University during the period of January 2005-December 2006; of which 1,975 registered in an individual unit were included for the retrospective analysis. Results: Most of the patients hailed from the various districts of UP and Bihar. Females outnumbered males with a ratio of 1.33:1. Females mostly belonged to the age group of 40-59 years; whilst males were a decade older. Major cancer sites in females were cervix and breast followed by head and neck. Leading cancer sites in males were head and neck, brain, bone, soft tissue and lung. Most of the cases presented in advanced stage of disease (74%). Squamous cell carcinoma was the most common histopathology (56%). A significant proportion of patients defaulted after undergoing preliminary investigations (16%). Only 53.9% of females and 58.5% of males took treatment out of which 68% and 63% completed the prescribed treatment. Compliance with follow-up was poor. Conclusions: The outcome of this study will significantly help us to define region specific strategies needed for cancer management in eastern Uttar Pradesh.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.216-223
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• 2001

Purpose : We evaluated retrospectively the outcomes of inoperable squamous cell lung cancer patients treated with radiotherapy to find out prognostic factors affecting survival. Materials and methods : Four hundred and eleven patients diagnosed as squamous cell lung cancer between November 1988 and December 1997 were the basis of this analyses. The planned dose to the gross tumor volume was ranged from 30 to 70.2 Gy. Chemotherapy was combined in 72 patients $(17.5\%)$ with the variable schedule and drug combination regimens. Follow-up period ranged from 1 to 113 months with the median of 8 months and survival status was identified in 381 patients $(92.7\%)$. Overall survival rate was calculated using the Kaplan-Meier method. Results : Age ranged from 23 years to 83 years with the median 63 years. The male to female ratio was about 16:1. For all 411 patients, the median overall survival was 8 months and the 1-year survival rate (YSR), 2-YSR, and 5-YSR were $35.6\%,\;12.6\%,\;and\;3.7\%$, respectively. The median and 5-YSR were 29 months and $33.3\%$ for Stage IA, 13 months and $6.3\%$ for Stage IIIA, and 9 months and $3.4\%$ for Stage IIIB, respectively(p=0.00). The median survival by treatment aim was 11 months in radical intent group and 5 months in palliative, respectively (p=0.00). Of 344 patients treated with radical intent, median survival of patients (N=247) who received planned radiotherapy completely was 12 months while that of patients (N=97) who did not was 5 months (p=0.0006). In the analyses of the various prognostic factors affecting to the survival outcomes in 247 patients who completed the planned radiotherapy, tumor location, supraclavicular LAP, SVC syndrome, pleural effusion, total lung atelectasis and hoarseness were statistically significant prognostic factors both in the univariate and multivariate analyses while the addition of chemotherapy was statistically significant only in multivariate analyses. The acute radiation esophagitis requiring analgesics was appeared in 49 patients $(11.9\%)$ and severe radiation esophagitis requiring hospitalization was shown in 2 patients $(0.5\%)$. The radiation pneumonitis requiring steroid medication was shown in 62 patients $(15.1\%)$ and severe pneumonitis requiring hospitalization was occurred in 2 patients $(0.5\%)$. During follow-up, 114 patients $(27.7\%)$ had progression of local disease with 10 months of median time to recur (range : $1\~87\;months$) and 49 patients $(11.9\%)$ had distant failure with 7 months of median value (range : $1\~52\;months$). Second malignancy before or after the diagnosis of lung cancer was appeared in 11 patients Conclusion : The conventional radiotherapy in the patients with locally advanced squamous cell lung cancer has given small survival advantage over supportive care and it is very important to select the patient group who can obtain the maximal benefit and to select the radiotherapy technique that would not compromise the life quality in these patients.

• The Journal of Korean Society for Radiation Therapy
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• v.33
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• pp.71-78
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• 2021

Purpose: To evaluate the inter-fractional position and respiratory reproducibility of lung and liver tumors using pressure conserving type(P-type) abdominal compressor in volumetric modulated arc therapy(VMAT). Materials and methods: Six lung cancer patients and three liver cancer patients who underwent VMAT using a P-type abdominal compressor were included in this study. Cone-beam computed tomography(CBCT) images were acquired before each treatment and compared with planning CT images to evaluate the inter-fractional position reproducibility. The position variation was defined as the difference of position shift values between target matching and bone matching. 4-dimensional cone-beam computed tomography(4D CBCT) images were acquired weekly before treatment and compared with planning 4DCT images to evaluate the inter-fractional respiratory reproducibility. The respiratory variation was calculated by the magnitude of excursions by breathing. Results: The mean ± standard deviation(SD) of overall position variation values, 3D vector in the three translational directions were 1.1 ± 1.4 mm and 4.5 ± 2.8 mm for the lung and liver, respectively. The mean ± SD of respiratory variation values were 0.7 ± 3.4 mm (p = 0.195) in the lung and 3.6 ± 2.6 mm (p < 0.05) in the liver. Conclusion: The use of P-type compressor in lung and liver VMAT was effective for stable control of inter-fractional position and respiratory variation by reproduction of abdominal compression. Appropriate PTV margin must be considered in treatment planning, and image guidance before each treatment are required in order to obtain more stable reproducibility

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1545-1549
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• 2014

Background: Published studies on clinical outcome of helical tomotherapy for lung cancer are limited. The purpose of this study was to evaluate clinical outcomes and treatment-related toxicity in inoperable non-small cell lung cancer (NSCLC) patients treated with helical tomotherapy in Korea. Materials and Methods: Twenty-seven patients with NSCLC were included in this retrospective study. Radiotherapy was performed using helical tomotherapy with a daily dose of 2.1-3 Gy delivered at 5 fractions per week resulting in a total dose of 62.5-69.3 Gy. We assessed radiation-related lung and esophageal toxicity, and analyzed overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and prognostic factors for overall survival. Results: The median follow-up period was 28.9 months (range, 10.1-69.4). The median overall survival time was 28.9 months, and 1-, 2-, and 3-year overall survival rates were 96.2%, 92.0%, and 60.0%. The median locoregional recurrence-free survival time was 24.3 months, and 1-, 2-, and 3-year locoregional recurrence-free survival rates were 85.2%, 64.5%, and 50.3%. The median distant metastasis-free survival time was 26.7 months, and 1-, 2-, and 3-year distant metastasis-free survival rates were 92.3%, 83.9%, and 65.3%, respectively. Gross tumor volume was the most significant prognostic factor for overall survival. No grade 4 or more toxicity was observed. Conclusions: Helical tomotherapy in patients with inoperable NSCLC resulted in high survival rates with an acceptable level of toxicity, suggesting it is an effective treatment option in patients with medically inoperable NSCLC.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3623-3626
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• 2014

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.43-50
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• 1993

We evaluated frequency and types of chromosomal aberrations by ionizing radiation in cancer patients treated with radiotherapy in our institution. Twenty-five patients with various types of carcinomas such as lung, uterine cervix, esophagus, rectum, head and neck and pancreatic cancers were studied immediately before and after external beam radiotherapy. The frequency of aberrant metaphase prior to treatment was $4.93{\%}$, which was higher than that of control group. Especially in lung cancer, the freuqency of aberrant metaphase was three times higher than control group. A comparison of chromosomal abnormalities observed before and after radiotherapy demonstrated that proportion of aberrant rnetaphases was significantly inreased to $22.13{\%}$. Major chromosomal aberrations like structural abnormalities showed remarkalbe increase from 65.45 to $88.45{\%}$ after the treatment. Also the numbers of chromosomal alterations per cell were increased by a factor of 6.5. Aberrations with two or more break points were more prominently increased, compared with aberrations with single break point. The number of chromosomal break points was noted to be higher than expected value in No.1, 3, 8 and 11 chromosomes and lower in No.13, 15, 17 and 21 chromosomes. Based on this study, we believe that the distribution of chromosomal breakage is related with gene and chromosomal rearrangement which could result in the development of cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3301-3306
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• 2015

Nucleolin (C23) is an important anti-apoptotic protein that is ubiquitously expressed in exponentially growing eukaryotic cells. In order to understand the impact of C23 in radiation therapy, we attempted to investigate the relationship of C23 expression with the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. We investigated the role of C23 in activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a critical protein for DNA double-strand breaks (DSBs) repair. As a result, we found that the expression of C23 was negatively correlated with the radiosensitivity of NSCLC cell lines. In vitro clonogenic survival assays revealed that C23 knockdown increased the radiosensitivity of a human lung adenocarcinoma cell line, potentially through the promotion of radiation-induced apoptosis and adjusting the cell cycle to a more radiosensitive stage. Immunofluorescence data revealed an increasing quantity of ${gamma}$-H2AX foci and decreasing radiation-induced DNA damage repair following knockdown of C23. To further clarify the mechanism of C23 in DNA DSBs repair, we detected the expression of DNA-PKcs and C23 proteins in NSCLC cell lines. C23 might participate in DNA DSBs repair for the reason that the expression of DNA-PKcs decreased at 30, 60, 120 and 360 minutes after irradiation in C23 knockdown cells. Especially, the activity of DNA-PKcs phosphorylation sites at the S2056 and T2609 was significantly suppressed. Therefore we concluded that C23 knockdown can inhibit DNA-PKcs phosphorylation activity at the S2056 and T2609 sites, thus reducing the radiation damage repair and increasing the radiosensitivity of NSCLC cells. Taken together, the inhibition of C23 expression was shown to increase the radiosensitivity of NSCLC cells, as implied by the relevance to the notably decreased DNA-PKcs phosphorylation activity at the S2056 and T2609 clusters. Further research on targeted C23 treatment may promote effectiveness of radiotherapy and provide new targets for NSCLC patients.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.193-200
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• 2019

Purpose: To explore the role of salvage radiotherapy (RT) for recurrent thymoma as an alternative to surgery. Materials and Methods: Between 2007 and 2015, 47 patients who received salvage RT for recurrent thymoma at Yonsei Cancer Center were included in this study. Recurrent sites included initial tumor bed (n = 4), pleura (n = 19), lung parenchyma (n = 10), distant (n = 9), and multiple regions (n = 5). Three-dimensional conformal and intensity-modulated RT were used in 29 and 18 patients, respectively. Median prescribed dose to gross tumor was 52 Gy (range, 30 to 70 Gy), with equivalent doses in 2-Gy fractions (EQD₂). We investigated overall survival (OS), progression-free survival (PFS), and patterns of failure. Local failure after salvage RT was defined as recurrence at the target volume receiving >50% of the prescription dose. Results: Median follow-up time was 83 months (range, 8 to 299 months). Five-year OS and PFS were 70% and 22%, respectively. The overall response rate was 97.9%; complete response, 34%; partial response, 44.7%; and stable disease, 19.1%. In multivariate analysis, histologic type and salvage RT dose (≥52 Gy, EQD₂) were significantly associated with OS. The high dose group (≥52 Gy, EQD₂) had significantly better outcomes than the low dose group (5-year OS: 80% vs. 59%, p = 0.046; 5-year PFS: 30% vs. 14%, p=0.002). Treatment failure occurred in 34 patients; out-of-field failure was dominant (intra-thoracic recurrence 35.3%; extrathoracic recurrence 11.8%), while local failure rate was 5.8%. Conclusion: Salvage RT for recurrent thymoma using high doses and advanced precision techniques produced favorable outcomes, providing evidence that recurrent thymoma is radiosensitive.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.303-309
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• 1993

Between November 1983 and December 1992, 121 patients with non-small cell lung cancer were treated with radiotherapy alone or combined with chemotherapy in Inje University, Seoul Paik Hospital. Of these,97 patients were evaluable and analyzed retrospectively. Group 1 (n=62)was treated with radiotherapy alone and group 2 (n=35) combined with chemotherapy. There were 7 patients, 1 patient with stage I and II ,20 patients, 11 patients with stage IIIA,28 patients, 20 patients with stage IIIB, and 6 patients, 3 patients with stage IV, respectively. Ninety percent of patients received more than 5000 cGy of radiaton. Median survival of patients in group 1 was 9 months, group 2 was 15 months. Overall 2 year survival rates of group 1 and 2 were $37\%\;and\;27\%$, respectively. Relapse free survival rates at 2 year were $27\%\;and\;15\%$, respectively. Overall survival rates at 5 year for group 1 and 2 were $15\%\;and\;11\%$, and relapse free survival rates were $16\%\;and\;6\%,$ respectively. Median survival of complete and partial responders was 47 months in group 1,18 months in group 2, and those of stable or progression was 6 months,11 months, respectively. The proportion of locoregional relapse and distant metastasis was not significantly different between group 1 and 2. The majority of relapse developed within 2 years. Although 2 cases of severe esophagitis and myelosuppression were noted in group 2, the treatment related toxicity was relatively acceptable. Our analysis showed no statistically significant differences between the two treatment groups in terms of response rate, survival, and sites of relapse.