Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

• Systematic review on neurotoxicity of TKI and concurrent cranial radiation in NSCLC.
• ALK: no data, concurrent EGFR–TKI and WBRT no increased neurotoxicity.
• WBRT combined with SRS and concurrent EGFR–TKI: increased neurotoxicity.
• Only one phase I study with solely NSCLC patients with activating EGFR-mutation.
• Only two studies with extensive neurocognitive function testing.

Recently, non-small cell lung cancer (NSCLC) has been partly subclassified into molecularly-defined oncogene “addicted” tumors for which targeted agents are available. Tyrosine kinase inhibitors (TKI) are currently approved for patients with an activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. In these patients, brain metastases are often the first site of progression while on TKI treatment. The TKI may however still be active on extra-cranial sites and clinicians are thus faced with the question if the TKI may be continued during cranial radiotherapy. Advantages of combining TKI with cranial radiotherapy would be a possible synergistic effect on the brain metastases and the prevention of a systemic disease flare-up. A disadvantage is the possibly increased risk of (neuro)toxicity. The present systematic review addresses the toxicity of combining TKI with cranial radiotherapy in NSCLC patients.