tbuckley/cabot-search huggingface dataset:
Phase I interim safety and efficacy of venetoclax (ABT-199/GDC-0199) monotherapy for relapsed/refractory (R/R) multiple myeloma (MM).
Authors: Shaji Kumar, Ravi Vij, Jonathan L. Kaufman, Joseph Mikhael, Thierry Facon, Philippe Moreau, Martine Amiot, Stefanie Alzate, Lura J Morris, Jeremy A Ross, Martin Dunbar, Ming Zhu, Suresh K Agarwal, Joel Leverson, Sari H. Enschede, Rod Humerickhouse, Cyrille Touzeau
Journal: Journal of Clinical Oncology (2015)

8576 Background: The anti-apoptotic protein BCL-2 has been implicated in mediating the survival of MM cells. Venetoclax (VEN) is a potent, selective, orally bioavailable small-molecule BCL-2 inhibitor. VEN induces cell death in MM cell lines and primary samples in vitro, especially in t(11;14)-positive (pos) cells, which express a high ratio of BCL2 to MCL1(VEN resistance factor). The current Ph 1 study evaluates safety and efficacy of VEN in pts with R/R MM. Methods: Primary objectives are to evaluate safety, PK, and RPTD; other objectives include preliminary efficacy and impact of chromosomal abnormalities. In dose-escalation cohorts, VEN was given PO daily at 300, 600, 900, or 1200 mg after a 2-week dose ramp-up. Pts were monitored for tumor lysis syndrome (TLS). Results: As of 12/19/2014, there were 28 pts with median age 65 (12/16 F/M); 9 ISS stage I, 11 stage II, 6 stage III. Median (range) prior therapies: 6 (1–13). 23 had prior bortezomib (15 refractory), 26 lenalidomide (12 refractory), and 13 auto-HSCT. 10 pts were t(11;14)-pos. AEs in ≥20% pts: diarrhea (32%), nausea (32%), neutropenia (21%), fatigue (21%). Grade 3/4 AEs (≥10%): thrombocytopenia (18%), anemia (14%), neutropenia (14%). 7 pts had SAEs, with 1 (epigastric pain) possibly related to VEN. 17 pts have discontinued (D/C): 14 due to PD, 2 for AEs (worsening shortness of breath, hypokalemia), and 1 withdrew consent; 11 still receiving therapy. 2 deaths occurred (both PD). 2 DLTs were seen at 600 mg (cohort was expanded): epigastric pain, nausea with abdominal pain. No pt had TLS. Preliminary PK (n=11; 300 and 600 mg): mean Cmax and AUC24 were ~dose-proportional with high intra-dose variability. 21 of 28 pts were evaluable for preliminary efficacy. Best response by t(11;14) status shown in Table. Conclusions: VEN monotherapy was well tolerated in heavily-pretreated R/R MM. Responses (including CR) and longer ToS were observed in t(11;14)-pos pts. RPTD was achieved; study is now enrolling in the safety expansion cohort at 1200 mg (with 2-week ramp-up). Clinical trial information: NCT01794520. n (%) t(11;14)-pos (n=7) t(11;14)-neg (n=14) CR 1 (14) 0 PR 1 (14) 0 MR 1 (14) 0 SD 2 (29) 9 (64) PD 1 (14) 2 (14) D/C 1 (14) 3 (21) ORR (CR+ PR) 2 (29) 0 Median (range) time on study (ToS) 5.1 (1.2–8.6) 1.9 (0.4–6.8)
Evaluation of the hematologic safety of same day versus standard administration of pegfilgrastim in gynecology oncology patients undergoing platinum-based chemotherapy.
Authors: Caroline C Billingsley, Samuel Jacobson, Sarah Crafton, Aleia Crim, Quan Li, Erinn Hade, David E. Cohn, Jeffrey Fowler, Larry J. Copeland, Ritu Salani, Floor Jennishens Backes, David M. O'Malley
Journal: Journal of Clinical Oncology (2014)

5569 Background: The safety of the timing of pegfilgrastim administration in women with gynecologic malignancies has been questioned. We aimed to assess the safety and efficacy of administration of pegfilgrastim on the same day (D1) as chemotherapy compared to standard administration (24-72 hours after chemotherapy) in patients with gynecologic malignancies. Methods: A retrospective review was conducted on gynecologic oncology patients who received pegfilgrastim to mitigate the myelosuppressive consequences of chemotherapy from January 1, 2002 through July 31, 2012. Data collected included demographics, pathology, blood counts, toxicity, chemotherapy regimen and day of pegfilgrastim administration. Results: 2071 injections of pegfilgrastim in 421 patients were identified. 506 doses of pegfilgrastim were given on D1 compared to 1565 standard administrations. The most common malignancy was ovarian cancer (79%). Median age was 60 years (23-90). 318 (76%) patients had stage III, IV, or recurrent disease and 83% of patients received their initial dose during their primary chemotherapy regimen. The most common chemotherapy regimen was carboplatin/paclitaxel (42%), followed by carboplatin/docetaxel (11%). The median ANC was 3888 cells/mL (68-57,724). Grade 3/4 neutropenia was observed in 2.6% of the D1 cohort versus 1.8% in the standard cohort (G3: 1.2% vs 1.3%, G4:1.4% vs 0.5%) (adjusted relative risk (aRR) 1.4 (90% CI: 0.8-3.2)). There was one episode of FN per group. Further comparing D1 to standard pegfilgrastim administration, dose modifications occurred in 6.5% and 4.9% (aRR: 1.3 (90% CI: 0.9-1.9), while treatment delays occurred in 7.3% and 9.4%, respectively (aRR: 0.8 (90%CI: 0.6-1.1)). Conclusions: The incidence of neutropenia, dose modification, and treatment delays did not differ substantially between patients who had pegfilgrastim administered on D1 compared to standard dosing. Pegfilgrastim can be safely administered on the same day as chemotherapy in patients receiving treatment for gynecologic malignancy. We report on the largest series of pegfilgrastim administration in gynecologic malignancies to date.
EARLY RECURRENCE OF VENTRICULAR TACHYCARDIA PREDICTS INCREASED MORTALITY AMONG PATIENTS WITH SEVERE HEART FAILURE
Authors: Michael Cowherd, Peter Rothstein, Alexis Tumolo, Natasha Altman, Prateeti Khazanie, Amrut Ambardekar, Andreas Brieke, Eugene Wolfel, William Cornwell, Matthew Zipse, Duy Nguyen, Lucas Marzec, Ryan Aleong, Christine Tompkins, Larry Allen, William Sauer, Wendy Tzou
Journal: Journal of the American College of Cardiology (2017)
PLASMA LDL-CHOLESTEROL LEVEL IS INDEPENDENTLY ASSOCIATED WITH INFARCT SIZE IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Mathijs Bodde, Maaike Hermans, R. Wolterbeek, Arnoud van der Laarse, Martin Schalij, Johan Jukema
Journal: Journal of the American College of Cardiology (2017)
Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.
Authors: Hemchandra Mahaseth, John S. Kauh, Edith Brutcher, Natalyn Nicole Hawk, Sungjin Kim, Zhengjia Chen, Bassel F El-Rayes
Journal: Journal of Clinical Oncology (2012)

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m 2 CIVI over 46 hours, leucovorin 400 mg/m 2 , oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.
USE OF POTENT P2Y12 INHIBITORS IN AFRICAN-AMERICAN PATIENTS TREATED WITH PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE CORONARY SYNDROMES
Authors: Michela Faggioni, Usman Baber, Jaya Chandrasekhar, Birgit Vogel, Samantha Sartori, Melissa Aquino, Annapoorna Kini, William Weintraub, Samir Kapadia, Sandra Weiss, Craig Strauss, Clayton Snyder, Catalin Toma, J. Muhlestein, Anthony DeFranco, Mark Effron, Stuart Keller, Brian Baker, Stuart Pocock, Timothy Henry, Sunil Rao, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
TRANSCATHETER AORTIC VALVE IMPLANTATION IS SAFE IN PATIENTS WITH LEFT ATRIAL THROMBUS OR SPONTANEOUS ECHO CONTRAST
Authors: Berhane M. Worku, Polydoros Kampaktsis, Iosif Gulkarov, Shing-Chiu Wong, Regis Chang, Abdullah Aftab, Arash Salemi
Journal: Journal of the American College of Cardiology (2017)
Rapid detection of UGT1A1 polymorphisms by a novel microarray assay: A validation study using 100 samples from patients with lung cancer treated by irinotecan
Authors: Y. Yamada, T. Shimizu, T. Ozaki, E. Hatashita, T. Kurata, M. Fukuoka, K. Tamura
Journal: Journal of Clinical Oncology (2006)

13019 Background: Irinotecan is one of the active drugs for the treatment of colorectal, gastric and lung cancer. SN-38, the active metabolite of irinotecan is metabolized through conjugation by uridine diphosphate glucuronosyl transferase (UGT1A1). Genetic polymorphisms of UGT1A1 in the specific locus have been reported to be significantly related to severe toxicities of Irinotecan. Although the polymorphisms are usually detected by direct sequence (DS) or PCR-restriction fragment length polymorphism (RFLP) analysis, these assays consume time and need deferent PCR product for each exon. We report a novel microarray (MA) technology to detect the UGT1A1 polymorphisms using 100 peripheral blood samples of lung cancer patients treated with irinotecan, and evaluate a consistence ratio in comparison with the confirmed results by RFLP or DS. Methods: One hundred lung cancer patients who had received irinotecan containing chemotherapy were enrolled in this study. Genomic DNA was extracted from whole blood and prepared into 100 ng/5μL. PCR were performed by random primers, and the PCR products were labeled by biotin. The labeled probe have hybridized the MA chips, and patterns of visualized dots informed us the polymorphisms in the deferent locus (*28, *6 *27), simultaneously. Polymorphisms of all samples were also confirmed by RFLP and DS for validation. Results: One homozygous (Hom), 14 heterozygous (Het) and 85 wild type (W) for UGT1A1*28 were confirmed by DS. Five Hom, 25 Het and 70 W for UGT1A1*6, and 1 Het and 99 W for UGT1A1*27 were confirmed by RFLP and DS. A single approach of the novel MA assay have revealed 79.3%, 96.6% and 100% consistence with the confirmed result for each exon (*28, *6 *27), respectively. Individual twice approach of the MA have revealed 94.3%, 98.9% and 100% consistence with the confirmed result for the each exon, respectively. We could assay all samples by the MA and needed only single day for detection. Conclusions: Our newly developed assay for detecting UGT1A1 polymorphisms is rapid, accurate and feasible and has potential to be used for screening before irinotecan in the future prospective clinical trials. No significant financial relationships to disclose.
Suppression of Medullar Erythropoiesis in Response to Bacterial Lipopolysaccharides (LPS) Involves Two Distinct TLR4-Dependent Mechanisms with Contrasted Requirements for G-CSF Receptors
Authors: Kavita Bisht, Rebecca Jacobsen, Bianca Nowlan, Crystal McGirr, Marion Brunck, Thomas Keech, Ingrid G Winkler, Jean-Pierre Levesque
Journal: Blood (2016)
EFFECT OF PFO CLOSURE FOR PREVENTION OF RECURRENT STROKE OR TIA IN HIGHLY SELECTED PATIENTS WITH CRYPTOGENIC STROKE
Authors: Minsu Kim, Woong Chol Kang, Jeonggeun Moon, Pyung Chun Oh, Yae Min Park, Wook-Jin Chung, Youngwoo Jang, Jongwook Yu, Taehoon Ahn
Journal: Journal of the American College of Cardiology (2017)
Value of positron emission tomography (PET) scan in treatment decision making for nodal metastases in head and neck squamous cell cancer
Authors: B. Mehrotra, R. Roy, N. Radhakrishnan, E. Gabalski, D. Myssiorek, S. Rush, D. Ebling, J. Pollack, S. Dubner, K. Heller
Journal: Journal of Clinical Oncology (2006)

5577 Background: Management of neck disease in patients with Head and Neck Squamous cell cancer (HNC) who are initially treated with combined radiation and chemotherapy (CRT) remains controversial. Standard treatment options include neck dissection (ND) or close observation. More recently PET scans have been used to stage and monitor response to therapy in patients with HNC. We performed a retrospective analysis of patients diagnosed with HNC stages N2b or higher, treated with combined CRT, and who were monitored for disease response by PET scans. Our observations on the utility of PET scans in monitoring response to therapy and in determining the role of elective NDs in this setting are reported. Methods: A retrospective review of medical records of all patients diagnosed at our institution with HNC Stages TxN2b, N2c or N3 between the years 2002 and 2005 was undertaken. IRB approval was obtained for this study.To be eligible for this analysis, patients must have had baseline and follow up PET scans at the end of CRT and prior to ND. Data regarding age, gender, primary tumor site, stage, baseline and follow up PET scan results, operative pathology of ND when performed, and local control were recorded. Results: Fifteen patients were identified. Median age was 55 years (range 37–76). Male: Female ratio was 13:2. Primary site of tumor was Pharynx (Base of tongue: n = 3, tonsil: n = 11); Lip and oral cavity: n = 1. Stages: IVa : n = 12; IVb: n = 3. N stage: N2b: n = 12; N2c: n = 1; N3: n = 2. Post CRT, all patients were followed with serial clinical examinations, PET ± CT scans. 13 of 15 patients had negative PET activity in the neck at the completion of CRT and remain disease free in the neck at a median follow up of one year. Post treatment PET scans were positive at the primary site in 2 of 15 patients; and positive in the neck in 2 of 15 patients. These 4 patients underwent ND after completing CRT. Operative pathology was positive for nodal disease in 2 of 4 patients who had persistent mild or significant activity on PET scan either at the primary site or in the neck. Conclusions: Post CRT PET negativity in the neck and at the site of primary tumor is associated with continued disease free status in the neck and these patients may be managed conservatively without requiring a neck dissection. No significant financial relationships to disclose.
Improved efficacy of gefitinib therapy in phospho-Akt positive patients with advanced non-small cell lung cancer
Authors: F. Cappuzzo, E. Magrini, S. Bartolini, G. Ceresoli, V. Ludovini, V. Gregorc, C. Ligorio, L. Lombardo, L. Crinò
Journal: Journal of Clinical Oncology (2004)

3004 Background: At the present time there is no reliable and identifiable marker that would help to identify those patients who are more likely to respond to gefitinib therapy. In some of the patients with NSCLC, EGFR may be the critical pathway signalling tumor growth. It is possible that responding patients are those in whom cell survival is maintained by activated EGFR-dependent pathways and in whom these pathways are suppressed by gefitinib. We investigated whether the evaluation of the Ras/raf/MAPK and the PI3K-AKT pathways before starting gefitinib therapy could help in identifying responding patients. This trial has been designed in order to possibly correlate Phospho-AKT/Phospho-MAPK status and gefitinib activity in terms of Response Rate (RR) and Time to Progression (TTP). Methods: Consecutive patients with NSCLC progressing or relapsing with standard therapy received gefitinib at a daily dose of 250 mg given until disease progression, unacceptable toxicity or refusal. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine P-AKT/P-MAPK status by immunohistochemistry. Results: One hundred-six NSCLC patients were enrolled onto the study in three Italian Institutions, and 103 were evaluable for P-AKT/P-MAPK status. P-AKT was positive in 51 (49.5%) and negative in 52 (50.5%) patients. P-MAPK resulted positive (2+/3+) in 23 (22.3%) and negative (0/1+) in 80 (77.7%). P-AKT positive status resulted significantly related to female gender (P<0.001), smoking history (P<0.05), and bronchioloalveolar histology (P<0.05). Compared to the P-AKT negative group, P-AKT positive patients had better RR (26.1% versus 3.9%, P=0.003), disease control rate (60.9% versus 23.5%, P<0.001), and significantly longer TTP (5.5 versus 2.8 months, P=0.004). No difference was observed in patients P-MAPK 0/1+ versus 2+/3 in terms of RR, disease control rate and TTP. Multivariate analysis confirmed that P-AKT positive status resulted in a significant reduction of disease progression risk (HR: 0.66, CI 95%:0.40–1.10). Conclusions: Gefitinib therapy resulted more active in P-AKT positive patients. No significant financial relationships to disclose.
Clinical Significance of Ck2 (CSNK2) and C-Myc Expression in Childhood Acute Lymphoblastic Leukemia
Authors: Paola Bonaccorso, Manuela La Rosa, Nellina Andriano, Valeria Iachelli, Emanuela Cannata, Francesco Bellia, Marinella Licciardello, Andrea Di Cataldo, Giovanna Russo, Luca Lo Nigro
Journal: Blood (2016)
CENTRAL FRACTIONAL PULSE PRESSURE PREDICTS CARDIAC POWER INDEX IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Sudheer Nanduri, Khaled Tuwairqi, Krishna Velagapudi, Abdulfattah Saidi, Omar Wever Pinzon, Elizabeth Dranow, Divya Ratan Verma, Rebecca Morris, Theophilus Owan
Journal: Journal of the American College of Cardiology (2017)
Association of decline in serum Ca19-9 after neoadjuvant therapy with improved survival among borderline resectable pancreatic cancer patients.
Authors: Susan Tsai, Anna Mahmoud, Ben George, Tracy R. Kelly, Paul S. Ritch, Beth Erickson, Douglas B. Evans, Kathleen K. Christians
Journal: Journal of Clinical Oncology (2013)

e15082 Background: Serum Ca19-9 (19-9) decline in response to therapy has been associated with an increased overall survival in metastatic pancreatic cancer patients (pts). However, the prognostic value of a 19-9 decline after neoadjuvant therapy in pts with localized disease is less well defined. Methods: We evaluated 73 pts with NCCN defined BRPC who received neoadjuvant therapy with induction chemotherapy (CRX) followed by chemoradiation (CRT). Staging with CT and 19-9 was obtained at three defined time points: baseline (bilirubin normal), after CRX, and following CRT (pre-surgical). Change in 19-9 (δ19-9) was defined as: (baseline 19-9- pre-surgical 19-9)/baseline 19-9. δ19-9 was classified as: absent (δ19-9&lt;0) or minimal (0 &lt;δ19-9&lt;0.25), low (0.25&lt;δ19-9&lt;0.50), moderate (0.50&lt;δ19-9&lt;0.75), high (δ19-9&gt; 0.75). Results: Of the 73 pts, 20 pts had normal/undetectable 19-9 and were excluded from the analysis. Of the remaining 53 pts, mean 19-9 levels at baseline, after CRX, and after CRT were 956, 164, and 139 U/mL, respectively. The mean change in 19-9 after CRX was 44%. Changes in 19-9 after CRX correlated with continued decline in 19-9 after CRT (Spearman rho = 0.81, p&lt;0.001). δ19-9 was high in 38 (71%), moderate in 9 (17%), min/low in 1 (2%), and absent in 5 (9%). Of the 53 pts, 49 (92%) were considered for surgery after neoadjuvant therapy and 38 (72%) underwent pancreatectomy. In a multivariate logistic regression, higher δ19-9 was associated with a 5.4 fold increased odds of completing all neoadjuvant therapy including surgery as compared to pts with no change in 19-9 (absent δ19-9; HR 5.4, p=0.12). Patients with absent δ19-9 had a worse overall survival than pts with minimal to high δ19-9 (median survival 11.5 mo vs. 30.1 mo, p = 0.0002). In a multivariate Cox proportional hazard, a decline in pre-surgical 19-9 from baseline was associated with improved survival (HR 0.21, p =0.02). Conclusions: Following neoadjuvant therapy, a decline in 19-9 is associated with surgical resection and improved overall survival. An increase in 19-9 above baseline (the absent δ19-9 group) prior to surgery is a poor prognostic marker and such patients may benefit from additional systemic therapy.
Single nucleotide polymorphisms and smoking status for prediction of non-small cell lung cancer.
Authors: Junjie Wu, Jie Liu
Journal: Journal of Clinical Oncology (2014)

1563 Background: Lung cancer has become the leading cause of death in all cancer. The 5-year survival rate of lung cancer is less than 15%, but the 5-year survival rate of up to 87.7% after treatment of early stage lung cancer. Therefore, timely detecting early stage lung cancer is the key to influence survival rate. However, the current level of lung cancer diagnosis did not increase the rate of detection of lung cancer. The objective of the current study is to introduce genetic factors SNPs to build predictive models of lung cancer for improving the detection rate of early stage lung cancer. Methods: SNPs that were identified of associations to NSCLC in several recent studies were reassessed using a pooled sample size of 3,637 Chinese subjects, with 1,597 cases and 2,040 controls from these studies. Multivariate logistic regression models were used to predict NSCLC using SNPs, age, with or without sex, with or without smoking status as predictors. The performance of prediction was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). Results: Overall, the AUC from a logistical regression model using all 6 SNPs plus smoking status and demographics as predictors was 0.63(95% CI: 0.61–0.65; P=1.6×10-38), higher than that of 0.60 (95% CI: 0.59–0.62; P=4.5×10-25) from a non-genetic model using smoking status and demographics. For female group and ever smoking group, the AUC from models only using 5 SNPs and 4 SNPs as predictors was 0.61(95% CI: 0.57–0.65;P=8.44×10-9) and 0.57 (95% CI: 0.55–0.60; P=1.53×10-7) respectively. For Adenosquamous group, the AUC from a model using 3 SNPs plus sex as predictors was 0.71(95% CI: 0.62–0.80; P=3.91×10-5), higher than that of 0.57 (95% CI: 0.48–0.66; P=0.157) from a non-genetic model using sex only. Conclusions: The combination of SNPs improved the performance of risk models for lung cancer. This study displays an significative role to integrate SNPs in predictive models for lung cancer risk. These findings show the importance of stratifying analysis by sex, smoking status and histology, to improve the performance of specific risk models for lung cancer.