tbuckley/cabot-search huggingface dataset:
Accuracy of oncology patients’ expectations of cure.
Authors: Paul Shin, Danielle R. Romano, Camila Bernal, Andrea Knezevic, Anjali V. Desai, Judith Eve Nelson, Andrew S. Epstein
Journal: Journal of Clinical Oncology (2020)

e24167 Background: Efficacy of chemotherapy in gastrointestinal (GI) cancers is a well-studied endpoint. Patients require a realistic understanding of likely benefits to make informed treatment decisions. Prior studies show that patients with incurable cancer do not understand the palliative role of treatment. Patient understanding of chemotherapy intent (curative v. palliative) across all stages of GI cancers and modifying factors is unknown. Methods: Ambulatory clinic patients with GI cancers newly presenting for treatment answered validated questions on illness and treatment intent 1 as part of an initiative integrating palliative care at diagnosis regardless of stage. Patients were asked to estimate probability of cure from chemotherapy with Likert responses (range ‘not at all likely’ to ‘very likely’). Two experienced oncologists (GI medical and surgical) independently assessed accuracy of patient response after reviewing patient data and grade one clinical evidence. (E.g. Patient with locally advanced stage II rectal cancer who felt chemotherapy was "somewhat likely" to be curative deemed to be 'accurate') Responses were coded as accurate or inaccurate and accuracy was compared between clinical factors with Chi-square test. Results: For 113 patients, median age was 59, 62% were male, 55% had stage IV disease. Patients were diagnosed with colon (27%), anorectal (25%), pancreatic (21%), biliary (13%), or other GI cancer (14%). There was 99% clinician agreement rating accuracy. 51 (45%) patients responded accurately. Accuracy was lower in stage IV vs. stage I-III disease (35% v 57%, p=0.02), lower in unresectable vs. resectable disease (32% v 64%, p=0.001) and higher in adjuvant vs. non-adjuvant setting of chemotherapy for stage I-III patients. (80% vs. 42%, p=0.007) Accuracy did not differ significantly by gender, age, cancer, prior surgeon visit or DNR status. Conclusions: Inaccurate perceptions about likelihood of cure with chemotherapy are prevalent across all stages of GI cancers, but particularly amongst patients with advanced GI cancer. Patients receiving adjuvant chemotherapy were more likely than metastatic patients to have accurate understanding. Next steps include mixed methods analysis of qualitative data from this cohort to evaluate factors driving inaccurate understanding of treatment. 1 Weeks J et al. “Patients’ expectations about effects of chemotherapy for advanced cancer.” NEJM 367 (2012): 1616-1625.
Bstrongximab-MMAE, a novel antibody-drug-conjugate for metastatic gastric and pancreatic cancers.
Authors: William Michael Schopperle
Journal: Journal of Clinical Oncology (2020)

e15620 Background: As of today, there are no current beneficial clinical therapeutic cancer treatments for advance metastatic gastric or pancreatic cancers. A new approach to finding effective and meaningful drugs to treat these cancers is based an emerging hypothesis that cancer is a reprogramming disease and its origin and development is due to retrograde-like malignant cells with primitive and embryonic characteristics which are responsible for the dissemination of the disease and the almost universal clinical response of tumor resistance when treated with standard current therapies. Methods: A pluripotent human germ cell tumor cell line, TERA-1, was used to isolate and purify embryonic antigens which where used to immunized mice and, with standard B-cell hybridoma technology, to generate monoclonal antibodies. Antibodies were screened by ELISA and SDS-PAGE Western blotting to identify antibodies specific to gastric and pancreatic cancers but not to normal tissues. A second assay was used to screen the potential of the antibodies to function as antibody-drug-conjugate therapeutics against cancer. Results: A lead therapeutic antibody, Bstrongomab, was identified in the antibody screens: it is positive for gastric and pancreatic cancers but does not react with normal tissues. Bstrongomab is an IgG1 monoclonal antibody which has high affinity and specificity to the embryonic target TRA-1-60. TRA-1-60 is a carbohydrate molecule which is highly expressed in normal embryonic stem cells and not expressed in normal tissues but is re-expressed in gastric and pancreatic cancers. Immunohistochemical tissue staining studies show TRA-1-60 is expressed in gastric and pancreatic cancers. Recent published scientific reports confirm this finding. A human/mouse therapeutic version of Bstrongomab was developed - Bstrongximab - and used to generate a novel therapeutic antibody-drug-conjugate with Bstongximab and the toxic payload MMAE (Monomethyl auristatin E). Pre-clinical i n-vitro and in-vivo studies show Bstrongximab-MMAE is a potent drug for gastric and pancreatic cancers. Conclusions: Bstrongximab is a novel IgG1 human/mouse chimeric therapeutic antibody that targets TRA-1-60, a novel and yet to be tried cancer target that is highly expressed in gastric and pancreatic cancers but not in normal tissues. Bstrongximab-MMAE has the potential to be a first-in-class cancer therapeutic that provides real and meaningful benefits to patients with metastatic gastric and pancreatic cancers.
The diagnostic value of Reid's coloposcompic index in uterine cervical diseases
Authors: Yan-xiang Cheng, Jing-hong Jiang, Li Jiang, Qiu-rong Xie, Xiu-zhi Wu, Ruo-yu Luo, Wei Zhang, Yan Bao
Journal: BMJ (2009)

Clinical data of 899 patients,who received colposcopic examination,were retrospectively analyzed.Both Reid's colposcopic index(RCI)score and biopsy were performed.The study showed that the value of RCI score was positively related to the severity of cervical lesions(F=2.043,P=0.03).The specificity of RCI for cervicitis,cervical intraepithelial neoplasia(CIN)Ⅰ were 98.8%,95.7% respectively;while sensitivity and negative predictive value for CIN Ⅱ,CIN Ⅲ were 77.7%,70.0%and 96.8%.97.4%,respectively.So RCI scoring can increase the diagnostic value of colposcope.

Key words: 
Uterine cervical disease;  Colposcopy
血液透析治疗盐酸地芬尼多中毒性休克一例
Authors: 王淑英, 汪坤
Journal: BMJ (2007)

患者女,23岁,农民.2003年7月8日20时自服盐酸地芬尼多(眩晕停)150片(25 mg/片),1 h后出现意识模糊至昏迷,于21:30时被急送我院急诊科.入院查体:体温35.0℃,脉搏126次/min,呼吸6～8次/min,血压65/40 mmHg(1 mm Hg=0.133 kPa).深昏迷,呼吸浅慢,全身皮肤湿冷,双侧瞳孔等大、等圆、固定约6.5 mm,对光反射消失,口唇及四肢末端发绀,双肺呼吸音弱,心率126次/min,律齐,肝脾未触及,双侧巴氏征阳性。
Characterization of clinical pharmacokinetics and exposure-response relationships of AMG 330, a bispecific CD33 T-cell engager antibody construct, in patients with relapsed/refractory AML.
Authors: Suresh K Agarwal, Sharvari Bhagwat, Khamir Mehta, Antreas Hindoyan, Anthony Selwyn Stein, Farhad Ravandi, Marion Subklewe, Roland B. Walter, Mojca Jongen-Lavrencic, Gert J. Ossenkoppele, Peter Paschka, Sophia Khaldoyanidi, Sandeep Dutta, Vijay V. Upreti
Journal: Journal of Clinical Oncology (2020)

7536 Background: AMG 330 binds both CD33 and CD3 and redirects T cells toward CD33 + cells leading to T-cell‒mediated cytotoxicity against AML blasts. An ongoing open label phase I dose-escalation study (NCT02520427) has shown preliminary activity and acceptable safety in relapsed or refractory (R/R) acute myeloid leukemia (AML) patients (pts) (Ravandi et al. ASH 2018). Pharmacokinetics and exposure-response (E-R) relationships of AMG 330 were characterized in this trial. Methods: A continuous IV infusion of AMG 330 was evaluated at escalating target doses (range from 0.5 to 720 μg/day) using a 3+3 design with pts receiving step dose/s prior to reaching target doses of ≥ 30 μg/day. Population pharmacokinetics (popPK) using non-linear mixed effects modeling and E-R analyses were conducted to characterize relationships between AMG 330 exposure (steady-state concentration [Css]) at target dose, the baseline tumor burden, clinical response per revised IWG criteria and incidence of cytokine release syndrome (CRS). Results: As of Dec 10, 2019, 55 patients (males, 56.4%; median age, 58.0 [18.0–80.0] years) were enrolled in 16 cohorts. AMG 330 PK was best described by a one-compartment linear PK model. Dose dependent increases were observed in AMG 330 Css exposures. Responders typically showed higher AMG 330 Css than non-responders. Preliminary exploratory analysis indicated that higher AMG 330 exposures, lower baseline leukemic burden in bone marrow and CD33+ AML cells in peripheral blood, and higher baseline Effector:Target cell ratio may be associated with clinical response. Additionally, a positive relationship was observed for AMG 330 exposures and baseline leukemic burden (p &lt; 0.05) with probability of CRS occurrence and severity. Based on the model, at a baseline leukemic burden of 20%, a 240 µg/day target dose is predicted to result in a 28% and 4% probability of developing CRS of grade ≥ 2 and ≥ 3, respectively. Conclusions: Clinical pharmacokinetic profile and E-R relationships of AMG 330 were characterized to identify optimal AMG 330 dosing regimens that minimize the risk for CRS in ongoing and planned clinical investigations. Clinical trial information: NCT02520427 .
Progress in diagnosis and treatment of restless legs syndrome
Authors: Caixia Yao, Liuqing Wang, Shoucheng Zhang
Journal: BMJ (2019)

Restless legs syndrome (RLS) is defined as a sleep-wake disorder, with the key feature being an urge to move, which can be classified as two types as primary RLS and secondary RLS. Iron deficiency is a key role of RLS, low levels of serum ferritin is noted in RLS lab tests. Pathophysiology of RLS is complex, genetic variants, anatomical network vulnerability, neurotransmission abnormalities and abnormal dopaminergic neurotransmission may all contribute to its pathogenesis. The mild RLS can choose non-drug therapy, but most of the patients need drug therapy especially the severe cases. The aboved aspects are discussed in this review based on recent literatures.


Key words: 
Restless legs syndrome; Sleeping disorder; Dopa; Iron
Acalabrutinib in treatment-naïve chronic lymphocytic leukemia: Mature results from phase II study demonstrating durable remissions and long-term tolerability.
Authors: John C. Byrd, Jennifer Ann Woyach, Richard R. Furman, Peter Martin, Susan Mary O'Brien, Jennifer R. Brown, Deborah Marie Stephens, Jacqueline Claudia Barrientos, Stephen Devereux, Peter Hillmen, John M. Pagel, Ahmed M. Hamdy, Raquel Izumi, Priti Patel, Min Hui Wang, Nitin Jain, William G. Wierda
Journal: Journal of Clinical Oncology (2020)

8024 Background: The next-generation Bruton tyrosine kinase inhibitor acalabrutinib was approved in patients (pts) with treatment-naïve (TN) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on two complementary phase 3 studies, ELEVATE-TN and ASCEND. This report of ACE-CL-001 (NCT02029443), the first phase 2 study of acalabrutinib, provides the longest safety and efficacy follow-up to date in symptomatic TN CLL pts. Methods: Adults with TN CLL/SLL were eligible if they met iwCLL 2008 criteria for treatment, were inappropriate for/declined standard chemotherapy and had ECOG performance status 0–2. Pts received acalabrutinib 100 mg BID or 200 mg QD, later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. Primary endpoint was safety. Events of clinical interest (ECI) were based on combined AE terms for infections, bleeding events, hypertension, and second primary malignancies (SPM) excluding non-melanoma skin, and on a single AE term for atrial fibrillation. Additional endpoints included investigator-assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), and event-free survival (EFS). Results: Ninety-nine pts (n = 62 100 mg BID; n = 37 200 mg QD), were treated [median age: 64 years, 47% Rai stage 3–4 disease, 10% del(17p), 62% unmutated IGHV]. At median follow-up of 53 months (range, 1–59), 85 (86%) pts remain on treatment; most discontinuations were due to AEs (n = 6) or PD (n = 3 [n = 1 Richter transformation]). Most common AEs (any grade) were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade ≥3 ECIs included infection (84%, 15%), bleeding events (66%, 3%), and hypertension (22%, 11%). Atrial fibrillation (all grades) occurred in 5% of pts (incidence: 1% in years 1, 2, 4; 3% in year 3). SPMs excluding non-melanoma skin (all grades) occurred in 11%. Serious AEs were reported in 38% of pts; those in &gt; 2 pts were pneumonia (n = 4) and sepsis (n = 3). ORR was 97% (7% complete response; 90% partial response). Median TTR was 3.7 months (range, 2–22). Response rates were similar across high-risk groups. Median DOR and median EFS were not reached; 48-month DOR rate was 97% (95% CI, 90%–99%), and 48-month EFS rate was 90% (95% CI, 82%–94%). Conclusions: Long-term data from ACE-CL-001 further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues. Clinical trial information: NCT02029443 .
Greater than two coexisting mutations in KRAS and NRAS identified in the circulating tumor DNA fraction of liquid biopsies by NGS and confirmed with ddPCR.
Authors: Hala Boulos, Robert Tell, Nike Beaubier, Richard Blidner
Journal: Journal of Clinical Oncology (2020)

e15563 Background: Liquid biopsies are increasingly utilized as a non-invasive tool in precision oncology to assess tumor mutational profiles in order to select targeted therapies, detect treatment resistance, and monitor disease progression in cancer patients. Additionally, liquid biopsies may provide a more comprehensive representation of tumor heterogeneity than standard tissue biopsies. However, limitations such as scarcity of circulating tumor DNA (ctDNA) and/or variants at low frequencies can be technically challenging to detect by next-generation sequencing (NGS) assays. Here, we use NGS to detect greater than two KRAS/NRAS mutations coexisting in single samples at low variant allele frequencies (VAFs). Methods: The Tempus xF liquid biopsy NGS assay is designed to detect actionable oncologic targets spanning 105 genes in plasma. The assay was validated to reliably detect single-nucleotide variants at 0.25% VAF, indels and copy number variants at 0.5% VAF, and fusions at 1% VAF with 96.2%-100% specificity and 97.4%-100% sensitivity. Pre-designed digital PCR assays were modified to measure 10ng of cell-free DNA (cfDNA) on a droplet-digital PCR (ddPCR) platform. Results: Overall, we report 100% positive predictive value and high correlation between ddPCR results and xF VAF, as well as in individual variants, such as KRAS G12D. Unexpectedly, we detected more than two coexisting KRAS/NRAS mutations at a low VAF in the plasma samples. To orthogonally confirm these results, ddPCR was deployed to independently measure the presence of each cfDNA variant with a sensitivity of 0.09% VAF. Subsequent ddPCR analysis of all targeted variants were concordant with NGS results. Conclusions: The occurrence of multiple KRAS and NRAS mutations in a single sample is quite uncommon and may be falsely interpreted as an NGS artifact. However, verification of this phenomenon by ddPCR confirmed the validity of the NGS liquid biopsy approach. These results highlight the capability of the Tempus xF assay to detect low-frequency variants, including those that fall below the validated detection threshold, which is essential for the diagnosis of early disease.
The impact of circulating free tumor DNA (cfDNA) in testicular germ cell tumors (TGCT) management.
Authors: Eugen Kubala, Violeta Bakardjieva-Mihaylova, Karolina Skvarova-Kramarzova, Martina Slamova, Petr Triska, Zuzana Donatova, Aneta Rozsypalova, Blanka Rosova, Jan Trka, Tomas Buchler, Ludmila Boublikova
Journal: Journal of Clinical Oncology (2020)

e17519 Background: The clinical management of testicular germ cell tumors (TGCT) has not changed much for decades; most importantly, novel prognostic factors indicating the need of adjuvant chemotherapy and factors related to the development of cisplatin resistance would be needed. Circulating free tumor DNA (cfDNA) is an easily available and valuable source of genetic material, which may bring clinically relevant information. Methods: After ethical committee approval and patient informed consent, peripheral blood (PB) samples were taken from TGCT patients at the diagnosis (after orchidectomy), after 2 cycles of chemotherapy, at the end of treatment, and at relapse or disease progression, if applicable. Clinical data of all patients were recorded. The PB samples were processed immediately after collection, plasma was separated by centrifugation, cfDNA was extracted by QIAmp Circulating Nucleic Acid kits (Qiagen), its quality and quantity was assessed by capillary electrophoresis (Agilent) and qPCR for a house-keeping gene. Selected samples were subjected to whole exome sequencing using SureSelectXT HS + Human All Exon v6 kits (Agilent) on NextSeq (Illumina) platform, together with the corresponding primary testicular tumor and peripheral blood mononuclears as a germ-line control. Statistical analyses were performed using non-parametric tests. Results: Sixty-three samples of 41 patients have been analyzed. The median amount of detected cfDNA did not significantly differ from non-malignant controls, was similar in seminoma and non-seminoma pts, but was significantly higher (p = 0.01) in pts with disease progression. In pts with elevated cfDNA levels, these decreased after 2 and 4 cycles of chemotherapy. In 5 sequenced pts, molecular aberrations (somatic missense or frameshift mutations) were found in genes CDC27 (2 pts), RBMX (4 pts), TPTE2 (3 pts), and TSPAN16 (1 pt). These aberrations were also detected in primary tumors but with lower frequencies, and were not present in germ-line DNA. CDC27 mutations have been described in TGCT previously. The other genes have not yet been linked to TGCT, although their role in spermatogenesis and cell proliferation is well known. The presence of mitochondrial DNA was not detected in cfDNA. Conclusions: High levels of cfDNA are detectable in pts with disease progression where they reflect the total tumor load; the molecular analysis of cfDNA revealed novel aberrations that may play a role in TGCT development. Supported by grants MH CZ - DRO00064190TN, CDRO00064203FNM and MEYS NPU I LO1604
Epidemiological survey of hepatitis B virus serologic markers among university freshmen in Beijing
Authors: Yonghong Wang, Chunping Xu, Xiaofeng Shen
Journal: BMJ (2015)

To analyze the test results of five serum markers of hepatitis B virus (HBV) among university freshmen from 2007 to 2012. Among a total of 10 827 freshmen, there were 5 021 freshmen from 2007 to 2009 with all five serum markers. The overall ratio of HBsAg positive was 4.5%, 4.8%, 4.8% and 4.0% for each year. And it had no statistically significant difference. The overall ratio of single-HBsAb positive was 34.8%, 37.4%, 29.0% and 37.9% for each year and the figure of 2008 was lower than those of 2007 and 2009 (P 40 U/L, including HBsAg positive (n=12), single anti-HBs positive (n=213) and five negatives (n=288). Approximate 50% university freshmen have no anti-HBs indicating a low level of immunity. And the students should acquire the knowledge of hepatitis B, improve the ratio of vaccination, strengthen the monitoring and prevent its spread through concerted measures.


Key words: 
Hepatitis B virus; Seroepidemologic studies
What are the challenges for building real world comparative cohorts in oncology?
Authors: Nikita Jeswani, Amanda McDonell, Finlay MacDougall, Jeff Paul Hodge
Journal: Journal of Clinical Oncology (2020)

e19285 Background: There has been a proliferation of single arm trials in oncology being presented to regulators. An external comparator using real world data (RWD) can help establish context to trial results and direct comparison to the treatment arm by mirroring the inclusion/exclusion criteria for the trial and examining trial outcomes in an RWD external comparator cohort. RWD has successfully supported some regulatory submissions, although there have been failures as well, with comparability of patients and endpoints under scrutiny. Methods: IQVIA has partnered with life sciences companies on &gt; 20 external comparator projects from 2017-present using a mix of data acquisition strategies (e.g., chart review, database extraction) and methods (e.g., real-world cohort vs. real-world benchmark, propensity matching vs. inverse probability treatment weighting). We collated, reviewed, and synthesised the challenges and risk mitigations documented throughout study execution in aggressive and indolent lymphomas, multiple myeloma, Merkel cell carcinoma, and synovial sarcoma. Results: Patient characteristics used to assess trial eligibility (e.g., biomarker expression, International Prognostic Index, ECOG status) and outcomes (e.g., response rate) are not often captured in a structured format in RWD or recorded in routine clinical practice. As a result, there is a greater reliance on chart reviews today over database extractions to fulfil external comparator requirements, though in some diseases, databases have proven to be a faster and more cost-effective solution. Conclusions: To improve the success of external comparator studies, trial design should be informed by existing RWD so that relevant real-world endpoints and outcome evaluation criteria are included alongside RCT standards. Advances are needed to facilitate RWD capture that matches trial data more closely. This could include bespoke data collaborations, biobank linkage, and natural language processing to drive study execution in databases in the future.
CT诊断腹腔纱布异物一例
Authors: 刘爱波, 田云, 赵汉田, 陶德成
Journal: BMJ (2006)

患者女,30岁.2个月前于外院行剖腹产术,术后时有阵发性右下腹痛,无肿块,无黑便.1个月前发现右下腹包块,固定,无压痛.查体:下腹部见横行手术切口,腹软,右下腹触及6 cm×5 cm肿块,质韧,表面光滑,活动差,轻压痛,无反跳痛,移动性浊音阴性,无腹胀、恶心及呕吐,肝脾未及.实验室检查未见异常。