In his application for a 2008 Career Development Award (CDA), colorectal oncology surgeon George J. Chang, MD, MS, outlined a research project to develop a Markov decision model for optimizing rectal cancer therapy. Dr. Chang, an Assistant Professor at The University of Texas M. D. Anderson Cancer Center in Houston, was 1 of 13 recipients in 2008 of the 3-year, $200,000 award given by The ASCO Cancer Foundation.

"A Markov model is a mathematical tool for simulating outcomes after different treatment scenarios," Dr. Chang explains, adding that the model has been commonly used in business forecasting.

Explaining that his overall research agenda is to improve outcomes in colorectal cancer, Dr. Chang says that the CDA he received has led to many other opportunities that support this work. "The Career Development Award has provided resources for research, education, and career development and provided opportunities for collaboration. It's helped me engage new areas of work and carry on existing work," he said.

Creating the Model

As part of the preparation for creating the decision model for rectal cancer therapy, Dr. Chang and his colleagues used data from more than 23,000 patients in the Surveillance, Epidemiology, and End Results (SEER) registry to analyze survival outcomes of patients who had preoperative or postoperative radiotherapy for rectal cancer. The study, published in Cancer, found that patients with persistent lymph node-positive disease after preoperative radiotherapy have impaired survival expectancy, and the authors recommended targeting this group for novel treatment strategies.¹

To refine the decision model, Dr. Chang is developing a prospective registry of health state utilities and quality of life in patients following multidisciplinary curative treatment for rectal cancer. In addition, he will soon launch a prospective single-arm phase II clinical trial at M. D. Anderson to obtain additional data about treatment outcome and survivorship in patients undergoing toxicity-optimized treatment for rectal cancer. Controlling for a number of factors such as the quality of surgery and the chemotherapy administered, the clinical trial will measure the quality of life in a population of patients who do not receive radiotherapy. "This will give us robust data to optimize our models," Dr. Chang said. He added, "These are the kinds of things that the CDA has definitely helped us to do."

Dr. Chang says that the decision model will permit simulation of different treatment strategies in order to measure their effects on the quality of life over a lifetime. "We can determine quality-adjusted life expectancy, and the net effect of treatment-related trade-offs, to inform decision-making about current therapy and future clinical investigations," he explained.

In related work, Dr. Chang and his colleagues have developed a model that provides important prognostic information for survivors of colon cancer. Using SEER data, they analyzed more than 83,000 patients diagnosed with colon adenocarcinoma between 1988 and 2000 to determine risk-adjusted conditional survival probabilities. As a result of this work-published in the Journal of Clinical Oncology-an online calculator for conditional survival has been made available to clinicians (www.mdanderson.org/coloncalculator).² ■

References

1. Chang GJ, Rodriguez-Bigas MA, Eng C, et al: Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome. Cancer 115:5432-5440, 2009.

2. Chang GJ, Hu CY, Eng C, Skibber JM, et al: Practical application of a calculator for conditional survival in colon cancer. J Clin Oncol 27:5938-5943, 2009.

© 2010. American Society of Clinical Oncology. All Rights Reserved.