tbuckley/cabot-search huggingface dataset:
P02.15 Expression and prognostic value of HER3 and HER4 in meningiomas - an immunohistochemical study
Authors: M B Arnli, S H Torp
Journal: Neuro-Oncology (2018)

Meningiomas are the most common primary intracranial tumors in adults. Despite their benign histology and slow growth, recurrence is rather frequent and unpredictable. Save morphological features, meningiomas lack both diagnostic and prognostic markers. HER3 and -4 are receptor tyrosine kinases (RTKs) of the EGFR family, and their expression and clinical role in meningiomas are scarcely explored. Expression of HER3/-4 was analyzed by immunohistochemistry in 186 human meningiomas on tissue microarrays (TMA), incorporating 129 benign, 56 atypical, and one malignant tumor. Semi-quantitative scores of expressions ranging from 0 to 9 were related to prognosis and WHO malignancy grade. HER3 was positive in 181/184 tumors with an average score of 8.51/9.00, and HER4 was positive in 182/183 tumors with an average score of 8.05/9.00. For both markers, staining was stronger in the cytoplasm than in the cellular membrane. Strong nuclear staining was observed for HER4 in most tumors. Non-neoplastic meninges were negative. There was no association between overall expression levels and survival (endpoints: time to recurrence and overall survival) or WHO malignancy grade (I vs II/III). Our immunohistochemical study revealed strong overexpression of both HER3 and HER4 in human meningiomas. However, there was no association to either survival, recurrence or malignancy grade. Thus, these two receptor proteins might assist in the work-up of meningiomas as diagnostic markers, whereas their prognostic value is doubtful.
Opioid Death Rate Acceleration in Jurisdictions Legalizing Marijuana Use
Authors: Archie Bleyer, Brian Barnes
Journal: JAMA Internal Medicine (2018)

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Patient blood management program in oncological surgery: A multicenter prospective study.
Authors: Alessandro Bonini, Lucia Merolle, Erminia Di Bartolomeo, Pamela Berni, Agostino Rossi, Chiara Marraccini, Monica Guberti, Thelma Pertinhez, Roberto Baricchi
Journal: Journal of Clinical Oncology (2018)

e18793 Background: Patient blood management (PBM) is an evidence-based, multidisciplinary and multimodal approach aiming to optimize the care of patients (pts) who might need blood transfusions.This study was designed to investigate the impact of PBM on transfusion appropriateness of consecutive oncological pts submitted to major surgery in two hospitals of Emilia Romagna-Italy. Methods: We conducted an observational, prospective, multicenter study between 2014 and 2017. We assessed the PBM impact by evaluating the number of pts transfused with Red Blood Cells (RBCs) units and the transfusion appropriateness. The evaluation has been limited to the post-operative period and was divided in 3 phases. Phase 1: baseline clinical audit on 400 consecutive pts, before PBM implementation, without any intervention; Phase 2: 3 months of teaching activity for personnel involved in the care of pts, followed by a second clinical audit on 300 pts; Phase 3: introduction of Point of Care (POC, Radical 7, Masimo) for continuous monitoring of hemoglobin level and perfusion pressure index on 228 consecutive pts in the post-operative period, followed by the enumeration of transfused pts. The study has been carried out at the Oncological Surgery Arcispedale Santa Maria Nuova AUSL-IRCCS in Reggio Emilia and at the Ospedale G. Saliceto in Piacenza. Results: 928 oncological pts were included in the analysis (Phase 1: 400; Phase 2: 300; Phase 3: 228). The 3 groups were similar according to gender, age, disease and kind of surgery. Baseline clinical audit evidenced an appropriateness of 50% (26/52 pts); whereas after phase 2 (teaching and training activity) the appropriateness of transfusion therapy increased to 76% (62/81 pts) After the insertion of POCs (Phase 3) the transfused pts were 39/228. Conclusions: In our experience the majority of pts receive transfusions during the post operative period. The preliminary evaluation showed that the application of PBM principles seemed to be an effective intervention for pts with cancer treated with surgery, providing a systematic approach to increase the appropriateness of transfusion therapy.
Career Development and Oncology Education in Europe: Final results from a survey conducted by the Hellenic Group of Young Oncologists (HeGYO).
Authors: Nikolaos Tsoukalas, Eleni Aravantinou-Fatorou, Konstantinos Kamposioras, Athanasios Korogiannos, Vasileios Papadopoulos, Ioannis Kostakis, George Lazaridis, Michail Nikolaou, Evangelos Voulgaris, Michael Liontos, Kostas Tsigaridas, Evangelos Bournakis, Athanasios Athanasiadis, Gerasimos Aravantinos, Alexandros Ardavanis, Ioannis Boukovinas, Eleni P. Galani, Giannis Mountzios, Zacharenia Saridaki, Ioannis Varthalitis
Journal: Journal of Clinical Oncology (2016)

e18202 Background: The importance of continuous medical education in oncology is obvious. The aim of this study was to shed light on the current status in Europe and to identify any obstacles in career development. Methods: Residents and specialized medical, clinical and surgical oncologists from Europe were invited to complete a comprehensive forty multiple-choice web-questionnaire. The study was kindly endorsed by scientific organizations such as ESMO YOC, ECCO, ESO and HeSMO. Results: These are the final results from 234 participants (61.1% males) who completed the questionnaire from 2/2015 to 1/2016. 70.1% are from Greece and 29.9% from 16 other European countries. 57.3% are 30-40 years old, 67.5% are medical oncologists while 37.2% are residents. 59.8% are ESMO and 30.3% ASCO members. 28.6% have ESMO accreditation, 30.3% GCP and 32.9% PhD degree. Interestingly, 35.5% were partly trained in two or more countries and 35% received further post-residency training in a specialized oncology center. Notably, 16.2% are not familiar with the ASCO/ESMO global core Curriculum in Medical Oncology and 19.2% feel dissatisfied with their training. 44% attend 1-3 national congresses and 70.5% 1-3 international congresses per year. More than 50% consider ASCO and ESMO website/newsletters useful and nearly 20% and 50% participated in ASCO or ESMO fellowships/educational activities respectively. Lack of time and financial issues are considered as the main problems for continuous professional development while clinical practice and on-line medical resources are considered the most effective ways to achieve continuous medical education. 54.7% consider clinical practice as their main career priority while 21.4% consider clinical research. Overall, 24.4% feel dissatisfied with their mentor’s guidance, 19.2% feel dissatisfied with their official training, 20.1% are not satisfied with their CV but 68.4% feel satisfied with their current job. Conclusions: It is apparent that oncologists are thriving for education. Although lack of time is identified as the greatest obstacle, most of them try to keep up-to-date with educational activities and web-based medical resources.
Pulmonary Venous Waveforms Predict Rehospitalization and Mortality After Percutaneous Mitral Valve Repair
Authors: Frank E Corrigan, John H Chen, Aneel Maini, John C Lisko, Lucia Alvarez, Norihiko Kamioka, Shawn Reginauld, Patrick T Gleason, Jose F Condado, Jane Wenjing Wei, Jose N Binongo, Patricia Keegan, Sharon Howell, Vinod H Thourani, Peter C Block, Stephen D Clements, Vasilis C Babaliaros, Stamatios Lerakis
Journal: JACC. Cardiovascular imaging (2018)
Impact of cytogenetics on myeloma immune microenvironment as reflected by the absolute lymphocyte/monocyte ratio.
Authors: Talib Dosani, Hugo Akabane, Marcos J.G. De Lima, James Joseph Driscoll, Ehsan Malek
Journal: Journal of Clinical Oncology (2016)

e23109 Background: Critical interactions with the bone marrow microenvironment promotes the homing, proliferation and survival of multiple myeloma (MM) cells. Specific cytogenetic abnormalities harbored within MM cells provide prognostic value, however their specific impact on the myeloma microenvironment is largely unknown. Tumor-associated macrophage content in MM microenvironment, reflected by the peripheral blood absolute monocyte count (AMC), represents a prominent element of tumor-related inflammation and predicts poor outcome in MM (Suyaný, Annals of hematology. 2013). The aim of the present study was to investigate the impact of specific cytogenetic derangements on absolute lymphocyte count (ALC), as surrogate of host immune status, and AMC, reflective of the MM-immune microenvironment. Methods: The study involved 325 MM patients (pts), diagnosed 2007-2014 at the University Hospitals in Cleveland and Cincinnati, OH. 155 pts met criteria and had cytogenetics and CBC differential at diagnosis.. Pts were stratified into hierarchical cytogenetic groups and multivariate regression modeling correlated cytogenetics with ALC, AMC and ALC/AMC. Results: Median pt age was 67 years (range 32-92 years), 54% were male and 46% female. There was no difference in the age distribution between the cytogenetic groups with a tendency for del(17p) to involve younger pts. The median AMC, ALC and ALC/AMC ratio at diagnosis was 410 cells/µL, 1,473 cells/µL and 3.6, respectively. Univariate analysis demonstrated that low ALC, high AMC and a low ALC/AMC ratio were correlated with presence of del(17p) and t(4,14) and light chain myeloma. Multivariate analysis indicated that the ALC and AMC were not associated with any specific cytogenetic group. However, the ALC/AMC ratio independently predict 17p and t(4,14) abnormalities (p = .041). Low ALC, high AMC, and low ALC/AMC ratio were associated with poor prognostic factors such as high β2-microglobulin. Conclusions: Multivariate analysis demonstrates that del(17p) and t(4,14) result in significant immuneparesis reflected by low ALC/AMC ratio. The mature data and subsequent analysis of progression-free and overall survival will be presented in the meeting.
A phase II study of pembrolizumab and paclitaxel in refractory extensive disease small cell lung cancer.
Authors: YuJung Kim, Bhumsuk Keam, Chan-Young Ock, Sanghoon Song, Miso Kim, Se Hyun Kim, Ki Hwan Kim, Jin-Soo Kim, Tae Min Kim, Dong-Wan Kim, Jong Seok Lee, Dae Seog Heo
Journal: Journal of Clinical Oncology (2018)

8575 Background: Patients with platinum refractory extensive disease (ED) small cell lung cancer (SCLC) have a poor prognosis and a little progress have been made. We aimed to investigate the efficacy and safety of pembrolizumab and paclitaxel in these patients. Methods: In this phase II, open-label, multi-center study, 26 patients who progressed after etoposide/platinum chemotherapy were enrolled. The patients received paclitaxel 175mg/m2 every 3 weeks for up to 6 cycles. Pembrolizumab 200mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analysis including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing (NGS), and flow cytometric analysis of peripheral blood immune cells. Results: The median age was 68.5 years, and 88% were male. Of the 26 evaluable patients, the ORR was 23.1% (complete response: 3.8%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease 7.7%, not evaluable 11.5%). Including unconfirmed PR, 38.4% responded, and disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI, 2.7-6.7) and 9.2 months (95% CI, 6.6-15.1), respectively. Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (8%), asthenia (8%), hyponatremia (8%) and type I diabetes (4%). Four patients showed PD-L1 positivity and no significant difference in PFS was observed according to PD-L1 positivity (5.0 vs. 3.9 months, P= 0.897). NGS was performed in 12 tumor samples, and we could not find significant differences in mutational load or specific genetic alteration, except for the MET copy number gain (PFS 10.5 vs. 3.4 months, P= 0.019). According to flow cytometric analysis, NK cell activity was significantly lower in responders after 2 cycles of treatment (P= 0.022). Conclusions: Pembrolizumab and paclitaxel combination therapy showed a moderate activity with an acceptable toxicity in refractory ED SCLC. Further studies are warranted to define a subset of patients who may benefit from the addition of pembrolizumab. Clinical trial information: NCT02551432.
Secretary leukocyte peptide inhibitor (SLPI) in pleural fluid is useful as a diagnostic marker of malignant pleural mesothelioma.
Authors: Nobukazu Fujimoto, Yoko Kojima, Takumi Kishimoto
Journal: Journal of Clinical Oncology (2017)

e23098 Background: There is no established diagnostic marker for malignant pleural mesothelioma (MPM). In particular, the differentiation from benign asbestos pleural effusion (BAPE) is challenging. Secretary leukocyte peptide inhibitor (SLPI) is an enzyme encoded by SLPI gene. SLPI gene is reported to be overexpressed in MPM cells. Methods: SLPI in pleural fluid was determined using Quantikine ELISA Human SLPI kit (R&amp;D Systems). Results: Exploratory research revealed that SLPI value in pleural fluid of patients with MPM (n = 52) were significantly higher than those in lung cancer (LC) (n = 69) and BAPE (n = 50) ( P= 0.000). Prospective validation study included 12 pts of MPM, 24 pts of LC, 26 pts of BAPE. Median values of SLPI in MPM, LC, and BAPE were 159 .6 ng/ml, 90.5 ng/ml, and 43.2 ng/ml, respectively. SLPI value in patients with MPM were significantly higher than those in other groups ( P= 0.000). Receiver operating characteristics ROC) analysis was performed to examine the usefulness of differentiation of MPM and other diseases, and demonstrated that area under the curve (AUC) value was 0.758. With the cut of value of 88.6 ng/ml, the sensitivity was 83.3% and the specificity was 59.8%. Concerning the differentiation between MPM and BAPE, AUC value was 0.904 and with the cut of value of 81.8 ng/ml, the sensitivity was 83.3% and the specificity was 92.3%. Conclusions: Pleural fluid SLPI is a useful biomarker for the diagnosis of MPM, in particular, for the differentiation from BAPE.
Efficacy of abiraterone or enzalutamide following docetaxel chemotherapy in the hormone-sensitive setting.
Authors: Nick Waldron, Thomas Young, Athanasios Pouptsis, Ramin Ajami, Debra Hannah Josephs, Simon Hughes, Stephen Morris, Sarah Maria Rudman, Deborah Enting, Simon Chowdhury
Journal: Journal of Clinical Oncology (2018)

e17022 Background: Docetaxel is now a standard of care for the treatment of newly diagnosed castrate-sensitive metastatic prostate cancer. However, the PREVAIL, AFFIRM and COU-AA studies demonstrating efficacy of enzalutamide and abiraterone in castration-resistant prostate cancer did not include patients treated in the castrate-sensitive setting with “upfront docetaxel”. Additionally, few patients in STAMPEDE received enzalutamide ( < 10%) or abiraterone ( < 25%) on progression, and no efficacy data has been reported. Efficacy of second-generation hormonal therapy following upfront docetaxel is not known. Methods: All patients at our institutions treated with upfront docetaxel were retrospectively identified using the chemotherapy database. Data collected included baseline characteristics, time to progression, subsequent treatment, response rate, time to progression to third line therapy, and duration of each treatment. Results: 71 patients received upfront docetaxel chemotherapy between 30/06/14 and 06/12/17. Median follow up was 14.5 months. 31 patients (45.1%) had progressed post-chemotherapy; 22/31 (71.0%) received enzalutamide, 8 abiraterone, and 1 cisplatin/etoposide. 13 out of 31 (41.9%) patients treated with enzalutamide or abiraterone achieved a PSA response of > 50% reduction from baseline to second-line treatment; 11/22 treated with enzalutamide (50.0%), and 2/8 treated with abiraterone (25.0%). 17 of the 31 patients (54.8%) progressed to third line treatment or death, with a median time to progression from starting second-line treatment of 124 days (range 65-480). Conclusions: Abiraterone and enzalutamide show efficacy as second-line therapies after upfront docetaxel, with combined PSA response rate of 41.9% in our cohort, but PSA response rates were lower and time to next therapy shorter than in the pivotal phase three studies. These results may be explained by a relative short follow-up period, selection of ‘early’ progressing patients with biologically more aggressive cancer, or by the non-trial population in this cohort. Further study is needed to understand the impact of upfront docetaxel on subsequent treatments for metastatic prostate cancer.
Impact of competitive landscape and ownership dynamics on oncology combination pricing.
Authors: Priya Madhavan, Katherine Infante, Bryan Harris, John Thomas Lucas, Colin Nash
Journal: Journal of Clinical Oncology (2018)

e18942 Background: Over the years, branded oncology combination therapies have become more widespread and expensive. This analysis aims to evaluate how number of competitors and ownership dynamics influence pricing of combination therapies. Methods: The study focused on seven recently approved combination oncology therapies across various indications, which were evaluated by the European HTAs. After a deep dive assessment of the selected analogues (i.e., HTA and pricing and reimbursement review), we identified product characteristics, unmet need, number of competitors and ownership dynamics as key pricing considerations. We calculated costs as cost/course and cost/month in USD and the scope markets included US, France, Germany, Italy, Spain, UK and Japan. Results: Considering the relationship between price and competition within a therapeutic area, we see that only 43% of therapies were the first combination regimen to launch in their respective indication. While limited given the small sample size, a minor correlation exists between number of competitors and price, where a greater number of competitors within a therapeutic area is associated with a lower pricing potential. Concerning the ownership dynamics, regional trends were observed among 57% of oncology combination therapies with multiple owners and 43% of therapies with single owners. In the US, majority of combination regimens developed by multiple manufacturers were associated with higher prices. In the EU, however, price of regimens developed by single or multiple manufacturers were comparable, indicating clinical efficacy is more impactful on combination price potential than ownership dynamics. Conclusions: While clinical efficacy continues to be the primary driver of a positive HTA evaluation, competition will decrease payer willingness to pay as more competitors within an indication enter the marketplace. As the number of combination regimens increases in oncology, competition will play a key role in the assessment and pricing of combination therapies.
Adding oxaliplatin (OX) to neoadjuvant therapy of locally advanced rectal cancer (LARC): Still a promising option?
Authors: Wojciech Rogowski, Lucjan Wyrwicz, Violetta Sulzyc-Bielicka
Journal: Journal of Clinical Oncology (2018)

e15570 Background: Fluoropyrimidine (5-fluorouracil or Capecitabine, FU)-based regimens and radiation are standard-of-care in neoadjuvant treatment of patients with LARC. Meta-analysis (2012) showed, that adding OX to FU significantly improved pathologic complete response (pCR), and reduced peri-operative metastases with significantly higher toxicity rate. Aim: to review a literature published after 2012, assessing the role of OX in neoadjuvant treatment of LARC and to consider meta-analysis feasibility. Methods: we searched PubMed, EMBASE, and Cochrane library after 2012 to select the studies with neoadjuvant OX. We also searched trial registries and conference proceedings with variably combined key words. Results: we identified 66 different studies with numerous phase II and III trials, including more than 3000 patients in total. They evaluated adding OX to existing chemotherapy (CHT) regimens (mFOLFOX6), combinations with drugs from other class (antiangiogenic – bevacizumab) or new drugs (S-1), and also combination with radiotherapy (RTH) with CHT given prior to, concomitant with, or following g RTH. Other category includes studies with combination with surgical treatment. Unfortunately, there are very different endpoints analyzed: resection rate, sphincter rate, pCR, downstaging, local-regional tumor event rate, local-regional tumor recurrence, DFS, OS. Results from elected studies are contradictory; some studies show that: adding OX to mFOLFOX6 is safe, effective and reasonable option; increasing of proportion of patients eligible for invasive treatment; significant improvement of DFS. On the other hand, others show that adding OX does not improve local-regional disease control, DFS, and OS. Conclusions: variety of studies published since 2012 till date will be presented and discrepancies regarding their results will be also discussed. We will also present some assumptions as regard to further up-dated meta-analysis.
TCT-672 Trends in Utilization of Surgical and Transcatheter Mitral Valve Repair in the United States
Authors: Tanush Gupta, Sahil Khera, Dhaval Kolte, Kashish Goel, J. Dawn Abbott, Gregg Fonarow, Chet Rihal, Deepak Bhatt, Giora Weisz
Journal: Journal of the American College of Cardiology (2018)