tbuckley/cabot-search huggingface dataset:
Impact on health-related quality of life of the addition of bevacizumab to cisplatin-pemetrexed in malignant pleural mesothelioma in the MAPS phase III trial.
Authors: Virginie Westeel, Guillaume Eberst, Amelie Anota, Arnaud Scherpereel, Julien Mazieres, Jacques Margery, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Olivier Molinier, Lena Herve, Frédéric Rivière, Isabelle Monnet, Valérie Gounant, Henri Janicot, Radj Gervais, Chrystele Locher, Franck Morin, Gerard Zalcman
Journal: Journal of Clinical Oncology (2018)

8505 Background: The IFCT-GFPC-0701 MAPS phase III trial highlighted a significant improvement in overall survival with the addition of bevacizumab to the standard first-line chemotherapy regimen, cisplatin plus pemetrexed, in advanced malignant pleural mesothelioma. We present the results of health-related quality of life (HRQoL), a secondary endpoint of MAPS. Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and the Lung Cancer specific module QLQ-LC13 at randomization and then every 9 weeks until progression. HRQoL deterioration-free survival (QFS), used to analyze longitudinal HRQoL data, was defined as the interval between randomization and the occurrence of the first clinically important deterioration of at least 5 points or death. Univariate and multivariate cox regression models were done to analyze variables associated with the QFS, including treatment arm. Results: A total of 448 patients were included in the MAPS trial between 2008 and 2014. At baseline, 428 patients (95.5%) completed the HRQoL questionnaire. We showed that the addition of bevacizumab to cisplatin and pemetrexed significantly improved QFS for two HRQoL dimensions: pain (Hazard Ratio (HR) = 0.81, 95% CI 0.67–0.99; p = 0.041) and peripheral neuropathy (HR 0.73, 95% CI 0.6–0.89, p = 0.002). A performance status 0-1, a hemoglobin level > 14g/dl and epithelioid histology were also associated with a longer QFS. Conclusions: This study shows that adding bevacizumab to standard chemotherapy in patients with advanced malignant pleural mesothelioma not only enhanced progression-free survival and overall survival, but resulted in a significant improvement in HRQoL. Clinical trial information: NCT00651456.
Phase 2 results of selinexor in advanced de-differentiated (DDLS) liposarcoma (SEAL) study: A phase 2/3, randomized, double blind, placebo controlled cross-over study.
Authors: Mrinal M. Gounder, Neeta Somaiah, Steven Attia, Sant P. Chawla, Victor Manuel Villalobos, Bartosz Chmielowski, Melissa Amber Burgess, Gary K. Schwartz, Richard F. Riedel, Margaret von Mehren, Andrew J. Wagner, Edwin Choy, Shailendra Verma, Boyd Mudenda, Mara Sadanowicz, Jatin J. Shah, Lingling Li, Sharon Shacham, Michael G. Kauffman, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2018)

11512 Background: Locally advanced DDLS is incurable with an overall survival of 11 – 20 mo with palliative therapies. Ideal imaging criteria for efficacy is currently undefined. Selinexor (S) is an oral, selective inhibitor of nuclear export that specifically blocks exportin 1, leading to the nuclear accumulation and reactivation of tumor suppressor proteins. S demonstrated anti-tumor activity against DDLS in preclinical studies and a Ph 1b study in patients (pts) with soft tissue sarcomas. Methods: Eligible pts had DDLS and progressive disease (PD) with ≥ 1 prior systemic therapy. Pts were randomized 1:1 to receive blinded S (60 mg) or placebo (P) twice weekly; 42 day cycle until PD or intolerability. Pts with PD on P may cross over to S. The primary endpoint was progression-free survival (PFS) by WHO criteria. Pre-specified analyses using RECIST v1.1 (R v1.1) was included. Results: Ph 2 enrollment is complete. 56 evaluable pts (33 M, 23 F) were randomized to S or P. Median age: 61 yrs and median prior treatments: 2 (1-9). Treatments for 51 pts were unblinded (24 S, 27 P). The main reason for ending blinded treatment was PD confirmed by Independent Central Radiological Review by WHO Criteria. Common AEs Grade 1/2 (S:P) were: nausea (85% : 31%), anorexia (62% : 14%), and fatigue (58% : 45%). Grade 3/4 AEs were: hyponatremia (15% : 0%), anemia (15% : 7%), and thrombocytopenia (12% : 0%). 12 pts on S had dose reductions due to AEs. There was no difference in median PFS by WHO. By R v1.1, median PFS on S: 5.6 mo; P: 1.8 mo, hazard ratio of 0.64 (p 0.21, not powered in Ph 2). (Table 1). Some pts ended treatment early with small changes in tumor burden due to PD by WHO criteria. Conclusions: R v1.1 may be better criteria than WHO to evaluate drug efficacy in DDLS. Improvement of PFS (R v1.1) is promising and supports continuation of the Ph 3 portion of S in DDLS. Clinical trial information: NCT02606461.Median PFS by R v1.1 and WHO criteria. Treatment Arm R v1.1 - PFS (mo) Hazard Ratio (95% CI) WHO - PFS (mo) Hazard Ratio (95% CI) Selinexor (N = 24) 5.6 0.64 (0.31, 1.32) p = 0.21 1.4 0.92 (0.52, 1.63) Placebo (N = 27) 1.8 1.4
Long-term outcomes of non-myeloablative allogeneic stem cell transplantation (alloSCT) in patients with relapsed mantle cell lymphoma (MCL).
Authors: Issa F. Khouri, Xuemei Wang, Francesco Turturro, Elias Jabbour, Adrian A. Carballo-Zarate, Martin Korbling, Amin Majid Alousi, Betul Oran, Paolo Anderlini, Stefan O. Ciurea, Krina K. Patel, David Marin, Loretta J. Nastoupil, Michelle A. Fanale, Barry I Samuels, Alison M Gulbis, L Jeffrey Medeiros, Joseph Khoury
Journal: Journal of Clinical Oncology (2016)

7551 Background: Patients with relapsed MCL remain incurable, especially if their tumors have a Ki-67 > 30%. We analyzed the long-term survival outcomes of 75 recipients of alloSCT. Methods: Patients were enrolled on 4 sequential protocols from 2005-2013; (80%) received the fludarabine, cyclophosphamide, rituximab-based regimen (Khouri et al, Blood 2012). Thirty-five (47%) patients also received alemtuzumab. Immunohistochemistry testing for Ki-67 was done on paraffin-embedded tissue sections of biopsy specimens that were obtained at last relapse pre-alloSCT. Results were assessed semiquantitatively. In addition, Ki-67 results in 20 cases were assessed by digital image analysis (Aperio Technologies, Vista, CA, USA). There were no discrepancies found between the 2 methods. Results: Sixty-seven (94%) of 71 biopsy specimens available were cyclin D1+ and 17 (23%) had blastoid morphology. Median age was 60 years and the median number of prior therapies received was 3 (range, 1-10). At the time of alloSCT, 67 (89%) had chemosensitive disease. A Ki-67 level of > 30% was found in 13 (38%) of 34 patients who had available samples. With a median follow-up time of 6.8 years (range, 2.1-14 years), the 5-year overall survival (OS) and progression free survival (PFS) rates were 49% and 37%, respectively. A plateau was observed after 5-years. A Cox model analysis was conducted for factors of interest including age, sex, International Prognostic Index (0 vs. > 0), LDH, PET, number of prior treatments, disease status, Ki-67, blastoid morphology, treatment with alemtuzumab, donor type, source of stem cells, and chimerism. Multivariate analysis showed that a higher number of prior treatments and mixed chimerism at day 100 were poor prognostic factors for both OS [HR 1.29, P = 0.007 and 2.4, (P = 0.01), respectively] and PFS [(HR 1.36, P = 0.002 and HR 3.14, (P = 0.0004), respectively]. There was no significant difference in OS according to Ki-67 of > or < 30% (P = 0.6). Conclusions: These long-term results suggest that alloSCT can overcome the negative prognosis of elevated Ki-67 and is curative in a significant proportion of patients with relapsed MCL, especially those with < 3 lines of therapy.
TCT-854 The PRECISE-DAPT score: relationship with clinical outcomes after drug-eluting stents implantation and with thrombotic-ischemic scores
Authors: Jose de la Torre Hernandez, Gabriela Veiga, Victor Fradejas, Virginia Frances, Tamara Garcia Camarero, Beatriz De Tapia Majado, Angela Alonso Miñambres, Mercedes Benito Alfonso, Maria Fuentes Martinez, Maria Sainz Gonzalez, Aritz Gil Ongay, Santiago Catoya, Dae-Hyun Lee Hwang, Fermin Sainz Laso, Jose Miguel Torres Viera, Javier Zueco
Journal: Journal of the American College of Cardiology (2018)
The significance of BCL6 abnormalities on fluorescence in situ hybridization (FISH) in chronic lymphocytic leukemia (CLL).
Authors: Patrick Eulitt, Qiuhong Zhao, Amy S. Ruppert, Lynne Abruzzo, Caitlin Coombes, Amber Gordon, Jeffrey Alan Jones, Farrukh Tauseef Awan, James Stewart Blachly, Leslie Ann Andritsos, John C. Byrd, Nyla A. Heerema, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2016)

e19005 Background: The clinical course of CLL is variable but can be predicted in part by recurrent cytogenetic abnormalities. BCL6 functions as a transcriptional repressor during germinal center formation, and alteration of 3q27 has been well characterized in some B cell malignancies. However, the incidence and significance of BCL6 abnormalities in CLL is unknown. Methods: Between 10/2007 and 6/2014, 1811 patients (pts) with CLL at our institution underwent FISH which included a probe for 3q27. Clinical and molecular data were reviewed for pts with rearrangements or extra copies of BCL6. Data were also obtained from pts participating in 4 sequential clinical trials of ibrutinib, and characteristics of pts with and without pre-treatment BCL6 abnormalities were compared. Results: 152 pts (8.4%) were found to have an abnormality of BCL6 at any time during their clinical course. Clinical and cytogenetic characteristics are summarized below. BCL6 abnormalities were present prior to first therapy in 28 pts, suggesting a primary abnormality. These pts had an early age at diagnosis (62.5 years), short time from diagnosis to first treatment (median 23.6 months), and relatively low 5-year survival (estimated at 62.9%). Pts with BCL6 abnormalities were likely to have complex karyotype and other high risk abnormalities including MYC rearrangement/copy gains and del(17p). Comparing pts with and without BCL6 abnormalities undergoing similar therapy, those with BCL6 abnormalities were more likely to have complex karyotype (p = 0.0007), MYC abnormalities (p < 0.0001), and del(17p) (p < 0.0001). Conclusions: BCL6 abnormalities are associated with other high risk markers in CLL, and these pts have early age at diagnosis, short time to first therapy, and relatively short survival. These data suggest that BCL6 FISH abnormalities may be an important biomarker in CLL. Work to further characterize the biologic basis for these findings is ongoing. All BCL6+ pts (n = 152) BCL6+ before first therapy (n = 28) Median age at diagnosis 58.0 years 62.5 years Median time from diagnosis to first therapy 15.5 months 23.6 months Karyotype complexity ( ≥ 3) 71.3% 64.3% Concurrent FISH abnormalities: MYC 49.0% 33.3% Del(17p) 57.9% 42.9%
Does training oncologists to have goals of care discussions increase and improve the quality of GoC discussions with advanced cancer patients?
Authors: Nina A. Bickell, Kerin B. Adelson, Jason Parker Gonsky, Jenny J. Lin, Sofya Pintova, Rebeca Franco, Natalia Egorova, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2018)

6597 Background: Advanced cancer patients often have a poor understanding of the incurability of their cancers and this correlates to higher rates of aggressive treatment near end of life. Goals of Care (GoC) discussions may affect patients’ decisions about aggressive treatment near end of life. We coached oncologists to improve communication skills and assessed its impact on prevalence and quality of GoC discussions. Methods: At an academic, community, municipal and rural hospital, we recruited & randomized solid tumor oncologists & their newly diagnosed advanced cancer patients with < 2 year prognosis. Prior to and after completing 4 coaching sessions, a post-imaging visit was audiotaped and reviewed by VitalTalk trained specialists to assess oncologists’ communication skills. Consented patients were surveyed after their 3 month post-imaging visit & GoC discussions defined as: cancer treatment preferences, what’s important to you in life given your diagnosis and prognosis. Results: We enrolled 22/25 eligible oncologists (88%) & 265 patients. On average, doctors were 44 yrs old (32-66) & in practice 14.5yrs (5-40). There was no significant difference between intervention (INT) and control (CNTL) oncologists’ prior communication skills training (58% v 56%; p = 0.80) & comfort having GoC discussions (58% v 56%; p = 0.80). On average, CNTL physicians had no change in the number of demonstrated skills (5.45 to 5.36/10); INT physicians increased from 6.6 to 8.3/10 skills (p = 0.04). Patients’ mean age was 63 yrs (20-89), 60% male, 52% white, 30% black & 19% Latino. Overall, 61% of patients reported their treatment’s goal was to cure their cancer; 40% reported cure to be likely. 49% had a complete GoC discussion (48% INT v 51%; p = 0.61). 65% of patients reported their oncologist talked about their GoC, “the very best” they could imagine (63% INT v 68% CNTL; p = 0.39). 51% did not report a GoC discussion with no difference between INT (52%) & CNTL (49%) patients (p = 0.61). Conclusions: Using a coaching model to teach oncologists’ communication skills improved skills to carry out a GoC discussion but did not increase rates of GoC discussions among advanced cancer patients with < 2 year life expectancy. Clinical trial information: NCT02374255.
Treatment of Chronic Hepatitis B Infection
Authors: Yi-Hua Zhou
Journal: JAMA (2018)

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Abstract 17998: Impairment of Vascular Bone Marrow Niche Predicts Death in Patients With Chronic Heart Failure
Authors: Kateryna Sopova, Lars Palapies, David Leistner, Konstantinos Stellos, Stephan Fichtlscherer, Florian Seeger, Stefanie Dimmeler, Birgit Assmus, Andreas Zeiher, Till Keller
Journal: Circulation (2015)

Background: The bone marrow vascular niche is essential for hematopoietic regeneration. Patients with chronic heart failure are characterized by myelosuppresion and anemia. Therefore, in order to investigate whether chronic heart failure is associated with an impairment in the vascular niche of the bone marrow, we measured in bone marrow plasma levels of the prototypical angiogenic factor PlGF (placental growth factor), as well as, its soluble inhibitor, sFlt-1 (Fms-like tyrosine kinase 1), which acts as a decoy receptor for PlGF, as a measure of the functional integrity of the vascular bone marrow niche. Methods and Results: Bone marrow plasma levels of sFlt-1 and PlGF were determined by ELISA in 187 patients (mean age: 62.2±11.3years) with chronic heart failure, who were enrolled in the Frankfurt Bone Marrow-Derived Mononuclear Cell Therapy Registry. Fifty-one patients died within the 5-year follow-up period. Patients with increased bone marrow-derived sFlt-1/PlGF ratio had a 1.35-fold increased risk for death (95%CI: 1.08 to 1.68, p=0.007). This association was robust after adjustment for age, gender, left ventricular ejection fraction (LVEF), eGFR and NT-proBNP serum levels (HR:1.3, 95%CI: 1.014 to 1.678, p=0.038) or the Seattle Heart Failure score (HR:1.38, 95%CI: 1.112 to 1.723, p=0.004). Importantly, this association remained significant even after adjustment for colony-forming unit capacity (HR:1.33, 95%CI: 1.051 to 1.675, p=0.018) and SDF-1-induced migratory capacity of bone marrow-derived cells (HR:1.35, 95%CI: 1.087 to 1.678, p=0.007). Conclusions: The present study for the first time discloses that an impairment of the angiogenic potential of the bone marrow microenvironment, defined as increased sFlt-1 to PlGF ratio in the bone marrow plasma, is independently associated with mortality in patients with chronic heart failure. These data further corroborate the importance of the bone marrow-heart axis to predict clinical outcome in patients with chronic heart failure.
Implementing pregnancy screening prior to chemotherapy: A quality improvement initiative.
Authors: Brittany Kayla Rogers, Andrew Kolarich, Merry Jennifer Markham
Journal: Journal of Clinical Oncology (2017)

e18274 Background: ASCO’s QOPI sets standards for excellence in oncologic care. One standard is screening appropriate female patients for pregnancy prior to chemotherapy. No guidelines exist regarding screening protocols or timing. Prior data collection at our institution from 2012-2014 revealed that 35% of women of childbearing potential were screened prior to chemo, with medical oncology performing only 7% of screening. Less than half (48%) of those tests were ordered within 14 days prior to treatment start. Methods: A quality improvement (QI) intervention was implemented at UF Health outpatient infusion center on 8/15/16 based on the above data. A checkbox was added to the pre-chemo checklist used by infusion nurses. For eligible patients (women ages 18-55 without prior tubal ligation or hysterectomy), a point of care pregnancy test, included in standing orders, was recommended. We reviewed data for women who received outpatient chemo during 9/16-11/16 to determine rates of pregnancy screening (PS) after intervention. Results: 49 women, ages 18-55, of childbearing potential were identified and presented for 174 chemo cycles from 9/1/16 to 11/30/16. Of these, 15 (30.6%) received PS before chemo. Fifty pregnancy tests were ordered during this period; all were negative. Of the 50 tests, 42 (84%) were ordered by medical oncology, 3 (6%) by a surgical oncology, 3 (6%) by radiation oncology, and 1 (2%) by emergency medicine. Of the PS tests ordered by medical oncology, 64.2% were within 14 days of chemotherapy. Conclusions: In three months of QI intervention, PS prior to chemo increased from 7% to 30.6%. Screening was 13% in women older than 45, but higher in women age 25-34 (60%) and 35-44 (67%). Although the screening rate improved, it remains below our goal of 80%. Possible explanations for low rates are inclusion of postmenopausal women and those older than 50. Excluding these patients could reduce screening burden while identifying appropriate patients. [Table: see text]
NRG Oncology BR005: Phase II trial assessing accuracy of tumor bed biopsies (Bx) in predicting pathologic response in patients (Pts) with clinical/radiological complete response (CR) after neoadjuvant chemotherapy (NCT) in order to explore the feasibility of breast-conserving treatment (BCT) without surgery.
Authors: Mark Basik, Joseph P. Costantino, Jennifer F. De Los Santos, Heidi Umphrey, Thomas B. Julian, Eleftherios P. Mamounas, Julia R. White, Peter C. Lucas, Jamie L. Wagner, Judy Angela Tjoe, Alastair Mark Thompson, Norman Wolmark
Journal: Journal of Clinical Oncology (2018)

TPS604 Background: The increased use of neoadjuvant chemotherapy (NCT) has enabled higher rates of breast-conserving surgery (BCS) as well as provided prognostic information for women with breast cancer. High pathological complete response (pCR) rates question the requirement for surgery, with its attendant morbidity. In order to avoid surgery, the ability to predict pCR prior to it must be very high. Trimodality imaging alone is inadequate to predict pCR prior to surgery. We hypothesize that performing core needle biopsy (bx) of the tumor bed in addition to trimodality imaging in pts having had a clinical complete response (cCR) will increase the ability to predict pCR. Utilizing predetermined imaging response criteria of complete or near-complete response coupled with a stereotactic core needle bx of the tumor bed, BR-005 aims to determine the predictive value of imaging followed by tumor bed bx for pCR and demonstrate its reproducibility across a multi-institutional setting. Methods: 175 pts with operable focal or multifocal (T1-T3), stage II/IIIA invasive ductal carcinoma [all receptor subtypes]) will be entered. Pts must have completed a minimum of 8 wks of standard neoadjuvant chemotherapy and achieved a complete or near-complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI, and undergo BCS. Following cCR and prior to surgery, pts will undergo a stereotactic-vacuum-assisted breast bx with clip placement. The primary endpoint is the proportion of pts with post-NCT neg image-directed bx who have a pCR. Residual cancer burden (RCB) scores and core bx pathology will be collected along with trimodality imaging data. Evaluation after 135 pts will allow for the possibility of early termination of the study. Results will provide the first step towards a paradigm change in the treatment of breast cancer, enabling a study to assess the criteria for successful avoidance of surgery in pts with high response rates to NCT. Accrual as of 1/19/2018: 13. Support U10CA180868, -180822, UG1CA189867 Clinical trial information: NCT03188393.