Cranial Irradiation Should Be Part of Small-Cell Lung Cancer Treatment

AMSTERDAM, Aug. 15 -- Prophylactic cranial irradiation improves overall survival in patients with small-cell lung cancer and should be a standard part of treatment, researchers said.

Patients were less likely to develop brain metastases and tended to survive about six weeks longer than their counterparts who did not receive irradiation (P=0.003), according to a study published in the Aug. 16, issue of the New England Journal of Medicine.

"Prophylactic cranial irradiation should be part of standard care for all patients with small-cell lung cancer who have a response to initial chemotherapy, and it should be part of the standard treatment in future studies involving these patients," concluded a research team led by Ben Slotman, M.D., Ph.D., of VU University Medical Center here.

Their study included 286 patients ages 18 to 75 who had extensive small cell-lung cancer but no evidence of brain or leptomeningeal metastases.

To be included in the study, patients could not have received any prior radiotherapy to the head or neck and must have shown a response to initial chemotherapy after four to six cycles.

Patients were randomized to receive irradiation or no further therapy for their cancer. There were no significant differences between the two groups at baseline.

Patients in the treatment group received radiation to two fields daily on a schedule of four to five fractions per week. The most commonly used schedules were 20 Gy given in five fractions, 30 Gy given in 10 fractions, 30 Gy given in 12 fractions and 25 Gy given in 10 fractions.

Only 24 of the 143 patients in the irradiation group developed brain metastases, compared with 59 of the 143 patients in the control arm.

The cumulative risks of symptomatic brain metastases were 4.4% and 14.6% at 6 and 12 months, respectively, in the irradiation group. By contrast, in the control group, the cumulative risks were 32% and 40.4% at 6 and 12 months, respectively.

There was no effect seen on extracranial progression at one year, but the irradiation did have positive effects on disease-free survival.

Patients in the irradiation group survived significantly longer without disease progression than did controls. Specifically, patients in the treatment group had a median of 14.7 weeks of disease-free survival versus 12 weeks among the patients who did not undergo prophylactic irradiation (P=0.02). The hazard ratio was 0.76 favoring irradiation.

At six months, the rate of survival without disease progression was 23.4% (95% CI, 16.6 to 30.9) in the irradiation arm and 15.5% (95% CI, 10.1 to 22.0) in the control group.

Overall survival was also longer in the patients who received cranial irradiation, the study showed (P=0.003). There was a median survival of 6.7 months in the irradiation group, compared with 5.4 months in the control arm. The hazard ratio for death in the irradiation arm was 0.68.

At one year, 27.1% (95% CI, 19.4 to 35.5) of patients in the irradiation group were alive, compared with 13.3 % (95% CI, 8.1 to 19.9) of the controls.

Patients generally tolerated the cranial irradiation, the researchers said. Acute reactions included headache, nausea and vomiting, fatigue, lethargy and rashes. Significant late reactions occurring after three months included mild headache or slight lethargy in 29 patients, moderate headache or severe lethargy in 15 patients and severe headache or central nervous system dysfunction in three patients.

These reactions may have been the result of tumor progression, not irradiation, the study authors pointed out. The cranial irradiation did not significantly influence patients' self-assessment of global heath status.

However, the authors pointed out, "a significant number of quality of life assessments were missing owing to the rapid clinical deterioration of the patients. The relatively low frequency of quality-of-life assessments may not have allowed us to detect a benefit resulting from a prolonged remission time in the irradiation group," they wrote.