tbuckley/cabot-search huggingface dataset:
Monitoring of the central blood pressure waveform via a conformal ultrasonic device
Authors: Chonghe Wang, Xiaoshi Li, Hongjie Hu, Lin Zhang, Zhenlong Huang, Muyang Lin, Zhuorui Zhang, Zhenan Yin, Brady Huang, Hua Gong, Shubha Bhaskaran, Yue Gu, Mitsutoshi Makihata, Yuxuan Guo, Yusheng Lei, Yimu Chen, Chunfeng Wang, Yang Li, Tianjiao Zhang, Zeyu Chen, Albert P. Pisano, Liangfang Zhang, Qifa Zhou, Sheng Xu
Journal: Nature Biomedical Engineering (2018)
Cost-effectiveness of maintenance therapy in advanced ovarian cancer: Paclitaxel, bevacizumab, niraparib, rucaparib, olaparib, and pembrolizumab.
Authors: Juliet Elizabeth Wolford, Jiaru Bai, Lindsey E. Minion, Robin Keller, Ramez Nassef Eskander, John K. Chan, Bradley J. Monk, Krishnansu Sujata Tewari
Journal: Journal of Clinical Oncology (2018)

5508 Background: Acquired drug resistance remains the greatest clinical hurdle in advanced ovarian cancer suggesting that effective maintenance therapies are lacking. We evaluated cost-effectiveness of available strategies, adjusting for pre-treatment medication costs, infusion center charges, and costs of managing adverse events. Methods: Registration trial data was used to obtain toxicity and median PFS for a) paclitaxel (GOG 212); b) bevacizumab (GOG 218, ICON 7, OCEANS, GOG 213); c) niraparib (NOVA), olaparib (SOLO-2), rucaparib (ARIEL-3); and d) pembrolizumab. Because anti-angiogenesis therapy was studied in different populations, each trial was modeled separately. As phase III randomized trials involving checkpoint inhibition in ovarian cancer are not mature, data for pembrolizumab (available via agnostic indication) were obtained from the phase IB ovarian cohort of KEYNOTE-028. Costs of germline/somatic BRCA testing and those associated with management of neuropathy and immune-mediated adverse events, including endocrinopathies, also factored into the model. Utilizing a Markov chain, patients transitioned through response, hematological and non-hematological complications, progression, and death. Using Medicare data, the costs of infusions and managing toxicities were estimated. Incremental cost-effectiveness ratios (ICER) and quality of adjusted life-months gained were determined for each therapy. Results: Maintenance paclitaxel was most cost-effective at $870/PFS month. Expected costs of PARP inhibitors (PARPi(s)) prior to progression were approx. $471,989 (18.8x paclitaxel, 6.9x pembrolizumab, and 2.2-2.7x bevacizumab). Comparing pembrolizumab to PARPi(s) in BRCA-deficient patients, anti-PD-1 maintenance yielded ICERs per month of life gained of $20,032 (niraparib), $18,444 (rucaparib), and $17,520 (olaparib). Conclusions: Using PFS as the benchmark, high costs of maintenance PARPi(s)/immunotherapy are not mitigated by adjusting for the sequelae that may manifest with maintenance chemotherapy/VEGF inhibition. In terms of economic toxicity, the current trend to study novel combinations is problematic.
Abstract 19479: Fibrosis Area Measured With Endomyocardial Biopsy Specimens Predicts Poor Long-Term Outcome of End-Stage Hypertrophic Cardiomyopathy
Authors: Yasuteru Nakashima, Yasuo Sugano, Toshiyuki Nagai, Hideki Kanzaki, Keiko Ogo, Yoshihiko Ikeda, Hastsue Ueda, Satoshi Yasuda, Toshihisa Anzai
Journal: Circulation (2016)

Background: Advanced left ventricular (LV) remodeling and decreased LV function infrequently develops in hypertrophic cardiomyopathy (HCM); generally called end-stage HCM. Despite highly poor prognostic feature of end-stage HCM, predictor of long-term outcome has not yet established. According to a recent report, late-gadlinium enhanced magnetic resonance imaging, which might reflect severity of myocardial fibrosis, could predict poor outcome of end-stage HCM. However, direct pathological evidence of myocardial fibrotic change has not been investigated thus far. Therefore, we sought to clarify the relationship between fibrosis area of endomyocardial biopsy sections and long-term outcome in end-stage HCM. Method: We studied consecutive 41patients of end-stage HCM (10 female, mean 55±14 years) between 2000 and 2014. All patients underwent cardiac catheterization including right ventricular endomyocardial biopsy to rule out secondary cardiomyopathies, sarcoidosis, amyloidosis or other metabolic heart disease...
Survival outcomes in patients with platinum-resistant (PL-R) ovarian cancer (OC): The Princess Margaret Cancer Centre (PM) experience.
Authors: Josee-Lyne Ethier, Lisa Wang, Amit M. Oza, Stephanie Lheureux
Journal: Journal of Clinical Oncology (2017)

e17049 Background: PL-R OC is associated with poor prognosis, and clinical trials indicate that overall survival (OS) is less than 12 months. Here, we describe real-world outcomes in patients with PL-R OC. Methods: Patients treated for PL-R OC presenting to PM from 2011-2015 were identified through the Oncology Patient Information System (OPIS) following research ethics board approval. Treatment data were extracted from OPIS. Baseline characteristics and survival data were obtained through linkage with the PM Survival Registry. Data were supplemented through individual chart review. OS was defined as time from first treatment for PL-R OC to date of death or last contact. Univariable and multivariable analyses were performed to assess the effect of patient characteristics (time from diagnosis to platinum resistance, OC subtype, tumor grade, PL-R or platinum-refractory [PL-RF] status, optimal debulking, clinical trial enrolment, number of treatment lines, germline BRCA1/2 status) on OS using cox proportional hazard models. P-values of 0.05 were considered significant. Results: Data from 165 patients with PL-R OC were included. Most patients had high grade (86%) and serous (84%) tumours. BRCA was mutated in 13%, wild-type in 49%, and unknown in 35%. The median number of lines received was 2 (range 1-6). Weekly paclitaxel (41%) and pegylated liposomal doxorubicin (41%) were the most common first-line regimens. Clinical trial participation was 36%. Median OS was 342 days (95% Confidence Interval 285-440), and was longer in PL-R (366 days) compared to PL-RF OC (302 days). Tumor grade and clinical trial participation were significantly associated with OS on univariable but not multivariable analysis. The number of treatment lines received for PL-R OC was independently predictive of OS (hazard ratio 0.63; p &lt; 0.001), but may reflect capacity for continued treatment in surviving patients (immortal time bias). Conclusions: Real-word outcomes in PL-R OC are similar to those observed in clinical trial populations, and are worse in PL-RF disease. Receipt of a greater number of treatments for PL-R disease is associated with longer OS, but may be due to immortal time bias.
Neoantigen-based personalized, immune cell therapy for patients with advanced NSCLC: A pilot study.
Authors: Zhenyu Ding, Li Yang, Han-Suo Yang, Heng Xu
Journal: Journal of Clinical Oncology (2018)

e15043 Background: Immune cell therapy remains a promising strategy for cancer therapy, however the lack of specificity restrains its application. Here a personalized, neoantigen-based dendritic cell (DC) therapy protocol was evaluated in this pilot study. Methods: Advanced NSCLC patients without standard of care with measurable tumor were enrolled. Whole exon sequencing was performed in DNA from the freshly obtained tumor tissues as well as the peripheral blood, while RNA-seq was performed in tumor-derived RNA. Somatic mutations were submitted to systematical program of neoantigen prediction, considering personalized MHC affinity, gene expression, tumor heterogeneity, and etc. Finally, 10-15 peptides with the highest score were synthesized and pulsed into PBMC-derived DC. DC was then introduced into patients together with cytokine-induced killer cells. All cells were prepared in a GMP workshop. The primary endpoint was safety and tolerability. Results: Totally six patients were enrolled up to now. All were adenocarcinoma with no known sensitive mutation. They were heavily treated (lines of previous therapy: 2, 5, 2, 2). Four out of these six patients (3 males and 1 female) finally received cell transfer, with one patient died rapidly before preparation of neoantigen-based cells, and the other one lacked candidate neoantigens. Patients 1 had 90% expression of PD-L1 on tumor cells while the other 3 patients were negative, while Patient 2 had been treated with nivolumab before enrollment. 35, 305, 51, and 68 candidate neoantigens were identified from each patient, respectively, and the top 10-15/patients were synthesized for DC cell stimulation. Totally 37 times of cell infusion was administered (8, 7, 17, and 5 for each). The cell infusion was safe and highly tolerable and no significant side effects were observed, even for those with poor performance. The treatment achieved SD in 3 patients, but it lasted for only 1-1.5 m in patient 1&2. Patient 3 remained well for 6 m and progressed. Patient 4 is now maintained on therapy. Conclusions: The neoantigen-based personalized immune cell therapy was highly tolerable without obvious side effects. Optimizations are required to improve anti-tumor efficacy. Clinical trial information: NCT02956551.
Comparative effectiveness of laparoscopic radical hysterectomy for cervical cancer.
Authors: Jung-Yun Lee, Jae-Weon Kim, Kidong Kim, Myong Cheol Lim, Jin Hee Kim
Journal: Journal of Clinical Oncology (2017)

e17015 Background: Despite the benefits of minimally invasive surgery for cervical cancer, population-level data describing the surgery’s effectiveness in unselected patients are lacking. We compared morbidity, cost, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. Methods: We used the Korean Health Insurance Review and Assessment Service database to identify women with cervical cancer who underwent radical hysterectomy from 2011 to 2014. Patient who underwent abdominal radical hysterectomy were compared with those who had minimally invasive hysterectomy. Perioperative morbidity, use of adjuvant therapy, and survival were evaluated. Results: We identified 6,335 patients including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. Uptake of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger and treated at larger hospital were more likely to undergo laparoscopic procedure (P&lt;0.001). Laparoscopic radical hysterectomy had lower rates of complication, less transfusion requirement, shorter hospital stays, and reduced total medical costs (P&lt;0.001). There was no significant association between use of laparoscopic approach and recurrence-free survival (P=0.194). Conclusions: Laparoscopic radical hysterectomy was associated with lower risk of perioperative complication and have comparable outcomes with abdominal radical hysterectomy.
Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) longitudinal monitoring of metastatic breast cancer (MBC).
Authors: Ricardo Lima Barros Costa, Giovanna Rossi, Zhaomei Mu, Laura Katherine Austin, Alfred Rademaker, William John Gradishar, Cesar Augusto Santa-Maria, Sarika Jain, Lisa E. Flaum, Francis J. Giles, Hushan Yang, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2016)

e23030 Background: Liquid biopsy provides a real-time assessment of MBC. We evaluated enumeration of CTCs and analysis of ctDNA to assess prognosis and detect molecular abnormalities in MBC. Methods: We conducted a prospective study 57 consecutive patients (pts) with locally advanced and MBC with a median follow-up of approximately 12 months. Pts had baseline and longitudinal assessment of CTCs using CellSearch system and ctDNA by Guardant360. A cutoff of ≥ 5CTCs (CTCs+) vs. < 5CTCs (CTCs-) was used for stratified overall survival (OS) analysis. A correlation analysis of ctDNA detected and CTCs was performed. Survival analysis testing was performed using Kaplan-Meier curves. Results: Fifty (88%) pts had stage IV and 70% had ER+ disease. The median follow-up was 11.3 months (0-25.6). 202 blood samples were collected. Thirty-eight pts had CTCs- and 19 pts had CTCs + at baseline. At the time of analysis 15 pts were deceased. Six of 19 CTCs+ at the last follow-up progressed with new sites of metastasis, including > 1 site (2 bone, 2 liver, 2 lung, 1 lymph nodes, (7 other sites)). The OS did not show statistically difference between CTCs- vs CTCs + (log rank p=0.07). The correlation between CTCs and number of ctDNA aberrations was as follows: # mutations = 0, 1 (n=24), 18 pts were CTCs- and 6 had CTC + disease (25%); # mutations = ≥ 2 (n=33), 20 were CTCs -, and 13 pts were CTC +(p= 0.39 by Fisher’s exact). The correlation between CTC enumeration and % ctDNA showed: CTC- (n=38), 17 patients had % ctDNA > 1.2; CTC + (n=19), 11 patients had % ctDNA > 1.2 (p = 0.41). In total there were 407 ctDNA aberrations, 91 of which were observed at baseline. Conclusions: We were able to monitor cfDNA changes with limited correlation with CTCs enumeration. Most ctDNA aberrations were identified during follow-up. Most common ctDNA aberrations. Baseline Follow-up TP53 26 72 PIK3CA 17 77 ERBB2 7 32 ATM 3 26 MYC 5 24
Alteration in red cell indices during palbociclib therapy.
Authors: Susan Bal, Mahmoud Charif
Journal: Journal of Clinical Oncology (2018)

e13031 Background: Palbociclib is a CDK 4/6 inhibitor approved for treatment of metastatic hormone receptor positive breast cancer with hormone therapy. We noticed variations in red cell indices in patients on therapy and performed a retrospective review to systematically assess change in red cell indices in patients on Palbociclib. Methods: We identified 46 patients with advanced hormone receptor (HR) positive, human epidermal growth factor receptor 2 negative breast cancer who were treated with Palbociclib at our institution from March 2015 to January 2018. The co-primary endpoint of our study was an increase in MCV greater than 10% and an increase in MCH greater than 10%. Secondary end points included increase in MCHC, RDW, assessment of progression free survival and change in MCV after discontinuation of Palbociclib. Results: 34 patients were included in the analysis. Median age was 61.5 (33-83) years. 32 (94.11%) patients were female. 20 (58.82%) patients received Palbociclib in first line setting. Both primary end points were met - mean delta MCV (18.07; t value 6.37; p < 0.0001) and mean delta MCH (20.97; t value 6.39; p < 0.0001) was statistically significant using t test. Mean increase in delta MCHC (2.38; p = 0.0026) and RDW (8.20; p = 0.0050) also reached statistical significance. No etiology of macrocytosis was apparent in the 9 patients tested. 24 (70.58%) patients were still on Palbociclib therapy without progression at the time of analysis. Four of the 10 patients who progressed had a decrease in MCV after discontinuation of Palbociclib (mean delta MCV -4.51%) suggesting reversal of macrocytosis with treatment discontinuation. Median duration of treatment was 8.5 months and estimated median progression free survival was 31 months. Conclusions: Palbociclib therapy is associated with significant increase in red cell indices which appears to be reversible with treatment discontinuation. CDK 4/6 inhibition results in cell cycle arrest which may lead to discordance between cytoplasmic and nuclear maturation in erythroid precursors leading to macrocytosis. This can be a simple test of compliance to oral therapy. Long term follow up is required to see if these changes correlate with response to therapy and/or survival.
VEGF-А in regulation of vascular endothelium functions and ascitic fluid production in ovarian cancer.
Authors: Tatiana Moiseenko, Elena Mikhaylovna Frantsiyants, Natalia D. Cheryarina, Yulia A. Pogorelova, Larisa Kozlova, Lyudmila Dmitriyevna Tkalya, Oksana E. Kravtsova, Meri Viktorovich Adamyan, Tatiyana Georgievna Chalabova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e17067 Background: Our purpose was to study VEGF-A, VEGF-R1, VEGF-C and FGF21 in the blood serum (BS) and ascitic fluid (AF) in stage I-IV ovarian cancer. Methods: BS in serous cystadenocarcinoma (CAC, n=76) and cystadenoma (CA, n=47) was studied. Histological control was performed in all cases. The data were compared to BS in uterine myoma (UM, n=20) and in 36 healthy donors (N), all women aged 51.5±2.6 years. Native AF was studied in patients with CAC affecting one ovary without treatment (n=26, T 3-4 N 0 M 0 ) and ovarian CA (n=12). Levels of VEGF-А, VEGF-R1, VEGF-С and FGF21 were measured by ELISA. Results: Levels of VEGF-A in CA BS exceeded N by 1.8, sVEGF-R1 – by 2, VEGF-C – by 1.7 and FGF21 – by 2.6 times. VEGF-A in T 1 N 0 M 0 CAC exceeded N and CA by 2.9 and 1.6, in T 2 N 0 M 0 – by 3.1 and 1.7, in T 3 N x M 0 – by 5.5 and 3, in T 4 N x-1 M 0 – by 5.8 and 3.1 times. sVEGF-R1 was similar in all CAC stages, on average twice higher than N, and similar to CA and UM. Differences were found between VEGF-А in CAC, CA and UM. sVEGF-R1 in all BS exceeded N (Р˂0.05 in all cases). VEGF-С in CA and UM BS exceeded N on average by 1.7 times, and in CAC it was significantly higher than in CA, UM and N. VEGF-С in BS in T 1 N 0 M 0 was higher than in N and CA by 2.0 and 1.2, in T 2 N 0 M 0 – by 2.6 and 1.6, in T 3 N x M 0 – by 2.5 and 1.5, in T 4 N x-1 M 0 – by 2.5 and 1.5 times, respectively. Differences in VEGF-С were found only in T 1 N 0 M 0 and T 2 N 0 M 0 by 1.3 times (Р˂0.05 in all cases). FGF21 in BS in UM and CA was similar, but differed from N by 2.6 times. FGF21 in all CAC stages exceeded BS and CA by 4 and 1.5 times. VEGF-А in CAC AF exceeded CA by 9.8, sVEGF-R1 – by 3.9; VEGF-C – by 1.6; FGF21 – by 1.7 times. VEGF-А, sVEGF-R1, FGF21 and VEGF-А/sVEGF-R1 in AF in UM and CA were similar to BS, and VEGF-С was lower than in BS by 1.7 times (Р˂0.05 in all cases). VEGF-А and sVEGF-R1 in BS in CAC were higher than in N by 2.9-5.8 and 2 times; in AF – higher than in UM by 9.9 and 4 times. VEGF-С in AF in CAC was lower than in BS on average by 1.6 times (Р˂0.05), and FGF21 did not differed in AF and BS. Conclusions: VEGF in SВ correlates with CAC stages distinguishing early and later ones. VEGF-А is higher than VEGF-C in BS and AF in all tumors. The VEGF family regulates functions of the endothelium of lymphatic and blood vasculature influencing oncogenesis and the occurrence of ascites.
A demonstration project: Providing colon cancer screening to homeless people—Capitalizing on community partnerships.
Authors: Leslie Foreman, Donna Akerson Green, Beverly Thorpe, Malia Haddock, William Burns, M.Parker Roberts, Scot C. Remick
Journal: Journal of Clinical Oncology (2017)

e18009 Background: Homeless people encounter many barriers to healthcare and preventative services, while having an increased prevalence of most risk factors for cancer. A group of homeless adults (40) receiving services from Preble Street in Portland Maine were successfully provided access, support and coaching to participate in colon cancer screening using Fecal Immunochemical Test (FIT) over a period of six weeks. Maine Medical Center Cancer Institute (MMCCI) recruited a Physician champion, while Preble Street gathered multiple internal and external community partners and together help plan the project identify resources needed, plan for data collection and address potential barriers for participation. Methods: Community partners (MMCCI, Preble Street, Casco Bay Surgery, NorDx, MaineHealth Care Partners and Homeless Health Partners Case Managers, Me Health LRC, and Maine Medical Center Magnet Council) created a detailed protocol to be used to overcome barriers and facilitate screening. The combination of a simple screening tool and caseworker relationship proved to be an effective strategy. Community Partners were used to identify barriers in the process, monitor all test results and navigate patients testing positive to colonoscopy. Small incentives of $10 food cards were provided for those participating in the screening event. Results: Of the 40 participants who were screened 8 (20%) tested positive and are in colonoscopy follow-up, with ages ranging from 50-74 years. The majority of participants 28 (70%) reported never having a provider conversation about colon cancer screening. Conclusions: Providing cancer prevention education and access to screening can have a positive impact on early detection in the homeless population. Identifying practical barriers and solutions are essential to improving cancer screening participation for homeless people.
The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells
Authors: Tingting Wang, Chaogang Fan, Anran Yao, Xingwei Xu, Guoxing Zheng, Yun You, Changying Jiang, Xueqiang Zhao, Yayi Hou, Mien-Chie Hung, Xin Lin
Journal: Immunity (2018)
Monitoring of thyroid function test abnormalities in cancer patients undergoing immune checkpoint inhibitor therapy in a community based cancer center.
Authors: Mehmet Sitki Copur, Spencer Evans, Jon Olsen, Sonja Schilling, Julie Wurdeman, Angela Mae Obermiller, Ryan C. Ramaekers, Dron Gauchan, David Crockett, Douglas Clark, Megan Schriner, Deborah Nelson, Monica McDonald, Jami Kezeor, Max Norvell
Journal: Journal of Clinical Oncology (2018)

e15064 Background: Immune-checkpoint inhibitor (ICI) therapy related thyroid function test (TFT) abnormalities are not uncommon. No well-established guidelines on the type, frequency, and duration of monitoring of TFTs exist in this setting. We retrospectively evaluated the practice patterns of TFT utilization for ICI treated cancer patients (pts) in our community based cancer program. Methods: Review of records of cancer pts receiving ICIs (Ipilimumab (I), Nivolumab(N) +/- Ipilimumab, Pembrolizumab(P), and Atezolizumab(A)) was performed utilizing electronic medical records at Catholic Health Initiatives St Francis Cancer Treatment Center, Grand Island Nebraska. TFT ordering patterns, results, and clinical management of pts were evaluated. Pts with prior TFT abnormalities were excluded from analyses. Results: Aug-2015 to Jan-2018, 130 pts (66F/64M), ages 32-94, received at least one dose of ICI therapy (N = 94, P = 26, A = 5 and N+I = 5). Median number of TFTs ordered by 8 providers (4 MDs/4PA/APRNs) was 14 (range 0-28). All pts had TSH, free T3 and free T4 tested. 62/130 (47%) pts had abnormal TFTs. Median number of abnormal TFTs was 10 (range 0-23). Median time to abnormal TFTs was 52 days. 34/130 (27 %) pts had TFTs checked every cycle of ICI therapy vs 96/130 (73 %) pts had TFTs checked every 3rd cycle of ICI therapy. All pts had TFTs monitored until the completion of ICI treatment. Both, pts who did not have abnormal TFTs until after 4 cycles and pts with abnormal TFTs who achieved euthyroid levels with treatment, remained euthyroid until the end of ICI treatments. There were no TFT related ICI treatment discontinuations. Conclusions: Incidence of TFT abnormalities with ICI therapy was higher than reported in our community based cancer practice. Monitoring of TFTs beyond initial 4 cycles or after achieving euthyrotid levels did not change the outcome. Our retrospective review suggests that in ICI treated cancer pts monitoring of TFTs with a baseline and every 3 cycles of ICI treatment and less frequently thereafter may be adequate unless clinically indicated. Prospective evaluation of this concept might help establish future definitive guidelines in this setting.
TCT-24 Impact of Bleeding on Outcome and Predictive Value of Bleeding Scores in Patients With Cardiogenic Shock - a Substudy of the CULPRIT-SHOCK trial
Authors: Anne Freund, Steffen Desch, Suzanne de Waha, Uwe Zeymer, Holger Thiele
Journal: Journal of the American College of Cardiology (2018)