tbuckley/cabot-search huggingface dataset:
Rationalization is rational
Authors: Fiery Cushman
Journal: Behavioral and Brain Sciences (2019)

Rationalization occurs when a person has performed an action and then concocts the beliefs and desires that would have made it rational. Then, people often adjust their own beliefs and desires to match the concocted ones. While many studies demonstrate rationalization, and a few theories describe its underlying cognitive mechanisms, we have little understanding of its function. Why is the mind designed to construct post hoc rationalizations of its behavior, and then to adopt them? This may accomplish an important task: transferring information between the different kinds of processes and representations that influence our behavior. Human decision making does not rely on a single process; it is influenced by reason, habit, instinct, norms, and so on. Several of these influences are not organized according to rational choice (i.e., computing and maximizing expected value). Rationalization extracts implicit information - true beliefs and useful desires - from the influence of these non-rational systems on behavior. This is a useful fiction - fiction, because it imputes reason to non-rational psychological processes; useful, because it can improve subsequent reasoning. More generally, rationalization belongs to the broader class of representational exchange mechanisms, which transfer information between many different kinds of psychological representations that guide our behavior. Representational exchange enables us to represent any information in the manner best suited to the particular tasks that require it, balancing accuracy, efficiency, and flexibility in thought. The theory of representational exchange reveals connections between rationalization and theory of mind, inverse reinforcement learning, thought experiments, and reflective equilibrium.
Anti-epidermal growth factor receptor therapy in combination with chemoradiotherapy for the treatment of locally advanced anal canal carcinoma: Results of a phase II study with panitumumab (FFCD 0904).
Authors: Thomas Aparicio, Philippe Ronchin, Louis Bazire, Karine Le Malicot, Claire Lemanski, Xavier Mirabel, Pierre-Luc Etienne, Astrid Lièvre, Wulfran Cacheux, Ariane Darut-Jouve, Christelle De La Fouchardiere, Gilles Breysacher, Delphine Argo Leignel, Alexandre Tessier, Nicolas Magne, Meher Ben Abdelghani, Come Lepage, Veronique Vendrely
Journal: Journal of Clinical Oncology (2019)

3570 Background: Standard treatment of anal squamous cell carcinoma is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study studied the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU based CRT. Methods: Patients with locally advanced tumor without metastases (Stage T2, T3 or T4, whatever N stage; Stage N1-N3 whatever T stage) were treated with two RT periods (45Gy in 5 weeks and a boost of 20Gy in 2 weeks) with concomitant CT sessions of 5FU/MMC at RT weeks 1 and 5. Pmab was administered on RT weeks 1, 3, 5 and 7 according to the doses defined by a previous phase 1.study (MMC: 10 mg/m² at J1 and J29; 5FU: 400 mg/m² from J1 to J4 and from J29 to J32, Pmab: 3mg/kg). The expected rate of CR at 8 weeks to continue in phase III was 80%. Results: Forty-five patients (male: 9 (20%), female: 36 (80%); median age: 60.1 [41.5-81]) were enrolled in 15 French centers. All patients but one completed the CRT. Median duration of CRT was 52 days [30-76].Fourteen patients had a RT interruption because of toxicity. Most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (28.8%) and asthenia (11.1%). On patient died because of mesenteric ischemia during the CRT (total dose: 36 Gy). In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 16.2 months [14.1-18.2]. Overall survival, recurrence-free and colostomy-free survival at one year were 94.6% [95%CI: 75.8-98.7], 72.2% [95%CI: 55.0-83.7] and 78.2% [95%CI: 60.6 – 88.6] respectively. Six (13%) patients had a colostomy with abdomino-perineal amputation due to a tumour recurrence. Conclusions: Despite an acceptable tolerance, panitumumab in combination with CRT for locally advanced anal cancer failed to meet the expected CR rate to justify further clinical trials. Clinical trial information: NCT01581840.
Risk of treatment-related death in carriers of pathogenic <i>DPYD</i> polymorphisms treated with fluoropyrimidine chemotherapy: A systematic review and patient-level analysis.
Authors: Karan Rai, Bhavina D O Batukbhai, Gabriel A. Brooks
Journal: Journal of Clinical Oncology (2019)

e15132 Background: Polymorphisms of the DPYD gene are present in 3-5% of the population and are associated with increased risk for grade ≥3 toxicity during treatment with fluoropyrimidine (FP) chemotherapy. Fatal toxicities in carriers of DPYD polymorphisms have been described in published reports, however reliable estimates of the risk of treatment-related mortality are lacking. Methods: We conducted a systematic review of the MEDLINE database to identify relevant manuscripts published before January 28, 2018. We searched for published studies of patients receiving standard-dose FP chemotherapy (5-fluorouracil or capecitabine) who had pre-treatment testing for ≥1 of 4 pathogenic DPYD polymorphisms (c.1236G &gt; A/HapB3, c.1679T &gt; G, c.1905+1G &gt; A/*2A, and c.2846A &gt; T) and who were systematically assessed for treatment-related toxicities. In the case of retrospective studies, we required that the cohort be defined by pretreatment characteristics (e.g., patients were not included on the basis of observed toxicity). Two reviewers extracted study- and patient-level data, with discrepancies resolved by consensus. The pooled data were analyzed to estimate the risk of treatment-related mortality among polymorphism carriers. Results: Of the 1290 references screened, 37 publications were included in the final analysis. Patient-level data identified 485 of 14,377 patients (3.4%) with pathogenic DPYD polymorphisms. There were 12 deaths among polymorphism carriers, resulting in a 2.5% risk of treatment-related mortality (95% CI 1.3-4.4%). Only 2 treatment-related deaths were reported in 13,892 patients without identified polymorphisms. Risk of death by genotype is shown in the table; two decedents were compound heterozygotes. Conclusions: Patients with pathogenic DPYD polymorphisms who are treated with standard-dose FP chemotherapy are at significant risk of death and can be prospectively identified through pharmacogenetic testing. [Table: see text]
Patient related outcomes in cancer patients in Croatia.
Authors: Dragan Trivanovic, Irena Hrstic, Anuska Budisavljevic, Boris Kopic, Bruno Nincevic
Journal: Journal of Clinical Oncology (2019)

TPS6650 Background: Accurate evaluation of symptom intensities is essential for optimal cancer care and improving the quality of life of patients. An inappropriate interpretation of symptoms may lead to treatment outcomes failure, overdose of medication, or may leave the patients undertreated. However, the perception of symptoms can vary between the treating physician and patient. Physicians appear to underestimate the patient symptoms. And this variation in the perception of side effects can lead to wrong assumptions and subsequent treatment changes, affecting treatment effectiveness and quality of life. There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, leaving open the question of whether the benefits of systems to reveal self-reports outweigh their added cost. There are several tools for assessment of symptoms in oncology. In cancer treatment clinical trials, the standard source of adverse symptom data is clinician reporting by use of items from PRO-CTCAE, developed by NCI. To address these questions, we conducted a single-center prospective trial to test whether systematic tablet computer-based collection of patient-reported symptoms during chemotherapy treatment, with automated alerts to clinicians for severe adverse events (grade 3-4) will change in questionnaire score at 6 months compared with baseline. Secondary endpoints will include difference in unscheduled clinic visits frequency, and survival. Methods: Patients initiating chemotherapy at General Hospital Pula Oncology Clinic for advanced or metastatic gastrointestinal, lung, breast, genitourinary, or gynecologic cancers will be enrolled in a nonblinded, prospective trial of self-reporting of symptoms, compare with usual care. Patients receiving chemotherapy and their clinicians will be independently asked on the same day to complete 10 symptoms (including fatigue, pain, nausea, vomiting, diarrhea, dysgeusia, appetite, sleep disturbance, fever and hair loss). Participants will remain on study until discontinuation of cancer treatment, withdrawal, or death. All participants will provide written informed consent and followed for up to 28 months or until death. To compare how patient’s vs clinician’s reports relate to clinical events, a time-dependent Cox regression model adjusted for covariates including cancer type, age, sex, and education level will be used to measure associations between reaching particular grade severity thresholds with the risk of death and unscheduled clinic visits. Clinical trial information: 2019-000855-15.
Cell-free DNA methylation markers for noninvasive early detection of nasopharyngeal carcinoma.
Authors: Dhruvajyoti Roy, David J Taggart, Lianghong Zheng, Dan Liu, Gen Li, Mingzhen Li, Kang Zhang, Richard A. Van Etten
Journal: Journal of Clinical Oncology (2019)

e14537 Background: Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignancies among populations native to Southeast Asia, the Mediterranean Basin and the Arctic. Early diagnosis of NPC is predicted to improve survival. The identification of cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is an established approach for detecting various cancers. In the present study, we evaluated the performance characteristics of a previously identified NPC methylation marker panel for the diagnosis of nasopharyngeal carcinoma. Methods: Retrospective samples were obtained for 168 subjects, including: 59 subjects diagnosed with NPC (Stage I to IV), 14 subjects diagnosed with benign nasopharyngeal disease and 43 healthy subjects. In addition, sample were obtained for 52 subjects diagnosed with breast, colorectal, liver or lung cancer. Samples were provided to the laboratory blinded for DNA methylation analysis by using the IvyGene Platform. Results: A total of 57 of the 59 samples drawn from subjects with NPC were correctly identified for an overall sensitivity of 97%, with little difference between the sensitivity of detecting Stage I to Stage IV nasopharyngeal carcinoma (range 92% to 100%). For subjects diagnosed with other cancers, 85% of colorectal cancer samples, 82% of lung cancer samples, 93% of both breast cancer and liver cancer samples, were correctly identified as negative for NPC, for a total calculated analytical specificity of 86%. Additionally, all 43 samples drawn from healthy donors and 14 samples drawn from subjects diagnosed with benign nasopharyngeal disease were correctly identified as negative for nasopharyngeal carcinoma for a combined specificity of 100%. Conclusions: The NPC methylation panel was demonstrated to be both sensitive and specific for the detection of nasopharyngeal carcinoma. The potential of cfDNA methylation markers for the early detection of nasopharyngeal carcinoma is predicted to improve patient outcomes through earlier detection of the disease.
Changing trends in HER-2 neu positive breast cancers in women: A study by a medical student and his preceptor.
Authors: Aaron Monga, Chaya Prasad, Rama Prasad, Rita Alcantara
Journal: Journal of Clinical Oncology (2019)

e12509 Background: Breast cancer affects 3.5 million women in the United States with 155, 000 women living with metastatic breast cancer in the US with 40,290 deaths every year. In particular, HER-2 NEU positive lesions are aggressively malignant, with increased recurrence and decreased survival but good response to Herceptin. This study reviews trends of breast cancers and looks in depth into prognostic indicators, in HER-2 NEU positive breast cancers. Methods: Anonymized medical data including demographics and tumor characteristics from San Antonio Regional Hospital’s (SARH) tumor registry database were collected from 2015-2017. Inclusion criteria included female patients with a diagnosis of invasive breast cancers. Data was stratified according to age at diagnosis, race of the patient, histologic grade, size of the tumor, lymph node status, HER-2 NEU status and stage (pathologic and clinical). Results: From 2015 to 2017 we identified 371 patients with invasive breast cancers. The percentages of HER-2 NEU positive patients in these years was 15.7%, 16.0%, and 9.4% in 2015, 2016 and 2017 respectively. This represented a 6.6% drop in HER-2 NEU positive patients from 2016 to 2017. We then looked at all HER-2 NEU positive breast cancers. In 2017, 71% of patients with HER-2 NEU positive tumors presented with a low pathologic size compared to 36% in 2016 and 44% in 2015, and 29% presented with low histologic grade compared to 14% in 2016 and 12% in 2015, and 0% of patients presented with lymph node metastases compared to 18% in 2016 and 20% in 2015. Overall 100% of patients with HER-2 NEU positive tumors presented at a low stage compared to 73% in 2016 and 52% in 2015. Conclusions: Our data shows a decrease in HER-2 NEU positive cancers from 2015 to 2017. It is important to note that these HER-2 NEU lesions were associated with, smaller pathologic size, lower histologic grade, lower incidence of lymph node involvement and lower clinical stage. The identification of this subset of low grade, low stage HER-2 NEU positive tumors may be attributed to newer imaging modalities such as digital tomosynthesis and more aggressive preventive screening measures. These sensitive screening techniques may ensure a good clinical outcome.
Recurrent and de-novo autoimmune hemolytic anemia in patients treated with immunotherapy for advanced cancer.
Authors: Natasha A. Jain, Kerry Anne Rogers, Tzu-Fei Wang, Songzhu Zhao, Lai Wei, Gregory Alan Otterson, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2019)

e14170 Background: Immunotherapy (IO) has brought dramatic clinical benefit to cancer patients. Serious immune-related adverse events (irAE) have been reported, however, hematological toxicities such as autoimmune hemolytic anemia (AIHA) remains poorly characterized. Here we performed a single institution retrospective study to determine the incidence and risk factors for AIHA and if prior positive direct anti-globulin test (DAT) or anti-RBC alloantibodies (alloAb) on type and screen predicts subsequent AIHA in patients treated with IO. Methods: This is a retrospective review of patients treated with IO between November 2012 and February 2017 at the Ohio State University. Patients who received IO either on clinical trial or as standard of care were included. The electronic medical records were reviewed for patients who developed AIHA. Overall survival (OS) was calculated from the date of initiation of IO to death from any cause or date or last follow-up. Medians and 95% CIs were estimated using Kaplan-Meier method and differences compared using the Log-Rank test. The association between irAE and DAT or alloAb testing was studied using Fisher’s exact test. Results: In 1,097 patients treated with IO, we identified 179 (16.6%) patients who had a DAT or alloAb testing at any time, 126 (11.5%) had this done prior to receiving IO. Of the 179 tested 10 (5.6%) had positive alloAb and 7 (3.9%) had a positive DAT. During treatment, two patients with prior history of AIHA experienced recurrence of AIHA during treatment. Three patients had positive DAT after IO, one was diagnosed as a delayed hemolytic transfusion reaction, and the patient required transfusion every 2 weeks since DAT positivity. The other two with positive DAT were not diagnosed with AIHA and did not require intervention. Patients with positive baseline alloAb (n = 6) had higher rate of irAE than patients without (n = 120) (13.3% vs 2.1%, p = 0.03), including 2 thyroid dysfunction, 2 skin rash, 2 myalgia, 2 hemolytic anemia. Patients with a positive DAT at baseline did not have a higher rate of irAEs (p = 0.09). Median OS for the entire cohort was 7.6 (5.8-9.9) months. No association was found between baseline positive DAT or alloAb and OS (p = 0.1748 and p = 0.3164 respectively). Conclusions: The incidence of hemolytic anemia in patients treated with IO was low. Presence of alloAb at baseline may predict irAE during IO treatment as patients with positive alloAb at baseline had a higher rate of irAE than those without.
Determination of AR-V7 in plasma in patients with metastatic prostate cancer using capillary Nano-immunoassay.
Authors: Alvaro Virseda, Juan Luis Garcia, Sara Marcos Asensio, Javier Garcia Garcia, Manuel Herrero POLO, Belen Cigarral Garcia, Irena Misiewicz-Krzeminska, Rogelio Gonzalez, Rocio Garcia, Juan J. Cruz-Hernández, Francisco Gomez Veiga
Journal: Journal of Clinical Oncology (2019)

e16574 Background: Liquid biopsy has the potential to provide information about cancers without invasive biopsy, using circulating biomarkers. The aim of present study was determinate the presence of androgen receptor splice variant 7 (AR-V7) in plasma using capillary nano-immunoassay in metastasis PCa and correlation with clinical and analytical data. Methods: Whole blood (10 ml) was collected and processed in EDTA tubes. Previously to determinate the presence of ARV-7 in plasma Capillary Electrophoresis Immunoassay or SimpleWestern analyses were performed using the WES™ machine. With this technique, proteins are separated by size, immobilised and probed with specific antibodies. The primary antibody used was Anti-Androgen Receptor antibody. Results: The study included 31 patients with diagnostic of PCa metatasic . Clinical characteristics of the patients were described in the table. AR-V7 signal was detected in 11 cases (36%). Twenty samples (64%) were considered as negative. The most of patients with expression positive for AR-V7, showed a Gleason score ≥ 8 (64% of cases). In AR-V7+, hemoglobine and dehydrogenase lactate levels were statistically significant (p &lt; 0,05) respect to ARV7-. So, in AR-V7+ patients showed increased of FA and Albumin. Conclusions: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 36% of the PCA metastasic. These findings lay the foundations for liquid biopsy as a means of obtaining biological data in a more convenient way for the patient.[Table: see text]
Longitudinal versus cross-sectional IL-6 measurements in tocilizumab-treated GCA. Response to: ‘Analysis of IL-6 measurement in GCA patients treated with tocilizumab should consider concomitant treatment with prednisone’ by Samson and Bonnotte
Authors: Christoph T Berger, Thomas Daikeler
Journal: Annals of the Rheumatic Diseases (2019)

Figure 1 Stratification of interleukin 6 (IL-6) blood levels based on daily cortisone dose or age.IL-6 plasma levels in subjects: (A) receiving or ≥20 mg of daily prednisone (PDN) in early time-points (left) and before tocilizumab (TCZ) was stopped (right); (B) younger versus older than 70 years of age.(C) Correlation matrix of: 'n TCZ'=total numbers of TCZ doses received, IL-6 after the second dose and IL-6 before TCZ was stopped, as well as daily prednisone doses at the time of TCZ start and discontinuation.Values indicate Spearman r correlation coefficients.'PDN at start' versus 'IL-6 after second dose' (p=0.008),'PDN at stop' versus 'n TCZ' (p=0.042) and 'IL-6 after second dose' versus 'at TCZ stop' (p=0.029) were significant.on July 12,
Evaluation of polyfunctional T cells to staphylococcal enterotoxins A and B in adults with atopic dermatitis
Authors: R. L. Orfali, M. N. Sato, L. M. S. Oliveira, V. G. D. Santos, T. D. O. Titz, C. de Lollo, V. Aoki
Journal: British Journal of Dermatology (2014)
High frequency of HER2-specific immunity observed in patients (pts) with HER2+ cancers treated with margetuximab (M), an Fc-enhanced anti-HER2 monoclonal antibody (mAb).
Authors: Jeffrey L. Nordstrom, John Muth, Courtney L. Erskine, Catherine Sanders, Erik C. Yusko, Ryan O Emerson, Min-Jung Lee, Sunmin Lee, Jane B Trepel, Seock-Ah Im, Yung-Jue Bang, Giuseppe Giaccone, Todd Michael Bauer, Howard A. Burris, Jan E. Baughman, Edwin P. Rock, Paul A. Moore, Ezio Bonvini, Keith L Knutson
Journal: Journal of Clinical Oncology (2019)

1030 Background: Previous studies have shown that 44-71% of trastuzumab (T)-treated pts develop HER2-specific immunity (Clin Cancer Res 2007, 13:5133; Cancer Res 2016, 76:3702; Breast Cancer Res 2018, 20:52). M is an Fc-engineered mAb that shares similar HER2 binding and antiproliferative activity as T. The Fc region of M has been engineered for increased affinity to the activating FcγRIIIA (CD16A) and lower binding to the inhibitory FcγRIIB (CD32B), attributes that may enhance the mAb’s immune function, such as antigen presentation. Methods: HER2+ cancer pts who progressed on prior therapy received M (0.1-6 mg/kg QW for 3 of every 4 weeks [N = 34]; or 10-18 mg/kg Q3W [N = 32]) in phase 1 trial NCT01148849. PBMC and plasma were collected pre-dose and 50 days post-dose for 46 pts and &gt; 4 years for 3 pts on long-term treatment. Response to HER2 or control antigens (Ag) was assessed by IFNγ ELISpot and antibody (Ab) ELISA. In 14 pts, T-cell antigen receptor (TCR) repertoire was assessed by immunosequencing. Results: Following M treatment, mean frequencies of IFNγ-producing T cells specific for intra- or extracellular fragments of HER2 increased by 2.5 to 6-fold (p &lt; 0.0027, paired t test). Most (95%) of subjects responded to ≥2 of 6 (median = 5) HER2 Ag. Mean HER2-specific Ab concentration increased by 19-54% (p &lt; 0.0001), with all subjects responding to ≥2 (median = 5) of the 6 Ag. A small 1.6-fold increase in IFNγ response to control CMV/EBV/Flu (but not tetanus or cyclin D1) peptides was observed; no increase in Ab response to control Ag was noted. Subsets of HER2-specific T-cell and Ab responses persisted during long-term treatment. Median TCR clonality increased by 54% (p = 0.003), with an average of 125 unique clones expanding, while overall TCR diversity remained unchanged (p = 0.19). Conclusions: Treatment of HER2+ cancer with M was associated with enhanced HER2-specific T-cell and Ab responses together with increased TCR clonality, indicative of a more focused T-cell repertoire. The high frequency of HER2-specific immunity in M-treated patients ( &gt; 95%) is consistent with its enhanced Fc region contributing to linkage of innate and adaptive immune responses.