tbuckley/cabot-search huggingface dataset:
Association between bone involvement on PET/CT and event free survival (EFS) in follicular lymphoma (FL) grade 3b.
Authors: Frederique St-Pierre, Stephen M Broski, Betsy LaPlant, Kay Ristow, William R. Macon, Thomas Matthew Habermann, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2020)

e20068 Background: FL grade 3B (FL3B) is an aggressive subtype of FL with a distinct morphologic, cytogenetic and immunohistochemical profile that is associated with higher mortality compared to other subtypes of FL. FL3B is a rare disease, and data regarding its prognostication beyond grading is lacking. Recent data suggests that spleen and extranodal (EN) involvement on PET/CT predict early clinical failure in FL grades 1-3A[1]. We aimed to determine the incidence of spleen and EN involvement on PET/CT in FL3B, and whether these can predict EFS. Methods: Patients with untreated FL3B diagnosed between 2003-2016, with available pre-treatment PET/CT, were identified using the Mayo Clinic Lymphoma Database and the University of Iowa/Mayo Clinic Lymphoma SPORE database. 27 patients were included in this analysis. All but two patients received treatment with immunochemotherapy. Associations with outcomes were assessed using EFS, defined as disease progression, relapse, transformation, or death. Results: 11/27 (40.7%) of patients had EN involvement on PET/CT. The most common EN site was bone, in 8/27 (29.5%) of patients. Soft tissue involvement was present in 4/27 (14.8%) of patients. Liver, brain, and endometrial involvement were each noted once. 11/27 (40.7%) of patients had spleen involvement on PET/CT. Presence of bone involvement as detected on PET/CT was associated with lower EFS (p = 0.02). EN involvement was associated with a trend toward a lower EFS but statistical significance was not reached likely secondary to low numbers in this cohort. Results in the table are compared to results obtained from our analysis in patients with FL grade 1-3A[1]. Conclusions: Bone involvement on pre-treatment PET/CT in FL3B was associated with early clinical failure in this small cohort of 27 patients. EN involvement at diagnosis may also be associated with poorer outcomes. These findings are similar to our analysis of a large (n = 613) cohort of patients with FL grade 1-3A. These findings may aid in the prognostication of patients with newly diagnosed FL3B, to guide therapy in select higher risk patients. [Table: see text]
Establishing analytical and clinical similarity between HD201 and herceptin.
Authors: Jocelyn Hii, Xavier Pivot, Kristi Mclendon, Kuo Wei Chan, Peggy Feyaerts, Jeong-Hyeon Lee, Felicia Ang, Martin Demarchi, Pierre Coliat, Filip Deforce, Marie_Paule Derde, Michael J Kim, Lisa Soyeon Park
Journal: Journal of Clinical Oncology (2020)

579 Background: Trastuzumab, an approved prescription drug by EMA and FDA under the name Herceptin has become the key treatment in patients with HER2 − positive breast cancer. HD201, developed by Prestige Biopharma Pte Ltd is a biosimilar candidate to Herceptin. The biosimilarity of HD201 was established based on systematic stepwise comparisons between HD201 and reference product, Herceptin. In order to confirm clinical similarity of HD201 to Trastuzumab, two clinical studies were undertaken. Methods: First, in a double-blind, randomised and parallel group study, 101 randomised healthy human subjects were subjected to a single 6 mg/kg IV dose by body weight over 90-min infusion of either HD201, EU- and US-Herceptin group by assessing pharmacokinetic (PK) and safety (TROIKA-I). The second study was a randomised, double-blind, parallel group, equivalence, multicentre clinical phase III trial (TROIKA) designed to compare the efficacy based on total pathological complete response rate (tpCR), safety, and pharmacokinetics of HD201 to EU-Herceptin in patients with HER2 positive early breast cancer. Each group of ~250 subjects were administered with either HD201 or EU-Herceptin in combination with chemotherapy in neoadjuvant followed by the antibody alone in the adjuvant phase. Results: TROIKA-I study demonstrated that HD201 was safe and well tolerated with comparable PK as EU- and US-Herceptin. Based on the neoadjuvant data from TROIKA study, the tpCR rate in the HD201 and Herceptin treatment groups was comparable and the 95% CI was included within the pre-defined margins of equivalence (Table). The incidence and severity of reported TEAEs did not imply any significant safety concerns and were comparable between both groups. In addition, the comparison of steady-state C trough between both arms in TROIKA study has established equivalence. Conclusions: The overall comparison exercise demonstrated the equivalence of HD201 to Herceptin. Clinical trial information: 2016-0040019-11 . [Table: see text]
Differences in real-world (RW) non-small cell lung cancer (NSCLC) treatment patterns among people living with HIV/AIDS (PLWHA) compared to those without HIV/AIDS (PWoHA).
Authors: Andrew J. Klink, Angelica Falkenstein, Ajeet Gajra
Journal: Journal of Clinical Oncology (2020)

7070 Background: NSCLC is the most common non-AIDS-defining cancer in PLWHA with an estimated prevalence 2-5 times that of PWoHA. Guidelines now support treatment of NSCLC among PLWHA to follow those for PWoHA. However, PLWHA have been often excluded from cancer clinical trials that test novel agents including immunotherapy (IO). This study aimed to assess differences in systemic therapy patterns for advanced NSCLC among PLWHA and PWoHA in the RW. Methods: Adult patients with ≥2 claims for NSCLC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics and comparisons by HIV status made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 60,278 NSCLC PWoHA who received systemic therapy. Of 1,344 PLWHA with NSCLC, 239 (18%) received systemic therapy. PLWHA differed significantly from PWoHA: median age at diagnosis (58 v 68 years), male preponderance (66% v 47%), payer mix (Medicare 26% v 42%; Medicaid 21% v 7%), Charlson Comorbidity Score (median 6 v 1), depression (13% v 5%) and liver disease (8% v 2%), respectively (all P&lt; 0.01). Differences in common systemic therapies among PLWHA v PWoHA include use of first line (1L) carboplatin + paclitaxel (28% v 19%; P&lt; 0.01), 1L erlotinib (6% v 11%, P= 0.02) and 2L gemcitabine (10% v 4%, P&lt; 0.01). IOs were used in 1L among 43 (18%) and 7,149 (12%) of PLWHA v PWoHA, respectively ( P&lt; 0.01). RW surrogates for PFS: median duration of 1L therapy was shorter among PLWHA (1.8 v 2.3 months, P&lt; 0.01); median times from 1L initiation to 2L were similar (5.4 v 4.9 months; P= 0.48). Similar proportion of patients continued onto 2L (32% and 30%) and 3L (10% and 9%) among PLWHA and PWoHA, respectively (all P&gt; 0.05). Total time from diagnosis to last follow-up (RW surrogate for overall survival) was 12.8 v 15.5 months in PLWHA and PWoHA ( P= 0 .07). Conclusions: PLWHA are younger at diagnosis of NSCLC and have higher comorbidity. Important differences in regimen selection and IO utilization exist across PLWHA and PWoHA. PLWHA have shorter 1L than PWoHA. Given higher risk and younger age at diagnosis, additional research is needed to establish screening and treatment guidelines for NSCLC in PLWHA.
Liquid biopsy of lung cancer by deep learning and spectroscopic analysis of circulating exosomes.
Authors: Hyunku Shin, Seunghyun Oh, Soonwoo Hong, Minsung Kang, Daehyeon Kang, Yong-gu Ji, Byeong Hyeon Choi, Ka Won Kang, Hyesun Jeong, Yong Park, Sunghoi Hong, Hyun Koo Kim, Yeonho Choi
Journal: Journal of Clinical Oncology (2020)

e15532 Background: Lung cancer has a high mortality rate because of belated diagnosis at advanced stages beyond the treatable condition. Early detection of lung cancer can improve the survival rate. A liquid biopsy that detects tumor-related biomarkers in body fluids has a great potential for the purpose. Particularly, tumor-derived exosomes in blood have been proposed as a promising biomarker. The tumor-derived exosomes carry molecules of their parental cells; thus, they provide information about the tumor in the body. Unfortunately, exosomal markers conducive to the early detection of lung cancer are still obscure. Therefore, using the molecular fingerprint of exosomes markers can be useful to detect the tumor exosomes. Raman spectroscopy is one of the representative methods for the purpose. However, because the exosomes have a heterogeneous composition in blood, interpreting their spectroscopic signals is hard. Thus, we utilized a deep learning approach to analyze the spectroscopic signal of the exosomes for liquid biopsy of lung cancer. Methods: The basic concept was to evaluate how much the exosomes in human plasma resemble cancer cell exosomes. As a proof of concept, exosomes of 43 non-small cell lung cancer (NSCLC) adenocarcinoma patients and 20 healthy controls were isolated from plasma of peripheral blood. Also, cell exosomes were isolated from culture media of adenocarcinoma cell lines and a human pulmonary alveolar epithelial cell line. Then, the spectroscopic signals were detected using surface-enhanced Raman spectroscopy (SERS). Further, the deep learning algorithm was employed to classify the signals. Then, we calculated the relative similarity to cancerous exosomes against human plasma exosomes. Results: Our method was able to classify cancer and normal cell exosomes with 95% accuracy. Also, Raman signals of cancer patients’ exosomes were more similar to the cancer cell exosomes than those of healthy controls. Notably, the similarity was proportional to cancer stages. Importantly, our method even detected stage I patients. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was 0.912 for stage I and II, and 0.910 for stage I. Conclusions: We reported a novel diagnostic method using deep learning analysis against spectroscopic signals of circulating exosomes. Our method that evaluates the similarity to cancer exosomes accurately identified lung cancer patients, even stage I with high accuracy.
Analysis of 27 cases one stage repair of penile hypospadias with urethroplasty improved transverse cutting island prepuce flap
Authors: Zun-jin Ke, Xin-xi Ding
Journal: BMJ (2008)

Twety seven children with penile hypospadias were treated using urethroplasty with transverse cutting island prepuce flap with local vascular pedicle from the dorsal penile rampant skin,and stabed hole at nonvascular region in middle of pedicle,reversed tubed flap through the penis to the ventral,anastomosed with the primary distal urethral.All cases were repaired successfully one stage,two cases with urethral fistula and one case with extemal orifice stricture of urethra.The appearance of the penis were satisfactory.It is suggested that one stage repair of penile hypospadias with urethroplasty improved transverse cutting island prepuce flap(Duckett's technique),the area of tubed flap sutured cling venial tunica albuginea penis,and bilateral is covered with vascular pedicle,greatly reduces the occurrence of urethral fistula.

Key words: 
Hypospadias;  Urologic surgical procedures,male
救治阿维菌素中毒一例
Authors: 李敬
Journal: BMJ (2009)

患者男,39岁,2009年2月1日14:00在家自服阿维菌素乳油剂约80 ml,约半小时后被家人发现急送当地医院.患者诉头晕、胸闷、气促、四肢乏力,无恶心、呕吐、惊厥,给予清水洗胃、输液及对症处理后转往我院,途中患者呼吸困难、意识模糊、周身青紫.立即行人工气囊辅助通气,经口咽通气管插管,吸痰等处理。
社区开展卫生科普教育的尝试
Authors: 马凤云, 常春
Journal: BMJ (2006)

中华医学会受国家科技部、卫生部委托,曾于2000年9月至2002年4月在北京市海淀区中关村地区开展全民卫生科普活动社区试点项目.参加的单位有:中华医学会,海淀区政府,区政府办公室,区街道工作办公室,区科委,区卫生局,区民政局,中关村街道办事处,中关村医院,各居民委员会等。
Changes of bone metabolic biochemical markers and bone mineral density in patients of Graves disease with different courses
Authors: Martin, Keuchel, Friedrich, Hagenmuller, 彭浩
Journal: BMJ (2009)

A total of 144 patients with Graves disease were divided into 3 groups according to their disease courses(≤1 year, 1 year 5 years). The bone metabolic biochemical markers and bone mineral density (BMD) of 144 patients with Graves disease and 26 normal controls were observed. Compared with control group, serum levels of calcium, phosphate, alkaline phosphatase and urinary levels of phosphate and magnesium in Graves disease patients were significantly increased(P<0.01 or P<0.05), but serum levels of magnesium and 25(OH)D3,1, 25(OH)2D3 were significantly decreased(P<0.01 or P<0.05). BMD of all sites in patients were significantly lower than that of normal controls(P<0.01 or P<0.05).


Key words: 
Bone mineral density; Biochemical marker
Application of problem-based learning in internal medicine teaching for residency training of general medicine
Authors: Yan Wang, Zhi-hong Pan
Journal: BMJ (2010)

To evaluate the effect of problem-based learning (PBL) in internal medicine teaching for residency training of general medicine.Fifty two residents of general medicine were divided randomly into PBL teaching and traditional teaching groups with 26 in each.The evaluation was conducted in combination of examination scores and questionnaire survey in both groups.In questionnaire survey the residents of PBL group responded positively about the use of PBL in teaching, and rated themselves as having much better competencies in problem solving and self-directed learning.The scores of case analysis examination in PBL group were higher than those in traditional teaching group ( 73.7 ± 4.1 vs.71.1 ± 4.8, P ＜ 0.05 ).The results suggest that the application of PBL has better effect than traditional teaching in residency training of general medicine.

Key words: 
Problem-based learning;  Education,medical,continuing
如何分析糖尿病患者的胰岛素释放试验结果
Authors: 傅汉菁
Journal: BMJ (2008)

对糖尿病患者测定血浆胰岛素及进行释放试验,对糖尿病的分型、判断胰岛β细胞功能及指导降糖药物的应用具有重要的意义.下面就如何阅读、评价糖尿病患者胰岛紊释放试验的化验结果,做一简要介绍。
Interpretation of the consensus statement on tremors classification by the task force on tremor of the International Parkinson and Movement Disorder Society (2017)
Authors: Yun Fan
Journal: BMJ (2018)

继1998年国际运动障碍协会(MDS)发表了关于震颤分类的共识声明后，2017年6月MDS对此共识声明进行了首次更新。新共识中首先明确了震颤的定义，其次采用统一的分类方法对错综复杂的震颤及震颤综合征进行了系统分类。本文主要就新共识中以上两部分内容进行解读，希望对读者增进对震颤的认识与理解有所帮助。
Clinical impact of hemizygous deletion detection and panel-size in comprehensive genomic profiling.
Authors: Kenta Takahashi, Yasuyuki Gen, Kousuke Tanimoto, Atsushi Kudo, Noriko Oshima, Daisuke Ban, Akira Takemoto, Iichiro Onishi, Yuichi Kumaki, Junko Yokobori, Eriko Takamine, Yoshihito Kano, Satoshi Miyake, Naoyuki Miyasaka, Minoru Tanabe, Johji Inazawa, Sadakatsu Ikeda
Journal: Journal of Clinical Oncology (2020)

e15671 Background: Comprehensive genomic profiling (CGP) identified single nucleotide variants (SNVs), copy number alteration (CNA), indels, and rearrangements in cancer-related genes. Only limited CGP detects hemizygous deletion. Also panel size differs among CGPs. Clinical impact of hemizygous deletion and panel-size are not well characterized. Methods: Formalin-fixed paraffin-embedded tissues from 10 cancer patients were analyzed by two CGPs: 1) test A (ACT Onc+) that interrogates SNVs, indels, rearrangement, and CNA including amplification, hemizygous and homozygous deletions in 440 genes, 2) test B that interrogates SNV, indels, rearrangement and CNA including amplification and homozygous deletion in 114 genes, but hemizygous deletion only in limited genes. Result was discussed in molecular tumor board and actionable genes and candidate drug were determined. Primary objective was the number of actionable genomic alterations. Secondary objectives are the number of candidate drugs, SNVs, CAN, and rearrangement. When there was difference of results in two tests, other validation test, such as PCR-based copy number evaluation, was performed. The difference of two tests was statistically evaluated using student t-test. Results: Median age of patients was 56 (range 48 – 70), and 50% were male. Tumor types were neuroendocrine tumor (60%), ovarian cancer (30%) and pancreatic cancer (10%). In 10 patients, actionable genes were found as follows: 39 in test A and 9 in test B (P = 0.0056). Total 64 genomic alterations were found in test A compared 12 in test B. SNV was not statistically different among two tests (10 in test A, 6 in test B; P = 0.269). However, the number of CNA was different: 54 in test A and 6 in test B (P = 0.007). Among CNA, hemizygous alteration explained majority of the difference (30 in test A and 1 in test B, P = 0.059), followed by amplification (24 in test A and 5 in test B, P = 0.201). The number of drug candidates was 38 in test A and 11 in test B (P = 0.014). Conclusions: Detection of hemizygous deletion and larger panel size resulted in more actionable genes and drug candidates, which might impact clinical practice. Future study of clinical utility of hemizygous deletion and panel size is warranted.
Identification of pathogenic <i>ROS1</i> alterations in cell-free DNA (cfDNA) from patients with breast cancer.
Authors: Jeremy Meyer Force, Mary Love Taylor, Leylah Drusbosky, Jennifer Yen, Paul Kelly Marcom, Carey K. Anders, Jeffrey R Marks
Journal: Journal of Clinical Oncology (2020)

1031 Background: ROS1 is an important proto-oncogene involved in the development of various cancers for which we have FDA approved therapies. While activation of the ROS1 tyrosine kinase receptor has been reported in 1-2% of lung cancers, the frequency and type of ROS1 alterations in breast cancer have not been fully explored. We previously described the incidence of ROS1 alterations from breast cancer tissue. The purpose of this study was to identify the incidence of ROS1 genomic alterations occurring in cfDNA from patients with breast cancer. Methods: We queried 16,053 breast cancer samples from the Guardant Health breast cancer database between June 2015 - October 2019 to identify the incidence of ROS1 alterations detected in cfDNA in breast cancer. We identified fusion partner genes and classified each alteration type into the following categories: fusion, single nucleotide variants (SNVs), and indels. Radical amino acid changes occurring at conserved regions across the ROS1 gene were identified. In vitro analyses were used to investigate the effect of ROS1 nonsynonymous mutations on the ROS1 protein. We made associations with ROS1 alterations and co-occurring mutated genes. Results: Nonsynonymous ROS1 alterations from the Guardant Health breast cancer database were found in 162 samples from 142 patients in the 16,053-patient cohort (1%). Alterations found included: 1 (0.6%) ROS1-SLC35F1 fusion, 155 (95.7%) SNVs, and 6 (3.7%) indels. Of the 155 SNVs, we identified 23 (14.8%) mutations occurring in the ROS1 kinase, of which, 20 (12.9%) occurred at highly conserved regions and 15 (9.6%) harbored radical amino acid changes. The top 5 co-occurring mutations in samples with ROS1 alterations were TP53 (50%), PIK3CA (44%), ESR1 (27%), EGFR (21%), and FGFR1 (18%). Conclusions: A modest incidence of ROS1 genomic alterations occurs in cfDNA from patients with breast cancer. New somatic alterations in the ROS1 gene were identified from Guardant Health that were not detected in publicly available databases. A portion of mutations occurred at highly conserved regions across the ROS1 gene suggesting these may be more actionable than currently recognized. In vitro analyses of ROS1 gene activation from these newly discovered somatic alterations are being investigated with results to be reported. Co-occurring mutations reveal a unique genotype associated with ROS1 alterations that may play a biologic role in ROS1-mediated pathogenesis.
Recurrence patterns following curative therapy for stage I NSCLC.
Authors: Emily Butts, Denise Gococo-Benore, Tanmayi Pai, Ruqin Chen, Rami Manochakian, Yanyan Lou
Journal: Journal of Clinical Oncology (2020)

e21069 Background: Lobectomy remains the standard of care for definitive management of stage I non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is considered primarily for patients who were either unwilling to have surgery or deemed to be medically unfit for surgery. Current NCCN guidelines indicate the use of CT for surveillance following curative-intent therapies and recommend CT every 6 months for 2-3 years followed by CT annually without clear guidance on how long to keep doing annual CT scans. This study aims to evaluate the patterns of lung cancer recurrence within and beyond five years post curative therapy. Methods: Patients diagnosed with stage I NSCLC and treated with either curative surgery or SBRT from 1998-2016 at Mayo Clinic Florida were identified. Through retrospective chart review, data was collected on clinical and demographic features, surveillance imaging, pathology, time to recurrence or new primary lung cancer, and location of recurrence (loco-regional vs. distant). Statistical analysis with chi-square test was performed to identify risk factors associated with recurrence. Results: In total, 203 patients with stage I NSCLC were identified with most patients treated with surgery (n = 181) compared with SBRT (n = 22). Median time of follow up is 85 months. Overall, 48 patients (23.6%) developed a recurrence, with the median time to recurrence of 22.3 (3.9-69.8) months. Most recurrences were identified within 5 years from curative therapy (42/48) with 6 patients having a recurrence between 5 and 10 years post curative therapy. Of the 37 patients followed for more than 10 years, there were no recurrences. Twenty seven patients had new primary lung cancers identified and among them, 15 were found within 5 years, 10 found between 5-10 years and 2 found beyond 10 years. Median time to new primary lung cancer was 58.1 months. A positive smoking history and stage IB were found significantly associated with lung cancer recurrence (chi-square test P = 0.007 and P = 0.04 respectively), while age, gender, histology, grade, and treatment type had no association. Conclusions: In this study of 203 patients with stage I NSCLC treated with curative intention, there was no evidence of recurrent disease after 10 years following curative therapy, questioning the utility of continued annual CT surveillance once patients hit this milestone.