tbuckley/cabot-search huggingface dataset:
Reconstruction of the superior vena cava in patients with thymic malignancies.
Authors: Lei Yu
Journal: Journal of Clinical Oncology (2020)

e21116 Background: Thymoma is a kind of mediastinal tumors usually with an indolent growth pattern but malignant because of potential for local invasion, pleural dissemination, and even systemic metastases. Different from other malignant tumors, thymoma is often associated with autoimmune disorder s, the most common one being myasthenia gravis (MG). Complete surgical excision has been regarded as the standard of care for patients with thymoma, esp. locally advanced thymoma. The aim of this study was to investigate the effectiveness of reconstruction (Y-shaped bypass) of the superior vena cava (SVC) to treat locally advanced thymoma with SVC syndrome. Methods: We retrospectively studied data from 24 consecutive patients with locally advanced thymoma and SVC syndrome, operated on from October. 2015 to Dec. 2018 in Beijing Tongren Hospital. Their clinical data including clinical presentation, operation procedure, postoperative drug, adjuvant radiochemotherapy and follow-up were documented. 18 cases had MG, one having dermatomyositis, and two having interstitial pneumonia. Results: There were no perioperative deaths. All patients underwent complete resection and replacement with a GORE-TEX Vascular Graft (Y-shaped bypass) of SVC. The number of typeAB, B1, B2, B3 thymoma, and thymic carcinoma in this data were 2, 2, 7, 7, and 6, respectively. 7 patients had postoperative complications: 3 (with MG) experienced myasthenia crisis, 3 had pneumonia, and one had pulmonary embolisms, respectively. Both unfractionated heparin and Warfarin were routinely used the second or third day after surgery to maintain INR (International Normalized Ratio) between 1.8 and 2.5. All patients received mediastinal radiation therapy within one month after surgery. All patients were followed up for 2 months to 42 months. There were no patients dying and recurring. Conclusions: Reconstruction of SVC (Y-shaped bypass) is an effective way to treat locally advanced thymoma with SVC syndrome. After surgery, postoperative anti-thrombotic agents should be applied to prevent acute graft occlusion.
Review: oral vitamin D prevents non-vertebral and hip fractures in a dose-dependent manner in patients ≥65 years of age
Authors: Bischoff-Ferrari, Ha, Willett, Wong, Jb, 季媛媛
Journal: BMJ (2010)

问题：在65岁以上患者中，口服维生素D能否预防非椎骨骨折及髋骨骨折？ 所涉及的研究评价了补充口服维生素D的效果并报道平均年龄65岁以上患者中一处以上骨折。研究必须为双盲并且随访1年以上。排除标准包括：非对照研究、观察研究或动物研究；研究对象有器官移植史或卒中史；研究对象正接受类固醇类药物治疗或正接受帕金森病治疗。结局为首发或复发的非椎骨骨折或髋骨骨折。
Two-year follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, for second-line (2L) treatment of non-small cell lung cancer (NSCLC).
Authors: Byoung Chul Cho, Tae Min Kim, David Vicente, Enriqueta Felip, Dae Ho Lee, Ki Hyeong Lee, Chia-Chi Lin, Maria José Flor, Massimo A. Di Nicola, Rosa Maria Alvarez, Isabelle Dussault, Christoph Helwig, Laureen S. Ojalvo, James L. Gulley, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2020)

9558 Background: Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Interim analysis of a global phase 1 study (NCT02517398) found an objective response rate (ORR) of 27.5% and a manageable safety profile in patients with NSCLC who received bintrafusp alfa 1200 mg in the 2L setting; median overall survival (OS) was not reached. Here we present the longest efficacy and safety follow-up in a cohort receiving bintrafusp alfa. Methods: Patients with advanced NSCLC unselected for PD-L1 expression level who progressed after first-line standard treatment (no prior immunotherapy) were randomized to receive bintrafusp alfa 500 or 1200 mg (n = 40 each) Q2W until disease progression, unacceptable toxicity or trial withdrawal. The primary objective was best overall response (BOR) per RECIST 1.1; secondary and exploratory objectives include safety and OS, respectively. Results: As of October 15, 2019, a total of 40 patients received bintrafusp alfa at the recommended phase 2 dose of 1200 mg Q2W for a median of 17 (range, 2-136) weeks, with a median follow-up of 128 weeks; 18 patients were still alive, 3 patients had an ongoing response, and 1 patient remained on treatment. Results for the 1200 mg dose cohort showed an ORR of 27.5%, and a median duration of response of 18 months. The 18- and 24-month progression-free survival and OS rates were 18.4% and 11.0%, and 49.7% and 39.7%, respectively. Duration of response rates at 18 and 24 months were 42.4% and 21.2%, respectively. Median OS in patients with positive (≥1%) PD-L1 expression was 21.7 months; 6 of 7 patients with high (≥80% with Ab clone 73-10, which is equivalent to ≥50% with 22C3) PD-L1 expression were still alive. The overall safety profile has remained consistent since the interim analysis, with no new safety signals or deaths and 1 additional treatment-related discontinuation (blood alkaline phosphatase increased). Conclusions: After two years of follow-up, bintrafusp alfa continues to show manageable safety with durable responses and encouraging long-term survival, especially in patients with high PD-L1 expression. A study evaluating bintrafusp alfa vs pembrolizumab as first-line treatment for NSCLC is ongoing in patients with high PD-L1 expression (NCT03631706). Clinical trial information: NCT02517398 .
Identification of SLX4 as the most frequently mutated gene in homologous recombination deficiency in Asian gastric cancer.
Authors: Shi Zhang, Tianhao Mu, Shiying Dang, Tanxiao Huang, Jingxian Duan, Shifu Chen, Guoqiang Wang
Journal: Journal of Clinical Oncology (2020)

4570 Background: Gastric cancer is the third most common malignancy worldwide. Homologous recombination (HR) is a type of genetic recombination, and homologous recombination deficiency (HRD) is highly involved in multiple types of cancers and can predict response to anticancer therapies. However, homologous recombination deficiency is not well characterized in patients with Asian gastric cancer. Methods: 196 Asian patients with gastric cancer were analyzed in this study. A list of 102 genes related to HRD was compiled based on previous literature. Haplox 605-gene panel was used to capture the sequencing library. Mutations related to HRD were analyzed following next-generation sequencing. In addition, tumor mutational burden (TMB) was calculated by dividing the total number of mutations by the size of the coding region. The correlation analysis between HRD and TMB was also conducted. Results: In total, 43 (21.94%) of 196 Asian patients with gastric cancer harbored at least one HRD gene. The top 10 mutant HRD genes included SLX4 (3.57%), ATR (2.04%), RECQL (1.53%), NBN (1.53%), ERCC4 (1.53%), BAP1 (1.53%), ATM (1.53%), RAD54L (1.02%), BRCA1 (1.02%) and PARP1 (1.02%). In addition, the occurrence of HRD mutations was significantly correlated with a higher TMB. The median TMB of HRD group (8.28 muts/Mb) was significantly higher than that of the Non-HRD group (3.07 muts/Mb) (p &lt; 0.01). The overall upper quantile value (4.80 muts/Mb) was used to screen patients with high TMB (TMB-H). The TMB-H in HRD group was significantly higher than the Non-HRD group (44.19% VS 17.92%, p &lt; 0.01). Conclusions: Our study described that SLX4 was the most frequently mutated HR-related gene in Asian gastric cancer. Moreover, the positive correlation with homologous recombination deficiency (HRD) and tumor mutational burden (TMB) was observed in these patients.
SAR-096: A phase II trial of ribociclib in combination with everolimus in advanced dedifferentiated liposarcoma (DDL), and leiomyosarcoma (LMS).
Authors: Sujana Movva, Margaret von Mehren, Elizabeth A. Handorf, Jeffrey A. Morgan, Michael Nathenson, Katherine Anne Thornton, Eric Daniel Tetzlaff, Emma Barker, Linda Thibodeau, Allisa Cherae Harley, April King, Rosanna Veggeberg, Juliet A. Leshner, Lori Rink, Suzanne George
Journal: Journal of Clinical Oncology (2020)

11544 Background: Inhibition of CDK4 is being studied in a variety of sarcomas, especially dedifferentiated liposarcoma (DDL) where prolonged progression free survival has been noted. Exposure to CDK4 inhibitors in Rb+ leiomyosarcoma (LMS) cell lines leads to decreased cell proliferation, and increased senescence, and G0/G1-phase arrest. When combined, ribociclib a CDK4 inhibitor and everolimus, an mTOR inhibitor show synergistic growth inhibition in multiple tumor models. Methods: Patients (pts) were enrolled to one of two cohorts: DDL or Rb+ LMS. LMS pts were required to have 1 prior line of therapy; DDL pts required no prior therapy. There were no limits to prior therapies in either group. Progression on prior therapy and measurable disease by RECIST 1.1 was also required. Ribociclib was given at 300 mg daily for 21/28 days and everolimus was given continuously at 2.5 mg daily in 28 day cycles. The primary endpoint was progression free rate at 16 weeks. A Simon two-stage design was utilized and if at least 8 out of 24 pts were progression free at 16 weeks, the treatment was declared promising for the cohort. Here in we present data on the LMS cohort. Results: Twenty-four LMS pts, 83% (n = 20) female, 58% (n = 14) uterine primary were treated. Median prior lines of therapy was 3.5 (range 1-9). Of 22 pts with complete data, 6 (27.2%) met the primary endpoint of non-progression at 16 weeks. Median PFS was 19.6 weeks (range 2.8-84), with progression as best response occurring in 13 pts. There were no objective responses. Five pts who had progressive disease on multiple lines of therapy experienced prolonged progression free survival (23-84 weeks). Grade 3-4, toxicities included neutropenia (29%), thrombocytopenia (12.5%) and leucopenia (12.5%) being most common. Tissue samples pre and on therapy as well as blood were collected in 21 and 18 pts respectively to evaluate pharmacodynamic changes. Conclusions: Final data on the primary endpoint for the LMS cohort is pending; it is notable that several heavily pre-treated LMS pts experienced prolonged progression free survival for &gt; 9 months. Updated results and biology correlatives will be presented. Clinical trial information: NCT03114527 .
Administration of immune checkpoint inhibitors using teleoncology model of care in Far North Queensland: A multicenter review of safety outcomes.
Authors: James Fletcher, Sebastian Kang, Amy Brown, Sabe S. Sabesan, Megan Lyle, Ritwik Pandey, Andrew Lui, Natalie Rainey, Barbara Kelly, Andrew Lachlan Schmidt, Abhishek Jagdish Joshi
Journal: Journal of Clinical Oncology (2020)

2084 Background: The Teleoncology model of care, as developed and implemented across health services in Far North Queensland (Australia), improves access to specialist oncology services, including telehealth supervised administration of Oncology drugs for patients in rural/remote towns. There is limited published data regarding the safety of checkpoint inhibitor immunotherapy when it is administered via Teleoncology. Aim: Evaluate safety of immunotherapy administration via Teleoncology, including immune-related adverse events (irAE), treatment delays, hospital admissions and interhospital transfers, in comparison to a retrospective control population. Methods: Retrospective review of all patients treated with immunotherapy via Teleoncology as part of Cairns and Hinterland Hospital and Health Service (CHHHS) and the Townsville Teleoncology Network (TTN) between January 2015 and April 2019. A retrospective cohort treated at Townsville Cancer Centre over the same time period was used as a control group. Results: Fifty-one patients received a total of 624 cycles of immunotherapy (all single agent anti-PD-1/L-1) via Teleoncology. The control population included 142 patients who received 1697 cycles of immunotherapy. Baseline characteristics were well matched between groups. Compared to the control population, patients treated via telehealth did not have statistically significant differences in the rate of Grade 3+ irAE (13.7% v 8%), hospital admissions (13.7% v 7.4%) or protocol suspensions due to immune toxicity (16% v 10%). One patient with Grade 3+ irAE required interhospital transfer for investigation and management, which occurred within 24 hours of presentation to hospital. There were no treatment-related mortalities in either group. Conclusions: Checkpoint inhibitor immunotherapy can safely be delivered using the Teleoncology model of care in rural and remote centres. The incidence of toxicity for single agent immunotherapy was predictably low and not significantly different between groups, however the numbers in this retrospective study were small. The time to recognition and management of immune mediated toxicity in rural and remote centres is an important factor that was not assessed in this study and will be considered in future work.
The outcome of vincristine, dactinomycin D, ifosfamide and doxorubicin (VAIA) as first-line therapy for adult-patients with metastatic ewing sarcoma; a single-center experience.
Authors: Jean Paul Atallah, Mahmoud Abdelsatar Elshenawy, Ahmed ali Badran, Maaz Kamal Alata, Ahmed Gad, Abdulrahaman H. Alharbi, Hisham N. Alquaydheb, Bader I Alshamsan
Journal: Journal of Clinical Oncology (2020)

e23501 Background: Ewing sarcoma family of tumors (ESFT) is a rare malignancy among adults. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy. We report our experience in the management of this disease among Arab ethnicity. The aim of this study is to assess the outcome of VAIA combination as a first-line treatment in Adult-patients with metastatic Ewing sarcoma. Methods: Patients who were newly diagnosed as metastatic Ewing sarcoma between 03/1997 and 11/2016 at King Faisal Specialist Hospital and Research Center, who received VAIA as first-line therapy were eligible. The patient's characteristics were summarized using Medians with interquartile ranges (IQR) and frequencies for continuous and categorical variables, respectively. Variables including age, sex, primary tumor size, site (skeletal vs extraskeletal) and extent of metastasis in correlation with progression and overall survival were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Thirty-nine patients were identified. Male (26, 66.7%), Female (13, 33.3%). Skeletal (27, 69.2%), Extraskeletal (12, 30.8%). The median longest diameter of the primary tumor 9.75 (IQR 8-15). The most common metastatic sites were Lungs (22, 56.4%) &amp; Bone (10, 25.6%), however, the least common sites were Bone Marrow (3, 7.7%) and liver (2, 5.1%). The median number of VAIA cycles was 10 cycles (IQR 5-14). Objective response rate (ORR) was noticed in 20 patients (51.2%) (Complete Remission (7, 17.9%), Partial Remission (13, 33.3%). One patient had stable disease and 12 (30.8%) patients had progressive disease. The assessment was not feasible in 3 (7.7%) patients. With a median follow up duration of 18 months (1-44).20 patients died (62.5%). The median PFS and OS was 10,18 months respectively with 3,5 years overall survival rate of;35.7%,26.9% respectively. Univariate analysis correlation among different variables were insignificant. Conclusions: VAIA chemotherapy combination showed poor outcomes among our patients in comparison to literature further improvement is needed in this aggressive malignancy in our region.
Real-world outcomes of immune-related adverse events in 2,125 patients managed with immunotherapy: A United Kingdom multicenter series.
Authors: Anna Claire Olsson-Brown, Mark Baxter, Caroline Dobeson, Laura Feeney, Rebecca Lee, Alec Maynard, Shagufta Mirza, Sohail Mughal, Shefali Parikh, Lisa Jane Rodgers, Abdulazeez Salawu, Rohan Shotton, Nadina Tinsley, Sizheng Steven Zhao, Christopher Jones
Journal: Journal of Clinical Oncology (2020)

7065 Background: Immune-related adverse events (irAE) are a recognised complication of immune checkpoint inhibitor (ICI) therapy. Previous characterisation of irAEs has been limited to clinical trial or registry populations and small case series. Here we present a multi-centre, granular, real-world analysis of the prevalence and outcomes of irAEs experienced by patients managed within a single comprehensive public health service. Methods: A multi-centre retrospective analysis of 2125 consecutive patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or combination therapy (CT). Data were collected using a standardised, pre-piloted, collection tool. IrAEs ≥ grade 2 or endocrinopathies of any grade were considered clinically significant and recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Descriptive statistics were employed using Stata v15 (College Station, TX). Results: Patients received αPD-1 (1757; 82%), combination αPD-1/αCTLA-4 (285, 13%), αCTLA-4 (51; 2%) and αPD-L1 (31; 1%) immunotherapy for malignant melanoma (961), non-small cell lung cancer (788) or renal cell carcinoma (335). The median age was 66 (MT) and 57 (CT). Clinically significant irAEs occurred in 732 (34%) individuals; 28% (524) on MT and 73% (208) on CT. Colitis (206,10%), thyroiditis (194, 9%), hepatitis (142, 7%) and dermatitis (126, 6%) were most commonly observed. Grade 1 endocrinopathies occurred in 20% (173) of cases. Grade 2 irAEs occurred in 43% (359), grade 3 31% (269) and grade 4 6% (51). The were 3 (0.4%) cases of grade 5 irAE; pneumonitis (2) and hepatitis, all following αPD-1 MT. 93% (680) required corticosteroids with 64% (490) requiring systemic corticosteroids and 11% (80) steroid sparing immunosuppression. 16% (336) of patients had pre-existing autoimmune disease of whom 40% (136) experienced irAEs. IrAEs led to admission in 42% (308) of cases, accounting for 2996 bed days. Length of stay was 7 days (1-67; IQR 4-13). Higher dependency care was required in 0.7% (15) of cases. Colitis (35%, 107) and hepatitis (25%, 77) accounted for the most admissions. Pneumonitis accounted for 3% (66) of irAEs but 12% of admissions. Conclusions: One third of patients experienced a clinically-significant irAE resulting in significant morbidity and admission burden highlighting the need for effective management strategies to optimise patient outcomes.
Application and evaluation of general practice assessment questionnaire Chinese version for patients' satisfaction in community health-care service
Authors: Sai Zhang, Ying Zhang, Lei Du, Juan Du, Ya-jing Hu, Kai-chen Gu, Xiao-qin Lu
Journal: BMJ (2011)

Objective To study application of Chinese general practice assessment questionnaire (GPAQ)consultation version 2.0 in evaluating patients' satisfaction with community health-care service (CHS).Methods First,origihal GPAQ consultation version 2.0 in English was translated into Chinese language by three experts in general practice/family medicine field,then translated it back into English,finally a Chinese version of GPAQ was formed.Ten medical doctors who were on duty on 25 April,2008 at each out-patient clinic from CHS of Daxing,Nancaiyuan,Yongning and Hancunhe were selected randomly as targets for evaluation of service satisfaction.A sample of the first 30 patients(1200 in total)aged more than 16 years who visited the clinic on that day were selected to fill out the Chinese GPAQ consultation version 2.0 to express their satisfaction with the medical doctors they visited,and reliability and validity of the questionnaire was then evaluated.Results Cronbach's alpha ranged 0.734 to 0.813 for each domain of the Chinese version of GPAQ2.0.and cumulated contribution of three common factors with the eigen-value more than one reached 58.722%.Scores of patients' satisfaction withreceptionists,access,continuity,doctor's communication skills andpatient enablement were significantly lower,as compared to those of national bench-mark in the United Kingdom,with t-values of -6.397,-11.729,-6.328,-59.871 and -2.210,and all P＜0.05.respectively.Conclusions The Chinese version of GPAO 2.0 achieves good reliability and modcrate validity,and can be used as an instrument for evaluating patient's satisfaction with quality of CHS in China as further revision in the future studies.

Key words: 
Community health services; Patient satisfaction; Reliability; Validity
X-ray examination vs CT scan in identifying simple lumbar vertebral wedge following trauma in the elderly
Authors: JamesGKennedy, 翟晓梅
Journal: BMJ (2004)

This retrospective study was to evaluate the sensitivity and specificity of X-ray and CT in diagnose of simple lumbar vertebral wedge.Thirty—two elderly patients with CT-confirmed simple lumbar vertebral wedge were analyzed retrospectively.Following X-ray examination,23 patients were found to have compression fracture,and 9 patients were diagnosed with simple lumbar vertebral wedge.Thus,CT scan may be more sensitive and specific than X-ray examination in the diagnosis of simple lumbar vertebral wedge after trauma in the elderly.

Key words: 
Spinal fracture;  Radiography
Breast cancer, cardiac events, and survival: Do outcomes differ in urban and rural populations? A retrospective analysis of a midwest population.
Authors: Nitin Tandan, Asad Cheema, Noupama Mirihagalle, Ruby Maini, Priyanka Parajuli, Manjari Rani Regmi, Odalys Estefania Lara Garcia, Cameron Koester, Sabree Abedrabo, Hamsa Sahib, Zurain Niaz, Abdisamad M. Ibrahim, Alexander Johnson, Bishal Bhandari, Kristin Delfino, Kathy Robinson, Meghna R. Desai, Abhishek Kulkarni
Journal: Journal of Clinical Oncology (2020)

e13620 Background: Breast cancer is the most common female malignancy diagnosed in the US. According to the CDC and WWAMI Rural Health Research Center, rural areas have a lower incidence of cancer than urban areas, yet have higher breast cancer related death rates (1,2). Adverse cardiac outcomes may contribute to decreased survival in rural populations. In this abstract, we discuss how environment impacts survival and cardiac outcomes in patients with breast cancer. Methods: An IRB-approved retrospective study was performed utilizing ICD codes to analyze patients diagnosed with biopsy-confirmed breast cancer between January 1, 2014 and December 31, 2017. 478 of 1618 de-identified patients qualified for this study. Statistical analysis was performed with SAS v9.4. Descriptive statistics were computed for all study variables. Continuous variables were described with measures of central tendency (mean, median) and dispersion (range, standard deviation). Categorical variables were summarized as frequencies and percentages. Comparisons between categorical variables were compared with the Chi-Square test (or Fisher’s Exact) where appropriate. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance is assumed at the p &lt; 0.05 level. Results: Of 478 eligible patients, the calculated HR was 0.323 with 95% CI between 0.074 and 1.397 (p = 0.130), suggesting greater likelihood of survival in the urban population as compared to the rural population. Cardiac events like heart failure and ACS resulted in Fisher’s Exact p-value of 1, suggesting no significant difference in cardiac outcomes between the two populations. While results were not statistically significant, the trend of decreased survival in the rural population is noteworthy. Conclusions: Per our study, urban populations may have higher propensity for survival as compared to rural populations. There was no statistically significant difference in cardiac events among the two different population. Socioeconomic factors may play a large role in improved survival outcomes in the urban population, which may include but are not limited to travel to/from appointments and cost of medical care. Further large-scale, prospective studies should be performed to confirm the aforementioned trends with respect to survival outcomes in urban and rural populations.