tbuckley/cabot-search huggingface dataset:
TRANSFORMER: Bipolar androgen therapy (BAT) versus enzalutamide (E) for castration-resistant metastatic prostate cancer (mCRPC).
Authors: Samuel R. Denmeade, Hao Wang, Harry Cao, Wei Fu, Ting Wang, Rehab Abdallah, Vanessa Bolejack, Neeraj Agarwal, David C. Smith, Michael Thomas Schweizer, Mark N. Stein, Vasily J. Assikis, Thomas W. Flaig, Russell Zelig Szmulewitz, Jeffrey Holzbeierlein, Channing Judith Paller, Michael Anthony Carducci, Mark Christopher Markowski, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2020)

5517 Background: Rapid cycling between high and low testosterone (T) (i.e BAT) produces tumor response in mCRPC, and may overcome resistance to newer AR therapies. Here we report a randomized study comparing BAT to E in men with mCRPC progressing on abiraterone (A). Methods: In this phase 2 trial, men received either T cypionate 400mg IM (BAT) once every 28 days or daily oral E 160mg. Primary endpoint was clinical/radiographic PFS; crossover was permitted at progression. Secondary endpoints were OS, PSA progression to primary and crossover therapy, PSA and objective responses (OR), time to PSA progression from randomization through crossover (PFS2), quality of life (QoL), and AEs. Results: 195 men were randomized (94 to BAT, 101 to E). Results are presented in table. Although diametrically opposed therapies, median PFS and PSA response in the intent-to-treat (ITT) population was not significantly different between BAT and E. OR and OS favored BAT. For those who received BAT and then crossed over to E the PSA50 response was 77.8% and time to PSA progression was 10.9 mo compared to 25.3% and 3.8 mo for those receiving E immediately after A. The sequence of treatment had a significant effect on median PSF2 which was 28.2 mo for men receiving BAT→E vs. 19.6 m for E→BAT. For men who crossed over from BAT to E, OS was 37.3 mo vs. 28.6 months for those receiving E without crossover. AEs were primarily grade 1-2 in the BAT arm and included fatigue, generalized pain, and lower extremity edema. BAT improved QoL (fatigue, physical functioning, sexual function) vs. E. Conclusions: BAT could be safely administered to asymptomatic men with mCRPC. BAT produced a comparable PFS to E in A-refractory mCRPC pts. However, PSA50 and OR after crossover, as well as PFS2, were significantly improved in men who received BAT→E versus E→BAT. OS in men receiving BAT→E was 37.3 mo, exceeding historical expectations. These results support the hypothesis that treatment with BAT is safe, has efficacy and can restore sensitivity to antiandrogens. Clinical trial information: NCT02286921 . [Table: see text]
Clinical significance of preoperative measurement of serum human epididymis protein 4, CA125 and CA19-9 in endometrial cancer patients
Authors: Liuqing Ye, Jinwang Ding, Jiansong Zhou, Fan Fan, Yuan Jin
Journal: BMJ (2014)

Preoperative serum specimens were collected from 249 endometrial cancers and 99 uterine leiomyomas and their concentrations of human epididymis protein 4(HE4), CA125 and CA19-9 were detected. The indices of diagnostic evaluation were calculated. Preoperative serum concentrations of HE4, CA125 and CA19-9 in endometrial carcinoma group were significantly higher than those of control group. The areas under curve of HE4, CA125 and CA19-9 were 0.736, 0.615 and 0.661 respectively and that of combined markers was 0.774. At a 90% specificity, the sensitivities for HE4, CA125, CA19-9 were 55.0%, 26.9% and 30.1% while that of combined markers was 56.2%. HE4 is an ideal tumor marker for endometrial cancer and combined detection improves diagnostic rate.


Key words: 
Endometrial cancer; Tumor marker
Randomized, phase II trial to evaluate the efficacy and safety of atezolizumab plus capecitabine adjuvant therapy compared to capecitabine monotherapy for triple receptor-negative breast cancer (TNBC) with residual invasive cancer after neoadjuvant chemotherapy (MIRINAE trial, KCSG-BR18-21).
Authors: In Hae Park, Gun Min Kim, Jee Hyun Kim, Hanjo Kim, Kyong Hwa Park, Yeon Hee Park, Sun Kyung Baek, Sung Hoon Sim, Hee Kyung Ahn, Gyeong-Won Lee, Kyoung Eun Lee, Ji Eun Lee, Seungtaek Lim, Kyung Hae Jung, Seock-Ah Im
Journal: Journal of Clinical Oncology (2020)

TPS597 Background: Triple negative breast cancer (TNBC), lack of ER, PR and HER2 expression, is known to have aggressive clinical features such as early recurrence, drug resistance, and frequent distant metastasis at the diagnosis. The most effective chemotherapy combinations used for early TNBC include anthracycline, taxanes, and/or platinum agents. Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) provides important prognostic information and is considered as a surrogate endpoint in many clinical trials especially with TNBC. Patients with residual invasive disease after NAC have a high risk for early relapse and worse prognosis compared to those with pCR. Therefore, patients who did not get pCR could be better candidates for additional adjuvant treatment because their risk of recurrence would be higher than those with pCR. The CREATE-X (capecitabine for residual cancer as adjuvant therapy) trial howed that adjuvant capecitabine treatment improved 5-yr rate of disease free survival in TNBC subtype. A recent study indicated that immunosuppressive microenvironment had developed even in early stage of TNBC with increased T cells with a high exhaustion signature which are targets of immune modulating agents. Therefore, earlier cooperation of immune modulating drugs would be beneficial by generating a long-lasting anti-tumor immune response to micrometastatic disease, thus preventing disease relapse or recurrence. Methods: This study is a phase II, multicenter, randomized open label trial of atezolizumab (anti-PD-L1 antibody) and capecitabine compared with capecitabine in patients with TNBC who had residual disease after NAC. 284 patients will be enrolled from 15 sites in Korea with a primary objective to access the 5-yr invasive disease-free survival (IDFS) rate. Secondary objectives include 5-yr IDFS rate in PD-L1 positive population, distant relapse free survival (DRFS), overall survival (OS), and safety. Major inclusion and exclusion criteria are followings; 1) histologically confirmed TNBC, 2) received anthracycline and taxane based NAC followed by complete breast surgery, 3) residual disease after NAC must be ≥1cm in the greatest dimension, and/or have macroscopically positive lymph nodes. The study is open with 13 patients enrolled at the time of submission. Clinical trial information: NCT03756298 .
Patient and tumor characteristics as determinants of overall survival (OS) in <i>BRAF</i> V600 mutant (mt) metastatic colorectal cancer (mCRC) treated with doublet or triplet targeted therapy.
Authors: Javier Ros Montañá, Giulia Martini, Iosune Baraibar, Guillermo Villacampa, Raquel Comas, Davide Ciardiello, Ariadna Garcia, Xavier Hernandez Yague, Bernardo Queralt, Antonieta Salud Salvia, Guillem Argiles, Jose Luis Cuadra, Rodrigo A Toledo, Irene Chicote, Nuria Mulet, Ana Vivancos, Hector G. Palmer, Rodrigo Dienstmann, Josep Tabernero, Elena Elez
Journal: Journal of Clinical Oncology (2020)

4112 Background: BRAF V600 mt mCRC is an aggressive disease with poor OS under standard chemotherapy. Treatment with doublet and triplet targeted combinations, such as BRAF inhibitor+ antiEGFR+/- MEK inhibitor, has been shown to improve outcomes. Prognostic factors in this targeted treated population remain to be studied. Methods: Prospective international cohort of patients who received doublet or triplet anti-BRAF combinations in clinical trials or as compassionate use. Univariate Cox models for OS were constructed and the strongest predictors in stepwise variable selection were used to develop a prognostic score. The final multivariate model with selected predictors was stratified by prior lines. Results: In total, 42 patients were enrolled. Median age 60.7 y (33-83), 61% female, 61% right-sided tumors, 26% received 2 or more prior chemotherapy lines. One patient (2.6%) achieved complete response and 36% had partial response with median follow-up of 14.3 months. Median progression-free survival was 5.5 months (CI95% 4.4-10.4) and median OS (mOS) was 10.7 months (CI95% 8.4-22.1). In univariate models, ECOG performance status (1 vs 0), CEA levels (high - &gt; 3.5 ng/mL- vs low - &lt; 3.5 ng/mL), CA 19.9 (high vs. low), LDH (high vs. low), number of metastatic sites and presence of liver metastasis were significant prognostic factors. On the other hand, MSI status and peritoneal or nodal metastasis did not associate with outcome. In multivariable model, strongest determinants of OS were ECOG and baseline CEA levels. If high-risk for both factors (ECOG 1 and CEA high, 46% of the patients), mOS was 5.6 months (CI95% 4.2-NA); if intermediate-risk (either ECOG 1 or CEA high, 33%), mOS was 13.5 months (CI95% 10.6-NA); if low-risk (ECOG 0 and CEA low, 21%), mOS not reached (CI95% 16.5-NA). Differences between intermediate- and high-risk prognostic groups compared to low-risk were significant (HR = 5.9, p = 0.03; and HR = 25.9, p &lt; 0.001, respectively). Conclusions: Patients characteristics such as ECOG and surrogates of tumor burden like CEA levels remain important OS determinants in BRAF V600 mt mCRC treated with doublet or triplet targeted therapy. In fact, there are not prognostic scores regarding BRAF mt mCRC treated with targeted therapies. Our study suggests that these prognostic factors may be considered as stratification factors in future clinical trials.
Correlation of insulin levels in diabetic mothers and fetal insulin resistance
Authors: Rui-ping Huang, Fang Cao, Bin Yu, Zi-qiang Zhu, Ming Zhang, Bin Zhang, Ye Shi
Journal: BMJ (2013)

To explore the relationship between maternal insulin levels and fetal insulin resistance. Maternal blood and venous cord blood samples were collected in gestational diabetes mellitus (GDM) mothers and control subjects. The glucose and insulin levels were measured and insulin resistance levels estimated. Maternal levels of insulin and homeostasis model of assessment for insulin resistance index (HOMA-IR) were significantly higher in the GDM group than those in the control group (P<0.05); fetal levels of insulin and HOMA-IR were significantly higher in the GDM group than in the control group (P<0.05). Maternal insulin level positively correlated with fetal insulin (r=0.326, P<0.05) and HOMA-IR levels (r=0.378, P<0.05). In this study, a higher level of fetal insulin resistance was reported in the GDM group. And maternal hyperinsulinemia might affect fetal insulin resistance in pregnant women with GDM.


Key words: 
Diabetes mellitus, gestational; Insulin resistance
全科团队模式运动干预对社区2型糖尿病的防治效果
Authors: 费凯, 姜萍, 何妹萍, 付嫦娥, 屠亚平
Journal: BMJ (2012)

30例2型糖尿病患者佩戴电子计步器进行运动,并由全科团队实施“1+1+N”模式的运动干预,每个团队由1名全科医生、1名公共卫生医师和5例患者组成.12个月后,患者的血脂、血糖代谢紊乱改善,BMI降低,均与干预前差异有统计学意义(P＜0.05)。
尿路感染
Authors: 周仲华
Journal: BMJ (2005)

我有一个小病人,男孩,9个月,有一天忽然发高烧,体温达到了39.5℃,但精神状态还好,仍然爱玩,不咳嗽,没有流鼻涕等症状,吃奶和睡眠也都正常.除了我注意到他的小便有异常的臭味外,就没有其他的症状,查体也没有发现阳性体征。
Features of iso-miR expression in colon tumor tissue.
Authors: Natalya N. Timoshkina, Denis S. Kutilin, Inna A. Novikova, Sergey I. Poluektov, Roman E. Tolmakh, Andrey V. Dashkov, Dmitry Haragezov, Evgeniy N. Kolesnikov, Vladimir A. Dontsov, Dmitry S. Petrov, Natalya V. Soldatkina, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2020)

e13518 Background: With the advent of deep sequencing, enormous variability in miRNA biogenesis was detected, which means that many different sequences can potentially be generated from the same miRNA precursor, potentially having different targets and opposite changes in expression. These variable forms of micro-RNA that differ from the reference sequence are called iso-miR. To date, features of iso-miR expression have not been studied in patients with colorectal cancer (CRC). The aim of the study was to analyze the differential expression of iso-miR in the tumor and normal tissues of patients with CRC. Methods: For iso-miR identification by method of multiple parallel sequencing, 18 patients with CRC (colon adenocarcinoma, G2-3) were selected. The mirVana miRNA Isolation Kit protocol (Ambion, Life Science Technologies, USA) was used to isolate small RNA fractions. The library was prepared using the TruSeq Small RNASample Preparation Kit (Illumina, USA). Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The determination of iso-miR expression was carried out by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the iso-miR differential expression, the DESeq method implemented in R medium was used. Results: Several iso-miR classes were found (exact, lv3p, mv (multiple variant), nta#T#1 (non-templated T addition)). The most represented is the exact class (corresponding to the canonical miRBase sequence) and lv3pE (3 'extended: it starts from the same position as the canonical sequence, but is longer than the canonical sequence). Statistically significant (p &lt; 0.001) differences in the expression of tumor tissue relative to normal were found for hsa-miR-143 (exact), hsa-miR-26a (exact) and hsa-miR-27b (exact) - a decrease in expression in 3, 32 and 6 times respectively, for hsa-miR-10a (lv3p), hsa-miR-10b (lv3p), hsa-miR-10b (mv) - a decrease of 2 times, for hsa-miR-143 (lv3p) - an increase of 2 times, hsa-miR-143 (nta # T # 1) - a decrease of 5 times, for hsa-miR-192 (lv3p) and (nta # T # 1) - a decrease of 16 and 3 times, respectively. Conclusions: Differential expression of 4 iso-miR classes (exact, lv3p, mv, nta # T) hsa-miR-26a, hsa-miR-27b, hsa-miR-10a, hsa-miR-10b, hsa-miR-143 and hsa-miR-192 was found in patients with CRC, which probably can affect the transcriptional activity of the genes they target. These iso-miRs are also likely to act as potential tumor markers.
Current status of primary health care institutions and personnels in China: challenges and issues
Authors: Xiaoxiao Li, Chunyuan Wang, Lili Bian
Journal: BMJ (2020)

The current status of primary health institutions and personnels in China were analyzed based on the data from China Health and Family Planning Statistics Yearbook 2016 and China Health Statistics Summary 2018. By the end of 2017, there were 253 000 general practitioners in China, accounting for 7.46% of all practicing physicians or assistant physicians in the country(339 000). In 2017, the number of general practice residents was 8 517, accounting for 11.92% of all residents(71 430), which was 1.70% lower than that in 2016(8 664). The registered nurses in primary health care institutions were not sufficient, even the proportion of nursing to medical staff did not reach 1∶1 in primary settings. The distribution of primary health care institutions was not balanced. In the township hospitals and village clinics the number of practicing physicians or assistant physicians was far from meeting the requirement of the service. In view of the current problems, the social resources would be applied to promote the development of primary health care institutions and to improve the primary medical services in multiple ways such as personnel training, hardware construction, network construction and financial support, etc.


Key words: 
General practice; Primary health care institution; Social resources
Integration of the stem cell biology-based genomic tool, StemPrintER, with clinicopathological parameters for the prediction of distant recurrence in ER+/HER2- breast cancer (BC) patients.
Authors: Salvatore Pece, Patrick Maisonneuve, Davide Disalvatore, Stefano Freddi, Paolo Veronesi, Marco Colleoni, Giuseppe Viale, Pier Paolo Di Fiore
Journal: Journal of Clinical Oncology (2020)

1057 Background: The StemPrintER risk score (SPRS) is a 20 gene-based predictor that estimates the “degree of stemness” of the primary tumor and provides additional prognostic information regarding distant metastasis (DM) risk in early stage ER+/HER2- breast cancer (BC) patients beyond that obtained from standard clinicopathological parameters. Here we describe a further refined model, that combines prognostic information from SPRS with tumor size (pT) and nodal status (pN), termed SPARE (SPRS for Personalized Adjuvant therapy in Receptor-Expressing patients). SPARE was compared to the clinical treatment score (CTS) for 10-year risk of DM in a consecutive-retrospective ER+/HER2- BC patient cohort (n=1,827) with 15-year complete follow-up from the European Institute of Oncology (IEO) in Milan. Methods: The SPARE model was developed in patients randomly assigned to a training set (n=609), using the ridge-penalized Cox regression, and tested in an independent validation set (n=1,218). Likelihood χ 2 (LRχ 2 ) and Kaplan-Meier survival analysis were used to compare the prognostic information from SPARE and CTS (based on age, pN, pT, endocrine treatment). Comparative analyses were made for the DM risk over the 10-year follow-up, as well as in the early (0-5 years) or late (5-10 years) interval, according to nodal status. Results: SPARE outperformed CTS in providing prognostic information for 10-year DM risk (LRχ 2 : SPARE = 141.2, P&lt;0.0001; CTS=118.1, P&lt;0.0001), with even greater differences in node-negative patients (LRχ 2 : SPARE=47.6, P&lt;0.0001; CTS=27.5, P&lt;0.0001) and in 1-3 node-positive patients (LRχ 2 : SPARE=30.6, P&lt;0.0001; CTS=15.1, P&lt;0.0001). When reciprocally adjusted for each other, SPARE added prognostic information to CTS (ΔLRχ 2 : CTS+SPARE vs. CTS = 25.2; P&lt;0.0001), while CTS did not provide any statistically significant information to SPARE (SPARE+CTS vs. SPARE = 2.1, P=0.14). Using predefined cut-offs to stratify chemo-naïve patients clinically estimated at low recurrence risk, SPARE identified low, intermediate and high risk patients based on their annual rate of DM in the early (low, 0.2%, intermediate, 0.8%, high, 3.3%) and late (low, 0.3%, intermediate, 0.9%, high, 1.6%) interval. Conclusions: SPARE represents a more refined clinical tool, compared to standard clinicopathological parameters, that could be used for personalized therapeutic decision making in ER+/HER2- BC patients.
A non-interventional retrospective study to describe early clinical experience with cabozantinib in patients with advanced renal cell carcinoma (aRCC) in the United Kingdom.
Authors: Manon Pillai, Thomas Powles, Bernadett Szabados, Philip Savage, Kate Fife, Bhupinder Klair, Valérie Perrot, Agnieszka Michael, Balaji Venugopal
Journal: Journal of Clinical Oncology (2020)

e17089 Background: Cabozantinib is approved in the UK in treatment-naïve adults with intermediate or poor risk aRCC or following prior VEGF-targeted therapy. Here we describe treatment pathways and clinical outcomes of patients with aRCC who received cabozantinib early and later in the UK managed access program (MAP) as disease severity may differ in these patient populations. Methods: A non-interventional retrospective chart review study was carried out in six specialist centres in the UK to describe early clinical experience with cabozantinib in patients with aRCC (CERES, NCT03696407). Progression-free survival (PFS) and overall survival (OS) were calculated from cabozantinib initiation using the Kaplan-Meier method. Patients were grouped into those who initiated cabozantinib early (Aug 2016-Feb 2017) or late (Mar-Aug 2017) in the MAP. Results: Overall 100 patients were eligible; median (95%CI) PFS was 6.01 (5.16; 7.85) months and median OS was 10.84 (7.92; 16.85) months. Patients in the early MAP group received a mean (SD) of 2.2 (1.4) lines of prior therapy, most commonly sunitinib (n = 32, 56.1%) and pazopanib (n = 30, 52.6%). Patients in the late MAP group received a mean of 1.9 (SD 1.2) lines of prior therapy, most commonly pazopanib (n = 23, 53.5%) and sunitinib (n = 19, 44.2%). At least one post-cabozantinib therapy was prescribed in 44.6% (25/57) and 27.9% (12/43) of patients in the early and late groups, respectively, most commonly nivolumab (both groups). See table for characteristics and outcomes by MAP group. Conclusions: Cabozantinib was effective in this small, real-world study of patients receiving treatment as part of a MAP. The results are supportive of the data seen in the registrational study, METEOR. Patients enrolled early in the MAP were possibly more heavily pre-treated but overall outcomes were similar to those who enrolled later. [Table: see text]
Real-world treatment patterns and clinical outcomes of advanced melanoma patients following disease progression on anti-PD-1-based therapy.
Authors: Leonel Fernando Hernandez-Aya, Matthew Burke, Jenna M Collins, Dennis Earle, Melissa Hamilton, Beth L Nordstrom, Ying Zhang, Shivani Srivastava
Journal: Journal of Clinical Oncology (2020)

e22036 Background: Despite the success of anti-programmed cell death-1 (PD-1) based therapies that prolong survival in advanced melanoma, some patients experience disease progression. Real-world treatment patterns and outcomes after progression on anti-PD-1 based regimens are unknown. Methods: Adults with advanced melanoma and a record of disease progression on anti-PD-1 treatment (alone or in combination) between 1 Sept 2014–31 Jan 2019 were selected from the Flatiron Health Oncology electronic medical record (EMR) database for this retrospective study. Index progression date was defined as an event where the treating clinician concluded in the patient record that there had been disease progression. The first subsequent therapy received was identified. Kaplan-Meier methods estimated overall survival (OS) with 95% confidence interval (CI) after the progression date. Analyses were run separately for BRAF mutant (mt) and wild type (wt). Results: Among 2,169 patients with advanced melanoma treated with an anti-PD-1, 213 BRAFmt and 302 BRAFwt had a record of progression following anti-PD-1 initiation and were included; an additional 82 BRAFmt and 138 BRAFwt were excluded due to death without a record of progression. Median age was 64 and 71 years, respectively; 27.7% and 9.9% had &gt;1 line of therapy prior to the anti-PD-1. Among the BRAFmt patients who progressed on anti-PD-1, 94 (44.1%) received no subsequent therapy, 80 (37.6%) BRAF±MEK (± IO), and 16 (7.5%) anti-CTLA4 alone or with anti-PD-1 after progression on the initial anti-PD-1; 11% received other treatments with no clear pattern of care. Median (95% CI) OS from the index progression date for BRAFmt was 11.9 (8.2–16.9) months. In a subgroup of these BRAFmt patients with BRAF treatment prior to or during the first anti-PD-1 line (N = 65), 52.3% had no subsequent therapy and a median OS of 4.0 (2.7–7.5) months. Among the BRAFwt patients who progressed on anti-PD-1, 186 (61.6%) received no subsequent therapy, 46 (15.2%) received anti-CTLA4 alone or with anti-PD-1, 26 (8.6%) switched anti-PD-1s, and 15% received other treatments. Median (95% CI) OS for BRAFwt was 10.1 (8.8–12.5) months. Conclusions: In this real-world retrospective study, &gt; 40% of BRAFmt and &gt; 60% of BRAFwt patients did not initiate a new regimen after progression on anti-PD-1 therapy. Median OS after progression was &lt; 1 year. This may be overestimated, as it excluded patients who died before progression was recorded in the EMR. These findings highlight a need for more effective treatments for advanced melanoma.