tbuckley/cabot-search huggingface dataset:
Impact of a comprehensive drug recovery system in a community cancer center.
Authors: Robert D. Siegel, Theresa Sandifer, Terra Spann, Michael Borron, Richard Slough, Dionne Pringle, Bonnie Helms, Kristina Stoeppler-Biege
Journal: Journal of Clinical Oncology (2018)

e18642 Background: The cost of oncology drugs has escalated rapidly while rollbacks in health care coverage and the emergence of high deductible and limited policies have made these drugs unaffordable for patients. Many pharmaceutical companies offer free drug replacement for those uninsured or for whom coverage is inadequate. Previously Bon Secours St. Francis Cancer Center (BSSFCC) had contracted with a third-party vendor to recover replacement drug from these pharmaceutical programs. In 2017, we opted to suspend that third-party contract and take the process internally. Methods: BSSFCC is located in Greenville, SC. Nearly1500 new cases of cancer were diagnosed in 2016, of which, 3.5% are uninsured. We hired 2.5 FTE's to manage our drug recovery program. After clearance with legal and compliance officers, limited power of attorney was obtained to pursue these efforts on the patients’ behalf. Patients who had no drug coverage, inadequate coverage, or off-label denials were identified at the time of chemotherapy education, pre-authorization, or by after-the-fact processing of claims. Our efforts at drug recovery are noted below. Results: We recovered drug for 71 patients during fiscal 2017. The total cost of those recovered drugs was $3.25 million. This compared with $389,000 recovered by our third-party vendor (pre-commission) in FY 2016. The three drugs accounting for the largest portion of the recovered costs included ipilimumab $1.6 million, nivolumab $388,000, rituximab $300,000. $824,000 was associated with patients who were self-pay and $2.4 million dollars for those with inadequate insurance. $575,000 was recovered due to denial for off label use. Conclusions: Embedding a process within a community cancer center to manage drug recovery for the un- and underinsured proved to have a substantial return on investment. The drug expenses which had to be written off were decreased substantially but most importantly, our ability to replace drug with some reliability allowed many of our patients to receive effective therapy that otherwise would have proven cost prohibitive. Although the ability to recover drugs in this fashion is both helpful and appreciated, our program does nothing to rein in the unsustainable rise in the cost of cancer care.
Treatment patterns, biomarker testing (BMx) practices and health care resource use (HCRU) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Ashwini Arunachalam, Smita Kothari, Thomas A. Burke, Xiting Cao, Min Huang, Aaron Mendelsohn, Cindy Lui, Dae Ho Lee
Journal: Journal of Clinical Oncology (2016)

e20577 Background: The treatment landscape for advanced/metastatic NSCLC has changed with new targeted therapies & use of companion diagnostics. Methods: The objective of this retrospective chart review study was to describe the treatment, biopsy, BMx practice patterns & HCRU in Australian & Korean, newly diagnosed Stage IIIB/IV NSCLC patients who initiated first line therapy (1LT) during Jan/1/2011-July/1/2013. Data were analyzed descriptively. Overall survival (OS) from start of 1LT & second line therapy (2LT) was estimated using Kaplan-Meier method. Results: In 210 Australian patients, 12% were never smokers & 77.6% had non-squamous histology (NSH). 62% (n = 130) received 2LT, 26% (n = 55) received 3L+ treatment (3L+T). The top three 1LT were carboplatin+gemcitabine (n = 112, 53%), carboplatin+paclitaxel (n = 19, 9%), cisplatin+etoposide (n = 10, 5%). 59% (n = 77) of patients received single agent 2LT, 49% of non-squamous patients (NSP) received pemetrexed (n = 50), 29% of squamous patients (SP) received docetaxel (n = 4). 95% of patients (n = 200) had a biopsy performed. Of 163 NSP, 72% (n = 117) received BMx. 98% (n = 115) received an EGFR test, 23% (n = 27) of which were positive. Median OS from start of 1LT & 2LT was 11.6 & 7.9 months respectively. In 150 Korean patients, 34% (n = 51) were never smokers & 75% had NSH. 64% (n = 96) received 2LT and 39% (n = 59) received 3L+T. The top three 1LT were carboplatin+paclitaxel (22%, n = 33), carboplatin+gemcitabine (21%, n = 31), carboplatin+pemetrexed (20%, n = 30). Majority of 2L patients received anti EGFR /anti ALK therapy (n = 50, 52%), most commonly gefitinib (27%, n = 26) and erlotinib (24%, n = 23). 94.0 % of patients (n = 141) had ≥ 1 biopsy performed. Of the 113 NSP, 89% (n = 101) were tested. 97% (n = 101) received an EGFR test, 40% (n = 39) of them were positive. Median OS for Korea from start of 1LT & 2LT was 11.1 and 6.0 months respectively. The average inpatient stay was 15.5 & 13.8 days/admission & the total inpatient admissions were 723 & 618 for Australia & Korea respectively. Conclusions: Platinum combination is commonly used 1LT, pemetrexed in Australia & anti-EGFR agents in Korea are commonly used 2LT in NSP. Among NSP > 70% received BMX.
TCT-414 Patient-specific computer simulation to optimise transcatheter heart valve sizing and positioning in bicuspid aortic valve morphology
Authors: Cameron Dowling, Alessandra Bavo, Peter Mortier, Nahid El Faquir, Peter de Jaegere, Ole De Backer, Lars Søndergaard, Philipp Ruile, Darren Mylotte, Hannah McConkey, Ronak Rajani, Jean-Claude Laborde, Stephen Brecker
Journal: Journal of the American College of Cardiology (2018)
Mortality and Other Studies Questioning the Evidence for and Value of Routine Anticoagulant Therapy in Acute Myocardial Infarction
Authors: Sidneyschnur
Journal: Circulation (1953)

This study of 1350 patients with acute myocardial infarction admitted to several hospitals during a 10-year period attempts to answer several questions currently in dispute: the correlation of the patient's condition on admission with the mortality rate, the relation of the patient's age to prognosis, and the value of routine anticoagulant therapy. It presents the major statistical objections to the study by the Committee for the Evaluation of Anticoagulants of the American Heart Association, questions the evidence upon which the Committee made its recommendations and concludes that incontrovertible proof of the advantages of routine anticoagulant therapy in patients mildly ill on admission to the hospital has not been presented thus far.
A proposal for a new staging system for extranodal natural killer T-cell lymphoma, nasal type, to predict the treatment strategy: A multicentre study from the Chinese Southwest Oncology Group and Asia Lymphoma Study Group.
Authors: Tongyu Lin, Huangming Hong, Yexiong Li, Soon Thye Lim, Chaoyong Liang, He Huang, Pingyong Yi, Tao Wu, Xin Du, Mingzhi Zhang, Jinghua Wang, Jun Zhu, Gang Wu, Yuan Zhu, Zhigang Peng, Junxin Wu, Qing Liu, Won Seog Kim
Journal: Journal of Clinical Oncology (2018)

7552 Background: The survival of patients with extranodal natural killer T-cell lymphoma (ENKTL), a rare and highly aggressive malignancy, is not accurately predicted by the routine lymphoma Ann Arbor staging system (AASS). Therefore, an optimal staging system for ENKTL is warranted. Methods: A training cohort of patients with newly diagnosed ENKTL from 19 Chinese centres was assessed to develop a new staging system for ENKTL. The results were validated in an independent cohort including patients from Korea, Singapore and China. The new staging system was named the Chinese Southwest Oncology Group and Asia Lymphoma Study Group staging (CA) system. Results: Based on analyses of the 1168-patient training cohort, the CA system used the following classification scheme: stage Ⅰ, lesions confined to the nasal cavity or nasopharynx without local invasiveness; stage Ⅱ, non-nasal-type disease or lesions confined to the nasal cavity or nasopharynx with local invasiveness and without lymph node involvement; stage Ⅲ, lesions with regional lymph node involvement; and stage Ⅳ, involvement of lymph nodes on both sides of the diaphragm or disseminated disease. The 5-year OS rates for stages Ⅰ through Ⅳ were 60.7%, 42.9%, 17.5%, and 32.1% for the AASS and 70.8%, 53.1%, 38.6%, and 29.9% for the CA (P < 0.001). Patient distribution was more balanced with CA than with the AASS. The 985-patient validation cohort produced similar survival and distribution results to those of the training cohort. CA exhibited better prognostic value than the AASS for all 2153 patients (ROC, 0.69; 95% CI, 0.64-0.74 vs 0.62; 95% CI, 0.68-0.56; P = 0·01) and predicted that the best treatment choice based on non- anthracycline treatment was radiotherapy alone for stage Ⅰ; chemotherapy combined with radiotherapy, regardless of the treatment sequence, for stage Ⅱ; induction chemotherapy followed by radiotherapy for stage Ⅲ; and intensive chemotherapy for stage Ⅳ patients. Conclusions: The CA system outperformed the AASS in staging ENKTL patients and could be useful for treatment strategy prediction and future clinical trial design.
Treatment effect of neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy on breast cancer outcomes.
Authors: Ashley Pariser, Sarah Schellhorn Mougalian, Tannaz Sedghi, Cary Philip Gross, Brigid K. Killelea
Journal: Journal of Clinical Oncology (2018)

e12630 Background: Over the last decade, there has been increased use of neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor (HR) positive breast cancer. Small clinical trials have demonstrated that for certain patients, NET is associated with similar rates of both complete response (CR) and similar rates of breast conservation surgery (BCS) compared to neoadjuvant chemotherapy (NAC). We aimed to compare the effectiveness of NET versus NAC with regards to complete pathologic response (pCR), change in stage, and breast conservation Methods: We performed a population-based assessment using the National Cancer Data Base to identify women diagnosed with stage II-III, HR-positive BC who received NET or NAC from 2004 through 2014 and subsequently underwent surgery. We ran logistic regression models to assess differences in outcomes between therapies, with inverse probability of treatment weighting using the propensity score to adjust for potential selection bias. Results: In our sample of 58,894 patients, 6584 received NET (11.2%) and 52,310 (88.8%) received NAC. NET was more frequently used in older women with multiple comorbid conditions, larger tumors, and higher nodal stage. After adjusting for multiple relevant covariates and cofounders, there was no significant difference between NET and NAC with regard to breast conservation (OR 0.91; 95% CI (0.82-1.01). Women who received NET were significantly less likely than those who received NAC to experience a pCR (OR 0.34; 95% CI (0.23-0.51) or a decrease in T stage (OR 0.39; CI (0.34-0.44). Conclusions: Our multivariate analysis determined that the odds of breast conservation remains equivalent between NET and NAC for women with HR-positive BC. Further research is needed to determine the population most likely to benefit from NET as it is infrequently utilized presently for neoadjuvant therapy.
Effect of ONC201 and bortezomib on apoptosis in non-Hodgkin's lymphoma (NHL) xenografts.
Authors: Mala Kiran Talekar, Junior Hall, Gerald B Wertheim, Daniel Martinez, Joshua E. Allen, Stephan A. Grupp
Journal: Journal of Clinical Oncology (2017)

e19016 Background: Our group has previously shown preclinical in vitro efficacy of novel small molecule, ONC201 across several pediatric NHL cell lines (Talekar et al, 2015) as a monoagent as well as in combination with chemotherapy agents, significantly cytarabine and bortezomib. We investigated the preclinical efficacy of ONC201 and bortezomib combination in vivo in a NHL mouse xenograft model. Methods: Burkitt’s lymphoma cell line (Ramos) transduced with lentiviral GFP was utilized to establish subcutaneous flank xenografts in 5-7 week(wk) old immunodeficient SCID mice [NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ]. All tumors were established by Day 10, detected by bioluminescent imaging and were serially imaged x1/wk. Mice were studied in 4 treatment arms (7 mice per arm) as tabulated in the table. Results: Mice in Arms 1, 2 &amp; 3 had continued tumor growth and were humanely euthanized during Wk 3- 4 of treatment when the tumor volume reached the maximum allowable size per the approved institutional IACUC protocol. Mice in Arm 4 showed gross tumor necrosis and had to be euthanized in Wk 4. Upon treatment initiation, 2 mice in each arm were sacrificed at 48 and 72 hours respectively and tumor samples harvested for histology and IHC analysis (TRAIL and CHOP/GADD). Histological analysis revealed that the control group had predominantly viable tumor cells at both 48 &amp; 72 H. The monoagent groups showed minimal cell death with bortezomib alone and modest cell death with ONC201 as monoagent in clustered regions. In contrast, the combination group showed: i) extensive global tumor necrosis with nuclear debris on H&amp;E, ii) prominent TRAIL induction by IHC analysis, and, iii) significant apoptotic cell death accompanied by CHOP /GADD overexpression indicating potential ER stress. Induction of these pharmacodynamic markers in Arm 4 were evident at 48H and more prominent at the 72H. Conclusions: ONC201 effectively synergizes with bortezomib to cause apoptotic tumor cell death in pediatric NHL murine xenograft and merits further investigation. [Table: see text]
A phase II trial of enzalutamide, docetaxel and androgen deprivation therapy (ENZADA) in patients with metastatic castrate sensitive prostate cancer (mCSPC).
Authors: Earle Frederick Burgess, Claud Grigg, Peter E Clark, Danielle Boselli, James Thomas Symanowski, Derek Raghavan
Journal: Journal of Clinical Oncology (2018)

TPS5094 Background: The addition of docetaxel (Doc) or abiraterone to androgen deprivation therapy (ADT) in men with mCSPC improves survival. Whether the triple combination of ADT, Doc and next generation endocrine therapy further improves patient outcome is unknown. Enzalutamide (Enz) is a potent anti-androgen that has activity in the advanced, castration-resistant setting. Preclinical data support the use of Enz in combination with Doc. Enz inhibits the ABCB1 drug efflux pump implicated in Doc resistance, and Doc may eradicate Enz-resistant clones harboring the androgen receptor splice variant 7 (ARv7). The combination of Enz with Doc at standard doses was safe in the phase I setting. This study tests the hypothesis that men with newly diagnosed mCSPC may benefit from adding Enz to standard Doc and ADT. Methods: This is a phase II, single arm trial of Enz plus Doc and ADT in men with newly diagnosed mCSPC. The study is designed to enroll 39 eligible participants who must have metastatic prostate adenocarcinoma with confirmed soft tissue and/or skeletal metastasis, ECOG 0-2, and PSA ≥ 5. Subjects who previously received up to 3 years of ADT with radiation for localized disease are eligible if ADT was discontinued > 6 months before diagnosis of mCSPC and testosterone recovery is confirmed. Prior treatment with cytotoxic chemotherapy or next generation endocrine therapy is not allowed. Patients will be stratified by volume of metastatic disease. Treatment consists of Doc 75 mg/m2 IV every 3 weeks for 6 cycles and Enz 160 mg daily commencing at enrollment and continued until radiographic progression or study withdrawal. Continuous ADT is required during the study period. The primary endpoint is 12-month PSA complete response rate. Secondary endpoints include adverse events, best PSA response, radiographic objective response, time to castration resistance, progression free and overall survival. Exploratory biomarker analysis includes sequential measurement of circulating tumor cell (CTC) levels and CTC ARv7 status during study treatment. Clinical trial information: NCT03246347.
Ablation of phospholamban rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+/calmodulin kinase II constitutive phosphorylation of ryanodine receptors
Authors: Carlos A Valverde, Gabriela Mazzocchi, Mariano N Di Carlo, Alejandro Ciocci Pardo, Nehuen Salas, María Ines Ragone, Juan I Felice, Alejandra Cely-Ortiz, Alicia E Consolini, Enrique Portiansky, Susana Mosca, Evangelia G Kranias, Xander H T Wehrens, Alicia Mattiazzi
Journal: Cardiovascular Research (2018)

Abstract Aims Abnormal Ca2+ release from the sarcoplasmic reticulum (SR), associated with Ca2+-calmodulin kinase II (CaMKII)-dependent phosphorylation of RyR2 at Ser2814, has consistently been linked to arrhythmogenesis and ischaemia/reperfusion (I/R)-induced cell death. In contrast, the role played by SR Ca2+ uptake under these stress conditions remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to attenuate reperfusion arrhythmias and cardiac injury elicited by increased RyR2-Ser2814 phosphorylation. Methods and results We used WT mice, which have been previously shown to exhibit a transient increase in RyR2-Ser2814 phosphorylation at the onset of reperfusion; mice with constitutive pseudo-phosphorylation of RyR2 at Ser2814 (S2814D) to exacerbate CaMKII-dependent reperfusion arrhythmias and cardiac damage, and phospholamban (PLN)-deficient-S2814D knock-in (SDKO) mice resulting from crossbreeding S2814D with phospholamban knockout deficient (PLNKO) mice. At baseline, S2814D and SDKO mice had structurally normal hearts. Moreover none of the strains were arrhythmic before ischaemia. Upon cardiac I/R, WT, and S2814D hearts exhibited abundant arrhythmias that were prevented by PLN ablation. In contrast, PLN ablation increased infarct size compared with WT and S2814D hearts. Mechanistically, the enhanced SR Ca2+ sequestration evoked by PLN ablation in SDKO hearts prevented arrhythmogenic events upon reperfusion by fragmenting SR Ca2+ waves into non-propagated and non-arrhythmogenic events (mini-waves). Conversely, the increase in SR Ca2+ sequestration did not reduce but rather exacerbated I/R-induced SR Ca2+ leak, as well as mitochondrial alterations, which were greatly avoided by inhibition of RyR2. These results indicate that the increase in SR Ca2+ uptake is ineffective in preventing the enhanced SR Ca2+ leak of PLN ablated myocytes from either entering into nearby mitochondria and/or activating additional CaMKII pathways, contributing to cardiac damage. Conclusion Our results demonstrate that increasing SR Ca2+ uptake by PLN ablation can prevent the arrhythmic events triggered by CaMKII-dependent phosphorylation of RyR2-induced SR Ca2+ leak. These findings underscore the benefits of increasing SERCA2a activity in the face of SR Ca2+ triggered arrhythmias. However, enhanced SERCA2a cannot prevent but rather exacerbates I/R cardiac injury.
BSPD guidelines for treatment of IH with propranolol
Authors: L. Solman, M. Glover, P.E. Beattie, H. Buckley, S. Clark, J.E. Gach, A. Giardini, I. Helbling, R.J. Hewitt, B. Laguda, S.M. Langan, A.E. Martinez, R. Murphy, L. Proudfoot, J. Ravenscroft, H. Shahidullah, L. Shaw, S.B. Syed, L. Wells, C. Flohr
Journal: British Journal of Dermatology (2018)

Infantile haemangiomas (IH) are common birthmarks in babies consisting of dilated blood vessels. They are also known as strawberry naevi. Most of them grow for a few months, then gradually shrink spontaneously over a period of months or years. However, in about 15% of cases they can cause serious functional problems when they involve important structures such as the eye, ear, mouth, nose and the peri‐anal area. In addition they can sometimes resolve, but leaving significant disfigurement. In 2008 it was reported that the beta‐blocker drug propranolol, given orally (by mouth), was very effective in causing these birthmarks to shrink rapidly. This paper is designed to provide guidance to doctors on how best to administer propranolol to children with IH. Developing the guidelines involved several stages: an international survey of current practice in eight European countries; a systematic review of the literature; collecting current local guidelines from 19 centres leading to the generation of 70 statements. These 70 statements were then scrutinised by 19 experts from relevant specialities (Dermatology, Paediatrics, Paediatric Cardiology and Paediatric ENT surgery). Using an established research protocol, agreement was reached by these experts on 47 statements covering eight categories. These categories include: indications for starting propranolol (i.e. it which situations it should be used); contraindications (i.e. in which situations it should not be used); pre‐treatment tests needed; initiation of treatment; monitoring during treatment and when to stop treatment. They also cover treatment of children with additional medical complications.Although these guidelines are UK‐based, the authors hope that they will be useful in other European countries also.
Glycemic disorders in melanoma patients treated with anti-PD1.
Authors: Quentin Magis, Caroline Gaudy Marqueste, Sandrine Monestier, Anderson Loundou, Marie-Aleth Richard, Nausicaa Malissen, Sophie Beliard, Jean-Jacques Grob
Journal: Journal of Clinical Oncology (2017)

9525 Background: Anti-PD1 are now the backbone of immunotherapy (IT) of metastatic melanoma (MM). Although they are overall well- tolerated, a number of severe immune-related adverse events (IRAE) have been described, among which type 1 diabetes. We observed 3 cases of fulminant diabetes (FD) in our center, and also had the impression that diabetics patients became more difficult to manage when receiving anti-PD1. Methods: Retrospective analysis of blood glucose samples collected before, during and after anti-PD1 treatment (trt ) in all mm patients (pts) receiving anti-PD1 in our department over a 36-month period. Study of FD cases observed. Results: A total of 163 pts were treated with 1920 cures of anti-PD1 including 27 treated within clinical trials. Anti-PD1 was the 1 st line of IT in 70% of cases. As a whole, 1470 glycaemia were available. There was no significant difference between the median pre and post-trt glycaemia (5.37 +/-1.6 vs 5.6 +/-1.3 mmol/L (p = 0.033)). In the 28 pts with a type I (n = 0) or II (n = 28) diabetes prior to trt, there was very slight drift toward an increase of glycaemia along with the successive trt infusions (+0.05mmol/L/Cure, p = 0.004 with linear regression tendency test) .Three pts (1.84%) developed a FD revealed by a severe episode of ketosis with acute polyuria polydipsia, hyperglycaemia until 50mmol/L and weight loss. Two additional cases of FD were observed in pts treated within clinical trial comparing anti-PD1 with anti-CTLA4 in adjuvant and metastatic situation (imputability of anti-PD1 likely but uncertain until unblinding). None of these pts had any glucose increase in weeks prior to FD diagnosis. Four out of 5 FD cases had an HLA group at risk for type 1 diabetes development (HLA DRB3/4), a rare group in general population (1%). Conclusions: We could not document any systematic tendency to glycemic disorder in mm pts treated by anti-PD1. In diabetic pts prior to trt, a slight drift toward increase of glycaemia may be explained by other interfering factors (diet, metastatic disease itself, corticosteroids, anxiety etc). FD is not exceptional (2% of patients in our series) and does not seem to be announced by any minor preliminary glycemic disorder. Despite apparently stochastic onset, FD may be associated with HLA DRB3/4 subgroup.