• Title/Summary/Keyword: Target Profile

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Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

  • Masaya Igase;Sakuya Inanaga;Shoma Nishibori;Kazuhito Itamoto;Hiroshi Sunahara;Yuki Nemoto;Kenji Tani;Hiro Horikirizono;Munekazu Nakaichi;Kenji Baba;Satoshi Kambayashi;Masaru Okuda;Yusuke Sakai;Masashi Sakurai;Masahiro Kato;Toshihiro Tsukui;Takuya Mizuno
    • Journal of Veterinary Science
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    • v.25 no.1
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    • pp.15.1-15.15
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    • 2024
  • Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Statics corrections for shallow seismic refraction data (천부 굴절법 탄성파 탐사 자료의 정보정)

  • Palmer Derecke;Nikrouz Ramin;Spyrou Andreur
    • Geophysics and Geophysical Exploration
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    • v.8 no.1
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    • pp.7-17
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    • 2005
  • The determination of seismic velocities in refractors for near-surface seismic refraction investigations is an ill-posed problem. Small variations in the computed time parameters can result in quite large lateral variations in the derived velocities, which are often artefacts of the inversion algorithms. Such artefacts are usually not recognized or corrected with forward modelling. Therefore, if detailed refractor models are sought with model based inversion, then detailed starting models are required. The usual source of artefacts in seismic velocities is irregular refractors. Under most circumstances, the variable migration of the generalized reciprocal method (GRM) is able to accommodate irregular interfaces and generate detailed starting models of the refractor. However, where the very-near-surface environment of the Earth is also irregular, the efficacy of the GRM is reduced, and weathering corrections can be necessary. Standard methods for correcting for surface irregularities are usually not practical where the very-near-surface irregularities are of limited lateral extent. In such circumstances, the GRM smoothing statics method (SSM) is a simple and robust approach, which can facilitate more-accurate estimates of refractor velocities. The GRM SSM generates a smoothing 'statics' correction by subtracting an average of the time-depths computed with a range of XY values from the time-depths computed with a zero XY value (where the XY value is the separation between the receivers used to compute the time-depth). The time-depths to the deeper target refractors do not vary greatly with varying XY values, and therefore an average is much the same as the optimum value. However, the time-depths for the very-near-surface irregularities migrate laterally with increasing XY values and they are substantially reduced with the averaging process. As a result, the time-depth profile averaged over a range of XY values is effectively corrected for the near-surface irregularities. In addition, the time-depths computed with a Bero XY value are the sum of both the near-surface effects and the time-depths to the target refractor. Therefore, their subtraction generates an approximate 'statics' correction, which in turn, is subtracted from the traveltimes The GRM SSM is essentially a smoothing procedure, rather than a deterministic weathering correction approach, and it is most effective with near-surface irregularities of quite limited lateral extent. Model and case studies demonstrate that the GRM SSM substantially improves the reliability in determining detailed seismic velocities in irregular refractors.

Quality Assurance for Intensity Modulated Radiation Therapy (세기조절방사선치료(Intensity Modulated Radiation Therapy; IMRT)의 정도보증(Quality Assurance))

  • Cho Byung Chul;Park Suk Won;Oh Do Hoon;Bae Hoonsik
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.275-286
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    • 2001
  • Purpose : To setup procedures of quality assurance (OA) for implementing intensity modulated radiation therapy (IMRT) clinically, report OA procedures peformed for one patient with prostate cancer. Materials and methods : $P^3IMRT$ (ADAC) and linear accelerator (Siemens) with multileaf collimator are used to implement IMRT. At first, the positional accuracy, reproducibility of MLC, and leaf transmission factor were evaluated. RTP commissioning was peformed again to consider small field effect. After RTP recommissioning, a test plan of a C-shaped PTV was made using 9 intensity modulated beams, and the calculated isocenter dose was compared with the measured one in solid water phantom. As a patient-specific IMRT QA, one patient with prostate cancer was planned using 6 beams of total 74 segmented fields. The same beams were used to recalculate dose in a solid water phantom. Dose of these beams were measured with a 0.015 cc micro-ionization chamber, a diode detector, films, and an array detector and compared with calculated one. Results : The positioning accuracy of MLC was about 1 mm, and the reproducibility was around 0.5 mm. For leaf transmission factor for 10 MV photon beams, interleaf leakage was measured $1.9\%$ and midleaf leakage $0.9\%$ relative to $10\times\;cm^2$ open filed. Penumbra measured with film, diode detector, microionization chamber, and conventional 0.125 cc chamber showed that $80\~20\%$ penumbra width measured with a 0.125 cc chamber was 2 mm larger than that of film, which means a 0.125 cc ionization chamber was unacceptable for measuring small field such like 0.5 cm beamlet. After RTP recommissioning, the discrepancy between the measured and calculated dose profile for a small field of $1\times1\;cm^2$ size was less than $2\%$. The isocenter dose of the test plan of C-shaped PTV was measured two times with micro-ionization chamber in solid phantom showed that the errors upto $12\%$ for individual beam, but total dose delivered were agreed with the calculated within $2\%$. The transverse dose distribution measured with EC-L film was agreed with the calculated one in general. The isocenter dose for the patient measured in solid phantom was agreed within $1.5\%$. On-axis dose profiles of each individual beam at the position of the central leaf measured with film and array detector were found that at out-of-the-field region, the calculated dose underestimates about $2\%$, at inside-the-field the measured one was agreed within $3\%$, except some position. Conclusion : It is necessary more tight quality control of MLC for IMRT relative to conventional large field treatment and to develop QA procedures to check intensity pattern more efficiently. At the conclusion, we did setup an appropriate QA procedures for IMRT by a series of verifications including the measurement of absolute dose at the isocenter with a micro-ionization chamber, film dosimetry for verifying intensity pattern, and another measurement with an array detector for comparing off-axis dose profile.

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Performance Evaluation of Radiochromic Films and Dosimetry CheckTM for Patient-specific QA in Helical Tomotherapy (나선형 토모테라피 방사선치료의 환자별 품질관리를 위한 라디오크로믹 필름 및 Dosimetry CheckTM의 성능평가)

  • Park, Su Yeon;Chae, Moon Ki;Lim, Jun Teak;Kwon, Dong Yeol;Kim, Hak Joon;Chung, Eun Ah;Kim, Jong Sik
    • The Journal of Korean Society for Radiation Therapy
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    • v.32
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    • pp.93-109
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    • 2020
  • Purpose: The radiochromic film (Gafchromic EBT3, Ashland Advanced Materials, USA) and 3-dimensional analysis system dosimetry checkTM (DC, MathResolutions, USA) were evaluated for patient-specific quality assurance (QA) of helical tomotherapy. Materials and Methods: Depending on the tumors' positions, three types of targets, which are the abdominal tumor (130.6㎤), retroperitoneal tumor (849.0㎤), and the whole abdominal metastasis tumor (3131.0㎤) applied to the humanoid phantom (Anderson Rando Phantom, USA). We established a total of 12 comparative treatment plans by the four geometric conditions of the beam irradiation, which are the different field widths (FW) of 2.5-cm, 5.0-cm, and pitches of 0.287, 0.43. Ionization measurements (1D) with EBT3 by inserting the cheese phantom (2D) were compared to DC measurements of the 3D dose reconstruction on CT images from beam fluence log information. For the clinical feasibility evaluation of the DC, dose reconstruction has been performed using the same cheese phantom with the EBT3 method. Recalculated dose distributions revealed the dose error information during the actual irradiation on the same CT images quantitatively compared to the treatment plan. The Thread effect, which might appear in the Helical Tomotherapy, was analyzed by ripple amplitude (%). We also performed gamma index analysis (DD: 3mm/ DTA: 3%, pass threshold limit: 95%) for pattern check of the dose distribution. Results: Ripple amplitude measurement resulted in the highest average of 23.1% in the peritoneum tumor. In the radiochromic film analysis, the absolute dose was on average 0.9±0.4%, and gamma index analysis was on average 96.4±2.2% (Passing rate: >95%), which could be limited to the large target sizes such as the whole abdominal metastasis tumor. In the DC analysis with the humanoid phantom for FW of 5.0-cm, the three regions' average was 91.8±6.4% in the 2D and 3D plan. The three planes (axial, coronal, and sagittal) and dose profile could be analyzed with the entire peritoneum tumor and the whole abdominal metastasis target, with planned dose distributions. The dose errors based on the dose-volume histogram in the DC evaluations increased depending on FW and pitch. Conclusion: The DC method could implement a dose error analysis on the 3D patient image data by the measured beam fluence log information only without any dosimetry tools for patient-specific quality assurance. Also, there may be no limit to apply for the tumor location and size; therefore, the DC could be useful in patient-specific QAl during the treatment of Helical Tomotherapy of large and irregular tumors.

The Brassica rapa Tissue-specific EST Database (배추의 조직 특이적 발현유전자 데이터베이스)

  • Yu, Hee-Ju;Park, Sin-Gi;Oh, Mi-Jin;Hwang, Hyun-Ju;Kim, Nam-Shin;Chung, Hee;Sohn, Seong-Han;Park, Beom-Seok;Mun, Jeong-Hwan
    • Horticultural Science & Technology
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    • v.29 no.6
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    • pp.633-640
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    • 2011
  • Brassica rapa is an A genome model species for Brassica crop genetics, genomics, and breeding. With the completion of sequencing the B. rapa genome, functional analysis of the genome is forthcoming issue. The expressed sequence tags are fundamental resources supporting annotation and functional analysis of the genome including identification of tissue-specific genes and promoters. As of July 2011, 147,217 ESTs from 39 cDNA libraries of B. rapa are reported in the public database. However, little information can be retrieved from the sequences due to lack of organized databases. To leverage the sequence information and to maximize the use of publicly-available EST collections, the Brassica rapa tissue-specific EST database (BrTED) is developed. BrTED includes sequence information of 23,962 unigenes assembled by StackPack program. The unigene set is used as a query unit for various analyses such as BLAST against TAIR gene model, functional annotation using MIPS and UniProt, gene ontology analysis, and prediction of tissue-specific unigene sets based on statistics test. The database is composed of two main units, EST sequence processing and information retrieving unit and tissue-specific expression profile analysis unit. Information and data in both units are tightly inter-connected to each other using a web based browsing system. RT-PCR evaluation of 29 selected unigene sets successfully amplified amplicons from the target tissues of B. rapa. BrTED provided here allows the user to identify and analyze the expression of genes of interest and aid efforts to interpret the B. rapa genome through functional genomics. In addition, it can be used as a public resource in providing reference information to study the genus Brassica and other closely related crop crucifer plants.

The Effect of Mobile Advertising Platform through Big Data Analytics: Focusing on Advertising, and Media Characteristics (빅데이터 분석을 통한 모바일 광고플랫폼의 광고효과 연구: 광고특성, 매체특성을 중심으로)

  • Bae, Seong Deok;Park, Do-Hyung
    • Journal of Intelligence and Information Systems
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    • v.24 no.2
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    • pp.37-57
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    • 2018
  • With the spread of smart phones, interest in mobile media is on the increase as useful media recently. Mobile media is assessed as having differentiated advantages from existing media in that not only can they provide consumers with desired information anytime and anywhere but also real-time interaction is possible in them. So far, studies on mobile advertising were mostly researches analyzing satisfaction with, and acceptance of, mobile advertising based on survey, researches focusing on the factors affecting acceptance of mobile advertising messages and researches verifying the effect of mobile advertising on brand recall, advertising attitude and brand attitude through experiments. Most of the domestic mobile advertising studies related to advertisement effect and advertisement attitude have been conducted through experiments and surveys. The advertising effectiveness measure of the mobile ad used the attitude of the advertisement, purchase intention, etc. To date, there have been few studies on the effects of mobile advertising on actual advertising data to prove the characteristics of the advertising platform and to prove the relationship between the factors influencing the advertising effect and the factors. In order to explore advertising effect of mobile advertising platform currently commercialized, this study defined advertising characteristics and media characteristics from the perspective of advertiser, advertising platform and publisher and analyzed the influence of each characteristic on advertising effect. As the advertisement characteristics, we classified advertisement format classified by bar type and floating type, and advertisement material classified by image and text. We defined advertisement characteristics of advertisement platform as Hedonic and Utilitarian media characteristics. As a dependent variable, we use CTR, which is the ratio of response (click) to ad exposure. The theoretical background and the analysis of the mobile advertising business, the hypothesis that the advertisement effect is different according to the advertisement specification, the advertisement material, In the ad standard, bar ads are classified as static framing, Floating ads can be categorized as dynamic framing, and the hypothetical definition of floating advertisements, which are high-profile dynamic framing ads, is highly responsive. In advertising, images with high salience are defined to have higher ad response than text. In the media characteristics classified as practical / hedonic type, it is defined that the hedonic type media has a more relaxed tendency than the practical media, and there is a high possibility of receiving various information because there is no clear target. In addition, image material and hedonic media are defined to be highly effective in the interaction between advertisement specification and advertisement material, advertisement specifications and media characteristics, and advertisement material and media characteristics. As the result of regression analysis on each characteristic, material standard, which is a characteristic of mobile advertisement, and media characteristics separated into 'Hedonic' and 'Utilitarian' had significant influence on advertisement effect and mutual interaction effect was also confirmed. In the mobile advertising standard, the advertising effect of the floating advertisement is higher than that of the bar advertisement, Floating ads were more effective than text ads for image ads. In addition, it was confirmed that the advertising effect is higher in the practical media than the hedonic media. The research was carried out with the big data collected from the mobile advertising platform, and it was possible to grasp the advertising effect of the measure index standard which is used in the practical work which could not be grasped in the previous research. In other words, the study was conducted using the CTR, which is a measure of the effectiveness of the advertisement used in the online advertisement and the mobile advertisement, which are not dependent on the attitude of the ad, the attitude of the brand, and the purchase intention. This study suggests that CTR is used as a dependent variable of advertising effect based on actual data of mobile ad platform accumulated over a long period of time. The results of this study is expected to contribute to establishment of optimum advertisement strategy such as creation of advertising materials and planning of media which suit advertised products at the time of mobile advertisement.

Species-specific Expression of Rpia Transcript in Cumulus-oocyte-complex (난자-난구세포 복합체에서 발현하는 Rpia 유전자의 종 특이적 발현)

  • Kim, Yun-Sun;Yoon, Se-Jin;Kim, Eun-Young;Lee, Kyung-Ah
    • Clinical and Experimental Reproductive Medicine
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    • v.34 no.2
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    • pp.95-106
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    • 2007
  • Objective: We previously identified differentially expressed genes (DEGs) between germinal vesicle (GV) and metaphase II (MII) mouse oocyte. The present study was accomplished as a preliminary study to elucidate the role of ribose 5-phosphate isomerase A (Rpia), the essential enzyme of the pentose phosphate pathway (PPP), in oocyte maturation. We observed expression of Rpia in the mouse and porcine oocytes. Methods: Expression pattern of the 11 MII-selective DEGs in various tissues was evaluated using RT-PCR and selected 4 genes highly expressed in the ovary. According to the oocyte-selective expression profile, we selected Rpia as a target for this study. We identified the porcine Rpia sequence using EST clustering technique, since it is not yet registered in public databases. Results: The extended porcine Rpia nucleotide sequence was submitted and registered to GenBank (accession number EF213106). We prepared primers for porcine Rpia according to this sequence. In contrast to the oocyte-specific expression in the mouse, Rpia was expressed in porcine cumulus and granulosa cells as well as in oocytes. Conclusion: This is the first report on the characterization of the Rpia gene in the mouse and porcine ovarian cells. Results of the present study suggest that the mouse and porcine COCs employ different mechanism of glucose metabolism. Therefore, the different metabolic pathways during in vitro oocyte maturation (IVM) in different species may lead different maturation rates. It is required to study further regarding the role of Rpia in glucose metabolism of oocytes and follicular cell fore exploring the regulatory mechanism of oocyte maturation as well as for finding the finest culture conditions for in vitro maturation.

Molecular Characterization and Expression Analysis of Clathrin-Associated Adaptor Protein 3-δ Subunit 2 (AP3S2) in Chicken

  • Oh, Jae-Don;Bigirwa, Godfrey;Lee, Seokhyun;Song, Ki-Duk
    • Korean Journal of Poultry Science
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    • v.46 no.1
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    • pp.31-37
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    • 2019
  • A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.

Distortion of the Dose Profile in a Three-dimensional Moving Phantom to Simulate Tumor Motion during Image-guided Radiosurgery (방사선수술에서 종양 움직임을 재현시킨 움직이는 팬텀을 이용하여 선량 분포의 왜곡에 대한 연구)

  • Kim, Mi-Sook;Ha, Seong-Hwan;Lee, Dong-Han;Ji, Young-Hoon;Yoo, Seong-Yul;Cho, Chul-Koo;Yang, Kwang-Mo;Yoo, Hyung-Jun;Seo, Young-Seok;Park, Chan-Il;Kim, Il-Han;Ye, Seong-Jun;Park, Jae-Hong;Kim, Kum-Bae
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.268-277
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    • 2007
  • Purpose: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. Materials and Methods: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. Results: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the $30{\sim}50$ mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. Conclusion: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.