tbuckley/cabot-search huggingface dataset:
FRI0488 Insufficient immunosuppressive use is the leading cause of vascular relapses in behcet’s disease
Authors: A. Aksoy, F. Alibaz Öner, T. Ergun, R.H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vascular involvement is observed in up to 40% in Behcet Disease (BD) patients, as an important cause of mortality and morbidity, especially for males (Kural-Syahi E et al,1984). <h3>Objectives</h3> Purpose of this study is to describe clinical-demographic properties, treatments and prognosis of vascular BD patients in a tertiary rheumatology clinic. <h3>Methods</h3> BD patients fullfilling ISG 1990 criteria are recruited from the multi-disciplinary Behcet's Clinic in Marmara University, Istanbul for this retrospective study. All data is collected from patient files (ISG for BD,1990). <h3>Results</h3> Mean age of BD patients (M/F:102/22) was 29.3±7.3 years at diagnosis and 32.4±9.5 years old during first vascular event. Median follow up was 47<sup>17–71</sup> months. Mean age of female patients was significantly older during first vascular event (table 1). 73.2% of vascular involvement was venous, mostly deep vein trombosis (table 2). 32% (n=40) of patients presented first with a vascular event and diagnosed as BD. Twenty (16%) patients were diagnosed with a median of 12<sup>1–120</sup> months after the first vascular event. 15 (6.5%) patients were using immunsupressive (IS- mainly azatiopirin) drugs either for resistant mucocutaneous symptoms or major other organ involvement during the first vascular event. Vascular relaps rate was 40.7% and it was similar between sexes (F: 33.3% vs M: 42.2%, p=0.6). After the first vascular event, 96 (85.7%) patients had been treated with ISs and 58.9% used anticoagulants. Median IS and anticoagulant usage duration was 25.5 (5–48) and 2 (0–12) months respectively. Relaps rate was higher in patients who had stopped ISs (87.5% vs 32.3%). IS treatment duration was shorter at relapsing patients (44 vs 64 months, p=0.001). Smoking rate was higher at male patients but no association was observed with vascular relapses. IVC: inferior vena cava, PAA: pulmoner arter aneurysmeı, PAT: pulmoner arter trombus, SVC: superior vena cava <h3>Conclusions</h3> Our results show that female BD patients have a vascular event at a later age compared to males, but the course of vascular disease is not influenced with gender. Early termination of immunosupressive treatments seems to be the most important cause of vascular relapses <h3>Disclosure of Interest</h3> None declared
Ironclad: A randomized phase III study of ibrutinib (Ibr) or no consolidation following autologous hematopoietic stem cell transplantation (AutoHCT) for relapsed/refractory activated-B-cell (ABC) subtype diffuse large B-cell lymphoma (DLBCL).
Authors: Charalambos Andreadis, Timothy S Fenske, Brian Thomas Hill, Patrick J. Stiff, David L. Grinblatt, Eric D. Hsi, Todd Kelley, Kristy L. Richards, Lale Kostakoglu, Heiko Schöder, Sin-Ho Jung, Brandy Pitcher, Kristen Pike, Teri Plona, Ryan Baugher, Stephanie Mellott, Nancy L. Bartlett, John Leonard, Thomas C. Shea, Steven Michael Devine
Journal: Journal of Clinical Oncology (2017)

TPS7566 Background: Relapsed DLBCL in the rituximab era portends a poor prognosis with only about 25% of patients achieving long-term disease control following 2 nd line therapy and AutoHCT. Patients with the ABC subtype have an inferior prognosis at diagnosis than those with GC and are overrepresented at relapse. In order to improve outcomes in ABC-DLBCL, we designed a study targeting disease pathobiology at the time of AutoHCT. Ibr has a safety profile allowing combination with cytotoxic chemotherapy and has single-agent activity with a 37% response rate in patients with relapsed/refractory ABC-DLBCL. Methods: This is an intergroup, randomized, placebo-controlled phase III study combining Ibr or placebo with high-dose chemotherapy during conditioning with AutoHCT and for 12 months following AutoHCT. Pts with relapsed or refractory DLBCL have tissue submitted centrally for real-time review and subtype assignment by GEP (Frederick Laboratory). Key eligibility criteria include no more than 3 prior regimens, no active CNS involvement, no need for long-term anticoagulation, and no progression on prior Ibr. Pts with chemosensitive ABC-DLBCL are randomized to Ibr 560 mg or placebo with BEAM or CBV chemotherapy until day 0. After engraftment, pts receive Ibr 560 mg daily or placebo for 12 additional cycles. Pts with progressive disease on placebo can cross over to Ibr monotherapy. An initial safety cohort of 6 pts is being enrolled to evaluate the tolerability of Ibr with concurrent BEAM and CBV therapy. The primary endpoint is superior 2-year PFS (Ha/H0: 67% vs 50%). Secondary endpoints include time to count recovery, post-transplant response rates, OS, PFS, and incidence of 2 ary malignancies. In correlative studies, we will assess the prognostic and predictive role of pre-transplant FDG-PET in the setting of Ibr or placebo therapy, the role of emergent BCR pathway mutations, double hit genetics, and pharmacogenetic determinants on treatment outcome and toxicities. We expect to accrue 296 patients over 4 years. An Alliance/BMT-CTN study: NCT02443077 Clinical trial information: NCT02443077.
Longitudinal study of arm impairments, function and quality of life following mastectomy.
Authors: Anne Swisher, Hannah Hazard, Jessica Freeman Partin, Mia Erickson, Erica Sengewalt, Sara Giebell, Melissa Hickman, Melodie Tweedlie, Carol Waggy, Valeriya Gritsenko, Garth Graebe, Mohamad Adham Salkeni
Journal: Journal of Clinical Oncology (2016)

10078 Background: Women undergoing mastectomy worry about effects on upper extremity function. Past research has shown long-standing problems with stiffness, lymphedema or weakness that impairs function. However, no studies to date have followed these patients over time to see if these impairments are normal or represent individuals who might need rehabilitation. Subjects: 24 women, mean age 55 yrs, stage 0-III breast cancer planning to undergo mastectomy Methods: Measurements of pain, arm girth, grip strength and shoulder motion were collected before and 1, 3, 6 and 12 months after surgery. Self-report ratings of quality of life (using FACT-B) and upper extremity function (using QuickDASH) were completed at the same time points. Data from each time point were analyzed descriptively and ANOVA was used to determine differences, expressed as percentage of pre-operative values. Results: Abduction decreased significantly (p < 0.05) at 1 month post-surgery (mean value, 80% of baseline) but was no different than baseline after that time point. External rotation did not differ from baseline at 1 month but was significantly higher than baseline at 3 months. No other measures were less than 90% of baseline at any time. FACT-B score improved from baseline to 1 month and remained elevated for the rest of the time points. QuickDASH scores increased at 1 month compared to baseline (mean impairment of 25% vs. 9%) suggesting increased disability and stayed elevated to 12 months. Conclusions: Following mastectomy, shoulder motion is limited for less than 3 months but mild self-reported disability is more long-standing. Grip strength and arm girth do not seem to be impaired by mastectomy. Quality of life is better after surgery than before, perhaps due to worries about the upcoming treatment and its effects. Women undergoing mastectomy for breast cancer can expect to have relatively mild and short-lasting impairments in the upper extremity and difficulty performing tasks with their affected arm. This is in contrast to past studies showing long-standing limitations. Those with less than 90% of baseline values should be evaluated for individualized rehabilitation.
Carboplatin AUC 10 in metastatic seminoma: Role of early PET scanning to reduce the amount of treatment while maintaining outcome—A phase 2 study (CarPET).
Authors: Jonathan Shamash, Rizwan Syed, Naveed Sarwar, Katherine Mutsvangwa, Peter Wilson, Shah-Jalal Sarker, Gordon J. S. Rustin
Journal: Journal of Clinical Oncology (2016)

4545 Background: Carboplatin montherapy for metastatic seminoma has not been pursued following two studies showing reduced progression-free survival compared to combination therapy. The doses were in-retrospect suboptimal and increased doses based on glomerular filtration rate have been associated with improved outcome. We postulated that an early response to carboplatin might allow de-escaltion of therapy without compromising efficacy Methods: Patients with metastatic untreated seminoma with IGCCCG good prognosis were recruited. PET scanning was performed prior to and post 1st cycle of carboplatin AUC 10 – based on an EDTA ( uncorrected) clearance. Those with a Deauville score of < 3 ( metabolic response) were given a total of 3 cycles, the rest received 4. Treatment was given every 21 days. Results: 48 patients were recruited ( 46 testicular, 2 extragonadal). 14 stage 2a, 23 stage 2b, 10 stage 2c The median age was 36 (24-66). 13 had an EDTA > 120 ml/min. One patient withdrew after 1 cycle due to severe Raynauds. He received radiotherapy and is progression-free. 20 had a metabolic response after 1 cycle and received 3 cycles. Overall radiologic response was 32 CR, 12 PR, 3 SD. With a median follow up of 22 months PFS was 97%, overall survival 100% at 2 years. Toxicity (Grade 3/4)neutropenia 19%, thrombocytopenia 13%, fatigue 2%, vomiting 2%, febrile neutropenia1%. Tinnitus (grade 1 in 12.4%, grade 2 in 4%), neuropathy - grade 1 in 8%. 15% of patients required blood and 9% required platelets overall. Conclusions: Carboplatin monotherapy is effective with low toxicity. PET scanning allows de escalation of therapy – comparison against combination therapy is warranted. Clinical trial information: EudracT 2009-009882-33.
The effect of aspirin and anticoagulation on tyrosine kinase inhibitors induced thrombotic events in chronic myeloid leukemia: A retrospective cohort.
Authors: Yazan Numan, Muhammad Jamil, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2017)

e18550 Background: The newer Tyrosine Kinase Inhibitors (TKI) versus imatinib recently were called into question due to reported long-term toxic effects. These include cardiovascular adverse events, arterial and venous thrombosis. Our objective is to determine the effect of antiplatelet and anticoagulation on arterial and venous thrombotic events during the use of TKI for chronic myeloid leukemia (CML). Methods: Multi-center retrospective cohort based on the use of antiplatelet and anticoagulation medications. Chi square test was used and regression analysis for the recorded confounding variables applied. Results: a total of 968 patients were identified from 4 large cancer centers. Preliminary results on the first 168 entered are the following: Average age of the sample is 48 years. 41% were females and the rest were male patients. Average BMI was 29. Average duration of treatment on TKI was 66 months. 20 % of patients were using Aspirin and 11% were using anticoagulation with therapeutic INR. 8% were using dual therapy. 10% developed a thrombotic event during TKI use, namely: MI (2.4%), DVT (3.1%), PE (0.7%), Stroke (2.4%). Our results show that Aspirin or dual therapy decrease the thrombotic events excluding MI only in newer TKI (26% vs 11% P value = 0.002) Fig-1. Conclusions: This study is the first to investigate the effect of anticoagulation and antiplatelet medications on patients receiving TKI. Our main objective after completion of analysis of 968 patients is to answer the question whether patients receiving TKI should receive a prophylactic antiplatelet or anticoagulation therapy and if TKI mediated thrombotic event has “Vasculitis induced thrombosis” pathway that is resistant to anticoagulation/antiplatelet therapy.
Incidental vs. clinical diagnosis of renal cell carcinoma (RCC): Population, treatment and outcome in a cohort of 828 patients followed at Instituto Oncológico Henry Moore (IOHM).
Authors: Dario Niewiadomski, Claudia Lorena Acuna, Eduardo L. Morgenfeld, Flavio Tognelli, Leonardo Smolje, Monica Montiel, Carlos Fernando Garcia Gerardi, Mariana Abal, Ernesto Gil Deza, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2017)

e16075 Background: For the past three decades, it has been observed in developed countries an increase in the incidence of RCC, at the expense of small tumors incidentally found. This study compares the epidemiology, treatment and evolution of the patients (pt) with incidental RCC (Group A) or clinical RCC (Group B). Methods: Between 1/1/2001 and 11/30/2016, 29,440 new pt with histological diagnosis of cancer were incorporated to the IOHM database. We selected all those coded under the WHO ICD10 code C64. The medical records were reviewed, registering the epidemiological data, treatments and evolution of each patient Results: We identified 828 pt out of 29,940 pt (2.8%) who met the inclusion criteria. Group A = 507 pt (61%) and Group B = 321 pt (39%). The table below shows the characteristics of both groups. Conclusions: 1) In this cohort the incidental diagnosis of RCC represented 60% of the cases and correlated with early stages and less aggressive tumors. 2) The appropriate selection of patients allowed partial nephrectomies in 103/828 Pt. (12% of the cases). 3) With a median follow-up of 30 months the survival rate of this population exceeded 90% in the early stages and was close to 50% in advanced cases. [Table: see text]
Effect of hepatitis C virus (HCV) on the outcome of hepatocellular carcinoma (HCC).
Authors: Rangaswamy Govindarajan, Sandra P Susanibaradaniya, Eric R Siegel
Journal: Journal of Clinical Oncology (2016)

e15634 Background: HCV infection is a major cause of HCC in the United States. In previous published subset analysis of HCC subjects treated with sorafenib, HCV subjects had better outcome. To evaluate the effect of HCV infection on survival in HCC and the interaction with local and systemic therapies, a retrospective cohort analysis of subjects in VA population was conducted. Methods: Veterans with HCC were identified from the VISN 16 tumor-registry from 2007-2012. Tumor stage, etiology of HCC [Hepatitis B virus (HBV), HCV, and non-viral causes], treatment received and outcome were collected. Results: 1035 HCC subjects were identified. Median age was 60 years (range 43-93); 99.4% were male; 63.4% Caucasian, 34.6% African-American. 76.4% had history of alcohol use; 47.3% were positive for Hepatitis C, 2.1% for Hepatitis B, and 1.1% for both. Subjects with HBV (N=34) were excluded from analysis due to their small number. Of the remaining 1001 subjects, 53.3% received no therapy, 16.2% received Sorafenib, 24.9% received loco-regional therapy (LRT) with radiofrequency ablation, trans-arterial chemo embolization (TACE), or ethanol injection, alone or in combination, and 5.7% had surgical resection. HCV subjects had a 19% reduction in mortality compared to uninfected subjects (HR=0.81; p=0.0028). The effect of HCV infection on overall survival within treatment subgroups is shown in the table. Conclusions: HCC subjects with hepatitis C appear to have better survival compared to those with other noninfectious etiologies. The beneficial effect was seen only in subjects who did not receive any therapy, probably from HCV having an effect on the natural history of the disease. The lack of evident effect in those who received Sorafenib, LRT and resection, may be due to small numbers and interaction with other influencing factors affecting such therapies. Therapy Total With HCV Median Survival, Months P N N (%) With hepatitis C No hepatitis No Treatment 533 246 (46) 8.1 3.8 0.036 Sorafenib Only 162 71 (43) 7.4 8.6 0.40 Loco-regional Therapy* 249 143 (57) 30.7 27.0 0.64 Resection/Lobectomy$ 57 30 (53) 56.4 60.1 0.85 *21 subjects also received Sorafenib. $13 subjects also had TACE, 5 received Sorafenib, 1received both.
Evaluation of the efficacy of anti-angiogenic agents, alone and in combination with pemetrexed in the zebrafish model.
Authors: Yinghua Jin, Lingxiao Wei, Qiuying Jiang, Xiaowei Song, Chong Teng, Chengjuan Fan, Yanju Lv, Ying Liu, Li Li, Dayong Huang, Tao Xin
Journal: Journal of Clinical Oncology (2018)

e24005 Background: The poor prognosis in non-small cell lung cancer has driven the development of angiogenesis inhibitors. However, information on clinical characteristics of inhibitors with different mechanisms is sparse. We performed a study to characterize three anti-angiogenic drugs (apatinib, bevacizumab and endostar) in terms of efficacy, toxicity and tumor suppression (alone and in combination with pemetrexed). Methods: Transgenic fluorescent zebrafish Tg(fli1:EGFP) at 2dpf was applied to explore anti-angiogenesis activities through subintestinal vessels examination. Wild-type embryos at 2dpf were injected with CM-Dil labeled human lung adenocarcinoma cell (A549) for antitumor assay. The 6hpf wild-type larvae were used to screen for drug toxicity, presented by their morphological changes. Results: The angiogenesis inhibition rates of apatinib (2.2μg/mL, 26%; 6.7μg/mL,32%; 20μg/mL, 35%), bevacizumab (28ng, 24%; 83ng, 26%; 250ng, 28%) and endostar (11ng, 26%; 33ng, 32%; 99 ng, 33%) were shown in a dose-dependent manner. Compared to control group, tumor growth inhibition effect of apatinib were not obvious whether its concentration was 0.057 or 0.167μg/mL. While increasing to 0.5μg/mL, the inhibition rate (23%) was significantly increased (p < 0.01). Both bevacizumab and endostar independently inhibited tumor growth (p < 0.01) (data not shown), while no synergistic effect in tumor growth inhibition was detected when combined with pemetrexed. At toxicity assay, apatinib (0.22, 0.67 and 2μg/mL) showed delayed yolk sac absorption. When apatinib concentration was 2µg/mL, morphological abnormality was observed, including pericardial edema, slowed heart rate, decreased eye size, and shortened body axis. Bevacizumab and endostar performed no obvious toxicity. Conclusions: All drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab revealed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstringed by its elevated toxicity at 35℃. The addition of pemetrexed to anti-angiogenesis therapy revealed no additional benefit.
Safety and efficacy of irreversible electroporation for aggressive fibromatosis: Initial experience.
Authors: Kyle Maughan, Ty Subhawong, Shree Venkat, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2018)

e23549 Background: Aggressive fibromatosis requires coordinated multidisciplinary care to manage. This first report explores the role of Irreversible Electroporation (IRE) in controlling the disease when conventional options are not available. We also explore the difficulty of assessment of imaging response. Methods: A retrospective evaluation of a single center experience from 05/2012 to 08/2017 revealed 6 patients with biopsy-proven aggressive fibromatosis referred to Interventional Radiology for IRE. Patients were poor surgical candidates who had either failed or declined non-surgical management (3 tumors had previously undergone surgical intervention). Three chest wall tumors, 1 thigh tumor, 1 popliteal tumor, and 3 calf tumors (total of 8 tumors) were treated with IRE (NanoKnife System, AngioDynamics). The patient age range was 24-54, 5 females and 1 male. A total of 10 procedures were performed as 2 lesions were managed in stages due to size. Tumor dimensions in three orthogonal planes were recorded; tumor:muscle signal ratios were calculated on contrast-enhanced MRI and response characterized according to RECIST1.1 and modified Choi Criteria. Pre- and post-ablation results were compared to assess tumor change. Adverse events were documented using common terminology criteria for adverse events (CTCAE V4.03). Results: All 8 tumors (100%) achieved a modified Choi PR (7 by tumor density, 1 by size) at a mean follow up of 124 days post-IRE, while none met criteria for RECIST1.1 PR. Five out of 8 eventually met criteria for RECIST1.1 PD with a mean time to progression (TTP) of 335 days post IRE. Four of 6 patients required additional therapy (chemotherapy or another systemic agent) after IRE due to disease progression, with a mean of 520 days until the next treatment. Five patients experienced an adverse event, including neuralgia (grade 1 and 2), peripheral sensory neuropathy (grade 1), or burns (grade 3). Conclusions: IRE can provide local control of aggressive fibromatosis, though a high rate of recurrence can be expected. Modified Choi criteria may be a more accurate reflection of early treatment response than RECIST1.1 as it captures changes of density when size does not reflect response.
Rapid Divergence of Genome Architectures Following the Origin of an Ectomycorrhizal Symbiosis in the Genus Amanita
Authors: Jaqueline Hess, Inger Skrede, Maryam Chaib De Mares, Matthieu Hainaut, Bernard Henrissat, Anne Pringle
Journal: Molecular Biology and Evolution (2018)

Fungi are evolutionary shape shifters and adapt quickly to new environments. Ectomycorrhizal (EM) symbioses are mutualistic associations between fungi and plants and have evolved repeatedly and independently across the fungal tree of life, suggesting lineages frequently reconfigure genome content to take advantage of open ecological niches. To date analyses of genomic mechanisms facilitating EM symbioses have involved comparisons of distantly related species, but here, we use the genomes of three EM and two asymbiotic (AS) fungi from the genus Amanita as well as an AS outgroup to study genome evolution following a single origin of symbiosis. Our aim was to identify the defining features of EM genomes, but our analyses suggest no clear differentiation of genome size, gene repertoire size, or transposable element content between EM and AS species. Phylogenetic inference of gene gains and losses suggests the transition to symbiosis was dominated by the loss of plant cell wall decomposition genes, a confirmation of previous findings. However, the same dynamic defines the AS species A. inopinata, suggesting loss is not strictly associated with origin of symbiosis. Gene expansions in the common ancestor of EM Amanita were modest, but lineage specific and large gene family expansions are found in two of the three EM extant species. Even closely related EM genomes appear to share few common features. The genetic toolkit required for symbiosis appears already encoded in the genomes of saprotrophic species, and this dynamic may explain the pervasive, recurrent evolution of ectomycorrhizal associations.