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Initial Whole-Brain Radiation for Brain Metastases Questioned

Posted on: 09/26/2008



Initial Whole-Brain Radiation for Brain Metastases Questioned


Zosia Chustecka



September 24, 2008 — Whole-brain radiation (WBR) after stereotactic radiosurgery (SRS) is a standard of care for patients with brain metastases, but it remains controversial. New results documenting its deleterious effect on neurocognitive functioning have led to suggestions that it should not be used in the initial treatment, that patients should be treated with radiosurgery alone, monitored closely, and then treated again after progression.

The findings come from a 7-year phase 3 trial presented at a plenary session during the American Society for Therapeutic Radiology and Oncology 50th Annual Meeting, in Boston, Massachusetts.

"Results of this study could change the practice of how brain metastases are managed in the United States," said lead researcher Eric Chang, MD, radiation oncologist at the MD Anderson Cancer Center, in Houston, Texas.

WBR is controversial because of its toxicity, but proponents argue that it is the best way to ensure that all the cancer is removed, Dr. Chang explained in an interview. Currently, the weight of arguments for and against this practice is about even, but clinicians who are for it can sometimes present the case so forcefully that patients feel unable to refuse, he said.

"I would say that radiosurgery alone offers a better chance of preserving neurocognitive functioning, and this may be the preferred strategy for initial management of patients with 1 to 3 metastases," he told Medscape Oncology.

Double the Impact on Neurocognitive Functioning

Dr. Chang and colleagues studied 58 patients who were newly diagnosed with 1 to 3 brain metastases. All of the patients underwent SRS, which delivers high doses of radiation directly to the tumor, and usually takes only 1 day. Half the patients then received 30 Gy of WBR in 12 courses, administered within a week of the SRS.

The trial was halted at an interim analysis because of the high statistical probability (96.4%) that learning and memory in patients who received both SRS and WBR would be affected to a greater extent than those who received only SRS (48% vs 20% predicted cognitive decline). The actual results approximately 4 months after treatment showed a 49% cognitive decline in patients who received both SRS and WBR, compared with 23% in those who received SRS alone.

Neurocognitive outcome was measured by the ability of patients to immediately recall a list of 12 words after 3 attempts. Nearly half the patients who received WBR lost the ability to recall 5 words from the same list after 3 attempts.

But More Progression With SRS Alone

However, the combination treatment was better at stopping cancer progression. After 1 year, all the patients in the SRS-plus-WBR group were free from progression with respect to brain metastases, compared with 67% in the SRS group (P = .012); the distant freedom from progression rate was 73% and 45%, respectively (P = .0023).

Patients were followed closely and treated again after progression had occurred. Among patients who were treated initially with SRS plus WBR, 2 went on to receive more SRS. In contrast, among patients who were treated initially with SRS alone, 4 went on to receive more SRS, 9 went on to receive surgery, and 6 went on to receive WBR.

However, the researchers pointed out that the toxic effect on learning and memory from WBR in the first place was greater than the effects of the increased progression of distant brain metastases.

"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," Dr. Chang commented. "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." Another aspect is that WBR leads to complete hair loss, whereas SRS does not; this can also be an important point for patients who are considering their options, he said.

"The research suggests that patients who receive SRS as their initial treatment and are then monitored closely for any recurrence will fare better," Dr. Chang said in a statement.

"Determining how to optimize outcomes with the smallest cost to quality of life is a treatment decision every radiation oncologist faces," Dr. Chang said. "While both approaches are used in practice and both are equally acceptable, the data from this trial suggest that oncologists should offer SRS alone as the upfront initial therapy for patients with up to 3 brain metastases."

The researchers have disclosed no relevant financial relationships.

American Society for Therapeutic Radiology and Oncology (ASTRO) 50th Annual Meeting: Late-breaking abstract. Presented September 22, 2008.

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