tbuckley/cabot-search huggingface dataset:
Combination trastuzumab and chemotherapy to induce immunity to multiple tumor antigens in patients with HER2-positive metastatic breast cancer: NCCTG (Alliance) studies N0337 and N98-32-52.
Authors: Raphael Clynes, Keith L. Knutson, Karla V. Ballman, Courtney L. Erskine, Nadine Norton, Susan V. Sumrall, Donald W. Northfelt, Winston Tan, Carmen Julia Calfa, Mark D. Pegram, Edith A. Perez
Journal: Journal of Clinical Oncology (2013)

521 Background: The addition of trastuzumab to chemotherapy improves responses to therapy and extends survival among patients with metastatic HER2 breast cancer. Several mechanisms have been proposed for the activity of this combination therapy. Trastuzumab, specifically, is thought to activate NK cells and blunt HER2 signaling. Prior work from us has shown that combination trastuzumab and chemotherapy induces HER2-specific antibodies which correlate with response to therapy. Despite that, it remains unclear whether the immunity that was induced was due to complexing of non-tumor derived HER2 or antigen derived from the tumor site. In the present work, we addressed this question by assessing if combination therapy induced epitope spreading to tumor antigens other than HER2. Methods: Pre-and post-treatment sera were obtained from 56 women enrolled in 2 NCCTG clinical trials, N0337 and 98-32-52. IgG antibodies to HER2 intracellular domain (HER2), p53, IGFBP2, CEA and tetanus toxoid (TT) were examined using ELISAs. Sera from an age-matched group (N=56) of controls and 12 patients treated in the adjuvant setting were also examined. Results: Prior to therapy, metastatic patients had higher IgG levels (≥ 2-fold) to p53 and HER2 but not CEA, IGFBP2 and TT, relative to the controls. Similarly, adjuvant patients had elevated IgGs to multiple tumor antigens prior to therapy, relative to controls. Following therapy, levels of IgG to IGFBP2, HER2, and p53 increased in 81% of metastatic patients, with mean increases of 3.2 (±0.6 sem), 6.2 (±2.7) and 2.7 (±0.7) fold, respectively (p&lt;0.05). Levels of antibodies to TT and CEA were not elevated by treatment. In contrast, IgGs were not increased in adjuvant patients; consistent with the idea that immunity depends on the presence of threshold levels of antigens. Conclusions: These results show that combination treatment induces adaptive immunity to antigens released by tumor and that metastatic patients remain capable of responding immunologically to their cancer. Thus, in metastatic breast cancer patients, combination trastuzumab and chemotherapy may behave as a vaccine.
Abstract 12623: A New ASCVD Risk Estimator is More Accurate Than the ACC/AHA Pooled Cohort Equation in Four Diverse Community-Based Populations in the U.S. and Canada
Authors: Alan S Go, Grace Tabada, Kristi Reynolds, Stephen P Fortmann, Amit Garg, Ronald D Scott, Joseph Young, Joan C Lo, Matthew D Solomon, Rong Wei, Michael J Allison, Eric McArthur, Danielle M Nash, Sue Hee Sung, Jamal S Rana
Journal: Circulation (2018)

Introduction: The Kaiser Permanente ASCVD Risk Estimator (KPARE) was developed to address the systematic overestimation of actual ASCVD risk by the ACC/AHA ASCVD Pooled Cohort Equation (ACC/AHA PCE...
Comprehensive Molecular and Pathologic Evaluation of Transitional Mesothelioma Assisted by Deep Learning Approach: A Multi-Institutional Study of the International Mesothelioma Panel from the MESOPATH Reference Center
Authors: Francoise Galateau Salle, Nolwenn Le Stang, Franck Tirode, Pierre Courtiol, Andrew G. Nicholson, Ming-Sound Tsao, Henry D. Tazelaar, Andrew Churg, Sanja Dacic, Victor Roggli, Daniel Pissaloux, Charles Maussion, Matahi Moarii, Mary Beth Beasley, Hugues Begueret, David B. Chapel, Marie Christine Copin, Allen R. Gibbs, Sonja Klebe, Sylvie Lantuejoul, Kazuki Nabeshima, Jean-Michel Vignaud, Richard Attanoos, Luka Brcic, Frederique Capron, Lucian R. Chirieac, Francesca Damiola, Ruth Sequeiros, Aurélie Cazes, Diane Damotte, Armelle Foulet, Sophie Giusiano-Courcambeck, Kenzo Hiroshima, Veronique Hofman, Aliya N. Husain, Keith Kerr, Alberto Marchevsky, Severine Paindavoine, Jean Michel Picquenot, Isabelle Rouquette, Christine Sagan, Jennifer Sauter, Francoise Thivolet, Marie Brevet, Philippe Rouvier, William D. Travis, Gaetane Planchard, Birgit Weynand, Thomas Clozel, Gilles Wainrib, Lynnette Fernandez-Cuesta, Jean-Claude Pairon, Valerie Rusch, Nicolas Girard
Journal: Journal of Thoracic Oncology (2020)
Ovarian granulosa cell tumors: Experience of National Institute of Oncology in Morocco.
Authors: Sakina Sekkate, Mouna Kairouani, Badr Serji, Brahim el Ghissassi, Hind Mrabti, Hassan Errihani
Journal: Journal of Clinical Oncology (2013)

e16527 Background: The granulosa cell tumors are malignancies with a relatively favorable prognosis. They are characterized by prolonged natural history and tendency to late recurrences. The aim of this study is to investigate the epidemiological and pathological characteristics of granulosa cell tumors, and the prognosis factor for recurrences in the national institute of oncology in Rabat in Morocco. Methods: The clinical data of patients with adult granulosa cell tumors of the ovary treated from January 2003 to december 2010 was investigated retrospectively. Data of age, clinical manifestation, imaging, diagnosis, treatment and follow up of the patients were reviewed and analyzed. Histology was obtained in postoperative for all patients. Results: Twenty-seven cases were retrieved. The median age was 53 years. The most common clinical manifestations at diagnosis were: abdominal pain, vaginal bleeding, abdominal distension and hormonal manifestations. The mean tumor size was 14 cm. The majority of patients had stage I (62,96%, n = 17), while (18,51%, n = 5) had stage III, (7,4%, n = 2) had stage IV, and (11,11%, n = 3) of patients had unknown stage.8 patients received adjuvant chemotherapy (4 : bleomycin etoposide, cisplatin (BEP); 1: bleomycin vepeside cisplatin (BVP); 1: endoxan cisplatin; 1: paclitaxel cisplatin; 1: tamoxifene), and 2 patients received chemotherapy for metastatic disease.For a median follow up of 63,44 months, 5 (18,51%) of patients relapsed. The median time to relapse was 41,8 months, (range : 18-62 months).The overall 5-year survival and 9-year survival rates for all stages were 91.3% and 77.3%, respectively. Following univariate Cox regression modeling, the survival depends on stage, it’s better in localized stages (p = 0,05). Conclusions: Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. A prolonged post therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form.
TRANSRADIAL CATHETERIZATION AND CABG: IS IT SAFE TO USE A PREVIOUSLY CATHETERIZED RADIAL ARTERY AS A CORONARY ARTERY BYPASS GRAFT?
Authors: Berhane Worku, Igor Mamkin, Ivan Gambardella, Helbert DeCastro, Anthony Acinapura, Mario Gaudino, Leonard N. Girardi, Terrence Sacchi, Robert F. Tranbaugh
Journal: Journal of the American College of Cardiology (2020)
Efficacy and tolerability of biweekly paclitaxel combined with cisplatin in the treatment of metastatic breast cancer (MBC) patients previously treated with anthracyclines
Authors: D. A. Donat, J. Pesic, J. Trifunovic, L. Muzikravic, S. Tesanovic, D. D. Donat
Journal: Journal of Clinical Oncology (2006)

10642 Background: Our aim was to assess the efficacy and tolerability of paclitaxel combined with cisplatin in the treatment of MBC patients previously treated with anthracyclines either as adjuvant treatment or as first-line chemotherapy for MBC. Methods: The study included 168 patients divided in two groups: 64 patients in group I who received adjuvant FAC and 104 patients in group II who received CMF as adjuvant therapy and FAC for MBC as first-line treatment. Participants received paclitaxel 90 mg/m 2 on day 1 and cisplatin 60 mg/m 2 on day 2 q/2w. Total number of cycles per patient was 3–9. Results: Evaluation was made after 3 cycles of chemotherapy. Obtained RR was: in group I, CR in 4 (6.26%), PR in 30 (46.87%), SD in 5 (7.81%), and PD in 25 (39.06%) patients, with ORR in 34 (53.13%) patients. In group II, the obtained results were: CR in 3 (2.88%), PR in 36 (34.6%), SD in 6 (5.77%), and PD in 59 (56.75%) patients, with ORR in 39 (37.49%) patients. Patients with CR received 3 more cycles and patients with PR received 3 or 6 therapies depending on the obtained results. Treatment evaluation of PR patients in group I after cycle 6 resulted with CR only in 1 (1.56%) patient and in group II showed CR in 2 (1.92%) patients. In those patients 3 more therapies were applied. Difference between the two groups in ORR is highly significant: p &lt; 0.04. Hematological toxicity grades 3 and 4 in both groups were rare and similar. Conclusions: The application of biweekly paclitaxel combined with cisplatin in our patients’ population is efficacious with good tolerability. In group I the obtained results in ORR was 53.13%, which is statistically significantly (p &lt; 0.04) better than in group II with ORR: 37.49%. No significant financial relationships to disclose.
PERCUTANEOUS INTERVENTION OF THE SAPHENOUS VENOUS GRAFT ARISING FROM DESCENDING AORTA TO THE LEFT CIRCUMFLEX: A RARE, TECHNICALLY COMPLICATED BUT FEASIBLE INTERVENTION
Authors: Jose Sleiman, Morvarid Zandiyeh, Rafael Miret, Hardik M. Bhansali, Mileydis Alonso, Diana Miranda Ruiz, Eduardo Perez, Nader Hanna, Luis Alonso Hernandez Mejia, Kevin Leung, Nicholas Ghiloni, Howard S. Bush
Journal: Journal of the American College of Cardiology (2020)
Response to EGFR tyrosine kinase inhibitor (TKI) retreatment after a drug-free interval in <i>EGFR</i>-mutant advanced non-small cell lung cancer (NSCLC) with acquired resistance.
Authors: Stephanie Heon, Mizuki Nishino, Sarah B. Goldberg, Jennifer Porter, Lecia V. Sequist, David Michael Jackman, Bruce E. Johnson
Journal: Journal of Clinical Oncology (2012)

7525 Background: Patients (pts) with advanced NSCLC and sensitizing EGFR mutations who initially respond to gefitinib or erlotinib eventually develop acquired resistance to the TKIs. Anecdotal and retrospective reports suggest that EGFR-TKI resistant cancers can respond again to gefitinib or erlotinib after an interval off the TKI. This retrospective study was undertaken to investigate the impact of EGFR-TKI retreatment after a drug-free interval in EGFR mutant NSCLC with acquired resistance to gefitinib or erlotinib. Methods: Pts with stage IV or relapsed NSCLC with sensitizing EGFR mutations and acquired resistance to EGFR-TKI seen at the DFCI/MGH between 8/00 and 8/11 who were retreated with single agent gefitinib or erlotinib after an EGFR-TKI-free interval were identified from a prospective trial. The objective tumor response (CR, PR, SD, PD) was determined using RECIST 1.1. Results: 19 pts were eligible and had adequate scans for radiographic assessments after the reinstitution of an EGFR-TKI. The response rate and median PFS to the initial course of gefitinib (n=4) or erlotinib (n=15) were 16/19 (84%) and 9.8 months (95% CI, 7.8-11.3) respectively. All pts were retreated with erlotinib after 1 to 4 intervening systemic regimens. The median interval from EGFR-TKI discontinuation to erlotinib retreatment was 11 months (range, 2-46). 4 of the 19 pts (21%) had PD as the best response to erlotinib retreatment, 14 (74%) had SD for at least 1 month, and 1 (5%) had a PR. The median PFS was 4.4 months (95% CI, 3.0-6.7). 3 pts remained on erlotinib without progression for 6 months. 3 pts had their tumors rebiopsied before (n=2) or during (n=1) erlotinib retreatment; 1 of the 3 had EGFR T790M in association with the initial sensitizing EGFR mutation, and another had a secondary PIK3CA mutation. Conclusions: Our findings suggest that erlotinib retreatment is an option for EGFR mutated NSCLC with acquired resistance to EGFR-TKI after a drug-free interval and progression on intervening therapy. Additional advanced NSCLC pts without a documented EGFR mutation who fulfill the clinical definition of acquired resistance are undergoing review to expand our cohort.
Statin use in uterine malignancies.
Authors: Lori Ann Spoozak, Eugenia Girda, Anne Van Arsdale, Mark H. Einstein, Gary L. Goldberg, Nicole Nevadunsky
Journal: Journal of Clinical Oncology (2013)

5592 Background: Statins, or 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are commonly used to manage hyperlipidemia. Epidemiologic studies have recently linked statins to improved cancer survival. Molecular pathways that explain this effect are not well defined, but may involve cell death and angiogenesis. Our aim was to determine the association between statin use and overall survival in a cohort of women with uterine malignancies. Methods: After IRB approval, a retrospective review of consecutive patients with uterine malignancies diagnosed between 01/2005 and 12/2009 at a single institution was performed. Age, race, diagnosis of hyperlipidemia, diabetes, hypertension, medication use including statins, beta-blockers, aspirin, pathology, and exposure to chemotherapy or radiation were abstracted from the time of initial diagnosis and treatment. Kaplan-Meier analysis, univariate, and multivariate Cox Proportional Hazard Regression were performed to assess the association between statin use, aspirin use, and survival. Results: Of 554 patients identified, 333 (60%) were not hyperlipidemic (NH), 165 (30%) were hyperlipidemic on statins (HS), and 56 (10%) were hyperlipidemic and not on statin therapy (HNS). The HS cohort was older, diabetic, hypertensive, used beta-blockers and aspirin. Stage, grade, and chemotherapy use were similar, but HS and HNS received more radiation (p&lt;0.05). Both patients in the HS and HNS groups had improved overall survival compared to NH patients (p=0.04). Further stratifying our subgroups by aspirin use revealed that HS+aspirin users had significantly improved survival compared to other non-HS+aspirin users (p=0.01). In multivariate analysis, women who used statins had a 45% decreased hazard of death compared to NH women (HR = 0.55, 95% CI; 0.35, 0.87). Additionally, aspirin users had improved survival compared to non-users (HR = 0.47, 95% CI; 0.29, 0.76). Women using statins and aspirin had an 84% decreased hazard of death in comparison to other groups (HR = 0.16, 95% CI; 0.07,0.38, p&lt;0.01). Conclusions: Statin and aspirin use are associated with improved overall survival in patients with uterine malignancy. Prospective evaluation of statin and aspirin use in uterine cancer is warranted.
ACUTE CORONARY SYNDROME AMONG YOUNG ADULTS WITH MODIFIABLE RISK FACTORS LINKED TO SEVERE CORONARY ARTERY DISEASE IN TRINIDAD &amp; TOBAGO
Authors: Ravi Ramlal, Nicholas Taklalsingh, Ronan Ali, Risshi Rampersad, Ronald E. Henry, Shane Gieowarsingh, Isaac Dialsingh, Terence Seemungal, Surujpal Teelucksingh
Journal: Journal of the American College of Cardiology (2020)
Susceptibility to Cardiac Arrhythmias and Sympathetic Nerve Growth in VEGF-B Overexpressing Myocardium
Authors: Johanna Lähteenvuo, Olli-Pekka Hätinen, Antti Kuivanen, Jenni Huusko, Jussi Paananen, Markku Lähteenvuo, Jussi Nurro, Marja Hedman, Juha Hartikainen, Nihay Laham-Karam, Petri Mäkinen, Markus Räsänen, Kari Alitalo, Anthony Rosenzweig, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2020)

VEGF-B gene therapy is a promising proangiogenic treatment for ischemic heart disease, but, unexpectedly, we found that high doses of VEGF-B promote ventricular arrhythmias (VAs). VEGF-B knockout, alpha myosin heavy-chain promoter (αMHC)-VEGF-B transgenic mice, and pigs transduced intramyocardially with adenoviral (Ad)VEGF- B186 were studied. Immunostaining showed a 2-fold increase in the number of nerves per field (76 vs. 39 in controls, p < 0.001) and an abnormal nerve distribution in the hypertrophic hearts of 11- to 20-month-old αMHC-VEGF-B mice. AdVEGF-B186 gene transfer (GT) led to local sprouting of nerve endings in pig myocardium (141 vs. 78 nerves per field in controls, p < 0.05). During dobutamine stress, 60% of the αMHC-VEGF-B hypertrophic mice had arrhythmias as compared to 7% in controls, and 20% of the AdVEGF-B186-transduced pigs and 100% of the combination of AdVEGF-B186- and AdsVEGFR-1-transduced pigs displayed VAs and even ventricular fibrillation. AdVEGF-B186 GT significantly increased the risk of sudden cardiac death in pigs when compared to any other GT with different VEGFs (hazard ratio, 500.5; 95% confidence interval [CI] 46.4-5,396.7; p < 0.0001). In gene expression analysis, VEGF-B induced the upregulation of Nr4a2, ATF6, and MANF in cardiomyocytes, molecules previously linked to nerve growth and differentiation. Thus, high AdVEGF-B186 overexpression induced nerve growth in the adult heart via a VEGFR-1 signaling-independent mechanism, leading to an increased risk of VA and sudden cardiac death.
Second-line chemotherapy with cabzitaxel and prednisolone (CP) in castratation-resistant prostate cancer (CRPC): Tolerability and efficacy—A U.K. institution experience.
Authors: Amir H Montazeri, Chinnamani Eswarvee, Helen Wong, Zafar I Malik
Journal: Journal of Clinical Oncology (2012)

e15128 Background: There are limited options for CRPC patients post docetaxel treatment. The majority of these patients have advanced disease with bone metastasis and often have reduced marrow reserve. Cabazitaxel is a novel taxane with activity in docetaxel-resistant/ sensitive cancers with proven clinical benefit in a phase 3 trial. Concerns have been expressed about efficacy and toxicity of this agent in a non trial population. Methods: In this retrospective case study, patients with CRPC treated with CP between Jan-Dec 2011 were included. Response rates (PSA, ALP, radiological) and toxicities (CTCAE) were recorded. All statistical analysis was performed using SPSS v18. Results: 22 men received CP with pegfilgrastim. 41% completed at least 6 cycles of CP and 23% completed 10 cycles. 27% had radiological partial response (RECIST). 36% of patients had ≥50% reduction in PSA level and 61% of patients with elevated ALP had ≥50% reduction. Median follow up was 7.9 months. Progression was defined as clinical, PSA or radiological. 3 patients discontinued treatment because of abnormal LFTs and a further 5 patients for toxicities summarised below. Conclusions: Response rates (RR) in our series (RECIST 27% &amp; PSA 36%) compared favourably with those in the TROPIC trial (14% &amp; 39% respectively) and support CP as an effective and well tolerated option in CRPC. An intriguing finding was the significant RR in ALP level with CP. This may reflect bone penetration of this agent and may correlate with symptom relief and improved clinical outcome. Further prospective studies are needed to investigate this marker with clinical outcome. Data for time to progression, progression free survival and overall survival is immature at this stage and will be updated for the meeting. To our knowledge this is the first case series of patients treated with CP presented outside a clinical trial. [Table: see text]
Measuring Ergonomic Risk in Operating Surgeons by Using Wearable Technology
Authors: Andrew J. Meltzer, M. Susan Hallbeck, Melissa M. Morrow, Bethany R. Lowndes, Victor J. Davila, William M. Stone, Samuel R. Money
Journal: JAMA Surgery (2020)

This case series study examines the ergonomic risk of surgery using wearable sensor inertial measurement units to monitor the ergonomics of surgeons at work.
OUTCOMES OF INTRAVASCULAR BRACHYTHERAPY IN RECURRENT DRUG-ELUTING IN-STENT RESTENOSIS
Authors: Michael Megaly, Matthew Glogoza, Iosif Xenogiannis, Evangelia Vemmou, Ilias Nikolakopoulos, Laura Willson, David J. Monyak, Patsa Sullivan, Larissa Stanberry, Paul Sorajja, Ivan Chavez, Michael R. Mooney, Jay Traverse, Yale Wang, Santiago Garcia, Anil Poulose, M. Nicholas Burke, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2020)
SMALL CELL CARCINOMA PRESENTING AS A MASSIVE BIATRIAL MASS WITH OBSTRUCTIVE PHYSIOLOGY DIAGNOSED BY UPPER ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION
Authors: Soomin Shin, Stephanie Hsiao, Sara Ratican, Hershon James, Stephanie Jeske, Christopher Hamerski, Eric Flagg, Yu Xie, Michael Pham
Journal: Journal of the American College of Cardiology (2020)
MODERATE AORTIC ENLARGEMENT IN TWO WEEKS OF ONSET IS THE SIGNIFICANT PREDICTOR FOR AORTA-RELATED ADVERSE EVENTS IN PATIENTS WITH TYPE B AORTIC DISSECTION
Authors: Yutaro Miyoshi, Shuichiro Kaji, Toshiaki Toyota, Kitae Kim, Takeshi Kitai, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2020)
HUMAN EPIDIDYMIS PROTEIN 4 INDUCES PROGRESSIVE CARDIAC FIBROSIS AND ADVERSE CARDIOVASCULAR EVENTS
Authors: Masahiro Yamamoto, Shinsuke Hanatani, Satoshi Araki, Toshifumi Ishida, Seiji Takashio, Yuichiro Arima, Taishi Nakamura, Satoru Suzuki, Yamamoto Eiichiro, Kenji Sakamoto, Koichi Kaikita, Kenichi Tsujita
Journal: Journal of the American College of Cardiology (2020)
Three-dimensional conformal involved-field radiotherapy for stage III non-small cell lung cancer
Authors: S. Yuan, J. Yu, X. Sun, M. Li
Journal: Journal of Clinical Oncology (2006)

7044 Background: Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field radiotherapy (IFRT) in patients with stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients with inoperable stage III NSCLC were enrolled and patients with previous treatment were ineligible, as were those with supraclavicular nodal metastases, pleural effusion, the Karnofsky performance status of &lt;80 or a weight loss exceeding 10% of baseline in the preceding 3 months. Two-hundred patients were treated with concurrent chemo-radiotherapy and randomized into IFRT group or ENI group. Two cycles of cisplatin-based chemotherapy (CHT) were delivered before radiotherapy, and another 2–3 cycles were followed after radiotherapy by the same or changed regime according to different response to the first 2 cycles of CHT. Radiotherapy was delivered using 3D treatment planning in once-daily fractions of 2 Gy to 68–74 Gy for IFRT or 60–64 Gy for ENI. The involved field consisted of the pre-CHT (or greatest) tumor volume, and any mediastinal nodes confirmed by biopsy or with a short-axis diameter of ≥1 cm on CT. Results: 193 patients had complete follow-up data. Radiation pneumonitis rate of patients with ENI was higher than patients with IFRT (29% vs. 17%, P = 0.044 ).The main cause of failure was local failure in 49% patients with ENI group and 41% with IFRT within 2 years. Only 7% of patients with IFRT developed a failure in an elective nodal region. Patients in IFRT group achieved a better overall response than ENI group (90% vs. 79%, P = 0.032). The overall survival at 1, 2, and 3 years was 59.7%, 25.6%, and 19.2% for ENI group vs. 67.2%, 38.7, and 27.3%for IFRT (P = 0.048). Conclusions: Local and distant failures remain the overwhelming modes of failure for stage III NSCLC patients. The omission of ENI did not result in any increase in isolated nodal failures, and it allowed a dose of 68–74 Gy to be safely administered to a substantial proportion of patients with inoperable Stage III NSCLC. Dose-escalation by conformal IFRT combined with CHT may improve the outcome for stage III NSCLC. No significant financial relationships to disclose.