• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• 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.15 no.2
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• pp.137-143
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• 1997

Purpose : Radiation pneumonitis is one of the complications caused by radiation therapy that includes a Portion of the lung tissue. The severity of radiation induced pulmonary dysfunction depends on the irradiated lung volume, total dose, dose rate and underlying Pulmonary function. It also depends on whether chemotherapy is done or not. The irradiated lung volume is the most important factor to predict the pulmonary dysfunction in breast cancer Patients following radiation therapy. There are some data that show the irradiated lung volume measured from CT scans as a part of treatment Planning with the tangential beams. But such data have not been reported in Korea. We planned to evaluate the irradiated lung volume quantitatively using CT scans for the breast tangential field and search for useful factors that could Predict the irradiated lung volume Materials and Methods : The lung volume was measured for 25 patients with breast cancer irradiated with tangential field from Jan.1995 to Aug.1996. Parameters that can predict the irradiated lung volume included; (1) the peruendicular distance from the Posterior tangential edge to the posterior part of the anterior chest wall at the center of the field (CLD) ; (2) the maximum perpendicular distance from the posterior tangential field edge to the posterior Part of the anterior chest wall (MLD) ; (3) the greatest perpendicular distance from the Posterior tangential edge to the posterior part of anterior chest wall on CT image at the center of the longitudinal field (GPD) ; (4) the length of the longitudinal field (L). The irradiated lung volume(RV), the entire both lung volume(EV) and the ipsilateral lung volume(IV) were measured using dose volume histogram. The relationship between the irradiated lung volume and predictors was evaluated by regression analysis. Results :The RV is 61-279cc (mean 170cc), the RV/EV is $2.9-13.0\%\;(mean\;5.8\%)$ and the RV/IV is $4.9-29.0\%\;(mean\;12.2\%)$. The CLD, the MLD and the GPD ave 1.9-3.3cm, 1.9-3.3cm and 1.4-3.1cm respectively. The significant relations between the irradiated lung volume such as RV. RV/EV, RV/IV and parameters such as CLD, MLD, GPO, L. $CLD\timesL,\;MLD\timesL\;and\;GPD\timesL$ are not found with little variances in parameters. The RV/IV of the left breast irradiation is significantly larger than that of the right but the RV/EVS do not show the differences. There is no symptomatic radiation pneumonitis at least during 6 months follow up. Conclusion : The significant relationship between the irradiated lung volume and predictors is not found with little variation on parameters. The irradiated lung volume in the tangential held is liss than $10\%$ of entire lung volume when CLO is less than 3cm. The RV/IV of the left tangential field is larger than that of the right but there was no significant differences in RV/EVS. Symptomatic radiation pneumonitis has not occurred during minimum 6 months follow up.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.25-31
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• 1996

Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to Postoperative radiotherapy in resectable rectal cancer. Materials and Methods : Between January 1989 and Mar 1994, 60 patients with resectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital. Fifty one patients were available for analysis: 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with Postoperative radiotherapy. In sandwich technique radiotherapy(RT), Patients were treated with preoperative RT 1500 cGy/5fx, followed by immediate curative resection. Patients staged as Astler-Coiler B2, C were considered for postoperative RT with 2500-4500 cGy. in postoperative RT total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-Sweets was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich RT group and postoperative RT group were $60\%$ and $71\%$, respectively(p>0.05). The 5-rear disease free survival rates for each group were $63\%$. There was no difference in local failure rate between two groups($11\%$ versus $7\%$) Incidence of distant metastasis was $11\%$(2/20) in the sandwich technique RT group and $20\%$(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of Postoperative RT alone group but reduced distant metastasis compared to Postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.41-52
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• 1996

Purpose : This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum, external radiation dose to the whole pelvis, ICR reference volume, TDF BED and the incidence of late rectal complications, retrospectively. Materials and Methods : From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department of Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachytherapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r, R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. Results : Twenty seven($30.7\%$) of the 88 patients developed late rectal complications:12 patients($13.6\%$) for grade 1, 12 patients($13.6\%$) for grade 2 and 3 patients($3.4\%$) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complication. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was Higher, $4093.3\pm453.1$ cGy, than that for the patients without complication, $3873.8\pm415.6$ (0.05$7163.0\pm838.5$ cGy, than that for the Patients without rectal complication, $0772.7\pm884.0$ (p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the iCR rectal doses(r, dr), ICR reference volume, TDF and BED. Conclusion : This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R) dose to the whole pelvis and the incidence of grade 2, 3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HOR ICR. Thus these rectal reference points doses and whole pelvis dose appear to be useful Prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.1-8
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• 1996

Purpose: We tried to evaluate the role of conventional radiotherapy alone or with neoadjuvant chemotherapy in oropharyngeal cancer in terms of survival rates and to identify prognostic factors affecting survival by retrospective analysis. Materials and Methods: Forty seven patients of oropharyngeal cancer were treated by conventional radiotherapy in our hospital from Nov. 1985 to APr. 1993. Of these, twenty six patients were treated by conventional radio-therapy alone, and 21 patients with neoadjuvant chemotherapy of mostly two or more cycles of cisplatin and pepleomycin. The Patient characteristics of radiotherapy alone group and neoadjuvant chemotherapy group were not different generally. Radiotherapy was performed by 6MV-LINAC and the total radiation doses of Primary tumors were 54.0-79.2 Gy and cervical lymph nodes were 55.8-90.0 Gy with a fraction size of 1.8 or 2.0 Gy per day. The range of follow-up periods was 3-102 months and median was 20 months. The range of a9e was 33-79 years old and median was 58 years old. Results : Overall 3-year actuarial survival rate (3YSR) of all patients was $39\%$. The 3YSRS of stage I (n=5), II (n=11), III (n=12) and IV (n=19) were 60, 55, 33 and $32\%$, respectively The 3YSRS of Tl+2, T3+4 and No, N+ were 55, $18\%$ (p=0.005) and 43, $36\%$ (p>0.1), respectively. There was no difference in 3YSRS between radiotherapy alone group and neoadjuvant chemotherapy group (38 vs $43\%$, p>0.1). According to the original site of primary tumor, the 3YSRS of tonsil (n=32), base of tongue (n=8), soft palate or uvula (n=6) and pharyngeal wall (n=1) were 36 38, 67 and $0\%$, respectively The Patients of soft palate or uvular cancer had longer survival than other primaries but the difference was not significant statistically (p>0.1). Of 32 patients of tonsillar cancer, 22 Patients who had primary extension to adjacent tissue showed inferior survival rate to the ones who had not Primary extension, but the difference was marginally significant statistically (24 vs $60\%$, p=0.08). On Cox multivariate analysis in entire patients with variables of age, T stage, N stage, total duration of radiotherapy, the site of primary tumor and the use of neoadjuvant chemotherapy, only T stage was a significant Prognostic factor affecting 3YSR. Conclusion : The difference of 3YASRS of conventional radiotherapy alone group and neoadjuvant chemotherapy group was not significant statistically. These treatments could be effective in oropharyngeal cancer of early stage, especially such as soft palate, uvular or tonsillar cancer which did not extend to adjacent tissue. But in order to improve the survival of patients of most advanced oropharyngeal cancer, other altered fractionated radiotherapy such as hyperfractionation rather than conventional fractionation or multi-modal approach combining radiotherapy and accessible surgery or concurrent chemotherapy might be beneficial.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.9-15
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• 1996

Purpose: The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer Provides anticipated cure rates of $10-65\%$ depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Materials and Methods : November 1983 to October 1994. 31 Patients with Stage III and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone, and IS patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy (median 7010 cGy). In combined group, 7 patients were treated with cisplatin plus 5-FU 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient ($66.6\%$) of the RT alone group and 14 patient ($93.3\%$) of the chemoradiation group. There was no statistical difference in CR rate between the two groups The overall survival rates at 5 years were $23.4\%$ in the radiation alone group, $23.5\%$ in the chemoradiation group Disease-free survival rates at 3 years were $44.5\%$ in the radiation alone group, $40\%$ in the chemoradiation group. There was no statistical differences in overall survival rates and disease-free survival rates between the two groups. Local recurrences occurred in $71.5\%$ of the radiation alone group, $72.7\%$ of the chemoradiation group and distant metastasis occurred in $14.4\%$ of radiation alone group, $9.1\%$ of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity Conclusion : Total response rates in the combined chemotherapy and radiotherapy was relatively higher than radiotherapy alone. But our result failed to show any survival benefit of the combined chemotherapy and radiotherapy. The accrual of large number of patients and long term follow-un may be necessary to confirm the present result of combined chemotherapy and radiotherapy.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.145-151
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• 1997

Purpose : To evaluate the loss of bone mineral contents(BMC) in lumbar spine within the radiation field for cervical cancer treatment, BMC in the irradiated patient group was compared with that of a normal control group. Method and materials : Measurements of BMC in the trabecular bone in lumbar spines(L3-L5) were performed in the both patient and normal control groups. Investigators used dual-energy quantitative computerized tomography(DEQCT) using Photon energy of 120 and 80kVp, The numbers of Patient and control groups were 43 in each with age distribution of fifth to seventh decade of women. The numbers of control group were 22 in fifth, 10 in sixth and 11 in seventh decade, those of patient group were 14 in filth, 14 in sixth, and 15 in seventh decade of women. The radiation field was extended to L5 spine for Pelvic irrdiation with 45-54Gy of external radiation dose and 30Gy of high dose rate brachytherapy in cervical cancer, Results : The BMC is decreased as increasing age in both control and patient groups. BMC in lumbar spine of patient group was decreased by about $13\%\;to\;40\%$ maximally. The BMC of L3 and L4 a region that is out of a radiation field for the Patient group demonstrated $119.5\pm30.6,\;117.0\pm31.7\;for\;fifth,\;83.3\pm37.8,\;88.3\pm46.8\;for\;sixth\;and\;61.5\pm18.3,\;56.2\pm26.6mg/cc$ for seventh, Contrasted by the normal control group has shown $148.0\pm19.9,\;153.2\pm23.2\;for\;fifth,\;96.1\pm30.2,\;105.6\pm26.5\;for\;sixth\;and\;73.9\pm27.9,\;77.2\pm27.2mg/cc$ for seventh decade, respectively The BMG of patient group was decreased as near the radiation field, while the lower lumbar spine has shown more large amounts of BMC in the normal control group. In Particular, the BMC of L5 within the radiation field was significantly decresed to $33\%,\;31\%,\;40\%$ compared with the control group of the fifth, sixth and seventh decades, respectively. Conclusion : The pelvic irradiation in cervical cancer has much effected on the loss of bone mineral content of lumbar spine within the radiation field, as the lower lumbar spine has shown a smaller BMC in Patient group with Pelvic irradiation in contrast to that of the normal control groups.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.1-10
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• 2000

Purpose : Although using the high energy Photon beam with conventional Parallel-opposed beams radiotherapy for nasopharyngeal carcinoma, radiation-induced xerostomia is a troublesome problem for patients. We conducted this study to explore a new parotid gland sparing technique in 3-D conformal radiotherapy (3-D CRT) in an effort to prevent the radiation-induced xerostomia. Materials and Methods : We peformed three different planning for four clinically node-negative nasopharyngeal cancer patients with different location of tumor(intracranial extension, nasal cavity extension, oropharyngeal extension, parapharyngeal extension), and intercompared the plans. Total prescription dose was 70.2 Gy to the isocenter. For plan-A, 2-D parallel opposing fields, a conventional radiotherapy technique, were employed. For plan-B, 2-D parallel opposing fields were used up until 54 Gy and afterwards 3-D non-coplanar beams were used. For plan-C, the new technique, 54 Gy was delivered by 3-D conformal 3-port beams (AP and both lateral ports with wedge compensator; shielding both superficial lobes of parotid glands at the AP beam using BEV) from the beginning of the treatment and early spinal cord block (at 36 Gy) was peformed. And bilateral posterior necks were treated with electron after 36 Gy. After 54 Gy, non-coplanar beams were used for cone-down plan. We intercompared dose statistics (Dmax, Dmin, Dmean, D95, DO5, V95, VOS, Volume receiving 46 Gy) and dose volume histograms (DVH) of tumor and normal tissues and NTCP values of parotid glands for the above three plans. Results : For all patients, the new technique (plan-C) was comparable or superior to the other plans in target volume isodose distribution and dose statistics and it has more homogenous target volume coverage. The new technique was most superior to the other plans in parotid glands sparing (volume receiving 46 Gy: 100, 98, 69$\%$ for each plan-A, B and C). And it showed the lowest NTCP value of parotid glands in all patients (range of NTCP; 96$\~$100$\%$, 79$\~$99$\%$, 51$\~$72$\%$ for each plan-A, B and C). Conclusion : We conclude that the new technique employing 3-D conformal radiotherapy at the beginning of radiotherapy and cone down using non-coplanar beams with early spinal cord block is highly recommended to spare parotid glands for node-negative nasopharygeal cancer patients.