Citations

ABSTRACT The public health implications of osteoporosis are enormous but the disease remains underdiagnosed and undertreated. In October 2018, the National Institutes of Health (NIH) convened a Pathways to Prevention (P2P) Workshop entitled “Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention” designed to identify research gaps, suggest future research opportunities, and advance the field through an evidence-based assessment. By design, the P2P report focused on “gaps” in our knowledge base. Unfortunately, however, the report did not sufficiently acknowledge the current evidence that unequivocally demonstrates the therapeutic efficacy of existing pharmacologic therapies for osteoporosis, which has the potential to exacerbate the current crises in osteoporosis diagnosis and treatment. © 2019 American Society for Bone and Mineral Research.

AbstractBackgroundPost‐operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post‐operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post‐operative pain and opioid consumption in patients undergoing liver resection.MethodsThis is a multi‐institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents—OME) and on pain scores (NRS‐11), we used generalized linear models and multivariable linear regression model, respectively.ResultsOne hundred and fifty‐three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post‐operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS‐11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively).ConclusionYounger patients and those with a history of analgesic use are more likely to report higher post‐operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

e13509 Background: Gliomas are a known risk factor for the development of spontaneous intracranial hemorrhage (ICH) independent of therapies directed against them, with studies reporting an incidence of 1.9-3.8%. Bevacizumab (BEV) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) FDA approved for recurrent glioblastoma. ICH is commonly considered to be a potential adverse effect of BEV use in patients with glioma, with previous retrospective studies describing incidence of intracerebral hemorrhage ranging from 1.9-3.3%. Methods: We performed a single center (Mayo Clinic, Rochester, MN) retrospective chart review of all patients who received BEV therapy at our institution for a diagnosis of primary CNS malignancy. We used ICD-9 and ICD-10 codes to identify adult patients with primary CNS neoplasms that subsequently developed ICH. Results: We screened 10,507 adult patients with a diagnosis of primary CNS neoplasm treated at our center from 01/31/2008 to 12/31/2018 and found 644 patients treated with bevacizumab. Of these, 23 (3.6%) suffered an ICH within 12 weeks of a BEV infusion (median 9 days post infusion, 1-24 IQR). The dose of BEV in all hemorrhages was either 10 mg/kg every two weeks (n = 21) or 15 mg/kg every three weeks (n = 2). No patients treated with infusions at 7.5 mg/kg every three weeks (n = 79) or 5 mg/kg every two weeks (n = 17) suffered ICH events, however this did not meet significance (P = 0.06) when compared to patients on 10 mg/kg or above. The median ICH score was 1 (0-2 IQR). There was an increase in ECOG scores documented at clinical follow up following the hemorrhage compared to the pre-hemorrhage functional status (ECOG 3.28 versus 1.2, p = < 0.0001), with 13 patients (56%) having developed severe debility or death (ECOG 4 n = 3, ECOG 5 n = 10). Conclusions: In our single-center cohort of patients with a primary diagnosis of CNS neoplasms treated with BEV, ICH occurred in 3.6% of patients. Those who experienced an ICH in proximity to BEV infusion had significant morbidity and mortality with a clear decline in functional status. There was a signal of dose response as far as ICH incidence in our cohort with dosages 10 mg/kg per infusion or above.

Abstract Background: Late recurrence is characteristic of ER+ breast cancers. Despite an apparently effective adjuvant endocrine therapy, many breast cancers recur years after their initial endocrine treatment. Why some tumors recur early (&lt;3 years) and some recur later (&gt;5 years) is poorly understood. If systemic endocrine therapies killed all cells, recurrence would reflect only the appearance of new disease. Thus, we hypothesized that cells that survive and lie dormant may be driven, in part, by altered wiring of their cell death signaling. We, therefore, studied how cell death signaling is differentially wired in primary tumors that will recur early versus those that will recur later. Method: Genes involved in apoptosis, autophagy, ferroptosis, necrosis, and pyroptosis were identified from KEGG to initiate network feature analysis of gene expression data from public and our first in-house gene expression dataset. Data were collected from ER+ breast cancer pre-endocrine treatment samples with up to 20 years follow-up. Publicly available datasets used were GSE6532, GSE2034, GSE7390, GSE17705, GSE12093, and TCGA. We applied our Knowledge-fused Differential Dependency Network (KDDN) analysis tool to the public datasets; KDDN has provided powerful new insights into signaling in breast and other cancers. Common gene-gene interactions (edges) predicted in at least two different datasets were extracted from all KDDN analyses results. To strengthen the relevance of these features, predicted network edges that represent known protein-protein interactions (PPI) were identified from the STRING database, and these edges were noted in the signaling graphs. Final network graphs were constructed using the common edges from all overlaid networks. We conducted IPA analysis on all nodes in the final network and selected those incorporating network hubs. We took a similar approach to our second in-house dataset, which we used for independent testing. Here, patients were included if their tumor exhibited an initial reduction in volume of at least 40% by four months in response to neo-adjuvant Letrozole. Patients were then classified into two groups during follow-up of up to 3.7 years: i) initial tumor size reduction followed by continued response (expected to recur late); ii) initial reduction followed by tumor regrowth (expected to recur early). KDDN analysis was performed on pretreatment samples from these two groups and a network created annotated with PPI information. Results: MAPK8 and CYCS (Molecular Mechanisms of Cancer, p=1.58E-52), TNFRSF1A Neuroinflammation Signaling Pathway, p=1.26E-54), RELA, and NFKB1 (Colorectal Cancer Metastasis Signaling, p=7.94E-35), were identified as hubs. Hubs may be critical signaling components driving the differences between tumors that will become dormant and recur late. Connections between SLC25A6 and SQSTM1 (p = 0.008), BIRC2 and GABARAP (p = 0.021) in the early group, and AKT3 and IRS2 (p = 0.014) in the late group, were shared between the two final networks. With longer follow-up time on the second in-house dataset, we will better define the two groups and identify additional common phenotype specific gene-gene interactions. Citation Format: Clarke R, Dixon M, Jin L, Pearce D, Turnbull A, Selli C, Hu R, Zwart A, Wang Y, Xuan J, Sengupta S, Sims A, Liu MC. Local network topology differences between early and late recurrence in ER+ breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-04-17.