Whole Brain Radiation Increases Risk of Learning and Memory Problems in Cancer Patients with Brain Metastases

Nearly half of patients experience impaired neurocognitive function, prompts possible change to standard practice

Cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone, according to new research from The University of Texas M. D. Anderson Cancer Center.

The findings of the phase III randomized trial were presented at today's 50th annual meeting of the American Society for Therapeutic Radiology and Oncology.

Led by Department of Radiation Oncology at M. D. Anderson, the study offers greater context to the ongoing debate among oncologists about how best to manage the treatment of cancer patients with one to three brain metastases.

The American Cancer Society estimates approximately 170,000 cancer patients will experience metastases to the brain from common primary cancers such as breast, colorectal, kidney and lung in 2008. More than 80,000 of those patients will have between one and three brain metastases.

Over the last decade, SRS, which uses high-doses of targeted x-rays, has gained acceptance as an initial treatment for tumors that have spread to the brain. SRS is also commonly used in combination with WBRT, radiation of the entire brain, to treat tumors that are visible and those that may not be detected by diagnostic imaging.

"Determining how to optimize outcomes with the smallest cost to the quality of life is a treatment decision every radiation oncologist faces," said Chang. "While both approaches are in practice and both are equally acceptable, data from this trial suggest that oncologists should offer SRS alone as the upfront, initial therapy for patients with up to three brain metastases." 

The seven year study observed 58 patients presenting with one to three newly diagnosed brain metastases who were randomized to receive SRS followed by WBRT or SRS alone. Approximately four months after treatment, 49 percent of patients who received WBRT experienced a decline in learning and memory function compared to 23 percent in those patients who received SRS alone.

An independent data monitoring committee halted the trial after interim results showed the high statistical probability (96.4 percent) that patients randomized to SRS alone would continue to perform better.

M. D. Anderson researchers measured participants' neurocognitive function using a short battery of neuropsychological tests, with the primary endpoint being memory function as tested by the Hopkins Verbal Learning Test Revised. Patient performance that decreased more than a predefined criteria relative to their baseline were considered to exhibit a marked decline. 

"This is a case where the risks of learning dysfunction outweigh the benefits of freedom from progression and tip the scales in favor of using SRS alone. Patients are spared from the side effects of whole brain radiation and we are able to preserve their memory and learning function to a higher degree" said Chang. "Here the research suggests patients who receive SRS as their initial treatment and then are monitored closely for any recurrence will fare better."

The study builds on previous research by senior author Christina A. Meyers, Ph.D., M. D. Anderson's chief of the Section Neuropsychology in the Department of Neuro-Oncology, examining neurocognitive function in patients with brain metastases treated with whole-brain radiation. "Unlike past studies comparing the two treatment strategies which did not use sensitive cognitive tests or closely follow patients after being treated with SRS, radiation oncologists in this trial were able to identify new lesions early and treat them with either radiosurgery, surgery, whole brain radiation or less commonly, chemotherapy," Meyers said. "We believe doctors and patients alike will favor this method over upfront whole brain radiation." 

M. D. Anderson is a leader in the application of SRS to cancers of the spine and head and neck, as well as research determining the effects toxic cancer treatment, like radiation therapy, has on brain function. Based on these results, future research studies are planned to determine if there are expanded indications of using SRS alone for patients with more than three brain metastases.

In addition to Chang and Meyers, M. D. Anderson researchers contributing to the study include Jeffrey S. Wefel, Ph.D., Department of Neuro-Oncology; Kenneth R. Hess, Ph.D., Division of Quantitative Sciences; Fredrick F. Lang, M.D., Department of Neurosurgery and Pamela K. Allen, Ph.D., David Kornguth, M.D., Anita Mahajan, M.D., Moshe Maor, M.D., Christopher Pelloski, M.D. and Shiao Y. Woo, M.D., all of the Department of Radiation Oncology. 09/22/08