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Pooling seven trials showed that irradiating the brain before any tumour appears there adds about five people alive in a hundred at three years.
Small-cell lung cancer seeds the brain early and the blood-brain barrier keeps chemotherapy out, so brain relapse is common even in patients whose chest disease has cleared. Individual trials of prophylactic cranial irradiation each showed fewer brain metastases but none was large enough to show a survival gain. The Prophylactic Cranial Irradiation Overview Collaborative Group pooled individual data on 987 patients in complete remission from seven randomised trials.
The relative risk of death with irradiation was 0.84 (95 percent confidence interval 0.73 to 0.97, p=0.01), corresponding to three-year survival of 20.7 percent against 15.3 percent, a 5.4 percent absolute gain. Disease-free survival also improved (relative risk of recurrence or death 0.75, 0.65 to 0.86).
The meta-analysis made prophylactic cranial irradiation standard in limited-stage disease that has responded, and Slotman's EORTC 08993 extended it to extensive-stage disease in 2007. Both are now qualified: the Japanese trial by Takahashi, which required a brain MRI at baseline and three-monthly MRI surveillance afterwards, found no survival benefit and a numerically worse result with irradiation, so in centres that can offer MRI surveillance the choice is genuinely open, and neurocognitive cost is weighed against a benefit measured in a pre-MRI era. Hippocampal avoidance is the current attempt to keep the benefit and lose the cost.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
987 analysed.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival at 3 yearsprimary | Prophylactic cranial irradiation | - | 20.7% | 0.84 (0.73 to 0.97) | 0.01 | link |
| No prophylactic cranial irradiation | - | 15.3% |
Shares EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer, Takahashi trial: prophylactic cranial irradiation with MRI surveillance in extensive-stage small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer.
Shares EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung cancer (all types), IMRT / IGRT (modern external beam).
Shares Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, IMRT / IGRT (modern external beam).
Shares Brain metastases (intracranial disease), Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Small-cell lung cancer.
Shares Curative intent vs palliative intent, Lung cancer (all types), IMRT / IGRT (modern external beam).
Shares Curative intent vs palliative intent, Limited-stage small-cell lung cancer, Lung cancer (all types), IMRT / IGRT (modern external beam).
Shares EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer, Lung cancer (all types).
Shares EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer, Takahashi trial: prophylactic cranial irradiation with MRI surveillance in extensive-stage small-cell lung cancer, Brain metastases (intracranial disease), Extensive-stage small-cell lung cancer.