tbuckley/cabot-search huggingface dataset:
THU0297 STEROID TREATMENT MAY IMPROVE ARTERIAL STIFFNESS IN PATIENTSWITH POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS: A PROSPECTIVE COHORT STUDY
Authors: Amir Emamifar, Torkell Ellingsen, Søren Hess, Per Syrak Hansen, Inger Marie Jensen Hansen, Peter Thye-Rønn
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Polymyalgia rheumatica (PMR)/Giant cell arteritis (GCA), common inflammatory diseases, are associated with increased risk of aortic stiffness, possibly due to an inflammatory process.<sup>1,2</sup> <h3>Objectives:</h3> To evaluate the effect of steroid treatment on aortic stiffness in patients with PMR/GCA. <h3>Methods:</h3> This is an ongoing 1-year prospective cohort study. 37 consecutive patients with newly diagnosed PMR/GCA were included. Aortic pulse wave velocity (PWV) and aortic augmentation index normalized to heart rate of 75 beats per minute (AIx@75) were measured at baseline and subsequently at 1<sup>st</sup> and 4<sup>th</sup> months of treatment initiation with oral prednisolone. <h3>Results:</h3> Of 37 patients, 3 pts. were excluded from the study because of lack of interest or a change in the initial diagnosis. Of all included pts. 61.8% were female and mean age was 71 (69-74) years. At diagnosis, 24 pts. presented with pure PMR symptoms, 2 pts. with pure cranial GCA, 8 pts.with concurrent PMR and GCA. The mean of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at baseline were 62.3±22.9 and 46.4±43.7, respectively. AIx@75 was significantly decreased after 4 months of treatment initiation (from 26.1±11.6 to 19.5 ±11.5, p=0.016). Though aortic PWV was decreased after 4 months of treatment initiation (from 12.3±2.4 to 11.6±2.4), the results was not statistically significant (p=0.070). We did not find any significant changes at 1<sup>st</sup> month, nor in aortic PWV neither in AIx@75. <h3>Conclusion:</h3> Steroid treatment may improve arterial stiffness in PMR/GCA patients due to suppression of the inflammatory process. However this is a time consuming effect and may not be seen as early as the first month. <h3>References:</h3> [1] Emamifar A, et al. Polymyalgia rheumatica and giant cell arteritis-three challenges-consequences of the vasculitis process, osteoporosis, and malignancy: A prospective cohort study protocol. Medicine (Baltimore). 2017;96(26):e7297. [2] Schillaci G, et al. Aortic stiffness is increased in polymyalgia rheumatica and improves after steroid treatment. Ann Rheum Dis 2012;71:1151-6. <h3>Disclosure of Interests:</h3> None declared
Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling
Authors: Matthew Ho, Tianzeng Chen, Jiye Liu, Paul Dowling, Teru Hideshima, Li Zhang, Eugenio Morelli, Gulden Camci-Unal, Xinchen Wu, Yu-Tzu Tai, Kenneth Wen, Mehmet Samur, Robert L. Schlossman, Ralph Mazitschek, Emma L. Kavanagh, Sinéad Lindsay, Takeshi Harada, Amanda McCann, Kenneth C. Anderson, Peter O’Gorman, Giada Bianchi
Journal: Leukemia (2019)

Multiple myeloma (MM) is an incurable cancer that derives pro-survival/proliferative signals from the bone marrow (BM) niche. Novel agents targeting not only cancer cells, but also the BM-niche have shown the greatest activity in MM. Histone deacetylases (HDACs) are therapeutic targets in MM and we previously showed that HDAC3 inhibition decreases MM proliferation both alone and in co-culture with bone marrow stromal cells (BMSC). In this study, we investigate the effects of HDAC3 targeting in BMSCs. Using both BMSC lines as well as patient-derived BMSCs, we show that HDAC3 expression in BMSCs can be induced by co-culture with MM cells. Knock-out (KO), knock-down (KD), and pharmacologic inhibition of HDAC3 in BMSCs results in decreased MM cell proliferation; including in autologous cultures of patient MM cells with BMSCs. We identified both quantitative and qualitative changes in exosomes and exosomal miRNA, as well as inhibition of IL-6 trans-signaling, as molecular mechanisms mediating anti-MM activity. Furthermore, we show that HDAC3-KD in BM endothelial cells decreases neoangiogenesis, consistent with a broad effect of HDAC3 targeting in the BM-niche. Our results therefore support the clinical development of HDAC3 inhibitors based not only on their direct anti-MM effects, but also their modulation of the BM microenvironment.
Molecular profile of ampulla of vater carcinoma (AVC): A rare tumor type with meaningful molecular alterations.
Authors: João Pinto, Helena Verdaguer, Maria Teresa Salcedo, Anna Pedrola, Jorge Hernando-Cubero, Juan David Assaf Pastrana, Daniel Acosta, Ana Vivancos, Rodrigo Dienstmann, Teresa Macarulla Mercade
Journal: Journal of Clinical Oncology (2019)

4119 Background: AVC is a rare type of cancer with dismal prognosis and limited therapeutic options due to the lack of specific clinical trials. Two histologic subtypes predominate, namely pancreatobiliary and intestinal. A variety of molecular alterations have been described in AVC, but their clinical and therapeutic implications have not been studied in detail. Methods: Retrospective cohort study of patients (pts) diagnosed with AVC treated in our institution from 2010 to 2018. We routinely performed Next Generation Sequencing in all AVC tumors. Our main objectives were to describe the molecular profile of AVC and correlate with clinical outcomes. Results: Out of 26 pts with AVC, 13 pts were male (50%), median age 65 (range 43-83), 7 pts (27%) had stage IV disease at diagnosis. Histologic type was pancreatobiliary in 18 pts (69%), intestinal in 7 pts (27%) and mixed in one case (4%). We identified KRAS mutations (mut) in 10 pts (7 pancreatobiliary, 2 intestinal, 1 mixed), TP53 mut in 6 pts (4/1/1), PIK3CA mut in 3 pts (3/0/0), ERBB2 mut in 3 pts (2/1/0), CTNNB1 mut in 3 pts (2/1/0). In pancreatobiliary we found single cases with RNF43, BRCA1 and CHEK2 mut; while in intestinal we found single cases with NRAS and BRAF mut. One tumor of intestinal subtype had microsatellite instability (MSI). Three pts were included in phase I clinical trials, 2 of them with trials based on tumor profile (ERBB2 mut with pan-HER inhibitor and MSI with immunotherapy). Median overall survival (OS) was 21 months for pts with stage I, II and III disease (95% CI 12.37-not reached) and 13.2 months for stage IV disease at diagnosis (95% CI 5.73-not reached). In cox models, median OS was not dependent on KRAS or TP53 mutation status, or histological subtypes. Conclusions: AVC is a rare type of cancer with two differentiated histological subtypes harboring unique molecular alterations that can be matched to investigational therapies. A broader knowledge of the biology of these tumors is needed to improve patient outcomes.
Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients.
Authors: Kimiharu Takamatsu, Ryuichi Mizuno, Nozomi Hayakawa, Eiji Kikuchi, Takeo Kosaka, Mototsugu Oya
Journal: Journal of Clinical Oncology (2019)

e16065 Background: The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. Methods: We retrospectively reviewed 150 mRCC patients received second-line molecular targeted therapy. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS) especially in intermediate risk group. Results: The median OS from second-line treatment of whole cohort and intermediate risk group were 24.6 (95%confidence interval, 95%CI:18.2-31.0) and 23.6 (95%CI:15.1-32.1) months. Thirty-three out of 82 (40%) intermediate risk patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group were 13.4 (95%CI:5.9-20.8) and 29.4 (95%CI:25.5-33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5,95%CI:1.4-4.2, p = 0.001). Conclusions: The serum CRP levels at second-line treatment initiation could divide intermediate risk mRCC patients into two prognostic subgroups.
Role of ultrasound contrast agent in a tertiary cancer center: Experience in 75 patients with liver biopsy.
Authors: Amir Ata Rahnemai-Azar, Elias Kikano, Daniel Arnold Smith, Nikhil H. Ramaiya, Nami R Azar
Journal: Journal of Clinical Oncology (2019)

e14671 Background: The sensitivity of B-mode ultrasound (US) in detecting hepatic lesions has been reported to be between 55-85%. A recently FDA approved US contrast agent has been shown to increase the detectability of liver lesions; yet, there is paucity of knowledge regarding its application in US guided biopsies. The aim of this study was to determine accuracy and applicability of contrast enhanced US (CEUS) guided biopsies of liver lesions in cancer patients. Methods: A prospective registry of 75 patients (M = 54%, F = 46%, Age: 63y±14), that underwent CEUS guided liver biopsy in 2017-2018, were retrospectively reviewed. The decision to apply US contrast was made based on pre-procedural and intra-procedural clinical findings. Lesions with negative biopsy results were reviewed in follow up imaging to determine any evidence of potential positive malignancy. Results: History of renal failure that precluded application of iodinated IV contrast was the main pre-procedural indication (17%). Intra-procedural indications included: poor visualization of lesions in B-mode US (78%), targeting enhancing part of lesions (necrotic, post ablation or cystic) (16%), and lesion selection (6%). Diameter of the lesions were ≤ 20mm in 46% of patients. Biopsy results were positive in 50 patients, and included 32% primary liver tumors (hepatocellular carcinoma and cholangiocarcinoma) and 68% metastasis (pancreas: 24%, breast: 12%, GI tract: 10%, lung: 8% and other: 14%). Of the 25 patients with negative biopsy results, 6 did not have follow up imaging and 3 were later found to have positive malignancy (Negative predictive value: 84%, accuracy: 96%). Genomic sequencing was established in 34% of the patients. Based on the biopsy/genomics results, patients underwent systemic treatment (56%), locoregional treatment (16%), combination (6%) or surgery (2%). 10% of patients selected hospice care and 10% lost follow up. Conclusions: CEUS increases the accuracy of US guided biopsies of focal liver lesions, by improving visualization, targeting viable parts and also in patients with renal failure, or small lesions. Findings from these biopsies could improve management of cancer patients by categorizing them into different treatment groups.
Using a video to introduce fertility preservation to women with cancer.
Authors: Abha A. Gupta, Talia Lenton-Brym, Rebecca Charow, Chelsea Paulo, Mahsa Samadi, Victoria Forcina, Shian Li Chen, Adrian Thavaratnam, Laura Mitchell, Armando J. Lorenzo, Janet Papadakos
Journal: Journal of Clinical Oncology (2019)

e18021 Background: Women with cancer risk premature ovarian insufficiency with implications for future fertility due to chemotherapy and radiotherapy. Still, infertility discussions are inconsistently provided. Options for egg cryopreservation exist for females, but discussing these topics can be overwhelming for patients and families. This paper aims to assess the understandability, actionability, and readability of a fertility preservation (FP) educational video, as well as patient (pt) and caregiver pre- and post-video perceptions and knowledge. Methods: A video was created by the institution's Adolescent and Young Adult Program to explain relevant anatomy, pathophysiology of ovulation and process of cryopreservation. Understandability and actionability were evaluated using the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-AV) and readability using the SMOG and Flesch-Kincaid indices. Pt perceptions and knowledge growth were captured using pre-post questionnaires. Female pts (n = 108) were recruited in oncology clinics over 2 months, using a convenience sample. Questionnaire responses were analyzed using SPSS to calculate descriptive statistics to conduct correlation analyses. Results: The median age of the participants was 28 (range 14-39 yrs). The average PEMAT-A/V score was 79% (±11.3%) for understandability and 72% (±13.1%) for actionability. A score of 70% is regarded as acceptable. The readability assessment determined that the video script was, on average, at a grade 8 reading level. Pts’ interest in learning about FP increased, with 14% of those initially uninterested or unsure wanting to learn more after viewing the video. Pts’ general knowledge on FP increased from the pre- to post-video questionnaire, from a mean score of 75% initially (±17.9%), to a mean score of 84% (±14.5%) after watching the video (t = -5.972, p = 0.000). On average, overall satisfaction with the video was 85% (±8.5%). Conclusions: Women commonly use online tools for researching health questions. This study demonstrates that the video is understandable and provides guidance for future discussion. It shows that videos can spark interest in sensitive discussions and can improve fertility knowledge. This video may encourage providers to more consistently initiate discussions about infertility. Furthermore, the video can be translated for related topics to help provide accurate information in a patient-friendly medium.
Ramucirumab (Ram) and durvalumab (Durva) treatment of metastatic non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, and hepatocellular carcinoma (HCC) following progression on systemic treatment(s).
Authors: Yung-Jue Bang, Talia Golan, Chia-Chi Lin, Laetitia Dahan, Siqing Fu, Victor Moreno, Ravit Geva, Martin Reck, Heather Ann Wasserstrom, Gu Mi, Naomi Laing, Laura Williams Goff
Journal: Journal of Clinical Oncology (2019)

2528 Background: A Phase 1b study (NCT02572687) was conducted to examine the combined effects of Ram (anti VEGFR2) and Durva (anti PD-L1). Methods: Patients (pts) with previously-treated, advanced NSCLC (Cohort [CH] A), G/GEJ adenocarcinoma (CH B), HCC (CH C), ECOG PS 0-1, and no prior Ram or IO therapy, received Ram (10 mg/kg) + Durva (1125 mg) Q3W (CH A) or Ram (8 mg/kg) + Durva (750 mg) Q2W (CH B, C). Primary objective was to assess safety; efficacy was also examined. PD-L1 expression of tumor cells (TC) +/- immune cells (IC) in pretreatment tumor biopsies were assessed using SP263 immunohistochemistry. “High” PD-L1 is ≥25% TC for NSCLC and ≥25% TC or IC for G/GEJ, HCC. Results: CH A, B and C enrolled pts with ECOG PS 1 (%) of 43, 66, 68; and average of 2, 2, 1 prior regimens, respectively. The most common grade 3/4 treatment-emergent adverse events (AE) are hypertension (HTN) (14.3, 17.2, 17.9%), anemia (3.6, 24.1, 21.4%), and fatigue (10.7, 10.3, 10.7%). Grade 3/4 AEs of special interest ( &gt; 5% total pts) for Ram: HTN, bleeding events (3.6, 10.3, 10.7%), Venous thromboembolic events (0, 10.3, 7.1%); for Durva: increase in lipase (10.7, 3.4, 10.6%) and AST (3.6, 3.4, 17.9 %). Data from CH B,C suggest a trend toward increased efficacy in pts with high PD-L1 expressing tumors. Conclusions: Ram + Durva generated no unexpected toxicities and demonstrated antitumor activity. Results in pts with high PD-L1 HCC and G/GEJ cancer warrant further evaluation. Clinical trial information: NCT02572687. [Table: see text]
Design and implementation of outpatient-based rapid MRI protocols to rule out metastatic spinal cord compression and brain metastases.
Authors: Jessica G. Fried, Michael Joseph Lariviere, Ravi Bharat Parikh, Patricia Zadnik Sullivan, Genevieve P. Kanter, John Y.K. Lee, Neil R. Malhotra, Steven Brem, Ali K. Ozturk, James M. Schuster, M. Sean Grady, Tracey L. Evans, Michelle Alonso-Basanta, Joshua Adam Jones, Robert Kurtz, Ronald Wolf, Hanna M. Zafar, Lawrence N. Shulman, Abigail T. Berman, Charles E. Kahn
Journal: Journal of Clinical Oncology (2019)

e18307 Background: Metastatic spinal cord compression (MSCC) and symptomatic brain metastases (mets) are potential emergencies that demand coordinated multidisciplinary management. Patients (pts) with concerning symptoms are often referred to the Emergency Department (ED) for expedited imaging, but most do not require subsequent ED or inpatient management. Unnecessary ED visits incur substantial cost to the health system and patients, and cause psychosocial stress for patients often near the end-of-life. To improve access to expedited outpatient imaging for high-risk pts and reduce unnecessary ED visits, we developed outpatient rapid MRI protocols and pathways to rule out MSCC and brain mets. Methods: Tailored abbreviated MRI protocols were developed to allow rapid acquisition of brain ( &lt; 13 minutes) and full spine ( &lt; 25 minutes) exams. Dedicated appointments were reserved on the daily MRI schedule. Exams were immediately interpreted and reported by Radiology to the ordering clinician. This pathway was piloted within the Thoracic Oncology group beginning in 10/2018. Results: Referring specialties included Radiation Oncology (50%), Medical Oncology (36%), Pulmonology (7%), and Surgery (7%). For 6 pts who had outpatient rapid brain imaging, median time from order to exam start was 4.3 h (1.8-31) and order to final report 6.8 h (3.2-34.1). Brain mets were found in 4/6 patients. Only 1/4 positive studies required subsequent ED management. For 8 pts referred for rapid spine imaging, median time from order to exam start was 14.4 h (2.2-72.5) and order to final report 16.7 h (4.0-74.4). Only 1 patient was found to have cord compression and required ED/inpatient management. Overall, 86% of patients did not require ED or inpatient admission. 3 pts (all with negative imaging) died a median 13.4 d (1.4-28.3) after order placement. Conclusions: Outpatient rapid MRI protocols facilitate same-day imaging, interpretation, and management, improving care for thoracic oncology pts with new concerning neurologic symptoms and reducing unnecessary ED visits. Future work will expand access beyond Thoracic Oncology and further quantify improvements in cost savings and patient quality of life.
Clinical and economic outcomes associated with sequential treatment in patients with advanced renal cell carcinoma (aRCC).
Authors: Meredith M. Regan, David F. McDermott, Michael B. Atkins, Apoorva Ambavane, Shuo Yang, Sumati Rao, M Dror Michaelson
Journal: Journal of Clinical Oncology (2019)

4566 Background: Immuno-oncology therapies (IOs) and tyrosine kinase inhibitors (TKIs) are recommended for the treatment of aRCC. As new drugs and combination regimens emerge, there is interest in gaining a deeper understanding of optimal treatment sequencing. We aimed to assess clinical and economic outcomes associated with treatment sequences for untreated aRCC patients with IMDC intermediate/poor risk. Methods: A discrete event simulation model was developed to estimate the total costs and survival (in life-years; LYs) over patients’ lifetimes when receiving sequential treatment with nivolumab + ipilimumab (N+I), sunitinib (SUN), pazopanib (PAZ), or cabozantinib (CAB) as first-line (1L) treatment, and nivolumab (NIVO), axitinib (AXI), PAZ, CAB, or lenvatinib + everolimus (LEN+EVE) as second line (2L). Efficacy inputs were derived from the CheckMate 214 trial and a network meta-analysis based on available literature. Safety and cost data were obtained from literature and publicly available sources. Results: N+I initiating sequences were estimated to provide longer survival in mean LYs and lower mean costs/LY versus sequences with 1L TKIs (table). The estimates of incremental cost-effectiveness ratio (ICER) for N+I initiating sequences with 2L TKI monotherapy were well below the willingness-to-pay threshold of $50,000. Using 2L LEN+EVE, compared with 2L monotherapies, provided an incremental survival gain but at costs/LY close to $100,000. Conclusions: Use of 1L N+I followed by TKI monotherapy is estimated to provide longer survival while being more cost-effective versus TKIs followed by IOs or sequences cycling TKIs, mainly driven by a longer time to 2L treatment and longer treatment-free survival with N+I. Clinical trials with head-to-head comparisons of treatment sequences would be necessary to validate the findings of the study. [Table: see text]
Clinical implications of hyperprogression with immune checkpoint inhibitors in patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Panagiota Economopoulou, Nikolaos Spiridon Spathas, George Papaxoinis, Maria Anastasiou, Maria Gkotzamanidou, Ioannis Kotsantis, Niki Gavrielatou, Nikolaos Oikonomopoulos, Euthymios Kirodimos, Elena Mihal Vagia, George Kavourakis, Amanda Psyrri
Journal: Journal of Clinical Oncology (2019)

6034 Background: Hyperprogressive disease (HPD) refers to paradoxical acceleration of tumor growth kinetics (TGK) after initiation of treatment with anti- PD-1/PD- L1 agents and has been reported across tumor types in 4-29% of patients using different definitions. Preliminary data suggest that HPD might affect response to subsequent therapies. Methods: We compared TGK prior and TGK upon immunotherapy (IO) in 62 patients (pts) with recurrent/metastatic (R/M) HNSCC treated with PD-1/PD-L1 inhibitors. The TGK ratio (TGKR, ratio of tumor growth velocity before and upon treatment) was calculated. The first imaging assessment was performed 3 months (mo) after IO initiation. HPD was defined as 1. Radiological HPD (TGKR≥2) or 2. Clinical HPD (Disease-related rapid clinical deterioration post IO). Results: After median follow-up of 12.3 mo (range, 0.4-28.1), 43 pts progressed and 38 died. Median PFS was 2.8 mo (95%CI, 2.2-3.4) and median OS 8.6 mo (95%CI, 4.2-12.9). HPD was observed in 16 pts (25.8%), while 15 pts had early PD (Time to Treatment failure, TTF &lt; 3 mo) and 31 late PD (TTF &gt; 3mo). Among 16 pts with HPD, 11 had radiological HPD and 10 had clinical HPD. 4 pts had both clinical and radiological HPD. Pts with late PD had median OS 11.3 mo (95%CI, 9.3-13.3), those with early PD 5.2 mo (95%CI, 3.1-7.3 months) and those with HPD 5.1 mo (95%CI, 4.4-5.9) (p &lt; 0.005). Regarding post-progression OS, pts with late PD had median 11.3 mo (95%CI 0-22.8), those with early PD 2.5 mo (95%CI 0.6-4.4) and those with HPD 4.2 mo (95%CI 1.7-6.7) (p = 0.001). Pts with HPD had a trend for longer median post-progression OS compared to pts with early PD (p = 0.121). Median PFS with chemotherapy after immunotherapy failure was 3.0 mo (95%CI 2.4-3.6) for pts with late PD, 2.1 mo (95%CI 0.9-3.4) for pts with early PD and 6.1 mo (95%CI 3.0-9.3) for those with HPD (p = 0.040). HPD was associated with longer median PFS with chemotherapy compared to pts with early PD (p = 0.016), while the difference in median PFS with chemotherapy between pts with HPD and late progressors was non-statistically significant (p = 0.260). Conclusions: Radiological or clinical HPD was observed in 25.8% of patients with R/M HNSCC treated with IO. Early progression to immunotherapy is an important predictor of short survival, while HPD was associated with improved PFS to subsequent chemotherapy.