Pathobiologic Markers of the Ewing Sarcoma Family of Tumors: State of the Art and Prediction of Behaviour

Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development

Estimating and modelling cure in population-based cancer studies within the framework of flexible parametric survival models

<p>Abstract</p> <p>Background</p> <p>When the mortality among a cancer patient group returns to the same level as in the general population, that is, the patients no longer experience excess mortality, the patients still alive are considered "statistically cured". Cure models can be used to estimate the cure proportion as well as the survival function of the "uncured". One limitation of parametric cure models is that the functional form of the survival of the "uncured" has to be specified. It can sometimes be hard to find a survival function flexible enough to fit the observed data, for example, when there is high excess hazard within a few months from diagnosis, which is common among older age groups. This has led to the exclusion of older age groups in population-based cancer studies using cure models.</p> <p>Methods</p> <p>Here we have extended the flexible parametric survival model to incorporate cure as a special case to estimate the cure proportion and the survival of the "uncured". Flexible parametric survival models use splines to model the underlying hazard function, and therefore no parametric distribution has to be specified.</p> <p>Results</p> <p>We have compared the fit from standard cure models to our flexible cure model, using data on colon cancer patients in Finland. This new method gives similar results to a standard cure model, when it is reliable, and better fit when the standard cure model gives biased estimates.</p> <p>Conclusions</p> <p>Cure models within the framework of flexible parametric models enables cure modelling when standard models give biased estimates. These flexible cure models enable inclusion of older age groups and can give stage-specific estimates, which is not always possible from parametric cure models.</p

Electron beam induced damage in PECVD Si3N4 and SiO2 films on InP

Phosphorus rich plasma enhanced chemical vapor deposition (PECVD) of silicon nitride and silicon dioxide films on n-type indium phosphide (InP) substrates were exposed to electron beam irradiation in the 5 to 40 keV range for the purpose of characterizing the damage induced in the dielectic. The electron beam exposure was on the range of 10(exp -7) to 10(exp -3) C/sq cm. The damage to the devices was characterized by capacitance-voltage (C-V) measurements of the metal insulator semiconductor (MIS) capacitors. These results were compared to results obtained for radiation damage of thermal silicon dioxide on silicon (Si) MOS capacitors with similar exposures. The radiation induced damage in the PECVD silicon nitride films on InP was successfully annealed out in an hydrogen/nitrogen (H2/N2) ambient at 400 C for 15 min. The PECVD silicon dioxide films on InP had the least radiation damage, while the thermal silicon dioxide films on Si had the most radiation damage

Modelling of amorphous polymer surfaces in computer simulation

We study surface effects in amorphous polymer systems by means of computer simulation. In the framework of molecular dynamics, we present two different methods to prepare such surfaces. {\em Free} surfaces are stabilized solely by van--der--Waals interactions whereas {\em confined} surfaces emerge in the presence of repelling plates. The two models are compared in various computer simulations. For free surfaces, we analyze the migration of end--monomers to the surface. The buildup of density and pressure profiles from zero to their bulk values depends on the surface preparation method. In the case of confined surfaces, we find density and pressure oszillations next to the repelling plates. We investigate the influence of surfaces on the coordination number, on the orientation of single bonds, and on polymer end--to--end vectors. Furthermore, different statistical methods to determine location and width of the surface region for systems of various chain lengths are discussed and applied. We introduce a ``height function'' and show that this method allows to determine average surface profiles only by scanning the outermost layer of monomers.Comment: 23 pages, 12 figure

A multi-state model incorporating estimation of excess hazards and multiple time scales

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population-level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multi-state models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, by allowing is to directly quantify the excess risk. This paper proposes a combination of these two frameworks, providing one approach to address (1)-(3). Using recently developed methods in multi-state modeling, we incorporate estimation of excess hazards into a multi-state model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user-friendly Stata software with accompanying example code

Differences in Management of Older Women Influence Breast Cancer Survival: Results from a Population-Based Database in Sweden

BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50–84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70–84 y of age compared to women aged 50–69 y, and the difference was most pronounced in stage IIB–III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone

Ariel - Volume 2 Number 6

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Stephen Flynn Shep Dickman Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Michael J. Blecker W. Cherry Light James J. Nocon Lynne Porter Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof