• Progress in Medical Physics
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• v.26 no.2
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• pp.79-86
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• 2015

The purpose of this study is to evaluate efficacy and feasibility of adaptive radiotherapy according to tumor volume change (TVC) in early stage non-small cell lung cancer (NSCLC) using stereotactic body radiotherapy (SBRT). Twenty-two lesions previously treated with SBRT were selected. SBRT was usually performed with a total dose of 48 Gy or 60 Gy in four fractions with an interval of three to four days between treatments. For evaluation of TVC, gross tumor volume (GTV) was contoured on each cone-beam computed tomography (CBCT) image used for image guidance. Intensity modulated radiotherapy (IMRT) planning was performed in the first CBCT (CBCT1) using a baseline plan. For ART planning (ART), re-optimization was performed at $2^{nd}$, $3^{rd}$, and $4^{th}$ CBCTs (CBCT2, CBCT3, and CBCT4) using the same angle and constraint used for the baseline plan. The ART plan was compared with the non-ART plan, which generated copying of the baseline plan to other CBCTs. Average GTV volume was 10.7 cc. Average TVC was -1.5%, 7.3%, and -25.1% in CBCT2, CBCT3, and CBCT4 and the TVC after CBCT3 was significant (p<0.05). However, the nine lesions were increased GTV in CBCT2. In the ART plan, $V_{20\;Gy}$, $D_{1500\;cc}$, and $D_{1000\;cc}$ of lung were significantly decreased (p<0.05), and $V_{30\;Gy}$ and $V_{32\;Gy}$ of the chest wall were also decreased (p<0.05). While D min of planning target volume (PTV) decreased by 8.3% in the non-ART plan of CBCT2 compared with the baseline plan in lesions with increased tumor size (p=0.021), PTV coverage was not compromised in the ART plan. Based on this result, use of the ART plan may improve target coverage and OAR saving. Thus ART using CBCT should be considered in early stage NSCLC with SBRT.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.155-164
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• 2002

Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD $(days)=0.26{\times}D$ (Gy)+0.13 in the radiation alone group, and the TGD $(days)=0.30{\times}D$ (Gy)+0.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 ($95\%$ confidence interval; $1.13\~1.27$). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.005) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor $(0.5\%\;vs.\;5.2\%,\;p=0.005)$. The blood flow was not changed with the GBE in normal muscle, but was increased by $23.5\%$ ( p=0.0004) in the tumor. Conclusion : Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.

• Radiation Oncology Journal
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• v.29 no.2
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• pp.83-90
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• 2011

Purpose: Flavopiridol enhanced radiation-induced apoptosis of cancer cells in our previous in vitro study. The purpose of this study was to assess if flavopiridol could enhance the radioresponse of mouse mammary tumors in vivo. Materials and Methods: Balb/c mice bearing EMT-6 murine mammary carcinoma were treated with flavopiridol only, radiation only, or both for 7 days. Flavopiridol was administered 2.5 mg/kg twice a day intraperitoneally (IP). Radiation was delivered at a 4 Gy/fraction at 24-h intervals for a total dose of 28 Gy. Tumor volume was measured and compared among the different treatment groups to evaluate the in vivo radiosensitizing effect of flavopiridol. Tumors were removed from the mice 20 days after treatment, and TUNEL and Immunohistochemical stainings were performed. Results: Significant tumor growth delay was observed in the radiation only and combined treatment groups, when compared with the control group. However, there was no significant difference between the tumor growth curves of the control and flavopiridol only group or between the radiation only and combination treatment group. Apoptotic cells of different treatment groups were detected by terminal deoxynucleotidyl transferase-medicated nick end labeling (TUNEL) staining. The expressions of Ku70 in tumor tissues from the different groups were analyzed by immunohistochemistry. Similarly, no significant difference was found between the apoptotic rate or Ku70 expression among the different treatment groups. Conclusion: Flavopiridol did not show evidence of enhancing the radioresponse of mouse mammary tumors in this study.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.29-34
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• 1993

Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diammihedichloroplatinum (cis-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of $10^3$ cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vitro studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 6.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was when cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cis-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 ${\mu}M$ cis-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adjuvant treatment.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• The Journal of Korean Society for Radiation Therapy
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• v.14 no.1
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• pp.15-22
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• 2002

1. 목적 : 방사선종양학과에서 3차원 치료계획용 전산화단층촬영 시 조영제 주입율에 따른 CT 값(hounsfield unit, H.U) 변화를 정량적으로 평가하여 최적의 영상증강효과 및 방사선치료계획을 위한 기초 프로토콜을 제시하고자 한다. 2. 대상 및 방법: 연세암센터 방사선종양학과에서 3차원 치료계획용 전산화단층촬영을 시행한 상복부(폐암)환자 20명을 대상으로 하였다. 조영제 양(130mL)은 일정하게 고정하였고, 조영제주입율을 1.2, 1.5, 2.0 mL/sec로 변화시켜가며 조영제를 주입하면서 3차원 방사선치료계획영상에 적합한 조영제주입율(contrast flow rate)과 지연시간(delay time)을 도출하였고, CT 값을 측정하여 정량적 평가를 시행하였다. 관심부위는 폐동맥과 폐정맥으로 하였다. 그리고, 환자 기본정보, 조영제주입율, H.U 등 영상증강에 영향을 미치는 인자들을 통계처리 프로그램인 SPSS를 이용하여 최적의 영상을 획득할 수 있는 기초 프로토콜을 작성하였다. 3. 결과 : 폐암환자의 전산화단층촬영영상 획득 시 3차원 방사선치료계획에 적합한 영상을 얻을 수 있는 조건중 조영제주입율은 1.5 mL/sec 이었고, 지연시간은 $60{\sim}70$초이었다. 통계처리를 수행한 결과 환자의 기본정보 및 조영제주입율 등이 영상증강에 영향을 미치는 인자임을 알 수 있었다. 본 연구에서 작성한 기초 프로토콜을 이용하여 3차원 방사선치료계획 시 정확한 종양 및 정상조직 설정이 용이하게 되어 방사선치료 효율을 극대화 할 수 있었다. 4. 결론 : 방사선종양학과에서 3차원 치료계획용 전산화단층촬영 시 사용할 수 있는 기초적인 영상획득 프로토콜을 도출하였고, 향후 더 많은 임상경험과 정량적 평가가 수반된다면 임상에 적극 사용할 수 있을 것이라 사료된다.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.153-160
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• 2018

Purpose : We retrospectively analyzed doses of each radiation therapy technique used in the treatment for left breast cancer patients after partial mastectomy through dose results for normalorgans and tumor volume to use this as a clinical reference for radiation therapy of domestic left breast cancer patients. Materials and Methods : 40 patients who underwent partial mastectomy on left breast cancer were classified in 3 treatment methods. The treatment plan was evaluated by HI(homogeneity index), $D_{95%}$, and CI(conformity index), and the $V_{hot}$ for gross tumor volume and clinical target volume of each treatment method. In Cyberknife treatment, tumor volume was the same as high dose volume in the other techniques, so no consideration was given to clinical target volume. Treatment plan evaluation for normal organs were evaluated by mean dose on ipsilateral lung, heart, left anterior descending artery, opposite breast and lung, and non-target tissue. Result : Treatment with volumetric arc radiotherapy(VMAT) showed $95.84{\pm}0.75%$ of $D_{95%}$ on the clinical target volume, significantly higher than that of 3D-CRT. The $D_{95%}$ value of the total tumor volume was slightly higher than the other treatments. In Cyberknife treatment, the dose to the normal organs was significantly lower than other treatments. Overall, the maximum dose and mean dose to the heart were $26.2{\pm}6.12Gy$ and $1.88{\pm}0.2Gy$ in VMAT treatment and $20.25{\pm}9.35Gy$ and $1.04{\pm}0.19Gy$ in 3D-CRT therapy, respectively. Conclusion : In comparison on 3D-CRT and VMAT, most of the dosimetric parameters for the evaluation of the treatment plan showed similar values, so that there is no significant difference in treatment plan evaluation. It is possible to select the treatment method according to the patient's anatomical structure or possibility of breath control. Cyberknife treatment is very useful treatment for normal organs because of its accurate dose exposure to the tumor volume However, it has restrictions to treat the local area, to have relatively long treatment time and to involve invasive procedure.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.7-14
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• 1992

Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin's lymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin's lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral brain edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracraniai tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.149-155
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• 2006

Meningeal hemangiopericytoma (HPC) is an uncommon dura-based tumor and can recur not only locally but also distantly in the neural axis or extraneural sites. We report our experience of radiation therapy, one preoperative and one elective postoperative, In two patients with meningeal HPC and reviewed the role of radiation therapy. A 41-year-old man (Case 1) presented with a 3-month history of headache and right hemiparesis. The mass was nearly unresectable at the first and second operation and diagnosed as meningeal HPC. Preoperative radiation therapy was given with a total dose of 55.8 Gy/31 fractions to the large residual mass of left frontoparietal area. Follow-up computerized tomography (CT) showed marked regression of tumor after radiation therapy. The third operation was peformed to remove the residual tumor at 6 months after the radiation therapy and a $2{\times}2cm$ sized tumor was encountered. The mass was totally removed. The serial follow-up CT showed no evidence of recurrence and he is alive without distant metastasis for 4 years and 10 months after the first operation. A 45-year-old woman (Case 2) presented with suddenly developed headache and visual impairment. Tumor mass occupying right frontal lobe was removed with the preoperative diagnosis of meningioma. It was totally removed with attached sagittal sinus and diagnosed as meningeal HPC. Elective postoperative radiation therapy was peformed to reduce local recurrence with a total dose of 54 Gy/30 fractions to the involved area of right frontal lobe. She is alive for 5 years maintaining normal activity without local recurrence and distant metastasis.

• The Journal of the Korean bone and joint tumor society
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• v.17 no.1
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• pp.36-43
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• 2011

Purpose: This study was designed to verify intermediate-term functional and radiological results of limb salvage operation using endoprosthetic replacement system ($MUTARS^{(R)}$) used in patients with a malignant bone tumor. Materials and Methods: Thirty one cases which used $MUTARS^{(R)}$ tumor prosthesis were reviewed. The mean age of the patients was 49.2 years and the mean follow up was 39.8 months. We retrospectively reviewed complications, and evaluated functionally and radiologically by Enneking functional score, ISOLS radiological implants evaluation system at last follow-up. Results: 3 patients had died of disease, distant metastasis was seen in 4 patients and local recurrence was seen in 1 patients. Complications were developed in 12 patients. (infection 6, leg length discrepancy 2, aseptic loosening 2, periprosthetic femoral fracture 1, screw loosening 1) Mean value of total functional scores were 81.2% in proximal femur, 77.4% in distal femur, 78.1% in proximal tibia, and 80.2% in proximal humerus. The overall radiological result was relatively satisfactory. Conclusion: Our results suggest limb salvage with the $MUTARS^{(R)}$ endoprosthesis is successful with good functional and radiological results. But we should be careful with complications such as infection.