• Radiation Oncology Journal
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• v.17 no.2
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• pp.100-107
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• 1999

Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.247-256
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• 2008

Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.99-106
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• 1998

Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.127-135
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• 2001

Purpose : This study is a prospective randomized clinical trial comparing the efficacy and complication of anti-emetic drugs for prevention of nausea and vomiting after radiotherapy which has moderate emetogenic potential. The aim of this study was to investigate whether the anti-emetic efficacy of ondansetron $(Zofran^{\circledR})$ 8 mg bid dose (Group O) is better than the efficacy of metoclopramide 5 mg lid dose (Group M) in patients undergoing fractionated radiotherapy to the abdominal region. Materials and Methods : Study entry was restricted to those patients who met the following eligibility criteria: histologically confirmed malignant disease; no distant metastasis; performance status of not more than ECOG grade 2; no previous chemotherapy and radiotherapy. Between March 1997 and February 1998, 60 patients enrolled in this study. All patients signed a written statement of informed consent prior to enrollment. Blinding was maintained by dosing identical number of tablets including one dose of matching placebo for Group O. The extent of nausea, appetite loss, and the number of emetic episodes were recorded everyday using diary card. The mean score of nausea, appetite loss and the mean number of emetic episodes were obtained in a weekly interval. Results : Prescription error occurred in one patient. And diary cards have not returned in 3 patients due to premature refusal of treatment. Card from one patient was excluded from the analysis because she had a history of treatment for neurosis. As a result, the analysis consisted of 55 patients. Patient characteristics and radiotherapy characteristics were similar except mean age was $52.9{\pm}11.2$ in group M, $46.5{\pm}9.5$ in group O. The difference of age was statistically significant. The mean score of nausea, appetite loss and emetic episodes in a weekly interval was higher in group M than O. In group M, the symptoms were most significant at 5th week. In a panel data analysis using mixed procedure, treatment group was only significant factor detecting the difference of weekly score for all three symptoms. Ondansetron $(Zofran^{\circledR})$ 8 mg bid dose and metoclopramide 5 mg lid dose were well tolerated without significant side effects. There were no clinically important changes In vital signs or clinical laboratory parameters with either drug. Conclusion : Concerning the fact that patients with younger age have higher emetogenic potential, there are possibilities that age difference between two treatment groups lowered the statistical power of analysis. There were significant difference favoring ondansetron group with respect to the severity of nausea, vomiting and loss of appetite. We concluded that ondansetron is more effective anti-emetic agents in the control of radiotherapy-induced nausea, vomiting, loss of appetite without significant toxicity, compared with commonly used drug, i.e., metoclopramide. However, there were patients suffering emesis despite the administration of ondansetron. The possible strategies to improve the prevention and the treatment of radiotherapy-induced emesis must be further studied.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.27-34
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• 1992

Cis-Platinum (DDP) was utilized as a radiosensitizer in a pilot study for stage III and IV squamous cell carcinoma between 1984-1987, and DDP 20 $mg/M^2$/day was administered for 4 days at 3 week interval with concurrent radiotherapy. This study consisted of three phases: cytoreduction phase, eradicative treatment phase and adjuvant phase. Total 59 patients were subjected to evaluate a tumor response and its toxicity. During the eradicative phase,27 patients underwent surgery (group I ), 29 patients were treated with radiotherapy only (group II) and 3 patients did not complete the second phase of therapy. At the cytoreduction phase, $95\%$ response rate with complete response (CR) $47.5\%$ and partial response (PR) $47.5\%$ was observed. Complete tumor clearance (CTC) rate following 2nd phase of therapy was $84\%$ (47/56) with 26/27($96\%$) in group I achieved CTC with surgery and 21/29 ($72\%$) patients In group II achieved CTC following 2nd phase. $67\%$ of primary lesions and $70\%$ of nodal diseases in group I showed no tumor in the surgical specimen. $34\%$ of patiets who achieved CTC at 2nd phase developed recurrence and median time to recur was 8 months. Actuarial disease free survival at 4 years was $59\%$ and $51\%$(24/27) of patients who achieved CTC at 2nd phase were alive without any evidence of disease at median follow-up 31 months (range, 10-48 months). There was no significant difference in overall and disease free survival between group I and II between CR and PR group following 1st Phase. Only significant Prognostic factor in this study was the complete tumor clearance following 2nd phase theapy. In general, toxicity was not excessive. Author concludes that this study confirmed the significant radiosensitizing effect of DDP with the acceptable toxicity and warrant the prospective study to determine optimum scheduling for DDP and radiotherapy which maximizes the therapeutic gain.

• Progress in Medical Physics
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• v.17 no.3
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• pp.131-135
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• 2006

A commercial ion chamber matrix was examined the characteristics and its performance for radiotherapy qualify assurance. The device was the I'mRT 2D-MatriXX (Scanditronix-Wellhofer, Schwarzenbruck, Germany). The 2D-MatriXX device consists of a 1020 vented ion chamber array, arranged in $24{\times}24cm^2$ matrix. Each ion chamber has a volume of $0.08cm^3$, spacing of 0.762 cm and minimum sampling time of 20 ms. For the investigation of the characteristics, dose linearity, output factor, short-term reproducibility and dose rate dependency were tested. In the testing of dose linearity. It has shown a good signal linearity within 1% in the range of $1{\sim}800$cGy. Dose rate dependency was found to be lower than 0.4% (Range: 100-600 Mu/min) relative to a dose rate of 300 Mu/min as a reference. Output factors matched very well within 0.5% compared with commissioned beam data using a ionization chamber (CC01, Scanditronix-Wellhofer, Schwarzenbruck, Germany) in the range of field sizes $3{\times}3{\sim}24{\times}24cm^2$. Short-term reproducibility (6 times with a interval of 15 minute) was also shown a good agreement within 0.5%, when the temperature and the pressure were corrected by each time of measurement. in addition, we compared enhanced dynamic wedge (EDW, Varian, Palo Alto, USA) profiles from calculated values in the radiation planning system with those from measurements of the MatriXX. Furthermore, anon-uniform IMRT dose fluence was tested. All the comparison studies have shown good agreements. In this study, the MatriXX was evaluated as a reliable dosimeter, and it could be used as a simplistic and convenient tool for radiotherapy qualify assurance.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.889-898
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• 1997

Pulmonary Embolism can develop in variable conditions, and presents with nonspecific symptoms and signs. If diagnosis is delayed, it can be resulted in catastrophic results. Therefore, early diagnosis and adequate treatment is crucial in Pulmonary Embolism. Lung Perfusion Scan is useful screening test. Negative result can exclude pulmonary embolism. But, perfusion defects don't always mean pulmonary embolism. To find the better methods of interpretation of lung perfusion scan and To evaluate the clinical course and outcomes of the patients, in whom pulmonary embolism was suspected by lung perfusion scan, we reviewed the clinical records of 49 cases suspected by lung perfusion scan at Seoul National University Hospital during the period of January, 1995 to July, 1996. The results are as follows. First impression of cases in which PE was present at time of admission were pulmonary embolism (63%), heart diseases (26%), and pneumonia (11%) in orders. Underlying diseases of cases in which PE developed during admission were malignancy (36.5%), ICH (22.7%), sepsis (13.7%), and SLE (9.1%) in orders. The predisposing factors were operation (20%), cancer (16%), immobility (16%), connective tissue disease (16%), heart dis. (10%), old age (10%), and preg/pelvic dis. (8%) The results, of lung perfusion scan were HPPE 40 cases(26.8 %), IPPE 21 cases(14.1%), LPPE 88 cases (59.1%), and cases(%) of treatment in these cases were HPPE 34 cases(85%), IPPE 9 cases(42.9%), LPPE 0 case(0.0%). Treatments were heparin and warfarin (69.5%), heparin alone (8.2%), warfarin alone (2.0%), embolectomy (4.1%), thrombolytics (2.0%), IVC filter (2.0%), and no treatment (12.2%) In 34 cases (69.4%), follow up could be done, and 5 cases were recurred (10.2%). The causes of recurrence was incomplete anticoagulant therapy (3 cases) and recurrence of predisposing factor (2 cases). Expired case due to pulmonary embolism was one who was expired just before trial of thrombolytic therapy. Conclusion : Efforts should be made to shorten the interval from onset of Sx to Dx, ie, high index of suspision.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.203-209
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• 1988

Thirty eight women with recurrent breast carcinoma involving chest wall and/or regional lymph nodes after surgery with or without systemic therapy were treated with radiation between 1979 and 1986. Among them, 5 patients were excluded from analysis because of incomplete treatment. The median follow up of survivors was 30 months (randged 1-79 months). Fifteen (45%)patients had their disease confined to the chest wall and eighteen patients had lymph node involvement as some of their locoregional recurrent disease. Within 36 months after the initial treatment, 87% of recurrences manifested themselves. All patients had radiotherapy to at least the site of involvement. In 8 patients, recurrent tumors were treated with complete excision followed by radiation. Of the remaining 25 patients,18 (72%) had complete response (CR) following radiotherapy. The actuarial 3-year survival of all patients following locoregional recurrence was 50% Three year survival was 24% in those 25 patients who had recurrences within 24 months of the initial treatment. For those 8 patients whose recurrences occurred after more than 24 month disease free interval, the 3-year survival was 100%. For those patients with recurrences confined to chest wall alone, 3-year survival was 57% The patients who had lymph node involvement as part of their locoregional recurrences had a 43% 3-year survival. The majority of them developed distant metastases. Those patients who had a CR showed 63% 3-year survival. On the other hand, 1 year survival was only 33% for those patients who had a less than CR. Three patients developed carcinoma of the contralateral breast following radiotherapy. Three year survival following locoregional recurrence was 40% for patients whose initial treatment for their primary breast carcinoma was surgery and adjuvant systemic therapy. For those patients whose primary breast carcinoma was treated by surgery alone, the 3-year survival following locoregional recurrence was 71%. In patients who had subsequent recurrence after radiotherapy, the actuarial survival was 25% at 2 years.

• The Journal of Korean Society for Radiation Therapy
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• v.19 no.1
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• pp.27-33
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• 2007

Purpose: We have performed SRS (stereotactic radiosurgery) for avm (arterry vein malformation) and brain cancer. In order to verify dose and localization of SRS, dose distributions from TPS ($X-Knife^{(R)}$ 3.0, Radionics, USA) and GafChromic $EBT^{(R)}$ film in a head phantom were compared. Materials and Methods: In this study, head and neck region of conventional humanoid phantom was modified by substituting one of 2.5 cm slap with five 0.5 cm acrylic plates to stack the GafChromic $EBT^{(R)}$ film slice by slice with 5 mm intervals. Four films and five acrylic plates were cut along the contour of head phantom in axial plane. The head phantom was fixed with SRS head ring and adapted SRS localizer as same as real SRS procedure. CT images of the head phantom were acquired in 5 mm slice intervals as film interval. Five arc 6 MV photon beams using the SRS cone with 2 cm diameter were delivered 300 cGy to the target in the phantom. Ten small pieces of the film were exposed to 0, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900 cGy, respectively to calibrate the GafChromic $EBT^{(R)}$ film. The films in the phantom were digitized after 24 hours and its linearity was calibrated. The pixel values of the film were converted to the dose and compared with the dose distribution from the TPS calculation. Results: Calibration curve for the GafChromic $EBT^{(R)}$ film was linear up to 900 cGy. The R2 value was better than 0.992. Discrepancy between calculated from $X-Knife^{(R)}$ 3.0 and measured dose distributions with the film was less than 5% through all slices. Conclusion: It was possible to evaluate every slice of humanoid phantom by stacking the GafChromic EBT film which is suitable for 2 dimensional dosimetry, It was found that film dosimetry using the GafChromic $EBT^{(R)}$ film is feasible for routine dosimetric QA of stereotactic radiosurgery.