tbuckley/cabot-search huggingface dataset:
Molecular profiling as predictor of outcomes in a Brazilian cohort of stage IV lung cancer.
Authors: Nicolas Peruzzo, Juliano Ce Coelho, Gabriel de Souza Macedo, Tiago Finger Andreis, Gustavo Gössling, Pedro Grachinski Buiar, Débora Leite Rocha, Patricia Ashton-Prolla
Journal: Journal of Clinical Oncology (2019)

e20668 Background: Lung cancer is the leading cause of cancer deaths globally. In stage IV non-small cell lung cancer (NSCLC), identification of a tumor driver mutation is critical, since it tailors treatment. We aimed to analyze clinical outcomes according to molecular profiling in patients (pts) with stage IV NSCLC. Methods: In this retrospective cohort study, we enrolled 57 pts with stage IV NSCLC treated at a public hospital in Southern Brazil between 2016 and 2018. Results: Median follow-up was 20.3 months, 53% were men, mean age was 65 years, 86% had smoked, 84% had de novo metastatic NSCLC and 96% had non-squamous carcinoma. Regarding molecular profiling, somatic mutations in KRAS, EGFR and BRAF were identified in 33%, 16% and 4% of pts, respectively. None of the pts had ALK mutations, and in 47% no identifiable driver mutation was found. In the EGFR-mutated subgroup, 67% had a deletion of exon 19, 22% had the exon 21 L858R mutation and 11% had exon 20 mutations. Palliative systemic therapy (PST) was delivered to 60% of the pts. Two or more lines of PST were delivered to 23%. The main reason for upfront best supportive care was ECOG PS 3-4 (poor). In the subgroup of pts with sensitizing EGFR mutations (8 pts), 75% received Gefitinib, the only anti-EGFR drug available in our public health system; the other pts died before recognition of the mutation. Median Progression Free-Survival was 6.3 months overall, 10.3 months for EGFR-mutated pts, 7.6 months for KRAS-mutated, 7.5 months for BRAF-mutated, and 5.2 months for pts with no mutation identified. Median Overall Survival (OS) was 7.7 months overall, 13.2 months for EGFR-mutated pts, 7.4 months for KRAS-mutated, 12.9 months for BRAF-mutated, and 5.3 months for pts with no mutation identified. In the Cox regression multivariate analysis, poor PS (HR 3.80, P &lt; 0.0001) and second-line PST (HR 0.23, P = 0.002) were independent predictors of OS. No driver mutations were predictors of OS, although we did find a tendency towards better OS in pts with EGFR mutations and worse OS in pts with KRAS mutations or no identifiable mutation. Conclusions: In this cohort, genotyping results did not predict survival outcomes. This is probably due to the small number of pts studied, and data should be reanalyzed in larger cohorts.
AB1173 ENDOCARDIAL LESIONS IN PATIENTS WITH RHEUMATIC DISEASES: CASE REVIEW
Authors: Sergio Rodríguez Montero, Consuelo Ramos Giráldez, PLAZA NAHIA, Jose Luis Marenco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The infection of a native or prosthetic heart valve usually occurs in patients with structural valvular anomalies that predispose to turbulent flows. Manifestations such as arthralgia, arthritis or back pain appear in up to 40% of patients, which acts as a confounding factor when this infection occurs in patients with rheumatic diseases. On the other hand, in the latter patients, noninfectious endocarditis has been described, which adds even more complexity to the diagnosis. <h3>Objectives</h3> To describe the characteristics of endocardial lesions in patients with rheumatic diseases. <h3>Methods</h3> Patients attending clinics at the Department of Rheumatology were analyzed to determine how many of them required hospitalization for causes directly related to endocardial lesion, from January 2015 until December 2018. The following information was recorded: age, sex, type of rheumatic disease, duration of the disease, immunosuppressive treatment, characteristics of endocardial lesions, complications of endocardial lesions, and cardiovascular risk factors. <h3>Results</h3> All patients were identified from an electronic database. Results regarding to demographic and clinical data are as follows: <h3>Conclusion</h3> The spectrum of endocardial involvement in patients with rheumatic diseases is variable. In this case review, we found lesions of different origin: infectious, thrombotic and tumoral. The appearance of fever of unknown origin in patients with rheumatic diseases, requires ruling out an endocarditis, needing transesophageal echocardiography in case the transthoracic study, which is less sensitive, is negative. It is striking the case of patient 3, a systemic sclerosis with calcinosis in limbs, whose endocardial wart, was studied histologically, revealing in its composition mainly calcium and fibrin. We have not found a bibliographic reference of calcium endocarditis in systemic sclerosis. In conclusion, patients with rheumatic diseases can develop infectious endocarditis, but also thrombotic valvular vegetations, as well as myxomas whose consequences, from their clinical debut, may pose life-threatening situations for the patient. The presence of fever, stroke or embolic events in these patients should put us on the track of an underlying endocardial involvement. <h3>References</h3> [1] Am J Med (2007) 120, e1-e2 [2] World J Cardiol 2014 September 26; 6(9): 993-1005 [3] Rev Esp Enferm Metab óseas 2002;11(2): 50-58 <h3>Disclosure of Interests</h3> Sergio Rodríguez Montero: None declared, Consuelo Ramos Giráldez Speakers bureau: Sanofi, NAHIA PLAZA: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen
Gene expression comparison between primary triple-negative breast cancer and matched axillary lymph node metastasis.
Authors: Marissa K. Srour, Bowen Gao, Farnaz Dadmanesh, Ying Qu, Xiaojiang Cui, Armando E. Giuliano
Journal: Journal of Clinical Oncology (2019)

565 Background: Sentinel lymph node (SLN) biopsy guides breast cancer treatment and prognostication. To date, there have been few studies examining the genetics of SLN metastasis in triple negative breast cancer (TNBC). The aim of this study is to characterize and compare gene expression patterns of primary breast cancers and autologous matched SLN metastases. Methods: Patients with stage 2-3 ER/PR negative, HER2 negative TNBC with macrometastasis to the SLN who did not have neoadjuvant therapy were selected. The tumor-specific area was isolated from breast and SLN paraffin embedded tissue sections. Gene expression of a panel of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Results were validated with RNA-scope assays for RNA in situ detection. Results: 18 pairs of TNBC and matched SLN metastasis were analyzed for 2567 genes. Compared with the primary TNBC, SLN metastasis had 34 statistically significant upregulated genes and 31 downregulated genes. SLN metastasis had at least a 5-fold change (FC) in upregulation in 3 genes and downregulation in 3 genes, compared to primary TNBC [Table]. Notably, there was an upregulation of anti-apoptosis and survival signaling genes (i.e. BIRC3) in the SLN metastasis. There was also an upregulation of chemotaxis genes (CCL13, CXCL19, CXCL21, CXCR5, TNFSF11, p&lt;0.001). The most striking feature is the downregulation of genes known to regulate cell microenvironment interaction (MMP2, MMP14, COL1A1, COL1A2, COL5A2, COL6A6, COL11A1, COL17A1). Conclusions: In TNBC, SLN metastasis has a distinct gene expression profile. Genes associated with anti-apoptosis, survival responses, and chemotaxis are upregulated, and genes associated with regulation of extracellular matrix are downregulated. Upregulated and downregulated genes with at least a 5-fold change in gene expression in lymph node metastasis compared with TNBC.[Table: see text]
Multi-parametric FDG PET/MRI as an early predictor of response to neoadjuvant chemotherapy in patients with epithelial ovarian cancer.
Authors: Melissa Kristen Frey, Zacharia Sawaged, Ana M Franceschi, Kent P Friedman, Kathleen Lutz, John Patrick Curtin, Stephanie V. Blank, Bhavana Pothuri
Journal: Journal of Clinical Oncology (2019)

5569 Background: For patients with ovarian cancer undergoing neoadjuvant chemotherapy, the effectiveness of treatment is not evaluable by conventional methods until all or much of the treatment has been given. The purpose of this study is to investigate the performance of FDG PET, dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR as early predictors of treatment response. Methods: Subjects with a new diagnosis of epithelial ovarian cancer underwent 3 cycles of standardized chemotherapy followed by cytoreduction. FDG PET/MR including DCE and IVIM was performed at baseline (T0), after cycle 1 (T1) and after cycle 3 (T2) of chemotherapy. Final responses were categorized at T2 by RECIST 1.1. Image volumes at T1 were analyzed as predictors of final response. Parametric images of molecular diffusion restriction (D), tissue perfusion (D*), vascular volume fraction (F), blood- &gt; interstitium constant of transfer (Ktrans), interstitum- &gt; plasma constant of transfer (Kep), extravascular/extracellular volume % (Ve) and plasma volume % (Ve) were investigated along with routine measures of SUV and ADC. Results: Nine subjects were enrolled, 8 were responders by RECIST at T2 and one had stable disease. At T0 the mean, min, and max SUVmax of dominant tumor deposits was 11.5, 6.3, 19.0, respectively. Mean, min, and max values were 1.0, 0.75 and 1.63 for ADCmean and 0.62, 0.30, 0.96 for ADCmin. At T1, ADCmean increased in 8 subjects by +0.22% (s.d. +/- 13%) and decreased by -3% in one subject. ADCmin increased in 8 subjects by +21% (s.d. +/-11%) and decreased by -23% in one subject. D increased for 8 subjects (average +29% s.d. +/- 13%) and decreased by -10% in one. D*, F, Kep, Ktrans, Ve and Vp had no recognizable pattern. At T2, SUVmax, SUVmin, and ADCmean maintained their change direction across all subjects with measurable lesions. The only subject with a complete response at T2 had the highest ADCmin and ADCmean change at +45% after one cycle of chemotherapy (T1). The subject with stable disease at T2 had no significant difference in changes amongst all metrics. Conclusions: FDG PET/MR SUVmax and ADCmean values obtained after one cycle of neoadjuvant chemotherapy were consistently associated with partial anatomical treatment responses after three cycles. Molecular diffusion restriction also was reliably associated with treatment response. Future studies evaluating FDG PET/MR in platinum-resistant patients may allow for early discontinuation of ineffective and toxic treatment.
Case 33-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, John J. Weiter, Wanda M. Szyfelbein
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 37-year-old woman was admitted to the hospital because of bilateral uveitis that was unresponsive to treatment.She was in excellent health until six months earlier, when she began to experience "throbbing" right retro-orbital headaches that occurred daily and were followed one month later by progressive blurring of vision in the right eye. She discontinued the use of contact lenses. Three months before admission there was a severe reaction to poison ivy that responded to treatment with orally administered prednisone.Two months before entry she was first seen at this hospital, where ophthalmologic examination showed that the . . .
Case 10-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Jules Baum, Daniel Albert
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 29-year-old woman was admitted to the hospital (Massachusetts Eye and Ear Infirmary) because of bilateral ulcerative keratitis.She was well until five months earlier, when she switched to soft contact lenses after having worn hard contact lenses for seven years. Six weeks later photophobia and erythema developed in both eyes. A physician found streak-shaped stromal opacities, with no anterior-chamber reaction. Chloramphenicol and prednisolone drops were prescribed. The patient's condition improved at first, but later examination disclosed bilateral disciform keratitis. Cultures of material from both eyes yielded no bacteria or fungi, and idoxuridine was added topically. The . . .
CTC versus biopsy tissue sequencing: A concordance analysis of genomic copy number profile from mCRPC patients (pts).
Authors: Howard I. Scher, Jerry Lee, Angel E. Dago, Ethan Barnett, Ramsay Sutton, Emily Carbone, Nicole A. Schreiber, Melanie Hullings, Nadia Ebrahim, Mark Andrew Landers, Yipeng Wang, David B. Solit, Michael F. Berger, Nikolaus Schultz, Ryan Dittamore
Journal: Journal of Clinical Oncology (2019)

3050 Background: MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), is a high throughput, targeted-DNA-sequencing panel for somatic mutations created by the Department of Pathology at Memorial Sloan Kettering Cancer Center (MSK). The MSK-IMPACT is FDA approved for tumor tissue profiling to guide treatment selection. Recognizing access to tumor tissue in many cancers is difficult and may harbor inter &amp; intra lesional heterogeneity, we sought to evaluate concordance of sequencing single CTCs vs. paired biopsy analyzed by MSK-IMPACT, to assess CTC vs. tumor clonality, and their relationship to outcomes. Methods: 148 biopsy samples from 138 mCRPC pts were submitted for IMPACT analysis and a blood draw within 30-day prior to initiation of a new line of treatment. Blood samples were sent to Epic Sciences for CTC detection. The detected CTCs underwent single cell low pass whole genome sequencing for copy number variation (CNV). For each set of matched samples, DNA copy number profiles from IMPACT and CTC sequencing were compared for similarity. Results: Of the 114 successfully sequenced samples 58 were from lymph nodes, 23 from bone, 25 from liver or lung, and 8 from other soft tissue. Of the 111 patients with CTCs analyzed, a total of 1073 CTCs were sequenced (range 1-27, median = 4 per pt). Of patients with both IMPACT &amp; CTC, &gt;80% pts had multiple subclones with distinguishable CNV. Concordance of genomics clones was found in 63%, and discordant in 37% cases. The clonal concordance between tissue biopsy and CTC was higher when the biopsy was obtained from bone marrow or a visceral site (71% concordance) than from a lymph node (53% concordance). Conclusions: Single CTC sequencing is often concordant to metastatic tissue, but unique CTC clones and the presence of multi-clonal disease highlight the potential to be underrepresented through tissue biopsy, especially when taken from the lymph node.[Table: see text]
Gemstone-301: A phase III clinical trial of CS1001 as consolidation therapy in subjects with locally advanced/unresectable (stage III) non-small cell lung cancer (NSCLC) who have not progressed after prior concurrent/sequential chemoradiotherapy (CRT).
Authors: Yi-Long Wu, Ming Chen, Qing Zhou, Hao Li, Wenyi Sun, Hongyan He, Dongmei Lu
Journal: Journal of Clinical Oncology (2019)

TPS8572 Background: In China, the standard of care for patients with unresectable Stage III NSCLC is platinum-based doublet chemotherapy given concurrently or sequentially with radiotherapy. However, the median progression-free survival (PFS) of those patients is poor (approximately 8-10 months) and 5-year overall survival (OS) rate is only 15%. Recently, treatment with durvalumab resulted in significantly longer PFS and OS than placebo for patients with locally advanced/unresectable NSCLC whose disease did not progress after definitive concurrent chemoradiotherapy (cCRT) in PACIFC trial. CS1001 is the first full-length, fully human programmed death ligand-1 (PD-L1) targeted immunoglobin G4 (IgG4, s228p) monoclonal antibody (mAb) developed by the OMT transgenic rat platform. The Phase Ia/Ib study (GEMSTONE-101, NCT03312842) demonstrated that CS1001 was well tolerated and had promising anti-tumor activities across a range of tumors including NSCLC. GEMSTONE-301 is a randomized, double-blind, Phase III study to compare the efficacy and safety of CS1001 versus placebo as consolidation therapy in Stage III unresectable NSCLC patients. This is the first Phase III trial on an anti-PD-(L)1 mAb initiated in China for this indication. Methods: In this trial, eligible patients with locally advanced/unresectable (Stage III) NSCLC who have not progressed after prior concurrent/sequential CRT are 2:1 randomized to receive CS1001 1200 mg, every 3 weeks or placebo, every 3 weeks. Stratification factors for randomization include ECOG status (0 versus 1), chemoradiotherapy (concurrent versus sequential) and total radiotherapy dose ( &lt; 60 Gy versus ≥ 60 Gy). Study treatment will be given for up to 24 months or until disease progression, intolerable toxicity, consent withdrawal, or discontinuation for other reason. Tumor assessments will be performed every 9 weeks in the first year and every 12 weeks thereafter by RECIST v1.1. AEs will be monitored throughout the study and graded according to NCI-CTCAE v4.03. Primary endpoint is PFS evaluated by investigators according to RECIST v1.1. Secondary endpoints are PFS evaluated by Blinded Independent Center Review (BICR), objective response rate, OS, time to death/distant metastasis (TTDM), safety and pharmacokinetics (PK) profile. Enrollment is ongoing across sites in China and will continue until 402 patients are randomized. Clinical trial information: NCT03728556.
The effect of the Affordable Care Act on genetic testing patterns and outcomes for inheritable cancer syndromes: A single institution experience.
Authors: Zhen Ni Zhou, Melissa Kristen Frey, Jessica Fields, Sushmita Gordhandas, Maria Paula Ruiz, Thomas A. Caputo, Kevin Holcomb, Eloise Chapman-Davis
Journal: Journal of Clinical Oncology (2019)

e13157 Background: National guidelines recommend genetic testing for women at increased risk for pathogenic mutations, however insurance coverage is a commonly cited barrier to test completion. The major provisions of the Affordable Care Act (ACA) became available in New York State (NYS) in January 2014. We sought to evaluate the effect of insurance status on genetic testing patterns following introduction of the ACA. Methods: Insurance status and genetic testing patterns at the hereditary breast and ovarian cancer center at a single institution were reviewed between 1/1/2013 and 12/31/2016. Insurance status and association with testing type and clinical outcomes were evaluated before and after January 2014. Results: During the study period, 1535 women underwent genetic counseling and genetic assessment. When comparing the cohort of women undergoing genetic testing prior to and following January 2014, significant increases in patients undergoing multigene panel testing were observed across all insurance types (6.3% vs. 40.6%, p &lt; 0.001). While a significant increase in the number of patients with private insurance or Medicaid as primary coverage was seen, the increase in insured women was largely attributed to insurance polices through the ACA exchange (p &lt; 0.001), with the majority being Medicaid ACA plans (80.3%). Conclusions: Since expansion of health insurance through the ACA in NYS, there has been a shift in the demographics of women undergoing genetic testing at a hereditary breast and ovarian cancer center with significantly more insured women and a rise in multigene panel testing. With insurance expansion and improved access to comprehensive genetic testing, insurance status should not be an obstacle for genetic testing.
FRI0220 OCULAR SURFACE INFLAMMATORY MARKERS CORRELATED WITH IMMUNOLOGICAL PARAMETERS IN PRIMARY SJöGREN’S SYNDROME
Authors: Nicolás Alfaro, Janett Carmen Riegatorres, Cesar Vidal Solis, David Vega Morales, Brenda Roxana Vázquez Fuentes, Dionicio Ángel Galarza-Delgado, Cassandra Michele Skinner Taylor, Mario Alberto Garza Elizondo, Karim Mohamed Noriega, Jesús Mohamed Noriega, César Alejandro Fernández de Luna, Fernando Morales Wong
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> In Sjögren's Syndrome (SS), ocular damage is mediated by inflammation induced by antibodies, enzymes, and other effectors that could be used as clinical indicators of the ocular surface damage. There is evidence suggesting that increased activity of matrix metalloproteinases (MMPs) is corelated with an increased ocular damage because of its potential inflamatory activity and could be used as a potential therapeutic target for dry eye<sup>1,2</sup>. Very few studies have addressed the rol betwen the ocular MMPS and the clinical parameters of SS. <h3>Objectives:</h3> To determine the level of correlation between the serological profile of autoantibodies with ophthalmological parameters at the cornea level. <h3>Methods:</h3> Cross-sectional, observational, and descriptive study. Sixty patients with a diagnosis of primary Sjögren's syndrome (pSS) classified according to the ACR/EULAR 2016 criteria were included. The following measurements were made: Schirmer test, lacrimal osmolarity, ocular staining score (OSS), and ocular surface disease index (OSDI) and metalloproteinase-9 (MMP-9) in tear and antibodies were measured in peripheral blood serum: RF isotypes (IgA, IgG, IgM), anti-SSA/Ro and anti-SSB/La in. <h3>Results:</h3> Fifty-eight women participated (96.7%) with an average age of 53 years (± 13.01) (Table 1). We found a positive correlation between OSS and RF-IgM (rho=0.385 P=0.002), RF-IgA (rho=0.256 P=0.049), and anti-Ro/SSA (rho=0.302 P&lt;0.019). We found a statistically significant association between the seropositivity of the Anti-SSA/Ro antibody and the presence of MMP-9 in tears (OR 4.38, CI 95% 0.877-21.92, P=0.057). A Spearman correlation test and the association between MMP9 and serology were evaluated whit χ2 test. <h3>Conclusion:</h3> A significant correlation was observed between serology, ocular surface damage (OSS), and ocular surface inflammation (MMP-9). The positivity of RF isotypes IgM and IgA could alert the clinician about the ocular damage to initiate a study directed to this organ. Nevertheless this present study shows preeliminary outcomes, we need to enroll more patients to obtain better outcomes. <h3>References:</h3> [1] Aluri, H. S., et al. (2015). Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome. Investigative ophthalmology &amp; visual science, 56(9), 5218-28. [2] Messmer, E. M., et al. (2016). Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay. Ophthalmology, 123(11), 2300–2308. https://doi.org/10.1016/j.ophtha.2016.07.028. <h3>Disclosure of Interests:</h3> None declared