The role of brain radiotherapy for EGFR- and ALK-positive non-small-cell lung cancer with brain metastases: a review

Abstract

Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) metastases affecting patients' life expectancy and quality. At the present clinical trials including neurosurgery, radiotherapy (RT) and systemic treatments alone or in combination have provided controversial results. CNS involvement is even more frequent in NSCLC patients with EGFR activating mutations or ALK rearrangement suggesting a role of target therapy in the upfront treatment in place of loco-regionals treatments (i.e. RT and/or surgery). So far clinical research has not explored the potential role of accurate brain imaging (i.e. MRI instead of the routine total-body contrast CT and/or PET/CT staging) to identify patients that could benefit of local therapies. Moreover, for patients who require concomitant RT there are no clear guidelines on the timing of intervention with respect to innovative precision medicine approaches with Tyrosine Kinase Inhibitors, ALK-inhibitors and/or immuno-oncological therapies. On this basis the present review describes the therapeutic strategies integrating medical and radiation oncology in patients with metastatic NSCLC (mNSCLC) adenocarcinoma with CNS involvement and EGFR activating mutations or ALK rearrangement.

Keywords: ALK inhibitors; ALK rearrangement; Brain metastases (BM); Central nervous system (CNS); EGFR driver mutation; Non-small cell lung cancer (NSCLC); Radiotherapy; Tyrosine kinase inhibitors (TKI).

Fig. 1

proposed workflow of clinical management of brain metastases in mNSCLC with druggable drivers’ mutations. SRT stereotactic radiotherapy, WBI whole brain irradiation, MRI magnetic resonance imaging; Systemic therapy with TKI should be considered for all the patients with brain metastases. *In this case it is mandatory the use of highly effect new generation TKI