CHICAGO, June 2 -- Prophylactic cranial irradiation after chemotherapy significantly reduces the risk of brain metastasis and doubles one-year survival in small-cell lung cancer (SCLC), a Dutch oncologist reported here.SCLC patients who exhibited any response to chemotherapy and then received prophylactic whole-brain irradiation had a 14.6% rate of symptomatic brain metastases at one year compared with 40.4% for those not getting radiation (P<0.001). Overall one-year survival was 27.1% with radiation and 13.3% without (P=0.003).
"I think these results should now make prophylactic cranial irradiation standard care for these patients and should be translated into practice," said Ben Slotman, M.D., Ph.D., of VU University Medical Center in Amsterdam, at the American Society of Clinical Oncology meeting here.
Interest in prophylactic whole-brain irradiation evolved from the recognition that two-thirds of SCLC patients have extensive disease at diagnosis, said Dr. Slotman. Brain metastases are common, and response to local and systemic therapy is poor.
Studies conducted primarily in the 1980s showed that patients with limited disease and complete response to chemotherapy had a reduced risk of metastasis and improved survival after prophylactic brain irradiation.
Extending prophylactic cranial irradiation to patients with extensive disease, Dr. Slotman and colleagues randomized 286 patients to irradiation or observation following four to six cycles of chemotherapy. Patients who had any form of response to chemotherapy, as determined by their treating physicians, were eligible for the trial. About 75% of the patient had evidence of residual disease in the lung, and in 70% the disease had spread beyond the lung.
Irradiation consisted of 20 to 30 Gy administered in five to 12 fractions. Such a protocol is usually well tolerated, Dr. Slotman noted, and no serious adverse events occurred during the study. The most common radiation-related effects were headache, nausea and vomiting, and fatigue.
During a year of follow up, radiation patients had a greater than 60% reduction in the occurrence of brain metastases, which translated into a hazard ratio of 0.27 compared with the control group. Similar to prior experience in patients with less extensive disease, radiation led to a doubling of one-year survival that was associated with a hazard ratio of 0.68 compared with the control group.
"Prophylactic cranial irradiation significantly reduces the risk of symptomatic brain metastases and significantly prolongs survival," said Dr. Slotman. "This prophylactic irradiation is well tolerated and does not adversely influence quality of life. Prophylactic cranial irradiation should now routinely be offered to all responding SCLC patients with extensive disease."
Dr. Slotman said in an interview that the radiation fends off symptomatic brain metastases by destroying micrometastases that have already taken up residence in the brain. The lesions are too small to detect by brain imaging but provide the genesis for malignant growth. Unfortunately, the benefits of prophylactic whole-brain irradiation do not extend beyond SCLC to the much more common non-small cell lung cancer, he added.
A U.S. oncologist familiar with the study but not involved in it agreed that prophylactic brain irradiation should become the standard of care. He also predicted that U.S. physicians will not be hesitant to adopt the therapy.
"I expect prophylactic cranial irradiation will be taken up quickly in the U.S., as well," commented Roy Herbst, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston. "I think this will take standards of care to a new level."
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