Tavish Nanda

Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation

BACKGROUND We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). METHODS A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. RESULTS Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P = .019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P = .071). Targeted therapy was a strong predictor of increased OS on univariate (P = .037) and multivariate (P = .022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P < .05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P = .003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P = .471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P = .577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. CONCLUSIONS This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

Risk of dry eye syndrome in patients treated with whole-brain radiotherapy

With improvements in systemic therapy, patients with cancer treated with whole-brain radiotherapy (WBRT) are living long enough to develop late toxicities, including dry eye syndrome. In general practice, dose to the lacrimal gland (LG) is not constrained (maximum constraint <40 Gy) in WBRT. The purpose of this study was to measure dose to the LG in WBRT and determine methods for reducing radiation exposure. We conducted a retrospective review of 70 3-dimensional (3D) conformal plans; thirty-six plans with a radiation prescription of 30 Gy in 10 fractions and 34 plans with a prescription of 37.5 Gy in 15 fractions. LGs were contoured in accordance with Freedman and Sidani (2015). Biological effective dose (BED)3 maximum constraints were calculated from 40 Gy and 20 Gy to be 32.17 Gy (30 Gy) and 36.70 Gy (37.5 Gy). Both regimens demonstrated supraorbital blocking by 3 methods: T1, bordering the supraorbital ridge; T2, no contact with supraorbital ridge; and T3, coverage of the supraorbital ridge. Mean dose for the plans with a 30-Gy prescription and the plans with a 37.5-Gy prescription was 27.5 Gy and 35.2 Gy, respectively (p ≤ 0.0001). BED3 maximum constraint (Dmax) was violated 16 of 26 (61.5%) in T1 (average Dmax: 32.2 Gy), 13 of 28 (46.4%) in T2 (average Dmax: 32.1 Gy), and 5 of 18 (27.8%) in T3 (average Dmax: 31.8 Gy) for the 30-Gy prescription. Dmax was violated in 32 of 32 (100%) in T1 (average Dmax: 40.1 Gy), 22 of 22 (100%) in T2 (average Dmax: 40.3 Gy), and 14 of 14 (100%) in T3 (average Dmax: 39.4) for the 37.5 Gy prescription. Average Dmax for the 37.5-Gy prescription was highly significant in favor of T3 (p = 0.0098). Patients who receive WBRT may develop dry eye syndrome as a late toxicity. Constraints are commonly violated with a prescription of 37.5 Gy. Methods to reduce dose include T3 supraorbital blocking, an easily implementable change that may dramatically improve patient quality of life.