Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

BACKGROUND: To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. METHODS: From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months. RESULTS: Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late > or = grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001). DISCUSSION: GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

PROBABILISTIC MODELING OF RAINFALL INDUCED LANDSLIDE HAZARD ASSESSMENT IN SAN JUAN LA LAGUNA, SOLOLÁ, GUATEMALA

The municipality of San Juan La Laguna, Guatemala is home to approximately 5,200 people and located on the western side of the Lake Atitlán caldera. Steep slopes surround all but the eastern side of San Juan. The Lake Atitlán watershed is susceptible to many natural hazards, but most predictable are the landslides that can occur annually with each rainy season, especially during high-intensity events. Hurricane Stan hit Guatemala in October 2005; the resulting flooding and landslides devastated the Atitlán region. Locations of landslide and non-landslide points were obtained from field observations and orthophotos taken following Hurricane Stan. This study used data from multiple attributes, at every landslide and non-landslide point, and applied different multivariate analyses to optimize a model for landslides prediction during high-intensity precipitation events like Hurricane Stan. The attributes considered in this study are: geology, geomorphology, distance to faults and streams, land use, slope, aspect, curvature, plan curvature, profile curvature and topographic wetness index. The attributes were pre-evaluated for their ability to predict landslides using four different attribute evaluators, all available in the open source data mining software Weka: filtered subset, information gain, gain ratio and chi-squared. Three multivariate algorithms (decision tree J48, logistic regression and BayesNet) were optimized for landslide prediction using different attributes. The following statistical parameters were used to evaluate model accuracy: precision, recall, F measure and area under the receiver operating characteristic (ROC) curve. The algorithm BayesNet yielded the most accurate model and was used to build a probability map of landslide initiation points. The probability map developed in this study was also compared to the results of a bivariate landslide susceptibility analysis conducted for the watershed, encompassing Lake Atitlán and San Juan. Landslides from Tropical Storm Agatha 2010 were used to independently validate this study’s multivariate model and the bivariate model. The ultimate aim of this study is to share the methodology and results with municipal contacts from the author's time as a U.S. Peace Corps volunteer, to facilitate more effective future landslide hazard planning and mitigation.

An Isopach Map and Discussion of the Marine Jurassic of Western United Sates and Canada

Recent demands for petroleum to carry on the war effort have resulted in widespread prospecting in the northern Great Plains. Nearly all oil wells now drilled are of a depth to penetrate the marine Jurassic formations. It is known that these strata differ in thickness from place to place, but information of distribution, thickness, and lithology has not yet been compiled.

A Discussion of the Geology and an Isopach Map of the Pennsylvanian System in Wyoming and Adjacent Areas

Pennsylvanian strata in Wyoming and adjacent areas have been the subject of much work and discussion. Most of the work has been due to the economic importance of the system as an oil producer in this region. Oil production from strata of Pennsylvanian age is rather recent history; and therefore, much of the available information is local­ized and incomplete.

An Isopach Map and a Discussion of the Permian in Wyoming and Adjacent Areas

The accelerated post-war demand for petroleum products with resultant high prices and dwindling reserves has spurred producers to an extensive search for new fields and for ad­ditional production in known fields. Exploration and discov­ery is dependent on the collection and correlation of vast amounts of data both in the field and that found in liter­ature.

An Isopach Map and a Discussion of the Cambrian Strata in the Central Cordilleran Area

In the past few years intensive studies have been going on concerning Cambrian formations as a locale for orebodies. Many of the dolomites and limestones of southwestern Montana are susceptible to replacement by mineralizing solutions, especially when overlain by a rather impervious layer of shale, as is the Pilgrim limestone of Upper Cambrian time.

An Isopach Map and Discussion of Triassic Strata in Southern Montana and Wyoming

Oil and gas have been found in the Triassic strata of Wyoming. Although the Triassic has not as yet proven to be a large producing horizon it is very probable that ad­ditional oil will be found in Triassic strata in the future, and it is one of the goals at which oil well drillers aim their tools.

On Graphically Checking Goodness-of-fit of Binary Logistic Regression Models

OBJECTIVES: This paper is concerned with checking goodness-of-fit of binary logistic regression models. For the practitioners of data analysis, the broad classes of procedures for checking goodness-of-fit available in the literature are described. The challenges of model checking in the context of binary logistic regression are reviewed. As a viable solution, a simple graphical procedure for checking goodness-of-fit is proposed. METHODS: The graphical procedure proposed relies on pieces of information available from any logistic analysis; the focus is on combining and presenting these in an informative way. RESULTS: The information gained using this approach is presented with three examples. In the discussion, the proposed method is put into context and compared with other graphical procedures for checking goodness-of-fit of binary logistic models available in the literature. CONCLUSION: A simple graphical method can significantly improve the understanding of any logistic regression analysis and help to prevent faulty conclusions.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

Dextran sulfate modulates MAP kinase signaling and reduces endothelial injury in a rat aortic clamping model

OBJECTIVE: Mitogen-activated protein kinases (MAPKs), including JNK, p38, and ERK1/2, noticeably influence ischemia/reperfusion injury (IRI). The complement inhibitor dextran sulfate (DXS) associates with damaged endothelium denudated of its heparan sulfate proteoglycan (HSPG) layer. Other glycosaminoglycan analogs are known to influence MAPK signaling. Hypothetically therefore, targeted intravascular cytoprotection by DXS may function in part through influencing MAPK activation to reduce IRI-induced damage of the vasculature. METHODS: IRI of the infrarenal aorta of male Wistar rats was induced by 90 minutes clamping followed by 120 minutes reperfusion. DXS (5 mg/mL) or physiologic saline (NaCl controls) was infused locally into the ischemic aortic segment immediately prior to reperfusion. Ninety minutes ischemia-only and heparinase infusion (maximal damage) experiments, as well as native rat aorta, served as controls. Aortas were excised following termination of the experiments for further analysis. RESULTS: DXS significantly inhibited IRI-induced JNK and ERK1/2 activation (P = .043; P =.005) without influencing the p38 pathway (P =.110). Reduced aortic injury, with significant inhibition of apoptosis (P = .032 for DXS vs NaCl), correlated with decreased nuclear factor kappaB translocation within the aortic wall. DXS treatment clearly reduced C1q, C4b/c, C3b/c, and C9 complement deposition, whilst preserving endothelial cell integrity and reducing reperfusion-induced HSPG shedding. Protection was associated with binding of fluorescein labeled DXS to ischemically damaged tissue. CONCLUSIONS: Local application of DXS into ischemic vasculature immediately prior to reperfusion reduces complement deposition and preserves endothelial integrity, partially through modulating activation of MAPKs and may offer a new approach to tackle IRI in vascular surgical procedures. CLINICAL RELEVANCE: The purpose of the present study was to determine the role of dextran sulfate (DXS), a glycosaminoglycan analog and complement inhibitor, in modulating intracellular MAPK signaling pathways, reducing complement activation and ultimately attenuating ischemia/reperfusion injury (IRI) in a rat aortic-clamping model, in part a surrogate model to study the microvasculature. The study shows a role for DXS in ameliorating endothelial injury by reducing IRI-mediated damage and intravascular, local inflammation in the affected aortic segment. DXS may be envisaged as an endothelial protectant in vascular injury, such as occurs during vascular surgical procedures.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.