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Purpose In patients with crizotinib-treated, anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC), initial disease progression often occurs in the CNS. We evaluated brigatinib, a next-generation ALK inhibitor, in patients with ALK-positive NSCLC with brain metastases. Patients and Methods Patients with ALK-positive NSCLC received brigatinib (90 to 240 mg total daily) in a phase I/II trial (phI/II; ClinicalTrials.gov identifier: NCT01449461) and in the subsequent randomized phase II trial ALTA (ALK in Lung Cancer Trial of AP26113; ClinicalTrials.gov identifier: NCT02094573; patients in arm A received 90 mg once daily; patients in arm B received 180 mg once daily with 7-day lead-in at 90 mg). Primary end points (systemic objective response rates [ORRs]) were previously reported. Independent review committees assessed intracranial efficacy in patients with baseline brain metastases. Results Most patients with ALK-positive NSCLC had baseline brain metastases (50 of 79 [63%], phI/II; 80 of 112 [71%] and 73 of 110 [66%] in ALTA arms A and B, respectively), many of whom had no prior brain radiotherapy (23 of 50 [46%], phI/II; 32 of 80 [40%], ALTA arm A; 30 of 73 [41%], arm B). All patients, except four in phI/II, had received crizotinib. Among patients with measurable (≥ 10 mm) brain metastases, confirmed intracranial ORR was 53% (eight of 15; 95% CI, 27% to 79%) in phI/II, 46% (12 of 26; 95% CI, 27% to 67%) in ALTA arm A, and 67% (12 of 18; 95% CI, 41% to 87%) in arm B. Intracranial ORRs were similar in subsets without prior radiation or progression postradiation. Among patients with any baseline brain metastases, median intracranial progression-free survival (iPFS) was 14.6 months (95% CI, 12.7 to 36.8 months), phI/II; 15.6 months (95% CI, 9.0 to 18.3 months), ALTA arm A; 18.4 months (95% CI, 12.8 months to not reached), ALTA arm B. Conclusion Brigatinib yielded substantial intracranial responses and durable iPFS in ALK-positive, crizotinib-treated NSCLC, with highest iPFS in patients receiving 180 mg once daily (with lead-in).

Background: Little is known about the postoperative complications experienced by patients with severe cerebral palsy (CP) (GMFCS IV-V) compared with otherwise healthy patients with hip pathology requiring surgery. The purpose of this study was to determine whether differences exist between these 2 groups with respect to the incidence, type, and severity of complications. In addition, we evaluated the risk factors for complications and the number and cost of additional visits, hospital admissions, and repeat surgeries due to complications., Methods: Retrospective matched cohort study of 55 patients aged 3 to 25 years with severe CP and 55 non-CP patients with hip dysplasia who underwent hip osteotomies (2000 to 2012). Postoperative complications were evaluated using the adapted Clavien-Dindo classification system. Binary and ordinal logistic regressions were used to identify risk factors for complications. The number and cost of unplanned visits, admissions, and surgeries were calculated., Results: CP patients experienced almost twice as many complications as the non-CP patients (P=0.004). All types of complications occurred in both groups except orthopaedic complications (P<0.001) were more frequent in the non-CP group. CP patients were 82% more likely to develop a complication compared with non-CP patients (relative risk=1.82; 95% confidence interval=1.21 to 2.76). The severity of complications was comparable with no significant differences in the relative distribution between the groups. There was a significant difference between groups for the number of unplanned clinic and emergency department visits (P≤0.001). The average cost for treating a complication was $1857.00 for CP and $1800.00 for non-CP (P=0.72)., Conclusions: Although patients with severe CP requiring hip surgery have a 65% chance of experiencing at least 1 postoperative complication compared with 36% of non-CP patients, most of the complications were medical in the CP patients (n=46, 83%) as opposed to the non-CP patient who experienced predominantly orthopaedic complications (59%). When these complications occur the associated costs are greater for CP patients as a whole, but are relatively similar per patient., Level of Evidence: Level III—Prognostic, case-control study.

Study Objectives: Although other specialties have examined the role of the chief resident (CR), the role and training of the emergency medicine (EM) CR has largely been undefined., Methods: A survey was mailed to all EM CRs and their respective program directors (PD) in 124 EM residency programs. The survey consisted of questions defining demographics, duties of the typical CR, and opinions regarding the level of support and training received. Multiple choice, Likert scale (1 strong agreement, 5 strong disagreement) and short-answer responses were used. We analyzed associations between CR and PD responses using Chi-square, Student's T and Mann-Whitney U tests., Results: Seventy-six percent of CRs and 65% of PDs responded and were similar except for age (31 vs. 42 years; p<0.001). CR respondents were most often male, in year 3 of training and held the position for 12 months. CRs and PDs agreed that the assigned level of responsibility is appropriate (2.63 vs. 2.73, p=0.15); but CRs underestimate their influence in the residency program (1.94 vs. 2.34, p=0.002) and the emergency department (2.61 vs. 3.03, p=0.002). The majority of CRs (70%) and PDs (77%) report participating in an extramural training program, and those CRs who participated in training felt more prepared for their job duties (2.26 vs. 2.73; p=0.03)., Conclusion: EM CRs feel they have appropriate job responsibility but believe they are less influential in program and department administration than PD respondents. Extramural training programs for incoming CRs are widely used and felt to be helpful.