• Radiation Oncology Journal
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• v.29 no.1
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• pp.44-52
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• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.205-210
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• 2001

Purpose : This study tried to evaluate the effectiveness of combined treatment using radiation therapy and concurrent cisplatin as a radiosensitizer in the management of locally advanced head and neck cancer. Materials and methods : From January 1995 to August 1998, 29 evaluable patients with locally advanced head & neck cancels (AJCC stage $II\~IV$) were received curative radiation therapy $(total\;70\~75.6\;Gy/35\~42\;fractions,\;1.8\~2\;Gy/fraction)$ and concurrent cisplatin chemotherapy ($100\;mg/m^2$, D1, D22, D43). The neck dissections were peformed for residual lymphadenopathy. Follow-up ranged from 5 to 55 months (median 24 months). Results : Twenty-one $(72.4\%)$ patients achieved clinical complete responses. The partial response and minimal response rates were $17.2\%\;and\;10.4\%$, respectively. Locoregional failure rate was $27.6\%$, and included 6 patients with local failures, 4 patients with regional failures, and 2 patients with combined local and regional failures. Four of 29 patients $(13.8\%)$ developed distant metastasis. The disease free survival rate at 3 years was $60\%$. Nasopharyngeal primary tumors or complete responders showed significantly higher disease free survival rate. The grade 3 mucositis and nausea/vomiting was noted in $34.5\%$, respectively. Major prolongation of radiation therapy duration was inevitable in three patients. Twenty-one patients $(72.4\%)$ completed 3 courses of cisplatin and 5 patients received 2 courses of cisplatin. Three patients received only one course of cisplatin due to nephrotoxicity and neurotoxicity, and then changed to 5-FU regimen. Conclusions : Concurrent cisplatin-radiation therapy in locally advanced head and neck cancer showed high response rate, reasonable locoregional control, and survival rate. As expected, acute toxicities were increased, but compliance to treatment was acceptable. Assessment of the effect of the combination in this setting requires further accrual and follow-up.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.349-357
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• 1995

Purpose : To analyze survival rate and late rectal and bladder complication for patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined with chemotherapy Materials and Methods : Between November 1984 and December 1993, 127 patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined therapy of radiation and chemotherapy. Retrospective analysis for survival rate was carried out on eligible 107 patients and review for complication was possible in 91 patients. The median follow-up was 47 months (range 3-118) and the median age of patiens was 56 years (range 31-76). 26 patients were stage IB by FIGO classification, 40 were stage IIA and 41 were stage IIB. 86 cases were treated by radiation alone and 21 were treated by radiation and chemotherapy. 101 patients were treated with intracavitary radiation therapy (ICRT), of these, 80 were received low dose rate (LDR) ICRT and 21 were received high dose rate (HDR) ICRT. Of the patients who received LDR ICRT, 63 were treated by 1 intracavitary insertion and 17 were underwent 2 insertions And we evaluated the external radiation dose and midline shield. Results : Actuarial survival rate at 5 years was $92{\%}$ for stage IB, $75{\%}$ for stage IIA, $53{\%}$ for stage IIB and $69{\%}$ in all patients Grade 1 rectal complications were developed in 20 cases ($22{\%}$), grade 2 were in 22 cases ($24{\%}$). 22 cases ($24{\%}$) of grade 1 urinary complications and 17 cases ($19{\%}$) of grade 2 urinary complications were observed But no patient had severe complications that needed surgical management or admission care. Maximum bladder dose for the group of patients with urinary complications was higher than that for the patients without urinary complications (7608 cGy v 6960cGy. p<0.01) Maximum rectal dose for the group of patients with rectal complications was higher than that for the patients without rectal complications (7041cGy v 6269cGy, p<0.01). While there was no significant difference for survival rate or bladder complication incidence as a function of dose to whole pelvis, Grade 2 rectal complication incidence was significantly lower for the patients receiving less than 4500cGy ($6.3{\%}$ v $25.5{\%}$, p<0.05). There was no significant differance between HDR ICRT group and LDR ICRT group for survival rate according to stage, on the other hand complication incidence was higher in the HDR group than LDR group, This was maybe due to different prescription doses between HDR group and LDR group. Midline shield neither improved survival rate nor decreased complication rate. The number of insertion in LDR ICRT group did not affect on survival and compication rate. Conclusion : In stage I and II carcinoma of uterine cervix there was no significant differance for 5 year survival rate by radiation therapy technique. Rectal complication incidence was as a function of dose to whole pelvis and there were positive correlations of maximum dose of rectum and bladder and each complication incidence. So we recommand whole pelvis dose less than 4500cGy and maximum dose of rectum and bladder as low as possible.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.16-25
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• 2007

[ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.233-243
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• 2000

Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.213-217
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• 1992

Locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate despite the advances in modern radiation therapy techniques. Combination of chemotherapy and radiation therapy demonstrated benefit in improving local control and possibly the overall survival. Twelve patients with advanced stages (Figo stage III, IV) or 11b with bulky tumors (>5 cm in diameter) were treated with combination of radiation therapy and concurrent weekly cisplatin between May of 1988 and September of 1991 at Inje University Paik Hospital. Cisplatin was administered in bolus injections of 50 mg at weekly intervals during the courses of radiation therapy. Median follow-up period was 34 months with ranges from 3 to 53 months. Eleven patients were evaluable for the estimation of response. Response was noted in all the 11 patients: complete response (CR) in 7 ($64\%$), partial response (PR) in 4 ($36\%$). Of the 7 patients with CR, all maintained local control, whereas only 1 of 4 with PR showed local control. Six of 7 with CR are alive disease free on the completion of follow-up. Eight of 11 patients ($73\%$) maintained local control in the pelvis. The median survival for CR patient is 27 months and 9 months for the PR patients. Analysis of survival by stage shows 11 b 4/5, III 2/3 and IV 1/3. Overall survival rate was $61\%$. Three patients recurred: 1 at local, 1 in distant site and 1 with local and distant site. Toxicity for the combination therapy was not excessive. These results are preliminary, but definitely encouraging in view of markedly improved response rate compared with the results of historical control group.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.59-66
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• 1994

Seventy-five patients with tumors of the head and neck treated with either radiation therapy alone or combined with surgery or chemotherapy were studied prospectively to evaluate the effects of radiation therapy to the neck on thyroid gland between September 1986 and October 1992. All patients were serially monitored for thyroid function tests before and after radiation therapy. Radiation dose to the thyroid gland ranged from 35 to 60 Gy with a median dose of 50 Gy. Median follow-up time was 30 months with a range of 11 to 85 months. The incidence of thyroid dysfunction was 40$ \% $: forty-five patients(60$ \% $) euthyroid, 2 patients(3$ \% $) clinical hypothyroidism, 27 patients(36$ \% $) subclinical hypothyroidism and 1 patient(1$ \% $) hyperthyroidism. No thyroid nodules or thyroid cancer were detected in any patients. Thyroid dysfunction appeared earlier in patients who underwent surgery than in those patients treated with radiation therapy alone or combination of chemotherapy and radiation therapy(P=0.0013). By multivariate analysis, risk factors that significantly influenced a higher incidence of thyroid dysfunction were female sex(p=0.0293) and combination of total laryngectomy and radiation therapy(p : 0.0045). In conclusion, evaluation of thyroid function before and after radiation therapy with periodic thyroid function tests are recommended to detect thyroid dysfunction in time and thyroid hormone replacement therapy is recommended whenever thyroid dysfunction develops.