Hippocampal avoidance during whole-brain radiotherapy is performed to prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless, the estimated risk of metastases in hippocampal avoidance area in small-cell lung cancer is unknown. The current study aimed to characterize the metastatic distribution within the brain relative to the hippocampus, estimate the incidence of hippocampal metastasis in patients with small-cell lung cancer, and identify clinical and radiographic variables that may be associated with the risk of hippocampal avoidance area metastasis.

Patients with small-cell lung cancer treated with therapeutic whole-brain radiotherapy between January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial magnetic resonance images obtained just before therapeutic cranial irradiation were retrieved and reviewed for each patient. The hippocampal avoidance area was defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account for necessary dose falloff between the hippocampus and the whole-brain planning target volume. Metastatic lesions within hippocampal avoidance area were defined as hippocampal metastasis. Hippocampal metastasis rate and characteristics of patients with hippocampal metastasis were analyzed and compared to patients without hippocampal metastasis.

Fifty-four patients evaluated with cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was 32% (17 patients). A total of 4.4% of all metastases involved the hippocampal avoidance area. The most common location was frontal lobe. Being younger than 65 years of age was found to be an independent risk factor for HM (odds ratio: 4.8, 95% confidence interval: 1-23.2, P = .049). The number of brain metastases was significantly higher in patients with hippocampal metastasis ( P = .027), and hippocampal metastasis rate was also higher in patients having larger hippocampus ( P = .026) and larger brain volumes ( P = .02).

Hippocampal metastasis might be more common in small-cell lung cancer. Reducing the dose to the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small-cell lung cancer may be risky for the development of HM compared with other malignant solid tumors.