Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development

Justyna Chalubinska-Fendler, Lucyna Kepka

Abstract

In non-small cell lung cancer (NSCLC) brain metastases (BM) will affect up to 50% of patients during whole disease period. BM themselves impact heavily not only on patient’s prognosis but also are a source of symptoms aggravating quality of life. Standard (pemetrexed), and non-standard chemotherapy (temozolomide) in patients with NSCLC failed to prevent them from BM. In terms of systemic treatment there are promising results showed when durvalumab (PACIFIC study), osimertinib (FLAURA trial) or alectinib (JALEX study) was used. However, those substances are effective only in small cohort with ALK or EGFR alterations. Prophylactic cranial irradiation (PCI) as a non-specific treatment has proven to be a powerful tool in preventing BM without affecting overall survival in neither way. That has been proved in nearly all earlier and all recent studies—NVALT11/DLCRG-02, RTOG 0214 update, Li et al. The positive effect of BM incidence reduction may draw fear form PCI usage due to potential cognitive toxicity the PCI may cause. Results of recent trials show that after PCI only mild cognitive disorders (MCD) may arise. Promising results in terms of reducing MCD are shown when memantine is used or/and hippocampal avoidance techniques are implemented. HA in PCI seem to be cost effective but calculations were made on small-cell lung cancer cohorts. Still even recent studies did not clarify finally which patients could benefit from PCI or other forms of preventing BM. It seems that new trials should focus on younger, fit and non- squamous histology patients and use the tests for mild cognitive disorders (MoCA, BHA) rather than screening tests for dementia (MMSE, HVLT, ADL). The main obstacle in performing new trials on PCI in NSCLC cohorts may be, however, patients’ accrual, as a difficulty which occurred during latest trials.