tbuckley/cabot-search huggingface dataset:
A phase I trial targeting advanced or metastatic pancreatic cancer using a combination of standard chemotherapy and adoptively transferred nonengineered, multiantigen specific T cells in the first-line setting (TACTOPS).
Authors: Brandon George Smaglo, Benjamin Leon Musher, Spyridoula Vasileiou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Tao Wang, Monica Francois, Carlos Almeida Ramos, LaQuisa Hill, George Van Buren, William Fisher, Tannaz Armaghany, Yvonne Sada, Juan Fernando Vera Valdes, Bambi Grilley, Adrian P Gee, Helen E. Heslop, Premal D. Lulla, Ann M. Leen
Journal: Journal of Clinical Oncology (2020)

4622 Background: Immunotherapy is emerging as a potent therapy for a range of hematologic malignancies and solid tumors. To target pancreatic carcinoma we have developed an autologous, non-engineered T cell therapy using T cell lines that simultaneously target the tumor-associated antigens (TAAs) PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin. These multiTAA-specific T-cell lines could be consistently prepared by culturing PBMCs in the presence of a Th1-polarizing/pro-proliferative cytokine cocktail, and adding autologous pepmix-loaded DCs as APCs. Methods: Patients with locally advanced or metastatic pancreatic adenocarcinoma who achieved cancer control with three months of standard chemotherapy were eligible to receive up to 6 infusions of multiTAA T-cells (fixed dose - 1x10 7 cells/m 2 ). While also continuing the same chemotherapy, T-cells were given at monthly intervals from month four, onwards. The primary study endpoints were safety and feasibility of completing all 6 planned infusions, with secondary and tertiary endpoints including anti-tumor effects, patient survival, in vivo expansion and T cell persistence of the infused cells as well as recruitment of the endogenous immune system. Results: Between June 2018 and December 2019, we treated 13 patients with multiTAA T-cells. For 12/13 patients, we generated sufficient cells for all 6 planned doses; 2 doses were available for the remaining patient. Of the 13 patients, 8 maintained cancer control for a longer than expected duration, compared to historical controls. With administration of T-cells, 3 of these 8 patients had partial responses and 1 patient had a radiographic complete response (per RECIST). These responses were seen in patients with metastatic cancer. Notably, no patient had infusion-related systemic- or neuro-toxicity. Thus, infusion of autologous multiTAA-targeted T cells directed to PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin has been safe and provided durable clinical benefit to patients with pancreatic adenocarcinoma. Conclusions: Autologous, TAA cytotoxic T-cells can reliably be generated and safely administered to patients in conjunction with standard of care chemotherapy. In some patients, addition of T-cells may extend duration of first line therapy cancer control and induce additional tumor responses, and activation of the endogenous immune system has been documented in all patients. Exploration in a higher phase study is warranted. Clinical trial information: NCT03192462 .
Bone pain associated with rhG-CSF or PEG-rhG-CSF in oncology patients.
Authors: Zhisong Fan, Yu Su, Long Wang, Yudong Wang, Jing Zuo, Fengling Liu, Da Jiang
Journal: Journal of Clinical Oncology (2020)

e19186 Background: Recombinant human granulocyte colonystimulating factor (rhG-CSF) and glycoPEGylated G-CSF (PEG-rhG-CSF) are two kinds of drugs in reducing the incidence and duration of neutropenia in oncology patients treated with chemotherapy. Although the acting time is different, bone pain is one of the most common adverse events in rhG-CSF and PEG-rhG-CSF. The purpose of this study is to describe the occurrence and management of bone pain in oncology patients receiving rhG-CSF and PEG-rhG-CSF. Methods: Two hundred and forty patients with malignant tumor received rhG-CSF or PEG-rhG-CSF after chemotherapy were enrolled to finish questionnaires about the side effect of bone pain. The incidence, location, duration, degree and treatment of bone pain after rhG-CSF or PEG-rhG-CSF used were collected and analyzed. Results: A total of 240 patients enrolled and 56.3% (135) patients had bone pain after rhG-CSF or PEG-rhG-CSF delivered. The most common parts of bone pain were thigh (35.6%), back (29.6%), waist (25.9%), shoulder (23.7%) and chest (21.5%). The bone pain of 39.2% patients last for 72h and 27.2% patients last less than 72h. The duration time of bone pain was longer in PEG-rhG-CSF than rhG-CSF. There was no significant difference in the rate of pain occurrence and the proportion of severe pain between rhG-CSF and PEG-rhG-CSF. Only 22.2% patients took drugs to relieve bone pain. Downregulated the doses of rhG-CSF or PEG-rhG-CSF could significantly relieve bone pain. Besides bone pain, 34.0% patients suffered muscle ache which was the second most side effect and occurred more often than runny nose and fever. Conclusions: The percentage of bone pain occurrence are similar in rhG-CSF and PEG-rhG-CSF, but the duration time was longer in PEG-rhG-CSF. For most patients, bone pain need not to deal with, Dose reductions can effectively relieve the mild to severe pain.
Flurbiprofen axetil reduces incidence of postoperative delirium in elderly patients undergoing orthopedic surgery
Authors: Lei Wu, Congxiao Zhang, Gengsheng Wei, Yi Jiang, Jingliang Wu
Journal: BMJ (2016)

对2014年7至12月北京市海淀医院骨科住院行手术治疗并且年龄≥60岁的97例患者，根据是否使用氟比洛芬酯分为氟比洛芬酯组(48例)和对照组(49例)，观察术后前3 d谵妄的发生率和疼痛视觉模拟评分(VAS评分)。氟比洛芬酯组谵妄的发生率15%(7/48)，显著低于对照组的24%(12/49，P＝0.000)，平均VAS评分(3.3±1.8)也显著低于对照组(5.4±2.3, P＝0.000)。
Tag-n-trak study: Preliminary analysis of an unselected biobank tumors with NTRK fusion transcript, the French SFCE society contribution.
Authors: Lauriane Lemelle, Delphine Guillemot, Hervé Brisse, Arnaud Gauthier, Matthieu Carton, Anne-Laure Hermann, Nadege Corradini, Angélique Rome, Hélène Boutroux, Anne Jourdain, Aude Marie Cardine, Sarah Jannier, Marie Pierre Castex, Anne Sophie Defachelles, Isabelle Aerts, Marie Karanian, Francois P. Doz, Olivier Delattre, Gaëlle Pierron, Daniel Orbach
Journal: Journal of Clinical Oncology (2020)

10540 Background: NTRK ( Neurotrophic receptor tyrosine kinase) fusion transcript was initially described in infantile fibrosarcoma (IFS) and is now known to be present in many other rare types of tumor with a lower incidence. The main objective of the study is to describe the presentation and outcome of unselected tumors with NTRK fusion transcript (NTRK-FTT) to better consider the role of TRK inhibitors (TRKi) in such entities. Methods: We selected patients (pts) from the Institut Curie biobank (adults and children) with NTRK-FTT and which were assessed by RT-qPCR then RNA sequencing in a prospective or retrospective process, between 2001 and 2019. Results: We identified 62 NTRK-FTT among 2119 screened tumors (2.2 cases/year with RT-qPCR and 6.9 cases/year with RNA seq after 2016), NTRK3 (44 cases) (including 41 NTRK3-ETV6), NTRK2 (9) or NTRK1 (9). Most of pts had under 2 years (y) (74%) and only 7 pts were adults. We report preliminary analysis of clinical observation for the first 27 pts. Median age was 0.4 y [0-60.2]. Pathologic diagnosis was IFS (12 cases), various CNS tumors (4), atypical teratoid rhabdoid tumor (1), myofibroblastic inflammatory tumor (2), benign tumors (3), cellular congenital mesoblastic nephroma (2), lipofibromatosis like neural tumor, myxoïd liposarcoma, unclassifiable sarcoma (1 each). Two pts had metastatic tumors. Among all, 22 had surgery (1 mutilating), 15 chemotherapy, 4 radiotherapy, and 5 received TRKi, as second line treatment (2 pts) or ≥ third line (3 pts). After a median follow-up of 50 months [range, 1-155], 20/27 pts remained in complete remission, 3 had stable residue, and 4 had progressive disease (associated to 1 disease-related and 1 toxic deaths). Five-year OS is 88% [95%CI, 73.5-100] and 5y-EFS 59.5% [95%CI, 41.7-84.9]. Conclusions: This descriptive study showed that NTRK-FTT is rare (2.9%), encompasses a variety of different histotypes (n = 14). Systematic RNA sequencing allowed to depict 3.5 times more NTRK-FTT than targeted RT-qPCR. Overall outcome is favorable despite frequent tumor events. According to tumor type and the uncertainties regarding the long-term side effects of TRKi, the benefit/risk ratio must be carefully evaluated before using these drugs in first line.
Optimizing infusion wait time: Redesigning medication order verification/approval at a comprehensive cancer center.
Authors: Neda Hashemi-Sadraei, Zoneddy R. Dayao, Shenthol Sasankan, Andrea Cox, Sandra Peacock, Janet Abernathy, Ronald Kittson, Bernard Tawfik, Nick Crozier, Richard C. Lauer
Journal: Journal of Clinical Oncology (2020)

e14042 Background: Nationwide, many cancer centers experience challenges with infusion center efficiency while maintaining high safety standards. Many factors contribute to long wait times for patients on the day of their infusion appointments. At University of New Mexico Comprehensive Cancer Center (UNMCCC), a contributing factor is the delays in verification or approval of medications. We conducted a project to improve order verification/approval workflow within a Plan-Do-Study-Act (PDSA) framework with the objective to decrease the infusion wait time. Methods: A multidisciplinary working group was formed consisting of the infusion floor physician lead, nurse lead, pharmacy lead, and analytics and process improvement leads. Upon exploring the infusion workflow database, disruptions in verification or approval of orders had a large impact on wait times. Order verification workflow was broken down into 3 steps: 1) physician assessment of patient and approval of orders, 2) infusion nurse assessment of patient, 3) pharmacist verification of order. Beginning Feb 2019, the following interventions were implemented in each section: 1) once patient was assessed by physician and orders approved, the patient was marked as “ready-to-treat”. 2) Pharmacist verified the order once “ready-to-treat” was communicated and initiated preparation of medications prior to arrival of patient to the infusion suit. 3) Infusion nurse assessment occurred once patient was seated on infusion chair. 4) Physicians were encouraged to pre-approve selected injections by the morning of patient appointment. Results: Prospective wait time was gathered for May 2019 using the real-time data available in the electronic medical record. Wait times were analyzed for patients receiving chemotherapy or flat dose injections. By marking appropriate patients “ready-to-treat” and moving pharmacist verification prior to infusion nurse assessment, there was an immediate decrease in wait time from 79 to 60 min. Selected injections which did not require mixing were pre-approved by the physician and stored in the medication dispensing system (Pyxis). This resulted in decrease in the injection wait time by 8.5 minutes, without wasting of drugs. Conclusions: Redesigning the medication order verification/approval workflow resulted in reduced wait times for patients receiving infusions or injections. We aim to further refine our PDSA cycles and ensure sustainability of change.
Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch
Authors: Huan-Jun Lu, Thien-Luan Nguyen, Gyu-Sang Hong, Sungmin Pak, Hyesu Kim, Hyungsup Kim, Dong-Yoon Kim, Sung-Yon Kim, Yiming Shen, Pan Dong Ryu, Mi-Ock Lee, Uhtaek Oh
Journal: Journal of Clinical Investigation (2020)

The baroreceptor reflex is a powerful neural feedback that regulates arterial pressure (AP). Mechanosensitive channels transduce pulsatile AP to electrical signals in baroreceptors. Here we show that tentonin 3 (TTN3/TMEM150C), a cation channel activated by mechanical strokes, is essential for detecting AP changes in the aortic arch. TTN3 was expressed in nerve terminals in the aortic arch and nodose ganglion (NG) neurons. Genetic ablation of Ttn3 induced ambient hypertension, tachycardia, AP fluctuations, and impaired baroreflex sensitivity. Chemogenetic silencing or activation of Ttn3+ neurons in the NG resulted in an increase in AP and heart rate, or vice versa. More important, overexpression of Ttn3 in the NG of Ttn3–/– mice reversed the cardiovascular changes observed in Ttn3–/– mice. We conclude that TTN3 is a molecular component contributing to the sensing of dynamic AP changes in baroreceptors.
The prevalence of germline mutations among patients with solid tumors with genomic alterations identified on tumor testing: Results from a tertiary care academic center molecular tumor board.
Authors: Catherine Watson, Sarah Tait, Lindsay Soo, Jennifer Kay Plichta, Tian Zhang, Edgardo Castellar, Andrew J. Armstrong, Rebecca A. Previs, John H. Strickler, Michelle Green, Michael Datto, Paul Kelly Marcom, Carolyn S. Menendez
Journal: Journal of Clinical Oncology (2020)

1516 Background: The proportion of germline versus somatic mutations identified on genomic tumor testing of solid malignancies is not well characterized. We compared somatic and germline testing results in patients with breast, ovarian, pancreatic or prostate cancer with a genomic alteration identified on tumor testing. Methods: Retrospective chart review was performed using a tertiary care academic center’s database of somatic tumor testing results obtained via FoundationOne and Guardant testing. Patients with breast, ovarian, pancreatic or prostate cancer who had a genomic alteration identified on tumor testing, including pathogenic and VUS variants, in BRCA1or BRCA2, CHEK2, ATM, BRIP1, RAD51C, RAD51D, PALB2and CDH1and who had also received germline testing were identified. Analysis was performed to assess prevalence of germline results. The association between mutant allele fraction (MAF) and germline mutation status was also assessed. Results: Results: 124 patients with breast, ovarian, pancreatic or prostate cancer were identified who had a genomic alteration of interest also tested for via germline testing. 54 (32.5%) of tumor mutations were also identified on germline testing. Proportion of genomic results that were germline was wide, ranging from 0-85.7% depending on the gene and variant classification (Table). Germline mutations were present in 36.4% of breast, 25% of ovarian, 53.3% of pancreatic, and 20.9% of prostate cancer patients who had a tumor alteration present. Alterations that were found to be concordant in both somatic and germline testing had an average MAF of 0.54, and alterations identified on somatic testing only had an average MAF of 0.30. Conclusions: Our findings suggest that approximately one-third of genomic alterations on tumor testing will be of germline origin. However, concordance rates may be gene and variant dependent. Higher MAF may be associated with germline alteration status, but further evaluation is needed. Thus, while information provided by genomic tumor testing may be suggestive of a correlating germline mutation, no single alteration type or MAF value is reliably predictive. [Table: see text]
Serum estriol and placenta growth factor levels in pregnant women with subclinical hypothyroidism after thyroxine therapy
Authors: Che Xu, Feifei Zhao, Fei Xie
Journal: BMJ (2018)

Sixty four pregnancy women with mildly raised TSH level (2.5-4.5 mU/L) in the 1st trimester were divided into two groups: only the thyroid function was monitored in study I group (n=32), while levothyroxine therapy was given in study Ⅱ group (n=32); 45 normal pregnant women with TSH level  0.05). The serum levels of uE3 (7.34 μg/L) and PlGF (76.3 ng/L) were elevated in study group Ⅱ; and the uE3 level was close to that in the control group (6.61 μg/L), while PlGF level was lower than that in the control group (169.1 ng/L). When TPO antibody was positive, the uE3 level in the study group Ⅰ (logarithmic value 0.37±0.31) was lower than those in other two groups (logarithmic value 0.81±0.37, 0.56±0.27), while there was no significant difference in PlGF levels among three groups. The results suggest that levothyroxine may improve placental function to some extent and TPO antibody might be one of the regulators in the expression of uE3.


Key words: 
Hypothyroidism; Hyroxine; Estriol
The association between breast density and HER2-positive breast cancer: A population-based case-control study.
Authors: Vivian Tan, Jennifer Payne, Nicole Paquet, Sian Iles, Daniel Rayson, Penny Barnes, Mohamed Abdolell
Journal: Journal of Clinical Oncology (2020)

e12556 Background: Little is known about the association between mammographic breast density and the subtypes of breast cancer including HER2-positive breast cancers (HER2-BrCa). The objective of this study was to assess the strength of association between breast density and HER2-BrCa in a population-based screening program. Methods: This is a population-based case-control breast cancer study of women aged 40 to 75 who underwent digital breast screening from 2009 to 2015 in Nova Scotia, Canada. Cases included women diagnosed with HER2-BrCa at screen or before their next screen (interval); controls included women without screen-detected cancer matched to cases by age and year of screen. Measures of mammographic breast density (percent density, BI-RADS-4th and -5th edition) were obtained from automated software (densitasai) and linked with clinical risk factor data (age, parity, total breast volume, post-menopausal status, hormone replacement therapy, family history and history of core biopsy). The association between breast density and cancer risk was assessed by calculating the odds ratios [OR] with 95% confidence intervals using multivariable logistic regression. Results: A total of 209 cases (median age, 58.8 years) and 6812 controls (median age, 59.4 years) were included. The risk of HER2-BrCa increased with increasing levels of percent breast density. High breast density according to BIRADS-4th and -5th editions was significantly associated with HER2-BrCa: BIRADS -4 th 3/4 vs 1: OR 2.50 (1.68 - 3.68); BIRADS-5 th C/D vs A: OR 2.58 (1.71 - 4.01). The association between higher breast density and increased risk of HER2-BrCa remained after adjustment for clinical factors. Conclusions: The risk of HER2-BrCa was associated with progressively higher mammographic breast density, although to a lesser extent than breast cancer in general. Accurate risk models including breast density may support the development of more breast-screening protocols that can lead to more strategic use of healthcare resources.
An analysis of inpatient and ED admissions within 30 days of chemotherapy: An OP-35 review.
Authors: Jay Carlson, Jiajing Chen, Michelle Smith, Jessica N. Snider, Mohan K. Tummala, Samir Dalia, Carla Kurkjian, Bethany G. Sleckman
Journal: Journal of Clinical Oncology (2020)

e19302 Background: To evaluate patients who were within 30 days of outpatient chemotherapy infusion for an admission or ED visit associated with a primary or secondary diagnosis of anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia or sepsis. Methods: A review of Epic was performed on all Mercy patients with cancer who received at least one outpatient chemotherapy between 1/1/16-12/31/18. Non leukemia patients ≥ 18 years of age with an inpatient admission(IPA) or ED visit (EDV) were further evaluated for either the primary or secondary diagnosis for referral with at least one of the following diagnoses: anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia, or sepsis. Univariate and multivariable analyses were performed to identify significant clinical variables associated with the risk of referral. Adjusted Odds Ratios were calculated for the significant variables with a p value &lt; 0.05 being significant. Results: Of the 9,590 cancer patients who presented to an outpatient infusion center during the study interval, there were 8,319 eligible patients excluding those with leukemia or age &lt; 18 (n = 503) or for a presentation in which a chemotherapy agent was not infused. There were 90,030 eligible chemotherapy encounters of which 16.8% of patients (n = 1400) had an IPA and 11.8% (n = 980) had an EDV within 30 days of infusion. Age, social deprivation status, NCI comorbidity index, Epic readmission score, ECOG performance score, smoking, and malnutrition were significantly associated with either an IPA or EDV in both settings. Sepsis, pneumonia, and anemia were the most common OP35 related diagnoses for an IPA at 47.2%, 26.9%, and 23.2%, respectively. Similarly, pain, dehydration and nausea were the most common OP35 related diagnosis for an EDV at 48.1%, 14.2%, and 14.1% respectively. Factors having the strongest association with an IPA were malnutrition (OR: 2.34 2.08-2.65; p &lt; 0.00001) and an antibiotic type of chemotherapy (OR: 2.16 1.72-2.72; p &lt; 0.0001). Factors having strongest association with an EDV were severe pain score (OR: 2.56 2.21-2.97; p &lt; 0.0001) and moderate to most deprived social deprivation status (OR: 2.10 1.62-2.72; p &lt; 0.0001). ER referrals for pain, dehydration, and anemia most commonly occurred during clinic hours. Conclusions: Many clinical variables were found to be significantly associated with an IPV or EDV. These variables are opportunities for outpatient interventional algorithms to enhance patient care.
Outcomes in children with Down syndrome (DS) and B-lymphoblastic leukemia (B-ALL): A Children’s Oncology Group (COG) report.
Authors: Karen R. Rabin, Zhiguo Chen, Meenakshi Devidas, Johann Hitzler, Eric Larsen, Michael Burke, Wanda L. Salzer, Reuven J. Schore, Andrew J Carroll, Nyla A. Heerema, Michael J. Borowitz, Brent L. Wood, William L. Carroll, Naomi J. Winick, Elizabeth A. Raetz, Stephen Hunger, Mignon L. Loh, Kelly W. Maloney, Anne L. Angiolillo
Journal: Journal of Clinical Oncology (2020)

10510 Background: Patients with DS and B-ALL experience increased rates of relapse and toxicities. Here, we report results from 4 COG trials (2003-2018). Methods: We analyzed clinical, and outcome data for DS (n = 743) and non-DS (n = 21,703) patients age 1-30 enrolled on standard-risk (SR) trials AALL0331 and AALL0932 and high-risk (HR) trials AALL0232 and AALL1131. Initially, DS-ALL patients on AALL0232/AALL0331 experienced excess mortality, prompting enhanced supportive care and omission of induction anthracycline except for slow responders on AALL1131. Other modifications included: non-random assignment to treatment strata without investigational agents; leucovorin rescue after intrathecal methotrexate (MTX); equal maintenance length for boys and girls; every 12-week maintenance vincristine/steroid pulses; and reduced anthracycline and intravenous MTX for HR patients. Results: Across all 4 trials, DS and non-DS patients did not differ significantly in age, sex, initial WBC, or CNS status. DS-ALL patients had significantly higher end of induction (EOI) minimal residual disease (MRD) vs non-DS patients on both AALL0932 and AALL1131, but the difference persisted at end of consolidation (EOC) only on AALL1131, with fewer EOI MRD+ DS patients achieving EOC MRD &lt; 0.01% (76.1 vs 88.0%, p = 0.001). 5-year EFS and OS were significantly poorer for DS vs non-DS across all trials (EFS 79.6+2.1% vs 86.3+0.3%, p &lt; 0.0001; OS 86.5+1.8% vs 93.1+0.2%, p &lt; 0.0001), as well as on each individual trial. In Cox regression analysis for all DS patients, inferior EFS was associated with several known risk factors (age &gt; 10, EOI MRD &gt;0.01%) but not with cytogenetics or CRLF2 status Induction death was more frequent in DS patients (3.4% vs 0.8%, p &lt; 0.0001) as was death in remission (4.8+0.8% vs 1.8+0.1%, p &lt; 0.0001). For death in remission, the increased frequency occurred pre-maintenance and in patients taken off protocol therapy, but not during maintenance, in contrast to prior reports. Grade &gt;3 mucositis, infections, and hyperglycemia were significantly more frequent in DS patients on all trials. Grade &gt;3 seizures were significantly more frequent in DS patients on HR but not SR trials (4.1% vs 1.7%. p = 0.001) and occurred in all phases pre-maintenance. Conclusions: Patients with DS and B-ALL continue to have inferior outcomes compared to non-DS, with increased relapse and toxicities. Less toxic approaches such as immunotherapies and targeted therapies hold promise to improve outcomes in both these areas.