tbuckley/cabot-search huggingface dataset:
Neoadjuvant endocrine therapy versus neoadjuvant chemotherapy in young women with breast cancer: Prognosis and axillary node surgery.
Authors: Sung-chan Gwark, Sei Hyun Ahn, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Gyungyub Gong, Sae Byul Lee, Jisun Kim, Il Yong Chung, Beom Seok Ko, jong Won Lee, Byung Ho Son, Seon-Ok Kim, Hee Jeong Kim
Journal: Journal of Clinical Oncology (2020)

e12626 Background: We aimed to evaluate patient-reported outcomes (PROs) in the NEST phase III trial, in which neoadjuvant endocrine therapy (NET) compared to conventional neoadjuvant chemotherapy (NCT) for hormone-responsive lymph node-positive premenopausal breast cancer. Methods: Premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients were enrolled. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with adriamycin plus cyclophosphamide (AC) followed by taxane (T) or neoadjuvant endocrine therapy with zoladex and tamoxifen. PROs were assessed at day 1 (baseline) and at the end of treatment, using the breast cancer module of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). ClinicalTrials.gov: NCT01622361. Results: 187 patients were randomly assigned to chemotherapy (n = 95) or endocrine therapy (n = 92), and 174 patients completed the 24 weeks of neoadjuvant treatment period (n = 87, both). Baseline scores were similar between arms. No statistically significant between-treatment differences were observed for the function scales including body image, sexual functioning, and sexual enjoyment although endocrine treatment showed significant improvement in future perspective (HR = 8.3, 95% CI:1.72-18.38; P= 0.021). Even though no alopecia was reported in NET group, no statistically significant difference between both arms in the “upset by hair loss” was observed, in which NET group showed even worse score. Conclusions: Patients who received NET had significant improvement in a future perspective, however, a similar emotional negative impact on hair loss was observed compared with NCT despite no reported alopecia. Key words: breast cancer, patient-reported outcomes, quality of life, hair loss, EORTC QLQ-BR 23. Clinical trial information: NCT01622361.
Prognostic and predictive factors for the outcomes of clear cell sarcoma (CCS) multidisciplinary treatment: The role of lymph node involvement.
Authors: Pawel Teterycz, Anna Malgorzata Czarnecka, Aleksandra Szmajdzinska, Magdalena Kalejta, Mateusz Spalek, Magdalena Rosinska, Jan Poleszczuk, Tomasz Switaj, Marcin Zdzienicki, Slawomir Falkowski, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2020)

e23554 Background: CCS is a rare aggressive sarcoma with melanocytic differentiation and specific genetic background of EWSR1/ATF1 or EWSR1/CREB1 translocations. It typically localizes in the tendons, fascia, and aponeuroses. The role of lymph node dissection (LND) remains to be elucidated in this sarcoma, although it was indicated to have a high rate of clinically occult regional lymph node (LN) metastases. Methods: 23 consecutive patients (pts) (15 women and 8 men) were referred, diagnosed and underwent multidisciplinary treatment in our Institute between 07/2000 and 12/2019. Kaplan-Meier estimator was used in survival analysis and univariate Cox proportional hazard model was used to investigate prognostic and predictive factors. Cases for whom local relapsed were not noted or those not known to be dead were censored at last visit. OS was compared for nodal involvement, including both: clinically detected and treated with therapeutic LND and microscopic metastases evaluated in sentinel LN biopsy (SLNB). Local relapse and radiotherapy were analyzed. Results: The median age at diagnosis was 32y (range:20-72). The median tumor size was 3.5cm (2-15cm). 15 pts underwent surgery of the primary tumor and 8 - resection of local relapse after non-complete resection outside the reference center. In 11 cases SNLB was performed, while in 7 – therapeutic LND. SLNB was positive in 2 (18%) cases and was followed by completion LND. For pts treated due to primary tumor, R0 resection was achieved in 12 cases and R1 in 3. After median follow-up of 65.6 months (m) (95% confidence interval, CI 55.3–NR) 11 (48%) pts are alive. Median OS was 59m (95%CI: 39-NR). Clinically detectable LN were correlated with shorter DFS (HR: 6.6, 95%CI: 1.5-28.8, p = 0.01). The number of involved LN also correlated with DFS (HR 1.7 per 1 LN; 95%CI:1.1-2.6, p = 0.009). No such correlations were found for OS. 5-year LRFS rate was 72.5% (95%CI: 53.8-97.7). 15 pts underwent neoadjuvant radiotherapy and for these pts 5-year LRFS rate was 75.0% (95%CI: 50.3-100). There was no statistical difference for LRFS if radiation therapy was not applied, which may be due to the number of pts. Conclusions: CCS is a highly aggressive sarcoma with poor prognosis. High quality surgery remains the gold standard for these pts, with the increasing role of SLNB and LND. Multimodal treatment should be considered in all cases. There is unmet need for new therapies for advanced CCS pts.
辛伐他汀致横纹肌溶解症一例
Authors: 陈章强, 洪浪, 王洪
Journal: BMJ (2008)

他汀类药物是细胞内胆固醇合成限速酶-羟-β-甲基戊二酰辅酶A(HMG-COA)还原酶抑制剂,具有降血脂、抗炎、抗动脉硬化等作用,在冠心病及动脉硬化性疾病的一、二级预防方面发挥重要的作用.随着这类药物的广泛应用,其安全性日益受到人们关注,尤其是不良反应横纹肌溶解症对生命造成严重威胁[1].现报道服用辛伐他汀(舒降之)致肌溶解症一例。
Temsirolimus combined with etoposide and cyclophosphamide for relapsed/refractory acute lymphoblastic leukemia: Therapeutic advances in Childhood Leukemia Consortium (TACL 2014-001) trial.
Authors: Susan R. Rheingold, Lewis B. Silverman, James A. Whitlock, Richard Sposto, Eric S. Schafer, Kirk R. Schultz, Raymond J. Hutchinson, Paul S. Gaynon, Caroline Bateman, Todd Michael Cooper, Theodore Willis Laetsch, Maria Luisa Sulis, Alan S. Wayne, Sarah K. Tasian
Journal: Journal of Clinical Oncology (2020)

10512 Background: PI3K/mTOR signaling, a critical pathway in cell proliferation, metabolism, and apoptosis, is often dysregulated in acute lymphoblastic leukemia (ALL). A phase 1 trial of the mTOR inhibitor temsirolimus combined with etoposide and cyclophosphamide was performed in children with relapsed/refractory (r/r) ALL. Methods: Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily days 1-5. The starting dose level (DL) of temsirolimus was 7.5 mg/m 2 (DL1) with escalation to 10 mg/m 2 (DL2), 15 mg/m 2 (DL3), and 25 mg/m 2 (DL4). MRD was performed centrally. PI3K pathway inhibition was measured by phosphoflow cytometry (PFC) analysis of peripheral blood (PB) from treated patients (pts). Results: Sixteen heavily pretreated r/r ALL pts ages 2-19 years with marrow blasts &gt; 25% were enrolled; 15 were evaluable [10 B-ALL/5 T-ALL]. One dose-limiting toxicity (DLT) of grade (Gr) 4 pleural and pericardial effusions with pneumonitis/lung infection leading to Gr 5 cardiorespiratory arrest occurred in a pt treated at DL3. No further DLTs were seen in the DL3 expansion and DL4 cohorts. Gr 3/4 non-hematologic toxicities occurring in ≥ 3 pts included febrile neutropenia, elevated ALT, hypokalemia, mucositis, and tumor lysis syndrome and were independent of dose. Of 15 evaluable pts, 4 (27%; 2 B-ALL/2 T-ALL) had a complete response (CR) after cycle 1, comprised of 1 pt at each DL. Three had MRD &lt; 0.01%. Three pts (20%; 2 B-ALL/1 T-ALL) had partial response (PR). Overall response rate (CR+PR = ORR) was 47%. Pharmacodynamic PFC studies compared phosphoprotein levels pre (day 0) and post treatment (days 3-5) in 9 consenting pts with available PB. All tested pts showed basal activation of PI3K pathway signaling. Dose-dependent inhibition of mTOR targets phosphorylated (p) S6 and/or p4EBP1 was observed in 9/9 and 6/9 pts, respectively, following temsirolimus and chemotherapy treatment. Various patterns of compensatory upregulation of pPI3K, pmTOR, pAkt, and/or pERK was observed. Conclusions: Temsirolimus at 25 mg/m 2 combined with salvage etoposide and cyclophosphamide has an acceptable safety profile in high-risk pediatric patients with r/r ALL. Responses were observed at all DLs. mTOR target inhibition was achieved and appeared to correlate with dose level. Future testing of other PI3K/mTOR pathway inhibitors in combination with chemotherapy may be warranted with a goal of further increasing response in r/r ALL. Clinical trial information: NCT01614197.
Effect of shorter time to treatment on survival in rural patients with breast cancer.
Authors: Suneel Deepak Kamath, Wei Wei, Katherine Tullio, Gregory S. Cooper, Alok A. Khorana
Journal: Journal of Clinical Oncology (2020)

7027 Background: Rural cancer care in the United States has unique challenges from variable access to care. This study examined differences in time to first treatment (TTT), a potential surrogate for access, and predictors of overall survival (OS) between rural and non-rural patients with breast cancer. Methods: Women with stage I-III breast cancer from 2004-2012 in the National Cancer Database of Commission on Cancer (CoC)-accredited facilities were included and categorized as rural and non-rural. Differences in demographic, disease and treatment characteristics, socioeconomic factors and TTT (&lt; 4 weeks, 4-8 weeks and &gt; 8 weeks) between rural and non-rural patients were assessed by Chi-square test. The effect of age, insurance status, cancer center type, community median income, community % no high school, and TTT on OS were assessed using univariate and multivariate Cox models. Results: The study included 1,205,031 patients, 18,417 (2%) of whom were rural. Compared to non-rural patients, rural patients were more likely to be age &gt; 65, Caucasian, receive care at non-academic centers, have government insurance, have lower income and less education (p &lt; 0.0001 for all). Significant demographic and socioeconomic differences are shown in Table. Rural patients had shorter mean TTT (3.72 vs. 4.35 weeks, p &lt; 0.0001). More rural patients had TTT &lt; 4 weeks (67% vs. 57%) and &lt; 8 weeks (94% vs. 90%), p &lt; 0.0001 for both. Shorter TTT (both &lt; 4 weeks vs. 8 weeks and 4-8 weeks vs. &gt; 8 weeks) was associated with improved OS (HR: 0.84, 95% CI: 0.82-0.86, p &lt; 0.0001 and HR: 0.82, 95% CI: 0.81-0.83, p &lt; 0.0001, respectively). After adjusting for demographic, socioeconomic, disease stage and treatment factors, rural status was associated with significantly better OS compared to non-rural status (HR: 0.92, 95% CI: 0.89-0.96, p &lt; 0.0001). Conclusions: Despite several adverse socioeconomic factors, rural patients with breast cancer with access to CoC-accredited facilities had significantly shorter TTT and better OS compared to non-rural patients. These data suggest improving TTT can mitigate disparities in rural cancer care. It is unclear whether our data apply to non-CoC-accredited facilities in rural United States. [Table: see text]
Disparities in utilization of palliative care during terminal hospitalizations in patients with metastatic cancer: A nationwide analysis.
Authors: Prasanth Lingamaneni, Krishna Rekha Moturi, Ishaan Vohra, Muhammad Zain Farooq, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

e19027 Background: Palliative care during the end of life is associated with greater patient satisfaction, improved quality of life and lower health care costs. Our aim was to study temporal trends of aggressive end of life care and palliative care during terminal hospitalizations in patients with metastatic cancer. We also studied disparities in palliative care in this population. Methods: Adult patients with metastatic cancer who died in the hospital from January 2012 to December 2017 were identified from the Nationwide Inpatient Sample database. Statistical tests for temporal trends of resource utilization were performed. Multivariable logistic regression was used to evaluate predictors of utilization of palliative care. Results: A total of 443,360 patients met the inclusion criteria. Mean age was 66.5 years. Patients were predominantly white (66.6%) with a slight male preponderance (51.9%). Most common primary cancers were lung (27.1%), GI tract (23.6%) and breast (7.6%). Use of chemotherapy and radiation decreased from 3.4% to 2.4% ( P &lt; 0.001) and 2.8% to 1.4% ( P &lt; 0.001), respectively, over the years. There was no statistically significant change in ICU care (26.6% to 27.2%, P= 0.61) or hospitalization costs ($22k to $23k, P =0.14). There was an increase in use of palliative care, from 45.7% to 61.2% ( P &lt; 0.001). Patients were more likely to receive palliative care if they were older, female or treated at teaching hospitals. Blacks and Hispanics were less likely receive palliative care. Compared to patients insured by Medicare, those with Medicaid and private insurance were more likely to be offered palliative care. ICU care and chemotherapy predicted decreased use of palliative services. Conclusions: There is an overall trend towards increased use of palliative services and decrease in chemotherapy and radiation in terminal admissions. There are racial disparities in the utilization of palliative care services, with previous studies attributing knowledge gap, with mistrust of the system in African Americans, and language barriers in Hispanics to be causes for racial disparities. There is a need to increase efforts towards development of palliative care programs in non-academic hospitals. [Table: see text]
氯沙坦钾氢氯噻嗪治疗高龄高血压患者的疗效及安全性分析
Authors: 田颖, 张文超, 陆锐
Journal: BMJ (2009)

研究报道[1],血管紧张素Ⅱ受体拮抗剂复方制剂具有协同降压作用,血压达标率高、不良反应小,但在高龄老年人中的应用报道不多,本研究目的是评价氯沙坦钾氢氯噻嗪(海捷亚)对高龄老年高血压患者的疗效及安全性。
左侧原发性巨输尿管合并右侧隐睾一例
Authors: 凌丰军
Journal: BMJ (2007)

患者男,14岁,左侧腰腹部间断性疼痛5年,加重半个月,于2005年12月24日入院.查体:左肾区叩击疼,右侧阴囊未触及睾丸,右侧腹股沟近内环口处可触及一3 cm×3 cm包块,质中、无压痛,可活动.左侧睾丸正常,阴茎发育良好.B超示:左侧肾、输尿管重度积水,右侧隐睾.静脉肾盂造影(IVU):左侧肾脏不显影,右侧正常.术前诊断:左侧输尿管梗阻,右侧隐睾.于2005年12月27日在硬膜外麻醉下行输尿管探查、睾丸固定术。
Bone turnover markers in primary and metastatic bone tumors.
Authors: Nailya K. Guskova, Larisa N. Vashchenko, Artem A. Barashev, Ekaterina V. Danilchenko, Anastasia S. Nozdricheva, Irina V. Tselishcheva, Aliya K. Donskaya, Olesya N. Selyutina, Svetlana V. Abakumova, Svetlana V. Belgova, Viktoria R. Zakharchenko, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e23513 Background: The purpose of the study was to reveal the levels of biochemical parameters for assessing the intensity of bone metabolism in patients with primary and metastatic bone tumors. Methods: The study included 29 patients aged 55.9±12.17 years with primary (group 1, n = 12) and metastatic (group 2, n = 17) bone tumors. Group 2 included patients with breast cancer (2a, n = 10) and renal cancer (2b, n = 7) with a history of pathological fractures. Serum levels of the bone turnover marker osteocalcin, TSH, the resorption marker β-Cross Laps (C-terminal telopeptide) (Cobas e411, Japan) and calcium (Vitros 5600, USA) were measured before and after (day 14) organ-preserving treatment. The data were compared with that in non-cancer patients of similar age (n = 15) and evaluated in the Statistika 10.0 program. Results: Osteocalcin levels in group 1 prior to surgery was 1.74 times (p &lt; 0.05) higher than in controls (13.56±1.35 ng/mL) and decreased by 35% (p &lt; 0.05) compared to the initial values. In group 2, changes in osteocalcin levels were multidirectional: group 2a – 24% (p &lt; 0.05) higher than in controls both before and after surgery; group 2b – similar to control values before surgery and decreased by 19% (p &lt; 0.05) after it. Levels of β-Cross Laps in all patients before surgery were within the control range (0.49±0.02 ng/mL). After surgery, the levels in groups 1 and 2a did not change, while group 2b showed an increase in β-Cross Laps by 1.5 times (p &lt; 0.05) and a decrease in calcium by 20% (p &lt; 0.05) from the initial levels (2.33±0.09 mmol/L), which, along with a decrease in osteocalcin, could be the result of specific kidney damage. TSH in groups 1 and 2b was similar to controls, but initial TSH levels in group 2a were increased by 86% (p &lt; 0.05) and did not change after surgery, as well as osteocalcin levels, which in the absence of changes in β-Cross Laps suggested a more favorable prognosis after organ-preserving treatment. Conclusions: Bone tissue remodeling processes are determined by the nature of the initial tumor. Measuring osteocalcin and β-Cross Laps in patients with specific bone lesions may be useful in assessing the risk of fractures.
Attributes of community medical service products and their development
Authors: Fulai Shen, Yuyang Cai, Jianping Wu, Tao Zhang, Huijiang Song, Kan Zhang
Journal: BMJ (2017)

As a new service form, community medical service provides primary health care for residents and it is operated with reasonable medical expenses. The function and service range of community medical service have reached consensus in medical industry, but the key issues of how to gain the market by competitive products and reasonable price have not been solved. This article analyzes the position of community medical service in healthcare system to clarify its unique attributes. The article further discusses the contents and pricing characteristics of community medical service, and the main influencing factors. The article introduces the issues dealing with community medical service product development, including the procedure of development, key points at different stages of development and the related research methods for the development of new service products.


Key words: 
Community health services; Medical services product
Simulation modeling of cost-savings from conversion of pegfilgrastim to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) and expanded access to biosimilar prophylaxis.
Authors: Ali McBride, Karen MacDonald, Ivo Abraham
Journal: Journal of Clinical Oncology (2020)

e19372 Background: Biosimilars have the potential to reduce the cost of prophylaxis of CIN/FN. To demonstrate this, we: 1) conducted a US comparative cost-efficiency analysis of CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim without or with on-body injector (PEG/PEG-OBI), 2) modeled budget-neutral expanded access to biosimilar pegfilgrastim-cbqv from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) estimated the number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of biosimilar pegfilgrastim-cbqv. Methods: Simulation modeling from the US payer perspective utilizing: average selling price (ASP) derived from CMS Q1 2020 reimbursement limits for PEG/PEG-OBI and pegfilgrastim-cbqv;between one and six cycles of prophylaxis in a panel of 20,000 cancer patients at risk for CIN/FN; and conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100% in this panel. Results: Using current ASP, cost-savings per patient of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI ranged from $223 (for 1 cycle) to $1,335 (6 cycles). In a panel of 20,000 cancer patients, the savings range from $445,163 (for one cycle of prophylaxis at 10% conversion) to $26,709,788 (6 cycles at 100% conversion). In a single cycle of chemotherapy, these savings translate into expanded access to prophylaxis with biosimilar pegfilgrastim-cbqv ranging from 115 doses at 10% conversion from PEG/PEG-OBI to 1,154 doses at 100% conversion. The savings over six cycles of chemotherapy could provide between 692 additional doses of biosimilar pegfilgrastim-cbqv prophylaxis (at 10% conversion) to 6,921 doses (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional dose of biosimilar pegfilgrastim-cbqv is 18. Conclusions: These models demonstrate that CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv can generate significant cost savings that could be reallocated on a budget-neutral basis to provide more patients and/or more cycles with CIN/FN prophylaxis.
Highly accurate automated tissue classification using deep learning on digital pathology images: A novel tool for resolving conflicts in diagnosis.
Authors: Stephen Charles Benz, Liudmila Beziaeva, Mustafa Jaber, Shahrooz Rabizadeh, Christopher Szeto
Journal: Journal of Clinical Oncology (2020)

3578 Background: Pathologist inspection of biopsy slides is the gold-standard for diagnosis and is crucial for effective therapy decisions. However, expert shortage is resulting in turnaround times exceeding College of American Pathologists’ (CAP) standards (Alshieban, 2015). Further, discrepancy between diagnoses can exceed 4% (Mukhopadhyay, 2018), and 2% of cases are designated as ‘carcinoma of unknown primary’ (CUP) negatively affect outcomes due to difficulty selecting therapies (Rassy, 2020). Here we sought to aid in diagnosing patients from whole-slide images (WSIs) using deep neural networks. Methods: &gt; 6.3K high-resolution H&amp;E-stained diagnostic WSI of formalin-fixed paraffin-embedded (FFPE) tumor block slices were selected from TCGA sources. Slide images were obtained from 30 different cancer subtypes including 368 Breast (5.6%), 324 Colon (5.12%), 287 Lung Adenocarcinoma (LUAD) (4.5%), Lung Squamous-Cell carcinoma (LUSC) (4.5%), and Stomach Adenocarcinoma (4.3%). Local regions containing tumor tissue were automatically identified by training an Inception V3 deep-learning network as previously presented. A separate Inception V3 network was trained to classify the primary tissue of 200mm 2 tumor regions in 60% of the images, which was validated in the remaining 40% testing cohort. Results: The proposed deep-learning model was 92.7% accurate in identifying the primary tissue within the test set of WSIs. As expected, most misclassification occurred in highly-related tissue-types: Rectal cancers misclassified as colon (25%) and vice versa (4.8%), uveal melanomas misclassified as cutaneous melanomas (18.6%), cholangiocarcinomas as hepatocellular carcinomas (8.6%), and LUSC misclassified as LUAD (6.0%) and vice versa (3.4%). Combining related tissues, the classifier achieves 94.6% accuracy across 24 primary types. Unexpectedly, cutaneous melanomas samples were misclassified as breast (9.1%) and LUSC (5.6%), suggestive of related molecular phenotypes. Conclusions: By focusing machine-vision attention on tumor regions, the automated system approaches pathologist accuracy. Used in conjunction with molecular profiling, rates of CUP or misdiagnosis can feasibly be minimized to improve patient care. This system is currently being validated in an external set of &gt; 4K unselected clinical cases from the NantHealth database.