Health system wide “big data” analysis of rheumatologic conditions and scleritis

Background The development of scleritis in the setting of autoimmune conditions has been well documented. Prior series have assessed the relationship between systemic autoimmune disorders and scleritis only in patients referred for rheumatologic or ocular inflammation. This can lead to a referral bias. We reviewed all charts within the electronic medical record (EMR) of a health system for patients with systemic autoimmune and scleritis diagnoses to determine the prevalence of both and which disorders had the highest relative risk of developing scleritis. Methods The EMR was searched for scleritis and systemic inflammatory diagnoses in the past medical history and diagnosis tabs, and for associated disease specific laboratory values. The intersection of scleritis and systemic inflammatory conditions was assessed through searching both SNOMED Clinical Terminology and ICD-10 codes for diagnoses. The prevalence of each autoimmune disorder, scleritis prevalence, the percentage of patients with an autoimmune condition having scleritis, the percentage of patients with scleritis having an autoimmune condition; the relative risk (RR) of scleritis patients having a specific autoimmune disorder were calculated. Results A total of 5.9 million charts were searched with autoimmune conditions identified in 148,993 patients. The most common autoimmune conditions overall were HLA-B27-associated diseases (n = 26,680; prevalence 0.45%); rheumatoid arthritis (RA)(N = 19,923; prevalence 0.34%). Conversely, 2702 patients were identified with scleritis (prevalence 0.05%), of which 31.4% had an associated autoimmune condition. Patients with RA represented the highest percentage of patients with an autoimmune condition having scleritis. Granulomatosis with polyangiitis (GPA) represented the highest the percentage of patients with scleritis having an autoimmune condition. Sjogrens was the third most common condition associated with scleritis- making up 4.5% of cases. An association with juvenile idiopathic arthritis (JIA) was seen in 0.3% of patients. Conclusions While this is the largest retrospective review examining the association between autoimmune disease and scleritis, the findings are similar to prior studies with nearly a third of scleritis patients having an underlying autoimmune diagnosis. Limitations of the study included accurate chart coding; having laboratory results within the searchable EMR. Future research is needed to delineate associations of systemic disease with the anatomic location of scleritis using EMR.

Comparing Glioblastoma Surgery Decisions Between Teams Using Brain Maps of Tumor Locations, Biopsies, and Resections

Purpose The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glioblastoma surgery decisions throughout the brain. Methods Adults undergoing first-time glioblastoma surgery from 2012 to 2013 performed by two neuro-oncologic teams were included. Patients had had a diagnostic biopsy or resection. Preoperative tumors and postoperative residues were segmented on magnetic resonance imaging in three dimensions and registered to standard brain space. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to compare patient referral bias, indication variation, and treatment variation. To evaluate the quality of care, subgroups of differentially resected brain regions were analyzed for survival and functional outcome. Results One team included 101 patients, and the other included 174; 91 tumors were biopsied, and 181 were resected. Patient characteristics were largely comparable between teams. Distributions of tumor locations were dissimilar, suggesting referral bias. Distributions of biopsies were similar, suggesting absence of indication variation. Differentially resected regions were identified in the anterior limb of the right internal capsule and the right caudate nucleus, indicating treatment variation. Patients with (n = 12) and without (n = 6) surgical removal in these regions had similar overall survival and similar permanent neurologic deficits. Conclusion Probability maps of tumor location, biopsy, and resection provide additional information that can inform surgical decision making across multidisciplinary teams for patients with glioblastoma.

Radium 223 (Ra-223) experience in twenty-four castration resistant prostate cancer (CRPC) patients treated at West Virginia University (WVU) 2014-2018.

e16502 Background: Ra-223 was FDA approved for CRPC with symptomatic bone metastases without visceral metastatic disease. Methods: De-identified IRB exempted records were abstracted for demographic, clinical, and laboratory data from CRPC men treated with Ra-223 at WVU 2014-2018. Results: 24 men had in total 95 Ra-223 infusions; 20 men (83%) were referred from outside institutions. Average ages (yrs; ranges) were 63 (48-87) at initial PC diagnosis; 68 (49-89) at first WVU-visit; and 69 (54-89) at first Ra-223 infusion. At diagnosis, 4 men (17%) had prostatectomy; 12 (50%) were M1/stage 4; PSAs ranged from 7-9,600 ng/mL. In 24 men, there were 73 courses of different androgen deprivation therapies (ADT); all had one, 22 (92%) two, 17 (71%) three, & 10 (42%) four or more; 68 (93%) of the 73 ADT trials preceded Ra-223. In 24 men, 19 (79%) had docetaxel or cabazitaxel chemoRx; 10 of 19 (53%) had 2nd line and 2 of 19 (11%) had 3rd - 4th line; chemoRx preceded Ra-223 in 18 of the 19 men (95%). In 24 men, 19 (79%) received 33 courses of radiation; in 9 of 33 (27%) the prostate was targeted; another 24 (73%) were palliative; 18 of 19 men (95%) had radiation before Ra-223. In 24 men, 24 had a 1st Ra-223 infusion, 21 (88%) a 2nd, 16 (67%) a 3rd, 12 (50%) a 4th, 12 (50%) a 5th, and 10 (42%) a 6th infusion; 14 men (58%) did not complete 6 infusions, most stopping for clinical decline or death. In 24 men, median overall survival (OS) from first Ra-223 infusion to last visit or death was 4.9 months (0-33); OS from last Ra-223 infusion was 1.2 months (0-28); 13 men (54%) remain alive & 3 (13%) continue Ra-223. Conclusions: Our CRPC patients’ best OS of 4.9 months with Ra-223 does not match the 14.9 months first reported (NEJM 2013; 369:213-223). Fourteen of our 24 men (58%) did not complete 6 planned Ra-223 infusions because of clinical decline or death. This may represent a “real world referral bias” of heavily pre-treated patients as documented above. Selecting more appropriate patients for Ra-223 is currently under review (https://www.esmo.org/Oncology-News/EMA-PRAC-Recommends-Restricting-Use-of-Prostate-Cancer-Medicine-Radium-223-Dichloride)

Population-based screening for BRAF V600E in metastatic colorectal cancer (mCRC) to reveal true prognosis.

3579 Background: BRAFV600E ( BRAF) mutations (mts) portend poor prognosis in mCRC and patients (pts) may die before ascertainment. Since 2014, Vancouver Coastal Health (VCH) has performed reflex hereditary screening of CRCs with BRAF and mismatch repair (MMR) immunohistochemistry (IHC). We evaluated this BRAF mt population-based cohort ( BRAFPOP) to establish the true prognosis of BRAF mts in mCRC. Methods: We reviewed all mCRCs from VCH between 4/2014 and 5/2018 for BRAF by IHC (VE1 antibody). Overall survival (OS) from stage IV diagnosis was compared to mCRCs with next generation sequencing (NGS) determined BRAF mts ( BRAFNGS) from BC Cancer & MD Anderson. BRAFNGS OS did not differ by center (p = 0.77). Results: See table for BRAF cohort baseline characteristic comparison. BRAFPOP pts had worse OS than BRAFNGS pts (HR 2.5, 95% CI 1.6 – 3.9, P < 0.0001). Median OS for all BRAF mt pts was 17.9 mos. Both groups had worse OS than wild type pts (P < 0.0001). 52 (81%) of BRAFPOP pts were referred to oncology, 40 (63%) received chemotherapy, and 12 (19%) had NGS BRAF testing. BRAFPOP pts who had NGS testing with BRAF mts had OS comparable to other BRAFNGS pts (P = 0.89) and better OS than BRAFPOP pts that never had NGS testing (HR 0.37, 95% CI 0.18-0.76, P = 0.030). Pts with BRAF mts and MMR deficiency (dMMR) (n = 40) had worse OS than MMR proficiency (pMMR, n = 202) (1.6, 95% CI 1.0-2.5, P = 0.011). This was driven by BRAFPOP dMMR pts (HR 1.9, 95% CI 0.9-4.0, P = 0.036) as no difference was seen by MMR in BRAFNGS pts (HR 1.3, 95% CI 0.8-2.2, P = 0.30). Conclusions: Current estimates of prognosis for mCRC with BRAF mts likely underestimate its impact due to referral bias for NGS testing. BRAF mts with dMMR are associated with worse prognosis than pMMR. This appears driven by BRAFPOP pts. [Table: see text]