Carcinoma of the prostate is the most commonly occurring cancer among men in the United States, and is second only to lung cancer in terms of the number of cancer-related deaths in this group. The American Cancer Society estimated an age-adjusted incidence of more than 190,000 newly diagnosed cases of prostate cancer in the U.S. during the year 2000, with more than 35,000 deaths. Radiotherapy (RT) is one of the primary treatment modalities for prostate cancer, but the radiation doses used for: conventional RT are limited by the need to avoid severe complications to adjacent normal tissues, notably the rectum and bladder. Technological advances such as 3- dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) allow radiation dose distributions that conform much more tightly to the prostate gland than with conventional RT, allowing safe dose escalation and improved tumor control, but the need for further improvement remains. Moreover, with increasing numbers of patients experiencing tumor control after RT, there is an increasing need to improve the quality of life among prostate cancer survivors by reducing the risk of normal-tissue toxicity. Since the range of possible conformal RT plans is enormous, quantitative methods are vitally needed to assess and compare large numbers of possible plans, in order to select the safest and most effective plan for each patient. We propose to develop quantitative models for the risk of late rectal and bladder toxicity as a function of the dose distribution received by those organs during treatment. The models will be derived by analyzing the data from protocol 94-06 of the Radiation Therapy Oncology Group of the American College of Radiology. Protocol RTOG 94-06, entitled """"""""A Phase l/ll Dose Escalation Study Using Three Dimensional Conformal Radiation Therapy for Adenocarcinoma of the Prostate"""""""" (Principal Investigator James D. Cox, M.D.), was a multi-institutional trial designed to establish the maximum radiation dose that can be tolerated by surrounding tissues during 3D-CRT of the prostate. The trial enrolled 1084 patients from 35 different institutions from May 1994 to October 2000. The dose distributions to rectum and bladder were accurately recorded, and normal-tissue toxicity has been carefully and consistently measured. Further, the data have mature patient follow-up and come from a large and representative sample of patients treated nationwide using high-quality 3D-CRT, with a sufficient variation in treatment designs to allow us to separate the effects of dose and volume of organ irradiated on the risk of normal-tissue injury. The quantitative dose-volume models developed in this study will be validated by testing their ability to predict complications in two different clinical data sets collected independently. We expect the results of our analyses to play an important role in furthering the development of conformal techniques in RT of the prostate and other pelvic sites.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA104342-02
Application #
7116758
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Stone, Helen B
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$184,317
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Biostatistics & Other Math Sci
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Tucker, Susan L; Michalski, Jeff M; Bosch, Walter R et al. (2012) Use of fractional dose-volume histograms to model risk of acute rectal toxicity among patients treated on RTOG 94-06. Radiother Oncol 104:109-13
Tucker, Susan L; Dong, Lei; Michalski, Jeff M et al. (2012) Do intermediate radiation doses contribute to late rectal toxicity? An analysis of data from radiation therapy oncology group protocol 94-06. Int J Radiat Oncol Biol Phys 84:390-5
Tucker, Susan L; Thames, Howard D; Michalski, Jeff M et al. (2011) Estimation of ?/? for late rectal toxicity based on RTOG 94-06. Int J Radiat Oncol Biol Phys 81:600-5
Michalski, Jeff M; Gay, Hiram; Jackson, Andrew et al. (2010) Radiation dose-volume effects in radiation-induced rectal injury. Int J Radiat Oncol Biol Phys 76:S123-9
Tucker, Susan L; Dong, Lei; Bosch, Walter R et al. (2010) Late rectal toxicity on RTOG 94-06: analysis using a mixture Lyman model. Int J Radiat Oncol Biol Phys 78:1253-60
Tucker, Susan L; Liu, H Helen; Liao, Zhongxing et al. (2008) Analysis of radiation pneumonitis risk using a generalized Lyman model. Int J Radiat Oncol Biol Phys 72:568-74
Cheung, M Rex; Tucker, Susan L; Dong, Lei et al. (2007) Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 67:1059-65
Tucker, Susan L; Liu, H Helen; Wang, Shulian et al. (2006) Dose-volume modeling of the risk of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys 66:754-61