On the use of radiobiological-based optimization functions in radiotherapy treatment planning for prostate and head and neck cases on Monaco and Eclipse TPS / Sobre el uso de funciones de costo basadas en radiobiología en la planeación de tratamientos de radioterapia para casos de próstata y cabeza y cuello en los TPS Monaco y Eclipse

INTRODUCTION Radiobiological-based optimization functions for radiotherapy treatment planning involve dose-volume effects that could allow greater versatility when shaping dose distributions and DVHs than traditional dose volume (DV) criteria. Two of the most commercially available TPS (Monaco and Eclipse) already offer biological-based optimization functions, but they are not routinely used by most planners in clinical practice. Insight into the benefits of using EUD, TCP/NTCP-based cost functions in Monaco and Eclipse TPS was gained by comparing biological-based optimizations and physical-based optimizations for prostate and head and neck cases. METHODS Three prostate and three H&N cases were retrospectively optimized in Monaco and Eclipse TPS, using radiobiological-based cost functions vs DV-based cost functions. Plan comparison involved ICRU Report 83 parameters D95%, D50%, D2% and TCP for the PTV, and NTCP and RTOG tolerance doses for OARs. RESULTS Although there were differences between Monaco and Eclipse plans due to their dissimilar optimization and dose calculation algorithms as well as optimization functions, both TPS showed that radiobiological-based criteria allow versatile tailoring of the DVH with variation of only one parameter and at most two cost functions, in contrast to the use of three to four DV-based criteria to reach a similar result. CONCLUSION Despite the use of a small sample, optimization of three prostate and three head and neck cases allowed the exploration of optimization possibilities offered by two of the most commercially available TPS on two anatomically dissimilar regions. Radiobiological-based optimization efficiently drives dose distributions and DVH shaping for OARs without sacrifice of PTV coverage. Use of EUD-based cost functions should be encouraged in addition to DV cost functions to obtain the best possible plan in daily clinical practice

INTRODUCCION Las funciones de optimización basadas en radiobiología para la planificación del tratamiento de radioterapia implican efectos dosis volumen que podrían permitir una mayor versatilidad a la hora de dar forma a las distribuciones de dosis y DVH que los tradicionales criterios dosis-volumen (DV). Dos de los TPS más disponibles comercialmente (Mónaco y Eclipse) ya ofrecen productos de funciones de optimización de base biológica, pero la mayoría de los planificadores no las utilizan de forma rutinaria en la práctica clínica. El conocimiento de los beneficios del uso de las funciones de costos basadas en EUD, TCP/NTCP en Mónaco y Eclipse TPS se obtuvo comparando optimizaciones de base biológica y optimizaciones físicas para casos de próstata y cabeza y cuello. MÉTODOS Tres próstatas y tres casos de H&N en Mónaco y Eclipse TPS fueron optimizadas retrospectivamente usando funciones de costos basadas en radiobiología vs funciones de costos basadas en DV. La comparación de planes involucró los parámetros del Informe ICRU 83 D95%, D50%, D2% y TCP para el PTV, y dosis de tolerancia NTCP y RTOG para OAR. Resultados. Aunque hubo diferencias entre los planes Mónaco y Eclipse, debido a sus diferentes algoritmos de optimización y cálculo de dosis, así como funciones de optimización, ambos TPS demostraron que el criterio basado en radiobiología permiten una adaptación versátil del DVH con variación de un solo parámetro y como máximo dos funciones de costos, en contraste con el uso de tres o cuatro criterios basados en DV para alcanzar un resultado similar. CONCLUSIÓN A pesar del uso de una muestra pequeña, la optimización de tres casos de próstata y tres de cabeza y cuello permitió la exploración de las posibilidades de optimización que ofrecen dos de los TPS más disponibles comercialmente en dos regiones anatómicamente diferentes. La optimización basada en radiobiología impulsa de manera eficiente las distribuciones de dosis y la configuración de DVH para OAR sin sacrificar Cobertura de PTV. Se debe fomentar el uso de funciones de costos basadas en EUD además de las funciones de costos DV para obtener el mejor posible plan en la práctica clínica diaria

Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview

Fibrates are a class ofmedication that mainly lowers theblood triglyceride levels. Theyreduce the LDL andincrease the levels of HDL C, in the blood.Clofibrate,the first member to bediscovered in 1962, and introduced in USA in 1967, is withdrawnin 2002, due to unexplained hepatomegaly,hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome, macrovascular and microvascular diabetic complications like stroke, myocardial infarction, peripheral vascular diseaseand diabeticretinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density LipoproteinCholesterol Intervention Trial) , FIELD trail. (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,ACCORD -Lipid trial (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and BIP (Bezafibrate Infarction Prevention Study) trial andangiography trials, like LOCAT(LopidCoronary Angiography Trial) and BECLAIT(Bezafibrate Coronary Atherosclerosis Intervention Trial)demonstrated thebeneficial effects of gemfibrozil and fenofibrate.Their mechanism of action remained obscure for three decades,ie till 1990s, when theirmode of actionwas found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involvingthevariousenzymes like LCAT (Lecithin-cholesterol acyl transferase)andCYP7A1 etc. (cholesterol 7-alpha-monooxygenase or cytochromeP450 7A1 (CYP7A1)) , transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP,OATP (Na+-dependent taurocholate transporter/ organic anion transporters) . These are the.) andnuclear factors like LXR, PPAR alfa etc. (liver orphan receptorα , and peroxisome proliferative nuclear factor) , in relation to the mechanismsof action of fibrates are discussed . Areas of current interests in literature are briefed.

A cross sectional study to assess the operationalization of national tobacco control program in a tertiary level hospital of central India

Background: To implement the Anti- Tobacco laws and to sensitize all stakeholders, The National Tobacco Control Programme (NTCP) was launched by the Ministry of Health and Family Welfare (MoHFW), Government of India in 2007- 08, during the 11th five year plan. This study aims to identify the level of the awareness of ill health effects of tobacco, the basic tenets of NTCP and COTPA among the hospital staff of the tertiary level medical college hospital (M.Y Hospital Indore) involved in the process.Methods: An analytical study. Was carried out in tertiary level medical college hospital among service providers involved in anti-tobacco cell using inter-personal interview of the service providers (Medical Officers, Staff Nurses, Health Care Personnel) using pre-designed pretested semi structured questionnaire based on the salient features of NTCP and provisions of COTPA- cigarettes and other tobacco products act, 2003.Results: Regarding the ill health effects of tobacco doctors had slightly better knowledge awareness than nurses. However, it was ironical that nurses had a slightly better awareness when it comes to NTCP. Doctors were better aware of new COTPA guidelines as compared to nurses. Thus, nurses had less knowledge about ill effects of tobacco consumption and new COTPA guidelines as compared to doctors.Conclusions: Although most of the health care personnel involved in operationalization of NTCP are aware of the basic tenets of NTCP, COTPA and ill health effects of tobacco there is a dire need of the refresher training of both the doctors and the nurses. Also this type of the present study should be contemplated on multi-centric basis on a larger scale for better data results.

Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1 cell model stably expressing human NTCP / 中国天然药物

NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 102 herbal medicinal ingredients. The results showed that ginkgolic acid (GA) (13 : 0), GA (15 : 1), GA (17 : 1), erythrosine B, silibinin, and emodin have inhibitory effects on NTCP uptake of TCNa in a concentration-dependent manner. Among them, GA (13 : 0) and GA (15 : 1) exhibited the stronger inhibitory effects, with IC50 values being less than 8.3 and 13.5 μmol·L(-1), respectively, than the classical inhibitor, cyclosporin A (CsA) (IC50 = 20.33 μmol·L(-1)). Further research demonstrated that GA (13 : 0), GA (15 : 1), GA (17 : 1), silibinin, and emodin were not substrates of NTCP. These findings might contribute to a better understanding of the disposition of the herbal ingredients in vivo, especially in biliary excretion.

Establishment and identification of HEK293 cell lines with stable and high expression of NTCP / 中国药理学通报

Abstrate:Aim To construct HEK293 cell line with stable and high expression of sodium taurocholate cotransporting polypeptide (NTCP ) efficiently and rapidly.Method Vector expressing EGFP-NTCP fusion protein was constructed and verified by DNA sequencing.The pEGFP-NTCP expression vector was transfected into HEK293 cells by FuGENE 6 transfection reagent. The transfected cells with high expression of green fluorescent protein were selected using fluorescence microscope for screening of G418 for 14 days to obtain cell lines stably and highly expressing NTCP.NTCP expression was detected by RT-PCR,qRT-PCR, Western-blot and the uptake experiment of taurocholic acid.Re-sult RT-PCR,qRT-PCR,Western-blot and the uptake experi-ment revealed that compared to the control cells,the expression of NTCP was significantly positive (P<0.01)in stable trans-fected cells showing green fluorescence (P<0.05 ).Conclusion The HEK293 cell line with stable and high expression of NTCP has been established efficiently and rapidly,which provides a cellular model for the study of the mechanism of the uptake of bile acid derivatives.

Anidamiento en las comunidades de parásitos en peces intermareales de Chile central: ¿Qué tan influyente es la longitud corporal del hospedero?

a estructura de la comunidad de parásitos, determinada mediante análisis de anidamiento, varía considerablemente en función de la especie hospedera y el tamaño corporal de la misma. El patrón anidado es aquel en el que comunidades pobres en especies constituyen subunidades de comunidades de mayor riqueza, lo cual también se observa en las comunidades de parásitos. Existen grandes diferencias de riqueza y abundancia de parásitos en función del tamaño del hospedero. Por lo tanto, en este estudio determinamos, mediante análisis de anidamiento, si la estructura de la comunidad de parásitos de peces del intermareal, se relaciona con la longitud corporal de los hospederos y los descriptores parasitológicos. Se recolectaron 2 435 individuos de cinco especies de peces del intermareal rocoso de Chile central (32º02'-33º57' S y 70º30'- 70º30' W); Helcogrammoides chilensis, Scartichthys viridis, Auchenionchus microcirrhis, Gobiesox marmoratus y Sicyases sanguineus. Cada especimen fue revisado con respecto a sus parásitos y medido en su longitud total (LT). Las cinco especies muestreadas fueron clasificadas en función de la longitud corporal (LT) en tres rangos, cada uno de los cuales constituye una infracomunidad del estudio, y para la que se calculó el índice de anidamiento. Se emplearon los modelos NTCP (Nestedness Temperature Calculator Program) y NODF (Nestedness metric based on the Overlap and Decreasing Fill), utilizando la presencia/ ausencia de especies parásitas. También se empleó el modelo WNODF (Weighted - NODF) utilizando la abundancia de parásitos por especie. Así mismo, se calculó la riqueza total de especies, el promedio de riqueza, abundancia, diversidad y dominancia a nivel de la infracomunidad, para relacionarlos con los índices de anidamiento. Las infracomunidades de parásitos de la mayoría de las especies presentaron patrones de anidamiento, excepto en G. marmoratus y H. chilensis, en algunos de sus rangos de LT. No se encontró una relación directa entre el índice de anidamiento y la LT de los peces. Sin embargo, se observaron correlaciones directas de los índices de anidamiento con la riqueza promedio, abundancia y la diversidad infracomunitaria de parásitos, pero no con la riqueza total, que mostró una correlación inversa con la LT del hospedero. Además, se detectó anidamiento en la comunidad componente de parásitos en todas las especies de peces. Concluimos que las comunidades de parásitos de peces provenientes de la zona intermareal son estructuradas y predecibles, y se encuentran vagamente condicionadas por la LT de los hospederos y las características agregadas de los parásitos, especialmente a un nivel infracommunitario.

tructure and richness of parasite communities varies substantially among species and body sizes of hosts, which can be determined by analyzing the nestedness. The nestedness pattern is originated when depauperate communities are subsets of those found in communities with greater species richness, and has normally used to study parasite communities. Therefore, in this study we determined whether the structure of parasite communities of the intertidal fish, of central Chile, relates to host lengths and parasitological descriptors, by the use of nested subset analyses. We collected 2 435 individuals of five fish species from the intertidal rocky zone of central Chile (32º02'-33º57' S - 70º30'-70º30' W): Helcogrammoides chilensis, Scartichthys viridis, Auchenionchus microcirrhis, Gobiesox marmoratus, and Sicyases sanguineus; each specimen was analyzed for parasites and its total body length (LT) was measured. The total species richness, average richness, abundance, diversity, and dominance of parasites infracommunity (all parasites in a host specimen) were calculated. Each fish species was classified into three LT ranges, to calculate the indices of nestedness and average of these parasitological descriptors in each LT range. We used the models given in the NTCP (Nestedness Temperature Calculator Program) and NODF (Nestedness metric based on Overlap and Decreasing Fill), considering the presence or absence of parasite species; we also used WNODF (Weighted-NODF) model for parasite abundances. The average of parasitological descriptors and LT of each host species, as well as the indices of nestedness were also calculated and related one another, considering the infracommunity and component community levels. The parasite infracommunity of most fish species exhibited a nestedness pattern structure, with the exception of G. marmoratus and H. chilensis, in some of the LT ranges. No relationship between the nestedness indices and fish LT was found. Nevertheless, direct correlations were observed among nestedness indices, average of richness, abundance and diversity of parasite infracommunity, and an inverse correlation with the parasite total richness (per LT range). Moreover, the nestedness pattern was present in all host species. We concluded that the parasite communities of intertidal fish are structured and predictable, and determined only minimally by the host LTs and the aggregated characteristics of the parasites, particularly at the infracommunity level. Rev. Biol. Trop. 63 (4): 995-1005. Epub 2015 December 01.

Study of Liver Damage Mechanism in Mice Caused by the Incompatibility of Daphne genkwa Combined with Glycyrrhiza uralensis / 中国药房

OBJECTIVE:To study the liver damage mechanism in mice caused by the incompatibility of Daphne genkwa com-bined with Glycyrrhiza uralensis in aspect of liver transporter. METHODS:40 mice were equally randomized into a normal control (isometric normal saline)group,a group of G. uralensis [15 g(medicinal matierias)/kg],a group of D. genkwa [15 g(medicinal tatierias)/kg],a group of D. genkwa with G. uralensis in the ratio of 1∶1 [15 g(crude drug)/kg],a group of D. genkwa with G. uralensis in the ratio of 1∶3 [15 g(medicinal matierias)/kg](n=8). The mice were given the corresponding drug,ig,once a day for 7 consecutive days. HE staining was performed and then the pathomorphology of liver tissues were observed under the light mi-croscope,and calculation was made for pathological grading. Western blot method was employed to determine the protein expre-ssion of the transporter Ntcp protein in the livers of mice. The contents of total bile acids(TBA)in livers of mice were determined. RESULTS:Compared to the mice in the normal control group,those in the group of 1∶1 and 1∶3 demonstrated higher protein ex-pression of Ntcp. In the group of 1∶1,the mice with grade“+++”hepatocyte degeneration were more (8). The mice with grade“+++”and“++”hepatocyte degeneration in the groups of 1∶3 were more (2 and 8 respectively). CONCLUSIONS:D. genkwa combined with G. uralensis can induce liver damage in mice by a mechanism which may be related to the accumulation of a large amount of TBA in the liver as a result of the increase in the expression of Ntcp in mice.

Analysis on the Calculated Dose in the Lung Radiation Surgery Planning Using TomoTherpay / 의학물리

The applicability and feasibility of TomoTherapy in the lung radiation surgery was analyzed by comparison of the calculated dose distribution in TomoTherapy planning with the results of conventional IMRS (intensity modulated radiation surgery) using LINAC (linear accelerator). The acquired CT (computed tomograph) images of total 10 patients whose tumors' motion were less than 5 mm were used in the radiation surgery planning and the same prescribed dose and the same dose constraints were used between TomoTherapy and LINAC. The results of TomoTherapy planning fulfilled the dose requirement in GTV (gross tumor volume) and OAR (organ at risk) in the same with the conventional IMRS using LINAC. TomoTherapy was superior in the view point of low dose in the normal lung tissue and conventional LINAC was superior in the dose homogeneity in GTV. The calculated time for treatment beam delivery was long more than two times in TomoTherapy compared with the conventional LINAC. Based on the results in this study, TomoTherapy can be evaluated as an effective way of lung radiation surgery for the patients whose tumor motion is little when the optimal planning is produced considering patient's condition and suitability of dose distribution.

Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy / 대한방사선종양학회지

PURPOSE: To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). MATERIALS AND METHODS: We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. RESULTS: For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). CONCLUSION: We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.

Comparison of Helical TomoTherapy with Linear Accelerator Base Intensity-modulated Radiotherapy for Head & Neck Cases / 의학물리

TomoTherapy has a merit to treat cancer with Intensity modulated radiation and combines precise 3-D imaging from computerized tomography (CT scanning) with highly targeted radiation beams and rotating beamlets. In this paper, we comparing the dose distribution between TomoTherapy and linear accelerator based intensity modulated radiotherapy (IMRT) for 10 Head & Neck patients using TomoTherapy which is newly installed and operated at National Cancer Center since Sept. 2006. Furthermore, we estimate how the homogeneity and Normal Tissue Complication Probability (NTCP) are changed by motion of target. Inverse planning was carried out using CadPlan planning system (CadPlan R.6.4.7, Varian Medical System Inc. 3100 Hansen Way, Palo Alto, CA 94304-1129, USA). For each patient, an inverse IMRT plan was also made using TomoTherapy Hi-Art System (Hi-Art2_2_4 2.2.4.15, TomoTherapy Incorporated, 1240 Deming Way, Madson, WI 53717-1954, USA) and using the same targets and optimization goals. All TomoTherapy plans compared favorably with the IMRT plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Our results suggest that TomoTherapy is able to reduce the normal tissue complication probability (NTCP) further, keeping a similar target dose homogeneity.

Development of Conformal Radiotherapy with Respiratory Gate Device / 대한방사선종양학회지

PURPOSE: 3D conformal radiotherapy, the optimum dose delivered to the tumor and provided the risk of normal tissue unless marginal miss, was restricted by organ motion. For tumors in the thorax and abdomen, the planning target volume (PTV) is decided including the margin for movement of tumor volumes during treatment due to patients breathing. We designed the respiratory gating radiotherapy device (RGRD) for using during CT simulation, dose planning and beam delivery at identical breathing period conditions. Using RGRD, reducing the treatment margin for organ (thorax or abdomen) motion due to breathing and improve dose distribution for 3D conformal radiotherapy. MATERIALS AND METHODS: The internal organ motion data for lung cancer patients were obtained by examining the diaphragm in the supine position to find the position dependency. We made a respiratory gating radiotherapy device (RGRD) that is composed of a strip band, drug sensor, micro switch, and a connected on-off switch in a LINAC control box. During same breathing period by RGRD, spiral CT scan, virtual simulation, and 3D dose planing for lung cancer patients were performed, without an extended PTV margin for free breathing, and then the dose was delivered at the same positions. We calculated effective volumes and normal tissue complication probabilities (NTCP) using dose volume histograms for normal lung, and analyzed changes in doses associated with selected NTCP levels and tumor control probabilities (TCP) at these new dose levels. The effects of 3D conformal radiotherapy by RGRD were evaluated with DVH (Dose Volume Histogram), TCP, NTCP and dose statistics. RESULTS: The average movement of a diaphragm was 1.5 cm in the supine position when patients breathed freely. Depending on the location of the tumor, the magnitude of the PTV margin needs to be extended from 1 cm to 3 cm, which can greatly increase normal tissue irradiation, and hence, results in increase of the normal tissue complications probability. Simple and precise RGRD is very easy to setup on patients and is sensitive to length variation (+2 mm), it also delivers on-off information to patients and the LINAC machine. We evaluated the treatment plans of patients who had received conformal partial organ lung irradiation for the treatment of thorax malignancies. Using RGRD, the PTV margin by free breathing can be reduced about 2 cm for moving organs by breathing. TCP values are almost the same values (4-5% increased) for lung cancer regardless of increasing the PTV margin to 2.0 cm but NTCP values are rapidly increased (60-70% increased) for upon extending PTV margins by 2.0 cm. CONCLUSION: Internal organ motion due to breathing can be reduced effectively using our simple RGRD. This method can be used in clinical treatments to reduce organ motion induced margin, thereby reducing normal tissue irradiation. Using treatment planning software, the dose to normal tissues was analyzed by comparing dose statistics with and without RGRD. Potential benefits of radiotherapy derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through the evaluation of the lung cancer patients treated with 3D conformal radiotherapy.

The Study of Normal Tissue Complication Probability (NTCP) for Radiation Pneumonitis by Effective Volume Method / 대한치료방사선과학회지

PURPOSE: In radiation therapy, NTCP is very important indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. METHODS AND MATERIALS: From August 1993 to December 1994, thirty six patients with locally advanced non-small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutic agents were mitomycin C, vinblastine, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of radiation pneumonitis by CT scan, chest x-ray and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumonitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung. Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. RESULTS: Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients, 6 had grade I severity and 2 had grade II. The average NTCP value of the patients who showed radiation pneumonitis was significantly higher than that of the patients without pneumonitis (66% vs. 26.4%). But the results of pulmonary function test was not correlated with NTCP. CONCLUSION: NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to analyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.