Prophylactic Cranial Irradiation in Advanced Lung Cancer Reduces Brain Metastases

Zosia Chustecka

June 06, 2007

June 6, 2007 (Chicago) — In patients with advanced small-cell lung cancer (SCLC) who responded to chemotherapy, administration of prophylactic cranial irradiation significantly reduced the risk of developing brain metastases and significantly improved overall survival. As a result, this intervention should become a new standard of care for this patient population, said lead researcher Ben Slotman, MD, PhD, chair of radiation oncology at VU University Medical Center, in Amsterdam, the Netherlands.

Hearing the results here at the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting, other lung cancer experts agreed. "I would predict that this intervention will be taken up very quickly," commented Roy Herbst, MD, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, who moderated an ASCO press briefing at which the study was highlighted. "These results can change clinical practice very quickly," he continued. "Radiation is already available at every clinic, so it could change practice this afternoon, it's not like hearing results with a drug that is still several years away from the market." Discussing the findings at a plenary session, Andrew Turrisi, MD, from the Karmanos Cancer Center, in Detroit, Michigan, congratulated the investigators and said the intervention "worked and the side effects were manageable."

The study, known as EORTC 08993-22993, was funded by the European Organization for the Research and Treatment of Cancer (EORTC). It was conducted in patients with extensive-disease SCLC who had responded to chemotherapy — "they were eligible if they had any response at all but were not included if they had no response," Dr. Slotman commented.

Responders were then randomized to either the control group or to receive prophylactic cranial irradiation, with 143 patients in each group. Radiation was administered at 20 Gy in 5 fractions in about two thirds of the patients, while the remainder received either 24 30 Gy in 8 to 12 fractions or 30 Gy in 10 fractions. Dr. Turrisi noted that these schedules were a little different from what is usually used in the United States, where 24 to 30 Gy in 8 to 12 fractions is most common, and suggested that there may be more study needed on the best dose to use.

Results after 1 year showed a significant reduction in the risk of developing brain metastases in the patients who had been irradiated and a significant improvement on survival. The 1-year cumulative incidence was 14.6% in the prophylactic cranial irradiation group compared with 40.4% in controls (P < .0001; hazard ratio (HR) = 0.27; 95% CI, 0.16 – 0.44). The 1-year survival rates were 27.1% with prophylactic cranial irradiation compared with 13.1% in the control group (P = .003; HR = 0.68; 95% CI, 0.52 – 0.88).

In his discussion, Dr. Turrisi said the results on overall survival were "really rather outstanding," as the patients had already survived 4 months while undergoing chemotherapy before the randomization started.

Prophylactic cranial irradiation was associated with adverse events such as nausea and vomiting (reported by 30% of patients) and mild headache as a late reaction (also 30% of patients). Dr. Slotman said the radiation was "well tolerated and did not adversely affect global quality of life." Dr. Turrisi noted that alopecia was seen, but reversed in 2 to 3 months, and "neurocognitive deficits are less common than once thought." Dr. Herbst commented, "Radiation to the brain is not as toxic as one might think, and if this intervention does become a standard of care, I predict the risk will be seen as worth taking." Brain metastases are devastating, he noted, and are already present in about 20% ofSCLC patients at diagnosis and are seen in more than 50% of patients after 2 years.

All the experts noted that prophylactic cranial irradiation had already shown to be beneficial in patients with limited-disease SCLC. Now, benefit has been shown in extensive disease, and Dr. Slotman suggested that it should be offered routinely.

"Our data suggest that all patients with extensive small-cell lung cancer who respond to chemotherapy could benefit from prophylactic cranial irradiation," Dr. Slotman commented to journalists. "Because improvements in treatment results for patients with advanced SCLC have been minimal in the past 2 decades, these findings represent a significant advance," he added.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 4. Presented June 4, 2007.


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