tbuckley/cabot-search huggingface dataset:
AB1109 Missed cases of macrophage activation syndrome in juvenile idiopathic arthritis (RETROSPECTIVE STUDY)
Authors: M.G. Zaki, A.Z. Elyasaki, D.S. Al-Zifzaf, A.H. Safar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Macrophage activation syndrome (MAS) is a complication of JIA which elevates morbidity and mortality. Early recognition, differentiation from activity of JIA itself and the subsequent introduction of aggressive treatment contributes to better prognosis. <h3>Objectives</h3> A retrograde study to investigate the occurrence of missed MAS among JIA patients to assess the extent of the problem among those patients. <h3>Methods</h3> The study included 100 JIA patients registered in paediatric departments over 2 years in urban areas of Cairo. All JIA subtypes where included. MAS was diagnosed according to preliminary diagnostic guidelines for MAS complicating sJIA.<sup><b>Ravelli et al., 2005)</b></sup> JIA patients who had history of recent infection, hepatitis or other liver disease, malignancy and pancytopenia were excluded. The hospital registry for JIA patients was scanned for medical history with special attention for records of history suggestive of MAS, Clinical examination, Laboratory investigations and radiological data. Complementary investigations were done when needed. <h3>Results</h3> Among the studied 100 JIA patients, 14% of patients fulfilled the criteria and were diagnosed awith MAS. Mortality rate was 2% of all JIA patients and 14% of JIA cases with MAS. Regarding gender, there were 10 females (71%) and 4 males (35%). Their age ranged from 3.5 to 18 years old (median 8 years). The disease duration ranged from 0.1 to 6 years (median 1.5 years). Ferritin level was elevated in all MAS patients. Renal affection was present in 10 MAS patients (71%) in the form of elevated serum creatinine level, In contrast to uncomplicated JIA where there was no significant renal involvement. <h3>Conclusions</h3> MAS is a potentially fulminant disorder whose incidence has increased due to raised manifestations awareness. It may be a complication of any JIA subtype but primarily systemic onset subtype. The diagnosis of MAS should be considered in presence of continuous fever, CNS, renal or haemorrhagic manifestation in JIA. <h3>Reference</h3> [1] Ravelli A, Magni-Manzoni S, Pistorio A, Besana C, Foti T, Ruperto N, Viola S, Martini A. (2005): Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr;146(5):598–604 <h3>Disclosure of Interest</h3> None declared
The outcome of patients with resected clinical N3 or M1 lung cancer.
Authors: Takehito Shukuya, Shiaki Oh, Ryota Kanemaru, Yuichiro Honma, Rina Shibayama, Ryo Koyama, Naoko Shimada, Kazuya Takamochi, Kenji Suzuki, Kazuhisa Takahashi
Journal: Journal of Clinical Oncology (2014)

e18527 Background: As the efficacy of chemotherapy for advanced lung cancer patients has been increased, some advanced lung cancer patients may benefit from combined modality therapy including surgery like other kinds of cancers. Methods: Between 1996 and 2013, 40 lung cancer patients whose clinical stage were N3 positive and/or M1 positive at diagnosis underwent surgery at Juntendo University. We retrospectively reviewed their clinical records and evaluate patients' characteristics, progression free and overall survival. Results: The median age was 59 (range 33-90). 13 patients were female and 27 were male. 18, 16, 5 and 1 patients had performance status of 0, 1, 2 and 3 before surgery, respectively. 30, 5 and 5 patients had adenocarcinoma, squamous cell carcinoma and others. 7 patients had sensitive EGFR mutation and 1 patient had EML4-ALK fusion gene. The primary treatment was chemotherapy/chemoradiotherapy in 13 patients, local therapy to metastatic lesion in 13 patients and pulmonary surgery in 14 patients which was followed by chemotherapy in 5 patients. Lobectomy, pneumonectomy, sleeve lobectomy, bilobectomy and partial resection were performed in 26, 7, 3, 2 and 2 patient, respectively. Median progression-free survival from operation was 186 days, and 2 year progression-free survival rate was 34.6%. 2 year survival rate from operation was 57.8%. 6 patients survived more than 5 years w/o disease progression. In the multivariate analysis, age, response to preoperative therapy and solitary brain metastasis at diagnosis were statistically significant good prognostic factors. There was no surgical mortality independence of the mode of surgery. Conclusions: The feasibility of salvage or upfront surgery was acceptable for stage IIIB or IV lung cancer. Oligometastasis and/or response to definitive medical treatment could be predictors for long-term survival which may due to additional local control. Variable Odds ratio 95% CI p Age (under 65 vs over 65) 3.46 1.04-12.0 0.044 PS (0-1 vs 2-3) 1.11 0.24-4.34 0.883 Histology (Ad vs non-Ad) 1.42 0.34-5.15 0.608 Solirtary brain metastasis at diagnosis (no vs yes) 0.16 0.00-0.74 0.017 Down stage by prior therapy (no vs yes) 0.00 0.00-0.21 0.001
Predictive factors of early death during 100 days after a comprehensive geriatric assessment in older patients with cancer: A prospective cohort study of 576 patients.
Authors: Rabia Boulahssass, Véronique Mari, Sebastien Gonfrier, Francine Auben, Cyrielle Rambaud, Jean-Marc Ferrero, Jean-Michel Turpin, Jean Marc Bereder, Bereder Isabelle, Abakar Mahamat, Gerard Cavaglione, Esma Saada, Philippe Follana, Emmanuel Benizri, Josiane Otto, Jerome Delotte, Daniel Benchimol, Patrice Brocker, Eric Francois, Olivier Guerin
Journal: Journal of Clinical Oncology (2014)

9511 Background: The purpose of this study is to analyse predictive factors of early death in older patients with cancer during 100 days after a geriatric comprehensive assessment (CGA) in order to help oncologist in the therapeutic decisions. Methods: 576 older patients with cancers are enrolled, 29 cases could not be analyzed because of difficulties of language (aphasia, mutism) finally in the study. This study is a cohort and prospective study approved by an ethics committee. A geriatric comprehensive assessment (CGA) has been done before the treatment decision. Geriatric data (MMSE, MNA, BMI, grip hand grip strength ,ADL, IADL, CIRSg, Gait speed, QLQC30, Charlson, G8 and Balduccci classification) are collected . Characteristics of the cancer, social and demographic data are also collected. During 100 days of follow up, the rate of death, treatments made and geriatric interventions are collected. Results: 22% of the patients have died during the follow up of 100 days. Mean age of the patients is 82 years old (70-96). In univariate analyzes, Patients with lower gait speed (HR=4,2 (2,7-6,2)), loss of autonomy in the ADL (HR=2,6(1,7-3,8) and in the IADL (HR=2,8(1,8-4,5), metastatic cancers (HR=2,1 (1,5-3,1)), poor nutritional status with MNA <17 (HR 8,2 (2,6-29)), home confinement (HR=3,3 (2,3-4,8)), Worse quality of life (HR=4(2,3-7,4)), G8<14 (HR=1,6(1,1-2,4)), Charlson pondered >6(HR=2,2(1,1-4,3)) and higher state score on Balducci's classification had significantly more risk to die.In multivariate analyses poor nutritional status with MNA<17 (HR=2,6(1,1-6,8)),metastatic cancers (HR=2,2(1,4-3,5)) and gait speed<0,8m/s (HR=2(1,1-3,7)) had significantly more risk to die. Conclusions: This study confirms the importance of the geriatric comprehensive assessment in oncogeriatric patients to predict risk factors of worse outcomes. It’s necessary to screen potential deficiencies to introduce geriatric interventions like care plan for nutrition or physiotherapy and could help oncologists in making therapeutic decisions.
Laparoscopic versus open surgery for locally advanced rectal cancer following neoadjuvant chemoradiotherapy with S-1: Short- and long-term outcomes of multicenter prospective phase II trials.
Authors: Takao Hara, Tomonori Akagi, Shinichiro Empuku, Kentaro Nakajima, Iwaki Kentaro, Seiichiro Kai, Tsuyoshi Etoh, Yu Takeuchi, Koichiro Tahara, Toshifumi Matsumoto, Koichi Ishikawa, Toshio Bando, Koshi Mimori, Norio Shiraishi, Masafumi Inomata
Journal: Journal of Clinical Oncology (2018)

793 Background: We have reported the effectiveness of neoadjuvant radiotherapy (RT) combined with S-1 in terms of compliance and pathologic response for locally advanced rectal cancer. In the present study, we aimed to evaluate the safety and efficacy of laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 in comparison with open surgery. Methods: Two multicenter prospective phase II trials were conducted (UMIN003396, UMIN003398). A total of 63 patients with locally advanced rectal cancer classified as T3-4, N0-3, and M0 were enrolled, and neoadjuvant RT combined with S-1 and total mesorectal excision with D3 lymphadenectomy was performed. Of these, 57 patients were analyzed and divided into a laparoscopic group (LAP, n = 43) and open group (OP, n = 14). We evaluated the short- and long-term outcomes of laparoscopic surgery compared with open surgery by univariate and multivariate analyses. Results: In the patient background, there were no significant differences between the two groups except that cases with T3 and N0 were significantly higher in the LAP compared with the OP. In the operative findings, operation time was longer (mean 447 min vs. 352 min, p = 0.007) and blood loss was lesser (median 220 ml vs. 485 ml, p = 0.033) in the LAP than those in the OP. Although there were no significant differences observed in the incidence of perioperative and late complications between the two groups, reoperation within 30 days was significantly less in the LAP compared with the OP (1 case vs. 5 cases, p = 0.0004). In the multivariate analysis, a distance of the tumor from anal verge within 3 cm was the independent risk factor for reoperation within 30 days. Furthermore, estimated 5-year disease-free survival (LAP 72 % vs. OP 73 %, p = 0.945) and 5-year overall survival (LAP 76 % vs. 75 %, p = 0.836) didn’t significantly differ between the two groups in the Kaplan–Meier curve. Conclusions: The findings of this study demonstrated that laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 could be an optional procedure in terms of short- and long-term outcomes. Clinical trial information: UMIN000003396, UMIN000003398.
Abstract 12132: A Genetic Risk Score is Associated With Atrial Fibrillation in the Malmö Prevention Project
Authors: Dov Shiffman, Marketa Sjögren, Judy Z Louie, Lance A Bare, Tord Juhlin, Latif Sarabi, Mariusz Kitlinski, James J Devlin, Olle Melander
Journal: Circulation (2016)

Introduction: Atrial fibrillation is associated with increased morbidity and mortality. A genetic risk score (GRS) comprising 12 single nucleotide polymorphisms (SNPs) has been found to be associated with atrial fibrillation in population-based prospective studies of middle aged participants but this association has not been investigated in the elderly. Hypothesis: A pre-specified GRS for atrial fibrillation is associated with incident atrial fibrillation in the elderly. Methods: The Malmö Prevention Project (MPP) is a population-based prospective study of 18,240 participants who were enrolled in the study between 2002 and 2006. After excluding those with prevalent atrial fibrillation or missing clinical information 4,678 participants (median age of 68.2 years (IQR 66.5 to 73.0)) were randomly selected from the cohort for the current analysis. Cox proportional hazards models were used to estimate the association between GRS and incident atrial fibrillation after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive medication, smoking, diabetes, coronary events, and heart failure. Results: Among 4,678 participants, 524 had a first atrial fibrillation event during a median 8.2 years follow-up. Participants in the top quintile of the GRS had two-fold greater risk of atrial fibrillation (HR = 2.03; 95%CI 1.54 to 2.67, P=5.0х10 -7 ) compared with those in the bottom quintile. The GRS was also associated in the elderly (those above median age, &gt;68.2 years): HR=1.82 for those in the top quintile compared with those in the bottom quintile (95%CI 1.31 to 2.52, P=0.0003) as well as in those below median age (HR =2.68; 95%CI 1.58 to 4.55, P =0.0003). Conclusion: A pre-specified GRS for atrial fibrillation comprising 12 SNPs was associated with incident atrial fibrillation in the elderly. Patients with high genetic risk for atrial fibrillation may benefit from aggressive monitoring and control of blood pressure.
Cellular level of Abelson interactor-1 as a marker predicting chemoresistance.
Authors: Anna Chorzalska, Ibrahem Salloum, Diana Treaba, Christoph Schorl, John Morgan, John Leonard Reagan, Eric S. Winer, Adam J. Olszewski, Patrycja Dubielecka
Journal: Journal of Clinical Oncology (2014)

7107 Background: In hematological malignancies, quiescent leukemic stem cells are responsible for persistence of minimal residual disease and relapse. Emerging evidence points to the involvement of the bone marrow microenvironment in survival and systemic retention of leukemic stem cells. Integrins, particularly α4β1, which controls hematopoietic stem cell trafficking, were shown to be required for leukemic stem cells lodging in the bone marrow niche, and were shown to be crucial for the persistence of minimal residual disease. We have just recently obtained evidence that α4 integrin interacts directly with Abelson interactor-1 (Abi-1) and this signaling cross-talk is involved in acquired drug resistance in Bcr-Abl positive leukemic cells. Methods: Gene expression analyses were performed on human Bcr-Abl positive CD34+ leukemic progenitor cells isolated at first diagnosis or at relapse. Imatinib mesylate resistant cell lines were used to confirm gene profiling data and determine the effect of deregulated α4-Abi-1 cross-talk on adhesion and cell cycle. Immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used in xenotransplant experiments to confirm critical role of Abi-1 in lodging of Bcr-Abl positive cells to the bone marrow. Results: We present evidence that signaling crosstalk between α4 integrin and Abi-1 is involved in acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl positive leukemia cells. Comparison of Abi-1 (ABI-1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl positive CD34+ progenitor cells demonstrated a reduction in Abi-1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate (IM) resistant leukemic cells. Conclusions: Obtained results indicate that the α4-Abi-1 signaling pathway may mediate acquisition of the drug resistant phenotype of leukemic cells and ABI-1/ITGA4 gene levels may be used as a markers predicting chemoresistance.
PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation
Authors: Philippe Armand, Yi-Bin Chen, Robert A. Redd, Robin M. Joyce, Jad Bsat, Erin Jeter, Reid W. Merryman, Kimberly C. Coleman, Parastoo B. Dahi, Yago Nieto, Ann S. LaCasce, David C. Fisher, Samuel Y. Ng, Oreofe O. Odejide, Arnold S. Freedman, Austin I. Kim, Jennifer L. Crombie, Caron A. Jacobson, Eric D. Jacobsen, Jeffrey L. Wong, Sanjay S. Patel, Jerome Ritz, Scott J. Rodig, Margaret A. Shipp, Alex F. Herrera
Journal: Blood (2019)
Final analysis: Randomized, blinded, placebo-controlled phase II trial of sorafenib with and without mapatumumab in patients with advanced hepatocellular carcinoma (HCC).
Authors: Tudor-Eliade Ciuleanu, Igor Bazin, Dan Lungulescu, Lucian Miron, Igor Bondarenko, Andrzej Deptala, Maribel Rodriguez-Torres, Bruce J. Giantonio, Weijing Sun, Norma Lynn Fox, Gursel Aktan, Paul Stephen Wissel, Jacki Egger, Meichun Ding, Rubana Kalyani, Matthew Joseph Gribbin
Journal: Journal of Clinical Oncology (2014)

4029 Background: TRAIL is a member of the tumor necrosis factor ligand super family that induces programmed cell death primarily in tumor cells (including liver tumors) through TRAIL death receptors. Mapatumumab (M) is an agonistic monoclonal antibody that targets one of the TRAIL death receptors, TRAIL-R1, and may promote apoptosis of cancer cells. Methods: Patients (Pts) with chemotherapy-naive advanced HCC were randomized 1:1 to sorafenib 400 mg BID continuously + IV Placebo (SP) or sorafenib 400 mg BID continuously + mapatumumab 30 mg/kg (SM) on day 1 every 21 days. Stratification variables were BCLC C vs B, and ECOG PS 0 vs 1, 2. Eligibility: bilirubin < 3 mg/dL, AST and ALT ≥ 5 x ULN, and INR ≥ 1.5. Radiologic progression was determined by blinded independent central review. The primary endpoint was time to progression (TTP). The sample size of 100 was sufficient to estimate median TTP with a precision of -1.9 to +2.6 months (mo). Results: 101 pts were in the ITT population: 51 SP and 50 SM. Treatment arms were balanced for the stratification variables. Demographics (SP vs SM): mean AFP 3177.7 vs 1534 mg/L, Male 76.5% vs 52%, Age 60.8 vs 60 years. Median (med) duration of M dosing was 3.3 mo and 84% pts received ≥ 90% of planned dose. Med cumulative sorafenib (S) dose (SP vs SM) was 73600 vs 75200 mg; 52.9% (SP) and 54% (SM) received ≥ 90% of the planned S dose. Conclusions: The addition of mapatumumab to sorafenib did not improve TTP (primary endpoint) or other efficacy endpoints. The combination did not substantially change the toxicity profile of sorafenib. Clinical trial information: NCT01258608.Efficacy and safety. Treatment groups SP SM N 51 50 Median TTP (mo)1 5.6 4.1 Median TTP at ECOG 0 (mo) ECOG 1 or 2 (mo) BCLC Stage C(mo) BCLC Stage B (mo) 6.9 5.6 5.4 11.1 4.1 4.2 4.2 4.1 Median OS (mo) 10.1 10.0 Overall Response (pts) 5 7 % % AEs of interest to S and M Diarrhea 37.3 32.0 Blood bilirubin increased 17.6 14.0 Rash 7.8 12.0 Related AEs to S/M Blood bilirubin increased 5.9/3.9 4.0/2.0 Fatal AEs 25.5 24.0 Serious AEs 51.0 40.0 Gastrointestinal disorders 11.8 12.0 1P-value 0.7382, HR (90% CI) 1.192 (0, 1.737). P-value for comparison of treatment groups from stratified log-rank test – stratified by BCLC and ECOG PS.
Patient age and treatment sequencing in patients with prostate cancer: Results of a multicenter observational study.
Authors: Jennifer Reichert, Frank Papatheofanis, Lorie Ellis, R. Scott McKenzie
Journal: Journal of Clinical Oncology (2014)

e16070 Background: New agents have offered greater treatment options for patients with metastatic prostate cancer. These include intravenous [cabazitaxel (C), sipuleucel-T (S)] and oral agents [abiraterone acetate (AA), and enzalutamide (E)]. Enzalutamide was approved in August 2012. To date, the impact of age on selected order of administration during patients’ treatment course, i.e. treatment sequencing, has not been reported based on observational data. Methods: Data were analyzed retrospectively from a deidentified electronic medical record system of community medical oncology practices across 14 states. Patients were selected based on a diagnosis of prostate cancer and initial treatment with docetaxel (D), C, S, AA, or E subsequent to September 2012. Treatment sequencing and mean age at treatment initiation were reported with comparison of age based using one-way ANOVA. Results: This analysis included 788 prostate cancer patients from 22 practices. The most commonly reported treatment sequences are reported in the table. Remaining treatment sequences represented ≤ 1.5% of patients each. Age at time of treatment initiation differed significantly between groups (P<0.001). Patients treated with oral medications only tended to be older than patients treated with intravenous therapies. Conclusions: Prostate cancer treatment sequencing patterns differed by age. Future research is warranted regarding reasons sequencing selection by patients and health care professionals. These data help health care professional understand current treatment patterns. Treatment sequence N (% of patients) Mean age (SD) abiraterone acetate 304 (38.6) 77 (10) docetaxel 127 (16.1) 72 (10) enzalutamide 68 (8.6) 76 (10) sipuleucel-T 68 (8.6) 73 (8) abiraterone acetate followed by enzalutamide 44 (5.6) 77 (8) enzalutamide followed by abiraterone acetate 16 (2.0) 78 (11) docetaxel followed by enzalutamide 15 (1.9) 73 (11) abiraterone acetate followed by docetaxel 15 (1.9) 73 (9) docetaxel followed by abiraterone acetate 13 (1.7) 72 (10)
Contact therapy: A feasible option for local treatment of rectal cancer in non-operable patients—A Danish experience.
Authors: Karen-Lise Garm Spindler, Peter Rasmussen, Irina Kryglikova, Lars Nyvang, Anni Ravnsbæk Jensen, Soeren Lauerberg, Jacob Christian Lindegaard
Journal: Journal of Clinical Oncology (2014)

e14543 Background: The median age of rectal cancer patients is high and an increasing fraction of patients suffer from significant co-morbidity precluding surgical procedures. Contact X-ray (CXR) delivers a high radiation dose to tumors with only limited irradiation of the healthy organs. Therefore, this approach is an attractive non-surgical option for local control of small rectal tumors in non-operable, elderly and frail patients. We report a single institute experience with CXR during the period from 2010-2012. Methods: Patients with rectal adenocarcinomas who were non-operable because they were elderly and frail or suffering from severe comorbidity, were offered local treatment with CXR by Papillion technique. Eye guided therapy was delivered using local anesthetics. Patients received 30 Gy per fraction to the tumor surface on day 1, 8, and 22 and one additional fraction of 20 Gy according to tumor response and supplementary external beam radiation therapy (EBRT) in a small group of patients with larger tumors. Patient reported outcome questionnaire (LARS score) was used to assess morbidity. Results: Thirty-one patients were treated, including a majority (n=25) of T2 tumors and 4 patient with T3-4. Median age was 82 years (54-97) and median tumor diameter was 30 mm. With CXR 90 Gy and 110 Gy was delivered to 23 and 8 patients, respectively. Additional EBRT with 25Gy/5F was delievered in seven patients. Treatment was well tolerated with no significant acute morbidity recorded in relation to CXR., Eleven treatment failures were recorded (35%), but long-term FU data is impaired by the advanced age and comorbidity of the majority of patients. The one year RFS was > 60%, despites the large number of T2+ tumors. LARS score was available from 25/31 of the patients. Seven cases of major LARS was reported. Conclusions: CXR is feasible with a positive outcome even in very old and fragile patients. This modality will be prospectively evaluated and in-cooperated into future treatment strategies for rectal cancer patients in Denmark.
Abstract 16481: A Novel Synthetic Omega-3 Epoxyeicosanoid Analogue Modulates Ca2+ Handling and Exerts Anti-Arrhythmic Effects
Authors: Robert Fischer, Tim Wesser, Anne Konkel, Janine Lossie, John R. Falck, Azinwi Phina Khan, Markus Kamler, Dobromir Dobrev, Wolf-Hagen Schunck
Journal: Circulation (2017)

Introduction: OMT-28 is a first-in-class drug candidate for rhythm stabilization and cardioprotection that has just entered clinical phase I (EudraCT No.: 2016-003445-28). Hypothesis: As a syntheti...