Recommended first-line management of asymptomatic brain metastases from EGFR mutant and ALK positive non-small cell lung cancer varies significantly according to specialty: an international survey of clinical practice.

Background: The role for radiotherapy or surgery in the upfront management of brain metastases (BrM) in epidermal growth factor receptor mutant (EGFRm) or anaplastic lymphoma kinase translocation positive (ALK+) non-small cell lung cancer (NSCLC) is uncertain because of a lack of prospective evidence supporting tyrosine kinase inhibitor (TKI) monotherapy. Further understanding of practice heterogeneity is necessary to guide collaborative efforts in establishing guideline recommendations. Methods: We conducted an international survey among medical (MO), clinical (CO), and radiation oncologists (RO), as well as neurosurgeons (NS), of treatment recommendations for asymptomatic BrM (in non-eloquent regions) EGFRm or ALK+ NSCLC patients according to specific clinical scenarios. We grouped and compared treatment recommendations according to specialty. Responses were summarized using counts and percentages and analyzed using the Fisher exact test. Results: A total of 449 surveys were included in the final analysis: 48 CO, 85 MO, 60 NS, and 256 RO. MO and CO were significantly more likely than RO and NS to recommend first-line TKI monotherapy, regardless of the number and/or size of asymptomatic BrM (in non-eloquent regions). Radiotherapy in addition to TKI as first-line management was preferred by all specialties for patients with ≥4 BrM. NS recommended surgical resection more often than other specialties for BrM measuring >2 cm. Conclusions: Recommendations for the management of BrM from EGFRm or ALK+ NSCLC vary significantly according to oncology sub-specialties. Development of multidisciplinary guidelines and further research on establishing optimal treatment strategies is warranted.

Impact of EGFR mutation on outcomes following SRS for brain metastases in non-small cell lung cancer.

INTRODUCTION: Patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) are at particularly high risk of developing brain metastases (BrM). In addition to EGFR targeting tyrosine kinase inhibitors (TKI), radiosurgery (SRS) has an important role in the management of EGFRm BrM. However, data specific to the response and toxicity of EGFRm BrM to SRS are sparse. We evaluated the incidence of local failure (LF) and toxicity of EGFRm and EGFR-wild-type (EGFRwt) BrM treated with SRS. METHODS: We analyzed a prospective registry of BrM patients treated at our centre between 2008 and 2017 and identified EGFRm and EGFRwt NSCLC patients treated with SRS ±â€¯systemic therapy for BrM. Incidences of local failure (LF) and radionecrosis (RN) were determined, and Cox regression was performed for univariate and multivariate analyses (MVAs). RESULTS: We analyzed data from 218 patients (615 lesions - 225 EGFRm and 390 EGFRwt). Median imaging follow-up per patient was 14.5 months (0.5-96.3). Prior to or concomitant with SRS, 62 % of EGFRm patients received TKI and 93 % received TKI post SRS. The 24-month incidence of LF was 6% and 16 % for EGFRm BrM and EGFRwt, respectively (0.43(0.19-0.95); p = 0.037). The 24-month incidence of RN was 4% and 6% for EGFRm and EGFRwt BrM, respectively (0.8(0.32-1.98) p = 0.63). On MVA, BrM size and prescription dose (PD) significantly correlated with a higher risk of LF and BrM size correlated with a higher risk of RN. CONCLUSION: We observed excellent rates of response and toxicity following SRS in EGFRm compared to EGFRwt NSCLC, suggesting that EGFRm BrM have a favourable risk benefit ratio compared to EGFRwt NSCLC.