• Radiation Oncology Journal
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• v.17 no.3
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• pp.195-202
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• 1999

Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

• Progress in Medical Physics
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• v.11 no.1
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• pp.59-71
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• 2000

It is possible to obtain a fast CT scan during breath holding with spiral technique. But the risk of radiation is increased due to detailed and repeated scans. However, the limitation of X-ray doses is not fully specified on CT, yet. Therefore, the purpose of the present study is to define the limitation of X-ray doses on CT The CT unit was somatom plus 4. Alderson Rando phantom, Solenoid water phantom, TLD, and reader were used. For determining adequate position and size of organs, the measurement of distance(${\pm}$2mm) from the midline of vertebral body was performed in 40 women(20~40 years). On the brain scan for 8:8(8mm slice thickness, 8mm/sec movement velocity of the table) and 10:10(10mm slice thickness, 10mm/sec movement velocity of the table) methods, the absorption doses of exposed area of the 10:10 were slightly higher than those of 8:8. The doses of unexposed uterus were negligible on the brain scan for both 8:8 and 10:10. On the chest scan for 8:8, 8:10(8mm slice thickness, 10mm/sec movement velocity of the table), 10:10, 10:12(10mm slice thickness, 12mm/sec movement velocity of the table) and 10:15(10mm slice thickness, 15mm/sec movement velocity of the table) methods, 8:8 method of the absorption doses of exposure area was the most highest and 10:15 method was the most lowest. The absorption doses of 8:10 method was relatively lower than those of the other methods. In conclusion, the 8:10 method is the most suitable to give a low radiation burden to patient without distorting image quality.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.28-35
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• 2011

Purpose: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. Materials and Methods: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. Results: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage 1, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 $Gy_{10}$. Among 20 lesions that received above 100 $Gy_{10}$, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. Conclusion: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 $Gy_{10}$ for peripheral T1 stage patients with NSCLC is recommended.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.227-232
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• 2007

Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin 01 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according to the individual cell line and it did not affect Akt activation of both cell lines.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.112-117
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• 2003

Purpose: The effects of hypefractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Materials and Methods: Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department of Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 : 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 75.8 Gy). Follow-up periods ranged between 3 and 136 months, with the median of 52 months. Results: The overall survival rates at 3 and 5 years in all patients were 66.7$\%$, and 52.4$\%$. The disease-free survival rates at 3 and S years (3YDFS, 5YDFS) in all patients were 66.7$\%$ and 47.6$\%$. The 3YDFS and 5YDFS in stage III patients were 81.8$\%$ and 63.6$\%$, and those in stage IV patients were 53.8$\%$ and 32.3$\%$. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25$\%$) died due to distant metastasis and 12.5$\%$ died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteo-radionecrosis of the mandible 58 months after treatment. Conclusion: Although this study was peformed on small patients group, we considered hypefractionated radiation therapy for the treatment of advanced stage head and neck cancer might improve the disease free survival and decrease the local failure with no increase in late complications despite of the slight Increase in acute complications.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.311-319
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• 1995

Purpose : To evaluate the survival and prognostic factors in patients with stage III non-small cell lung cancer treated with curative radiotherapy alone or combined with chemotherapy Materials and Methods : A retrospective analysis was undertaken of 35 patients who had locally advanced non-small-cell lung cancer and treated with curative radiotherapy in Department of Therapeutic Radiology, Kangdong Sacred Heart Hospital, from January 1991 through December 1993. According to AJCC staging, 15 patients were stage IIIA, and 20 were stage IIIB. Radiotherapy was delivered with 1 8-2 Gy per fraction/day. 5 days per week using 6 MV X-ray, to a total dose ranging from 48.8 Gy to 66.6 Gy (median, 61.2 Gy) in 4 to 9 weeks. Ten patients received neoadjuvant or concurrent chemotherapy with FIP (5-FU, ifosfamide, and cisplatin) or FP (5-FU and cisplatin) Results : For all Patients, median survival was 6 months. 1-year and 2-year survival rates were 23.3% and 6.7%, respectively The median survival was 8 months in stage IIIA and 5.5 months in stage IIIB. In patients treated with radiation therapy alone, median survival was 5 months and 1-year survival rate was 9%. In patients who received chemotherapy, median survival was 11 months and 1-year survival rate was 60%. The difference of survival between these two groups was statistically significant (p=0.03). Total radiation dose, degree of response, and Post-treatment ECOG score were also significantly associated with survival. But it was not affected by age, sex, pretreatment ECOG score, presence or absence of weight loss, tumor location. pathologic type, N stage, and degree of response to treatment. Conclusion : Conventional radiotherapy alone is unlikely to achieve long term survival in patients with stage III NSCLC. Radiotherapy with altered fractionation schedule or multimodality treatment combined with surgery and/or chemotherapy should be considered if feasible.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.121-128
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• 1997

Purpose : To evaluate the effect of postoperative adjuvant radiation therapy and chemotherapy on the survival, pattern of failure and complication for locally advanced rectal carcinoma Materials and Methods : From October 1992 to September 1995, twenty eight patients with rectal carcinoma were treated by postoperative adjuvant radiation therapy and chemotherapy Radiation therapy was delivered with 6MV and 15MV linear accelerator, 180c0y fractions 5 day per week. Total radiation doses were 5040cGy in $B_{2+3}$ and 5580cGy in $C_{2+3}$. Within 4 weeks after radical surgery. 5-FU$(400mg/m^2/day)\;and\;Leucovorin(20mg/m^2/day)$ were administered by intravenous injection for 4 days during the first and fifth week of radiation therapy. The median follow up was 19 months with a range 2 to 47 months. Results : The 2 year overall survival and disease free survival rates were $78.6\%\;and\;70.8\%$, respectively. The 2 year overall survival was $93.0\%\;in\;B_{2+3}$ and $76.2\%\;in\;C_{2+3}$(p=0.11) The 2 year disease free survival was $79.4\%\;in\;B_{2+3}\;and\;69.2\%\;in\;C_{2+3}(p=0.13)$. The overall failure rate was $21.42\%$(6/28) including $10.72\%$(3/28) locoregional recurrence, $3.62\%$(1/28) distant metastasis and $7.12\%$(2/28) locoregional recurrence with distant metastasis. The overall locoregional recurrence rate was $17.92\%$(5/28). The 2 year locoregional recurrence rates were $13.32\%(2/15)\;and\;23.12\%$(3/13) for respectively for $B_{2+3}\;and\;C_{2+3}$ The difference between the locoregional recurrence of $B_{2+3}\;and\;C_{2+3}$ patients was not significant(p=0.07). Complications developed in 13 patients$(46.42\%)$, including 8 dermatitis, 7 loose stool, 6 leukopenia, 4 tenesmus, 2 diarrhea. In Univariate analysis, there was no statistically significant factor except for tumor grade in locoregional recurrence, disease free survival and overall survival rate(p=0.04, 0.05, 0.04). Conclusion : This study sugges1s that postoperative adjuvant radiation therapy and chemotherapy is effective in patients with locally advanced rectal cancer. Therefore these results need to be confirmed with a long term follow-up and larger number of patients with the further clinical trials including prospective controlled studies.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.245-251
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• 2001

Prupose : The genes involved on the suppression or radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. Materials and methods : K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For X-ray irradiation and drug treatment, cultures were prepared at $2\times10^5\;cells/mL$. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA), Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at $37^{\circ}C$ for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. Results : Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. Conclusion : We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.299-305
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• 2003

Purpose: In order to develop the national guide-lines for the standardization of radiotherapy we are planning to establish a web-based, on-line data-base system for laryngeal cancer. As a first step this study was performed to accumulate the basic clinical information of laryngeal cancer and to determine the items needed for the data-base system. Materials and Methods: We analyzed the clinical data on patients who were treated under the diagnosis of laryngeal cancer from January 1998 through December 1999 In the South-west area of Korea. Eligiblity criteria of the patients are as follows: 18 years or older, currently diagnosed with primary epithelial carcinoma of larynx, and no history of previous treatments for another cancers and the other laryngeal diseases. The items were developed and filled out by radiation oncologlst who are members of forean Southwest Radiation Oncology Group. SPSS vl0.0 software was used for statistical analysis. Results: Data of forty-five patients were collected. Age distribution of patients ranged from 28 to 88 years(median, 61). Laryngeal cancer occurred predominantly In males (10 : 1 sex ratio). Twenty-eight patients (62$\%$) had primary cancers in the glottis and 17 (38$\%$) in the supraglottis. Most of them were diagnosed pathologically as squamous cell carcinoma (44/45, 98$\%$). Twenty-four of 28 glottic cancer patients (86$\%$) had AJCC (American Joint Committee on Cancer) stage I/II, but 50$\%$ (8/16) had In supraglottic cancer patients (p=0.02). Most patients(89$\%$) had the symptom of hoarseness. indirect laryngoscopy was done in all patients and direct laryngoscopy was peformed in 43 (98$\%$) patients. Twenty-one of 28 (75$\%$) glottic cancer cases and 6 of 17 (35$\%$) supraglottic cancer cases were treated with radiation alone, respectively. The combined treatment of surgery and radiation was used in 5 (18$\%$) glottic and 8 (47$\%$) supraglottic patients. Chemotherapy and radiation was used in 2 (7$\%$) glottic and 3 (18$\%$) supraglottic patients. There was no statistically significant difference in the use of combined modality treatments between glottic and supraglottic cancers (p=0.20). In all patients, 6 MV X-ray was used with conventional fractionation. The iraction size was 2 Gy In 80$\%$ of glottic cancer patients compared with 1.8 Gy in 59$\%$ of the patients with supraglottic cancers. The mean total dose delivered to primary lesions were 65.98 ey and 70.15 Gy in glottic and supraglottic patients treated, respectively, with radiation alone. Based on the collected data, 12 modules with 90 items were developed or the study of the patterns of care In laryngeal cancer. Conclusion: The study Items for laryngeal cancer were developed. In the near future, a web system will be established based on the Items Investigated, and then a nation-wide analysis on laryngeal cancer will be processed for the standardization and optimization of radlotherapy.