tbuckley/cabot-search huggingface dataset:
Effect of race and insurance status on stage at diagnosis and overall survival of triple-negative breast cancer (TNBC): Analysis of the National Cancer Data Base (NCDB).
Authors: Rafiullah Khan, Inas Abuali, Eric J. Vick, Luke Smart, Changchun Xie, Mahmoud Charif
Journal: Journal of Clinical Oncology (2020)

e19086 Background: TNBC is a heterogeneous sub-type of breast cancer characterized by younger age of onset, more aggressive course, and higher incidence among African Americans who also experience disparities in access to health care including health insurance coverage and cancer screening. Methods: We performed a retrospective analysis of the NCDB to study the impact of race and insurance status on the stage at diagnosis and overall survival of people with TNBC. Chi-square tests analysis was used for univariate analysis. Cox models were used to test for survival differences between race and insurance status adjusted for other covariates such as age at diagnosis, gender. Results: Among 1,148,016 people with TNBC registered in the NCDB from 2010 to 2016, 87.7% were identified as white and 12.3% were identified as black. The majority (99%) were female. Mean age at diagnosis was 62.0 years for females and 65.9 years for males. Among white patients, 1.8% were uninsured while 3.6% of black patients were uninsured. Advanced stage at diagnosis was less common among white people (9.4%, Stage 3; 4.9%, Stage 4) than black people (13.3%, Stage 3; 7.6%, Stage 4). Uninsured patients had more advanced disease at time of diagnosis (16.2%, Stage 3; 14.1%, Stage 4) than insured patients (9.8%, Stage 3; 5.0%, Stage 4). Overall survival after adjustment for age at diagnosis, gender and insurance status was greater for white patients compared to black patients (harm ratio 0.60). Overall survival after adjustment for age at diagnosis, gender and race was lower for uninsured patients than insured patients (harm ratio 2.25). Conclusions: Racial disparities significantly affect TNBC patients, with black women having lower insurance coverage and worse overall survival. [Table: see text]
A female case of ectopic mediastinal hyperparathyroidism
Authors: Yunming Zhang, Mingqiang Song, Jinqiao Zhao, Zhongqiao Li, Bing Han, Meng Tian, Cuilan Xu, Jin Ju, Guogang Gao, Liming Yu, Quanxu Ge
Journal: BMJ (2018)

报道1例前上纵隔异位甲状旁腺功能亢进患者临床资料。患者女性，58岁。以髋关节区域疼痛起病，血液检查证实有高钙、低磷和高甲状旁腺激素(PTH)血症，影像学检查证实头部、胸部和下肢多发骨质破坏，前上纵隔显示瘤性占位。手术证实为纵隔异位甲状旁腺腺瘤，手术切除后钙、磷代谢和PTH水平恢复正常，疾病痊愈。
Targeted therapy based on germline analysis of tumor-normal sequencing (MSK-IMPACT) in a pan-cancer population.
Authors: Zsofia Kinga Stadler, Anna Maio, Yelena Kemel, Margaret Sheehan, Erin E. Salo-Mullen, Karen Anne Cadoo, Maria Isabel Carlo, Alicia Latham, Michael Francis Walsh, Alexander E. Drilon, Michael F. Berger, David B. Solit, Ozge Birsoy, Diana Mandelker, Luis A. Diaz, Kenneth Offit, Mark E. Robson
Journal: Journal of Clinical Oncology (2020)

1500 Background: Tumor mutational profiling for identification of somatic alterations for targeted treatment is increasingly being performed in advanced cancer patients (pts). We sought to assess the clinical utility of germline mutation profiling for targeted therapeutic interventions in a pan-cancer patient population. Methods: All pts who had germline genetic testing through a prospective protocol via a next-generation sequencing panel (MSK-IMPACT) were identified (N=11,975) from 2015-5/2019. The medical record of pts with likely pathogenic/pathogenic germline (LP/P) alterations in genes with known therapeutic targets were reviewed to identify germline-targeted treatment either in a clinical or research setting. Results: We identified 2,043 (17.1%) pts who harbored LP/P variants in a cancer predisposition genes including 777 (6.5%) in genes with potentially targetable therapeutic implications: 416 BRCA1/2, 149 DNA mismatch repair genes (Lynch syndrome, LS), 122 ATM, 45 PALB2, 26 RAD51C/D, 7 RET, 4 TSC, 3 PTCH1, 2 ALK, 1 EGFR, 1 MET and 1 KIT. Of those with advanced disease (n=554), 45.3% received targeted therapeutic treatment (Table) including 50.9% BRCA1/2, 58.3% LS (67.4% of microsatellite-high LS cases), 41.7% PALB2, 36.8% RAD51C/D and 19.3% ATM carriers. Of patients receiving a poly (ADP-ribose) polymerase inhibitor (PARP-I) in the setting of a BRCA1/2 mutation, 55.1% had breast or ovarian cancer; however, 44.8% had other tumors, including pancreas, prostate, bile duct, gastric, wherein the drug was given in a research setting. Among PALB2 pts receiving PARP-Is, 53.3% (8/15) had breast or pancreas cancer; 46.7% had cancer of the prostate, ovary or unknown primary. Conclusions: In our pan-cancer analysis, 6.5% of pts harbored a targetable germline variant highlighting the importance of germline analysis in advanced cancer pts for selection of both FDA-approved treatments and clinical trial participation with germline-targeted therapeutics. [Table: see text]
Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): Results from a phase III, prospective, multicenter study (CONDOR).
Authors: Michael J. Morris, Peter R. Carroll, Lawrence Saperstein, Frederic Pouliot, David Josephson, Jeffrey Y.C. Wong, Austin R. Pantel, Steve Y. Cho, Kenneth Gage, Morand Piert, Andrei Iagaru, Janet H. Pollard, Vivien Wong, Jessica Donato Jensen, Nancy Stambler, Michael A. Gorin, Barry Siegel
Journal: Journal of Clinical Oncology (2020)

5501 Background: Current imaging modalities are inadequate for localizing and characterizing occult disease in men with BCR PCa, particularly in pts with low PSAs (&lt;2 ng/mL). There is a need for improved diagnostic imaging to better inform treatment planning. 18 F-DCFPyL (PyL) is a novel PET imaging agent that binds selectively with high affinity to PSMA, which is overexpressed in PCa cells. Methods: Men ≥18 years- with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy) were enrolled. A single 9 mCi (333 MBq) ± 20% dose of PyL was injected, followed by PET/CT 1-2 hours later. Primary endpoint was correct localization rate (CLR), defined as percentage of pts with a 1:1 correspondence between at least one lesion identified by PyL-PET/CT and the composite standard of truth: pathology, correlative imaging, or PSA response. The trial was successful if the lower bound of the 95% confidence interval (LLCI) for CLR exceeded 20% for two of three independent, blinded central PyL-PET/CT reviewers. The secondary endpoint, impact of PyL-PET/CT on clinical management of pts was based on the treating physician’s documented clinical plans before and after PyL-PET/CT. Results: 208 men (median PSA 0.8 [0.2 - 98.4] ng/mL) underwent PyL PET/CT. The study achieved its primary endpoint: CLR of 84.8% to 87.0% among the three PyL-PET/CT readers; the LLCI for CLR by all three reviewers was &gt;77%. Here we report the clinical impact. Based on local radiology assessment, PSMA-avid lesion(s) were identified in 69.3% (142/208) of pts. 63.9% (131/205) had a change in intended management after PyL-PET/CT, of which 78.6% (103/131) were attributable to positive PyL finding(s) and 21.4% (28/131) to negative PyL scans. Changes included: salvage local therapy to systemic therapy (n=58); observation before initiating therapy (n=49); noncurative systemic therapy to salvage local therapy (n=43); and planned treatment to observation (n=9). PyL was well tolerated with one drug-related SAE (hypersensitivity) and the most common AE being headache (n=4; 1.9%). Conclusions: PSMA-targeted PyL-PET/CT detected and localized occult disease in most men with BCR presenting with negative or equivocal conventional imaging. PyL-PET/CT led to changed management plans in the majority of pts, thus providing evidence that clinicians find PSMA PET imaging useful in men with recurrent or suspected metastatic PCa. Clinical trial information: NCT03739684 .
A survey on hypertension knowledge mastering among in-service training general practitioners
Authors: Haiqing Wang, Zhihong Zheng, Chunyan Zhao, Xiuhua Wang, Lige Liu
Journal: BMJ (2014)

A survey was conducted on a sample of 67 general practitioners(GPs)receiving in-service training in Beijing in 2012. Hypertension knowledge mastering and training status were investigated through a self-administered questionnaire. Results showed that the accuracy rates of the 4 domainitems (basic knowledge and skill, lifestyle modification, drug therapy, health management) were 42.3%(340/804), 48.0%(225/469), 27.8%(96/335) and 70.6%(473/670), respectively with an overall accuracy rate of 49.8%(1 134/2 278). Trainees from urban scored higher than those from rural areas (P<0.01). About one third of trainees indicated that the 3 main teaching sessions they took part in did not cover the content of hypertension management. The hypertension guideline (primary care version 2009) was most frequently used for training GPs, but only 33.9%(21/62) accessed such training. The results indicate that hypertension knowledge level seems to be generally low among GPs on in-service training in Beijing and the current training situation need to be further improved, particularly for those from rural areas.


Key words: 
General practitioners; Inservice training; Hypertension
Perceptions of research training in a hematology/oncology fellowship program.
Authors: Stephanie L Pritzl, Laura M Lang, Joshua Michael Lang, Sam Joseph Lubner, Amanda Marie Parkes
Journal: Journal of Clinical Oncology (2020)

11030 Background: Current research training in Hematology/Oncology (Heme/Onc) fellowship is typically limited to mentoring relationships, which are highly variable due to the absence of standardized training for mentors and different perceptions of successful mentor-mentee relationships. Formal research productivity assessment is challenging and lacking in our current educational framework. Methods: Electronic surveys were developed to assess research training during fellowship at the University of Wisconsin (UW). Surveys were sent to current Heme/Onc fellows (n = 9), members of fellowship leadership (n = 4), and core research faculty (n = 5) with prior successful mentorship to trainees. Results: Surveys were completed by 6 fellows, 3 fellowship leadership, and 5 core research faculty. Both faculty and trainees recognized the research mentor-mentee relationship to be critical, with 5/6 (83%) fellows and 3/5 (60%) core research faculty identifying research mentors as the most meaningful training source. However, despite 5/6 (83%) fellows having a research mentor identified, there were large variations in the perceived level of proficiency in core research topics. While 3 fellows felt only slightly prepared in basics of clinical trial design, 1 fellow felt very prepared and 2 felt somewhat prepared. Furthermore, 2 fellows each felt very prepared, somewhat prepared, or not at all prepared in assembling grant components. There was also variable confidence reported by core research faculty in the ability of trainees to obtain funding and conduct independent research after fellowship, with 1 extremely confident, 2 somewhat confident, and 2 only a little confident. All individuals surveyed recognized manuscript publication, abstract presentation, and grant acquisition as important measures of research productivity. Beyond that, however, only 1/5 (20%) core research faculty and 0/3 (0%) fellowship leadership noted using rubrics for critical review of trainee academic progress despite 3/6 (50%) fellows believing that such rubrics were being used for their evaluation. Conclusions: The divergent experiences identified among research mentors and mentees and the lack of clearly defined metrics of research productivity highlights the need for a more standardized educational framework and formative evaluation tools. These identified needs have led to a pilot program at UW that intends to create a professional learning community for research mentors, define competencies for research training, and design a research training portfolio and accompanying assessment rubric.
Photoselective vaporization of prostate for the treatment of very elderly patients with benign prostatic hyperplasia
Authors: Wan-feng Zhang, Hong-jie Wang, Gui-ping Wang, Jia-lin Qu, Xiao-hui Ding, Hui-en Liu
Journal: BMJ (2009)

A total of 156 elderly patients (aged ≥ 70 years) with symptomatic bladder outlet obstruction as a result of benign prostatic hyperplasia (BPH) underwent trmsurethral photoselective vaporization (PVP). Pre- or post-operative urine flow rate, residual urine volume level, International Prostate Symptom Score (IPSS), and quality of life (QOL) score were recorded. Our data showed that maximum urine flow rate and residual urine volume were improved at 1, 12, 24, and 36 months following the treatment. There was statistically significant difference in IPSS and QOL when the intervention was considered (P < 0. 05). PVP might be a treatment of choice for high-risk elderly patients with obstructive BPH.

Key words: 
Prostatic hyperplasia;  laser surgery
Cardiovascular Disease and Androgen Axis–Targeted Drugs for Prostate Cancer
Authors: Celestia S. Higano
Journal: New England Journal of Medicine (2020)

Cardiovascular disease is the leading cause of death in men in the United States and in the developed world. Men with prostate cancer have a higher incidence of cardiovascular disease than those without, and among men with prostate cancer, cardiovascular disease is the principal non–cancer-related cause of death.1,2 The relationship of androgen-deprivation therapy (ADT) to fatal cardiovascular events is uncertain because of conflicting evidence; nonetheless, the general consensus is that men with preexisting cardiovascular disease are at increased risk for cardiovascular toxic effects when treated with ADT.3 The phase 3 HERO trial now reported in the Journal shows that relugolix, . . .
Studies on the efficacy of pyrotinib in the treatment of HER-2 positive advanced solid tumors.
Authors: Shaoshuang Fan, Da Jiang, Yalei Lv, Yanzhi Cui, Yan Kong, Qian Dong, Fang Huang, Xue Zhang, Long Wang, Xinliang Zhou, Hui Jin, Ying Li, Ran Hou
Journal: Journal of Clinical Oncology (2020)

e15639 Background: To explore the efficacy and safety of pyrotinib in the treatment of HER-2 positive advanced solid tumors patients. Methods: Patients with HER-2 positive advanced solid tumors in oncology department of our hospital from October 2018 to Janurary 2020 were collected. All the patients were given oral pyrotinib 400mg once a day in a 28-day cycle. The clinicopathological characteristics, treatment history, and curative effect were collected, and the adverse reactions related to the treatment were recorded. Results: 13 patients with HER-2 positive advanced solid tumors were enrolled, including 11 patients with metastatic breast cancer, 3 patients with metastatic colon cancer, 3 patients with gastric cancer. Among them, 10 patients were evaluated for efficacy and(or) side effect, of which 3 patients were excluded because they were not taken pyrotinib according to the medical order or they had no complete follow up data. The total mPFS was 5.63 months (95%CI: 2.533-5.467), partial remission (PR) were 3 cases(30%), stead diease(SD) were 6 cases(60%), progress diease was 1 case(10%). The overall response rate (ORR) and the disease control rate (DCR) were 23.1%, 69.2%, respectively. 2 patients received first-line treatment and 11 patients received second-or-further-line treatment. 11 cases of trastuzumab were changed to anti-HER-2 after treatment failure, of which 2 cases were treated with pirotinib after trastuzumab and lapatinib failed treatment. 12 cases with HER-2 overexpression and 1 case with HER-2 amplification. The incidence of pyrotinib side effects was 100%, which occurred in the first cycle of treatment and was common in grade 1 and 2. The common symptoms were diarrhea (100%), hand and foot skin reaction (38%), rash (8%), etc. Grade 3 to 4 adverse events occurred in 1 patient (8%) received pyrotinib plus capecitabine. 1 patient reduced pyrotinib dosage because of diarrhea. Nevertheless, diarrhea did not lead to discontinuation. Conclusions: The treatment of HER-2 positive advanced solid tumors with pyrotinib have good exact affect, and the toxicity could be controlled.
Laboratory cross-comparison of tumor BRCA1/2 analysis in a multicenter epithelial ovarian cancer series: The BORNEO GEICO60-0 study.
Authors: Ignacio Romero, Ana Oaknin, Zaida Garcia-Casado, Raul Marquez, Alfonso Yubero Esteban, Alejandro Gallego, Ana Beatriz Sanchez, Cristina Perez Segura, Jesus Alarcon, Maria Pilar Barretina-Ginesta, Isabel Palacio Vázquez, Lorena Farinas-Madrid, Juan Fernando Cueva, Judit Matito, Andres Poveda, Jose Antonio Lopez Guerrero, Ana Vivancos
Journal: Journal of Clinical Oncology (2020)

6055 Background: Epithelial ovarian cancer (EOC) identification of BRCA1 and BRCA2 mutations is usually carried out in germline, representing around 17% in high grade serous ovarian cancer (HGSOC) and further 5-7% are only identified in the tumor (somatic). The aim of this study was to identify in EOC tumor BRCA mutation frequency and inter-laboratory reproducibility using different Next-generation Sequencing (NGS) approaches. Methods: In an ambispective study design, a population of unselected consecutive non mucinous EOC was clinically annotated and Formalin-Fixed Paraffin-Embedded (FFPE) tumor BRCA1/2 mutation analysis was undertaken in two laboratories (Lab-1 and Lab-2) simultaneously. Both laboratories used their own validated NGS panels; variant allele frequency threshold was 5% for single nucleotide polymorphism and 10% for indels. Each laboratory classified variants into three categories based on ACMG criteria: non-mutated (class 1-2), Variants of Uncertain Significance (VUS: class 3) and likely pathogenic/pathogenic (class 4-5). Germline BRCA analysis was available according to local clinical practice or centralized in Lab-1 if histology was low grade. Results: Ninety FFPE samples were received, 8 had insufficient material to be analyzed in both laboratories and 6 cases were discarded due to tumor cellularity below 20% leaving 76 cases to be sequenced. The population had a median age of 58 (25-84) years, 87% (66/76) of HGSOC histology and 70% of advanced stages (III-IVB: 53) and 14.5% (11) germline BRCA mutations (3 with not available results). Lab-1 identified 17 class 4-5 mutations, 11 correspond to germline, 4 (5.3%) are just somatic and 2 have germline results not available yet. Lab-2 had one not valuable analysis and identified 16 class 4-5 mutations, 10 corresponding to germline and 4 somatic variants. Percentage of concordance between both laboratories was 96% (kappa coefficient 0.883; p value &lt; 0.0001). Three discordant out of 18 class 4-5 mutations included 2 undetected (VAF of 14.9% and 60.3% respectively) and one class 4 in Lab-2 classified as VUS in Lab-1 due to different interpretation criteria. Conclusions: The global BRCA mutation frequency in our series was 22.3% for Lab-1 and 21.0% for Lab-2. Concordance between tumor BRCA mutation analysis was high (96%). Nevertheless, further effort is required on harmonizing the technical and analytical aspects in tumor mutational analysis.
Real-word incidence and management of durable complete response in de novo metastatic HER2-positive breast cancer.
Authors: Claire Elizabeth Powers Smith, Paul Kelly Marcom, Zahi Ibrahim Mitri
Journal: Journal of Clinical Oncology (2020)

e13017 Background: HER2-directed therapies enable a small number of patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long term durable responses (DR). However, clinic-pathologic factors that correlate with DRs in de novo HER2+ MBC are unknown. Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice, especially the effect on cardiotoxicity, are lacking in the literature. Methods: This is a retrospective case control study of patients with de novo HER2+ MBC who received treatment with trastuzumab at two NCI designated cancer centers between the years 2012-2017. Patients were included if ≥2 years of follow up data were available or if patients were deceased. DRs are defined as radiographic complete or partial response without progression or death at any point after diagnosis. Controls are patients with evidence of radiographic progression or death any point after diagnosis. Age at diagnosis, ER/PR status, site of metastasis, and initial treatment were analyzed. An un-paired T test for age and fisher exact test for categorical variables were used. Results: A total of 96 patients with de novo HER2+ MBC, 28 with DRs and 68 with progression, were identified. Average follow up length for patients with DR was 90 months (range 27-224 months). Patients who progressed had a mPFS of 17.5 months and a mOS of 60 months. Results are shown in Table. Additionally, six patients (6.3%) developed reduced ejection fraction, one with DR, five with progression. Nine patients have been receiving trastuzumab for over ten years with no evidence of disease. Only one patient opted to discontinue this therapy a year after complete response and is disease free five years from diagnosis. Conclusions: Nearly a third of patients with de novo metastatic HER2+ MBC in our dataset achieved DR. Factors that predict DRs include single organ involved by metastatic disease and more intensive upfront chemotherapy including trastuzumab and pertuzumab. The majority of patients with DR continued HER2 directed therapy indefinitely with minimal cardiotoxicity. In the absence of predictive biomarkers of DRs, indefinite trastuzumab administration is common practice for these patients. [Table: see text]
Changes in prostate symptoms and quality of life in patients with symptomatic benign prostate hyperplasia before and after transurethral resection of the prostate
Authors: Hui-zhong Tian, Zhi-jin Wu, Xiao-dong Zhang, Yong Yang
Journal: BMJ (2010)

Objective To investigate changes in symptoms and quality of life (QOL) score before and after transurethral resection of the prostate ( TURP), and their related factors. Methods Forty-seven elderly male patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms were enrolled in the study, with an average age of 72 years. They all were undergone with TURP and evaluated with international prostate symptoms score (IPSS), QOL score, maximal urine flow rate (Qmax), residual urine volume, pressure-urine flow rate and prostate size before and after the procedure. Changes in these parameters and their related factors were analyzed. Results No complication was observed during TURP in the 47 patients. After TURP, two patients suffered from distal urethra stricture, one from retrograde ejaculation and six from aggravated urgent incontinence, and symptoms relieved with symptomatic treatment in all of them. Significant difference in overall IPSS, irritant score and obstructive score pre- and post-operation was observed P ＜ 0.01, i. e. , 22.7 ±4.9 and 10.5 ± 5.8, 10.5 ± 5.8 and 6.3 ± 3.5, and 12.1± 3.9 and 4.2 ± 3.3, respectively. QOL score was 4.6 ± 0.9 and 2.3 ± 1.3, Qmax (5.8 ± 2.9 ) ml/s and (12.4 ±5.2) ml/s and residual urine volume (99 ± 16) ml and (34 ± 19) ml pre- and post-operation,respectively ( all P ＜ 0.01 ). Follow-up time after the procedure, prostate volume and bladder volume at urgent urination desire all correlated with post-operation IPSS ( r = 0.751, P ＜ 0.05 ), and follow-up time after the procedure and age also significant correlated with post-operation QOL score (r = 0.470, P ＜ 0.05 ).Conclusions Overall IPSS, irritant score, obstructive score and QOL score improved significantly after TURP in symptomatic BPH patients, probably by varied related factors.

Key words: 
Lower urinary tract symptoms;  Transurethral resection of prostate;  Quality of life