tbuckley/cabot-search huggingface dataset:
Effect of ARID1a oncogenic loss of function mutations on overall survival in metastatic breast cancer patients.
Authors: Veronica Mariotti, Hatem Hussein Soliman
Journal: Journal of Clinical Oncology (2020)

e13068 Background: ARID1a (AT Rich Interactive Domain 1A) is part of the SWI/SNF complex, which regulates gene transcription. Its inactivation has been shown to determine resistance to endocrine therapy via enrichment of basal-like gene expression features [Xu G., 2020]. We recently reported that ARID1a lower gene expression might be associated with worse overall survival (OS) [Mariotti V., 2019]. The aim of this study was to analyze the effect of ARID1a mutations on survival in metastatic breast cancer patients (pts). Methods: Breast cancer patients prospectively consented for inclusion in the ORIEN genomic database with known metastatic disease were analyzed using cBioPortal. Predicted biologic effect of mutations from RNASeq data was determined by OncoKB. OS was calculated from initial breast cancer diagnosis to death from any cause. OS analysis using Kaplan Meier and descriptive statistics were performed on SPSS. Results: We identified 644 pts with metastatic breast cancer. Of these, 88 (12.8%) pts harbored an ARID1a mutation. 62 (70.5%) mutations were missense (biologic effect unknown), the remaining 26 (29.5%) were oncogenic loss of function (OLF) changes (frame-shift, deletion, insertion, or nonsense). Median OS was significantly better in patients harboring missense mutations compared to OLF and wild type mutations [median OS 58.2 months (95% CI 44.5-71.8) with missense mutations vs 22.8 months (95% CI 10.8-34.7) with OLF mutations and 27.48 months (95% CI 24.5-30.3) with wild type]. Demographics, tumor features and chemotherapy use were generally equally distributed among the subgroups (table). Conclusions: In our study the median OS was worse in metastatic breast cancer pts harboring OFL ARID1a mutations compared to pts with wild type ARID1a or harboring missense ARID1a mutations. Further studies are warranted to assess how specific ARID1a mutations might affect survival in metastatic breast cancer pts. [Table: see text]
Variability in multimodality treatment influences survival in non-metastatic gastric cancer patients.
Authors: Tuyen Hoang, Farshid Dayyani, Ariceli Alfaro, Jasmine Huynh, Jingran Ji, Andrew H. Ko, May Thet Cho, Darryl Hiyama
Journal: Journal of Clinical Oncology (2020)

e16588 Background: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions. Methods: California Cancer Registry of demographic and clinical data were collected for nmGC patients who underwent surgery with curative intent from 2010-2018. We conducted chart reviews of the patients’ electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes. Results: Demographics of study cohort (n = 326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) versus 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant, 25% adjuvant, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median follow-up after surgery of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries was associated with lower lymph node recovery (median = 15 vs 19, p = .0042), which in turn was associated with a significant decrease in overall 5-year survival after adjusted for tumor stage (hazard ratio HR = 1.9, p = .0012). Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival. In contrast, greater lymph node recovery plus chemotherapy were associated with improved survival in patients with loco-regional tumors (HR = 0.3, p = .0020). Conclusions: This study highlights major practice differences in the management of nmGC across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.
加强过程管理提高全科医师培训质量
Authors: 陈丽芬, 樊洁, 贾建国
Journal: BMJ (2011)

北京市于1999年在全国率先启动了全科医师规范化培训工作,宣武医院作为首批全科医师基地开始接收学员.2008年北京市卫生局对已有的全科医师基地进行了重新评审认定,自此,宣武医院作为全科医师规范化培训基地开始接收新一批学员进行为期三年的全科医师规范化培训。
Impact of autologous stem cell transplant utilization in a vulnerable multiple myeloma population.
Authors: Tamer Othman, Yingyu Wang, Shelly Gupta, Daniel Wu, Rohan Gupta, Larissa Celles, Gregorianna Lane, Matthew Genyeh Mei, James Yeh, Sarah Tomassetti
Journal: Journal of Clinical Oncology (2020)

e20556 Background: Despite improvements in the survival of multiple myeloma (MM) patients, disparities in outcomes persist in underserved populations, in part due to variable access to treatments including autologous stem cell transplant (ASCT), a standard treatment for fit patients. Harbor-UCLA Medical Center (HUMC) is a safety net hospital in Los Angeles with a population of socially and medically vulnerable patients, many of whom possess limited English proficiency. Historically, access to ASCT at tertiary centers has been challenging for patients at HUMC. We present the outcomes for 160 newly diagnosed MM patients between 1998 and 2019 during which our referral process for ASCT markedly improved. Methods: We retrospectively analyzed 160 MM patients evaluated at HUMC between 1998 and 2019. The cohort was divided into 2 groups based on year of diagnosis: 1998-2013 and 2014-2019. Referral for and utilization of ASCT, and 5-year survival rates were recorded. Survival rates were calculated through a Kaplan-Meier analysis. Results: 160 MM patients were included in the analysis. 93 patients were diagnosed in 1998-2013 and 64 in 2014-2019. Three patients had an unknown diagnosis date. Patient characteristics are described in Table. ASCT referrals increased from 23% to 59% (P&lt;0.001) after designating a nurse practitioner to coordinate referrals, and implementing a standardized referral template and an electronic medical record system to send and track requests. With an increased referral rate, ASCT utilization showed an increasing trend from 15% between 1998-2013 to 27% between 2014-2019 (P=0.11). Five-year survival rate was 49% (95% CI, 37.8%-62.5%) from 1998-2013 and 70% (95% CI, 57.5%-84.6%) from 2014-2019, and was greater in patients who received ASCT compared to those who did not, 95% (95% CI, 85.2%-100.0%) versus 55% (95% CI, 40.2%-75.1%) (P=0.01). Conclusions: Increased ASCT utilization was associated with improved survival in our underserved MM population, suggesting that adherence to the most evidence-based treatments, such as ASCT utilization, may help overcome the disadvantages of a resource-limited setting. Continued refinements in our referral process will likely increase ASCT utilization. [Table: see text]
γ9δ2T cell diversity and the receptor interface with tumor cells
Authors: Anna Vyborova, Dennis X. Beringer, Domenico Fasci, Froso Karaiskaki, Eline van Diest, Lovro Kramer, Aram de Haas, Jasper Sanders, Anke Janssen, Trudy Straetemans, Daniel Olive, Jeanette Leusen, Lola Boutin, Steven Nedellec, Samantha L. Schwartz, Michael J. Wester, Keith A. Lidke, Emmanuel Scotet, Diane S. Lidke, Albert J.R. Heck, Zsolt Sebestyen, Jürgen Kuball
Journal: Journal of Clinical Investigation (2020)

γ9δ2T cells play a major role in cancer immune surveillance, yet the clinical translation of their in vitro promise remains challenging. To address limitations of previous clinical attempts using expanded γ9δ2T cells, we explored the clonal diversity of γ9δ2T cell repertoires and characterized their target. We demonstrated that only a fraction of expanded γ9δ2T cells was active against cancer cells and that activity of the parental clone, or functional avidity of selected γ9δ2 T cell receptors (γ9δ2TCRs), was not associated with clonal frequency. Furthermore, we analyzed the target-receptor interface and provided a 2-receptor, 3-ligand model. We found that activation was initiated by binding of the γ9δ2TCR to BTN2A1 through the regions between CDR2 and CDR3 of the TCR γ chain and modulated by the affinity of the CDR3 region of the TCRδ chain, which was phosphoantigen independent (pAg independent) and did not depend on CD277. CD277 was secondary, serving as a mandatory coactivating ligand. We found that binding of CD277 to its putative ligand did not depend on the presence of γ9δ2TCR, did depend on usage of the intracellular CD277, created pAg-dependent proximity to BTN2A1, enhanced cell-cell conjugate formation, and stabilized the immunological synapse (IS). This process critically depended on the affinity of the γ9δ2TCR and required membrane flexibility of the γ9δ2TCR and CD277, facilitating their polarization and high-density recruitment during IS formation.
A phase I study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors.
Authors: Thomas Cash, Hunter C. Jonus, Maya Tsvetkova, Jan Hendrik Beumer, Jasmine Y Lee, Curtis Henry, Dolly Aguilera, R. Donald Harvey, Kelly C. Goldsmith
Journal: Journal of Clinical Oncology (2020)

10541 Background: HMG-CoA reductase inhibitors (statins) can inhibit IL-6-mediated STAT3 activation, a critical pathway in pediatric CNS and solid tumors. Statins also inhibit tumor proliferation, angiogenesis, and restore apoptosis in preclinical pediatric solid tumor models. We therefore conducted a phase 1 trial of simvastatin in combination with topotecan and cyclophosphamide in children with relapsed/refractory (r/r) solid and CNS tumors. Methods: Eligible patients were 1-29 years of age with a r/r solid or CNS tumor. Simvastatin was administered orally twice daily on days 1-21, with topotecan 0.75 mg/m 2 /dose IV and cyclophosphamide 250 mg/m 2 /dose IV on days 1-5. Four dose levels (DLs) were planned: 140, 180, 225, 290 mg/m 2 /dose. A 3+3 design was used to determine the maximum tolerated dose (MTD). Pharmacokinetic and pharmacodynamic analyses were performed. Results: The median (range) age of 14 eligible patients was 11.5 years (1 - 23). Diagnoses included neuroblastoma (N = 4), sarcoma (N = 7), and one each of malignant rhabdoid tumor of kidney, medulloblastoma, and Wilms tumor. Eleven DLT-evaluable patients received a median of 4 cycles (range: 1-6). There were 3 cycle 1 DLTs, grade 3 diarrhea and grade 4 creatine phosphokinase (CPK) increased at DL 1, and grade 4 CPK increased at DL 0 (100 mg/m2/dose). Grade 3/4 treatment-related cycle 1 adverse events occurring in ≥ 10% patients were neutropenia (100%), leukopenia (100%), thrombocytopenia (91%), lymphopenia (91%), anemia (55%), febrile neutropenia (55%) and CPK increased (18%). Best overall response was partial response in 1 patient and stable disease in four. Simvastatin and simvastatin acid C max (geomean 82.5 and 12.6 ng/mL) and AUC 0-6 (geomean 82.5 and 12.6 ng•h/mL) were comparable with reported pediatric literature values (C max 3.5 and 0.4-2.1 ng/mL; AUC 0-8 10.7 and 3.8 ng•h/mL) after correction for the higher doses (3.77 vs 0.16 mg/kg) used in our study. Patient peripheral blood mononuclear cells showed maximum phospho-(p)STAT3 inhibition on Day 5, with recurrence by Day 21 despite continued simvastatin dosing. Plasma IL6 levels showed sustained IL6 inhibition with decrease to normal values by Day 21 in all patients, indicating potential on target effects. Conclusions: For this first-in-pediatrics trial of statins as anti-cancer therapy, the MTD of simvastatin with chemotherapy was 100 mg/m 2 /dose. This combination was well-tolerated with predominantly hematologic toxicity and predictable DLTs related to simvastatin. Clinical trial information: NCT02390843.
乳房外Paget病一例
Authors: 姚树成
Journal: BMJ (2007)

患者男,67岁.因会阴部红斑伴瘙痒5年,加重2周,于2006年5月30日就诊.5年前无明显诱因阴囊左侧出现指甲大小淡红色斑片伴瘙痒,先后在当地多家医院诊治,诊断为湿疹、股癣等.内服外用抗过敏和抗真菌药物治疗,疗效不佳,经过反复多次治疗,皮损不能控制且逐渐扩大,局部出现糜烂、渗出,皮损波及阴茎根部及右侧阴囊上部.2周前使用联苯卞唑乳膏后局部渗出加重,就诊我院皮肤性病科门诊.患者病程中无发热,大小便、睡眠尚可.无药物过敏史,家族中无类似病史。
糖尿病患者口服降糖药治疗血糖不达标时的胰岛素应用
Authors: 舒晓春
Journal: BMJ (2011)

目前,有关2型糖尿病的阶梯治疗方案并不合理.英国前瞻性糖尿病研究(UKPDS)结果显示,6年内单独饮食治疗使265例患者的胰腺功能降低了50%.研究表明,从首次单独二甲双胍治疗糖化血红蛋白(HbAlc)>8.0%到改变治疗方案的时间为14个月,而首次单独磺脲类治疗HbAlc>8.0%到改变治疗方案的时间则为20个月,治疗上的延迟更导致血糖控制不理想。
Accomplishments of standardized residency training programs in Shanghai
Authors: Lin Mei, Jiajie Jin, Jiayan Huang, Zhiqiang Wan, Rong Zhou, Kan Zhang
Journal: BMJ (2018)

The overall situation of standardized residency training program in Shanghai was analyzed in terms of resource input, implementation and output of the program. The results showed that 50 hospitals offered residency training programs by 2015, with total 12 557 mentors. There was a certain increase in resource input from both government and hospitals, and organizational management was continuously improved. From 2010 to 2016, a total of 16 241 residents were recruited, and number of residents were increased greatly. Compared with 2010, the recruitment of residents in general practice, pediatrics and anesthesiology in 2016 was increased by 113.3%, 98.6% and 157.4%, respectively. The passing rate of medical licensing examination in institutions providing standardized resident training was 20 percent higher than others, and the passing rate of residency training reached 97%-98%, which showed that the effect of standardized resident training program in Shanghai was satisfactory. In the future, more attentions should be paid to strengthening the training bases, training specialists in the shortage fields and standardizing the training of trainers.


Key words: 
Standardized resident; General practitioners; Training program
Quality-of-life (QOL) analyses in patients with multiple myeloma: Results from the selinexor (KPT-330) treatment of refractory myeloma (STORM) phase IIb study.
Authors: Sundar Jagannath, jyotsna mehta, Janis Breeze, Gabriel Tremblay, Lingling Li, Noa Biran, Sharon Shacham, Michael G. Kauffman, Jatin J. Shah
Journal: Journal of Clinical Oncology (2020)

e20522 Background: Selinexor, a novel oral selective inhibitor of nuclear export, was recently approved for use in relapsed/refractory multiple myeloma (MM). The efficacy and safety of selinexor and dexamethasone was evaluated in a phase 2b, single-arm, open-label, multicenter trial in patients with penta-exposed, triple-class refractory MM. Patient-reported outcomes were measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) assessment. While minimal clinically important differences (MCID) have been established for other FACT scales, there is no known, validated definition of MCID for the FACT-MM. This study reports results of QoL analyses in patients with MM enrolled in the STORM phase 2b trial and examines two approaches to calculate MCID for the FACT-MM. Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week cycle, and at end of treatment (EOT) during the STORM phase 2b trial. Change from baseline was analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain. Two approaches for evaluating MCID were explored: the first based on patient-reported assessment of meaningful change, defined as 10% of the instrument range (Ringash 2007), and the second based on mean baseline differences between ECOG groups (0 vs 1 to 2) based on patient level data. Additional analyses were performed to identify trends among treatment responders and non-responders, including a difference-in-difference (DID) analysis to compare changes between baseline and EOT. Results: Eighty patients had sufficient data to be included in longitudinal QOL analyses. MCID analyses demonstrated that most patients did not experience decline during the first six cycles of treatment; this pattern was consistent with MCID defined either as 10% of the instrument range (range 54% to 75% of patients), or as an ECOG-based anchor (range: 54% to 73% of patients). The DID analysis found that the mean change in QoL of non-responders decreased significantly between baseline and EOT, while responders had no significant change. This difference between responders and non-responders was significant for the FACT-G. Conclusions: Most patients did not experience QoL decline during the early cycles of selinexor treatment during the STORM 2b trial. The MCID decline, evaluated by two approaches, was greater among treatment non-responders than responders. A DID approach demonstrated greater decline between baseline and EOT for non-responders. Clinical trial information: NCT02336815.
糖尿病合并稳定性心绞痛的药物治疗
Authors: 秦明照
Journal: BMJ (2008)

研究显示,约80%的冠心病患者合并糖代谢异常,其中53%合并糖尿病,新诊断的糖尿病50%以上患者有冠心病,因此这两种病常常出现在同一患者身上,此时发生心血管事件的风险明显升高.在社区患者中糖尿病合并稳定性心绞痛相对其他类型冠心病更常见。
Development of cardiac events in postmenopausal breast cancer patients treated with Aromatase inhibitor (AI) and Selective estrogen receptor modulator (SERM).
Authors: Priyanka Parajuli, Manjari Rani Regmi, Ruby Maini, Odalys Estefania Lara Garcia, Nitin Tandan, Noupama Mirihagalle, Asad Cheema, Sabree Abedrabo, Zurain Niaz, Cameron Koester, Hamsa Sahib, Bishal Bhandari, Alexander Johnson, Abdisamad M. Ibrahim, Kristin Delfino, Kathy Robinson, Meghna R. Desai, Abhishek Kulkarni
Journal: Journal of Clinical Oncology (2020)

e12529 Background: Breast cancer is the most common cancer diagnosed in women. Cardiovascular diseases (CVD), alternatively, is the leading cause of mortality in women worldwide. Adjuvant endocrine therapy including AI and SERM is offered to almost 75% of patients with estrogen receptor–positive (ER + ) disease and potentially raises concerns for negative effects in cardiovascular health. Our study aims to evaluate cardiac events including acute coronary syndrome (ACS) and heart failure requiring hospitalization (HF) in post-menopausal patients treated with AI and SERM. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Development of ACS and heart failure requiring hospitalization upon initiating AI or SERM was considered an adverse cardiac event. Statistical analysis was performed with SAS v9.4. software. Chi Square (or Fisher’s Exact test) was used to test associations between various medication and cardiac events. Student’s T-test (or non-parametric equivalent when violations occurred) was used to assess if there was a difference in delta between those on and those not on medication categories. All significance was assumed at the p &lt; 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Of the 336 patients, 55% (n = 185) and 22% (n = 77) were offered therapy with AI and SERM, respectively. 6.49 % (n = 12) developed cardiac event with AI compared to 7.10 % (n = 13) who were not on AI therapy, (p = 0.814). Similarly, 6.49 % (n = 5) developed cardiac event with SERM compared to 6.87 % (n = 20) who were not on SERM therapy, (p = 0.9064). Moreover, an interesting finding in patients treated with SERM therapy compared to those not on SERM therapy was the delta of left ventricular ejection fraction (LVEF). Median LVEF of 3.5% (0 to 21%) was noted in patients treated with SERM compared to a median LVEF of 5% (0 to 55%) in patients who were not treated with SERM, p = 0.048. Conclusions: Our findings revealed AI and SERM therapy did not increase adverse cardiac events in our patient cohort. Cardiac safety of the patients is less likely to be compromised with AI and SERM therapy and therefore, should be initiated early in the course of treatment for better patient outcome. Furthermore, since SERM therapy can possibly have an effect in the LVEF of patients, a frequent evaluation LVEF is warranted to prevent any unwarranted complications.
Using a bi-directional digital health platform for cancer care coordination and monitoring to enhance the cancer care continuum between patients, clinicians and caregivers.
Authors: Sharon Hensley Alford, Shilpa Mahatma, Rohit Mahatma, Sagar Amode, Rupal Sethia, Kartik Mahatma, Hitesh Mahatma, Varun Mahatma, Nayan Sonawane, Kanchan Chawla, Pooja Patil, Pravin Solankar, Shital Belote, Sneha Wasu, Srishti Mahatma, Tarun Kumar
Journal: Journal of Clinical Oncology (2020)

e14105 Background: It has been recognized that current electronic medical record (EMR) systems detract from the patient-provider relationship and that an innovative technology is needed to re-center medical encounters on the patient-provider engagement. This is especially important in oncology during new patient onboarding, care coordination in between medical visits and survivorship planning. Methods: We built a HIPAA compliant role-based digital health platform to support providers in patient engagement and care coordination. In this pilot at a non-profit oncology center in India, nurse navigators onboarded the patients using the mobile application. The technology was used to digitize past medical records and parse the clinical history. In addition, self-reported patient past medical history, family history, as well as social, reproductive and surgical history was collected as needed. The system collated the information into an easy to consume case summary for the oncologists. The system was tested with 3 clinicians and consented cancer patients. Results: Nearly 200 cancer patients participated in the pilot study. Patients’ medical records were digitized by oncology nurse navigators. The summarized longitudinal view of the patient’s medical history was used by oncologists for diagnosis and treatment planning. Participating clinicians noted that the digital case summary saved time and effort in treatment planning. In addition, it was noted that collaboration between nursing staff, medical oncologist, surgical oncologist and radiation oncologist was substantially improved. Conclusions: We demonstrate the value of using digital health technology to support the care coordination of cancer patients in a low-resource, non-profit clinical center in India.