• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1115-1118
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• 2016

Background: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. Materials and Methods: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis. Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Results: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ${\leq}7.4ng/ml$ had the highest diagnostic strength to predict successful ablation in all patients. Conclusions: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline $sTg{\leq}7.4ng/ml$ is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2101-2107
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• 2012

Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.323-329
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• 1994

Purpose: In supraglottic cancer, radiation therapy is used to preserve the laryngeal function but combined surgery and radiation therapy is required in advanced stage. The authors Present the results of radiation therapy alone and combined surgery Plus Postoperative radiation therapy for supraglottic cancer. Methods and Materials: A retrospective analysis was done for 43 patients with squamous cell carcinoma of the supraglottic larynx who were treated from Feburary 1982 to December 1991, in the Department of Radiation Oncology, Korea University Hospital. Patient distribution according to the AJCC staging system was as follows: I, 3($7.0\%$); II, 7($16.3\%$); III, 17($39.5\%$); IV, 16($37.2\%$). Patients' age ranged from 30 to 72 years(median 62). Follow up durations were from 21 to 137 months(median 27). Seventeen patients($39.5\%$) were treated by radiation therapy alone with radiation doses of 6840-7380 cGy and 26 patients($60.5\%$) were treated with surgery plus postoperative irradiation with doses of 5820-6660 cGy. Results: Overall five-year survival rate for all stage was $51.8\%$, with $100\%$ for Stage I and II, $47.3\%$ for Stage III, and $29.2\%$ for Stage III. The difference of the survival rate by stage was statistically significant(p=0.0152). Five-year survival rates were $100\%$ for locally confined tumor in the supraglottic larynx, $37.5\%$ for transglottic extension, $26.7\%$ for hypopharynx extension, and only two of 5 patients with both transglottic and hypopharynx extension were alive(p=0.0033). Five-year survival rates by neck node status were as follows: $55.0\%$ for NO, $64.3\%$ for N1, $50.0\%$ for N2, and all 2 of N3 were died of disease. Overall survival rate for radiation therapy alone group was $42.8\%$, and it was $56.7\%$ for surgery plus postoperative radiation therapy group with no statistically significant difference(p=0.5215). In Stage I and II, all Patients survived. In Stage III and IV, 5-year survival rate for radiation therapy alone group was $28.5\%$ and $43.4\%$ for surgery plus postoperative irradiation group(p=0.5103). Local control rate was $58.8\%$(10/17) for radiation therapy alone group and $73.1\%$ (19/26) for surgery plus postoperative irradiation group. Three patients from surgery plus postoperative radiation therapy group developed distant metastasis in lungs. Conclusion: Treatment results of radiation therapy alone was excellent in early stage supraglottic cancer. In advanced stage, even the difference was statistically not significant, the result of postoperative radiation therapy group was superior compared with radiation therapy alone group. Since 1992, concomitant chemoradiotherapy with hyperfractionated radiotherapy is being used to improve the result of the treatment and preserve the laryngeal function in advanced stage supraglottic cancer.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.35-41
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• 1992

Forty eight patients with adenoid cystic carcinoma (ACC) in the head and neck treated between 1979 and 1990 were reviewed according to treatment modalities and clinical courses. The common site of origin was minor salivary gland ($69\%$), mostly hard palate and maxillary sinus. 11 patients received radiation therapy (RT) alone and 37 patients received combined surgery and radiation therapy. The follow-up period of the survivors ranged from 4 to 118 months (median 49.5 months). The 5 year local control rate was $69.3\%$, $67.3\%$ and 83.9$\%$ in RT alone, conservative operation (OP)+RT and radical OP+RT group, respectively (p>0.05). The control of local disease was best achieved with radical OP+RT. In postoperative RT, high dose ($\ge$60 Gy) and generous field size($\ge$64 cm$^2$) yielded a better local control rate. Actuarial overall survival rate was $79.0\%$, at 5 years and $19.2\%$ at 10 years. Distant metastases (DM) developed in $40\%$ of patients, mostly in the lung. Disease-free (NED) survival rate was $45.8\%$ at 5 years and significant differences did not exist according to primary sites and treatment options. Survival rate after the onset of DM was $19.5\%$ at 5 years. Occurrence of DM tends to lower survival significantly. In an effort to find the role of RT in the treatment of ACC, our data suggest that a well-planned postoperative RT employing a high dose and generous field size can produce high local control rate and remaining urgent problem of distant metastasis demands more effective chemotherapy for the purpose of improving survival of ACC patients.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.19-26
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• 1997

Purpose : This study is to report experience with Fractionated Stereotactic Radiation Therapy (FSRT) for locally recurrent nasopharynx cancer after curative conventional radiation therapy. Materials and Methods : Three Patients with locally recurrent and symptomatic nasopharynx cancer were given FSRT as reirradiation method between the Period of September of 1995 and August of 1996 For two Patients, application of FSRT is their third radiation therapy directed to the nasopharynx. Two patients were given low dose chemotherapy as radiation sensitizer concurrently with FSRT Authors used 3-dimensional coordinate system by individually made, relocatable Gill-Thomas-Cosman (GTC) stereotactic frame and multiple non-coplanar arc therapy dose Planning was done using Xknife-3. Total of 45 Gy/18 fractions or 50 Gy/20 fractions were given. Results : Authors observed satisfactory symptomatic improvement and remarkable objective tumor size decrease by follow-up MR images taken 1 month Post-FSRT in ali three patients, while no neurologic side effect attributable to reirradiation was noticed. Two died at 7 and 9 months with loco-regional and distant seeding outside FSRT field, while one patient is living for 4 month. Conclusion Authors experienced satisfactory therapeutic effectiveness and safety of FSRT as reirradiatlon method for locally recurrent nasopharynx cancer Development of more effective systemic chemotherapeutic regimen is desired for distant metastasis

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.120-127
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• 2003

Purpose: To evaluate diagnostic sensitivity of nuclear imaging in the detection of residual thyroid tissue and metastatic lesion, we have compared neck scintigrams with Tc-99m pertechnetate (Tc-99m scan) and high dose I-131 iodide (I-131 scan) in patients with differentiated thyroid cancer. Subjects and Methods: One hundred thirty-five thyroidectomized patients for differentiated thyroid cancer were enrolled in this study. Twenty-three had a previous history of radioiodine therapy. Planar and pin-hole images of anterior neck with Tc-99m were acquired at 20 minutes after injection, followed by I-131 scan three days after high-dose radioiodine therapy within 7 days interval. Patients were asked to discontinue thyroid hormone replacement more than 4 weeks. Results: All subjects were in hypothyroid state. Seventy out of 135 patients (51.9%) showed concordant findings between Tc-99m and I-131 scans. I-131 scan showed higher number of uptake foci in all of 65 patients showing discordant finding. Tc-99m scan showed no thyroid bed uptake in 34 patients, whereas 23 of them (67.6%) showed bed uptake in I-131 scan. Tc-99m scan did not show any uptake in thyroid bed in 11 of 112 patients without previous history of radioiodine therapy, but 9 of them showed bed uptake in I-131 scan. Tc-99m scan showed no bed uptake in all of the 23 patients with previous history of radioiodine therapy, in contrast 14 of them (60.9%) showed bed uptake in I-131 scan. Conclusion: These results suggest that Tc-99m scan has poor detectability for residual thyroid tissue or metastatic lesion in thyroidectomized differentiated thyroid cancer patients, compared to high dose I-131 therapy scan. Tc-99m scan could not detect any remnant tissue or metastatic lesion in patients with previous history of radioiodine treatment, especially.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.182-190
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• 1998

Background: Most of the cancers of maxillary sinus are the squamous variety, but various histopathologic types of malignant tumor can occur in the maxillary sinus. These non-squamous cell tumors have quite different patterns of clinical behavior compared with squamous variety, such as invasive characters, route of metastasis, treatment modality, and so on. Objectives: The authors intend to establish the clinical characteristics and treatment modalities of non-squamous cell tumors of the maxillary sinus. Material and Methods: We experienced 16 cases of non-squamous cell tumors arisen from the maxillary sinus during the 10-year period from 1987 to 1996. We analyzed their clinical features, therapeutic modalities and results with review of literatures. Results: According to AJCC TNM system, 13 patients presented with $T_{1-2}$, 3 with $T_{3-}4$, Two patients were treated with surgery after radiotherapy, 3 patients with surgery after chemotherapy and radiotherapy, 4 patients with chemotherapy and radiotherpy, 5 patients with chemotherapy and radiotherapy after surgery. Conclusion: In cases of adenoid cystic carcinoma, adenocarcinoma and sarcoma, we believe that the best form of therapy is wide surgical excision. If there is microscopic evidence of disease at or close to the resection margin, postoperative radiation was used to achieve better local control. In cases of undifferentiated carcinoma, preoperative chemotherapy and radiation therapy showed improved outcomes.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.263-268
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• 1998

Many myocutaneous flaps have been used for the reconstruction of intraoral defects caused by the excision of oral cancer. Among these myocutaneous flaps, cervical island flap has been introduced by Farr et al. Although different in detail, this flap was designed as the platysma myocutaneous flap by Futrell et al in the supraclavicular site. Since many authors applied this flap to cover intraoral defect, they discussed deeply the blood supply of this flap. To improve further flap survival, it was modified by Tashiro et al. This flap makes its vascularity highly reliable. The amount of tissue needed for reconstruction can be accurately planned. The surgical and reconstruction procedure can be performed simply, rapidly, and effectively. Oral functions including deglutition, speech, and denture fitting are not compromised. With it's minimal deformity, new donor fields is not necessory. Of course, we keep in mind that this flap has limitations in patients where much bulk of tissue defects is needed and more than 3000 rad radiation due to the metastasis of neck lymph node is exposed. In three patients with intraoral squamous cell carcinoma($T_{1-3}N_0M_0$), we performed induction chemotherapy with FP regimen including pepleomycin. Thereafter, we ablated oral cancer and peformed reconstruction of intraoral defects with cervical island flap designed by Tashiro et al. Due to these significant benefits and minimal limitations, we have found that this flap is adequate for reconstruction of most intraoral defects following cancer ablation.