M Ferreira

Transition on the entropic elasticity of DNA induced by intercalating molecules

We use optical tweezers to perform stretching experiments on DNA molecules when interacting with the drugs daunomycin and ethidium bromide, which intercalate the DNA molecule. Our results show that the persistence length of the DNA-drug complexes increases strongly as the drug concentration increases up to some critical value. Above this critical value, the persistence length decreases abruptly and remains approximately constant for larger drug concentrations, at least in the concentration range used in our experiments. Measured intercalators critical concentrations for the persistence length transition coincide with the reported values for the helix-coil transition of DNA-drug complexes obtained from sedimentation experiments. The contour length of the molecules increases monotonically and saturates as the drug concentration increases. The neighbor exclusion model fits to our results for the total drug concentration as a function of the relative increase of the contour length.

Neurofibromatosis type 1: more frequent and severe then usually thought

OBJECTIVE To study prevalence of clinical features among Brazilian patients diagnosed with neurofibromatosis type 1(NF1), comparing these features with international data to evaluate the severity and visibility of the disease and quantify less frequent manifestations such as short stature, macrocephaly, muscle strength, voice abnormalities and oral motor disorders. METHODS 183 patients diagnosed with NF1, attended at the Neurofibromatosis Outpatient Reference Center, were evaluated for clinical manifestations and complications of NF1. Severity and visibility were verified using the Riccardi and Ablon scales respectively. Voice abnormalities and oral motor disorders were quantified using the Vox-Metria software and maximal voluntary muscle strength (MVMS) was quantified using a handgrip dynamometer. RESULTS Clinical manifestations of NF1 observed were comparable to those described in literature. However, more then 50% of patients presented severity and visibility classified as moderate and severe. The incidence of macrocephaly and short stature was higher among the Brazilian patients. Voice abnormalities and oral motor disorders were quantified for the first time, with hoarseness and oral motor disorders observed in more then 60% the patients. Maximal voluntary muscle strength was found to be reduced in 67% of patients. CONCLUSION The main clinical features of these patients are similar to those reported in previous studies. More then one-half of the patients presented moderate and severe levels of NF1 (severity and visibility), including short stature, macrocephaly, voice abnormalities and oral motor disorders and decreased muscle strength. These results are in disagreement with the traditional concept that NF1 is a benign disease and also disclosed some clinical aspects not previously reported.

Total error shift patterns for daily CT on rails image-guided radiotherapy to the prostate bed

BackgroundTo evaluate the daily total error shift patterns on post-prostatectomy patients undergoing image guided radiotherapy (IGRT) with a diagnostic quality computer tomography (CT) on rails system.MethodsA total of 17 consecutive post-prostatectomy patients receiving adjuvant or salvage IMRT using CT-on-rails IGRT were analyzed. The prostate beds daily total error shifts were evaluated for a total of 661 CT scans.ResultsIn the right-left, cranial-caudal, and posterior-anterior directions, 11.5%, 9.2%, and 6.5% of the 661 scans required no position adjustments; 75.3%, 66.1%, and 56.8% required a shift of 1 - 5 mm; 11.5%, 20.9%, and 31.2% required a shift of 6 - 10 mm; and 1.7%, 3.8%, and 5.5% required a shift of more than 10 mm, respectively. There was evidence of correlation between the x and y, x and z, and y and z axes in 3, 3, and 3 of 17 patients, respectively. Univariate (ANOVA) analysis showed that the total error pattern was random in the x, y, and z axis for 10, 5, and 2 of 17 patients, respectively, and systematic for the rest. Multivariate (MANOVA) analysis showed that the (x,y), (x,z), (y,z), and (x, y, z) total error pattern was random in 5, 1, 1, and 1 of 17 patients, respectively, and systematic for the rest.ConclusionsThe overall daily total error shift pattern for these 17 patients simulated with an empty bladder, and treated with CT on rails IGRT was predominantly systematic. Despite this, the temporal vector trends showed complex behaviors and unpredictable changes in magnitude and direction. These findings highlight the importance of using daily IGRT in post-prostatectomy patients.

Plexiform neurofibroma: an unusual cause of GI bleeding and intestinal obstruction.

ulating an intrahepatic mass. Am J Gastroenterol 1979;72:75-8. 9. Epstein BM, Conidaris C. Pseudocysts involving the left lobe of the liver: CT demonstration. Br J Radiol 1982;55:928-30. 10. Ammann R, Munch R, Largiader F, et al. Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis. Gastroenterology 1992;103:560-5. 11. Les I, Cordoba V, Guarner R, et al. Pancreatic pseudocyst located in the liver. Rev Esp Enferm Dig 2006;98:616-20. 12. Lantink JA, Heggelman BGF, Geerdink RA. Intrahepatic rupture of a pancreatic pseudocyst: sonographic and CT demonstration. AJR Am J Roentgenol 1989;152:1129. 13. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology 1991;100:1362-70. 14. Lehman GA. Pseudocysts. Gastrointest Endosc 1999;49:S81-4. 15. Bhasin DK, Rana SK, Chandail VS, et al. An intra-hepatic pancreatic pseudocyst successfully treated endoscopic transpapillary drainage alone. JOP 2005;6:593-7. 16. Siegelman SS, Copeland BE, Saba GP, et al. CT of fluid collections associated with pancreatitis. AJR Am J Roentgenol 1980;134: 1121-32. 17. Lederman E, Cajot O, Canva-Delcambre V, et al. Pseudocysts in the left hepatic lobe: an unusual complication of acute pancreatitis. Gastroenterol Clin Biol 1997;2:340-1. 18. Wang SJ, Chen JJ, Changchien CS, et al. Sequential invasions of pancreatic pseudocysts in pancreatic tail, hepatic left lobe, caudate lobe, and spleen. Pancreas 1993;8:133-6. 19. Atienza P, Couturier D, Grandjouan S, et al. Intrahepatic liquid collections of pancreatic origin. One case and a review of the literature. Presse Med 1987;16:1195-8. 20. Roche J, Frairot A, Volle L, et al. Intrahepatic localization of pancreatic pseudocyst. Treatment by simple puncture under ultrasonography. Presse Med 1987;16:2230. 21. Gautier-Benoit C, Luez J, Cecile JP. Pseudocyst of the pancreas with intrahepatic development [French]. Sem Hôp 1974;50:1235-7. 22. Quevedo FC, Achille P, De Franco MF. Pancreatic pseudocysts involving the liver and the spleen. Report of 2 cases. Rev Hosp Clin Fac Med Sào Paulo 1975;30:371-4. 23. Hospitel S, Guinot B, Teyssou H, et al. Intrahepatic false cysts of the pancreas. J Radiol 1983;64:355-8. 24. Kralik J, Pesula E. A pancreatic pseudocyst in the liver. Rozhl Chir 1993; 72:91-3. 25. Shimayama T, Katsuki T, Kosai S, et al. A case of pancreatic pseudocyst intruded into the right lobe of the liver. Nippon Shokakibyo Gakkai Zasshi 1988;85:1708-11. 26. Hamm VB, Franzen N. Atypically located pancreatic pseudocyst in liver, spleen, stomach wall and mediastinum: their CT diagnosis. Rofo 1993;159:522-7. 27. Gumaste VV, Dave PB. Pancreatic pseudocyst drainage: the needle or the scalpel? J Clin Gastroenterol 1991;13:500-5. 28. Carr-Locke DL, Gregg JA. Endoscopic manometry of pancreatic and biliary sphincter zones in man: basal results in healthy volunteers. Dig Dis Sci 1981;26:7-15. 29. Brennan PM, Stefaniak T, Palmer KR, et al. Endoscopic transpapillary stenting of pancreatic duct disruption. Dig Surg 2006;23:250-4. 30. Varadarajulu S, Noone TC, Tutuian R, et al. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. Gastrointest Endosc 2005;61:568-75. 31. Telford J, Farrell JJ, Saltzman JR, et al. Pancreatic stent placement for duct disruption. Gastrointest Endosc 2002;56:18-24.

SU-E-T-352: Why Is the Survival Rate Low in Oropharyngeal Squamous Cell Carcinoma?

PURPOSE Tumors are composed of a large number of clonogens that have the capability of indefinite reproduction. Even when there is complete clinical or radiographic regression of the gross tumor mass after treatment, tumor recurrence can occur if the clonogens are not completely eradicated by radiotherapy. This study was to investigate the colonogen number and its association with the tumor control probability (TCP) in oropharyngeal squamous cell carcinoma (OSCCA). METHODS A literature search was conducted to collect clinical information of patients with OSCCA, including the prescription dose, tumor volume and survival rate. The linear-quadratic (LQ) model was incorporated into TCP model for clinical data analysis. The total dose ranged from 60 to 70 Gy and tumor volume ranged from 10 to 50 cc. The TCP was calculated for each group according to tumor size and dose. The least χ2 method was used to fit the TCP calculation to clinical data while other LQ model parameters (α, β) were adopted from the literature, due to the limited patient data. RESULTS A total of 190 patients with T2-T4 OSCCA were included. The association with HPV was not available for all the patients. The 3-year survival rate was about 82% for T2 squamous cell carcinoma and 40% for advanced tumors. Fitting the TCP model to the survival data, the average clonogen number was 1.56×1012 . For the prescription dose of 70 Gy, the calculated TCP ranged from 40% to 90% when the tumor volume varied from 10 to 50 cc. CONCLUSION Our data suggests variation between the clonogen number and TCP in OSCCA. Tumors with larger colonogen number tend to have lower TCP and therefore dose escalation above 70 Gy may be indicated in order to improve the TCP and survival rate. Our result will require future confirmation with a large number of patients.

SU-E-T-112: Dose Distribution of Praseodymium-142 Microspheres in Microcapillary Using Radiochromic Film Dosimetry and Applications in Hepatocellular Carcinoma Microsphere Brachytherapy.

PURPOSE This work verified simulations of beta-minus emitter Praseodymium-142 (Pr-142) for microsphere brachytherapy by performing absolute dose measurements for Pr 142 microspheres in a microcapillary as a simplified model for a single blood vessel for the treatment of Hepatocellular Carcinoma (HCC). METHODS Pr-142 microspheres (mass: 0.169g, average diameter: 29.7±3.9μm) were activated by thermal neutron activation at the University of Missouri Research Reactor. Experimental setup consisted of a microsphere solution (initial activity 36.6mCi in 0.1ml of sterile water) within a glass microcapillary (internal and external diameter: 305μm and 453μm, respectively) placed for 51h in a custom made Gammex Solid Water™ phantom. GAFCHROMIC™ EBT2 film calibrated with a 6MeV electron beam was used to access the dose fall-off of microspheres. The microcapillary was modeled in MCNPX2.6 in order to compare with experiments. RESULTS The radial dose fall-off on the transverse plane due to scatter and attenuation in the solid water phantom was analyzed using ImageJ for both film and MCNPX2.6 simulations. Isodose analysis showed close agreement among the methods used, i.e. measurements and simulations agree within 3.9% for doses below 1600cGy. Experimental and simulated doses obtained at 0.5 cm radially from the source were 1547cGy and 1610cGy respectively. Discrepancies for points close to the microcapillary surface were observed between MCNPX2.6 and measurements due to film saturation for high doses. Dose due to Pr-142 3.7% gamma emission was below the threshold of detection for the film. CONCLUSION A detailed dosimetric study was performed for Pr-142 glass microspheres within a single microcapillary. MCNPX2.6 simulations were verified by means of direct measurement. Based on these results, Pr-142 appears to be a viable choice of radionuclide for treating HCC.

SU-E-T-216: Intercomparison of CyberKnife and GammaKnife Stereotactic Radiosurgery Treatment Plans for Metastatic Brain Tumors

PURPOSE Over 40,000 patients are treated annually for metastatic brain tumors. A common method of treatment for these patients is stereotactic radiosurgery (SRS). Two commercially available options for treatment of SRS are the CyberKnife and GammaKnife. The purpose of this work was to perform a detailed comparison of the quality of the two techniques for the treatment of metastatic brain tumors using quantitative parameters. METHODS Six patients with small metastatic brain tumors (Range: 2.2cc- 14.6cc) that had previously received SRS treatment via the GammaKnife system were planned for equivalent treatment using the CyberKnife treatment planning system. To quantify the quality of the individual plans, the conformity number (CN), homogeneity index (HI) and gradient score index (GSI) were measured and compared. Both plans were created to delivery equivalent tumor coverage (Range: 10-14Gy) to the equivalent prescription volume. This was typically 99% prescription dose coverage to the GTV for both plans. RESULTS The calculated average HI was 0.497±0.155 versus 0.600±0.049, CI was 0.596±0.159 versus 0.865±0.022, and GSI was 41.4±17.8 versus 65.1±20.09 for CyberKnife vs GammaKnife respectively. Lower HI values imply a higher uniformity of dose throughout the target. CI ideally would be 1.000, and the closest to this value is to one, the better is the conformality to the treated site. High values for GSI implies a steeper dose falloff from the tumor to normal tissue and therefore is preferable. For this study statistical significance was achieved for CI, however due to the small sample size differences in HI and GSI were not statistically significant. CONCLUSION This data suggests that SRS treatments on CyberKnife and GammaKnife are of similar quality, with Gamma Knife able to deliver a slightly more conformal plan for the treatment of brain metastases.

SU‐E‐J‐183: Modeling of a Single Blood Vessel Embolized with Yttrium‐90 Or Praseodymium‐142 Glass Microspheres Using Monte Carlo Simulation

Purpose: To develop a realistic model for the dosimetric distribution and to evaluate biological effective dose (BED) of Praseodymium‐142 (Pr‐142) and Yttrium (Y‐90) glass microspheres in blood vessel within tumor for treating hepatocellular carcinoma (HCC). Methods: Blood vessels filled with uniformly distributed microspheres were modeled and positioned along the central axis of the tumor. Cylindrical blood vessels had diameters ranging from 25.0 to 75.0 μm, while tumor radii were varied from 0.2 to 1.0 cm, based on average values reported in the literature. Physical dose distributions due to a single blood vessel were simulated using Monte Carlo (MCNPX2.6) for large combinations of blood vessel and tumor sizes. HCC doubling times (DT) ranging from 17 to 720 days were used as a parameter in the BED calculations. To quantify the BED coverage throughout the entire tumor volume, a BED volume histogram (BEDVH) was calculated for each nuclide. Results: The physical dose distribution for both nuclides was comparable, e.g. dose per decay of 1.95 × 10−12 Gy and 2.36 × 10−12 Gy were obtained for Pr‐142 and 90‐Y point source at the same point, respectively. Pr‐142 distribution yielded higher BED coverage of the tumor volume for all DT, blood vessel sizes, and tumor sizes. The differences were higher for fast proliferating tumors and smaller tumor and blood vessel sizes, e.g. for 17 days DT, 20 μm blood vessel diameter and 0.2 cm tumor radius, BED coverage of 150 Gy was 48.7 % higher for Pr‐142. Conclusion: Blood vessels modeled within tumors made possible the quantification of the dose range due to a single embolized blood vessel. From BEDVH evaluation it appeared that the biological effectiveness throughout the tumor was sensiμtive to the radionuclide used, tumor sizes, and blood vessel sizes. The work was partially supported by a Ralph E. Powe Junior Faculty Enhancement Award provided by Oak Ridge Associated Universities.

WE‐A‐BRB‐08: Dosimetric Investigation of Praseodymium‐142 Microspheres for Microsphere Brachytherapy of Nonresectable Hepatic Tumor

Purpose: To evaluate the dosimetric parameters of Praseodymium‐142 (1 4 2Pr) glass microspheres and its potential application in microsphere brachytherapy of nonresectable hepatic tumor for faster dose delivery and facilitated quality assurance, while maintaining comparable dose distribution of the currently used radionuclides. Methods:Dose profiles for a 1 4 2Pr point source were obtained using BRAIN‐DOSE dose point kernel code and MCNPX2.6 Monte Carlo simulation. Microspheres containing 14 2Pr were studied and their dose distributions were compared to the doses of the currently used radionuclide Yittrium‐90 (9 0Y). Dose distributions due to glass microspheres ensembles within different sizes of spherical tumors were simulated. Physical properties, e.g. time to deliver 90% of the total dose for 1 4 2Pr and 9 0Y, were studied. Results:Dose rates from BRAIN‐ DOSE calculation for ‘ 1 4 2Pr and 9 0Y were 4.42 mGy/hr and 5.53 mGy/hr at 0.5 cm away from a 1 μCi source. From MCNPX2.6 the beta dose per decay at the tumor center for 142Pr and 9 0Y were 2.02 × 10−12 Gy and 2.36 × 10−12 Gy, respectively, for a tumor of 2.5 cm radius. For this case, simulation showed that the total dose in the tumor vicinity and therefore to adjacent organs due to the gamma yield was small, e.g. 0.03 Gy at 10 cm from the tumor center for 150 Gy total physical dose.Conclusions: Total dose per decay due to beta emissions were similar for both 1 4 2Pr and 9 0Y. Shorter half‐life is an advantage of ‘ 1 4 2Pr, enabling faster dose delivery. The physical properties of 1 4 2Pr make it suitable for microsphere brachytherapy. Total gamma contribution of 1 4 2Pr was small, therefore may not be clinically relevant. Gamma radiation, however, opens possibilities for quality assurance, biodistribution imaging and dose distribution assessments.

SU‐GG‐T‐373: The Effect of Vessel Material on Fricke Dosimeter Yield

Purpose: To investigate the effect of solid water vessel in contact with the fricke dosimeter yield in terms of surface to volume ratio and storage time. Material and methods: Fricke solution was made up with the highest pure commercial available chemicals. The optical density was measured using the Varian Cary 400 UV‐Vis spectrophotometer provided with a temperature controller. Three set of ten cylindrical containers (internal radius of 0.5 cm and height 3.5 cm) were made of solid water, polystyrene, and PMMA. Containers have been filled with fricke solution of 4.3, 4.5, and 5 cm−1surface to volume ration, and sealed with Mylar material. Optical density readings at 304 nm were performed in 120 minutes time interval, 30 minute step. The effects of solid water material on the Fricke dosimeter yield (surface to volume ratio and storage time) were compared against those values obtained for polystyrene and PMMA materials. Results: The deviation of the optical density for a surface to volume ratio ranging from 4.3 to 5 cm−1 was 0.01%, 0.01%, and 0.02% for PMMA, Polystyrene, and solid water, respectively. The maximum deviation among the different materials in the same surface to volume ratio range did not exceed 0.04%. Within the uncertainty of measurement (0.06%) no effect of solid water, polystyrene, and PMMA containers was observed on the Fricke dosimeter yield during the storage time interval of 120 minutes. Conclusion: Solid water plastic can be used to store Fricke solution and can still be comparable to polystyrene and PMMA. It has the advantage to have physical properties very close to water. Keywords:Surface to volume ratio, PMMA, Fricke dosimeter yield, solid water