Citations

e18321 Background: Despite the availability of targeted therapy for ROS1 NSCLC since 2016, there is limited information on real-world ROS1 testing practices to identify patients potentially eligible for targeted treatment among community practices. The objective of this study was to characterize ROS1 testing rates and identify potential barriers to ROS1 testing. Methods: The Flatiron Health EHR-derived database was used to identify patients diagnosed with advanced NSCLC between 7/1/2016 - 7/30/2018 and received systemic treatment in a community practice setting. Descriptive statistics were used to summarize the population, biomarker testing rates and timing of testing. Logistic and multinomial regressions including patient demographics and clinical characteristics were used to identify factors associated with the following outcomes: ROS1 testing, testing for biomarkers other than ROS1 (PDL1, ALK, EGFR) , longer times from advanced diagnosis (adv. dx) to ROS1 test results and initiation of therapy prior to ROS1 testing. Results: Of 9,275 eligible patients, ROS1 testing rates in squamous (SQ) and non-squamous histologies increased over the study period (30% to 52%, 62% to 75% respectively). Older age, males, poorer performance status, SQ histology, history of smoking and recurrent disease (RD) patients were significantly less likely to be tested. Among patients not tested for ROS1, 62% were tested for other biomarkers including > 50% of non-squamous patients tested for PDL1, EGFR or ALK and 51% of squamous patients tested for PDL1. The median time from adv. dx to test result was 24 days, with patient characteristics (i.e. Hispanic ethnicity, history of smoking) as well as test type predicting longer times to test results ( > 41 days vs. < 24 days after adv. dx). Patients who had a delay in test results were more likely to receive other therapy prior to availability of their ROS1 test results (25+ days vs. < 24 days OR [95% CI]: 9.18 [7.87, 10.70]). Conclusions: In real-world practice, patient characteristics were associated with ROS1 testing and testing delays which may result in some patient subgroups being less likely to be identified for potential targeted therapy.

e18240 Background: The time between a patient’s positive biomarker test result and initiation of targeted therapy may vary due to a number of factors, including the use of chemotherapy prior to or after the biomarker test result. The objective of this study was two-fold: first, to investigate the impact of delayed ALK inhibitor (ALKi) therapy on overall survival (OS) and second, to examine the association between the use of chemotherapy prior to or after biomarker testing and OS. Methods: The Flatiron Health EHR-derived database was used to identify patients with ALK-positive (ALK+) advanced NSCLC diagnosed between 1/1/2011 - 9/30/2018. The median time from ALK+ test result to ALKi start was used to separate patients into early versus delayed treatment cohorts. To account for potential immortal time bias, times from ALK+ test result to ALKi start from the delayed cohort were sampled with replacement and used to create modified index dates among the early cohort. Cox proportional hazards models adjusting for baseline characteristics (i.e. ECOG) were used to assess the association between delayed ALKi start and OS and the use of chemotherapy with OS. Results: 422 patients with ALK+ aNSCLC were included in this analysis with a median time from test result to ALKi start of 3 weeks. 88 patients (20.9%) received chemotherapy prior to starting their ALKi. Delayed ALKi use was associated with a 2.3 fold increase in risk of mortality (HR [95% CI]: 2.30 [1.28, 4.15], p < 0.01). There was no difference in survival observed between those who had received chemotherapy prior to initiating their ALKi and those who did not receive chemotherapy (HR [95% CI]: 0.99 [0.62, 1.58]). Among those who initiated chemotherapy prior to their ALK+ test result, the continued use of chemotherapy prior to initiating an ALKi did not result in differences in OS compared to those who switched to an ALKi without continuing chemotherapy (HR [95% CI]: 1.03 [0.44, 2.41]). Conclusions: Delayed initiation of ALKi may result in poor outcomes in patients with ALK+ NSCLC. Receipt of chemotherapy prior to ALKi or the duration of chemotherapy did not impact survival. Future strategies to improve the time to therapy initiation may be useful in improving patient outcomes.

5047 Background: We identified plasma cell free DNA (cfDNA) based copy number variations (CNV); single nucleotide variants (SNVs) & TMPRSS-ERG fusion in four sub states of metastatic prostate cancer (mPCa) and determined the impact on survival. Two mHSPC cohorts included treatment naïve, gp-1 and mHSPC patients (pts) responding to chronic androgen ablation (AA) (gp-2). Two mCRPC cohorts included mHSPC pts with PSA relapse on chronic AA (gp-3) and a clinically progressive mCRPC cohort post AA (gp-4). Methods: Enrollment of mPCa pts was performed from 2009-14 who were followed until 2018. Plasma from collected blood was used for extracting cfDNA. NGS was performed using Illumina HiSeq X for a preselected target panel of 129 genes including DNA damage repair genes. Statistical analyses of genomic aberrations were performed in R 3.5.1 and Cox proportional-hazard models were used for survival analyses. Results: A total of 255 pts were enrolled with 215 having adequate cfDNA that passed NGS QC. Median study follow up was 90.2 (Range:73;99) months. The table highlights pts in each gp with CNV, SNV, fusion events. ARamplification was higher in mCRPC gps3&4 (20/103 pts) compared to 3/106 pts in mHSPC gps1&2 (p < 0.001) and was prognostic for poor survival in mCRPC (p < 0.001;HR:3.34; 95%CI: 1.9-5.76). 54/103 pts in gp3&4 had SNVs in TP53 compared to 34/106 pts in mHSPC gps1&2 (P < 0.01). SNVs in APC, AR, CDK12 and BRIP1 were also increased in gps3&4 (p < 0.01). Gp1 mHSPC pts with SNVs in ATM/ CHEK2 had shorter response to AA (p < 0.001; HR:3.66; 95%: CI:1.81-7.39). Conclusions: Plasma cfDNA based somatic aberrations are detected with increased prevalence in mHSPC to mCRPC states. The ease of specimen collection and the need for molecular profiling in mPCa increases its potential for clinical applications in pt care. [Table: see text]

A decrease in cerebrospinal fluid pressure may result in an endolymphatic hydrops through a patent cochlear aqueduct or through the fundus of the internal auditory canal. This hydrops typically leads to low-frequency sensorineural hearing loss. We describe the case of a man who presented with a subjective and objective hearing loss in addition to a headache 4 days after he had undergone a dural puncture. We treated him with a standard epidural blood patch. Immediately after treatment, his hearing improved and his headache resolved.

ObjectiveBecause the American College of Rheumatology (ACR) practice guidelines affect the United States' and international treatment practice, we used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to characterize the quality of the guidelines and to identify potential areas for improvement.MethodsUsing the six quality domains in the AGREE II online tool, four reviewers assessed the practice guidelines available at the ACR website and the immediately previous version to summarize the domain scores for each guideline and examine trends over time.ResultsAs of April 2016, the ACR website listed nine guidelines, four with immediate previous versions. Based on AGREE II, the minimum and maximum for each domain (with higher being better) of the current guidelines were 78‐99 for Scope and Purpose, 57‐99 for Stakeholder Involvement, 87‐ 96 for Rigor of the Methodology, 83‐99 for Clarity of Presentation, 49‐78 for Applicability, 69‐85 for Editorial Independence, and 71‐96 overall. Over time, although the average domain quality of the guidelines improved for all, the Applicability and Editorial Independence domains had the least amount of improvement. For the four guidelines with previous versions, the mean (SD) absolute improvements for each domain were 18 (±11) for Scope and Purpose, 13 (±8) for Stakeholder Involvement, 38 (±22) for Rigor of the Methodology, 25 (±15) for Clarity of Presentation, 22 (±12) for Applicability, 24 (±17) for Editorial Independence, and 31 (±5) overall.ConclusionBased on the AGREE II instrument, the ACR guidelines have achieved high quality over the past 16 years. The Applicability and Editorial Independence domains have the greatest potential for future improvement.

PURPOSE To provide evidence-based recommendations on the treatment of multiple myeloma to practicing physicians and others. METHODS ASCO and Cancer Care Ontario convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and some phase II studies published from 2005 through 2018. Outcomes of interest included survival, progression-free survival, response rate, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 124 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed for patients with multiple myeloma who are transplantation eligible and those who are ineligible and for patients with relapsed or refractory disease.

We hypothesize that the prevalence of chronic kidney disease (CKD) among patients with cirrhosis has increased due to the increased prevalence of CKD‐associated comorbidities, such as diabetes. We aimed to assess the characteristics of hospitalized patients with cirrhosis with CKD and its impact on renal and patient outcomes. The North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) prospectively enrolled nonelectively admitted patients with cirrhosis and collected data on demographics, laboratory results, in‐hospital clinical course, and postdischarge 3‐month outcomes. CKD positive (CKD+) patients, defined as having an estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease–4 variable formula) of ≤60 mL/minute for >3 months, were compared with chronic kidney disease negative (CKD–) patients for development of organ failures, hospital course, and survival. There were 1099 CKD+ patients (46.8% of 2346 enrolled patients) who had significantly higher serum creatinine (2.21 ± 1.33 versus 0.83 ± 0.21 mg/dL in the CKD– group) on admission, higher prevalence of nonalcoholic steatohepatitis cirrhosis etiology, diabetes, refractory ascites, and hospital admissions in the previous 6 months compared with the CKD– group (all P < 0.001). Propensity matching (n = 922 in each group) by Child‐Pugh scores (9.78 ± 2.05 versus 9.74 ± 2.04, P = 0.70) showed that CKD+ patients had significantly higher rates of superimposed acute kidney injury (AKI; 68% versus 21%; P < 0.001) and eventual need for dialysis (11% versus 2%; P < 0.001) than CKD– patients. CKD+ patients also had more cases of acute‐on‐chronic liver failure as defined by the NACSELD group, which was associated with reduced 30‐ and 90‐day overall survival ( P < 0.001 for both). A 10 mL/minute drop in eGFR was associated with a 13.1% increase in the risk of 30‐day mortality. In conclusion, patients with CKD should be treated as a high‐risk group among hospitalized patients with cirrhosis due to their poor survival, and they should be monitored carefully for the development of superimposed AKI.

Abstract Articular cartilage is critical for painless and low‐friction range of motion; however, disruption of articular cartilage, particularly in the knee joint, is common. Treatment options are based on the size and depth of the chondral defect, as well as involvement of subchondral bone. The gold standard for evaluation of articular cartilage is with arthroscopy, but it is limited by its ability to objectively judge the depth and severity of chondral damage. Optical reflection spectroscopy has been introduced to objectively assess the thickness of cartilage. We present a technique to systematically evaluate the articular cartilage of the knee using BioOptico optical reflection spectroscopy (Arthrex) to better evaluate those with visible chondral and subchondral defects. Technique Video video See video under supplementary data.

There is increasing awareness that sleep disorders may be associated with increased perioperative risk. The Society of Anesthesia and Sleep Medicine created the Narcolepsy Perioperative Task Force: (1) to investigate the current state of knowledge of the perioperative risk for patients with narcolepsy, (2) to determine the viability of developing perioperative guidelines for the management of patients with narcolepsy, and (3) to delineate future research goals and clinically relevant outcomes. The Narcolepsy Perioperative Task Force established that there is evidence for increased perioperative risk in patients with narcolepsy; however, this evidence is sparse and based on case reviews, case series, and retrospective reviews. Mechanistically, there are a number of potential mechanisms by which patients with narcolepsy could be at increased risk for perioperative complications. These include aggravation of the disease itself, dysautonomia, narcolepsy-related medications, anesthesia interactions, and withdrawal of narcolepsy-related medications. At this time, there is inadequate research to develop an expert consensus or guidelines for the perioperative management of patients with narcolepsy. The paucity of available literature highlights the critical need to determine if patients with narcolepsy are at an increased perioperative risk and to establish appropriate research protocols and clearly delineated patient-centered outcomes. There is a real need for collaborative research among sleep medicine specialists, surgeons, anesthesiologists, and perioperative providers. This future research will become the foundation for the development of guidelines, or at a minimum, a better understanding how to optimize the perioperative care of patients with narcolepsy.