Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

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Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigate the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single fraction SRS for BMs. A total of 113 BMs (91% intact, 9% post-operative) were treated with median dose 21Gy (15-24Gy). Ipi was given at 3mg/kg (54%) or 10mg/kg (46%) for a median of 4 doses (1-21). Adverse events were recorded using CTCAE 3.0. Kaplan-Meier methods were used to estimate survival and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with timing of SRS/Ipi (p=0.035) and melanoma-specific graded prognostic assessment (p=0.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence (RR) than those treated with SRS after Ipi (1-yr OS 65% vs. 56% vs. 40%, p=0.008; 1-yr RR 69% vs. 64% vs. 92%, p=0.003). SRS during Ipi also yielded a trend toward less local recurrence (LR) than SRS before or after Ipi (1-yr LR 0% vs. 13% vs. 11%, p=0.21). On MRI, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but only 13% of patients treated after Ipi. Grade 3-4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly due to enhanced immunomodulatory effect.

Objective We sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients. Methods We used a multistage process combining consensus methodology and literature reviews to arrive at the American College of Rheumatology's (ACR) Top 5 list. Rheumatologists from diverse practice settings generated items using the Delphi method. Items with high content agreement and perceived high prevalence advanced to a survey of ACR members, who comprise >90% of the US rheumatology workforce. To increase the response rate, a nested random sample of 390 rheumatologists received more intensive survey followup. The samples were combined and weighting procedures were applied to ensure generalizability. Items with high ratings underwent literature review. Final items were then selected and formulated by the task force. Results One hundred five unique items were proposed and narrowed down to 22 items during the Delphi rounds. A total of 1,052 rheumatologists (17% of those contacted) participated in the member‐wide survey, whereas 33% of those in the nested random sample participated; respondent characteristics were similar in both samples. Based on survey results and available scientific evidence, 5 items (relating to antinuclear antibodies, Lyme disease, magnetic resonance imaging, bone absorptiometry, and biologic therapy for rheumatoid arthritis) were selected for inclusion. Conclusion The ACR Top 5 list is intended to promote discussions between physicians and patients about health care practices in rheumatology whose use should be questioned and to assist rheumatologists in providing high‐value care.