tbuckley/cabot-search huggingface dataset:
Dose escalation and expansion from the phase I study of DS-1062, a trophoblast cell-surface antigen 2 (TROP2) antibody drug conjugate (ADC), in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Aaron Elliott Lisberg, Jacob Sands, Toshio Shimizu, Jonathan Greenberg, Penny Phillips, Ferdinand M. Guevara, Yutaka Noguchi, Tadashi Toki, Alexander I. Spira, Noboru Yamamoto, Melissa L. Johnson, Funda Meric-Bernstam, Kiyotaka Yoh, Edward B. Garon, Rebecca Suk Heist
Journal: Journal of Clinical Oncology (2020)

9619 Background: TROP2 is an intracellular calcium signaling transducer overexpressed in NSCLC, portending poor survival. DS-1062 is a TROP2-targeting ADC with a novel topoisomerase 1 inhibitor (exatecan derivative, DXd) and promising preclinical antitumor activity. Updated results inclusive of 24 additional dose escalation pts and 32 dose expansion pts from an ongoing phase 1 study of DS-1062 in advanced/metastatic NSCLC are reported (NCT03401385/J101). Methods: Pts aged ≥18 (US) or ≥20 (Japan) with unresectable NSCLC refractory to/relapsed from standard treatment with measurable disease (RECIST v1.1) and available tumor for retrospective TROP2 evaluation were eligible. Primary objectives include maximum tolerated dose (MTD) identification, safety, and tolerability and secondary objectives include efficacy, pharmacokinetics, and incidence of anti-drug antibodies against DS-1062. Pts were eligible regardless of TROP2 level. Results: As of November 16, 2019, 95 pts were treated with ≥1 dose of DS-1062. 63 pts were treated during escalation at 0.27 (n = 4), 0.5 (n = 5), 1.0 (n = 7), 2.0 (n = 6), 4.0 (n = 6), 6.0 (n = 19), 8.0 (n = 8), and 10.0 (n = 8) mg/kg and 32 pts were treated in expansion at the MTD of DS-1062, 8 mg/kg. 59 pts (62%) discontinued (25 [42%] due to progressive disease per RECIST v1.1). Pts were exposed to a median of 3 treatment cycles (range, 1-19). In 88 response-evaluable pts, 22 had partial response (1 PR/6 pts at 2.0 mg/kg, 2 PR/6 pts at 4.0 mg/kg, 5 PR/18 pts at 6.0 mg/kg, 13 PR/34 pts at 8.0 mg/kg, and 1 PR/8 pts at 10.0 mg/kg; 14 PRs were confirmed and 8 PRs are awaiting confirmation). Treatment emergent adverse events (TEAEs) regardless of causality were reported in 91 of 95 pts (96%; 44 pts [46%] experienced ≥grade 3, 30 pts [32%] had serious events). Treatment-related TEAES were reported in 76 of 95 pts (80%; 17 pts [18%] experienced ≥grade 3, 8 pts [8%]) had serious events). Potential interstitial lung disease (ILD) occurred in 8 pts (8%; 2 at 6.0 mg/kg and 6 at 8.0 mg/kg); 6/8 with potential ILDs adjudicated as treatment-related (1 at 6.0 mg/kg [grade 2] and 5 at 8.0 mg/kg [1 grade 1, 2 grade 2, 1 grade 3, and 1 grade 5]). 14 escalation pts and 22 expansion pts remain on trial. Updated trial details/results will be presented. Conclusions: In this first-in-human study of DS-1062, treatment was well tolerated up to 8 mg/kg, and a dose effect on antitumor activity was observed over 2.0-10.0 mg/kg in heavily pretreated pts with prior progression on standard treatment. Clinical trial information: NCT03401385 .
Geographic and demographic disparities in colorectal cancer: A population-based study.
Authors: Navpreet Kaur Rana, Rohit Gosain, Riccardo Lemini, Chong Wang, Steven J. Nurkin, Emmanuel M. Gabriel, Patrick M Boland
Journal: Journal of Clinical Oncology (2020)

e19047 Background: Colorectal cancer is one of the leading causes of cancer deaths in the US. Area of residence affects survival in many cancers, though largely unknown in colorectal cancer. The purpose of this study is to evaluate disparities between the metropolitan, urban and rural populations and the impact on survival in colorectal cancer. Methods: Data was obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal data sets. Patients (pts) were categorized by area of residence: metropolitan (MA), urban (UA), or rural (RA). Gender, race, insurance status, income, marital status, and tumor related data was collected. Univariate and multivariate analyses were performed to evaluate variables affecting overall survival (OS). Results: A total of 973,139 pts, spanning 2004-2013 were included in the study, 83% MA, 15% UA, 2% RA. RA and UA pts were more likely to be white than MA pts (92.7 v 91.4% v 83%). RA and UA were more likely to have lower income, with slightly lesser amounts of women and pts with no comorbidities. Uninsured rates were similar (3.3%). On univariate analysis, OS was worse for RA (HR 1.10) and UA (1.06) pts, as compared with MA. On multivariate analysis, small differences persisted with worse OS for RA (HR 1.02, p = .043) and UA (HR 1.01, p = .003). Black (HR 1.14) and native American (HR 1.17) pts had worse outcomes, while Asian (HR 0.8) pts had improved OS. Women (HR 0.88) and pts with higher incomes ( &gt; 46K or 63K) had improved OS (HR 0.88). Conclusions: This study identifies socio-demographic disparities in colorectal cancer outcomes. Pts from rural and urban areas had worse OS, even though the proportion of minority pts with poor outcomes was lower. The difference in OS for RA and UA remained statistically significant in multivariate analysis, though it was largely corrected when adjusting for influencing variables. Part of this difference may be due to economic disparities, as lower income was linked to worse OS. This can independently limit access to care, especially for geographically isolated individuals. Additional research efforts are needed in order for us to better understand the key issues facing and the optimal means to improve outcomes in at risk populations.
局部应用新癀糊剂辅助治疗牙周炎及其细菌学检查
Authors: 苑芃, 张博伟
Journal: BMJ (2004)

用常规洁治术加局部应用新癀糊剂治疗牙周炎,报告如下. 1.对象与方法:按文献[1]标准选择牙周炎患者50例70颗牙,男14例,女36例,23～54岁,排除全身其他疾病,3个月内未服用抗生素,6个月内未进行牙周治疗.将病情近似的同名患牙以中线为准分为左右两组,进行自身对照,右侧为实验组共35牙,左侧为对照组共35牙,观察疗效,记录结果.
急性碳酸钡中毒三例诊治体会
Authors: 于飞, 朱崇晖, 王清峰
Journal: BMJ (2008)

碳酸钡属不溶性钡盐,本无毒性,但口服进入人体后与胃液中的盐酸反应生成氯化钡,故有剧毒[1].临床上偶见误将碳酸钡作为发酵粉而致集体中毒的病例,我院于2007年1月12日收治3例,均已痊愈,现将诊治体会总结如下。
Survival outcomes of metaplastic breast carcinoma: An Indian tertiary care center data.
Authors: Lalnun Puii, Vinu Sarathy, Lalram Sangi, Beulah Elsa Thomas, Samuel Luke Koramati, Hrishi Varayathu, Suhail Sayeed Mufti, Smruthy Ann Mathew, Satheesh Chiradoni Thungappa, Radheshyam Naik, Basavalinga Sadasivaiah Ajaikumar
Journal: Journal of Clinical Oncology (2020)

e12579 Background: Metaplastic breast carcinoma is a rare histological subtype that has basal like characteristics and is reported to have a poorer prognosis than no specific type/ductal carcinoma (ductal/NST). We aimed to investigate clinicopathological features and outcome from a single institution based registry. Methods: Clinical records of breast cancer patients treated during 2012-2019 were screened and 31 cases of metaplastic breast carcinoma were found. Descriptive analysis was done for patients’ demographics and clinicopathological features. Kaplan Meier method was used to assess survival outcomes. Results: The incidence of metaplastic breast cancer was 0.5% (31/6180) in our study out of which the most common histopathological differentiation was squamous (45.16%). The second most common was sarcomatoid histology (32.25%), followed by chondroid (9.68%) and mixed histology (12.9%). The median age at diagnosis was 60 years ranging from 28 to 82 years. 64.15% of patients were post-menopausal. At presentation, three (9.67%) patients had metastatic disease while the rest were diagnosed with early (51.61%) and locally advanced cancers (38.72%). Triple negative cancers (ER/PR/Her2 negative) constituted the vast majority with 22 cases (80.6%) while hormone receptor positive (ER/PR positive, Her-2 negative) and Her-2 neu positive (ER/PR negative) made up the rest with three patients (9.67%) each group respectively. The median overall survival was found to be 39 months (95% CI 25.46 - 52.53). Conclusions: After a thorough search in PubMed and Google Scholar, we could not find a larger case series from India with clinical outcomes for metaplastic breast carcinoma. Our results suggest that metaplastic breast carcinoma is a heterogenous disease. Outcomes of metaplastic breast carcinoma are relatively worse when compared with literature for triple negative breast cancer and breast cancer in general. Further biological understanding may offer valuable insights for newer targets and therapeutic approaches to metaplastic breast cancer.
Risk of bleeding and significant thrombocytopenia in cancer patients treated with immune checkpoint inhibitors.
Authors: Tariq Zuheir Kewan, Ramsha Ahmed, Sura Alqaisi, Fahrettin Covut, Monica Flores, Arslan Babar, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2020)

e15000 Background: Immune checkpoints inhibitors (ICIs) are associated with multiple side effects. Complications can affect any organ system including; endocrine, gastrointestinal, pulmonary, and less frequently hematological system.We evaluated the risk of bleeding and significant thrombocytopenia in cancer patients (pts) treated with ICIs. Methods: Cancer pts treated with ICIs between 01/2015 and 7/2019 at Cleveland Clinic Foundation were retrospectively reviewed. Platelets (plts) count and hemoglobin (hb) level at baseline, after one month and 3 months of treatment were reviewed. Thrombocytopenia was defined as plts count &lt; 150,000. In pts with thrombocytopenia at baseline, more than 50% drop in the plts count was considered significant. Pts were followed-up for one year after ICIs treatment initiation for significant bleeding. Results: We identified 555 cancer pts treated with ICIs. Of these pts 65% were males. Among all included pts, 53% had lung cancer, 23% had genitourinary cancers, 17% had melanoma, 3% had gastrointestinal cancers, and 5% had other cancer types. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab were used in 62%, 27%, 14%, and 12% respectively. Clinically significant bleeding, thrombocytopenia after one month and 3 months of treatment were identified in 21%, 6%, and 7% respectively. Of all pts who developed bleeding, 8% had gastrointestinal bleeding, 5% had intracerebral hemorrhage, and 3 % had hemoptysis. Only 23% of the pts who developed bleeding were receiving anticoagulation therapy. In multivariate analysis, breast cancer as primary malignancy (p = .03) and atezolizumab (p = 0.02) were predictors of clinically significant bleeding. Also, nivolumab was associated with increased risk of significant thrombocytopenia after one month of treatment (p = .02). There was no significant association between the use of specific medication and the development of significant anemia. Median overall survival time was not statistically different in patients who had bleeding compared to no bleeding group, 12.6 months (95% CI:10.8-14.5) and 12.4 months (95% CI:10.3-15) respectively (p = .21). Conclusions: In this cohort study, atezolizumab and breast cancer were significantly associated with increased risk of bleeding. The use of nivolumab was associated with a greater risk of thrombocytopenia after one month of treatment. Prospective studies are needed for better understanding of the hematological side effects of ICIs.
Patient-initiated approach to prevent oxaliplatin induced peripheral neuropathy: A social media experiment.
Authors: Dana Cardinas, Manju George, Amber Norton, Renee Gentzel
Journal: Journal of Clinical Oncology (2020)

e16140 Background: Oxaliplatin continues to be the standard of care in the adjuvant and palliative setting in colorectal cancer (CRC). Although effective in CRC treatment, it is associated with a high risk of chemotherapy induced peripheral neuropathy (CIPN), which can debilitate the patient, prevent completion of care, and deteriorate their quality of life. Methods: Colontown is a Facebook-based CRC patient and caregiver support, education and advocacy group. Live Wire, a Colontown neighborhood that was formed in 2018 to help members manage CIPN, consists of over 700 CRC patients. One member of this group applied ice on hands and feet (‘icing’) during oxaliplatin infusion to limit exposure to chemotherapy via cold-induced vasoconstriction. The member was able to prevent CIPN, gaining the attention of the entire group. Results: Subsequently, popularization of icing occurred, as administrators communicated patient experiences and relayed published results on the effect of oral icing to patients. Several Colontown members voluntarily tried it during their chemotherapy, and reported successful outcomes. Live Wire created an “icing protocol” and distributed it to patients, oncologists, and care teams, both in-person and on social media (sm). Conclusions: This real-world example highlights the role of educated patient advocates on sm. Working with these groups directly can provide insights for the medical community on measures patients can do to prevent chemotherapy-associated side effects. The limited publications on icing to prevent CIPN, although promising, have not been enough to make it a recommended standard practice. Meanwhile, voluntary participation using icing for CIPN is growing in Colontown. At this time, Colontown is discussing with oncologists and cancer centers the potential of creating a clinical trial to verify the efficacy icing has during oxaliplatin infusion as a strategy to counter CIPN. Our hope is that this patient-informed icing protocol will be able to guide the design of a clinical trial on icing. Furthermore, with this “experiment”, we hope to illustrate the advantages of serious engagement with a large patient population through the modern use of social media.
Updated anticoagulation therapy in atrial fibrillation
Authors: Yihong Sun
Journal: BMJ (2016)

心房颤动的血栓栓塞防治的传统抗凝药物是华法林，近年来直接口服抗凝药物取得了重要进展，并且直接口服抗凝药物的研究中纳入了相当一部分合并瓣膜病变的患者。所有非瓣膜病房颤患者均应该基于血栓和出血风险给予抗凝治疗。多数患者直接口服抗凝药物的剂量相对固定，但是仍然需要考虑年龄、肾功能等因素采取适当的剂量。出血风险极高不能口服抗凝药物的患者可采用机械装置或手术治疗，但还需要更多研究证实。
Demonstrating the value of liquid biopsy for lung cancer in a public health care system.
Authors: Rosalyn A. Juergens, Doreen Anuli Ezeife, Janessa J. Laskin, Jason Scott Agulnik, Desiree Hao, Scott Andrew Laurie, Jennifer H. Law, Lisa W Le, Lesli Ann Kiedrowski, Frances A. Shepherd, Victor Cohen, Aria Shokoohi, Rachel Vandermeer, Janice Juanning Li, Inna Hanson, Roxanne Fernandes, Alexandra Maria Salvarrey, Richard B. Lanman, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2020)

3546 Background: Given the challenges of molecular profiling in patients with advanced lung cancer, this prospective study examines clinical outcomes and utility of liquid biopsy in treatment naive stage IV lung adenocarcinoma patients (Cohort 1) and in the setting of resistance to targeted therapy (Cohort 2; not reported here). Methods: This study is being conducted at 6 Canadian centres (NCT03576937) using Guardant 360 (G360), a validated cell-free DNA next-generation sequencing assay that identifies variants in 74 cancer-associated genes, including fusions and copy number gain. Cohort 1 (N = 150) includes patients with treatment-naïve advanced non-squamous lung carcinoma, ≤10 pack-year smoking history, and measurable disease. Patients received standard of care tumour tissue (TT) molecular profiling ( EGFR, ALK +/- ROS1) and liquid biopsy (LB). The primary endpoint was response rate to first-line therapy (RECIST 1.1); secondary endpoints include incremental targetable alterations identified through G360 ( EGFR, ALK, BRAF, ERBB2, KRAS (G12C), NTRK, MET (amplification, exon 14 skipping), RET, ROS1), turn-around time (TAT) and successful molecular profiling rates. Results: To date, 84 eligible patients with clinical data have been accrued to Cohort 1. Median age is 64 (range 23-91), 64% are female, 85% never smokers, 96% have adenocarcinoma. Actionable targets have been identified in 55% of patients using G360 ( EGFR/ALK in 37%), 39% using standard TT profiling. Eight EGFR/ALK aberrations were identified in TT but not LB, while 6 were identified in LB but not TT. TT profiling for EGFR/ALK was unsuccessful in 8% of patients (insufficient tissue, failed biopsy). Fourteen patients (17%) had no ctDNA alterations detected by G360 (low disease burden vs. non-shedding). Of 75 patients receiving first-line treatment, 57% received targeted therapy, 28% chemotherapy combinations, 11% checkpoint inhibitors and 4% were observed. Treatment decisions were informed by G360 alone in 37% and by G360+TT results in 27% (by physician report). Among 46 evaluable patients, ORR was 54% (25/46). Using G360, ORR was 75% (15/20) in those with actionable alterations and 38.5% (10/26) in those without. Using TT, ORR was 67% (14/21) in those with actionable alterations and 44% (11/25) in those without. Mean TAT was 7.9 days (SD+/-1.7) for LB vs 19.9 days (SD+/- 9.8) for TT. Conclusions: Liquid biopsy using G360 identifies actionable targets beyond tissue profiling alone in newly diagnosed lung cancer patients, has faster TAT and yields similar outcomes with targeted and non-targeted therapy. Clinical trial information: NCT03576937 .
Systemic therapy for patients with breast cancer and one to three brain metastases (BM).
Authors: Zaid A Soomro, Omar Alhalabi, Ryan Sun, Aya Albittar, Limin Hsu, Vicente Valero, Nuhad K. Ibrahim
Journal: Journal of Clinical Oncology (2020)

1090 Background: Despite advances in systemic therapies and improved overall survival of metastatic breast cancer (MBC) patients, the development of brain metastases (BMs) remains a challenging complication that affects quality of life and increases morbidity and mortality. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable systemic disease. Methods: We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) after diagnosis of the initial 1-3 BMs on the patient’s progression-free survival time (PFS), defined as time to death, to a second BMs or to extracranial metastases. All MBC patients with 1 to 3 BMs only (without extracranial disease) treated at our institution between 2002 and 2017 were identified. For each patient, full information on follow-up and administered therapies were mandatory for inclusion. Hazard ratios (HR) were calculated using the Cox proportional hazard model. We also computed the restricted mean survival time (RMST) up to 5 years of follow-up. Results: Among the 2645 patient with BM treated at our institution, 80 were included for analysis. In regards to primary BMs management in patients, 46 of 80 (57%) were treated by radiation therapy, 6 of 80 (7.5%) underwent surgical resection, and 28 of 80 (35%) were managed by a combination of surgery and radiation therapy. All patients had staging imaging documenting lack of extracranial metastases at the time of local therapy of BMs. Following the primary management of BM, we observed that providers changed systemic therapy in 32 of 80 (40%), defined as the CST group. CST included both initiation of therapy in 16 of 80 (20%) and switching of adjuvant therapy in 16 of 80 (20%). Median PFS among CST was 7.7 months vs. 7.2 months among no CST (HR = 0.855, 95% confidence interval (CI) 0.53-1.38, p = 0.52). 5-year RMST for the CST group was 16.6 months vs. 12.8 months in no CST group. The difference of 3.8 months (95% CI 4.3-11.8) was not statistically significant. Conclusions: Patients with 1-3 BMs without extracranial disease had a median PFS close to 7.5 months after local therapy. Consistent with current standard of care of maintaining the same systemic therapy approach upon developing isolated BMs, our findings did not demonstrate a significant difference in PFS between patients who experienced a change in systemic therapy compared to those who did not.
Analysis of gene copy number in esophageal patient-derived tumor xenografts.
Authors: Ekaterina A. Lukbanova, Natalya N. Timoshkina, Evgeniy N. Kolesnikov, Mikhail A Kozhushko, Sergei Kit, Sergey V. Sanamyants, Aleksandr E. Anisimov, Anna S. Goncharova, Tatiana P. Protasova, Denis S. Kutilin, A. V. Volkova, M. V. Mindar, Sergey Yu. Tkachev, Ekaterina V. Zaikina, D. V. Khodakova, Aleksey Yu. Maksimov, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2020)

e13648 Background: Patient-derived tumor xenograft (PDX) models are a valuable resource for studying cancer biology and antitumor drug evaluation. The suitability of tumor models in vivo depends on how accurately they mimic a human disease and reproduce the histotype and molecular genetic features of a human tumor. The purpose of the study was to create a PDX model of human cancer and analyze its characteristics. Methods: PDX models of esophageal cancer were obtained by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the BALB/c Nude athymic mice (n = 10 for one PDX generation). Preservation of the tumor histotype was confirmed histologically (hematoxylin and eosin staining). 5 PDX were generated. An analysis of the relative copy number of the YAP1 and KDM6A genes (Real-Time qPCR) in xenograft and donor tumor tissues was performed in each generation. Results: A decrease in the copy numbers of the YAP1 and KDM6A genes by 3.8 and 2.2 times, respectively, was observed in PDX tumor samples (F3 generation) compared to normal donor tissues (p &lt; 0.05). This trend maintained in F4 and F5 generation PDX samples. No changes in the copy numbers of the YAP1 and KDM6A genes were detected in PDX tumor samples in F1 and F2 generations. A cluster analysis (Hierarchical Clustering, Euclidean distance) demonstrated that samples of the first and second generations of esophageal cancer PDX models were closest to the patient tumor tissues in gene copy numbers. Conclusions: Later generations of esophageal cancer PDX models are characterized by changes in the genes copy numbers due to changes in the tumor and clonal selection. Early PDX generations better reproduce genetic, molecular and morphological features of tumors.
Reasons for encounter and diagnosis of pediatric patients at general practice clinic affiliated to a tertiary hospital
Authors: Wen-juan Huang, Zhong-hua Zhou, Jing-zhu Guo, Shi-yin Chen
Journal: BMJ (2013)

This study reviewed the reasons for encounter (RFE), diagnoses and the diagnostic categories of patients aged 0-14 y in general practice clinic affiliated to a tertiary hospital from June 2011 to May 2012. The results showed that the most frequent RFE was cough, at a rate of 29.6 per 100 encounters; the second one was fever (21.4%) and the third was nasal problems (9.5%). Medical examinations, skin rashes and follow-up encounters occurred at equal rates(5.2%). The most frequent diagnosis was acute upper respiratory tract infection (41%). Medical examination (6.3%), other viral diseases (5.1%), pneumonia (3.6%) and no detected disease (3.6%) were also common diagnoses. The diagnostic categories included all systems, and the problems of the respiratory system (56.4%) were most common. The results suggest that pediatric care comprises a very important part of primary care.


Key words: 
Child; General practice