tbuckley/cabot-search huggingface dataset:
FRI0351 DISTINCTION BETWEEN TELANGIECTASIA SECONDARY TO CONNECTIVE TISSUE DISEASE AND CUTANEOUS COLLAGENOUS VASCULOPATHY
Authors: Noreen Walsh, Phillip Moss, Thaiyen Ly, Sylvia Pasternak, Peter Green, Chris Gallant, Mary Lou Baxter, Colleen Kelly, Ariel Burns, Kerri Purdy, Elana Murphy, John Hanly
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cutaneous collagenous vasculopathy (CCV), a recently described, rare, superficial dermal microangiopathy of unknown etiology, shares clinical and histopathological features in common with cutaneous lupus erythematosus and dermatomyositis. Fewer than 50 cases have been reported in the literature. Concurrence of CCV and connective tissue diseases (CTD) may present a diagnostic quandary. <h3>Objectives</h3> To determine whether CCV cases at our center were associated with CTD and to identify distinguishing features between CCV and cutaneous manifestations of CTD. <h3>Methods</h3> The laboratory information system at a single academic health care center (2000-2018) was searched to identify cases with a diagnosis of CCV. All pathological material and clinical charts were reviewed. The demographic, clinical and pathological data were documented. <h3>Results</h3> We identified 6 cases of CCV (4 female, 2 male; median age 57 years). Clinically, a telangiectatic eruption was present in all patients, affecting the lower limbs and other sites (N= 5) and the abdomen and arms (N=1). All patients had been seen by a dermatologist and 3 by a rheumatologist. A concurrent CTD was present in 2 cases; Sjogrens syndrome (N=1) and undifferentiated connective tissue disease (N=1). In both, the clinical differential diagnosis included CCV and cutaneous involvement by the CTD. In all 6 cases, histopathological examination revealed a non-inflammatory vasculopathy, with PAS-positive, diastase resistant, hyaline thickening of ectatic superficial capillary walls, and loss of pericytes. These hallmarks of CCV excluded skin disease attributable to CTD in the two relevant cases. <h3>Conclusion</h3> Concurrence of CCV and CTD, though uncommon, presents a diagnostic challenge. The clinical distribution of the CCV eruption, favouring the lower limbs, and its non-inflammatory character histopathologically distinguish it from cutaneous involvement by a CTD. <h3>Disclosure of Interests</h3> Noreen Walsh: None declared, Phillip Moss: None declared, ThaiYen Ly: None declared, Sylvia Pasternak: None declared, Peter Green: None declared, Chris Gallant: None declared, Mary Lou Baxter: None declared, Colleen Kelly: None declared, Ariel Burns: None declared, Kerri Purdy: None declared, Elana Murphy: None declared, John Hanly Consultant for: Eli Lilly Canada.
Propensity score matching analysis of the survival outcome and toxicity of different treatment modalities for the elderly nasopharyngeal carcinoma patients.
Authors: Mingyu Tan, Mei Feng, Yecai Huang, Peng Xu, Ke Xu, Jun Yin, Lu Li, Yunxiang Qi, Jinyi Lang
Journal: Journal of Clinical Oncology (2019)

e23029 Background: With the aging society was coming, more elderly nasopharyngeal carcinoma NPC patients should be pay attention. However, no guideline is proposed for them due to lack of prospective clinical trials. We aimed to use propensity score matching method to evaluate the survival outcome and toxicity of the different treatment modalities for them. Methods: II-IV(UICC 8th) elderly NPC patients (≥65 years) were retrospectively enrolled between 2004 to 2016 in our center. All the patients received definitive IMRT, and were allocated into radiotherapy only (RT), concurrent chemoradiotherapy (CCRT) and neoadjuvant chemotherapy followed with CCRT (NACT). Cisplatin-based chemotherapy was used. Survival outcomes and toxicity were analyzed using propensity score-matching method. Results: There were 142 patients included, and the median age was 68 years. The median follow-up time was 47 months. 23 patients received RT only, 61 patients received CCRT and 58 patients received NACT. After matching for gender, age, T and N stage, chemotherapy and non-chemotherapy patients (22 pairs) were analyzed and shown the chemotherapy group had a better OS (86% vs 68%, p= 0.031). The 3-years LRFS, DMFS and DFS of chemotherapy and non-chemotherapy was 95% and 85% ( p= 0.251), 95% and 86% ( p= 0.307), 86% and 73% ( p= 0.309). Furthermore, 41 pairs who underwent chemotherapy were sub-analyzed according to different modalities. CCRT group showed a comparable 3-years LRFS (100% vs 94%, p= 0.143), DMFS (87% vs 89%, p= 0.608), DFS (81% vs 84%, p= 0.892) and OS (79% vs 66%, p= 0.080) with NACT. For acute toxicity, the incidence of G3-5 bone marrow suppression in non-chemotherapy was significantly lower than chemotherapy group (8.7% vs 36.4%, p= 0.31), and the incidence of G3-5 mucositis was similar ( p= 0.517). Besides that, there was no significant difference in the incidence of G3-5 bone marrow suppression and mucositis between CCRT and NACT group ( p= 0.824, p= 0.618). Conclusions: Chemoradiotherapy could improve the survival rate of the elderly NPC patients compared with radiotherapy only. The acute toxicity of CCRT and NACT was similar and acceptable. CCRT was still the standard treatment modality for them. As for the elderly NPC patients who are in good performance status and comorbidity conditions, NACT might be also worthy of recommendation.
Abstract 17112: Continuous Preload Measurement to Modulate Treatment of Heart Failure
Authors: David E Haines, Wilson Wong, Robert C Canby, Coty Jewell, David Pederson, Mahmoud Houmsse, Lissa Sugeng, John E Porterfield, Anil T Kotam, John A Pearce, Jonathan W Valvano, Sandeep Sagar, Marc D Feldman
Journal: Circulation (2016)

Introduction: In managing heart failure, increased physician intervention and medication-adjustment in response to changes in hemodynamic status has been proven to reduce morbidity. In practice, th...
Renal cell carcinoma in kidney transplant recipients at Guy’s and King’s College Hospital (UK) between 1987-2018.
Authors: Sabeeh-Ur-Rehman Butt, Barbara Chow, Sapna Shah, Iain MacDougall, Catriona Shaw, Dimitrios Kirmizis, Simon Chowdhury, Sarah Maria Rudman, Debra Hannah Josephs, Rhana Zakri, Jonathon Olsburgh, Deborah Enting
Journal: Journal of Clinical Oncology (2019)

e16066 Background: The increased incidence of cancer after renal transplantation is well recognised. Differences in cancer risk depend on the type of cancer but overall the incidence of solid cancer in kidney transplant recipient is at least twofold. Long term immunosuppression, oncogenic viruses and changes in immune surveillance are contributing factors. The incidence of renal cell carcinoma (RCC) is approximately six-fold greater than in the general population. Screening for RCC in the post-transplantation setting is not routine. Methods: Retrospective case series of kidney transplant recipients who underwent transplantation between 1987 and 2018 at Guy’s Hospital (London, UK). Collected data on patients who developed RCC post-transplant included: baseline demographics, renal disease, transplant survival, tumour characteristics, cancer treatment and survival. Results: 2968 patients underwent kidney transplantation between 1987 and 2018 at our Centre. 52 patients (1.8%) developed RCC. 40 (74%) were male with a median age of 51 years. 37% (71%) were white and 12 (23%) were black. The causes of end stage kidney disease included IgA nephropathy, hypertension and polycystic kidney disease. Median time to RCC diagnosis after transplant was 9 years (range 0-27). 86% of patients presented with stage 1/2 tumours, with the majority (72%) occurring in native kidneys. Most underwent radical nephrectomy although 5 patients were managed with radiofrequency-ablation (RFA) or surveillance (donor kidneys). Of 6 patients with metastatic disease, 5 received pazopanib and 1 everolimus. 4 patients continued systemic therapy for over 3 months and all derived clinical benefit with a median drug exposure of 19 months .15 patients required further kidney transplant or dialysis. Overall only 2 patients died from RCC. Conclusions: This retrospective study is the largest single-centre UK study to our knowledge. Kidney transplant recipients experience a marked increased risk of developing RCC. Most diagnosed RCCs are small and disease-specific mortality is low. With a third of tumours arising in donor organs, questions around optimum loco-regional approach and screening of high-risk population remain unanswered.
Abstract 18501: Pre-Dialysis Transition High vs Moderate Dose Statin Use and Post-Dialysis Transition All-Cause Mortality
Authors: Elani Streja, Melissa Soohoo, Hamid Moradi, Moti L Kashyap, Miklos Z Molnar, Daniel L Gillen, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Journal: Circulation (2017)

Introduction: Prior randomized control trials have suggested that statin use may be beneficial in non-dialysis dependent chronic kidney disease patients, but exhibits a lack of benefit for dialysis...
Do oral antineoplastic treatment data differ between Concerto Health AI Definitive Oncology EMR and Symphony Claims Data?
Authors: Laura Kay Chu, Nayan Chaudhary, Li Chen, William Bruce Wong
Journal: Journal of Clinical Oncology (2019)

e18180 Background: Electronic Medical Records (EMRs) are increasingly being used for health outcomes research because they contain a rich array of clinical data. Oral medications are captured via structured medication order fields or abstracted from the clinical notes; however, it’s unknown how these correspond with dispensations. The objective of this study was to better understand how oral antineoplastic orders captured from an EMR database compare to dispensations from pharmacy claims. Methods: The Concerto Health AI Definitive Oncology Dataset is a deeply curated cohort of patients (pts) derived from a wide range of oncology practices throughout the United States. Concerto Health AI has a co-exclusive partnership with ASCO CancerLinQ &amp; collects data from multiple other sources. These data were deterministically linked to US Symphony Health’s (SH) Integrated Dataverse, an anonymized, HIPAA-compliant data set. Only advanced (stage IIIb/IV) non-small cell lung cancer (aNSCLC) pts with curated data via manual review by nurse practitioners &amp; oral antineoplastics prescribed for lung cancer were included in this analysis. Among a subset of pts that had a dispensation within 90 days of their 1 st EMR order, treatment duration was calculated as time from 1 st to last order/claim (before a 30-day gap) plus 30 days supply, for EMR &amp; claims, respectively. Results: Of 19,175 aNSCLC pts from Concerto, 8,864 pts were linked to SH. Among linked pts, there were 2,057 pt-drug instances; 750 (36.5%) were in both Concerto and SH, 1,160 (56.4%) in Concerto but not SH, and 147 (7.1%) in SH but not Concerto. Median time from 1 st order in Concerto to 1 st dispensation in SH was 16 days (interquartile range (IQR): 6, 78), with 76% of pt-drug instances having a dispensation within 90 days of 1 st Concerto order. Median treatment duration was 44 (IQR: 30, 125) and 93 (IQR: 41, 241) days based on Concerto and SH, respectively. Conclusions: Concerto EMR orders identified more pts treated with oral antineoplastics, though treatment durations were longer using SH claims. Limitations of this analysis include use of orders from EMR instead of abstracted start and end dates and use of open claims with limited specialty pharmacy data. Linked datasets may provide more robust capture of orals data and warrant further research.
First-in-class hafnium oxide nanoparticles NBTXR3 in the treatment of liver cancers.
Authors: Enrique Chajon, Marc Pracht, Yan Rolland, Thierry De Baere, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, Antonio Sa Cunha, Anne-Sophie Baumann, Laurent Valérie, Emmanuel Rio, Samuel Le Sourd, Pierre Gustin, Christophe Perret, Didier Peiffert, Eric Deutsch
Journal: Journal of Clinical Oncology (2019)

e15642 Background: Hafnium oxide nanoparticles, NBTXR3, increase the effect of radiotherapy (RT) by enhancing local energy dose deposit within tumor cells, resulting in increased cell death compared to the same dose of RT alone. NBTXR3 efficacy was demonstrated in a phase II/III study in soft tissue sarcoma (NCT02379845) and is currently evaluated in other solid tumors including liver cancers. The use of this radio enhancer is particularly relevant in liver cancer management, a difficult to treat heterogenous population, due to the presence of underlying liver dysfunction. Methods: Phase I/II study of NBTXR3 activated by RT in patients (pts) with HCC (with/without portal vein tumor thrombus) or liver metastasis (mets) [NCT02721056]. The dose escalation part followed a 3+3 design with tested dose levels equivalent to 10%, 15%, 22% and 33% of baseline tumor volume. Patients were treated with a single intralesional injection (ILI) of NBTXR3 followed by Stereotaxic Body RT (SBRT: 45 Gy/3 fractions/5 to 7 days). Determination of recommended dose(s) and early dose limiting toxicities (DLT) were primary endpoints. Secondary endpoints include assessment of global safety profile, liver function evaluated by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST/RECIST 1.1). Results: The 4 levels of ILI dose escalation were finalized (n = 17): 6 pts at 10% (2 SBRT doses tested due to organs constraints), 4 pts at 15% and 22% (due to fiducial displacement and ILI shift) and 3 pts at 33% were included. ILIs were successful and SBRT was delivered as planned with no observed DLT or NBTXR3-related SAE at all levels. Only one grade 1 AE (fatigue) related to NBTXR3 was reported at dose level 33%. No relevant change of CPS or APRI was observed over time. Among 7 evaluable HCC pts the best target lesion responses by mRECIST were: 3 CR and 4 PR and among 5 evaluable mets pts: 2 PR, 1 SD and 2 PD. Conclusions: This study demonstrated the feasibility and good tolerance of the first in class NBTXR3 ILI. These results have supported a protocol amendment adding a higher dose of NBTXR3 (42% of the tumor volume). This innovative approach might constitute a valuable solution for patients with unresectable liver tumors and liver dysfunction. Clinical trial information: NCT02721056.
MET exon 14 skipping analogs: Rare but potentially clinically actionable.
Authors: Rebecca Feldman, Michelle Ellis, Jeffrey Swensen, Wolfgang Michael Korn, Zoran Gatalica
Journal: Journal of Clinical Oncology (2019)

3141 Background: The DpY motif within the exon 14 juxtamembrane domain of the MET receptor gene is critical for Cbl-mediated negative regulation. Splicing alterations that delete this residue, known as exon 14 skipping mutations (ex14sk mt), lead to prolonged MET protein stability and oncogenic signaling. Specific mt at the Y1021 (aka 1003) residue are thought to lead to similar effects as ex14sk, but due to their rarity, their role in NSCLC is unknown. We sought to identify and characterize non-ex14sk mt that include/surround Y1021. Methods: Retrospective review of molecular profiles for non-ex14sk mt that include/surround the DpY motif (Y1021) in MET. Two NGS platforms were included: MiSeq (2014-2017; n=2865) and NextSeq (2017-2019; n=6084). Immunohistochemistry (IHC) of cMET (SP44) and co-occurring alterations (EGFR, KRAS, ALK, ROS) were also reviewed. Results: Of 8,949 NSCLC patients with successful NGS of MET gene by either platform, 13 cases or 0.2% were identified to have an alteration within the amino acids of interest. Eleven cases included substitutions at Y1021 (5 phenylalanine, 4 histidine and 3 arginine) and the remaining two cases included small insertion-deletions p.E1017_Y1021delinsH and p.D1020_Y1021delinsV, the latter was later excluded as it co-harbored an ex14sk mt. Conclusions: Similar to patients with ex14sk mt, substitutions and small indels at Y1021 exhibit Clinicopathological features such as previous smoking history and older age, mutual exclusivity with oncogene drivers and MET protein overexpression. The rarity of these analogous ex14sk mt suggests deletions of exon 14 provide cellular advantages beyond Cbl-mediated ubiquitinylation of MET. Although rare, the impact of these mt on efficacy of Met-directed therapy deserves further exploration.[Table: see text]
Randomized use of anti-GD<sub>2</sub> antibody dinutuximab beta (DB) long-term infusion with and without subcutaneous interleukin-2 (scIL-2) in high-risk neuroblastoma patients with relapsed and refractory disease: Results from the SIOPEN LTI-trial.
Authors: Holger N. Lode, Dominique Valteau-Couanet, Juliet Gray, Roberto Luksch, Aleksandra Wieczorek, Victoria Castel, Shifra Ash, Genevieve Laureys, Vassilios Papadakis, Cormac Owens, Alberto Garaventa, Carla Manzitti, Nikolai Siebert, Sascha Troschke-Meurer, Evgenia Glogova, Ulrike Poetschger, Ruth Lydia Ladenstein
Journal: Journal of Clinical Oncology (2019)

10014 Background: We determined the role of scIL-2 combined with long term infusion (LTI) of DB in patients (pts) with high-risk relapsed/refractory neuroblastoma. Methods: 160 pts were enrolled into an open label SIOPEN Phase II clinical trial (EudraCT 2009-018077-31). Pts were randomly assigned to receive up to 5 cycles of 100 mg/m 2 DB-LTI (d8-17) and 160 mg/m 2 oral isotretinoin (d19-32) (81 pts) with and without 6x10 6 IU/m 2 scIL-2 (d1-5; 8-12) (79 pts). Endpoints were toxicity, response rates and 2yrs-event free and -overall survival. Results: Between 07/2014 and 07/2017, 160 pts from 11 countries were randomised. Median follow-up is 2.6 years. Pts were well balanced between arms according to stage, age, MYCN amplification, patients with relapse and remission status. The 2yrs-EFS and -OS for DB (81 pts) vs. DB combined with scIL-2 (79 pts) was 59%±6% vs 65%±6% (p = 0.721) and 79%±5% vs 84%±4% (p = 0.904). In 97 pts with evaluable disease, a response rate of 49% (9% CR, 40% PR) vs 52% (26% CR, 26% PR) after treatment with DB vs DB and scIL-2 was observed. Grade 3&amp;4 fever (16% vs 46%, P = 0.000), allergic reaction (1% vs 14%, P = 0.004), hematological toxicity (46% vs 66%, P = 0.013) and neurotoxicity (0% vs 8%, p = 0.003) were significantly worse in the combination arm, but no difference was seen for capillary leak, gastrointestinal, liver enzyme elevation and pain. Paraplegia possibly related to the treatment was observed in 2 pts in the combination arm, none in the arm without scIL-2, and one resolved to baseline. A subgroup of 34 pts who had a relapse and measurable disease at treatment start, showed a 2yrs-EFS and -OS in DB (17 pts) vs DB combined with scIL-2 (17 pts) of 35%±12% vs 69%±12% (p = 0.116) and 59%±12% vs 81%±10% (p = 0.167). However, this trend was statistically not significant. Pharmacokinetic and HACA response between both arms was not different with overlapping antibody concentration-time curves and a HACA response of 15/81 (19%) (DB) vs 16/79 (20%) (DB and scIL-2). Conclusions: No significant difference in efficacy of DB combined with scIL-2 and increased toxicity in this arm suggests that this schedule of scIL-2 is of no additional benefit. Clinical trial information: 2009-018077-31.
Phase I study of a brain penetrant mutant IDH1 inhibitor DS-1001b in patients with recurrent or progressive <i>IDH1</i> mutant gliomas.
Authors: Atsushi Natsume, Toshihiko Wakabayashi, Yasuji Miyakita, Yoshitaka Narita, Yohei Mineharu, Yoshiki Arakawa, Fumiyuki Yamasaki, Kazuhiko Sugiyama, Nobuhiro Hata, Yoshihiro Muragaki, Ryo Nishikawa, Naoki Shinojima, Toshihiro Kumabe, Ryuta Saito, Kazumi Ito, Masaya Tachibana, Yasuyuki Kakurai, Soichiro Nishijima, Hiroshi Tsubouchi
Journal: Journal of Clinical Oncology (2019)

2004 Background: WHO grade II/III gliomas frequently harbor isocitrate dehydrogenase 1 ( IDH1) mutations, resulting in intratumoral accumulation of oncometabolite 2-hydroxyglutarate (2-HG) and subsequent clonal expansion. DS-1001b is an oral selective inhibitor of mutant IDH1 R132X that was designed to penetrate the blood-brain barrier. Methods: In this first-in-human, multicenter, phase I study (NCT03030066), eligible patients (pts) with recurrent/progressive IDH1 mutant glioma received DS-1001b twice daily (bid), continuous. A modified continual reassessment method was used for dose escalation. RANO and RANO-LGG criteria were used to assess tumor response. Pts who planned to undergo salvage surgery after developing progressive disease (PD) and who provided informed consent received DS-1001b treatment until surgery. Tumor samples were also obtained from those pts to measure the free form of DS-1001b and 2-HG levels. Results: Between Jan 2017 and Oct 2018, DS-1001b (125-1400 mg bid) had administered for 45 pts (median age 44 yrs, prior radiation therapy 100%, prior chemotherapy 82%), and 17 pts were continuing treatment. Maximum tolerated dose (MTD) was not reached. Most AEs were Gr 1-2. Gr 3 AEs were observed in 42.2% of pts. No Gr 4 or 5 AEs or serious drug-related AEs were reported. One dose limiting toxicity was Gr 3 white blood cell count decreased (1000 mg bid). Common AEs ( &gt; 20%) were skin hyperpigmentation, diarrhea, pruritus, nausea, rash, and headache. Of 29 evaluable pts with contrast enhancing gliomas, one, three and 10 achieved complete response, partial response and stable disease (SD), respectively. Of evaluable nine pts with contrast non-enhancing gliomas, two achieved minor response and seven achieved SD. Peak plasma concentration (Cmax) and area under the curve (AUC) increased dose-dependently. The brain/plasma ratio of free form of DS-1001b ranged 0.19‒0.77 in 3 pts. Conclusions: DS-1001b was well tolerated up to 1400 mg bid with favorable brain distribution, and MTD was not reached. Recurrent/progressive IDH1 mutant glioma pts responded to treatment. Investigation is ongoing to determine the recommended Phase II dose. Clinical trial information: NCT03030066.