tbuckley/cabot-search huggingface dataset:
Clinical activity of MCLA-128 (zenocutuzumab) in combination with endocrine therapy (ET) in ER+/HER2-low, non-amplified metastatic breast cancer (MBC) patients (pts) with ET-resistant disease who had progressed on a CDK4/6 inhibitor (CDK4/6i).
Authors: Barbara Pistilli, Hans Wildiers, Erika Paige Hamilton, Ana Alexandra Ferreira, Florence Dalenc, Maria Vidal, Joaquín Gavilá, Anthony Goncalves, Carmen Murias, Marie-Ange Mouret-Reynier, Jean-Luc Re Canon, Fernando Bazan, Sylvain Ladoire, L. Andres Sirulnik, Mohamed Bekradda, Kees Bol, Viktoriya Stalbovskaya, Anastasia Murat, Jim Ford, Francois Clement Bidard
Journal: Journal of Clinical Oncology (2020)

1037 Background: MCLA-128 (zenocutuzumab) is an ADCC-enhanced humanized bispecific antibody targeting HER2 and HER3 and potently blocking HER3-ligand induced receptor dimerization. Upregulation of Her2:Her 3 pathway is a means of resistance to ET in HR+ breast cancer, indicating a potential role for MCLA-128. In preclinical studies, the combination of MCLA-128 with ET in breast cancer xenografts outperformed single drug treatments. The current study explores the use of MCLA-128 to rescue pts with ET-resistant MBC who have progressed on a CDK4/6i. Methods: This phase II, open-label trial planned for up to 40 evaluable women with HR+, HER2 low (IHC 1+/IHC 2+ with negative FISH) MBC, who had progressed on a CDK4/6i and up to 3 lines of ET, who had received ≤ 2 chemotherapy regimens in the metastatic setting. Pts received MCLA-128 (750 mg, 2h IV, flat dose) q3w combined with last ET on which the pt had previously progressed immediately prior to study entry. Disease control rate (DCR; RECIST 1.1, per investigator), best overall response (BOR), overall response rate (ORR), safety, and PK, are evaluated. Data cut off was 14Nov2019. Results: 48 pts were treated, all of whom had progressed on a CDK4/6i. Pts had received a median 2 prior ET lines (range 1-5) and 1 line (range 1-3) of chemotherapy. Pts had a median number of 3 metastatic sites (range 1-6) and 42 (88%) had visceral involvement. Among 42 pts evaluable for efficacy, DCR was 45% (90% CI 32-59) with 2 pts having unconfirmed PR and 19 pts SD as BOR. Common related AEs (all grades; G3-4) were asthenia/fatigue (27%; 2%), diarrhea (25%; 0), nausea (21%; 0). No clinically significant LVEF decline was seen. At the end of cycle 1, mean trough level of MCLA-128 was 15.5 µg/mL, and mean terminal half-live was 102 h (n = 19-21). Data on the primary endpoint, clinical benefit rate at 24 weeks, and biomarkers will be provided. Conclusions: The addition of MCLA-128 to the last line of ET showed clinical activity after ET+CDK4/6i failure and a favorable safety profile. Clinical trial information: NCT03321981 .
Evaluation of DNA repair biology signatures to predict specific carboplatin (C) versus docetaxel (D) benefit in advanced triple-negative breast cancer (aTNBC).
Authors: Holly Tovey, Joel S. Parker, Katherine A. Hoadley, Richard D. Kennedy, Orsolya Sipos, Lucy Kilburn, Sarah Kernaghan, Patrycja Gazinska, Syed Haider, Sarah E Pinder, Judith Bliss, Charles M. Perou, Anita Grigoriadis, Andrew Tutt, Maggie Chon U Cheang
Journal: Journal of Clinical Oncology (2020)

1074 Background: In the Triple Negative Trial we observed no improved response rate (RR) to C over D in aTNBC [Tutt et al, Nat Med 2018], but we did in BRCA1/2 mutated (mut) patients (pts). We hypothesise tumors with other aberrant DNA damage response (DDR) characteristics having higher RR to DNA damage inducing C than D. Methods: We tested the predictive value of DDR process related gene expression signatures (PARPi7, chromosomal instability CIN70, TP53 &amp; DDR Deficiency (DDRD)) on 192 treatment naïve primary tumours (PT) by total RNA-sequencing. Odds ratio (OR) for RR are reported. Paired PT &amp; recurrent (REC) signature scores were compared. Results: Unexpectedly, high DDRD and PARPi7 were associated with higher RR to D than C ( p =0.01 &amp; 0.06). No effect was observed for CIN70 or TP53 signature. To assess whether the unexpected results were due to biological changes 12 PT-REC pairs were available from pts who received chemotherapy (CT) between PT &amp; REC. CIN70 increased from PT to REC, DDRD (non-significantly) &amp; PARPi7 decreased. 4/5 TP53 wildtype classified PT samples classified as mut in REC. The BRCA1/2 &amp; DDRD-treatment interactions only held in pts who received CT before trial entry (table). The PARPi7-treatment interaction only held in CT naïve pts. In CT naïve pts, high CIN70 tumors suggested higher C RR as hypothesized. Restricted to the 149 PAM50 basal-like pts, results were non-significant but similar trends seen. Conclusions: In this trial of aTNBC, DDRD high pts with prior CT had better RR to D than C. A possible explanation for this unexpected result is selective pressure of adjuvant DNA damaging CT and selection for relative taxane sensitivity in those who recur despite a high DDRD score. The hypothesised CIN70 treatment interaction was observed in CT naïve pts. Our results suggest care is required in application of signatures to initial diagnostic material when predicting response to DNA damaging agents at REC particularly in pts with prior CT. [Table: see text]
Patterns of disease presentation, treatment choices and survival in real world for patients diagnosed with advanced melanoma: A prospective observational study by Spanish Melanoma Group (GEM-1801).
Authors: Ivan Marquez-Rodas, Miguel Ángel Berciano Guerrero, Eva Muñoz-Couselo, Jose Luis Manzano Mozo, Pablo CEREZUELA Fuentes, Guillermo Crespo, Teresa Puértolas, Alfonso Berrocal, Ainara Soria, Margarita Majem, Lorena Bellido, Enrique Espinosa, Almudena García Castaño, Lourdes Gutierrez Sanz, Javier Medina, Luis Antonio Fernandez-Morales, Carlos Aguado De La Rosa, Rafael López Castro, Pablo Ayala de Miguel, Salvador Martin-Algarra
Journal: Journal of Clinical Oncology (2020)

e22022 Background: In the past decade, melanoma treatment has improved due to the advances in targeted therapy and immunotherapy. There are few data, however, about the treatment elections and the outcomes of the patients in the real world setting, specifically in a prospective manner. Methods: GEM1801 is a prospective cohort study that analyses the clinical and pathological disease presentation patterns, the different lines of treatment choices and the health outcomes derived from these treatments in 400 patients (pts) diagnosed with resected stage III (N = 47) and irresectable III/IV melanoma (N = 353). Here we focus on the pts diagnosed with advanced melanoma and the first line (1L) treatments. Results: Pts diagnosed after Jan 2018 were included from 35 hospitals in 15 different Spanish regions (recruitment Aug 2018 to Aug 2019). A survival cutoff was made by January 2020. 55.2% pts were male; median age was 65.1 (23.3- 95.2). 66% were cutaneous, 5.4% acral, 2.8% uveal, 17.3% non-disclosed and 4.2% were classified as “other” subtypes. According to AJCC 8 th edition, 9.3% were unresectable IIIB/C/D and 90.7% IV (27.5% A, 16.6% B, 37.5% C and 18.4% D). ECOG was 0-1 in 85%; LDH levels were available in 282 pts (79.9%), being normal in 61.7%, &gt; 1x to 2x ULN in 29.8% and &gt; 2x ULN in 8.5%. BRAF was evaluated in 344 pts (97.5%), being 52.9% mutated. Median survival follow up was 9.7 months (0.2-24) with 73.9% patients alive at time of analysis (over 345 pts with data available). Median overall survival was not reached, with a median follow up of 9.7 months (0.2-24.0). 72.2% of pts were alive at the time of analysis. Table summarize the 1L options according to BRAF status in the 326 pts with data available (17 received no systemic treatment and in 10 was unknown). Conclusions: this study reflects real world data in a representative cohort of pts with melanoma in Spain. Survival results, pending on more follow up, could be considered consistent with the results of modern clinical trials. TT is the most frequent 1L choice for patients with BRAF+ melanoma (almost 2/3 of cases). In terms of IT, monotherapy based in anti PD-1 is the most frequent 1L choice, with a rank between 75-90% of cases. [Table: see text]
肋骨固定钉在多发性肋骨骨折治疗中的应用
Authors: 姜杰, 杜好信, 耿国军, 姚成才, 陈端阳, 李水文
Journal: BMJ (2007)

2006年5月至2006年9月,我科对经胸部X线片和(或)胸部CT肋骨三维重建检查确诊的8例多发性肋骨骨折患者施行肋骨固定钉内固定术,术后患者呼吸痛明显减轻,胸廓畸形恢复,呼吸功能明显改善.表明肋骨固定钉在多发性肋骨骨折手术治疗中操作简便,临床效果好。
A phase III study of venetoclax plus low-dose cytarabine in previously untreated older patients with acute myeloid leukemia (VIALE-C): A six-month update.
Authors: Andrew H. Wei, Pau Montesinos, Vladimir Ivanov, Courtney Denton Dinardo, Jan Novak, Kamel Laribi, Inho Kim, Don A. Stevens, Walter M. Fiedler, Maria Pagoni, Olga Samoilova, Jianxiang Wang, Achilles Anagnostopoulos, Julie Bergeron, Jing-Zhou Hou, Takahiro Yamauchi, Qi Jiang, Wellington Mendes, John W. Hayslip, Panayiotis Panayiotidis
Journal: Journal of Clinical Oncology (2020)

7511 Background: VIALE-C was designed to compare the safety and efficacy of the BCL-2 inhibitor venetoclax (VEN) or placebo (PBO) plus low-dose cytarabine (LDAC) in previously untreated patient (pts) with acute myeloid leukemia (AML; ≥75 yr or ≥18 yr with comorbidities precluding intensive chemotherapy). The primary overall survival (OS) analysis showed a clinically meaningful improvement with VEN+LDAC, although the primary endpoint was not met. Herein, we present a 6-mo update after primary analysis, with a focus on OS. Methods: This double-blind, PBO-controlled phase 3 study (NCT03069352) randomized pts 2:1 to VEN (600 mg orally QD, days [d]1–28) with 4-d ramp-up in first cycle or PBO in 28-d cycles, plus LDAC (20 mg/m 2 subcutaneously QD, d1–10). The primary endpoint was OS; secondary endpoints included response, transfusion independence (TI; red blood cells [RBC] or platelets), and event-free survival (EFS). OS and EFS were analyzed by the Kaplan-Meier method and compared between arms using the log-rank test stratified by AML status (de novo vs secondary) and age (18 to &lt; 74 vs ≥75). The planned sample size was 210 pts (n = 140, VEN; n = 70, PBO) to detect a hazard ratio (HR) of 0.545 in OS with 2-sided alpha of 5% and power of 90%. Results: As of 15 Aug 2019, 211 pts were randomized (n = 143, VEN; n = 68, PBO); median age: 76 yr in both arms (range: 36–93); secondary AML: 38% (88% post-MDS/CMML); prior hypomethylating agent: 20%. With a median follow-up of 17.5 mo (range: 0.1–23.5), median OS was 8.4 mo vs 4.1 mo in the VEN+LDAC and PBO+LDAC arms (HR 0.70; 95% CI 0.50–0.99; P= .04), representing a 30% reduction in the risk of death. Complete remission (CR)/CRi and CR/CRh (CR with partial hematologic recovery) rates were both 48% for the VEN+LDAC arm, and 13% and 15%, respectively, for PBO+LDAC. RBC/platelets TI rates were 43%/49% vs 19%/32% for VEN+LDAC and PBO+LDAC. Median EFS was 4.9 mo vs 2.1 mo in the VEN+LDAC and PBO+LDAC arms (HR 0.61; 95% CI 0.44–0.84; P= .003). Grade ≥3 adverse events (AEs [ &gt; 30%]; VEN+LDAC/PBO+LDAC) included neutropenia (49%/18%), thrombocytopenia (45%/38%), and febrile neutropenia (32%/29%); serious AEs ( &gt; 10%) were febrile neutropenia (17%/18%) and pneumonia (14%/10%); tumor lysis syndrome occurred in 5.6%/0%. Conclusions: VEN+LDAC demonstrates a clinically meaningful improvement in OS compared with PBO+LDAC, with a tolerable and manageable safety profile. These data support VEN+LDAC as a frontline treatment option for older pts with AML, as well as those considered unfit for intensive chemotherapy. Clinical trial information: NCT03069352 .
M.D. Anderson experience of immune checkpoint inhibitor therapy in classical Hodgkin lymphoma.
Authors: Ranjit Nair, Chelsea Camille Pinnix, Jillian Rebecca Gunther, Paolo Strati, Jason Westin, Luis Fayad, Fredrick B. Hagemeister, Swaminathan Padmanabhan Iyer, Loretta J. Nastoupil, Simrit Parmar, Maria Alma Rodriguez, Raphael Steiner, Bouthaina Shbib Dabaja, Penny Fang, Christopher Flowers, Mansoor Noorani, Lei Feng, Sattva Swarup Neelapu, Sairah Ahmed, Hun Ju Lee
Journal: Journal of Clinical Oncology (2020)

e20013 Background: Nivolumab and Pembrolizumab are effective immune checkpoint inhibitor (ICI) therapies targeting PD-1/ PDL-1 immune axis. The drugs are currently approved for relapsed/ refractory classical Hodgkin lymphoma (cHL)based on phase I and II trial data. Methods: We conducted a retrospective study of patients (pts) with relapsed refractory cHL treated with ICI therapy at M.D. Anderson Cancer center from 4/2013 to 5/2019 to evaluate the efficacy of this treatment. The responses were assessed using revised response criteria according to the Lugano classification Results: Ninety-two pts treated with nivolumab (66) and pembrolizumab (26) were included. Fifty six pts (63%) were advanced stage at diagnosis, most treated initially with ABVD (88%) and BV-AVD (3%). Seventy percent pts had primary refractory disease or relapsed &lt; 12 months after frontline therapy. At the time of ICI initiation, pts had the following characteristics: median age 35 (range 18-86), extranodal disease - 28 pts (37%), prior BV exposure in 81 pts (89%) with 66% considered BV refractory. Sixty one percent patients were refractory to the last prior line of salvage therapy. Median prior lines of therapy was of 3 (range 1-13) and 53 pts (58%) had a prior HSCT. At a median follow-up time of 20.2 months (range: 1.58 - 55.98 months), median progression free survival was 12.3 months and median overall survival was not reached. Among the 39 patients with no prior transplant, 11 patients who achieved CR with ICI were consolidated with HSCT (autologous - 7 and allogeneic - 4). Of this cohort, 2 pts (1 post auto, 1 post-allo) have relapsed. Five patients in our cohort were treated with an alternative ICI for subsequent relapse; of four patients with response assessment, 3 achieved CR and 1 experienced PD. Conclusions: In this cohort of cHL pts, ICI offered high response rates before and after HSCT supporting the possibility for using ICI earlier in the treatment course for refractory or early relapsed HL.
空肠恶性间质瘤二例
Authors: 符智深
Journal: BMJ (2007)

例1 患者男,38岁.因脐周阵发性绞痛、消瘦2个月入院.自诉腹痛时可及包块,疼痛与进食、体位无明显关系,无呕吐、腹泻、黏液血便或便秘.查体:营养不良,慢性痛苦病容,浅表淋巴结未触及.心肺无异常,腹平软,未见胃肠蠕动波,脐左旁可扪及一约3 cm×5 cm包块,质中,边界不清,可推动,无压痛.移动性浊音阴性,肠鸣音稍增强。
澳大利亚社区康复对上海社区卫生服务的启发
Authors: 林桦
Journal: BMJ (2007)

2006年2月至4月,上海市静安区卫生局组织全科医生和康复医生赴澳大利亚悉尼短期培训学习,并参观了悉尼市的养老院、老年病科康复病房、皇家康复中心、皇家北岸医院、曼利医院、社区卫生服务中心以及部分慈善机构等,在3家私立医疗中心进行了3周的见习.2个月的访问学习使我们对澳大利亚康复服务体系有了初步印象,并认为对上海社区卫生服务建设有许多启示和可借鉴之处。
HealthTree Patient Portal mediated myeloma patient-reported vaccination and antibiotic use.
Authors: Michael A. Thompson, Jenny Ahlstrom, Nathan W. Sweeney
Journal: Journal of Clinical Oncology (2020)

e20567 Background: Multiple myeloma (MM) is a cancer of the immune system. Infection is a major cause of morbidity and mortality in MM. Vaccines are the first line of prevention for infectious diseases. Anti-microbial prophylaxis may improve patient (pt) outcomes, but real-world use has not been well characterized. In order to engage the pt community regarding vaccination we utilized HealthTree (www.healthtree.org). Methods: An investigator-submitted online survey asking about infection prophylaxis and vaccinations was fielded to 4,944 pts from May 10, 2019, to January 9, 2020. The HealthTree platform queries pts about sharing data for research purposes. De-identified responses were aggregated and reviewed. The study was determined to be exempt by the Western Institutional Review Board. Results: 458 MM pts participated in the surveys and were able to select more than one option with the total response indicated below. Abbreviated questions and simplified responses are noted in Table including: 1. Have you ever been vaccinated in the last 5 years with a pneumococcal vaccine (PV)? 2. In the last 3 flu seasons, have you received the influenza vaccine (FV)? 3. After you began myeloma treatment, did you ever receive the anti-Varicella Zoster Virus (VZV, shingles) vaccine? 4. Were you (or are you currently) treated with anti-viral prophylaxis? 5. Were you (or are you currently) treated with antibiotic bactrim? 6. Were you (or are you currently) treated with levofloxacin prior to stem cell transplant or at the beginning of your MM therapy? Conclusions: Both FV and PV were fairly high in this self-selected cohort of volunteers compared with a large health system ( http://ow.ly/O8Dx30b9Wuc ) and a global registry ( http://ow.ly/Uofg30h6Qen ). Most did not receive an anti-VZV vaccine, but a few received a live vaccine. Anti-viral prophylaxis was common, but not universal. Anti-PJP and levofloxacin use were reported by a minority of participants. Pt reported interventions via an online portal can help investigators survey the pt community and result in hypothesis generating research questions including investigating vaccine: types, dosing, sequencing, and use of anti-infective interventions. [Table: see text]
Clinical evaluation of combination assay of serum tumor markers in non-small-cell lung cancer patients
Authors: Ping Wang, Yong-tong Cao, Jing-hua Li, Tie Zhang
Journal: BMJ (2013)

The pre-treatment serum levels of carbohydrate antigen 125 (CA125), cytokeratin 19 fragment 21-1 (CYFRA21-1), squamous carcinoma associated antigen (SCC-Ag), and tissue polypeptide antigen (TPA) were measured in 111 patients with primary non-small-cell lung cancer. And 103 benign lung disease cases and 97 healthy volunteers were also studied as controls. Enzyme linked immunosorbent assay (ELISA) was employed to detect the serum contents of SCC-Ag and TPA. The levels of CA125 and CYFRA21-1 were measured by electrochemical luminescence. The serum level of CYFRA21-1, SCC, TPA and CA125 in cancer patients were significantly higher than those of normal control and benign disease groups (P<0.01). The combined detection of tumor markers could significantly improve the sensitivity and specificity. And the levels of tumor markers were also correlated with the clinical stages and differentiation degrees.


Key words: 
Carcinoma，non-small-cell lung; Early diagnosis
Relationship between insulin resistance and other metabolic disorders in hypertensive patients
Authors: 刘成国, 阮连生, 郑海斌, 郭琼瑶
Journal: BMJ (2007)

目的 探讨高血压病患者胰岛素敏感性与其他代谢异常的关系.方法 用正常血糖胰岛素钳夹技术测定26例健康者和84例高血压病患者的葡萄糖代谢率,用盐负荷升压及减钠降压试验测定盐敏感性.结果 高血压病患者葡萄糖代谢率比正常人明显降低(P＜0.01),84例高血压病患者中有47例(55.9%)存在胰岛素敏感性降低,50例(59.5%)存在盐敏感.按葡萄糖代谢率数值把84例高血压病患者分为两组:高血压病合并胰岛素敏感性降低组(降低组)47例,胰岛素敏感性正常组(正常组)37例.经方差分析,纠正体重指数后,降低组的各项代谢指标仍比正常组高,盐敏感发生率分别为58.1%,21.7%(P＜0.01).结论 胰岛素敏感性降低加重了高血压病患者盐、血脂及血尿酸等的代谢紊乱,胰岛素抵抗可能是其他各项代谢异常的根源。
在全科医疗实践中不断学习
Authors: 周仲华
Journal: BMJ (2008)

在全科医疗工作中,有时会遇到自己不熟悉的问题.我学习全科医学的启蒙老师Peter医生曾经对我说过一句话,一直鼓励着我如何面对自己不熟悉的临床问题,他说:我们全科医生不可能知道所有问题的答案,但是重要的是当不知道答案的时候我们知道去哪里找到答案.
Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.
Authors: Alexey Rumyantsev, Alexandra Tyulyandina, Ilya Pokataev, Konstantin Morkhov, Valentina Mikhailovna Nechuskina, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2020)

e18066 Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size &gt; 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m 2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.
Fulminant amoebic enteritis presenting with metastatic right lower abdominal pain: report of one case with literature review
Authors: Pu Zhou, Yiming Wang, Min Hu, Minwei Zhou, Xiaodong Gu, Zhongwen Zhou, Jianbin Xiang, Jingwen Gu
Journal: BMJ (2020)

阿米巴感染性肠炎是一种较少见的胃肠道感染性疾病，临床症状表现为不同程度的腹痛、腹泻伴血便，暴发型阿米巴肠病为其最严重的并发症，病死率高。本文回顾性分析复旦大学附属华山医院收治的1例以转移性右下腹痛表现起病，最终确诊为暴发型阿米巴肠病患者的临床资料和治疗过程，并结合国内外文献分析该病临床特点、影像学表现、病理特点及治疗。