tbuckley/cabot-search huggingface dataset:
Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1
Authors: Michelle A. Sugimoto, Ana Luíza C. Ribeiro, Bruno R. C. Costa, Juliana P. Vago, Kátia M. Lima, Fernanda S. Carneiro, Mylena Maira O. Ortiz, Graziele Letícia N. Lima, Aline A. F. Carmo, Renata M. Rocha, Denise A. Perez, Alessandra C. Reis, Vanessa Pinho, Lindsey A. Miles, Cristiana C. Garcia, Mauro M. Teixeira, Lirlândia P. Sousa
Journal: Blood (2017)
포스터전시 : 간세포암종에서 방사선치료로 인한 간독성 예측인자로서 ICG-R15 검사의 임상적 유용성 (초)
Authors: 윤홍인, 금웅섭, 이익재, 김자경, 한광협, 성진실
Journal: Clinical and Molecular Hepatology (2010)
Long-term responders to first-line bevacizumab-based therapy among patients (pts) with HER2-negative metastatic breast cancer (MBC): Retrospective results of an ambispective observational study.
Authors: Manuel Ramos Vazquez, Andrés Redondo, Ismael Ghanem, Miguel J. Gil Gil, Isabel Garau Llinas, Ramon Perez-Carrion, Elisa Garcia-Garre, Cesar Augusto Rodriguez, Jose Ignacio Chacon, Guillermo Lopez-Vivanco, Antonia Perello, Ruth Espinosa Aunion, Serafin Morales, Vanessa Ortega, José Ángel Garcia Saenz, Noelia Martinez, Paula Gonzalez, Angels Arcusa Lanza, Maria Jose Echarri, Ana Medina
Journal: Journal of Clinical Oncology (2013)

e12558 Background: LORENA is an ambispective observational study evaluating B-based therapy in a real world setting which purpose is to assess clinical features, treatments and prognosis of HER2-negative MBC pts with ≥12 months (mo.) of PFS to 1 st -line B-based chemotherapy (CT). Methods: Pts with MBC receiving 1 st -line CT and B are enrolled. No prespecified schedules, doses or assessments. Data since the introduction of the treatment with B were collected at inclusion (retrospective phase), and prospectively at 18 mo. after enrollment for the patients alive at the time of inclusion, including B-targeted adverse events (AEs). Relevant baseline and on-study variables were analyzed by Cox model to identify independent effects on PFS. Results: By Jan 2013, complete retrospective data were available for 84 pts, 33 (39.3%) of them having stage III-IV at diagnosis. Median age, 50 years (r: 29–77); age ≥65 years, 13%; triple negative, 20.2%; bone/liver/lung metastases (%), 55/27/40; ≥2 metastases sites: 46.4%; ECOG status 0-1: 91.7%, ≥2: 5.9%, UK: 2.3%. 67% of pts have received prior (neo)adjuvant CT, with 56 and 30% of them with anthracyclines and taxanes, respectively. The objective response was 78%, including complete responses in 23%. A further 22% had stable disease. Median duration of B-based therapy was 12.4 mo. PFS events had been recorded in 44% of pts. Median PFS: 19.5 mo. (95%CI: 15.6-23.2). Cox proportional hazard multivariate regression model showed that B-based therapy ≥15 vs &lt;15 mo was associated with improved PFS (26.5 vs 14.0 mo, p= 0.009; HR 0.40 [95%CI: 0.19-0.81]). The most common grade ≥3 B-related AEs were: Hypertension 9.5%, proteinuria 3.5%, bleeding 3.5%, and thromboembolic events 1.1%. No B-related death was reported. Conclusions: Outcomes in routine oncology practice for LORENA patients are consistent with those from prospective trials of 1st-line B-containing therapy and ATHENA study. These results suggest a benefit from a maintained VEGF suppression and that B continuation either as a single agent or combined with CT, until disease progression is recommended. Follow-up is ongoing.
Breast cancer prognosis in <i>BRCA1/2 </i>mutation carriers: A case control study.
Authors: Grazia Arpino, Matilde Pensabene, Valeria Forestieri, Caterina Condello, Maria Anna Sarno, Raffaella Ruocco, Ivana Cerillo, Carmine De Angelis, Rossella Lauria, Anna Crispo, Sabino De Placido
Journal: Journal of Clinical Oncology (2012)

1554 Background: We evaluated the clinical impact of germ-line BRCA1/2 mutations and variants of unknown clinical significance (VUS) for BRCA1/2 in patients (pts) with early breast cancer (BC). Methods: Twenty-eight BRCA-positive (BRCA+) BC pts with germ-line BRCA1 /2 mutations and 16 VUS BC pts were selected from our database and matched (1:3) with 154 nonhereditary BC controls (sporadic controls, SC, defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. Clinical characteristics, recurrence (rec) pattern, disease free survival (DFS) and overall survival (OS) were analyzed. Results: Compared with VUS and SC, BRCA+ pts were less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively p&lt;.005) and progesterone receptor (64% vs. 86% vs. 59% respectively p&lt;.005) but more likely to be triple negative (0 vs. 3.4% vs 47.4% respectively p&lt;.005). Compared with VUS and SC, BRCA+ pts were more likely treated by radical mastectomy (37.5% vs. 26.4% vs. 59.3% % respectively p&lt;.005). Pattern of rec was also different. Compared with VUS and SC, BRAC+ pts developed more second tumors (11% vs. 6.3% vs. 1.9% respectively p&lt;.0001) but less local or distant rec (31% vs. 2.6 vs. 0% for local rec and 12% vs. 16% vs. 11% for distant rec respectively p&lt;.0001). Controlateral BC was more frequent in VUS compared to the BRAC+ and SC pts (12% vs. 7% vs. 1% respectively, p&lt;.0001). At a median follow up of 88 months, at univariate analysis, BRAC+ but not VUS pts had worse OS compared to SC (p=.006). No difference in DFS was observed for VUS or BRAC+ when compared to SC pts. After adjustment for age, stage, grade, nodal status, hormone receptors, adjuvant therapy and year of diagnosis, BRCA+ pts continued to have and increased risk of death compared to SC (HR 5.9, 95% CI 1.9-18.1, p&lt;.002). Most of the deaths observed in BRAC+ pts were not cancer related. Conclusions: Despite decrease incidence of local or distant recs, BRAC+ pts seems to be more likely to die compared to SC. Development of second cancers and unknown effects of BRCA1/2 mutations on nonneoplastic diseases that cause death may account for this findings.
Correlation between total lesion glycolysis in 18F-FDG PET/CT and KRAS mutation and clinical features in patients with resectable colon cancer.
Authors: Ji Hyung Hong, Jae Ho Byun, Eun Kyoung Choi, Jin Kyoung Oh, Ji-Hun Kim, YS Lee
Journal: Journal of Clinical Oncology (2017)

555 Background: Recently, novel metabolic parameters in 18 F-FDG PET/CT such as total lesion glycolysis (TLG) and metabolic tumor volume (MTV) as well as maximum standardized uptake value (SUVmax) have been reported to be prognostic and be related with genomic aberration. We evaluated the prognostic role of these metabolic parameters and the correlation with clinical features in resected colon cancer. Methods: This study included 212 colon cancer patients who underwent surgical resection of stage II and III disease and conducted pre-treatment 18 F-FDG PET/CT between February 2009 and December 2013. TLG, MTV of the primary tumors as well as SUVmax were analyzed according to clinical features including KRAS mutation, pre-treatment carcinoembryonic antigen (CEA) and recurrence free survival (RFS). Results: TLG was significantly higher in patients with right colon cancer than those with left colon cancer ( P = 0.015) and in patients with elevated CEA than those with normal range of CEA ( P = 0.034), while MTV and SUVmax were not correlated with cancer location and CEA level. KRAS mutation analysis using peptide nucleic acid-mediated real-time polymerase chain reaction clamping was conducted in 94 patients and forty-one (43.6%) patients showed KRAS mutation in tumor tissues. TLG was significantly higher in patients with mutated KRAS compared with in those with wild KRAS ( P = 0.021). CEA was significantly higher in patients with mutated KRAS than those with wild KRAS ( P-value = 0.024). CEA and TLG could predict KRAS mutation showing odds ratio 1.07 and 1.02 in the multivariate logistic analysis ( P-value = 0.024, 0.048). There was no difference of RFS between in patients with high TLG and in those with low TLG. Conclusions: Based on the result that TLG had a predictive role for KRAS mutation and was related with tumor location and CEA value, we suggested that TLG might reflect genomic alteration and other clinical features as well as tumor burden. It could be useful for differentiating different population of colon cancer and further study is clinically warranted.
Safety and durability of ponatinib in patients with Philadelphia chromosome-positive (Ph+) leukemia: Long-term follow-up of an ongoing phase I study.
Authors: Michael J. Mauro, Jorge E. Cortes, Hagop M. Kantarjian, Neil P. Shah, Dale Bixby, Ian Flinn, Thomas O'Hare, Simin Hu, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G. Haluska, Brian J. Druker, Michael W. N. Deininger, Moshe Talpaz
Journal: Journal of Clinical Oncology (2013)

7063 Background: Ponatinib is a potent oral pan–BCR-ABL tyrosine kinase inhibitor (TKI) that is active against native and mutated forms of BCR-ABL. The safety and anti-leukemic activity of ponatinib in patients (pts) with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) were evaluated in a phase I clinical trial. Methods: Pts (N=81) with resistant/refractory hematologic malignancies were enrolled in this ongoing, open-label, dose escalation, phase I study. Ponatinib was dosed once daily (2–60 mg). 65 pts had Ph+ leukemia and are included in the present analysis (data as of 9 Nov 2012). Median follow-up was 25 (0.5–44) mos. Results: The median age of pts was 55 yrs; median time since diagnosis was 6.5 yrs. Pts were heavily pretreated (94% had received ≥2 prior TKIs, 62% ≥3). 65% had baseline BCR-ABL mutations. 46% (67% chronic phase [CP] CML) of pts remained on study. Progression and adverse events (AEs) were the most common reasons for discontinuation (17% each). The most common treatment-related AEs were rash (42%), thrombocytopenia (34%), arthralgia (20%), and increased lipase (20%). Significant anti-leukemic activity was observed (Table). Responses (major cytogenetic response [MCyR] for CP-CML or major hematologic response [MaHR] for accelerated phase [AP] CML, blast phase [BP] CML, or Ph+ ALL) were observed against the following mutations detected in &gt;1 pt at baseline: 14/19 T315I, 4/7 F317L, 2/4 G250E, 2/2 M244V, 2/2 M35IT, and 1/2 F359V. Among CP-CML pts, 73% with complete cytogenetic response (CCyR) and 63% with major molecular response (MMR) are estimated to maintain response at 2 yrs (Kaplan-Meier). Of 28 CP-CML pts with CCyR, 25 remained on study (19 with continuous CCyR); of 22 pts with MMR, 21 remained on study (15 with continuous MMR). Updated data will be presented. Conclusions: Significant and durable responses were observed in heavily pretreated CP-CML pts, regardless of mutation status, and ponatinib was generally well tolerated. Clinical trial information: NCT00660920. [Table: see text]
A phase I trial of binimetinib in combination with gemcitabine (G) and cisplatin (C) patients (pts) with untreated advanced biliary cancer (ABC).
Authors: Maeve Aine Lowery, Eileen Mary O'Reilly, James J. Harding, Erica Salehi, Ellen Hollywood, Margaret Bradley, Nickolas A Sophos, Michele Ly, Marinela Capanu, Scott R. Gerst, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2015)

e15125 Background: Activating mutations in the RAS/RAF/MEK/ERK signaling pathway are commonly found in ABC. Binimetinib is an oral, selective small molecule inhibitor of MEK1/2; single agent activity of Binimetinib in ABC has previously been observed. Preclinical data support anti-tumor synergy for Binimetinib when combined with G & C, administered in an interrupted dosing schedule. Methods: A Single arm, non-randomized, open-label, phase I,evaluated Binimetinib in combination with G and C in pts with untreated ABC, who had advanced measurable disease, ECOG 0-1, adequate bone marrow, renal, hepatic and cardiac function. The primary endpoint was to determine the MTD. Tumor tissue for targeted gene sequencing, blood samples for peripheral blood pERK expression and cell cycle analysis were evaluated. Patients received oral Binimetinib twice daily with G and C IV infusions day 8 and 15 of a 21 days cycle in a standard 3 + 3 dose escalation scheme. Binimetinib was held for 2 days prior to and on day of each G and C infusion. Results: Between 09/13 and 08/14, 12 pts were enrolled. Male = 5, Female = 7. Median age 64 years (range 48- 76). Intrahepatic cholangiocarcinoma (IHC) = 8, gallbladder cancer = 3, 1 patient mixed IHC/Hepatocellular carcinoma. 1 pt received prior adjuvant G. Best response: 6 PR (50%), 4 SD (33%), 2 PD (17%). Median progression-free survival (PFS) was 6.4 months (95% CI 1.7 – 10.9), Median OS was 9.1 months (95% CI 1.7 – 16.1). 5 pts remain on study. See table 1 for dose limiting toxicities. Conclusions: The MTDs of Binimetinib, G and C were 45mg PO BID, 800 mg/m2 and C 20mg/m2 respectively. Encouraging activity of the combination was noted. An expansion single arm phase II trial evaluating the safety and activity of Binimetinib at this dose with C & G is underway in patients with untreated metastatic ABC (clinicaltrials.gov NCT01828034). Clinical trial information: NCT01828034.Toxicities and DLT. Dose level Binimetinib G (mg/m2) C (mg/m2) No of pts DLT(tox) Dose reduction G & C (G3 tox) Dose reduction Binimetinib 1 30 mg PO BID 800 20 3 0 2 (G3 fatigue) (G3 LFTs) 1 (G3 rash) 2 45 mg PO BID 800 20 6 0 2 (G3 fatigue) (G3 platelets) 0 3 45mg PO BID 1000 20 3 2 (G4 ANC) 3 (G3 ANC) 1 (G3 rash)
Clinical factors affecting HE4 and CA125 in women at high risk of developing ovarian cancer.
Authors: Archana Raamanathan, Laura L. Holman, Diana L Urbauer, Keith A. Baggerly, Yu Shen, Robert C. Bast, Karen H. Lu
Journal: Journal of Clinical Oncology (2013)

1569 Background: CA125 is often used to screen high-risk patients (pts) for ovarian cancer (OC), but levels are affected by many factors, especially in premenopausal pts. In prior studies of low-risk pts, HE4 is more stable than CA125. The objective of this study was to determine how clinical variables affect CA125 and HE4 in pts at high risk for ovarian cancer. Methods: Serum from 373 pts at high risk of OC was collected every 3-12 mo from 2006-2012, for a total of 1081 samples. Serum CA125 and HE4 were measured in duplicate utilizing a commercially available multiplexed sandwich immunoassay (MagPlex). Multilevel regression models were used to examine the associations of clinical factors with CA125 and HE4, while considering the inter-correlated nature of outcomes measured periodically from the same subject. Results: The mean age was 44.6 years, 51.2% were premenopausal, 72.7% were white, 9.1% were Ashkenazi Jewish, 65.2% had a history of breast cancer, and 81.5% had a BRCA mutation. Log transformed CA125 was found to be 0.32 units higher in premenopausal pts compared to postmenopausal pts (p=0.0023), and 0.27 units higher in pts with active breast cancer (BC) compared to pts with no active BC (p=0.0044). In premenopausal pts, CA125 varied throughout the menstrual cycle, with highest levels noted at menstruation (p&lt;0.0001). Age, smoking status, and hormone use did not affect CA125 levels. Interestingly, there was no significant association between HE4 levels and any of the evaluated variables, including age, menopausal status, active BC, smoking status, hormone use, or point in menstrual cycle (all p&gt;0.05). Conclusions: In women at high-risk for OC, HE4 levels fluctuate less with the menstrual cycle and are less likely to be elevated in BC than CA125. This finding is important as many high-risk pts that undergo screening are pre-menopausal and have a BC history. HE4 may provide a valuable addition to the current screening regimen of high-risk pts.
Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine resistant HER2-/HR+ breast cancer.
Authors: Fabrice Andre, Richard Greil, Neelima Denduluri, Alejandro Javier Yovine, Cathy Reddick, Matthew Squires, Yong Zhang, Kimberly Blackwell
Journal: Journal of Clinical Oncology (2012)

TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients (pts) have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy but can be overcome via FGFR1 inhibition in preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor tyrosine kinase inhibitor that demonstrated antitumor activity in heavily pretreated breast cancer pts with FGF pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and is studied here to determine if it can improve outcomes when combined with fulvestrant. Methods: Postmenopausal HER2-/HR+ locally advanced or metastatic breast cancer pts (N»150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting will be enrolled in this multicenter, randomized, double blind, placebo controlled, phase II trial. Pts will prospectively undergo molecular screening to enrich for FGF-amplification (FGFR1, FGFR2, or FGF3 amplification by qPCR; 45 amplified and 30 non-amplified pts per arm). Pts will be randomized 1:1 to receive fulvestrant (500 mg q4w [with an additional dose 2 wks after the initial dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or placebo until disease progression, unacceptable toxicity, or death. The primary endpoint is progression-free survival, with tumor assessments performed q8w. Secondary endpoints include overall response rate per RECIST v1.1, duration of response, overall survival, ECOG performance status and patient reported outcome scores over time, and safety. The pharmacodynamic effect of dovitinib on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to dovitinib will be explored.
The incidence and clinical impact of bone metastases in non-small cell lung cancer.
Authors: Michael Kuchuk, Iryna Kuchuk, Brian Hutton, Mark Clemons, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2013)

e19024 Background: Non-small cell lung cancer (NSCLC) is the leading global cause of cancer death. Bone metastases (BM) in NSCLC are a common cause of morbidity, but use of bone targeted agents (BTA) is variable. We investigated the incidence and impact of BM in an unselected NSCLC population. Methods: With ethics approval, we performed a retrospective chart review of all patients (pts) with NSCLC seen at our institution in 2007. Baseline demographics, stage and initial treatment goals were recorded. In pts with advanced disease (mNSCLC) metastatic sites were identified. In BM pts, skeletal related events (SRE), interventions and outcomes were recorded. Results: In total, 374 pts were identified. Median age was 68 years (IQR 60-76), 54% female. Histological subtypes were adenocarcinoma (36%), squamous (18%), and other (46%). Overall 91% were current or ex-smokers. At initial diagnosis 37% had stage I-IIIa, 18% IIIb and 46% stage IV disease. A total of 160 pts (43%) were treated with curative intent; 211 (56%) were considered palliative. Of the 160 curative therapy pts, 90 (56%) subsequently relapsed, with a median time from diagnosis to relapse of 14.9 months. Of the 301 pts with mNSCLC, common sites of metastasis were lung/pleura (80%), mediastinal lymph nodes (69%), bone (39%), brain (30%), and liver (24%). In total 116 pts had BM; a higher incidence was observed in pts ≤70 years than pts &gt;70 (36% vs 23%). SREs were observed in 69 pts (59%), the median number of SREs per BM pt was 1 (0-16). The incidence of SREs was radiotherapy (63%), fractures (22%), spinal cord compression (6%) and surgery to bone (5%). Factors associated with ≥2 SREs were smoking status (28% never smokers vs 9% ex/current smoker) and younger age (15% vs 5%). In BM pts, 64% required opioid analgesia, only 6% received BTA. Overall survival (OS) in pts with mNSCLC was 7.3 months (IQR 3.1-20.5). Pts with BM had significantly shorter OS compared to those without BM (5.5 vs. 9.9 months, p=0.02). Median OS in pts with or without SRE were 5.5 and 6.4 months (p=0.58). Conclusions: BM in NSCLC pts are common, and most pts will develop an SRE and/or require opioids. In mNSCLC, the presence of BM is associated with significantly shorter survival, which raises challenging questions around the use of BTA.
Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration
Authors: A Bolu Ajiboye, Francis R Willett, Daniel R Young, William D Memberg, Brian A Murphy, Jonathan P Miller, Benjamin L Walter, Jennifer A Sweet, Harry A Hoyen, Michael W Keith, P Hunter Peckham, John D Simeral, John P Donoghue, Leigh R Hochberg, Robert F Kirsch
Journal: The Lancet (2017)
Utilization of primary chemoradiotherapy for anal squamous cell carcinoma in the elderly: An analysis of the NCDB.
Authors: Benjamin Mitchell Motz, Patrick Daniel Lorimer, Kendall K Walsh, I'sis N Perry, Danielle Boselli, Richard L. White, Jonathan C. Salo, Joshua S. Hill
Journal: Journal of Clinical Oncology (2017)

726 Background: Definitive chemoradiotherapy (CHEMORT) is the treatment of choice for anal squamous cell carcinoma (SCC), while surgery is typically reserved for salvage therapy. Patients (pts) who are frail due to advanced age or medical comorbidities often have difficulty completing therapy. Methods: The NCDB was queried for pts with anal SCC (2004-2012). Pts &lt; 50 years, and those with in situ or metastatic disease, or with incomplete CHEMORT treatment data were excluded. The primary outcome was completion of CHEMORT. Secondary outcome was requirement of salvage surgical therapy. Statistical analyses include Chi-square, univariate and multivariable logistic regression. Results: N = 11918. 5907 (49.5%) did not complete recommended CHEMORT. 9862 (82.8%) received CHEMO, 6011 (61.0%) of whom completed RT with dosage &gt; 45Gy. Factors significantly associated with failure to complete therapy on multivariable analysis include: older age at diagnosis, higher Charlson-Deyo score, earlier year of diagnosis, male gender, and earlier clinical T and N stages (Table 1). 41.7% of pts who did not complete CHEMORT required salvage surgical therapy, versus 25.1% of pts completing CHEMORT (OR: 2.14 95% CI [1.97, 2.31], p &lt; 0.01). Conclusions: Approximately half of pts older than 50 years of age with anal SCC failed to complete definitive CHEMORT. This study highlights the negative impact of frailty on the ability of pts to receive optimal therapy, resulting in more operative interventions. Medical optimization of older pts with more comorbidities in order to improve utilization of CHEMORT is one possible area of improvement in the management of anal SCC. [Table: see text]