Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration

Background: Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. Objective: To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. Design, setting, and participants: This is a retrospective, international, multi-institutional cohort analysis. There was amedian follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. Intervention: Open SRP. Measurements: BCR after SRP was defined as a serum prostate-specific antigen (PSA) >= 0.1 or >= 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancerspecific death. Results and limitations: Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period. Conclusions: In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in > 75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Cost-Effectiveness of Palliation of Unresectable Esophageal Cancer

Introduction Different modalities of palliation for obstructive symptoms in patients with unresectable esophageal cancer (EC) exist. However, these therapeutic alternatives have significant differences in costs and effectiveness. Methods A Markov model was designed to compare the cost-effectiveness (CE) of self-expandable stent (SES), brachytherapy and laser in the palliation of unresectable EC. Patients were assigned to one of the strategies, and the improvement in swallowing function was compared given the treatment efficacy, probability of survival, and risks of complications associated to each strategy. Probabilities and parameters for distribution were based on a 9-month time frame. Results Under the base-case scenario, laser has the lowest CE ratio, followed by brachytherapy at an incremental cost-effectiveness ratio (ICER) of $4,400.00, and SES is a dominated strategy. In the probabilistic analysis, laser is the strategy with the highest probability of cost-effectiveness for willingness to pay (WTP) values lower than $3,201 and brachytherapy for all WTP yielding a positive net health benefit (NHB) (threshold $4,440). The highest probability of cost-effectiveness for brachytherapy is 96%, and consequently, selection of suboptimal strategies can lead to opportunity losses for the US health system, ranging from US$ 4.32 to US$ 38.09 million dollars over the next 5-20 years. Conclusion Conditional to the WTP and current US Medicare costs, palliation of unresectable esophageal cancers with brachytherapy provides the largest amount of NHB and is the strategy with the highest probability of CE. However, some level of uncertainly remains, and wrong decisions will be made until further knowledge is acquired.

Cost-effectiveness analysis of routine rotavirus vaccination in Brazil

Objective. The objective of this study was to conduct a cost-effectiveness analysis of a universal rotavirus vaccination program among children : 5 years of age in Brazil. Methods. Considering a hypothetical annual cohort of approximately 3 300 000 newborns followed over 5 years, a decision-tree model was constructed to examine the possible clinical and economic effects of rotavirus infection with and without routine vaccination of children. Probabilities and unit costs were derived from published research and national administrative data. The impact of different estimates for key parameters was studied using sensitivity analysis. The analysis was conducted from both healthcare system and societal perspectives. Results. The vaccination program was estimated to prevent approximately 1735 351 (54%) of the 3 210 361 cases of rotavirus gastroenteritis and 703 (75%) of 933 rotavirus-associated deaths during the 5-year period. At a vaccine price of 18.6 Brazilian reais (R$) per dose, this program would cost R$121 673 966 and would save R$38 536 514 in direct costs to the public healthcare system and R$71 778 377 in direct and indirect costs to society. The program was estimated to cost R$1 028 and R$1 713 per life-years saved (LYS)from the societal and healthcare system perspectives, respectively. Conclusions. Universal rotavirus vaccination was a cost-effective strategy for both perspectives. However, these findings are highly sensitive to diarrhea incidence rate, proportion of severe cases, vaccine coverage, and vaccine price.

A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.

A Comparison of Bayesian and Sampling Theory Inferences in a Probit Model

HE PROBIT MODEL IS A POPULAR DEVICE for explaining binary choice decisions in econometrics. It has been used to describe choices such as labor force participation, travel mode, home ownership, and type of education. These and many more examples can be found in papers by Amemiya (1981) and Maddala (1983). Given the contribution of economics towards explaining such choices, and given the nature of data that are collected, prior information on the relationship between a choice probability and several explanatory variables frequently exists. Bayesian inference is a convenient vehicle for including such prior information. Given the increasing popularity of Bayesian inference it is useful to ask whether inferences from a probit model are sensitive to a choice between Bayesian and sampling theory techniques. Of interest is the sensitivity of inference on coefficients, probabilities, and elasticities. We consider these issues in a model designed to explain choice between fixed and variable interest rate mortgages. Two Bayesian priors are employed: a uniform prior on the coefficients, designed to be noninformative for the coefficients, and an inequality restricted prior on the signs of the coefficients. We often know, a priori, whether increasing the value of a particular explanatory variable will have a positive or negative effect on a choice probability. This knowledge can be captured by using a prior probability density function (pdf) that is truncated to be positive or negative. Thus, three sets of results are compared:those from maximum likelihood (ML) estimation, those from Bayesian estimation with an unrestricted uniform prior on the coefficients, and those from Bayesian estimation with a uniform prior truncated to accommodate inequality restrictions on the coefficients.

The use and abuse of population viability analysis

A recent study by Brook ef al. empirically tested the performance of population viability analysis (PVA) using data from 21 populations across a wide range of species. The study concluded that PVAs are good at predicting the future dynamics of populations. We suggest that this conclusion is a result of a bias in the studies that Brook et al, included in their analyses, We present arguments that PVAs can only be accurate at predicting extinction probabilities if data are extensive and reliable, and if the distribution of vital rates between individuals and years can be assumed stationary in the future, or if any changes can be accurately predicted. In particular, we note th at although catastrophes are likely to have precipitated many extinctions, estimates of the probability of catastrophes are unreliable.

Characterizing mixing and measurement in quantum mechanics

What fundamental constraints characterize the relationship between a mixture rho = Sigma (i)p(i)rho (i) of quantum states, the states rho (i) being mixed, and the probabilities p(i)? What fundamental constraints characterize the relationship between prior and posterior states in a quantum measurement? In this paper we show that then are many surprisingly strong constraints on these mixing and measurement processes that can be expressed simply in terms of the eigenvalues of the quantum states involved. These constraints capture in a succinct fashion what it means to say that a quantum measurement acquires information about the system being measured, and considerably simplify the proofs of many results about entanglement transformation.

Set-valued Markov chains and negative semitrajectories of discretized dynamical systems

Computer simulation of dynamical systems involves a phase space which is the finite set of machine arithmetic. Rounding state values of the continuous system to this grid yields a spatially discrete dynamical system, often with different dynamical behaviour. Discretization of an invertible smooth system gives a system with set-valued negative semitrajectories. As the grid is refined, asymptotic behaviour of the semitrajectories follows probabilistic laws which correspond to a set-valued Markov chain, whose transition probabilities can be explicitly calculated. The results are illustrated for two-dimensional dynamical systems obtained by discretization of fractional linear transformations of the unit disc in the complex plane.

Two-link approximation schemes for loss networks with linear structure and trunk reservation

Loss networks have long been used to model various types of telecommunication network, including circuit-switched networks. Such networks often use admission controls, such as trunk reservation, to optimize revenue or stabilize the behaviour of the network. Unfortunately, an exact analysis of such networks is not usually possible, and reduced-load approximations such as the Erlang Fixed Point (EFP) approximation have been widely used. The performance of these approximations is typically very good for networks without controls, under several regimes. There is evidence, however, that in networks with controls, these approximations will in general perform less well. We propose an extension to the EFP approximation that gives marked improvement for a simple ring-shaped network with trunk reservation. It is based on the idea of considering pairs of links together, thus making greater allowance for dependencies between neighbouring links than does the EFP approximation, which only considers links in isolation.

On the importance function in splitting simulation

The splitting method is a simulation technique for the estimation of very small probabilities. In this technique, the sample paths are split into multiple copies, at various stages in the simulation. Of vital importance to the efficiency of the method is the Importance Function (IF). This function governs the placement of the thresholds or surfaces at which the paths are split. We derive a characterisation of the optimal IF and show that for multi-dimensional models the natural choice for the IF is usually not optimal. We also show how nearly optimal splitting surfaces can be derived or simulated using reverse time analysis. Our numerical experiments illustrate that by using the optimal IF, one can obtain a significant improvement in simulation efficiency.

A real symmetric Lanczos subspace implementation of quantum scattering using boundary inhomogeneities

We present an efficient and robust method for calculating state-to-state reaction probabilities utilising the Lanczos algorithm for a real symmetric Hamiltonian. The method recasts the time-independent Artificial Boundary Inhomogeneity technique recently introduced by Jang and Light (J. Chem. Phys. 102 (1995) 3262) into a tridiagonal (Lanczos) representation. The calculation proceeds at the cost of a single Lanczos propagation for each boundary inhomogeneity function and yields all state-to-state probabilities (elastic, inelastic and reactive) over an arbitrary energy range. The method is applied to the collinear H + H-2 reaction and the results demonstrate it is accurate and efficient in comparison with previous calculations. (C) 2002 Elsevier Science B.V. All rights reserved.

Lanczos subspace time-independent wave packet calculations of S(D-1)+H-2 reactive scattering

In this paper. we present the results of quantum dynamical simulations of the S (D-1) + H-2 insertion reaction on a newly developed potential energy surface (J. Chem. Phys. 2001, 114, 320). State-to-state reaction probabilities. product state distributions, and initial-state resolved cumulative reaction probabilities from a given incoming reactant channel are obtained from a time-independent wave packet analysis, performed within a single Lanczos subspace. Integral reaction cross sections are then estimated by J-shifting method and compared with the results from molecular beam experiment and QCT calculations.

Chebyshev real wave packet propagation: H+O-2 (J=0) state-to-state reactive scattering calculations

In this paper we explore the relative performance of two recently developed wave packet methodologies for reactive scattering, namely the real wave packet Chebyshev domain propagation of Gray and Balint-Kurti [J. Chem. Phys. 108, 950 (1998)] and the Lanczos subspace wave packet approach of Smith [J. Chem. Phys. 116, 2354 (2002); Chem. Phys. Lett. 336, 149 (2001)]. In the former method, a modified Schrodinger equation is employed to propagate the real part of the wave packet via the well-known Chebyshev iteration. While the time-dependent wave packet from the modified Schrodinger equation is different from that obtained using the standard Schrodinger equation, time-to-energy Fourier transformation yields wave functions which differ only trivially by normalization. In the Lanczos subspace approach the linear system of equations defining the action of the Green operator may be solved via either time-dependent or time-independent methods, both of which are extremely efficient due to the simple tridiagonal structure of the Hamiltonian in the Lanczos representation. The two different wave packet methods are applied to three dimensional reactive scattering of H+O-2 (total J=0). State-to-state reaction probabilities, product state distributions, as well as initial-state-resolved cumulative reaction probabilities are examined. (C) 2002 American Institute of Physics.

Branching processes and computational collapse of discretized unimodal mappings

In computer simulations of smooth dynamical systems, the original phase space is replaced by machine arithmetic, which is a finite set. The resulting spatially discretized dynamical systems do not inherit all functional properties of the original systems, such as surjectivity and existence of absolutely continuous invariant measures. This can lead to computational collapse to fixed points or short cycles. The paper studies loss of such properties in spatial discretizations of dynamical systems induced by unimodal mappings of the unit interval. The problem reduces to studying set-valued negative semitrajectories of the discretized system. As the grid is refined, the asymptotic behavior of the cardinality structure of the semitrajectories follows probabilistic laws corresponding to a branching process. The transition probabilities of this process are explicitly calculated. These results are illustrated by the example of the discretized logistic mapping.

Making decisions about treatment for localized prostate cancer

Objective To describe the decision-making processes used by men diagnosed with localized prostate cancer who were considering treatment. Patients and methods Men newly diagnosed with localized prostate cancer from outpatient urology clinics and urologist's private practices were approached before treatment. Their decision-making processes and information-seeking behaviour was assessed; demographic information was also obtained. Results Of 119 men approached, 108 (90%) were interviewed; 91% reported non-systematic decision processes, with deferral to the doctor, positive and negative recollections of others' cancer experiences, and the pre-existing belief that surgery is a better cancer treatment being most common. For systematic information processing the mean (SD, range) number of items considered was 4.19 (2.28, 0-11), with 57% of men considering four or fewer treatment/medical aspects of prostate cancer. Men most commonly considered cancer stage (59%), urinary incontinence (55%) and impotence (51%) after surgery, and low overall mortality (45%). Uncertainty about probabilities for cure was reported by 43% of men and fear of cancer spread by 37%. Men also described uncertainty about the probabilities of side-effects (27%), decisional uncertainty (25%) and anticipated decisional regret (18%). Overall, 73% of men sought information about prostate cancer from external sources, most commonly the Internet, followed by family and friends. Conclusions In general, men did not use information about medical treatments comprehensively or systematically when making treatment decisions, and their processing of medical information was biased by their previous beliefs about cancer and health. These findings have implications for the provision of informational and decisional support to men considering prostate cancer treatment.