Improving Cervical Cancer Nodal Boost Radiation Therapy by Quantifying Uncertainties and Exploring Advanced Radiation Therapy Modalities

Radiation therapy for patients with intact cervical cancer is frequently delivered using primary external beam radiation therapy (EBRT) followed by two fractions of intracavitary brachytherapy (ICBT). Although the tumor is the primary radiation target, controlling microscopic disease in the lymph nodes is just as critical to patient treatment outcome. In patients where gross lymphadenopathy is discovered, an extra EBRT boost course is delivered between the two ICBT fractions. Since the nodal boost is an addendum to primary EBRT and ICBT, the prescription and delivery must be performed considering previously delivered dose. This project aims to address the major issues of this complex process for the purpose of improving treatment accuracy while increasing dose sparing to the surrounding normal tissues. Because external beam boosts to involved lymph nodes are given prior to the completion of ICBT, assumptions must be made about dose to positive lymph nodes from future implants. The first aim of this project was to quantify differences in nodal dose contribution between independent ICBT fractions. We retrospectively evaluated differences in the ICBT dose contribution to positive pelvic nodes for ten patients who had previously received external beam nodal boost. Our results indicate that the mean dose to the pelvic nodes differed by up to 1.9 Gy between independent ICBT fractions. The second aim is to develop and validate a volumetric method for summing dose of the normal tissues during prescription of nodal boost. The traditional method of dose summation uses the maximum point dose from each modality, which often only represents the worst case scenario. However, the worst case is often an exaggeration when highly conformal therapy methods such as intensity modulated radiation therapy (IMRT) are used. We used deformable image registration algorithms to volumetrically sum dose for the bladder and rectum and created a voxel-by-voxel validation method. The mean error in deformable image registration results of all voxels within the bladder and rectum were 5 and 6 mm, respectively. Finally, the third aim explored the potential use of proton therapy to reduce normal tissue dose. A major physical advantage of protons over photons is that protons stop after delivering dose in the tumor. Although theoretically superior to photons, proton beams are more sensitive to uncertainties caused by interfractional anatomical variations, and must be accounted for during treatment planning to ensure complete target coverage. We have demonstrated a systematic approach to determine population-based anatomical margin requirements for proton therapy. The observed optimal treatment angles for common iliac nodes were 90° (left lateral) and 180° (posterior-anterior [PA]) with additional 0.8 cm and 0.9 cm margins, respectively. For external iliac nodes, lateral and PA beams required additional 0.4 cm and 0.9 cm margins, respectively. Through this project, we have provided radiation oncologists with additional information about potential differences in nodal dose between independent ICBT insertions and volumetric total dose distribution in the bladder and rectum. We have also determined the margins needed for safe delivery of proton therapy when delivering nodal boosts to patients with cervical cancer.

Comparison of Tumor Shrinkage and Cumulative Dose Distribution for Lung Cancers

Background: The physical characteristic of protons is that they deliver most of their radiation dose to the target volume and deliver no dose to the normal tissue distal to the tumor. Previously, numerous studies have shown unique advantages of proton therapy over intensity-modulated radiation therapy (IMRT) in conforming dose to the tumor and sparing dose to the surrounding normal tissues and the critical structures in many clinical sites. However, proton therapy is known to be more sensitive to treatment uncertainties such as inter- and intra-fractional variations in patient anatomy. To date, no study has clearly demonstrated the effectiveness of proton therapy compared with the conventional IMRT under the consideration of both respiratory motion and tumor shrinkage in non-small cell lung cancer (NSCLC) patients. Purpose: This thesis investigated two questions for establishing a clinically relevant comparison of the two different modalities (IMRT and proton therapy). The first question was whether or not there are any differences in tumor shrinkage between patients randomized to IMRT versus passively scattered proton therapy (PSPT). Tumor shrinkage is considered a standard measure of radiation therapy response that has been widely used to gauge a short-term progression of radiation therapy. The second question was whether or not there are any differences between the planned dose and 5D dose under the influence of inter- and intra-fractional variations in the patient anatomy for both modalities. Methods: A total of 45 patients (25 IMRT patients and 20 PSPT patients) were used to quantify the tumor shrinkage in terms of the change of the primary gross tumor volume (GTVp). All patients were randomized to receive either IMRT or PSPT for NSCLC. Treatment planning goals were identical for both groups. All patients received 5 to 8 weekly repeated 4-dimensional computed tomography (4DCT) scans during the course of radiation treatments. The original GTVp contours were propagated to T50 of weekly 4DCT images using deformable image registration and their absolute volumes were measured. Statistical analysis was performed to compare the distribution of tumor shrinkage between the two population groups. In order to investigate the difference between the planned dose and the 5D dose with consideration of both breathing motion and anatomical change, we re-calculated new dose distributions at every phase of the breathing cycle for all available weekly 4DCT data sets which resulted 50 to 80 individual dose calculations for each of the 7 patients presented in this thesis. The newly calculated dose distributions were then deformed and accumulated to T50 of the planning 4DCT for comparison with the planned dose distribution. Results: At the end of the treatment, both IMRT and PSPT groups showed mean tumor volume reductions of 23.6% ( 19.2%) and 20.9% ( 17.0 %) respectively. Moreover, the mean difference in tumor shrinkage between two groups is 3% along with the corresponding 95% confidence interval, [-8%, 14%]. The rate of tumor shrinkage was highly correlated with the initial tumor volume size. For the planning dose and 5D dose comparison study, all 7 patients showed a mean difference of 1 % in terms of target coverage for both IMRT and PSPT treatment plans. Conclusions: The results of the tumor shrinkage investigation showed no statistically significant difference in tumor shrinkage between the IMRT and PSPT patients, and the tumor shrinkage between the two modalities is similar based on the 95% confidence interval. From the pilot study of comparing the planned dose with the 5D dose, we found the difference to be only 1%. Overall impression of the two modalities in terms of treatment response as measured by the tumor shrinkage and 5D dose under the influence of anatomical change that were designed under the same protocol (i.e. randomized trial) showed similar result.

Understanding and Characterizing Shared Decision-Making and Behavioral Intent in Medical Uncertainty

Applying Theoretical Constructs to Address Medical Uncertainty Situations involving medical reasoning usually include some level of medical uncertainty. Despite the identification of shared decision-making (SDM) as an effective technique, it has been observed that the likelihood of physicians and patients engaging in shared decision making is lower in those situations where it is most needed; specifically in circumstances of medical uncertainty. Having identified shared decision making as an effective, yet often a neglected approach to resolving a lack of information exchange in situations involving medical uncertainty, the next step is to determine the way(s) in which SDM can be integrated and the supplemental processes that may facilitate its integration. SDM involves unique types of communication and relationships between patients and physicians. Therefore, it is necessary to further understand and incorporate human behavioral elements - in particular, behavioral intent - in order to successfully identify and realize the potential benefits of SDM. This paper discusses the background and potential interaction between the theories of shared decision-making, medical uncertainty, and behavioral intent. Identifying Shared Decision-Making Elements in Medical Encounters Dealing with Uncertainty A recent summary of the state of medical knowledge in the U.S. reported that nearly half (47%) of all treatments were of unknown effectiveness, and an additional 7% involved an uncertain tradeoff between benefits and harms. Shared decision-making (SDM) was identified as an effective technique for managing uncertainty when two or more parties were involved. In order to understand which of the elements of SDM are used most frequently and effectively, it is necessary to identify these key elements, and understand how these elements related to each other and the SDM process. The elements identified through the course of the present research were selected from basic principles of the SDM model and the “Data, Information, Knowledge, Wisdom” (DIKW) Hierarchy. The goal of this ethnographic research was to identify which common elements of shared decision-making patients are most often observed applying in the medical encounter. The results of the present study facilitated the understanding of which elements patients were more likely to exhibit during a primary care medical encounter, as well as determining variables of interest leading to more successful shared decision-making practices between patients and their physicians. Understanding Behavioral Intent to Participate in Shared Decision-Making in Medically Uncertain Situations Objective: This article describes the process undertaken to identify and validate behavioral and normative beliefs and behavioral intent of men between the ages of 45-70 with regard to participating in shared decision-making in medically uncertain situations. This article also discusses the preliminary results of the aforementioned processes and explores potential future uses of this information which may facilitate greater understanding, efficiency and effectiveness of doctor-patient consultations.Design: Qualitative Study using deductive content analysisSetting: Individual semi-structure patient interviews were conducted until data saturation was reached. Researchers read the transcripts and developed a list of codes.Subjects: 25 subjects drawn from the Philadelphia community.Measurements: Qualitative indicators were developed to measure respondents’ experiences and beliefs related to behavioral intent to participate in shared decision-making during medical uncertainty. Subjects were also asked to complete the Krantz Health Opinion Survey as a method of triangulation.Results: Several factors were repeatedly described by respondents as being essential to participate in shared decision-making in medical uncertainty. These factors included past experience with medical uncertainty, an individual’s personality, and the relationship between the patient and his physician.Conclusions: The findings of this study led to the development of a category framework that helped understand an individual’s needs and motivational factors in their intent to participate in shared decision-making. The three main categories include 1) an individual’s representation of medically uncertainty, 2) how the individual copes with medical uncertainty, and 3) the individual’s behavioral intent to seek information and participate in shared decision-making during times of medically uncertain situations.

Strange bedfellows: The ethics and politics of medical futility in Texas

Background: Futile medical treatments are interventions that are not associated with a benefit to the patient. The definition and concept of medical futility are controversial. The Texas Advance Directives Act (TADA) was passed in 1999 to address medically inappropriate interventions by allowing providers to withdraw inappropriate interventions against a surrogate decision maker's wishes following a review, attempt to transfer the patient, and 10-day waiting period. The original legislation was a negotiated compromise by players across the political spectrum. However, in recent years there has been increasing controversy regarding TADA and attempts to alter its applicability in Texas. ^ Purpose: The purpose of this project was to apply Paul Sabatier's advocacy coalition framework (ACF) to gain understanding into the historical, ethical, and political basis of the initial compromise, and determine the sources of conflict that have led to increased opposition to TADA. ^ Methods: Using the ACF model, key actors within the medical futility policy debate in Texas were aggregated into coalitions based on shared beliefs. A narrative summary based analysis identified the core elements of the policy subsystem, as well as the constraints and resources of the subsystem actors. Externalities that promoted adjustments to coalition beliefs and tactics used by coalition participants were analyzed. Data sources included review of the published literature regarding medical futility, as well as analysis of published newspaper accounts and editorials regarding the medical futility issue in Texas, legislative testimony, and review of weblogs and online commentaries dealing with the issue. ^ Results: Primary coalition participants in developing compromise legislation in 1999 were the Providers and Vitalists, with Autonomists gaining a prominent role starting in 2006. Internal factors associated with the breakdown of consensus included changes to the makeup of the governing coalition and changes in individual case information available to the Vitalist coalition. Externalities related to the intertwining of the Sun Hudson case and the Terri Schiavo case generated negative publicity for the TADA from progressive and conservative viewpoints. Dissemination of information in various venues regarding contentious cases was associated with more polarization of viewpoints, and realignment of coalition alliances. ^ Conclusions: The ACF provided an outline for the initial compromise over the creation of the Texas Advance Directives Act as well as the eventual loss of consensus. The debate between the Provider, Vitalist, and Autonomist coalitions has been affected by internal policy evolution, changes in the governing coalition, and important externalities. The debate over medical futility in Texas has had much broader implications in the dispute over Health Care Reform.^

Development and implementation of a dynamic heterogeneous proton equivalent anthropomorphic thorax phantom for the assessment of scanned proton beam therapy

DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY by James Leroy Neihart, B.S. APPROVED: ______________________________David Followill, Ph.D. ______________________________Peter Balter, Ph.D. ______________________________Narayan Sahoo, Ph.D. ______________________________Kenneth Hess, Ph.D. ______________________________Paige Summers, M.S. APPROVED: ____________________________ Dean, The University of Texas Graduate School of Biomedical Sciences at Houston DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY A THESIS Presented to the Faculty of The University of Texas Health Science Center at Houston andThe University of TexasMD Anderson Cancer CenterGraduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE by James Leroy Neihart, B.S. Houston, Texas Date of Graduation August, 2013 Acknowledgments I would like to acknowledge my advisory committee members, chair David Followill, Ph.D., Peter Balter, Ph.D, Narayan Sahoo, Ph.D., Kenneth Hess, Ph.D., Paige Summers M.S. and, for their time and effort contributed to this project. I would additionally like to thank the faculty and staff at the PTC-H and the RPC who assisted in many aspects of this project. Falk Pӧnisch, Ph.D. for his breath hold proton therapy treatment expertise, Matt Palmer and Jaques Bluett for proton dosimetry assistance, Matt Kerr for verification plan assistance, Carrie Amador, Nadia Hernandez, Trang Nguyen, Andrea Molineu, Lynda McDonald for TLD and film dosimetry assistance. Finally, I would like to thank my wife and family for their support and encouragement during my research and studies. Development and implementation of a dynamic heterogeneous proton equivalent anthropomorphic thorax phantom for the assessment of scanned proton beam therapy By: James Leroy Neihart, B.S. Chair of Advisory Committee: David Followill, Ph.D Proton therapy has been gaining ground recently in radiation oncology. To date, the most successful utilization of proton therapy is in head and neck cases as well as prostate cases. These tumor locations do not suffer from the resulting difficulties of treatment delivery as a result of respiratory motion. Lung tumors require either breath hold or motion tracking, neither of which have been assessed with an end-to-end phantom for proton treatments. Currently, the RPC does not have a dynamic thoracic phantom for proton therapy procedure assessment. Additionally, such a phantom could be an excellent means of assessing quality assurance of the procedures of proton therapy centers wishing to participate in clinical trials. An eventual goal of this phantom is to have a means of evaluating and auditing institutions for the ability to start clinical trials utilizing proton therapy procedures for lung cancers. Therefore, the hypothesis of this study is that a dynamic anthropomorphic thoracic phantom can be created to evaluate end-to-end proton therapy treatment procedures for lung cancer to assure agreement between the measured and calculated dose within 5% / 5 mm with a reproducibility of 2%. Multiple materials were assessed for thoracic heterogeneity equivalency. The phantom was designed from the materials found to be in greatest agreement. The phantom was treated in an end-to-end treatment four times, which included simulation, treatment planning and treatment delivery. Each treatment plan was delivered three times to assess reproducibility. The dose measured within the phantom was compared to that of the treatment plan. The hypothesis was fully supported for three of the treatment plans, but failed the reproducibility requirement for the most aggressive treatment plan.