Durg Vijay Rai

Zinc as a nutritional approach to bone loss prevention in an ovariectomized rat model.

Objective In this study, we have investigated the role of zinc supplementation (a nutritional antioxidant) in an ovariectomized osteopenic rat model. Methods Forty-eight female Wistar rats were assigned to four groups: control, zinc, ovariectomy (OVX), and OVX + zinc. Analysis was performed to compare the study groups on bone metabolism markers, bone antioxidant enzymes, and zinc and copper levels in serum and bone tissues. Electron microscopy was also performed to assess morphological changes. Results Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. In the OVX + zinc group, these levels were regulated; however, estradiol levels were still significantly lower than those in controls. The OVX group showed significantly higher urinary excretion of hydroxyproline, which recovered upon zinc supplementation but was higher than normal levels. The activities of catalase and superoxide dismutase decreased in ovariectomized animals and up-regulated upon zinc supplementation. Zinc supplementation in the OVX group revoked reduced glutathione levels and elevated malondialdehyde levels. Reduction in zinc and copper levels was observed in the bone tissues and serum of the OVX group. Zinc administration restored these levels to normal. Electron microscopic studies revealed a looser structure and resorbed areas in ovariectomized rat cortical bone. Zinc administration restored bone tissue morphology. Conclusions These findings suggest that changes in cortical bone attributed to estrogen deficiency are arrested by zinc supplementation, which can be a sustainable approach to improving bone health.

Dose optimization in gynecological 3D image based interstitial brachytherapy using martinez universal perineal interstitial template (MUPIT) -an institutional experience

The aim of this study was to evaluate the dose optimization in 3D image based gynecological interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT). Axial CT image data set of 20 patients of gynecological cancer who underwent external radiotherapy and high dose rate (HDR) interstitial brachytherapy using MUPIT was employed to delineate clinical target volume (CTV) and organs at risk (OARs). Geometrical and graphical optimization were done for optimum CTV coverage and sparing of OARs. Coverage Index (CI), dose homogeneity index (DHI), overdose index (OI), dose non-uniformity ratio (DNR), external volume index (EI), conformity index (COIN) and dose volume parameters recommended by GEC-ESTRO were evaluated. The mean CTV, bladder and rectum volume were 137 ± 47cc, 106 ± 41cc and 50 ± 25cc, respectively. Mean CI, DHI and DNR were 0.86 ± 0.03, 0.69 ± 0.11 and 0.31 ± 0.09, while the mean OI, EI, and COIN were 0.08 ± 0.03, 0.07 ± 0.05 and 0.79 ± 0.05, respectively. The estimated mean CTV D90 was 76 ± 11Gy and D100 was 63 ± 9Gy. The different dosimetric parameters of bladder D2cc, D1cc and D0.1cc were 76 ± 11Gy, 81 ± 14Gy, and 98 ± 21Gy and of rectum/recto-sigmoid were 80 ± 17Gy, 85 ± 13Gy, and 124 ± 37Gy, respectively. Dose optimization yields superior coverage with optimal values of indices. Emerging data on 3D image based brachytherapy with reporting and clinical correlation of DVH parameters outcome is enterprizing and provides definite assistance in improving the quality of brachytherapy implants. DVH parameter for urethra in gynecological implants needs to be defined further.

A unified dose response relationship to predict high dose fractionation response in the lung cancer stereotactic body radiation therapy

Aim: This study is designed to investigate the superiority and applicability of the model among the linear-quadratic (LQ), linear-quadratic-linear (LQ-L) and universal-survival-curve (USC) models by fitting published radiation cell survival data of lung cancer cell lines. Materials and Method: The radiation cell survival data for small cell (SC) and non-small cell (NSC) lung cancer cell lines were obtained from published reports, and were used to determine the LQ and cell survival curve parameters, which ultimately were used in the curve fitting of the LQ, LQ-L and USC models. Results: The results of this study demonstrate that the LQ-L(Dt-mt) model, compared with the LQ and USC models, provides best fit with smooth and gradual transition to the linear portion of the curve at transition dose Dt-mt, where the LQ model loses its validity, and the LQ-L(Dt-2α/β) and USC(Dt-mt) models do not transition smoothly to the linear portion of the survival curve. Conclusion: The LQ-L(Dt-mt) model is able to fit wide variety of cell survival data over a very wide dose range, and retains the strength of the LQ model in the low-dose range.

Zinc Improves the Bone Mechanical Strength in Ovariectomized RatModel by Restoring Bone Composition and Hydroxyapatite CrystalliteDimension

Purpose: Osteoporosis is a bone metabolic disorder which is well known to increase bone porosity and is the outcome of various factors like ageing, genetic, nutritional deficiency, decreased calcium uptake, and last but the most important hormonal imbalances. Hormonal imbalance is one of the major factors affecting women worldwide and leading to osteoporosis. Trace elements play a very essential role in number of pathological conditions. Ingestion of zinc in the early stages of bone loss may be more beneficial in mitigating bone loss and also in improving the overall strength of the bone. In the current work, we have intended to extract the information pertaining to the mechanical strength of bone, bone tissue composition and hydroxyapatite crystallite size upon supplementing zinc in the osteopenic condition. Methods: Forty eight wistar female rats in two set of twenty four animals each were assigned to four groups: Control, Zinc, Ovariectomized (OVX) and OVX+Zinc. Duration of the treatment period was of eight weeks. Biochemical estimations were carried out to make comparison between the treatment groups based on bone metabolism markers in serum. Bone mechanical strength of both the bones i.e., femur and tibia, was assessed using texture analyzer. Also, bone matrix analysis using Fourier transformer infrared spectroscopy and X-ray diffraction studies were carried out for all the treatment groups. Results: Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. Zinc supplemented following ovariectomy regulated these levels. The OVX group showed significantly higher serum alkaline phosphatase levels, which recovered upon zinc supplementation. Further, zinc plays a potential role in preventing bone tissue deterioration by restoring its composition and microstructure in the post-menopausal condition, thereby, maintaining the mechanical strength of the bone. Conclusion: These findings suggested that alterations in the bone tissue material properties following estrogen deficiency can be averted by zinc if administered at early stages of bone loss.

SU‐F‐T‐37: Dosimetric Evaluation of Planned Versus Decay Corrected Treatment Plans for the Treatment of Tandem‐Based Cervical HDR Brachytherapy

PURPOSE This study evaluated dosimetric parameters for actual treatment plans versus decay corrected treatment plans for cervical HDR brachytherapy. METHODS 125 plans of 25 patients, who received 5 fractions of HDR brachytherapy, were evaluated in this study. Dose was prescribed to point A (ICRU-38) and High risk clinical tumor volume (HR-CTV) and organs at risk (OAR) were, retrospectively, delineated on original CT images by treating physician. First HDR plan was considered as reference plan and decay correction was applied to calculate treatment time for subsequent fractions, and was applied, retrospectively, to determine point A, HR-CTV D90, and rectum and bladder doses. RESULTS The differences between mean point A reference doses and the point A doses of the plans computed using decay times were found to be 1.05%±0.74% (-2.26% to 3.26%) for second fraction; -0.25%±0.84% (-3.03% to 3.29%) for third fraction; 0.04%±0.70% (-2.68% to 2.56%) for fourth fraction and 0.30%±0.81% (-3.93% to 2.67%) for fifth fraction. Overall mean point A dose difference, for all fractions, was 0.29%±0.38% (within ± 5%). Mean rectum and bladder dose differences were calculated to be -3.46%±0.12% and -2.47%±0.09%, for points, respectively, and -1.72%±0.09% and -0.96%±0.06%, for D2cc, respectively. HR-CTV D90 mean dose difference was found to be -1.67% ± 0.11%. There was no statistically significant difference between the reference planned point A doses and that calculated using decay time to the subsequent fractions (p<0.05). CONCLUSION This study reveals that a decay corrected treatment will provide comparable dosimetric results and can be utilized for subsequent fractions of cervical HDR brachytherapy instead of actual treatment planning. This approach will increase efficiency, decrease workload, reduce patient observation time between applicator insertion and treatment delivery. This would be particularly useful for institutions with limited resources or large patient populations with limited access to care.

Dosimetric evaluation of tandem-based cervical high-dose-rate brachytherapy treatment planning using American Brachytherapy Society 2011 recommendations

Purpose This study evaluated dosimetric parameters for cervical high-dose-rate (HDR) brachytherapy treatment using varying dose prescription methods. Methods This study includes 125 tandem-based cervical HDR brachytherapy treatment plans of 25 patients who received HDR brachytherapy. Delineation of high-risk clinical target volumes (HR-CTVs) and organ at risk were done on original computed tomographic images. The dose prescription point was defined as per International Commission in Radiation Units and Measurements Report Number 38 (ICRU-38), also redefined using American Brachytherapy Society (ABS) 2011 criteria. The coverage index (V 100 ) for each HR-CTV was calculated using dose volume histogram parameters. A plot between HR-CTV and V 100 was plotted using the best-fit linear regression line (least-square fit analysis). Results Mean prescribed dose to ICRU-38 Point A was 590·47±28·65 cGy, and to ABS Point A was 593·35±30·42 cGy. There was no statistically significant difference between planned ICRU-38 and calculated ABS Point A doses ( p =0·23). The plot between HR-CTV and V 100 is well defined by the best-fit linear regression line with a correlation coefficient of 0·9519. Conclusion For cervical HDR brachytherapy, dose prescription to an arbitrarily defined point (e.g., Point A) does not provide consistent coverage of HR-CTV. The difference in coverage between two dose prescription approaches increases with increasing CTV. Our ongoing work evaluates the dosimetric consequences of volumetric dose prescription approaches for these patients.

Anatomy-based definition of point A utilizing three-dimensional volumetric imaging approach for high-dose-rate (HDR) intracavitary brachytherapy dose prescription when treating cervical cancer using limited resources

This study was designed to determine whether volumetric imaging could identify consistent alternative prescription methods to Manchester/point A when prescribing radiation dose in the treatment of cervical cancer using HDR intracavitary brachytherapy (ICBT). One hundred and twenty-five treatment plans of 25 patients treated for carcinoma of the cervix were reviewed retrospectively. Each patient received 5 fractions of HDR ICBT following initial cisplatin-based pelvic chemoradiation, and radiation dose was originally prescribed to point A (ICRU-38). The gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV) were contoured in three dimensions on the CT datasets, and inferior-superior, anterior-posterior, and left-right dimensions HR-CTV were recorded along with multiple anatomic and skeletal dimensions for each patient. The least square-best fit regression lines were plotted between one half of the HR-CTV width and pelvic cavity dimension at femoral head level and at maximum cavity dimension. The points in both plots lie reasonably close to straight lines and are well defined by straight lines with slopes of 0.15 and 0.17; intercept on y-axes of -0.08 and -0.03, point A, at the same level as defined based on applicator coordinates, is defined using this correlation, which is a function of distance between femoral heads/dimensions of maximum pelvic cavity width. Both relations, defined by straight lines, provide an estimated location of point A, which provides adequate coverage to the HR-CTV compared to the point A defined based on applicator coordinates. The point A defined based on femoral head distance would, therefore, be a reasonable surrogate to use for dose prescription because of subjective variation of cavity width dimension. Simple surrogate anatomic/skeletal landmarks can be useful for prescribing radiation dose when treating cervical cancer using intracavitary brachytherapy in limited-resource settings. Our ongoing work will continue to refine these models. PACS number(s): 87.55.D-, 87.55.ne.This study was designed to determine whether volumetric imaging could identify consistent alternative prescription methods to Manchester/point A when prescribing radiation dose in the treatment of cervical cancer using HDR intracavitary brachytherapy (ICBT). One hundred and twenty‐five treatment plans of 25 patients treated for carcinoma of the cervix were reviewed retrospectively. Each patient received 5 fractions of HDR ICBT following initial cisplatin‐based pelvic chemoradiation, and radiation dose was originally prescribed to point A (ICRU‐38). The gross tumor volume (GTV) and high‐risk clinical target volume (HR‐CTV) were contoured in three dimensions on the CT datasets, and inferior–superior, anterior–posterior, and left–right dimensions HR‐CTV were recorded along with multiple anatomic and skeletal dimensions for each patient. The least square–best fit regression lines were plotted between one half of the HR‐CTV width and pelvic cavity dimension at femoral head level and at maximum cavity dimension. The points in both plots lie reasonably close to straight lines and are well defined by straight lines with slopes of 0.15 and 0.17; intercept on y‐axes of ‐0.08 and ‐0.03, point A, at the same level as defined based on applicator coordinates, is defined using this correlation, which is a function of distance between femoral heads/dimensions of maximum pelvic cavity width. Both relations, defined by straight lines, provide an estimated location of point A, which provides adequate coverage to the HR‐CTV compared to the point A defined based on applicator coordinates. The point A defined based on femoral head distance would, therefore, be a reasonable surrogate to use for dose prescription because of subjective variation of cavity width dimension. Simple surrogate anatomic/skeletal landmarks can be useful for prescribing radiation dose when treating cervical cancer using intracavitary brachytherapy in limited‐resource settings. Our ongoing work will continue to refine these models. PACS number(s): 87.55.D‐, 87.55.ne

Motion management of lung tumors: A retrospective analysis to see dosimetric differences in different respiratory phases

To study the effect of respiration (end expiration [EE] and end inspiration [EI]) on tumor and normal structure doses and volumes in carcinoma lung. Five patients with squamous cell carcinoma of the lung were selected for this retrospective study. Computerized tomography (CT) data set was subsequently obtained for all patients in EE and EI phases of the respiratory cycle. Gross tumor volume, clinical target volume, planning target volume (PTV) and organs at risk were delineated in both EE and EI on CT data sets. Prescribed dose was 60 Gy in 30 fractions for all patients. The PTV coverage and organs at risks (OARs) were evaluated using radiation therapy oncology group conformity indices (CI) and homogeneity indices (HI) and volume doses respectively. The CI and HI were comparable for both phases. Volumes of all OARs were comparable except the lung. OAR doses were almost same in both phases. Significantly higher normal lung volume was found in the EI phase. Based on our dosimetric data and statistical analysis we conclude that both EE and EI are dosimetrically comparable.

SU‐E‐T‐699: Dosimetric Evaluation of Tandem‐Based Cervical HDR Brachytherapy Treatment Planning Using ABS 2011 Recommendations

Purpose: This study evaluated dosimetric parameters for cervical HDR brachytherapy treatment using varying dose prescription methods. Methods: We evaluated 20 unique tandem‐based cervical HDR brachytherapy treatment plans. Radiotherapy dose was originally prescribed to a defined point (Point A, ICRU‐report 38) for all plans. For this study, tumor volumes (HR‐CTV) and organs at risk (OAR) were retrospectively delineated on the original 3D treatment planning CT datasets by the original treating physicians. We also carefully redefined the dose prescription point using ABS 2011 criteria. The coverage index (V100) for each HR‐CTV was calculated using DVH parameters. A plot between HR‐CTV volume (V) and V100 was generated using the best fit linear regression line (least‐square fit analysis). Results: Mean prescribed dose to Point A (average of Rt and Lt point A doses) was 590.47 cGy ± 28.65cGy (range 499.10–612.45cGy; 95%CI 586.73–594.22cGy). Mean prescribed dose to ABS 2011 point A (average of Rt and Lt points) was 593.35 cGy ± 30.42cGyrange 501.00–625.50cGy; 95%CI 589.38–597.32cGy). There was no statistically significant difference between the original planned point A and new calculated ABS point A doses (p=0.23, paired t‐student test). The plot between V and V100 was well defined and was described by the best fit linear regression line: V100= −0.0064V+1.0858, with correlation coefficient of 0.9519. Therefore, as V increases the coverage index decreases: when V 95%; when V>20cc and 29cc, V100<90%. Conclusion: For cervical HDR brachytherapy, dose prescription to an arbitrarily defined point (e.g., point A) does not provide consistent coverage of HR‐CTV. The difference in coverage between the two dose prescription approaches increases with increasing CTV volume. Our ongoing work evaluates the dosimetric consequences of volumetric dose prescription approaches for these patients.

Ovariectomy and its Antioxidative Effect on Bone

Ovarian hormone deficiency increases the generation of reactive oxygen species. Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. There is increasing evidence of the role of free radicals in bone resorption and bone loss. Ovariectomised female wistar rats had been used as the animal model for the study of osteoporosis. Even though, there are studies portraying the role of free radicals in bone loss, the defense mechanism adapted by bone in ovariectomised animals remains obscure. So, the impact of ovariectomy on the bone antioxidant system in rats was investigated. Twenty female wistar rats were taken and divided into two groups: ovariectomised and control. It had been found that a significant (p<0.001) decrease in the activity of various enzymes like CAT (catalase), SOD (superoxide dismutase) (p<0.001), GST (glutathione-s-transferase). However, an increase in the malondialdehyde levels was found to be 30% in the ovariectomised rats as compared to the controls. Thus the study elucidates the oxidative stress in bone under ovariectomy.Copyright