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OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventriculomegaly, gait difficulty, incontinence, and dementia. The symptoms can be ameliorated by CSF drainage. The object of this study was to identify factors associated with shunt-responsive iNPH. METHODS The authors reviewed the medical records of 529 patients who underwent shunt placement for iNPH at their institution between July 2001 and March 2015. Variables associated with shunt-responsive iNPH were identified using bivariate and multivariate analyses. Detailed alcohol consumption information was obtained for 328 patients and was used to examine the relationship between alcohol and shunt-responsive iNPH. A computerized patient registry from 2 academic medical centers was queried to determine the prevalence of alcohol abuse among 1665 iNPH patients. RESULTS Bivariate analysis identified associations between shunt-responsive iNPH and gait difficulty (OR 4.59, 95% CI 2.32-9.09; p < 0.0001), dementia (OR 1.79, 95% CI 1.14-2.80; p = 0.01), incontinence (OR 1.77, 95% CI 1.13-2.76; p = 0.01), and alcohol use (OR 1.98, 95% CI 1.23-3.16; p = 0.03). Borderline significance was observed for hyperlipidemia (OR 1.56, 95% CI 0.99-2.45; p = 0.054), a family history of hyperlipidemia (OR 3.09, 95% CI 0.93-10.26, p = 0.054), and diabetes (OR 1.83, 95% CI 0.96-3.51; p = 0.064). Multivariate analysis identified associations with gait difficulty (OR 3.98, 95% CI 1.81-8.77; p = 0.0006) and alcohol (OR 1.94, 95% CI 1.10-3.39; p = 0.04). Increased alcohol intake correlated with greater improvement after CSF drainage. Alcohol abuse was 2.5 times more prevalent among iNPH patients than matched controls. CONCLUSIONS Alcohol consumption is associated with the development of shunt-responsive iNPH.

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8573 Background: There are few treatment options for thymic carcinoma after chemotherapy. We completed a single institution phase II study of pembrolizumab (P) in patients with recurrent thymic carcinomas. Methods: Main eligibility criteria included: progression after ≥ 1 chemotherapy line, ECOG PS 0-2, no history of autoimmune disease, and adequate organ function. P was given at 200mg IV every 3 weeks. The primary objective of the study was response rate (RR) by RECIST v1.1 criteria; secondary objectives were PFS and OS, and safety. Results: From 3/2015 to 12/2016 we accrued 41 patients. Of 40 eligible patients, 29 were male, 19 Caucasians, median age was 57 years (range 25-80), 14 had squamous carcinoma histology, and 19 ECOG PS 0. Median number of cycles delivered was 6 (range 1-31). The most common side effects were mild fatigue (10), diarrhea (4) and rhinorrhea (4). Six patients developed multiple grade 3-4 immune-relates AEs (irAEs): myocarditis/myositis (1), myositis/myocarditis/hepatitis/myasthenia gravis (1), myositis/hepatitis (1), bullous pemphigoid (1), hepatitis (1), hepatitis/pancreatitis/diabetes mellitus type 1 (1). There were no treatment related deaths. The 2 patients who developed myocarditis required a pacemaker. Three patients interrupted treatment because of irAEs (all responders) and 3 because of progression around the time of the irAE. irAEs were more frequent in females (4/6; p = .026). Five patients developed hypothyroidism and 1 hyperthyroidism. RR assessed in all 40 eligible patients was 22.5%: 1 complete response, 8 partial responses (plus 1 unconfirmed), 20 stable disease and with 11 progressions. Two partial responses show minimal residual disease with no PET uptake. Two responders have progressed and 5 responses are beyond 12 months duration. Of 29 cases tested for PD-L1 staining (Dako 22C3), high PD-L1 (≥50% tumor cells positive) was seen in 8 (28%); 6/9 responders had high PD-L1 expression. Targeted NGS in 15 cases did not show correlation between mutational burden and response. Conclusions: P has activity in patients with thymic carcinoma. irAEs are more frequent than in other tumors. Further analysis of NGS, Nanostring and PD-L1 expression and updated survival will be presented. Clinical trial information: NCT02364076.