The Role of Cell Sterilization In Population Based Studies of Radiogenic Second Cancers Following Radiation Therapy

<p>Advances in radiotherapy have generated increased interest in comparative studies of treatment techniques and their effectiveness. In this respect, pediatric patients are of specific interest because of their sensitivity to radiation induced second cancers. However, due to the rarity of childhood cancers and the long latency of second cancers, large sample sizes are unavailable for the epidemiological study of contemporary radiotherapy treatments. Additionally, when specific treatments are considered, such as proton therapy, sample sizes are further reduced due to the rareness of such treatments. We propose a method to improve statistical power in micro clinical trials. Specifically, we use a more biologically relevant quantity, cancer equivalent dose (<em>D</em>_CE), to estimate risk instead of mean absorbed dose (<em>D</em>_MA). Our objective was to demonstrate that when <em>D</em>_CE is used fewer subjects are needed for clinical trials. Thus, we compared the impact of <em>D</em>_CE vs. <em>D</em>_MA on sample size in a virtual clinical trial that estimated risk for second cancer (SC) in the thyroid following craniospinal irradiation (CSI) of pediatric patients using protons vs. photons. Dose reconstruction, risk models, and statistical analysis were used to evaluate SC risk from therapeutic and stray radiation from CSI for 18 patients. Absorbed dose was calculated in <em>two</em> ways: with (1) traditional <em>D</em>_MA and (2) with <em>D</em>_CE. <em>D</em>_CE and <em>D</em>_MA values were used to estimate relative risk of SC incidence (<em>RR</em>_CE and <em>RR</em>_MA, respectively) after proton vs. photon CSI. Ratios of <em>RR</em> for proton vs. photon CSI (<em>RRR</em>_CE and <em>RRR</em>_MA) were then used in comparative estimations of sample size to determine the minimal number of patients needed to maintain 80% statistical power when using <em>D</em>_CE vs. <em>D</em>_MA. For all patients, we found that protons substantially reduced the risk of developing a second thyroid cancer when compared to photon therapy. Mean <em>RRR</em> values were 0.052±0.014 and 0.087±0.021 for <em>RRR</em>_MA and <em>RRR</em>_CE, respectively. However, we did not find that use of <em>D</em>_CE reduced the number of patents needed for acceptable statistical power (i.e, 80%). In fact, when considerations were made for <em>RRR</em> values that met equipoise requirements and the need for descriptive statistics, the minimum number of patients needed for a micro-clinical trial increased from 17 using <em>D</em>_MA to 37 using <em>D</em>_CE. Subsequent analyses revealed that for our sample, the most influential factor in determining variations in sample size was the experimental standard deviation of estimates for <em>RRR </em>across the patient sample<em>. </em>Additionally, because the relative uncertainty in dose from proton CSI was so much larger (on the order of 2000 times larger) than the other uncertainty terms, it dominated the uncertainty in <em>RRR</em>. Thus, we found that use of corrections for cell sterilization, in the form of<em> D</em>_CE, may be an important and underappreciated consideration in the design of clinical trials and radio-epidemiological studies. In addition, the accurate application of cell sterilization to thyroid dose was sensitive to variations in absorbed dose, especially for proton CSI, which may stem from errors in patient positioning, range calculation, and other aspects of treatment planning and delivery.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2011

Author dc:creator

• Giebeler, Annelise

Contributors dc:contributor

• Wayne D. Newhauser, Ph.D.
• Carol Etzel, Ph.D.
• Rebecca Howell, Ph.D.

• Second radiogenic cancer
• thyroid
• pediatric craniospinal irradiation
• sample size in mirco-clinical trials
• passively scattered protons
• field-in-field photon planning
• statistical power for small samples
• cell sterilization
• alternate dose models
• Clinical Trials
• Medicine and Health Sciences
• Neoplasms
• Other Physics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/214

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1244