tbuckley/cabot-search huggingface dataset:
Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma
Journal: Hepatology (2000)

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage. As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with HCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection.
PROGNOSIS OF OBSTRUCTIVE AND NON-OBSTRUCTIVE STENTS BY CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY: THE CONFIRM REGISTRY
Authors: Mahn Won Park, Ji Hyun Lee, Briain O. Hartaigh, Asim Rizvi, Donghee Han, Hadi Mirhedayati Roudsari, Subhi Al'Aref, Khalil Anchouche, Ashley Beecy, Heidi Gransar, Yao Lu, Jessica Pena, James Min, Fay Lin
Journal: Journal of the American College of Cardiology (2017)
Activity and tolerance of biweekly CapeOx-cetuximab in 1st line therapy of metastatic colorectal cancer (mCRC): Relation to <i>K-ras</i> mutation status
Authors: Y. Yuan, H. Ma, D. J. Cohen, T. Ryan, H. Choi, E. Love‘, M. Awad, S. Khambata-Ford, D. Mauro, H. Hochster
Journal: Journal of Clinical Oncology (2009)

e15018 Background: This novel q2w schedule trial combined oxaliplatin (Ox), flat dose capecitabine (Cape) and cetuximab(C) in first line therapy of mCRC. C was given weekly initially and then q2w. We report the response rate, toxicity and influence of K-ras mutation status in first-line patients treated with biweekly CapeOx-C in this phase II trial. Methods: Pts with previously untreated, histologically confirmed, metastatic colon adenocarcinoma, ECOG PS 0–1, and adequate organ function were eligible. Pts were treated with C (initially 250mg/m 2 q week and later amended to 500mg/m 2 q2w) and Ox (85mg/m 2 ) combined with flat dose Cape (2500mg po bid x 7days) q2w. Endpoints included response (RECIST), toxicity (CTCAE v3) and relationship to K-ras mutation status as determined in codons 12/13 of exon 2 in genomic tumor DNA by PCR, blinded to clinical data. Results: Between 8/04 and 8/08, 27 pts were enrolled. One pt failed screening, 1 withdrew prior to rx and 2 too early for assessment. 25 pts were treated: M/F (15/10), PS 0/1 (13/12), median age 65 yrs (37–80). 12 pts were treated weekly with C and 13 q2w. 23 pts were eligible for both toxicity and efficacy analysis. The most common grade 3/4 toxicities (N=23) were diarrhea (26%), thrombosis (22%), neuropathy (17%), rash (13%), hand-foot syndrome (9%), hypersensitivity reaction (9%), stomatitis (9%). Toxicity profiles between the two C schedules were comparable. Of 23 pts evaluable for response, there were 2 CR, 12 PR, and 3 SD (ORR 61%; disease control rate (DCR) 74%). K-ras status was determined in 18 pts: 9 were K-ras wild-type (WT) and 9 mutant (MT) with ORR and DCR = 66%, 89% for WT vs. 44%, 44% MT. Time on study was 6 mon for WT vs 3 mon for MT (p&lt;0.05). Grade 0–1 vs. 2–3 skin rash was 33% vs. 67% for WT and. 89% vs. 11% in MT pts. Conclusions: The novel combination of biweekly CapeOx-C, with flat dose Cape was well tolerated and very active (regardless of K-ras status) as first line treatment in mCRC. C 500 mg/m 2 q2w appears equal to weekly dosing. Analysis of the K-ras mutation status showed a trend toward increased benefit by response rate and time on study, with more cutaneous toxicity in K-ras WT pts. [Supported in part by grant from BMS.] [Table: see text]
IS PLATELET REACTIVITY ASSOCIATED WITH ISCHEMIC EVENTS FOLLOWING SUCCESSFUL CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTION
Authors: Matthew Finn, Michael Cloney, Dimitrios Karmpaliotis, Ajay Kirtane, Philip Green, Thomas McAndrew, Claire Litherland, Bjorn Redfors, Witzenbichler Bernhard, Giora Weisz, Thomas D. Stuckey, Bruce Brodie, Michael Rinaldi, Franz-Josef Neumann, David Metzger, Timothy Henry, David Cox, Peter L. Duffy, Ernest Mazzaferri, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Efficacy and Tolerability of Bosutinib and Imatinib in Older Versus Younger Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia–BELA Trial
Authors: Carlo Gambacorti-Passerini, Tim H Brümmendorf, Dong-Wook Kim, Irina Dyagil, Hagop M Kantarjian, Dmitri Pavlov, Karin Gogat, Ladan Duvillie, Mark Shapiro, Jorge E Cortes
Journal: Blood (2012)
GENDER SPECIFIC COMPARATIVE EFFECTIVENESS OF ORAL ANTICOAGULANTS IN ELDERLY MEDICARE PATIENTS WITH NEWLY DIAGNOSED ARIAL FIBRILLATION: A PROPENSITY MATCHED ANALYSIS
Authors: Ghanshyam Palamaner Subash Shantha, Prashant Bhave, Saket Girotra, Denice Hodgson-Zingman, Alexander Mazur, Michael Giudici, Elizabeth Chrischilles, Mary Vaughan-Sarrazin
Journal: Journal of the American College of Cardiology (2017)
Selinexor (KPT-330) Induces Tumor Suppression through Nuclear Sequestration of IκB and Downregulation of Survivin
Authors: Jayasree S. Nair, Elgilda Musi, Gary K. Schwartz
Journal: Clinical Cancer Research (2017)

Purpose: Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic malignancies with the evidence of clinical activity in sarcoma as a single agent. Treatment options available are very few, and hence the need to identify novel targets and strategic therapies is of utmost importance.Experimental Design: The mechanistic effects of selinexor in sarcomas as a monotherapy and in combination with proteasome inhibitor, carfilzomib, across a panel of cell lines in vitro and few in xenograft mouse models were investigated.Results: Selinexor induced IκB nuclear localization as a single agent, and the effect was enhanced by stabilization of IκB when pretreated with the proteasome inhibitor carfilzomib. This stabilization and retention of IκB in the nucleus resulted in inhibition of NFκB and transcriptional suppression of the critical antiapoptotic protein, survivin. Treatment of carfilzomib followed by selinexor caused selinexor-sensitive and selinexor-resistant cell lines to be more sensitive to selinexor as determined by an increase in apoptosis. This was successfully demonstrated in the MPNST xenograft model with enhanced tumor suppression.Conclusions: The subcellular distributions of IκB and NFκB are indicative of carcinogenesis. Inhibition of XPO1 results in intranuclear retention of IκB, which inhibits NFκB and thereby provides a novel mechanism for drug therapy in sarcoma. This effect can be further enhanced in relatively selinexor-resistant sarcoma cell lines by pretreatment with the proteasome inhibitor carfilzomib. Because of these results, a human clinical trial with selinexor in combination with a proteasome inhibitor is planned for the treatment of sarcoma. Clin Cancer Res; 23(15); 4301-11. ©2017 AACR.
NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019
Authors: William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Vishala T. Neppalli, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Mary A. Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2019)

Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.
A single-arm, multicenter, phase II study of panitumumab in combination with capecitabine/oxaliplatin in first line, wild-type KRAS metastatic colorectal cancer patients.
Authors: Dimitrios G. Pectasides, Vasilios Karavasilis, Vassiliki Kotoula, Epaminontas Samantas, Zoi Alexopoulou, Flora Zagouri, Konstantinos N. Syrigos, Andreas Koureas, Dimitrios Dionysopoulos, Georgios Lazaridis, Ioannis Efstratiou, Dimitra Apessou, George E. Pentheroudakis, George Papaxoinis, George Fountzilas
Journal: Journal of Clinical Oncology (2015)

e14563 Background: Panitumumab (P) has shown activity in terms of response and survival in patients (pts) with all RAS wild-type (WT) metastatic colorectal cancer (mCRC). The activity and toxicity of oxaliplatin (O)-capecitabine (C) (capox) with P have been questioned by previous studies. Methods: Pts with exon 2 KRAS WT mCRC received first-line chemotherapy with the combination of O 130 mg/m2, C 2000 mg/m2 and P 9 mg/Kg, repeated every 3 weeks for at least 6 cycles or until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR). According to Simon's 2-stage optimal design, assuming the expected ORR to be at least 60% and the minimum acceptable ORR 45%, 77 pts were required at the final step. Results: 78 pts were enrolled. Median age was 65.5 years, males 58%, females 42%, ECOG performance status 0 (80%), 1 (19%) and 2 (1%). 44 pts (54%) completed 6 cycles. Most frequent reasons of discontinuation were PD (11 pts), toxicity (7 pts), pt refusal (7 pts) and doctor’s decision (4 pts). Relative dose intensities were 99.8% for P, 96.6% for O and 81.8% for C. Grade 3-4 toxicities were anemia (4%), leukopenia (1%), neutropenia (3%), thrombocytopenia (4%), skin toxicity (19%), diarrhea (10%), neuropathy (5%), hypokalemia/hypomagnesemia (5%), hand-foot syndrome (4%) and mucositis (3%). Two toxic deaths from cardiac arrest occurred (3%), the first in a pt with grade 4 neutropenia and the other in a pt with grade 3 diarrhea. ORR was 56% (complete 8%, partial 49%), stable disease 18%, PD 8%, non-evaluable pts 2.5% and early discontinuation 14%. After a median follow-up of 30 months, median PFS was 8.1 (95% CI 6.8-9.4) and median OS 20.2 (95% CI 15.4-25.8). Among 61 pts evaluated for mutations, 8 (13%) had an exon 3-4 KRAS nutation, 2 (3%) NRAS, 4 (7%) BRAF, 4 (7%) PIK3CA and 2 (3%) AKT1 nutations. Patients with KRAS, NRAS or BRAF mutations compared with all RAS/BRAF WT patients did not differ in terms of ORR (50% vs. 55%, respectively), PFS (7.7 vs 8.1, respectively) and OS (20.2 vs 19.2, respectively). Conclusions: First-line capox-P did not appear to exhibit improved safety and activity in pts with KRAS WT mCRC. (NCT: 01215539) Clinical trial information: NCT01215539.
Long-term follow-up of chemotherapy-induced remissions in patients with disseminated nonseminomatous germ cell tumors
Authors: Y. Ehrlich, M. J. Brames, S. D. Beck, R. S. Foster, L. H. Einhorn
Journal: Journal of Clinical Oncology (2009)

5029 Background: There is controversy concerning management of patients (pts) with nonseminomatous germ cell tumor (NSGCT) who obtain a chemotherapy-induced complete radiographic (&lt;1cm node diameter) and serologic remission (CR). It has been our policy not to recommend retroperitoneal lymph nodes dissection (RPLND). Proponents of mandatory RPLND cite a 20% to 30% rate of residual microscopic tumor, mostly teratoma, despite achieving CR. Methods: Retrospective analysis of 141 patients with metastatic NSGCT who obtained CR to cisplatin-based first-line chemotherapy. All were observed without RPLND. Included were 78 consecutive pts treated between Jan 1987 and Sept 1994. Additionally included were 63 pts recruited in 4 prospective trials between Oct 1984 and Apr 2005. Seven pts were lost to follow-up (FU) after &lt;2 year. Results: At a median a FU of 15 years (range 3 months to 23.8 years), 12 pts recurred and 4 are dead of disease (DOD). The estimated 15 year recurrence free and disease specific survival was 90% and 97% respectively. The estimated 15 years recurrence free survival for 109 pts with good risk and 32 pts with intermediate or poor risk was 95% and 73% respectively (p = 0.001). Five pts recurred &gt;2 years (range 3–13 years). All 5 are currently disease free. Six pts recurred in the RP and 2 are DOD. Six pts recurred outside the RP. Two of these 6 are DOD. Conclusions: Pts obtaining CR after primary chemotherapy can be safely observed without RPLND. Relapses are rare and potentially curable with further treatment. No significant financial relationships to disclose.
Dose escalation stage of a first-in-class phase I study of the novel oral ERK 1/2 kinase inhibitor BVD-523 (ulixertinib) in patients with advanced solid tumors.
Authors: Jeffrey R. Infante, Filip Janku, Anthony W. Tolcher, Manish R. Patel, Ryan J. Sullivan, Keith Flaherty, Richard D. Carvajal, Anna M. Varghese, Deborah Jean Lee Wong, Mario Sznol, Jeffrey Alan Sosman, Andrea Wang-Gillam, Howard A. Burris, Antoni Ribas, Sapna Pradyuman Patel, Dean J. Welsch, Saurabh Saha
Journal: Journal of Clinical Oncology (2015)

2506 Background: Aberrant MAPK pathway signaling and resultant ERK kinase activity is evident in many oncogene-dependent cancers, and persistent or reactivated ERK signaling is common in intrinsic and acquired drug resistance to approved RAF or MEK inhibitors. This first-in-human trial of BVD-523 (ulixertinib), a selective ERK1/2 kinase inhibitor, was initiated based on its promising preclinical profile. Methods: Patients (pts) with advanced solid tumors were recruited into an accelerated 3+3 dose escalation protocol. Primary study objectives included determination of dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objectives included pharmacokinetic, pharmacodynamic, and preliminary efficacy assessments. Results: The dose escalation phase included 27 pts treated with BVD-523 at dose levels of 10, 20, 40, 75, 150, 300, 600, 750, and 900 mg twice a day. DLTs were observed in 5 pts: two with grade 3 rash, one with grade 3 pruritus and elevated AST, one with grade 3 diarrhea, vomiting, dehydration and elevated creatinine, and one with grade 2 hypotension, elevated creatinine, and anemia. The MTD was 600 mg twice a day. The most common adverse events included diarrhea, nausea, vomiting or constipation (89%), rash (any form), dermatitis, or pruritus (78%), fatigue (70%), decreased appetite (37%), dyspnea (33%), and anemia (26%). Pharmacokinetics were generally linear and dose proportional up to 600 mg twice a day. Phosphorylation of the ERK substrates RSK1/2 was inhibited in peripheral blood samples starting at 75 mg twice a day. Metabolic response was observed in 5 of 16 evaluable pts assessed by FDG-PET. One (1) of 26 pts assessed by CT had a best response of partial response, and 7 had stable disease for at least 3 months. Conclusions: The ERK 1/2 inhibitor BVD-523 (ulixertinib) achieved pharmacologically relevant exposure and manageable tolerability at its MTD of 600 mg twice a day. Additional safety and preliminary efficacy assessments are underway in a cohort expansion stage of this study in patients with specific tumor genotypes and clinical characteristics treated at the RP2D, as well as in additional phase I and phase II studies. Clinical trial information: NCT01781429.
Young and strong: A randomized study to improve care for young women with breast cancer.
Authors: Ann H. Partridge, Kathryn Jean Ruddy, William Thomas Barry, Mary Greaney, Jennifer A. Ligibel, Kim Sprunck-Harrild, Shoshana M. Rosenberg, Emily Baker, J. Russell Hoverman, Karen Emmons
Journal: Journal of Clinical Oncology (2015)

9588 Background: Research has revealed that needs of young women with breast cancer are not being met, particularly fertility concerns. A QOPI audit found rates of attention to fertility of < 30% in practices. We conducted a cluster-randomized study to determine the effect of an exportable education and support intervention for young women with breast cancer (YWI) and their oncologists. Methods: Sites were randomized 1:1 to YWI or a physical activity intervention (PAI) stratified by academic or community; up to 15 women age < 45 with newly diagnosed breast cancer were enrolled at each academic site, 10 at community sites. The primary endpoint was attention to fertility prior to systemic treatment by medical record review. Pts were surveyed at 3, 6, and 12 mos; physicians surveyed after enrolling their first patient. The study was designed to have 80% power to detect an improvement in attention from 10% with PAI to 38% with YWI using General Estimating Equations, two-sided alpha = 0.05. Results: 467 patients across 54 sites (14 academic, 40 community) enrolled between 7/2012 -12/2013. Median age at dx was 40yrs (range 22-45); patient characteristics did not vary by arm. Attention to fertility by 3 mos after enrollment was observed in 55% YWI pts and 58% on PAI (p = 0.88). Rates were strongly correlated with age (p < 0.0001), highest in pts < 30 (100% YWI, 94% PAI) vs. 30-40 (68% YWI, 59% PAI) vs. 40-45 (42% YWI, 52% PAI) although interaction testing age x intervention was not significant (p = 0.12). At 3 mos, pts rated YWI/PAI as valuable in educating them (64% YWI, 63% PAI). Of responding providers (145/171, 85%), most reported YWI/PAI educated providers (55% YWI/51% PAI) and pts (79% YWI, 77% PAI), and improved care (79% YWI, 60% PAI). Conclusions: This study failed to show improvement in attention to fertility with YWI vs. PAI. Rates were high in both arms, especially in women < 40 and the study had limited power to detect an age-dependent effect. Pts and providers valued both interventions. This work serves as a novel model to educate and support patients and providers to improve care. Clinical trial information: NCT01647607.
Interferon alpha-2b and thalidomide in previously treated patients with disseminated malignant melanoma: SWOG 0026
Authors: L. Hutchins, J. Moon, J. Clark, J. Thompson, K. Yost, V. Sondak
Journal: Journal of Clinical Oncology (2004)

7527 Background: SWOG 0026 was a phase II evaluation of antiangiogenesis therapy using interferon alpha-2b, given in an antiangiogenetic schedule, with thalidomide in patients with disseminated melanoma. The six-month progression-free survival (PFS) rate, response rate, and evaluation of toxicities were goals. Methods: 26 of 35 planned patients with Stage IV melanoma were registered. Patients had measurable or non-measurable disease, a performance status of 0–2, and adequate renal and hepatic function. One prior systemic therapy for Stage IV disease was required. Interferon 1 MU subcutaneously bid and thalidomide in an escalating manner consisting of 200 mg days 1–7, 300 mg days 8–14 and 400 mg days 15-study completion was administered each evening. Response evaluations using RECIST criteria were performed every 12 weeks. Results: After two sudden deaths, and one patient with grade 4 pulmonary embolism, this study was temporarily closed (9/10/02). An additional patient with deep vein thrombosis and 2 patients with cardiac arrhythmias were reported. The relationship of these cardiovascular events to the antiangiogenic treatment was worrisome but not definitive. Grade 3 treatment related adverse events were observed in 13 patients. Upon review, with safety as a concern, the study was closed 5/1/03. From the 26 registered patients: one was ineligible and 4 eligible patients were without measurable disease, 21 were available for response (the early death and inassessable patients are counted as failures). No responses were seen. The estimated six-month PFS is 19% (95% C.I.: 3% - 34%), and the estimated six-month overall survival is 60% (95% C.I.: 40% - 79%). The estimated response probability is 0 of 21 (95% C.I.: 0% - 16%). Conclusions: This regimen had excess-toxicity and further study of interferon alpha-2b and thalidomide in this setting is not warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering
Clinical characteristics and chemotherapy options of triple-negative breast cancer: Role of classical CMF regimen.
Authors: Min Hee Hur, Tae Ho Kang, Ra Joo Im, Se Won Kim, Chan Seok Yoon, Seung Sang Ko, Haekyung Lee, Ji Hyun Lee, Sung-Soo Kang
Journal: Journal of Clinical Oncology (2012)

1053 Background: Triple-negative breast cancer is a high risk breast cancer that lacks the benefit of specific targeted therapy. We investigated the clinicopathologic characteristics between triple-negative breast cancers (TNBC) and non-TNBC. And we also analyzed the effect of chemotherapy options such as classical CMF regimen, anthracycline-based, or taxane-based chemotherapy. Methods: A total of 826 invasive breast cancer patients were evaluated from March 2003 to December 2008. We investigated them retrospectively, who had the median follow-up for 88 months. We examined the differences between TNBC compared with non-TNBC in relation to the clinicopathologic parameters, chemotherapy regimen, overall survival (OS). Results: 156 (18.9%) cases among 826 patients were triple negative breast cancers. There were significantly positive associations with younger age (below 35 years), large tumor (&gt;2cm), high stage, poorly differentiated nuclear grade, poorly histologic grade in TNBC. Positive lymph node, lymphovascular invasion were not significantly different between TNBC and non- TNBC. A total of 677 patients were treated with chemotherapy. In TNBC patients, 142 (93.4%) patients were treated with chemotherapy more than in 535 (61.4%) of non- TNBC patients. The chemotherapy in TNBC patients was composed of classical CMF (47.9%), anthracycline-based regimen (25.4%), taxane-based regimen (26.8%). 19 cases (12%) of TNBC experienced locoregional or systemic metastases. 48 (7.2%) patients of non- TNBC did local or systemic metastases. Patients with TNBC had worse 5-year OS than with non-TNT (95.7% vs 98.6%, p=0.01). Interestingly, patients treated with CMF regimen were better 5-year OS than with anthracycline-based, or taxane-based regimen in TNBC (100% vs 96.9% vs 89.2%, p=0.001). There was no survival difference among chemotherapy regimens in non-TNBC patients. Conclusions: Patients with TNBC have poor prognosis compared with non-TNBC. Classical CMF regimen for TNBC patients may be more effective than anthracycline-based or taxane-based regimens.
Clinical Outcomes Related to the Use of Monoclonal Antibody Therapy for Steroid Refractory Acute Graft-Versus Host Disease after Allogeneic Hematopoietic Cell Transplantation
Authors: Fevzi Yalniz, Mehrdad Hefazi, Kristen B. McCullough, Mark Litzow, William J Hogan, Robert C Wolf, Hassan B Alkhateeb, Ankit Kansagra, Moussab Damlaj, Mrinal M Patnaik
Journal: Blood (2016)