tbuckley/cabot-search huggingface dataset:
Project facilitate: A review of the FDA oncology center of excellence expanded access pilot program.
Authors: Natasha L Kormanik, Mitchell Chan, Jessica Boehmer, Tamy Kim, Gideon Michael Blumenthal, Richard Pazdur
Journal: Journal of Clinical Oncology (2020)

7023 Background: Expanded Access (EA), also known as “compassionate use,” is a regulatory pathway in which a patient with an immediate life-threatening condition or disease can gain access to an investigational product for treatment when no satisfactory therapy is available. Oncology practices may lack the regulatory experience or administrative support to use EA. In response, FDA OCE launched Project Facilitate (PF), a call center to assist oncology healthcare providers requesting EA. An analysis of single-patient investigational new drugs (IND) was performed to assess the first 10 months of PF compared to the period prior to its launch. Methods: Preliminary data was extracted from the FDA’s central database that yielded 719 single-patient INDs between May 31-November 30, 2018 &amp; 2019 in the Office of Oncologic Diseases (OOD). Data collected included IND receipt date, acknowledgment date, application status, drug name, underlying malignancy of patient, address of requesting physician, withdrawal date, and patient demographics. A manual review of INDs was performed to assess for actual processing dates and to capture demographics not captured by the database. A total of 28 INDs were excluded due to duplications, cancellation by Sponsor prior to issuance of FDA decision, or coding errors in the database. Industry denial explanations were reported by the provider by emails. Results: Data from 692 INDs were analyzed and 692 (100%) were granted safe to proceed. The median processing time was 1 day (mean=2) in 2018 and 1 day (mean= 1.5) in 2019. Our findings indicate that the volume of oncology EA requests increased by 76 (19%) in 2019 vs 2018. A total of 207 unique drugs were requested. Malignancies most frequently involved included: Acute myeloid leukemia (n = 84, 8.3%), soft tissue sarcoma (n = 77, 7.6%), and non-small cell lung cancer (n = 60, 5.9%). States with the highest requests included: California (n = 82, 11.8%), New York (n = 81, 11.7%), and Massachusetts (n = 42, 6.1%). A majority of requests were from major academic centers (77%). All denied requests (N = 9) by industry were due to company’s decision to not provide products outside of a clinical trial. Conclusions: The positive trends in decreased processing times and increased number of requests are consistent with OCE’s mission to improve efficiency of the EA program and ensure equitable access to all oncology patients. [Table: see text]
Smoking status and immunotherapy outcomes in smoking-associated cancers.
Authors: Tomi Jun, Teja Ganta, Qian Qin, Vaibhav G. Patel, Bo Wang, George Mellgard, Mahalya Gogerly-Moragoda, Amanda Leiter, Emily J. Gallagher, William K. Oh, Matt D. Galsky, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e15097 Background: Improved immunotherapy (IO) outcomes have been observed among non-small cell lung cancer patients with a current or former smoking history. This is thought to be a consequence of increased immunogenic mutation burden among smoking-related cancers. We set out to explore the association between smoking status and immunotherapy outcomes in lung and other smoking-associated cancers. Methods: This was a retrospective analysis of 200 consecutive patients with advanced, smoking-associated solid tumor types, treated with single-agent anti-PD1/PDL1 therapy at a single center between July 2014 and February 2018. The primary outcome was overall survival from date of IO initiation. The secondary outcome was overall response, defined as radiographic complete response or partial response, by RECIST 1.1 criteria. The primary predictor was smoking status (former/current smoker vs. never smoker). The primary and secondary outcomes were analyzed using multivariable Cox proportional hazards models and multivariable logistic regression models, respectively. Models were adjusted for age and sex, and stratified by cancer type. Results: The majority of patients were male (64%) with a history of smoking (72%); the average age was 67.1 ± 11.4 years. Cancer types represented were: non-small cell lung cancer (NSCLC, N = 81), hepatocellular carcinoma (HCC, N = 41), urothelial carcinoma (BLCA, N = 39), head and neck squamous cell carcinoma (HNSC, N = 21), and renal cell carcinoma (RCC, N = 18). Over a median follow-up of 11.3 months (range 0.5-53.2), there were 96 deaths and 27% of evaluable patients achieved radiographic response. Response was not evaluable in 27 patients. In multivariable regression analysis, smoking status was not significantly associated with overall survival nor overall response in any cancer type examined (Table). Conclusions: Smoking status was not associated with outcomes in our cohort of IO-treated patients with smoking-associated cancers, though sample size was limited. [Table: see text]
AVID200, first-in-class TGF-beta 1 and 3 selective and potent inhibitor: Safety and biomarker results of a phase I monotherapy dose-escalation study in patients with advanced solid tumors.
Authors: Timothy A Yap, Nehal J. Lakhani, Daniel Vilarim Araujo, Jordi Rodon Ahnert, Sreenivasa R Chandana, Manish Sharma, Jean-François Denis, Tina Gruosso, Gilles Tremblay, Maureen O'Connor, Ria Ghosh, Sandra Sinclair, Debra L. Wood, Paul I. Nadler, Lillian L. Siu
Journal: Journal of Clinical Oncology (2020)

3587 Background: AVID200 is a rationally designed first-in-class, selective inhibitor of transforming growth factor-beta (TGF-beta) that neutralizes TGF-beta 1 &amp; 3 with pM potency and 4,000 fold selectivity over TGF-beta 2. TGF-beta 1 &amp; 3 signaling has been associated with immune checkpoint inhibitor resistance and immunosuppression in the tumor microenvironment while TGF-beta 2 is required for normal cardiac function and hematopoiesis. Methods: NCT03834662 (AVID200-03) is a multicenter Phase 1 study following a standard 3 + 3 dose escalation to evaluate safety and tolerability of AVID200 given IV every 3 weeks to patients (pts) with advanced solid tumors. Peripheral target engagement was assessed in blood by ELISA and a cell-based functional assay, and in skin biopsies by immunohistochemistry (IHC). Pharmacodynamic markers of TGF-beta signal modulation and immune activation were evaluated in serum using the InflammationMAP v 1.0 (Myriad RBM) and in paired tumor biopsies by IHC and Imaging Mass Cytometry. Results: Nineteen pts (ECOG 0-1, median age 63 [range 39-77], 52.6% male) received AVID200 at 3 planned dose levels of 180 (N = 7), 550 (N = 6), and 1100 mg/m 2 (N = 6) (~5, 15, and 30 mg/kg). The maximum tolerated dose was not reached. Three Grade (G) 3 treatment-related adverse events (TRAEs) were reported in 2 pts (diarrhea and lipase elevation, anemia); no &gt; G3 TRAEs were observed. Serum exposure was dose-proportional and AVID200 sequestered all active TGF-beta 1 &amp; 3, but not beta 2, in blood across the entire dosing period at all dose levels, providing proof-of-mechanism of AVID200. SMAD2 phosphorylation in skin biopsies was detectably reduced on Day 4 at 15 and 30 mg/kg. Pro-inflammatory markers in serum were increased on Day 8 versus baseline in a dose-dependent manner. Tumor biopsies of pts treated at 15 mg/kg showed modulation of TGF-beta signaling and immune activation. A best response of RECIST stable disease &gt; 12 weeks was observed in 2 pts: 1 with adenoid cystic carcinoma (5 mg/kg; 8.7 months); 1 with breast carcinoma (30 mg/kg; 3.1 months). Conclusions: AVID200 was safe and well tolerated at dose levels of 5-30 mg/kg, with peripheral target engagement across the entire dosing period. AVID200 led to TGF-beta target modulation and immune activation. These data provide proof-of-principle that AVID200-mediated selective and potent inhibition of TGF-beta 1 &amp; 3 is feasible in the clinic. The AVID200 monotherapy data warrant exploration of rational combination with a PD-(L)1 inhibitor. Clinical trial information: NCT03834662 .
男童胃恶性间质瘤伴大出血一例
Authors: 尹勇, 李兆丽
Journal: BMJ (2011)

患儿男性,11岁.因呕血、黑便伴阵发性上腹部疼痛18 h,于2009年5月29日急诊入院.入院前患儿呕血一次,量约200 ml,解成形黑便两次,量约150 g.体格检查:体温37.6 ℃,脉搏103次/min,呼吸26次/min,血压108/71mm Hg(1 mm Hg=0.133 kPa).神志清楚,贫血貌,全身浅表淋巴结未触及肿大。
Endoscopic management of buried bumper syndrome using a novel grasping-type scissor forceps
Authors: Timo Rath, Francesco Vitali, Andreas Nägel, Markus F. Neurath
Journal: Endoscopy (2020)

With an incidence ranging between 0.3 % and 2.4 %, buried bumper syndrome (BBS) is a relatively rare complication after percutaneous endoscopic gastrostomy (PEG) in which the internal fixation device of the cannula – the retention bumper – migrates partially (incomplete BBS) or completely (complete BBS) into the gastric wall with subsequent mucosal overgrowth [1] [2]. Management of complete BBS can be challenging, and a variety of endoscopic devices have been described for endoscopic treatment, including needle-knives, wire-guided papillotomes, the sphincterotome-like Flamingo device, or a combination of different techniques [3] [4] [5].
Treatment-free remission in chronic myeloid leukemia: the patient perspective and areas of unmet needs
Authors: Giora Sharf, Celia Marin, Jennifer A. Bradley, Zack Pemberton-Whiteley, Felice Bombaci, Rita I. O. Christensen, Bahija Gouimi, Nigel B. Deekes, Mina Daban, Jan Geissler
Journal: Leukemia (2020)

Abstract In CML, treatment-free remission (TFR) refers to having a stable deep molecular response without the need for ongoing tyrosine kinase inhibitor treatment. Whilst recommendations exist about the technical management of stopping and re-starting therapy, much is still unknown about the experiences of those considering and undertaking TFR. This study sought to obtain the patient perspective, identify areas of unmet needs and create recommendations for improvements. Fifty-six percent of patients reported fear or anxiety during treatment discontinuation, whereas only 7% of patients were asked if they needed psychological support during this period. Where patients re-initiated treatment; 59% felt scared or anxious, and 56% felt depressed. Twenty-six percent of re-initiated patients received psychological and/or emotional support at this time. Sixty percent of patients experienced withdrawal symptoms whilst discontinuing treatment, however, 40% of patients who experienced withdrawal symptoms reported that they were not fully supported by their doctor in managing all the symptoms. Healthcare professionals should further consider how they monitor the psychological well-being of patients who are discontinuing or re-initiating treatment, and review what support is offered in response to identified concerns. Surveillance of withdrawal symptoms should be a priority during treatment discontinuation, along with how healthcare professionals assist in the management of these.
急性心肌梗死的现场心电图判断
Authors: 冯庚
Journal: BMJ (2004)

仅仅掌握急性心肌梗死(AMI)心电图的基本特征是不够的,很多因素都可以对AMI心电图诊断产生影响,因此对AMI心电图综合因素的判断至关重要.下面是院前急救时AMI心电图判断最重要的参考依据。
牙龈转移性肉瘤样癌一例
Authors: 李志萍, 孟箭
Journal: BMJ (2011)

患者女性,54岁.因发现口内牙床包块2个月于2010年11月来本院口腔科就诊.2个月前,患者发觉右上牙龈长一蚕豆大小的肿物,于当地医院切除,病理结果示牙龈瘤.术后1周发现原手术部位及左下牙龈再次长出2个肿物,抗感染治疗效果不佳,肿物生长较快,极易出血,影响进食.病程中无憋喘、胸闷等不适,否认系统性疾病史.体检:一般状况尚可,面部发育对称,口内右七后牙腭侧牙龈见一约3.0cm×2.0cm×3.0cm的外牛性肿块,波及第一磨牙至侧切牙,左下前磨牙至尖牙舌侧牙龈见一约2.0 cm×1.0 cm×1.5 cm的粉红色赘生物,质脆,界限尚清,局部见溃烂充血面,触之易出血,无明显压痛.颌下、颈部及腋下等浅表淋巴结无肿大.曲面断层X线片示右上第一磨牙至侧切牙、左下前磨牙至尖牙区牙槽骨水平骨吸收至根中1/3.入院后生化检查、腹部彩超及胸部X线片检查,前二者未见异常,胸部X线片示右肺4.0 cm×4.0 cm×5.0 cm的占位,胸部CT示右上肺肿物(图1),经呼吸科会诊建议肺部穿刺活检定性.初步诊断:①牙龈肿瘤;②肺部占位. 关键词：牙龈肿瘤
儿童发热的评价和处理
Authors: 金世红
Journal: BMJ (2006)

有一次,一个小患者来就诊.他1岁半,一向很健康,足月出生,生长发育正常,按计划预防接种.一天前突然高热,体温达到了39.3℃,因此他妈妈带他来看病.这个孩子没有咳嗽、流鼻涕,也没有呕吐或腹泻.虽然看上去他状态还好,吃饭、大小便及睡觉都正常,也仍然爱玩,但他妈妈很担心,认为孩子得了很严重的病,要求点滴抗生素。
Expression of the senescence biomarker <i>p16<sup>INK4a</sup></i> among childhood, adolescent, and young adult cancer survivors.
Authors: Andrew Brian Smitherman, Vanessa L Ayer Miller, Natalia Mitin, Allison Mary Deal, Hyman B. Muss
Journal: Journal of Clinical Oncology (2020)

10556 Background: The mechanism of accelerated aging among survivors of childhood, adolescent, and young adult cancer is not clearly understood. Cellular senescence may contribute to this process. We measured peripheral blood T lymphocyte p16 INK4a expression, a biomarker of cellular senescence and aging, among pediatric and young adult cancer survivors hypothesizing that p16 INK4a expression is higher due to chemotherapy exposure and among frail survivors. Methods: Two cohorts were enrolled from January 2018 to December 2019 at an academic medical center. One, a cross-sectional cohort of young adult cancer survivors and age-matched, cancer-free controls in whom we assessed p16 INK4a expression and clinical frailty. Frailty was measured with the modified Fried Frailty Index that evaluates skeletal muscle index, weakness, slowness, leisure energy expenditure, and exhaustion. A second cohort underwent prospective measurement of p16 INK4a expression before and after cancer chemotherapy. Eligibility among survivors and newly diagnosed patients required treatment with an alkylating agent, an anthracycline / anthracenedione, or both. Multivariable linear regression was used to model expression of p16 INK4a by patient age at assessment, treatment intensity, and frailty status. Results: The cross-sectional cohort enrolled 60 young adult survivors and 29 age-matched, cancer-free controls with median age 21 years and range 17-29 years for both groups. Survivors were a median of 5.5 years from end of treatment. The prospective cohort enrolled nine newly diagnosed patients (range 1-18 years). Expression of p16 INK4a was higher among young adult cancer survivors as compared to age-matched controls (9.6 v. 8.9 log 2 p16 units, p &lt; 0.01) representing a 25-year age acceleration in the survivors. Expression of p16 INK4a increased among newly diagnosed patients from matched pre- to post-treatment samples (7.3 to 8.9 log 2 p16 units, p = 0.002). Nine survivors (16%) met criteria for being frail and had higher p16 INK4a expression as compared to robust survivors (10.5 [frail] v. 9.5 [robust] log 2 p16 units, p = 0.055). Conclusions: Chemotherapy is associated with increased cellular senescence in pediatric and young adult cancer survivors as reflected in expression of p16 INK4a indicating an increase in molecular age following chemotherapy exposure. The large proportion of frail survivors in this study also exhibited higher levels of p16 INK4a suggesting that cellular senescence may be associated with early aging observed among these survivors.
Research on the basic path of the integration of medical social work into general medicine at general hospital
Authors: Xiaoyang Liang, Mei Feng, Xiaoxu Wang, Yi Li
Journal: BMJ (2019)

The general practitioners are facing a series of issues in aspect of medical humanities: incomprehensive humanity care, insufficient subjective components in medical records, low service efficiency particularly during heavy work load in outpatient service. To adapt the challenges, a general hospital in Shanxi province had explored a pathway to integrate the medical social work into patient care in general practice since 2017. The medical social workers jointed the general practice team, involved in outpatient service and patient education, generated humanity records to improve the humanistic care, and to promote doctor-patient communication. The general medical services were significantly improved after the program implementation in the hospital.


Key words: 
Social work; General practice; Medical services
Breast cancer in younger patients in Southeast of Brazil: 10-year analysis.
Authors: Sabina B. Aleixo, Jose Zago Pulido, Narelle Parmanhane
Journal: Journal of Clinical Oncology (2020)

e13567 Background: Breast cancer in Brazil is the most common cancer among women and is also responsible for the highest number of cancer deaths in this group. For Brazil, 66,280 new cases of breast cancer are estimated for the year 2020. This corresponds to an estimated risk of 61.61 new cases per 100 thousand women. For Espírito Santo, the estimate is 790 new cases.. Affection in women under the age of 40 is still infrequent, but it has been growing in the country with more aggressive and advanced cancer at diagnoses. It happens that in Brazil, with the publication of Ordinance 61/2015 by the Ministry of Health, the procedure became exclusive to women aged 50 to 69 years, contrary to what Federal Law 11.664 / 2008 requires, which determines the right mammography exam for all women over 40 years of age. In other words, asymptomatic women who are under 50 or over 70 years of age cannot take the exam on the public network. Methods: The data presented in this study correspond to patients diagnosed with breast cancer from 2007 to 2017 and were extracted from the database of the Hospital Cancer Registry of the Evangelical Hospital of Cachoeiro de Itapemirim (RHC / HECI) through SisRHC, a tool of management of the computerized database for Hospital Cancer Records. Results: Over the 10 years analyzed, in the south Espírito Santo region, 1,546 women started treatment for breast cancer and of these 528 were aged 49 years or less, stratified by age group: 15-24 years 9 cases (1.71%), 25-34 years 64 cases (12.13%)., 35-39 years 96 cases (18.18%), 40-44 years 156 cases (29.54%), 45-49 years. 203 cases (38.44%). A very important factor when making the diagnosis is the clinical staging (EC) of the disease, a fact that directly influences the type of treatment and the woman's survival. Of the cases analyzed, 464 had complete staging data, of these 27 (5.82%) of the cases were EC 0, EC I were 89 (19.18%), 193 (41.60%) with EC II, 122 ( 26.30%) with EC III and, finally, 33 (7.10%) in EC IV. Conclusions: In Brazil, there is a divergence between the guidance of the INCA (National Cancer Institute), an organ linked to the Ministry of Health, which recommends routine mammography after the age of 50, and the Brazilian Mastology Societies and the Brazilian College of Radiology, which indicate the exam for women over 40 years of age. In this scenario, the reduction in the supply of mammograms puts the country against the recommendations of specialists and medical societies. Mammography is a right for all Brazilian women over 40 years of age. This is the law and we need to enforce it, since the incidence of cancer cases in this age group represented one third of the cases.
Do irinotecan (IRI) dose reductions driven by UGT1A1*28 genotyping prevent IRI-related severe neutropenia? A real-world study.
Authors: Nicola Personeni, Rossana Mineri, Angelica Michelini, Silvia Bozzarelli, Tiziana Pressiani, Valeria Smiroldo, Maria Teresa Sandri, Laura Giordano, Armando Santoro, Lorenza Rimassa
Journal: Journal of Clinical Oncology (2020)

e16116 Background: IRI is widely used in the treatment of gastrointestinal cancers. Consistent with current guidelines, UGT1A1 genotyping may drive IRI dose reductions, but the usefulness of this approach is still unclear. We assessed potential clinical variables that may predict grade ≥3 neutropenia and more specifically the upfront genotyping of UGT1A1 polymorphisms associated with IRI toxicity, according to predefined IRI dose reductions. Methods: We genotyped UGT1A1*28 polymorphisms in 247 patients with metastic colorectal, gastric and pancreatic cancers who received second or third-line IRI-based chemotherapy in clinical practice at a single academic center. Concomitant DPYD sequencing was undertaken in 179 patients receiving also fluoropyrimidines. We compared the incidence of severe neutropenia with full-dose IRI in UGT1A1 6/6 and 6/7 carriers, and in UGT1A1 7/7 carriers who underwent initial IRI dose reductions by at least 30%. Results: The incidence of UGT1A1 7/7, 6/7, 6/6 genotypes was 11.3%, 51.4%, and 37.2%, respectively. IRI dose reductions were significantly more frequent with UGT1A 7/7 and 6/7 genotypes (odds ratio [OR] = 9.5; 95% confidence interval [CI]: 4.3-21.7), and combination chemotherapy (OR = 3.8; 95%CI: 1.3 – 11.1). Other clinical parameters, including sex, cancer type, baseline neutrophils levels, performance status were not significantly associated with IRI dose reductions. Despite initial IRI reductions driven by the UGT1A1 panel, patients with UGT1A1 7/7 genotype had an increased, albeit non-significant, risk of grade ≥3 neutropenia, compared to patients with UGT1A1 6/6 and 6/7 genotypes who received full dose IRI (incidence: 39% versus 21%; OR = 2.4; 95%CI: 0.85 – 7.03). Conclusions: UGT1A1 testing is a determinant of IRI dose reductions, however this strategy does not reduce the burden of grade ≥3 neutropenia in UGT1A1 7/7 carriers. Further studies beyond the UGT1A1*28 genotype are needed to fully understand the increased risk of neutropenia in patients candidate to IRI-based chemotherapy.
ENGOT-OV44/FIRST study: a randomized, double-blind, adaptive, phase III study of standard of care (SOC) platinum-based therapy ± dostarlimab followed by niraparib ± dostarlimab maintenance as first-line (1L) treatment of stage 3 or 4 ovarian cancer (OC).
Authors: Anne-Claire Hardy-Bessard, Kathleen N. Moore, Mansoor Raza Mirza, Bernard Asselain, Andres Redondo, Jacobus Pfisterer, Sandro Pignata, Diane M. Provencher, David Cibula, Anna K.L. Reyners, Lubomir Bodnar, Rosalind Glasspool, Christos Papadimitriou, Rami Eitan, Sileny N. Han, Linda R. Duska, BJ Rimel, Gupta Divya, Jian Chen, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2020)

TPS6101 Background: Despite surgery and CT (paclitaxel + carboplatin ± bevacizumab [bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3 or 4 OC. Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that has recently demonstrated efficacy in 1L therapy. Dostarlimab (TSR-042) is an anti-programmed death (PD)-1 humanized monoclonal antibody that has shown clinical activity as monotherapy in early phase trials. The currently enrolling ENGOT-OV44/FIRST study will compare efficacy and safety of CT + dostarlimab + niraparib ± bev (Arm 3) vs CT + niraparib ± bev (Arm 2). Methods: Eligible pts are ≥18 years of age, with FIGO stage 3 or 4 non-mucinous epithelial OC, ECOG performance status &lt; 2, and tumor tissue available for PD-1 ligand (PD-L1) testing. After cycle 1 of CT, pts are stratified by concurrent bev use, BRCA mutation/homologous recombination repair status, and disease burden, then randomized 1:2 into trial Arms 2 and 3 (Table). Dostarlimab is administered at 500 mg IV Q3W during the CT period, then 1000 mg IV Q6W during the maintenance period. Niraparib dosing is 200 mg PO QD for pts with baseline bodyweight (BW) &lt; 77 kg and/or platelet count (PC) &lt; 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. The dual primary endpoints are PFS, based on investigator assessment per RECIST v1.1, in both PD-L1+ and all patients. Initially the study enrolled pts to Arm 1. This arm was discontinued following positive results from the PRIMA/ENGOT-OV26/GOG-3012 and PAOLA-1/ENGOT-OV25 studies. This allows investigators to offer the current standard of care to all patients. Clinical trial information: NCT03602859, EUDRACT 2018-000413-20. [Table: see text]