Hippocampal avoidance in prophylactic cranial irradiation for small cell lung cancer: benefits and pitfalls

Small cell lung cancers (SCLC) are a group of cancers that are clinically and pathologically different from other lung cancers. They are associated with high recurrence rates and mortality, and many patients present with metastatic disease. Approximately ten percent of SCLC patients have brain metastases at time of diagnosis, and the cumulative incidence of brain metastases increases to more than fifty percent at two years, even with optimal treatment. Hence, in patients without brain metastases at presentation, prophylactic cranial irradiation (PCI) is an important component of treatment along with systemic chemotherapy and radiotherapy. The goal of PCI is to decrease the incidence of subsequent symptomatic brain metastases in patients who show an initial response to the systemic treatment. Various clinical trials have evaluated the utility of PCI and found substantial benefit. Unfortunately, the long-term toxicity associated with PCI, namely the neuro-cognitive impairment that may develop in patients as a result of the radiation toxicity to the hippocampal areas of the brain, has raised concern both for patients and their treating physicians. Various techniques have been tried to ameliorate the neuro-cognitive impairment associated with PCI, including pharmacological agents and highly conformal hippocampal avoidance radiation. All of these have shown promise, but there is a lack of clarity about the optimal way forward. Hippocampal avoidance PCI appears to be an excellent option and a number of groups are currently evaluating this technique. Although there is clear benefit with this specialized radiation treatment, there are also concerns about the risk of disease recurrence in the undertreated hippocampal areas. This review attempts to compile the available data regarding the benefits and pitfalls associated with hippocampal avoidance PCI in the setting of SCLC.