Efficacy
The evidence supporting this protocol is provided by a meta-analysis involving 987 patients comparing prophylactic cranial irradiation (PCI) with no PCI in patients with complete response (CR) to induction therapy for small cell lung cancer.r In some trials CR was assessed by chest X-ray, others required bronchoscopy or CT of the chest or brain. In the analysis, 526 patients were randomised to receive PCI and 461 patients were randomised to receive no PCI. Of these, there were 464 patients with limited stage (LS) SCLC in the control group and 383 in the PCI group. For the overall group (including extensive disease) the 3-year cumulative incidence of brain metastases (BM) was 33.3% with PCI (compared to 58.6%, p= <0.001) and the 3-year overall survival (OS) in the PCI group was 20.7% (compared to 15.3%, p=0.01). For the subgroup with LS-SCLC the relative risk (RR) of brain metastases was 0.48 (0.38–0.60) with PCI and the Relative Risk of death was 0.85 (0.73-0.99).
Dose-fractionation
The evidence for recommending 25 Gy in 10 fractions is provided by a randomised clinical trial of 720 patients with LS-SCLC and CR after chemoradiation therapy (CRT).r This trial compared standard dose PCI (25 Gy in 10 fractions) versus higher doses (36 Gy in 18 fractions or 24 Gy in 16 bi-daily fractions). In the trial, 360 patients were randomised to receive standard dose PCI and 360 to higher dose PCI. There was no significant difference in the 2-year incidence of brain metastases (29% and 23%), however there was a better 2-year OS in the standard-dose group (42% vs. 37%, p= 0.05).
Neurotoxicity in patients over 60 years old
In patients older than 60 years, consider the impact of treatment on quality of life and chronic neurotoxicity especially in the presence of likely risk factors for neurocognitive effects such as advanced age, smoking, cerebrovascular disease and diabetes.rr
Hippocampal sparing
In a recent phase III trial, 150 patients with SCLC (71.3% with limited disease) were randomised to standard PCI (25 Gy in 10 fractions) or hippocampal avoidance (HA)-PCI.r Cognitive function was assessed with the Free and Cued Selective Reminding Test (FCSRT). Decline on delayed free recall from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%). Decline on the total recall was reduced with HA at 3 months (8.7% v 20.6%), 6 months (20.3% v 38.9%) and 24 months (14.2% v 47.6%). The incidence of brain metastases, overall survival, and quality of life were not significantly different.
Another phase III trial included 168 patients with SCLC treated with standard PCI or HA-PCI at a dose of 25 Gy in 10 fractions.r Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms. The cumulative incidence of brain metastases at 2 years did not differ according to treatment arms and was 20% for the PCI arm and 16% for the HA-PCI arm.