tbuckley/cabot-search huggingface dataset:
Radiochemotherapy with gemcitabine as radiosensitizer in patients with soft tissue sarcoma.
Authors: Marinela Augustin, Martin Wilhelm, Bert Reichert, Gabriele Margareta Siegler, Juergen Dreier, Michael Rottmann, Martin Blos, Alexander Kalisch, Sabine Dressler, Hubert Stein, Jens Koehler, Thomas Papadopoulos, Christian Meyer, Peter Hohenberger, Jens Jakob, Nikolaos Vassos, Christian Grehn, Clemens Albrecht
Journal: Journal of Clinical Oncology (2020)

e23559 Background: Radiation therapy is an essential backbone of the management of patients (pts.) with soft tissue sarcoma (STS) as part of a multimodal curative or palliative treatment. Concurrent external-beam radiation therapy (EBRT) and chemotherapy with doxorubicin (doxo) and ifosfamide (ifo) may be indicated as well, but is associated with relevant toxicity. Gemcitabine (gem) is a known radiosensitizer and has shown activity in STS. The purpose of this study was to evaluate the efficacy and toxicity of concurrent EBRT and gemcitabine. Methods: A single center, retrospective analysis of 12 patients (pts) with STS treated with concurrent EBRT and gemcitabine from Nov 2017 to Dez 2019 in a neoadjuvant (6 pts) or palliative setting (6 pts). Gemcitabine (gem) was administered with 150-300mg/m2 once weekly for the duration of the EBRT (50 Gy in 25 fractions over 5 weeks). In the neoadjuvant treated group, 4 pts had undifferentiated pleomorphic sarcoma (UPS) G3, 1 leiomyosarcoma (LMS) G2 and 1 retroperitoneal G1 liposarcoma (LPS). The pts. were either not eligible for a neoadjuvant systemic treatment with doxo/ifo or received the EBRT/gem treatment in addition to it. Results: 5/6 pts. with neoadjuvant EBRT/gem had R0 resection and 1/6pt. R1. The IUCC stage was IIIB in 5/6 pts and IB in 1/6 pt. The tumor regression grade (TRG) was &gt; 99% in 3/4 pts. with UPS G3 (75%) and 80% in 1/4 pt. with UPS G3. The TRG for the G2 LMS and for the G1 LPS was 20%. All pts treated in palliative setting had high grade sarcoma and responded to the treatment with partial remission, the 6 months’ local control rate was 83% (5/6 pts) for symptomatic fast growing lesions, 1/6 pt. being in PR at 4 months follow up. The combination treatment was well tolerated with reversible skin toxicity CTCAE grade I. As expected transient thrombocytopenia was observed without limiting effect on the planned EBRT. Conclusions: The combination therapy of EBRT and gemcitabine as sensitizer in pts. with STS is feasible und well tolerated. The treatment is an option for patients not eligible for neoadjuvant systemic treatment with doxo/ifo and in the palliative setting as well. It might be more potent than radiation only in achieving tumor regression and local control for high grade STS.
缺铁性贫血初治无效原因分析及治疗策略
Authors: 吴少玲, 赵新东, 汪洪毅, 史雪
Journal: BMJ (2012)

对80例缺铁性贫血初始治疗无效患者进行原因分析,显示原因主要为月经过多(40.3％)、饮食方式不良(22.5％)、幽门螺杆菌(Hp)感染(18.8％)、服药方式不当(15.0％)、钩虫感染(1.3％)等,改进相应的治疗措施后,治愈率达到98.8％。
Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy for breast cancer: Results from a prospective institutional database.
Authors: Megan Tesch, Nathalie LeVasseur, Christine E. Simmons, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2020)

e12619 Background: There has been growing interest in the optimal sequencing of anthracyclines and taxanes in neoadjuvant chemotherapy (NACT) for breast cancer. However, data comparing efficacy of administering taxanes prior to anthracyclines as opposed to the opposite sequence remains limited and inconsistent. The objective of our study was to assess the impact of sequence order on pathologic and clinical outcomes in a real-world setting. Methods: A prospective institutional database was analyzed to identify all HER2-negative breast cancer patients treated with NACT from 2012 to 2019. Rates of pathologic complete response (pCR), down-staging, and breast-conserving surgery were compared between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Chi-square and independent sample non-parametric tests were used to test for associations between variables and outcomes. Results: Of the 270 patients who met eligibility criteria, 175 (65%) received AC-T and 95 (35%) received T-AC. Median age was 55 (IQR 24-86). Overall, 83% of patients had stage IIB or greater tumors, 40% had grade 3 histology, and 36% had triple-negative disease. Characteristics were balanced between the AC-T and T-AC groups (all p &lt; 0.05). Median duration of treatment with NACT was 102 days (IQR 29-203). Rates of pCR (19% vs 21%, p = 0.750), down-staging (68% vs 61%, p = 0.188), and conversion to breast-conserving surgery (26% vs 20%, p = 0.314) were similar for AC-T vs T-AC, respectively. pCR was higher in triple-negative compared to hormone-positive cases (33% vs 13%, p &lt; 0.001). Conclusions: In this small population-based cohort, sequence order of anthracyclines and taxanes did not demonstrate statistically significant differences in evaluated outcomes from NACT for breast cancer. This supports the current variation in prescribing practice and highlights the need for further studies in this area.
Abstract 9578: Impact of Data From a Prior Transthoracic Echocardiogram in the Identification of a Potential Cause for Syncope
Authors: Amrita Mukhopadhyay, Changyu Shen, Nicholas Kiefer, Ari Kriegel, Karima Ali, Warren J Manning
Journal: Circulation (2019)

Background: Transthoracic echocardiography (TTE) is frequently obtained to evaluate syncope. With the common use of TTE, many patients presenting with syncope are likely to have had a prior TTE per...
Genomically informed longitudinal monitoring of circulating tumor DNA (ctDNA) to predict outcomes of cancer therapy.
Authors: Mohamed Alaa Gouda, Helen J Huang, Sarina Anne Piha-Paul, S. Greg Call, Daniel D. Karp, Siqing Fu, Aung Naing, Vivek Subbiah, Shubham Pant, Apostolia Maria Tsimberidou, David S. Hong, Jordi Rodon Ahnert, Funda Meric-Bernstam, Filip Janku
Journal: Journal of Clinical Oncology (2020)

3533 Background: Short fragments of ctDNA can be detected and quantified from blood samples of patients with cancer. We hypothesize that dynamic changes in quantity of ctDNA in patients with advanced solid cancers during the first few weeks of therapy can predict treatment outcomes reported by standard imaging. Methods: We enrolled patients with advanced cancers treated with experimental therapies, who had blood collection for ctDNA isolation and testing at baseline, mid-cycle and at the time of restaging imaging. Patients who were treated with multiple treatment lines were included with separate record for each therapy. Genomically informed molecular testing of ctDNA was performed using unamplified droplet digital PCR (QX200, Bio-Rad) designed based on known molecular profile of tumor tissue and ctDNA was quantified as aggregate variant allele frequency (VAF%) for detected molecular aberrations. Patients were classified based on results of their first restaging imaging as responders (complete [CR] or partial response [PR]) vs. non-responders (stable disease [SD], progressive disease [PD]) and progressors (PD) vs. non-progressors (CR, PR, SD). Results: Total of 85 patients who received 132 courses of therapies between May 2012 and June 2019 were analyzed. Breast (N = 21), melanoma (N = 14) and cholangiocarcinoma (N = 14) were most frequent tumor types. Aggregate VAF at mid-cycle was higher in non-responders (3.98%) compared to responders (0.40%, P = 0.016) and in progressors (4.40%) compared to non-progressors (2.10%, P = 0.019) as measured by 5% trimmed mean. Similarly, aggregate VAFs at first imaging restaging was higher in non-responders (5.10%) compared to responders (0.10%, P = 0.001) and in progressors (10.80%) compared to non-progressors (0.90%, P &lt; 0.001). Progressors demonstrated increase in ctDNA VAF at the time of the first imaging restaging compared to decrease in non-progressors (0.7% vs. -4%, P = 0.015). In addition, increase in ctDNA VAF at the first imaging restaging was associated with more PD (44% vs. 8%, P = 0.019) and less PR/CR (0% vs. 31%, P &lt; 0.001). Median time-to-treatment failure was shorter in patients with increase in ctDNA VAF at the time of the first imaging restaging (52 days vs. 89 days, P = 0.002). Conclusions: Dynamic changes in quantity of blood-derived ctDNA within the first few weeks of therapy correspond with treatment outcomes reported by the first restaging imaging and time-to-treatment failure.
The clinical significance of neoadjuvant therapy in breast cancer
Authors: 杨晨, 沈坤炜
Journal: BMJ (2009)

乳腺癌新辅助治疗(neoadjuvant therapy)也称为新辅助全身性治疗(neoadjuvant systemic therapy,NST)、初始全身性治疗(primary systemic therapy,PST)或术前治疗(preoperative therapy),是指在手术切除乳腺原发病灶之前所采用的伞身性的药物治疗.随着术后辅助治疗中疗效的确认,继化疗药物后,目前内分泌药物和分子靶向药物也应用于乳腺癌的NST.NST现已成为局部晚期乳腺癌的标准治疗方案,并给可手术的早期乳腺癌的治疗方案提供了一种新的选择,成为乳腺癌多学科综合治疗的重要组成[1-2]。
Analysis of monitoring information about infant congenital heart disease in Changzhou
Authors: Lin Zhang, Jinxiu Wang
Journal: BMJ (2014)

Screening of CHD of infants (11 178) born from May 1st 2012 to April 30th 2013. 92 infants were screening positive, 68 were diagnosed.The detectable rate of CHD was 6.08‰, while boys were 3.31‰, girls were 2.77‰.68 CHD patients, the top three were VSD(2.14‰), PDA(1.34‰) and ASD(0.89‰). In these infants, detectable cardiac souffle were 61, abnormal pulse oximetry were 40.The detectable rate of CHD among infants was identical compare the average level of whole country, but the distributional characteristics was disparity.The screening of CHD was feasible, and cardiac souffle and pulse oximetry were recommended.


Key words: 
Infants, newborn; Heart defects, congenital
SPEARHEAD-1: A phase II trial of ADP-A2M4 SPEAR T cells in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.
Authors: Dejka M. Araujo, Mihaela Druta, Mark Agulnik, Sandra P. D'Angelo, Jean-Yves Blay, Sandra J Strauss, Claudia Valverde, Albiruni Ryan Abdul Razak, Erin Van Winkle, Trupti Trivedi, Swethajit Biswas, Dennis Williams, Elliot Norry
Journal: Journal of Clinical Oncology (2020)

TPS11569 Background: ADP-A2M4 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered to target MAGE-A4 + tumors in the context of HLA-A*02. MAGE-A4 has been described as having high expression in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) [1, 2]. This Phase 2 trial was initiated based on the favorable benefit:risk profile of ADP-A2M4 observed in a Phase 1 trial (NCT03132922) of ADP-A2M4 which demonstrated compelling clinical responses in patients with SS. Methods: This Phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety and tolerability of ADP-A2M4 in patients with advanced/metastatic SS or MRCLS who are HLA-A*02 positive and whose tumors express the MAGE-A4 protein. Enrolled patients are to undergo apheresis, and their isolated T-cells are then transduced with the MAGE-A4 c1032 TCR, and expanded. Prior to ADP-A2M4 infusion, patients are to receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m 2 /day x 4 days) and cyclophosphamide (600 mg/m 2 /day x 3 days). Patients are to receive 1 – 10 × 10 9 transduced T-cells. An independent Data Safety Monitoring Board will review ongoing safety and benefit:risk during the interventional phase of the study. Disease will be assessed by independent review per RECIST v1.1 by CT/MRI at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression. As of 24 Jan 2020, there were 17 clinical sites open in the US, one in Canada, and two in Spain. References: 1. Iura K, et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Human Pathology 2017; 61:130-139. 2. Iura K, et al. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1. Virchows Archiv 2017;471:383–392. Clinical trial information: NCT04044768 .
以发热及上腹胀痛为主的大动脉炎伴腹主动脉瘤一例
Authors: 谢聪颖, 谭诗云, 肖艳萍
Journal: BMJ (2010)

患者男,21岁,学生,因发热、上腹痛半月入院.患者于半个月前无明显诱因出现发热,病初最高体温可达38.8℃,以后体温多波动在37.5℃左右,无时间规律.伴上腹部阵发性胀痛,有时向两季肋区放射,间断发作。
Bioinformatic profiling of tumor immunity from patient biopsies to predict survival and response to immunotherapy.
Authors: Yamil Damian Mahmoud, Florencia Veigas, Joaquin Merlo, Monica Balzarini, Dario Rocha, Gabriel Adrian Rabinovich, Elmer Fernandez, Maria Romina Romina Girotti
Journal: Journal of Clinical Oncology (2020)

e15198 Background: Immunotherapies have revolutionized cancer treatment, but responses are not universal and patients who initially respond to therapy develop resistance. The accurate quantification of tumor-infiltrating immune cells holds the promise to reveal the role of the immune system in human cancers and its involvement in tumor escape mechanisms and response to therapy. We present MIXTURE, a new algorithm for tumor immune cell-type proportions deconvolution from transcriptomic data that overcomes competitive methods and revealed novel associations of immune cell types with patient survival and immunotherapy response. Methods: We applied MIXTURE to transcriptomic data from BRCA (n = 1095), LUAD (n = 506), SKCM (n = 472), HNSC (n = 499) and COAD (n = 521) cohorts from TCGA and five published datasets of melanoma patients treated with anti-PD-1/anti-CLTA-4. Results: The analysis of TCGA breast cancer biopsies showed high proportions of M2-macrophages associated with poor patient survival (p &lt; 0.001). In contrast, we found that proportions of follicular T helper cells were associated with better outcome (p &lt; 0.001). We observed a differential immune composition in biopsies of lung adenocarcinoma patients with mutations in TP53 (WT; n = 247; Mut; n = 259) and EGFR (WT, n = 438; Mut, n = 68) related with their different response to immunotherapy (p &lt; 0.05). We found correlations between immune cells proportions and current biomarkers of response to immunotherapy such as TMB, intratumoral heterogeneity, MSI and PD-L1 expression in the TCGA cohorts (p &lt; 0.05). The meta-analysis of melanoma patients treated with immunotherapy showed a distinct immune infiltrate in patients who responded to anti-PD-1 with an increase of immune effector cells such as CD8, CD4 memory activated and gamma-delta T cells, and a decrease in immunosuppressive M2-macrophages (p &lt; 0.05; R = 81; NR = 107). According with the latest findings, we observed higher presence of B cells in responders to anti-PD-1 on-treatment (p = 0.033; R = 31; NR = 23) and in baseline of responders to anti-CTLA-4 (p = 0.028; R = 14; NR = 26). Interestingly, patients that previously progressed to anti-CTLA-4 showed a differential immune profile that was associated with response to anti-PD-1 (p &lt; 0.05; Ipi-Prog = 59; Ipi-Naïve = 102). Conclusions: We demonstrated the potential of MIXTURE to understand the tumor immune microenvironment and its relationship with patient survival and response to immunotherapies. MIXTURE is available for the wider scientific community as web application and as packages for R and Python.
Provider and patient insights into the cancer care journey.
Authors: Sarah McLarty, Kjel Johnson, Ann Francis, Melissa Johlie, Christine Sawicki, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2020)

e14019 Background: Research regarding primary care physicians’ (PCPs) involvement in the cancer treatment journey is limited. When a patient is first diagnosed with cancer, navigating healthcare can be confusing without the proper guidance. We conducted this study to understand a PCP’s involvement in the cancer care journey and how to optimize a patient’s journey through healthcare once diagnosed with cancer. Methods: We conducted a cross-sectional survey of 53 PCPs who have practiced over two years and have had at least one patient referred to an oncologist in the past year. We asked PCPs their method of oncologist referral, utilization of an oncologist selection tool that directs patients to high-quality and low-cost oncologists, and when an advanced directive should be established. We conducted a second survey with 112 current and previous cancer patients over the age of 25 who had received chemotherapy. We asked participants to reflect upon their oncologist’s referral, utilization of an oncologist selection tool that identifies high-quality and low-cost providers, participation in clinical trials, and guidance in creating an advanced directive during their cancer care journey. We conducted both surveys through online survey panels in June 2019. Results: PCPs tend to refer patients to oncologists that are part of their health system (67.9%) and who they know through networking (39.6%). While the majority of PCPs (79.2%) were not currently utilizing an oncology selection tool, the majority (77.3%) expressed a willingness to use such a tool for their newly diagnosed cancer patients. The majority of PCPs (69.8%) believe that cancer diagnosis is the best time to talk about establishing an advance directive, which should be initiated by the patient’s PCP (64.2%) or oncologist (56.6%). Patients ranked a PCP referral (52.7%) as “very important” when selecting an oncologist. One-third of patients used an oncology selection tool; 65.2% responded that a tool to understand true quality and cost of an oncologist would be “somewhat important” or “very important.” Most (71.4%) patients reported that it would be “somewhat important” or “very important” to participate in a clinical trial even though none participated in one. Most patients (54.5%) had an advance directive, although most (54.1%) had completed one before their cancer diagnosis. Conclusions: These results present a compelling rationale for developing a data-driven oncologist selection tool, optimize clinical trial involvement and expand the portion of patients who have an advanced directive at the start of their cancer care.
Endoscopic management of the rare situation where a gastric stromal tumor specimen falls into the nasopharynx
Authors: Jun Yi, Yu Wu, Honghui Chen, Xiaowei Liu
Journal: Endoscopy (2020)

Endoscopic submucosal excavation (ESE) is a safe and effective minimally invasive method for the treatment of gastrointestinal submucosal tumors, especially for those originating from the muscularis propria [1] [2] [3]. Endoloop or vacuum aspiration are traditionally used to collect large specimens, but shedding or damage to specimens sometimes occurs. Here we describe a case in which unusually an endoscopic specimen dropped into the nasopharynx and provide an endoscopic solution for this rare situation ([Video 1]).
A mixed methods study for the evaluation of a digital health solution for cancer multidisciplinary team meetings using simulation-based research methods.
Authors: Clarissa Gardner, Saira Ghafur, Gianluca Fontana, Chaohui Guo, Matthew Stewart Prime, Hutan Ashrafian
Journal: Journal of Clinical Oncology (2020)

e14063 Background: Simulation-based research (SBR) methods involve setting up structured scenarios to replicate real-world situations, with the aim of eliciting real-world reactions and behaviours. SBR is useful for the evaluation of new healthcare solutions without compromising patient safety or navigating complex ethical review processes. However, there are few trials using SBR methods for the evaluation of digital health interventions (DHIs), the adoption of which has been hindered in the NHS due to a lack of evidence-base for their efficacy. SBR methods could be an appropriate tool for testing digital solutions. Methods: The Institute of Global Health Innovation (IGHI) developed a series of simulated lung cancer multidisciplinary team (MDT) meetings to test the NAVIFY Tumor Board solution by Roche Diagnostic Information Solutions, a digital solution for the preparation and conduct of cancer MDTs. To provide an environment for participants to evaluate the capabilities of the NAVIFY Tumor Board solution, 10 simulation sessions were organised in which groups of five to six clinicians were recruited to discuss up to 10 mock patient cases across two simulated MDTs, first using standard tools commonly used to conduct MDTs and then using the NAVIFY Tumor Board solution. The cases were developed by the study team at IGHI and consultants in respiratory medicine and oncology. 56 healthcare professionals (respiratory physicians, oncologists, radiologists, histopathologists, clinical nurse specialists and thoracic surgeons) were recruited. The sessions were video recorded and observations were noted by the study team, followed by a focus group in which participants provided feedback about their experience of the simulated MDTs. Results: Through this study we were able to generate evidence and multi-professional recommendations for Roche regarding the functionality, usability and applicability of the solution in the NHS, as well as beneficial features and those which could be improved. Participants reported that the simulations were realistic and a meaningful way of conducting evaluations of digital health solution without impacting clinical practice or patient safety. Conclusions: This study demonstrated the utility and validity of testing commercial tools in simulated settings to generate meaningful insights from endusers. SBR methods were shown to be an acceptable way for frontline practicing clinicians to participate in the testing and development of digital health tools in a standardised setting.
贝赫切特综合征误诊一例
Authors: 董笑影, 巩路
Journal: BMJ (2005)

患者男,45岁,主因反复皮疹、口腔溃疡14年,间断发热、咯血伴阴部溃疡3年,加重20 d,于2003年11月1日收入我科.患者1989年10月无明显诱因出现双下肢结节性红斑,局部发硬有压痛,抗炎治疗后消退,后反复发作,有时出现全身皮肤带脓头的红色丘疹,静脉穿刺后也可出现.此间还反复出现口腔黏膜溃疡,疼痛明显,1～2周后可自行愈合.2000年11月突然出现发热,体温最高时≥39 ℃,口腔溃疡发作加重,于口腔医院应用糖皮质激素治疗后好转。