tbuckley/cabot-search huggingface dataset:
Anti-PD-1 responsive circulating immune cells as biomarkers of response to neoadjuvant chemotherapy in HER2+ breast cancer (BC).
Authors: Nicola Gaynor, Norma O'Donovan, John Crown, Denis Collins
Journal: Journal of Clinical Oncology (2020)

e12646 Background: HER2+ BC patients (pts) achieving a pathological complete response (pCR) to neo-adjuvant therapy have better long-term survival outcomes. Alternative treatment strategies may be more beneficial for pts that will not achieve a pCR but there are no predictive biomarkers for stratification of pts to appropriate clinical studies. Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by immune cells like NK cells can be elicited by therapeutic antibody therapies including the HER2-targeting trastuzumab (T). We hypothesised that the presence of immune checkpoint-inhibited ADCC-mediating immune cells in the blood may identify pts with an immune-suppressed tumour microenvironment who will not achieve a pCR. We used an in vitro functional assay to assess the PD-1-inhibited ADCC response of pre-treatment peripheral blood mononuclear cells (PBMCs) from HER2+ BC pts as a potential biomarker of pCR. Methods: Pre-treatment PBMC samples (n = 21) were obtained from HER2+ BC pts who received neo-adjuvant chemotherapy (docetaxel, carboplatin) with a HER2-targeted therapy (T n = 5, T and lapatinib (L) n = 13, or L alone n = 3), ICORG 10-05 (NCT01485926). Pt response was determined as pCR (n = 7), partial response (PR, n = 10) or non-response (NR, n = 4). The immune function assay used a flow cytometry-based method to determine the T (10µg/µl)-mediated ADCC (T-ADCC) capacity of the PBMCs +/- the anti-PD-1 therapy pembrolizumab (P) (10µg/µl). The HER2+ BC cell line SKBR3 was used as the target cell line. Direct PBMC-mediated cytotoxicity against the non-MHC Class I-restricted leukemic K562 cell line was also determined. Statistical analysis was carried out using the MedCalc program. Results: There was no significant difference in direct cytotoxicity against K562 (pCR vs NR p = 0.13, pCR vs PR p = 0.52, PR vs NR p = 0.40), or in T-ADCC against SKBR3 (pCR vs NR p = 0.71, pCR vs PR p = 0.52, PR vs NR p = 0.32), between response cohorts in the absence of P. When T-ADCC was examined in individual pt samples, the addition of P resulted in significant increases in T-ADCC vs T-ADCC in the absence of P in 3/4 NR (p = 0.03, p = 0.01, p = 0.002) and 4/10 PR (p = 0.003, p = 0.007, p = 0.009, p = 0.01). No significant increase in T-ADCC was observed in the pCR cohort (0/7) as a result of the addition of P. Using pre-treatment PBMCs, the assay detected 7/14 (50%) of HER2+ BC pts who did not achieve a pCR. Conclusions: PD-1-inhibited ADCC-capable immune cells may identify a subset of HER2+ BC pts who will not achieve a pCR. Further investigation is warranted using a larger patient cohort.
Weight establishment of the community teaching base evaluation system for general practitioner in Shanghai
Authors: Huiling Xia, Sunfang Jiang, Juan Shou, Shanzhu Zhu
Journal: BMJ (2017)

Objective
To establish the weight of the evaluation index system for community teaching base of general practitioner (GP) standardized training.


Methods
The weight assignment of the evaluation index system for community teaching base of GP training was established by using analytic hierarchy process, based on the literature review and two rounds of Delphi consultation.


Results
The evaluation index system for community teaching base was composed of four first-class indexes, eight second-class indexes and 27 third-class indexes. Four first-class indexes were basic conditions (weight 0.195 3), teaching conditions (weight 0.138 1), teaching staff (weight 0.276 1) and teaching practice (weight 0.390 5). The top three second-class indexes were: teaching management (weight 0.195 3), teaching assessment and evaluation (weight 0.195 3), and teaching ability (weight 0.184 1). All levels of index weights were satisfied with the consistency test, and the weights were acceptable.


Conclusion
Weight establishment improves the index selection system of community training base for GPs, having better rationality and operability, which may provide a rational assessment tool for community base of GP training in future.


Key words: 
General practitioners; Standardized training; Teaching evaluation
X-ray-gulded three-lumen nasogastrojejunal tube in postsurgical gastroparesis syndome
Authors: Rui-hong Li, De-chun Li, Xiao-peng Lu
Journal: BMJ (2009)

The three-lumen nasogastrojejunal tube was placed through guide wires under X-ray monitoring for 21 patients with postsurgical gastroparesis syndrome.The suction cavity was placed at sinus ventriculi for decompression and the feeding cavity was placed at jejunum for nourishment.The tube was successfully placed in all patients except one who need the help of gastroscopy.The time of procedure was 5-38 min with an average of 16 min.The duration for the nutrient tube staying was 9-51 d with an average of 23 d.All patients cured.Three-lumen nasogastrojejunal tube placed under X-ray monitoring proves to be a safe, convenient, highly tolerable and effective procedure.

Key words: 
Catheterization;  Enteral nutrition
Serum soluble CD25 and ferritin in distinguishing patients with uncomplicated hematologic malignancies from patients with hematologic malignancies complicated by hemophagocytic lymphohistiocytosis.
Authors: Adi Zoref Lorenz, Liron Hofstetter, Jun Murakami, Oren Pasvolsky, Elad Guber, Joanne Yacobovich, Martin Ellis, Michael Jordan
Journal: Journal of Clinical Oncology (2020)

e20072 Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory syndrome with distinct clinical and laboratory features. In adults, HLH is often associated with underlying malignancy, most commonly hematologic malignancies (HM). HLH occurs in 1% of adults with HM and overall survival can be low as 10-20%. Abnormal serum levels of the inflammatory markers sCD25 and ferritin are diagnostic criteria for familial HLH. However, because these reactants are often elevated in malignancy, appropriate levels for diagnosis in HM-HLH are unknown. In this study, we establish optimal sCD25 and ferritin levels for the diagnosis of HM-HLH in adults. Methods: Patients from three centers in Israel and Japan with HM-HLH and HM in whom sCD25 testing was performed were studied. The diagnosis of HLH was according to the HLH 2004 diagnostic criteria. Initial (at HLH presentation) and the maximum ferritin levels were analyzed. Sensitivity, specificity, and optimal cutoffs were calculated by receiver operating characteristic (ROC). Results: 62 patients with HM's without HLH and 40 patients with HM-HLH were included. The distribution of ages and HM subtypes was similar between groups (mostly B cell, T/NK cell, and Hodgkin's lymphoma). The median sCD25 concentration in HM was 1776 U/ml versus 8077 U/ml in HM-HLH. The median initial/ maximum ferritin levels were 190/202 ng/ml for the HM group and 2267/4515 ng/ml for the HM-HLH group. Both sCD25 and ferritin were very sensitive but nonspecific. sCD25 &gt; 2400 U/ml had a sensitivity/specificity of 95%/65%, while initial ferritin &gt; 500 ng/ml had a sensitivity/specificity of 95%/75%. ROC analysis demonstrated optimal confirmatory cutoff values (maximizing specificity) of &gt; 10,056 ng/ml for sCD25 (sensitivity/specificity 47%/95%). While initial ferritin demonstrated a cutoff of &gt; 5231 ng/ml (sensitivity/specificity 22.5%/95%, AUC = 0.88) the maximum ferritin performed better with the cutoff of &gt; 5748 ng/ml (sensitivity/specificity 45%/95%, AUC = 0.92). Conclusions: Our data suggest that the current HLH 2004 criteria of ferritin &gt; 500 ng/ml and sCD25 &gt; 2400 U/ml are effective screening criteria for the complication of HLH in HM patients. sCD25 &gt; 10,000 U/ml and initial ferritin &gt; 5,200 ng/ml are highly specific. Patients with suspected HM- HLH should have serial ferritin testing which increases specificity of this test. Future prospective studies are needed to confirm these findings.
REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors—Results of the non-MSI-H metastatic colorectal cancer (mCRC) cohort.
Authors: Sophie Cousin, Carine A. Bellera, Jean Philippe Guégan, Carlos A. Gomez-Roca, Jean-Philippe Metges, Antoine Adenis, Simon Pernot, Coralie Cantarel, Michèle Kind, Maud Toulmonde, Kevin Bourcier, Isabelle Soubeyran, Alban Bessede, Antoine Italiano
Journal: Journal of Clinical Oncology (2020)

4019 Background: Regorafenib (R) has been shown to modulate anti-tumor immunity by different mechanisms including reduction of tumor-associated macrophages (TAMs). Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical models. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of R (160 mg QD 3weeks/4) + Avelumab (A) (10 mg/kg every 2 weeks) combination in non MSI-H mCRC patients (pts). The primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline and C2D1. Results: Between Nov. 2018 and Oct. 2019, 48 pts were enrolled in 4 centers. Median age was 61.8 (range: 26.3-78.7). Median follow-up was: 7.2 months. Median number of previous treatment lines was: 3 (range: 1-7). 41 (87.2%) pts experienced at least 1 dose modification or treatment interruption. The most common grade 3/4 adverse events were palmar-plantar erythro-dysesthesia syndrome (29.8%), hypertension (23.4%) and diarrhea (12.8%). No death was related to the treatment. Among 40 pts who had at least one imaging tumor assessment, 12 (30%) had reduction in tumor burden. Best response was stable disease for 23 pts (57.5%) and progressive disease for 17 pts (42.5%). The median PFS and OS were 3.6 months (CI 95% : [1.8 – 5.4]) and 10.8 months (CI 95% : [5.9 – NA]) respectively. Baseline tumor samples and paired biopsies were available for 24 and 15 pts respectively. High infiltration by TAMs at baseline was significantly associated with adverse outcome (PFS: 1.9 vs 3.7 months, p=0.045; OS: 4.8 months vs NR, p=0.027). Increased tumor infiltration by CD8+ at C2D1 compared to baseline was significantly associated with better PFS (p=0.011). Combining low TAMs infiltration and low tumor cells to CD8+ T cells distance enabled the identification of a subgroup of pts (n= 6/24, 25%) more likely to benefit from R+A combination: median PFS: 5.3 vs 1.9 months (p=0.037); median OS: NR vs 5.3 months (p=0.02). Conclusions: The R+A combination achieved PFS and OS that compared favourably with historical data of R alone in this clinical setting. High-resolution analysis of tumor samples identified a composite score based on TAMs infiltration and tumor cell to CD8+ T cells distance which could be used as a biomarker in further studies investigating this approach in mCRC pts. Clinical trial information: NCT03475953 .
Correlation between HER2 amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2 positive breast cancer.
Authors: Silvia Antolin, Lucía García-Caballero, Cristina Reboredo, Aurea Molina Diaz, Joaquín Mosquera, Angel Vázquez-Boquete, Rosalía Gallego, Maria Paz Santiago, Angel Concha, Maria EVA Perez, Lourdes Calvo, Tomás García-Caballero
Journal: Journal of Clinical Oncology (2020)

e12641 Background: HER2 targeted therapy in combination with chemotherapy have changed the aggressive natural history of HER2-positive tumors. To select patients to be treated with this type of agents, determination of HER2 status is usually carried out by immunohistochemistry, followed by in situ hybridization in equivocal cases (2+). There are contradictory data in literature regarding correlation between level of HER2 amplification determined by FISH and early and long-term treatment benefits. Objectives: The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEN17 and number of HER2 signals/nucleus) with the grade of response to neoadjuvant treatment with trastuzumab and chemotherapy. Methods: We analyzed 100 consecutive cases of stage I-III breast carcinomas treated with trastuzumab and chemotherapy in the neoadjuvant setting at A Coruña University Hospital between 2005 and 2016. At Santiago University Hospital, 4 tissue microarrays were prepared and the IQFISH (Dako-Agilent) technique was performed using pretreatment biopsies. Results: HER2 amplification was found in 92 of 100 cases studied. Pathological Complete Response (pCR) (Miller-Payne grading system) was obtained in 58% of the patients whose tumors showed amplification. No pCR was obtained in the 8 patients whose tumors were negative by FISH (not amplified). Analysis of the quantitative results demonstrated a statistical significant direct correlation between pCR and both HER2/CEN17 ratios and HER2 gene copies/nucleus (p = 0.002 and p= 0.004, respectively). We also demonstrated an association between the HER2 amplification level (both ratios and numbers of HER2 signals) and a trend toward improved disease free survival (DFS) (p = 0.451 and p= 0.619, respectively). Conclusions: HER2 amplification level determined by FISH it is a good and available predictive factor of response and must be included in pathologic reports because it can provide valuable information to oncologists on the possibilities of achieving pCR after neoadjuvant treatment in HER2-positive breast cancer. Key words: Breast cancer, FISH, HER2 amplification, trastuzumab, neoadjuvant therapy, pathological complete response.
The skin types closely related to development of the facial acneiform rash and the therapeutic effects of EGFR inhibitors in RAS wild-type metastatic colorectal cancer: Ancillary analysis of FAEISS study.
Authors: Syusuke Yoshikawa, Naoya Yamazaki, Yoshio Kiyohara, Keiko Nozawa, Haruhiko Fukuda, Taro Shibata, Akiko Hasegawa, Masanobu Takahashi, Toshiki Masuishi, Akihito Kawazoe, Tetsuya Hamaguchi, Takahiro Tsushima, Ryunosuke Machida, Katsuko Kikuchi, Yasuo Nakai, Sumiko Takatsuka, Tomohiro Nisina, Hitoshi Mizutani, Atsuo Takashima
Journal: Journal of Clinical Oncology (2020)

3637 Background: At ESMO2019, we reported the primary results of a randomized controlled trial (FAEISS study) investigating the efficacy of topical corticosteroid treatment to facial acneiform rash (AR) by EGFR inhibitors comparing groups starting with a very strong topical corticosteroid and the standard weak topical corticosteroid. As an ancillary analysis, we investigated the association between AR and the pre-treatment skin types, as well as between the skin types and therapeutic effects of EGFR inhibitors on the primary disease. Methods: Utilizing pre-treatment clinical photos of the face taken according to the method determined by FAEISS study protocol, we divided the skin types into categories including enlarged pore, oiliness, xerosis, wrinkles, skin color/redness, and allocated the score (1-3) by central review. The severity of AR occurred during the study was graded and was evaluated the association with the specific skin type by Fisher’s exact test. We also investigated the association between the skin types and the best overall response (RECISTv1.1) to EGFR inhibitor therapy on the primary disease using the Cochran-Armitage trend test. Results: Of the registered 172 cases of RAS wild-type metastatic colorectal cancer [104 men and 68 women, median age = 68 (26-79)], omitting the cases with unevaluable data, finally we analyzed 146 cases for associations between the skin types and AR and 147 cases for best overall response. Interestingly, AR developed 13.6% of enlarged pore score 1, 29% of score 2 and 45.8% of score 3, and patients with enlarged pore tended to have more AR (p = 0.058). Surprisingly, the response(CR/PR/SD) of the primary disease were 59.1% of the enlarged pore score 1, 70.6% of score 2 and 87.0% of score 3, and showed statistically significant trend(p &lt; 0.038). Conclusions: This study suggested that a skin type (enlarged pore) is a possible marker predicting AR risk in EGFR inhibitor therapy for RAS wild-type metastatic colorectal cancer, and better therapeutic effects of EGFR inhibitors.
Efficacy of laryngeal mask airway proseal and laryngeal mask airway classic in gynecological patients undergoing laparoscopic surgery
Authors: Sheng-kai Gong, Xue-ping Han, Yan Zhang, Yan-li Ma, Yan-zi Chang
Journal: BMJ (2012)

Sixty gynecological patients undergoing laparoscopic surgery during October 2010 to June 2011were randomly divided into 2 groups:laryngeal mask airway proseal ( PLMA group,n =30 ) and laryngeal mask airway classic (CLMA group,n =30).Laryngeal mask was inserted after induction.The heart rate (HR),mean arterial pressure (MAP),airway sealing pressure,the average time of placement,the pulmonary satisfaction and complications were recorded.There was no significant difference in heart rate and MAP between the two groups(P＞0.05).The airway sealing pressure [ (26 ±6) cm H2O ( 1cm H2O =0.098 kPa) vs.(16±5) cm H2O],the average time of placement [(36±5) vs.(24±6) s)] and the excellent lung ventilation(90％ vs.73％ ) in the PLMA group were more significantly increased than those in the CLMA group(P ＜0.05).PLMA can assure good airway sealing and is more suitable for gynecological patients undergoing laparoscopic surgery.

Key words: 
Laryngeal mask; Laparoscopy
Trends in conditional survival and predictors of late death in neuroblastoma.
Authors: Hannah Olsen, Kevin M. Campbell, Rochelle Bagatell, Steven G. DuBois
Journal: Journal of Clinical Oncology (2020)

10533 Background: Significant advances in the treatment of neuroblastoma have been made in the past several decades. There are scant data examining how these improvements have changed over time and differentially affected conditional survival among high- and non-high-risk patient groups. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Database. We analyzed clinical characteristics and survival outcomes for 4717 neuroblastoma patients. Kaplan-Meier methods were used to estimate overall survival (OS) and conditional overall survival (COS) conditioned on having survived 1, 2, or 5 years from diagnosis, with estimates compared between groups using log-rank tests. Results: Five-year OS was 41.46% (95% CI 38.77-44.13) for the high-risk group and 91.13% (95% CI 89.49-92.53) for the non-high-risk group. Both groups saw significant improvements in OS by decade (p&lt;0.001). Five-year COS among 1-year survivors was 52.69% (95% CI 38.77-44.13) for the high-risk group and 96.75% (95% CI 95.57-97.62) for the non-high-risk group. One-year survivors in the high-risk group showed a statistically significant improvement in COS over time. No difference in COS was observed among 5-year high-risk survivors. There were no statistically significant changes in COS over time for 1- and 5-year survivors in the non-high-risk group. In the high-risk and non-high-risk groups, 82% and 32% of late deaths (&gt;5 years from diagnosis) were attributable to cancer, respectively. Statistically significant adverse prognostic factors for late death were age &gt;1 year at diagnosis, metastatic disease, and non-thoracic primary site (p=0.001). Conclusions: Improvements in COS over time have largely benefited high-risk patients, though they are still at higher risk for late death due to cancer when compared to non-high-risk patients. Age, stage, and primary site, but not treatment decade, influence outcomes among 5-year survivors. [Table: see text]
Assessment of Telestroke Capacity in US Hospitals
Authors: Jessica V. Richard, Andrew D. Wilcock, Lee H. Schwamm, Lori Uscher-Pines, Kori S. Zachrison, Arham Siddiqui, Ateev Mehrotra
Journal: JAMA Neurology (2020)

This study describes the growth of telestroke capacity in US hospitals and compares the characteristics of the hospitals with and without telestroke capacity.
Short-term training of direct observation procedural skills (DOPS) for community general practitioner trainers
Authors: Jie Gu, Zhi-gang Pan, Shan-zhu Zhu
Journal: BMJ (2013)

Objective
To evaluate the efficacy of short-term training of direct observation procedural skills (DOPS) for community general practitioner (GP) trainers.


Methods
Thirty six GP trainers participated in one-day workshop of DOPS. The participants were interviewed with questionnaire before and after the training program and the training video was scored.


Results
47.2%(17/36) of GP trainers knew and briefly understood DOPS before the training. 41.7%(15/36) of them had a rough idea of how to use it and only 2.8%(1/36) had used it before. All of these trainers wanted to learn how to perform DOPS. The vast majority of GP trainers completely or basically understood the standards for evaluation of 11 items of DOPS after the training. The accuracy rates of 4 items were close to or more than 50.0% in 9-point scale and 7 items exceeded 50.0% in 3-rank system. There was significant difference in accuracy rates of 6 items between the two scoring system (all P <0.01).


Conclusions
Community GP trainers recognize the advantages of DOPS in assessment of clinical skills and have strong intention of application. The efficacy of short-term workshop is satisfactory, but the evaluators need more training and practice.


Key words: 
General practitioner; Teacher training; Direct observation of procedural skills