• Radiation Oncology Journal
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• v.38 no.1
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• pp.11-17
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• 2020

Purpose: Definitive radiotherapy remains a primary treatment option for early stage glottic cancer. Intensity-modulated radiation therapy (IMRT) has emerged as the standard treatment technique for advanced head and neck cancers, whereas three-dimensional conformal radiotherapy (3D-CRT) has remained standard for early glottic cancers. We used the National Cancer Database (NCDB) to identify predictors of IMRT use and effect on outcome in these patients. Materials and Methods: We queried the NCDB from 2004-2015 for squamous cell carcinoma of the glottic larynx staged Tis-T2N0 treated with radiation alone. Logistic regression was used to identify predictors of IMRT. Cox regression was used to identify factors predictive of overall survival. Propensity matching was conducted to account for indication bias. Results: We identified 15,627 patients, of which 11% received IMRT. IMRT use rose from 2% in 2004 to 16% in 2015. Predictors of IMRT include: increased comorbidity, T2 stage, urban location, chemotherapy, treatment at an academic center, and later treatment year. Predictors of improved survival were female gender, higher income, lower stage, no chemotherapy, academic facility, and more remote year. There was no difference in survival between 3D-CRT and IMRT across all stages. Conclusions: The rate of IMRT use for early stage glottic laryngeal cancer has increased over time. There was no difference in outcome in patients receiving IMRT versus 3D-CRT across the cohort.

• Advances in pediatric surgery
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• v.13 no.2
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• pp.162-168
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• 2007

Adrenocortical tumors are very rare in children and the clinical course is not clearly understood. The aim of this study is to review the clinical characteristics and courses of pediatric adrenocortical tumors. The medical records of patients who underwent surgery for primary adrenal tumor at the Department of Surgery, Seoul National University hospital, from Jan. 1986 to Feb. 2006 were reviewed. There were 10 adrenocortical tumor patients; 5 had adrenocortical adenoma and 5 adrenocortical carcinoma. All of the adrenocortical adenomas presented as functioning tumors, i.e., Cushing syndrome or virilization. However, only 2 patients had functioning adrenocortical carcinoma. Median size of adenoma was 5 (3.3-6) cm, and carcinoma 12.5 (6.5-13) cm. Adenomas were smaller than 6 cm and carcinomas were larger than 6.5 cm. Surgical resection alone cured all adrenocortical adenoma patients, and they were all alive without recurrence. Three of 5 adrenocortical carcinoma patients died of tumor recurrence despite radical surgery and chemotherapy. There were 2 long-term survivals for adrenocortical carcinoma, one patient survived 10 years without recurrence until he died of newly developed osteosarcoma, and the other patient is alive without recurrence for 20 years. As the prognosis of pediatric adrenocortical carcinoma is poor, peri-operative aggressive chemotherapy is suggested in addition to radical surgery.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.47-53
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• 2005

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

• Korean Journal of Head & Neck Oncology
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• v.37 no.2
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• pp.19-24
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• 2021

Background/Objectives: The aim of this national population-based retrospective study was to analyze the status and treatment outcome in patients with hypopharyngeal cancer. Materials & Methods: Participants were included in the KNHIS national sample cohort who received a KNHIS health check-up in 2008 and 2009, and we followed these individuals until 2017. Patients were defined as having hypopharynx cancer if they had admissions records for hypopharynx cancer in their national health insurance data from 2010 to 2017. Results: The study cohort included 3,922 patients. According to our nationwide data, 3,533(90.1%) were male with a median age of 65.03±11.04 years at the time of diagnosis. Among parametric models for hypopharyngeal cancer prognosis, old age (Hazard ratio [HR]:1.92; 95% confidence interval[CI]:1.76-2.09), female (HR:0.77; 95% CI:0.66-0.89), and low socioeconomic status (HR:1.216; 95% CI:1.114-1.327) were significantly associated with survival. Compared with concurrent chemoradiotherapy, patients who received no treatment (HR, 1.88; 95% CI, 1.31-2.70), neoadjuvant chemotherapy followed by surgery (HR, 1.21; 95% CI, 1.04-1.41), and chemotherapy alone (HR, 1.16; 95% CI, 1.03-1.27) showed poor prognosis in hypopharyngeal cancer. Conclusion: Our data indicated that age, sex, and income were significant predictors of lifetime survival in patients with hypopharyngeal cancer. Treatment modalities were also associated with prognosis. The data have implications for treatment investigations and prevention strategies.

• Journal of Chest Surgery
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• v.55 no.5
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• pp.397-404
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• 2022

Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.145-155
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• 2022

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.10.1-10.14
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• 2020

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.81-87
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• 2006

Purose: This study is to evaluate the xerostomia following 3-dimensional conformal radiation therapy (3D CRT) in nasopharynx cancer patients using the xerostomia questionnaire score (XQS). Materials and Methods: Questionnaire study was done on 51 patients with nasopharynx cancer who received 3D CRT from Dec. 2000 to Aug. 2005. 3D CRT technique is based on 'serial shrinking field' concept by 3 times of computed tomography (CT) simulation. Total target dose to the primary tumor was 72 Gy with 1.8 Gy daily fractions. Xerostomia was assessed with 4-questions XQS, and the associations between XQS and time elapsed after RT, age, sex, stage, concurrent chemotherapy, and parotid dose were analyzed. Results: Concurrent chemotherapy was given to 40 patients and RT alone was given to 11 patients. The median time elapsed after 3D CRT was 20 ($1{\sim}58$) months and the mean XQS of all 51 patients was $8.4{\pm}1.9\;(6{\sim}14)$. XQS continuously and significantly decreased over time after 3D CRT ($X^2$=-0.484, p<0.05). There was no significant difference in XQS according to sex, age, and stag. However, XQS of concurrent chemotherapy patients was significantly higher than RT alone patients (P=0.001). XQS of patients receiving total mean parotid dose ${\ge}35 Gy$ was significantly higher than <35 Gy (p=0.05). Decreasing tendency of XQS over time after 3D CRT was observed. Concurrent chemotherapy and total mean parotid dose ${\ge}35 Gy$ were suggested to adversely affect radiation-induced xerostomia.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.215-223
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• 1995

Purpose : The aim of this study was to assess the effectiveness, survival rate and complication of radiation in nasopharyngeal cancer. Materials and Methods : From January 1980 to May 1989. Fifty patients who had nasopharyngeal carcinoma treated with curative radiation therapy at Kosin Medical Center were retrospectively studied. Thirty seven patients($74{\%}$) were treated with radiation therapy alone(Group I) and 13 patients ($26{\%}$) treated with combination of chemotherapy and radiation (Group II). Age distribution was 16-75 years(median : 45.8 years). In histologic type, squamous cell carcinoma was in 30 patients($60{\%}$), undifferentiated carcinoma in 17 patients($34{\%}$), and lymphoepithelioma in 3 patients($6{\%}$). According t AJCC staging system. 4 patients($8{\%}$) were in $T_1$, 13 patients($26{\%}$) in $T_2$. 20 patients($40{\%}$) in $T_3$, 13 patients($26{\%}$) in $T_4$ and 7 patients($14{\%}$) in $N_0$, 6 patients($12{\%}$) $N_1$, 23 patients($46{\%}$) in $N_2$, 14 patients($28{\%}$) in $N_3$. Total radiation dose ranges were 5250-9200cGy(median : 7355 cGy) in Group I and 5360-8400cGy(median : 6758cGy) in Group II Radiotherapy on 4-6MV linear accelerator and/or 6-12MeV electron in boost radiation was given with conventional technique to 26 patients($52{\%}$), with hyperfractionation(115-120cGy/fr., 2times/day) to 16 patients($32{\%}$), with accelerated fractionation(160cGy/fr., 2 times/day) to 8 patients($16{\%}$). In chemotherapy, 5 FU 1000mg daily for 5 consecutive days, pepleomycin 10mg on days 1 and 3, and cisplatin 100mg on day 1 were administered with 3weeks interval, total 1 to 3 cycles(average 1.8cycles) prior to radiation therapy. Follow up duration was 6-140 months(mean : 58 months). Statistics was calculated with Chi-square and Fisher's exact test. Results : Complete local control rates in Group I and II were $75.7{\%},\;69.2{\%} Overall 5 year survival rates in Group I and II were $56.8{\%},\;30.8{\%}$. Five year survival rates by histologic type in Group I and II were $52.2{\%},\;14.3{\%}$ is squamous cell carcinoma and $54.5{\%},\;50{\%}$ in undifferentiated carcinoma. Survival rates in Group I were superior to those of Group II though there were not statistically significant. In both group, survival rates seem to be increased according to increasing total dose of radiation up to 7500cGy, but not increased beyond it. There were not statistically significant differences in survival rates by age, stage, and radiation techniques in both group. Twenty four patients($48{\%}$) experienced treatment failures. Complications were found in 12 patients($24{\%}$). The most common one was osteomyelitis(4 patients, $33.3{\%}$) involving mandible (3 patients) and maxilla(1 patient). Conclusion : Chemotherapy in combination with radiotherapy was found to be not effective to nasopharyngeal cancer and the survival rate was also inferior to that of radiation alone group though it was statistically not significant due to small population in chemotherapy combined group.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.30-35
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• 2002

Objective: To determine the effectiveness and toxicity of chemoradiation therapy in nasopharyngeal carcinoma by comparing with radiation therapy alone. Materials and Methods: Between October 1989 and July 2000, One hundred eleven patients with newly diagnosed and histologically proven nasopharyngeal carcinoma treated in Department of Radiation Oncology, Asan Medical Center were retrospectively reviewed. Forty-five patients were treated with radiation therapy alone (Group I) and 66 patients were treated with radiation therapy and concurrent cisplatin (Group II). Cisplatin was administered once a week, on the first day of each successive week of treatment, starting on day 1 of radiation therapy and given as a intravenous bolus at a dose of $20mg/m^2$ of body-surface area. Radiation therapy was given in doses of 1.8Gy, once a day, 5 days per week with 4MV or 6 MV photons. Initial field was received a total of 60Gy and a primary tumor and enlarged lymph nodes were boosted with an high dose intracavitory brachytherapy and 3D conformal therapy. Results: The complete response rate was 86.7% in Group I, and was 90.9% in Group II. The 5 year overall survival rate for Group I was 60% and for Group II was 45% (p=0.2520). The 5 year disease free survival rate was 52% versus 45%, respectively (p=0.7507). The median follow up was 44 months versus 34 months, respectively. Conclusion: Analysis of the III patients showed no significant difference in disease free survival and overall survival in two treatment group. This retrospective analysis did not demonstrate benefit with concurrent chemoradiation using cisplatin at a dose of $20mg/m^2$ of body-surface area in treatment result than radiation alone.