Bioinformatics Methods for Learning Radiation-Induced Lung Inflammation from Heterogeneous Retrospective and Prospective Data

Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined

Stochastic Norton-Simon-Massagu\ue9 Tumor Growth Modeling: Controlled and Mixed-Effects Uncontrolled Analysis

Tumorigenesis is a complex process that is heterogeneous and affected by numerous sources of variability. This study presents a stochastic extension of a biologically grounded tumor growth model, referred to as the Norton-Simon-Massagu\ue9 (NSM) tumor growth model. We first study the uncontrolled version of the model where the effect of chemotherapeutic drug agent is absent. Conditions on the model\u2019s parameters are derived to guarantee the positivity of the tumor volume and hence the validity of the proposed stochastic NSM model. To calibrate the proposed model we utilize a maximum likelihood- based estimation algorithm and population mixed-effect modeling formulation. The algorithm is tested by fitting previously published tumor volume mice data. Then, we study the controlled version of the model which includes the effect of chemotherapy treatment. Analysis of the influence of adding the control drug agent into the model and how sensitive it is to the stochastic parameters is performed both in open-loop and closed-loop viewpoints through different numerical simulations

Uncertainty and Margin Study for IMRT, VMAT, and Proton Beam Therapy for Treatment After Radical Prostatectomy

Purpose/Objective(s): To compare the uncertainties of 3D dose distributions, caused by the geometrical uncertainty of patient setup, in IMRT, VMAT, and proton plans for post-prostatectomy treatment. To test the effectiveness of a common margin recipe in these three types of treatment plans. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Parents' Perspectives on the School Experiences of Children with Cancer

Interviews with 59 parents of school age children with cancer indicate problems children encountered in returning to school: missing significant amounts of school due to illness and treatments, teasing by classmates and peers, and strained relations with teachers. Most parents report that despite missing much school their child was caught up with schoolwork, suggesting that academic difficulties are not paramount. Most parents also report receiving substantial help from sympathetic and competent educators. However, parents also indicate that some teachers were insensitive to their child's condition, while others were overprotective, suggesting the need for a delicate balance in defining appropriate teacher behavior. A responsive yet normalizing school environment can be facilitated by vigorous and proactive partnerships among the medical staff, family, and school system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68682/2/10.1177_027112148600500405.pd

Preoperative MRI-radiomics features improve prediction of survival in glioblastoma patients over MGMT methylation status alone

Background: Glioblastoma (GBM) is the most common malignant central nervous system tumor, and MGMT promoter hypermethylation in this tumor has been shown to be associated with better prognosis. We evaluated the capacity of radiomics features to add complementary information to MGMT status, to improve the ability to predict prognosis. Methods: 159 patients with untreated GBM were included in this study and divided into training and independent test sets. 286 radiomics features were extracted from the magnetic resonance images acquired prior to any treatments. A least absolute shrinkage selection operator (LASSO) selection followed by Kaplan-Meier analysis was used to determine the prognostic value of radiomics features to predict overall survival (OS). The combination of MGMT status with radiomics was also investigated and all results were validated on the independent test set. Results: LASSO analysis identified 8 out of the 286 radiomic features to be relevant which were then used for determining association to OS. One feature (edge descriptor) remained significant on the external validation cohort after multiple testing (p=0.04) and the combination with MGMT identified a group of patients with the best prognosis with a survival probability of 0.61 after 43 months (p=0.0005). Conclusion: Our results suggest that combining radiomics with MGMT is more accurate in stratifying patients into groups of different survival risks when compared to with using these predictors in isolation. We identified two subgroups within patients who have methylated MGMT: one with a similar survival to unmethylated MGMT patients and the other with a significantly longer OS

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: Implications for radiation dose escalation in carcinoma of the pancreas

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel

Discovery of a peculiar Cepheid-like star towards the northern edge of the Small Magellanic Cloud

For seven years, the EROS-2 project obtained a mass of photometric data on variable stars. We present a peculiar Cepheid-like star, in the direction of the Small Magellanic Cloud, which demonstrates unusual photometric behaviour over a short time interval. We report on data of the photometry acquired by the MARLY telescope and spectroscopy from the EFOSC instrument for this star, called EROS2 J005135-714459(sm0060n13842), which resembles the unusual Cepheid HR 7308. The light curve of our target is analysed using the Analysis of Variance method to determine a pulsational period of 5.5675 days. A fit of time-dependent Fourier coefficients is performed and a search for proper motion is conducted. The light curve exhibits a previously unobserved and spectacular change in both mean magnitude and amplitude, which has no clear theoretical explanation. Our analysis of the spectrum implies a radial velocity of 104 km s$^{-1}$ and a metallicity of -0.4$\pm$0.2 dex. In the direction of right ascension, we measure a proper motion of 17.4$\pm$6.0 mas yr$^{-1}$ using EROS astrometry, which is compatible with data from the NOMAD catalogue. The nature of EROS2 J005135-714459(sm0060n13842) remains unclear. For this star, we may have detected a non-zero proper motion for this star, which would imply that it is a foreground object. Its radial velocity, pulsational characteristics, and photometric data, however, suggest that it is instead a Cepheid-like object located in the SMC. In such a case, it would present a challenge to conventional Cepheid models.Comment: Correction of typos in the abstrac

Intermediate-mass star models with different helium and metal contents

We present a comprehensive theoretical investigation of the evolutionary properties of intermediate-mass stars. The evolutionary sequences were computed from the Zero Age Main Sequence up to the central He exhaustion and often up to the phases which precede the carbon ignition or to the reignition of the H-shell which marks the beginning of the thermal pulse phase. The evolutionary tracks were constructed by adopting a wide range of stellar masses ($3\leq$\msun$\leq15$) and chemical compositions. In order to account for current uncertainties on the He to heavy elements enrichment ratio, the stellar models were computed by adopting at Z=0.02 two different He contents (Y=0.27, 0.289) and at Z=0.04 three different He contents (Y=0.29, 0.34, and 0.37). To supply a homogeneous evolutionary scenario which accounts for young Magellanic stellar systems the calculations were also extended toward lower metallicities (Z=0.004, Z=0.01), by adopting different initial He abundances. We evaluated for both solar (Z=0.02) and super-metal-rich (SMR, Z=0.04) models the transition mass $M^{up}$ between the stellar structures igniting carbon and those which develop a full electron degeneracy inside the CO core. This evolutionary scenario allows us to investigate in detail the properties of classical Cepheids. In particular, we find that the range of stellar masses which perform the blue loop during the central He-burning phase narrows when moving toward metal-rich and SMR structures.Comment: 25 pages, 10 figures (4 postscript + 6 gif files), 7 postscript tables. accepted for publication on ApJ (November 2000