Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses

<p>Abstract</p> <p>Background</p> <p>To compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning.</p> <p>Methods</p> <p>We analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images.</p> <p>Results</p> <p>Patients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (<it>P <</it>0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum.</p> <p>Conclusion</p> <p>The CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.</p

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA

Proctitis following stereotactic body radiation therapy for prostate cancer

Background Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. Methods Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. Results The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. Conclusions In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations

Interactions between metal ions and DNA

84 years elapsed between the announcements of the periodic table and that of the DNA double helix in 1953, and the two have been combined in many ways since then. In this chapter an outline of the fundamentals of DNA structure leads into a range of examples showing how the natural magnesium and potassium ions found in nature can be substituted in a diversity of applications. The dynamic structures found in nature have been studied in the more controlled but artificial environment of the DNA crystal using examples from sodium to platinum and also in a range of DNA-binding metal complexes. While NMR is an essential technique for studying nucleic acid structure and conformation, most of our knowledge of metal ion binding has come from X-ray crystallography. These days the structures studied, and therefore also the diversity of metal binding, go beyond the double helix to triplexes, hairpin loops, junctions and quadruplexes, and the chapter describes briefly how these pieces fit into the DNA jigsaw. In a final section, the roles of metal cations in the crystallisation of new DNA structures are discussed, along with an introduction to the versatility of the periodic table of absorption edges for nucleic acid structure determination