tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of consolidation chemotherapy after preoperative chemoradiation (preop CRT) versus CRT alone for locally advanced rectal cancer (LARC).
Authors: Sun Young Kim, Tae Won Kim, Yong Sang Hong, Jeong Eun Kim, Keun Wook Lee, Ji-Won Kim, In Gyu Hwang, Beom Gyu Kim, Joong Bae Ahn, Ho-Suk Oh, Dae Young Zang, Jungnam Joo, Dae Yong Kim, Jae Hwan Oh, Ji Yeon Baek
Journal: Journal of Clinical Oncology (2017)

3606 Background: In LARC, preop CRT followed by total mesorectal excision (TME) is a standard of care. Recently consolidation chemotherapy after CRT was shown to be safe and to improve pathologic complete response (pCR) rate in LARC. We aimed to evaluate downstaging (DS) rate (the proportion of ypT0-2N0M0) of CRT followed by consolidation chemotherapy (capecitabine and oxaliplatin: CapOx) compared to that of CRT alone. Methods: Patients (pts) with adenocarcinoma of rectum(≤ 12cm from anal verge), ECOG PS 0 or 1, and cT3-4NxM0 were enrolled. CRT (50-50.4Gy/25-28fx) with Cap (825mg/m 2 /day for 5 days per week throughout CRT) followed by TME was planned in Arm A (control arm). In Arm B, 2 cycles of CapOx was given a week after completion of CRT before TME (Cap 850mg/m 2 /day from day 1 to day 14; Ox 100mg/m 2 on day 1; q 3w). 110 pts (55 per arm) were needed to show improvement of DS rate in per-protocol population (PP set) from 30% to 50% in arm B with one-sided α = 0.15, 1- β = 0.85, and follow-up loss in 5%. Results: From 9/2014 Sep to 2/2016, 110 (56 in arm A; 54 in arm B) were enrolled; 108 (55 in arm A; 53 in arm B) were randomized and started study treatment. Median age was 56 years; male/ECOG PS 1/cT4 was 76%/70%/18%. 100 pts (54 in arm A; 46 in arm B) completed CRT ± CapOx and surgery (R0 or R1 resection), while 8 (1 in arm A, 7 in arm B) dropped out mainly due to consent withdrawal. 2 of each arm underwent non-TME; that leaves 96 (52 in arm A and 44 in arm B) in PP set. Relative dose intensity of CapOx was 96% (Cap) and 95% (Ox). The main treatment outcome is described in table. The mean interval days between completion of CRT and surgery was significantly longer in arm B (52.9 vs 61.3, p &lt; 0.0001). Conclusions: 2 cycles of CapOx after completion of CRT was feasible and safe, and it showed improvement in DS rate, even with high dropout rates (13%). Clinical trial information: NCT01952951. [Table: see text]
Differences in survival outcomes in advanced endometrial cancer due to variation in adjuvant therapy and histology.
Authors: Emily Meichun Ko, Colleen Brensinger, Diego J Aviles, Ashley Ford Haggerty, Robert Lawrence Giuntoli, Nawar A. Latif, Mark Aloysuis Morgan, Lilie L. Lin
Journal: Journal of Clinical Oncology (2018)

5588 Background: To determine the impact on overall survival (OS) of the sequence-order of adjuvant radiation (RT) and chemotherapy (CT) on different advanced endometrial cancer (EC) histologies. Methods: Stage 3 endometrioid (EAC), serous (SER), clear cell (CC), and carcinosarcoma (CS) patients who underwent primary surgical staging from 1999-2011 were identified in SEER-Medicare. Sequence, timing, and modality of RT and CT were analyzed using Kaplan-Meier estimates, log rank tests, and multivariable cox modeling. Treatment groups with n < 10 were excluded in cox modeling. Results: Of 2375 cases identified (1537 EAC, 485 SER, 96 CC, 257 CS), 31.3% received no AT. The remainder received RT or CT alone, concurrent RT-CT, serial or sandwich modalities (table 1). OS differed by receipt of AT overall as well as within each histologic subtype (log rank p < 0.05, all). After adjusting for age, race, substage, region, and histology, all patients receiving AT except for concurrent RT-CT followed by CT, had improved OS over no treatment (all p < 0.05). However, differences by histology were seen. For EAC the sandwich arm had the greatest reduction in death (72%), whereas for SER and CC the concurrent RT-CT arms fared best. For CS receipt of any CT improved OS, whereas above RT alone did not. (Table1). Conclusions: OS for advanced EC significantly differs by histology and mode of adjuvant therapy. Future studies should evaluate whether sandwich therapy for EAC, concurrent RT-CT for SER and CC, and CT alone for CS may most effectively improve OS. Adjuvant therapy: adjusted HR for OS. Type of AT (%) All histology EAC SER CC CS None 31.3 ref ref ref ref ref RT 26.2 0.80 (0.71, 0.91) 0.78 (0.67, 0.92) 0.96 (0.67, 1.36) 0.90 (0.45, 1.81) 0.73 (0.49, 1.09) CT 24.8 0.60 (0.52, 0.70) 0.60 (0.48, 0.74) 0.69 (0.53, 0.90) 0.60 (0.26, 1.36) 0.45 (0.30, 0.67) Concur RT-CT 9.5 0.51 (0.41, 0.64) 0.60 (0.45, 0.79) 0.43 (0.26, 0.69) 0.29 (0.10, 0.82) 0.50 (0.29, 0.87) Serial CT- RT 4.4 0.52 (0.38, 0.72) 0.56 (0.37, 0.84) 0.68 (0.38, 1.22) Serial RT-CT 1.6 0.60 (0.39, 0.93) 0.55 (0.32, 0.95) Sandwich 1.3 0.53 (0.31, 0.90) 0.28 (0.12, 0.69) Concur RT-CT, then CT 0.6 0.69 (0.32, 1.46)
End of life services for cancer patients: A population-based evaluation.
Authors: Scott David Ramsey, Veena Shankaran, Bernardo H. L. Goulart, Catherine R. Fedorenko, Karma L. Kreizenbeck, Gary H. Lyman, Ted Conklin, Csaba Mera, Bruce Smith
Journal: Journal of Clinical Oncology (2016)

6524 Background: Many studies suggest that end-of-life (EOL) care in the United States is variable and misaligned with patient and family preferences. Several metrics were characterized as part of a regional effort of patients, clinicians, researchers and health plan representatives to identify high-priority quality indicators for palliative care and identify opportunities for interventions to improve palliative care. Methods: Surveillance, Epidemiology, and End Results (SEER) records for patients diagnosed with cancer in Western Washington state between January 1, 2007 and May 31, 2014 were linked with enrollment and claims from two regional commercial insurance plans primarily covering individuals < 65. Using claims and SEER records, algorithms were developed to characterize end-of-life care. Results: The patient’s location or service at death was measured and is presented in order of most to least used: hospice care inpatient or outpatient (45%), hospital inpatient (34%), home/other (16%), nursing home (3%), emergency department (2%). These results varied by cancer type, with colorectal and lung cancer the most likely to receive hospice care (46% and 45% respectively), breast cancer patients having the highest proportion who die in an inpatient setting without hospice (41%), and prostate cancer having the highest proportion who die at home (33%) and who die in the emergency department (7%). Conclusions: These analyses demonstrate a variety of both desirable and potentially unnecessary care. The results suggest that there is a need and opportunities for interventions to improve working age cancer patients' care at the end of life. Patient utilization of measured services. EOL Services Description Time period in relation to death Last 90 days Last 30 days Last 14 days Last day Chemotherapy/Radiation Use of radiation therapy(greater than 3 days) or chemotherapy 44% 24% 11% 1% Advanced Imaging The use of CT, MRI, PET and/or bone scans 79% 49% 31% 2% Hospital Use Inpatient admissions and emergency department visits 80% 63% 52% 28% Hospice Use Hospice service 2% 16% 26% 45% Narcotic Use Supplied opiates 52%
Comparison between real costs and patient's perceptions of the chemotherapy in a Brazilian cancer care facility.
Authors: Vinicius Lorandi, Marcio Debiasi, Stephen D. Stefani, Leticia Ribeiro, Marieni da Costa, Bibiana Trevisan
Journal: Journal of Clinical Oncology (2017)

e18343 Background: Cancer is growing very fast and is responsible for roughly 7 million deaths annually. Cancer patients throughout the world suffer from both psychosocial and financial distress early in the time they are diagnosed with the disease. While anti-cancer therapy can magnify such effects by consuming extra intellectual energy from the patient and their family, further burden derived from the economic implications of cancer treatment have been ranked by many as an urgent issue. Methods: 46 patients with diagnosis of prostate, breast, lung or gastrintestinal cancer were asked to fill out a form while receiving chemotherapy. It contained 14 questions. Nurses were responsible for data collection. Wilcoxon test was used to test for interaction. Results: The mean age of patients was 62.2 (±13) and 58% of them were women. Aproximately half of them declared having completed higher education or more. The majority of patients had breast cancer (40%) followed by colorectal (38%), prostate (16%) and lung (5%). Most of the patients believed to be treating a localized disease and thought cure was their treatment goal. 31% of patients said they spent more than expected with their treatment and nearly half thought cost to be a concern. When reviewing patient's expectations and real treatment goals we noticed that the majority of patients had stage IV disease (56%) and that 60% were under palliative care. The median actual cost declared by patients was R$3,000 while the real cost median was R$7,055 which accounts for a 40% downstaging of the real cost. At last, 78% of patients estimated the costs to be less than it really is. Conclusions: There is still a large gap between patient's perceptions about chemotherapy goals and disease stage. When it comes to costs of the treatment the majority of patients tend to underestimate it. That may be in part because most brazilian private health care providers do not work with co-participation and therefore all costs are covered.
Effect of metformin on survival in CLL and risk stratification using age-adjusted comorbidity indexes: A retrospective analysis of the Roswell Park CLL Database.
Authors: Anil Rabindranath Singh, Othman Salim Akhtar, Robert Ferdman, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2018)

e19511 Background: CLL is an indolent disease with long disease course and is notable for one of the oldest median ages of onset of all cancers. As such, patients have the potential for many years of life after diagnosis. Prior studies in solid tumors, as well as our own prior research with DLBCL, have shown that Metformin improves outcomes. We sought to investigate the Roswell Park CLL database to look at real world trends from our experience. Methods: 977 patients were identified from the Roswell Park database that were seen for CLL between Jan 1990 to June 2017. 629 of those patients were seen primarily at Roswell Park with the other 348 being seen as second opinions. Investigation of Latency (time from diagnosis to first progression), progression free survival (PFS) and overall survival (OS) were analyzed based on factors such as TP53 mutation, cytogenetics, IGHV mutation, CD38, presence of Diabetes and/or use of metformin at the time of first line treatment, Charlson Comorbidity Index (CCI) and age-adjusted comorbidity index (AACI). Results: Metformin at the time of first line treatment was not associated with improved latency or OS compared to patients who were not diabetic, or were diabetic and were on other agents. Presence of TP53 mutation at the time of diagnosis was associated with a trend to shorter latency and OS, although this did not reach statistical significance. IGHV mutation > 2% and CD38 < 30% were both associated with improved OS (Mean OS 7312 vs. 4084 days with p = 0.036 and Mean OS 5577 vs 4810 days with p = 0.018 respectively). Individual cytogenetic changes (del11q, del17p, normal, +12, del13q) at the time of each progression were not associated with significant differences in PFS. There was no significant difference in PFS1 and OS comparing chemotherapy to newer agents, as well as comparing individual chemotherapy regimens. When stratified based on CCI and AACI groups, there was a statistical difference in OS with higher CCI and AACI groups having worse OS. Conclusions: Use of Metformin was not associated with improvements in latency, or OS. The AACI appears to be a good tool for risk stratification among CLL patients at the time of diagnosis.
Nonspecific tumor markers in the era of value based medicine: Role of CA 19-9 in the pelvic mass workup.
Authors: Jenny Underwood, Haleema Saeed, Esther Y. Chae, Rabbie Kriakoss Hanna
Journal: Journal of Clinical Oncology (2017)

e18194 Background: When encountering a pelvic mass, CA 125 and CEA are usually obtained to evaluate for ovarian or colon cancer. The clinical importance of ordering a CA 19-9 level is unknown. Does it offer valuable information or merely add confusion and additional workup if elevated? Methods: 3,370 women were retrospectively identified via CPT codes for pelvic mass and CA 19-9. Initial analysis reviewed the subspecialty of the primary investigator using CA 19-9 in their initial workup, and its correlation to a gynecologic pathology. In the cases where an OBGYN was the primary investigator additional tumor markers, age, race, menopausal status, imaging, surgical interventions and final pathology were further analyzed. Results: Out of 3,370 women 982 had an abnormal CA 19-9. The distribution of subspecialties that utilized CA 19-9 in their initial work up was Hematology Oncology 31.6%, Internal Medicine 18.7%, Gastrointestinal 18.2%, Gynecology 9.2%, Surgery 8.8%, Emergency Medicine 5.7%, Transplant 4.9%, and Family Medicine 2.9%. Of the patients evaluated by Gynecology, 32.2 % were found to have elevated CA19-9 which led to additional work-up of the upper GI tract in 18.9% including MRI, and PET preoperatively. Further analysis revealed that there was no correlation between the elevation of CA 19-9 and whether the tumor was malignant or benign [p value = 0.45] even after being adjusted for: menopausal status, presence of endometriosis, or pathology including mucinous cell type. Conclusions: The majority of adnexal masses are benign; the main goal of diagnostic evaluation is to exclude malignancy. Value based medicine is implemented to help improve health care quality, and efficient utilization of health care resources. Based on this retrospective analysis the use of CA 19-9 in evaluation of a pelvic mass does not offer information that directly improves patient outcome, but rather correlates to the increased misuse of health care resources.
Effect of some cytokine combinations on growth and metastasis of experimental melanoma.
Authors: Elena Yurievna Zlatnik, Ekaterina I. Zolotareva, Evgeniya M. Nepomnyashchaya, Oksana G. Shulgina, Inna Arnoldovna Novikova, Yury Valentinovich Przhedetskiy, Victoria V. Pozdnyakova, Sergey Kochuev, Viktoria Przhedetskaya
Journal: Journal of Clinical Oncology (2017)

e21081 Background: The purpose of the study was development and experimental validation of new methods of melanoma immunotherapy involving cytokines. Methods: The study included 30 С57Bl/6 mice with transplantable B16 melanoma. Dynamics of tumor growth, melanoma metastases to the lungs and spleen, morphology of melanoma, spleen and thymus and lymphocyte subsets in the blood and spleen after injected combinations of immunomodulators based on recombinant cytokines – IL-2 (Roncoleukin), IFN-γ (Ingaron) and TNF-α with thymosin (Refnot) – were studied. Results: Roncoleukin+Ingaron was the most effective combination that inhibited tumor growth during the therapy and after it by 30-38% and had a marked antimetastatic effect, up to complete absence of metastases in all animals. Morphological study demonstrated that thymus was the most active in this group of mice (a well-developed cortex with densely packed thymocytes); apparently, it was the cause for the increased levels of T-cells in the blood and Th (CD3e+CD4+) in the spleen of tumor-bearing mice compared to controls. The spleen of the mice showed a well-developed white pulp with large follicles, and Th level was the maximal – 47.9±1.5%, while in other groups it ranged from 15 to 35%. Morphological study of tumors revealed extensive necrosis (up to 2/3 of the tumor area), leukocyte infiltration, bleeds, blood clots in the vessel lumen and degenerative changes in tumor cells in all combinations of immunomodulators. Melanoma structure in the control group was typical, and most mice developed small and large metastases, sometimes multiple ones with extensive lung lesions; spleen metastases were observed in some mice. Conclusions: The study demonstrated the benefits of a search for optimal combinations of cytokine-based immune drugs to influence effectively an experimental transplantable tumor.
Unsupervised hierarchical clustering of surface antigen expression to identify normal karyotype AML patients with distinct disease characteristics and poor outcome.
Authors: Madlen Jentzsch, Marius Bill, Luba Schuhmann, Juliane Grimm, Julia Schulz, Karoline Schubert, Maria Knyrim, Laura Schmalbrock, Stefanie Beinicke, Janine Häntschel, Wolfram Pönisch, Vladan Vucinic, Georg-Nikolaus Franke, Gerhard Behre, Dietger Niederwieser, Sebastian Schwind
Journal: Journal of Clinical Oncology (2017)

7042 Background: Surface antigen expression evaluation is part of the standard work-up at acute myeloid leukemia (AML) diagnosis. The biological &amp; prognostic implications of surface antigen expression patterns in normal karyotype (NK) AML patients (pts) remain unknown. Methods: The diagnostic antigen expression patterns of mononuclear cells in bone marrow (BM) of 111 NK-AML pts were assessed using a standard flow cytometric panel. At diagnosis common AML gene mutations (mut) &amp; expression levels were analyzed. Pts received stem cell transplantation (SCT, 98% allogeneic, 2% autologous; median age 63 years [y, range 26-74y]) after induction therapy at our institution. Median follow up was 3.3y. With R’s gplot package unsupervised hierarchical clustering of surface antigens was performed &amp; revealed 4 distinct clusters. Results: Pts in cluster 1 (n = 36) had higher expression of immature, in cluster 2 (n = 31) of thrombocytic/T-cell/erythroid, in cluster 3 (n = 24) of monocytic &amp; in cluster 4 (n = 20) of myeloid surface antigens. All 4 clusters associated with distinct clinical &amp; molecular features. At diagnosis, compared to all others, pts in cluster 1 had a higher CD34+/CD38- cell burden ( P&lt; .001), higher blood blasts ( P&lt; .03) &amp; BM blasts ( P&lt; .06) by trend. They had less NPM1 mut ( P&lt; .001) &amp; DNMT3A mut ( P= .02), were more likely to be EVI1 positive ( P= .03) &amp; had higher EZH2 ( P= .02), RUNX1 ( P= .009), BAALC ( P&lt; .001), ERG ( P= .02) &amp; MN1 ( P&lt; .001) expression. Compared to all others, pts in cluster 1 had a higher cumulative incidence of relapse (CIR, P= .002, at 1y 41% vs 15%) &amp; shorter event-free survival (EFS, P= .02, at 1y 50% vs 69%). In multivariate analysis, cluster 1 pts had a significantly higher CIR (Hazard Ratio [HR] 5.4, P= .01) after adjustment for FLT3-ITD &amp; shorter EFS (HR 2.1, P= .02) after adjustment for FLT3-ITD, age &amp; disease status at SCT. Conclusions: Pts in cluster 1 had high expression of immature surface antigens (eg CD34, CD117, CD13), genes involved in stem cell renewal &amp; worse outcome. Our data indicate a relationship between easily accessible surface antigen expression patterns at diagnosis, molecular disease features &amp; aggressiveness of the NK-AML phenotype.
Phase IB trial of carboxyamidotriazole orotate (CTO) and radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in newly diagnosed glioblastoma (GBM).
Authors: Antonio Marcilio Padula Omuro, Kathryn Beal, Katharine Anne McNeill, Alissa A. Thomas, Xuling Lin, Thomas Joseph Kaley, Lisa Marie DeAngelis, Ingo K. Mellinghoff, Eli L. Diamond, Timothy An-thy Chan, Robert J. Young, Yoshiya Yamada, Greg Gorman, Michael Lamson, Linda M. Bavisotto, Rashida A. Karmali
Journal: Journal of Clinical Oncology (2016)

2060 Background: CTO is an oral inhibitor of non-voltage-dependent calcium signaling achieving simultaneous modulation of several receptor-mediated signaling pathways. A single-agent phase I trial determined the maximum tolerated dose (MTD) at 427 mg/m2, with a safe toxicity profile. A phase IB in combination with TMZ for TMZ-refractory glioma found therapeutic brain tissue concentrations and early evidence of activity, prompting this study in newly diagnosed GBM. Methods: Following a 3+3 design, pts received escalating doses of daily CTO (219-481mg/m2) added to the standard GBM RT regimen (60 Gy concurrent with TMZ 75 mg/m2 daily, followed by adjuvant TMZ 150-200 mg/m2 x 5/28 days). Results: Accrual is complete. All pts (N = 15) had GBM (methylated MGMT: 33%; unmethylated: 67%). ChemoRT was well tolerated at CTO doses of 219-481 mg/m2. CTO-related adverse events ( > 10%) included fatigue, nausea, constipation, ALT, rash, and headache; in addition to these, AE likely-related to TMZ included decreased platelets and neutrophils. No dose-limiting toxicities (DLT) were observed up to 481 mg/m2 (maximum administered dose- MAD), but cumulative toxicities emerging after the DLT evaluation period prompted de-escalation to 370 mg/m2, which was better tolerated. Exploratory efficacy analysis shows median PFS of 17m, and median OS not reached (median follow-up of survivors: 15m). The 1-y OS is 92% (95% CI 57-99%). Three pts have already completed 12+ cycles. One MGMT unmethylated completed cycle 12, discontinued CTO and has not recurred after 3+ months. One patient continuing CTO is on cycle 17 and has had a durable partial response for 12+ months. One patient continuing CTO has stable disease after 15+ cycles. PK data confirmed therapeutic levels starting at 219 mg/m2. One patient operated during study (481 mg/m2 cohort) showed tumor concentration of 5900 ng/g, with a plasma level of 3460 ng/mL. Conclusions: CTO combined with RT and TMZ is safe and well tolerated. The MAD was 481 mg/m2 and recommended phase II dose is 370 mg/m2. Given encouraging preliminary signals of activity including durable disease control, a randomized study is warranted. Clinical trial information: NCT01107522.
Abstract 15053: New Insights into the Development of the Protease Proprotein Convertase Subtilisin-Like Kexin Type 9 Antagonists
Authors: Nabil A Elshourbagy, Harold V Meyers, Shaker A Mousa, Sherin S Abdel-Meguid
Journal: Circulation (2016)

Protease proprotein convertase subtilisin-like kexin type 9 (PCSK9) is an important target for the treatment of hypercholesterolemia. PCSK9 is synthesized as a zymogen that undergoes autocatalytic ...
TCT-156 The Absorb Bioresorbable Vascular Scaffolds Demonstrate Lower Wall Shear Stress Compared to Metallic Xience V: Interim Analysis from the ABSORB III Imaging Study
Authors: Arnav Kumar, Bill Gogas, Elizabeth Thompson, Hossein Hosseini, David Molony, David Sternheim, Mohamad Raad, Sonu Gupta, Adrien Lefieux, Mostafa Vasigh, Kalina Machado, Sameer Khawaja, Karthic Chandran, Sonali Kumar, Won Lee, Rounak Gandhi, Don P. Giddens, Alessandro Veneziani, Spencer King, Habib Samady
Journal: Journal of the American College of Cardiology (2018)