tbuckley/cabot-search huggingface dataset:
Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors.
Authors: Navid Hafez, Hatem Hussein Soliman, Siqing Fu, Karen A. Gelmon, Albiruni Ryan Abdul Razak, Pamela N. Munster, Ulka N. Vaishampayan, Shumei Kato, Primo Lara, Elizabeth M. Swisher, Andrew B. Nixon, Abhijit Patel, Yu Shyr, S. Percy Ivy, Patricia LoRusso, Joseph W. Kim
Journal: Journal of Clinical Oncology (2020)

1077 Background: Cediranib, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in patients with germline BRCA1/2 mutations and HER2-negative metastatic breast cancer. We therefore tested the anti-tumor activity of the combination of cediranib and olaparib in patients (pts) with metastatic triple-negative breast cancer (TNBC). Methods: This multi-institutional, two-stage, phase II study enrolled patients with metastatic TNBC previously treated with a minimum of one prior line of systemic therapy in the advanced setting. Patients were treated with cediranib 30mg po daily plus olaparib 200mg po BID until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by RECIST v1.1. Baseline tumor biopsies were obtained for biomarker analyses. Results: Baseline characteristics of the 37pts enrolled are summarized below. The overall objective response rate was 14% (95% CI: 0.025, 0.2453). Median duration of response was 2.0 months (mos) with a range of 1.8 to 6.3 mos. Disease control rate ((# of pts with CR, PR or SD)/(# of evaluable pts)) was 81% (95% CI: 0.6846, 0.937). Median PFS was 3.7 mos (95% CI: 2.1, 4.3). Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 25 of 38 (66%).G3/4 AEs occurring in &gt; 5% of pts were hypertension (24%) and dyspnea (11%), diarrhea (8%) vomiting (8%). Conclusions: The cediranib/olaparib combination resulted in promising objective responses in 14% of biomarker-unselected patients with heavily pre-treated, metastatic TNBC. The regimen required prompt initiation of antihypertensives, but AEs were overall manageable. Analyses of mutation status in homologous recombination DNA repair genes are ongoing and will be correlated with clinical outcome. Clinical trial information: NCT02498613 . [Table: see text]
Outcomes of patients with left ventricular assist device receiving cancer directed therapies.
Authors: Ilana Schlam, Raja Zaghlol, Binaya Basyal, Selma Mohammed, Christopher Gallagher, Ana Barac
Journal: Journal of Clinical Oncology (2020)

e19335 Background: Left ventricular assist devices (LVAD) are increasingly utilized in advanced heart failure (HF). There is a paucity of data regarding outcomes of cancer-directed therapies (CDT) in patients with LVAD. The aim of this study was to describe outcomes in this newly identified group of patients. Methods: Institutional LVAD database review to identify patients with cancer diagnosis who had at least 6 months of follow up. Chart review to capture cancer history, CDT and high-severity complications. Results: 12 of the 588 patients who received LVAD were diagnosed with cancer and received CDT. Six patients were males, 9 African Americans and 3 Caucasians. Ischemic cardiomyopathy (CM) was the etiology of HF in 4 (33%) patients, 9 (66%) patients had non-ischemic CM (including: chemotherapy induced n = 3, idiopathic n = 3, myocarditis n = 1, sarcoidosis n = 1). Cancer diagnoses, staging and high severity complications are described in table. The median age of cancer diagnosis was 59 (41-72). The median time from LVAD placement to cancer diagnosis was 21.5 months (3-47). The median number of hospitalizations was 4 (range 1-7). Conclusions: Cancer diagnosis after LVAD placement requires a multidisciplinary approach due to high rates of adverse cardiovascular and cancer related outcomes. To the best of our knowledge this is the first report of patients with LVAD receiving chemo-immunotherapy, they did not tolerate the combination and immunotherapy was discontinued after one cycle, a larger study is required to assess safety in LVAD patients. Larger prospective studies are required to determine outcomes in this complex patient population. [Table: see text]
肺结节病15例临床分析
Authors: 张英凯, 杜海莲, 李霞, 张眷亮, 石雪杰
Journal: BMJ (2008)

结节病(sarcoidosi)是一原因未明的非干酪性类上皮细胞肉芽肿性疾病,常侵犯全身多个脏器,尤其胸部器官.在我国发病率低,临床表现缺乏特异性,易误诊误治.对我院近年收治的15例患者资料分析如下。
First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).
Authors: Daniel Peter Petrylak, Xin Gao, Nicholas J. Vogelzang, Mary Harlow Garfield, Ian Taylor, Marcia Dougan Moore, Ronald Alan Peck, Howard A. Burris
Journal: Journal of Clinical Oncology (2020)

3500 Background: Proteolysis Targeting Chimera (PROTAC) protein degraders induce selective degradation of targeted proteins by engaging the ubiquitin proteasome system. ARV-110 is an orally bioavailable PROTAC that specifically degrades AR ≥ 95% and achieves anti-tumor activity in ENZ-naïve and -resistant prostate cancer xenograft models. Methods: To define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARV-110, pts with ≥ 2 prior therapies for mCRPC, including ENZ and/or ABI, received ARV-110 orally once daily. Dose escalation is per 3+3 design. Endpoints include dose limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics (PK), biomarkers (e.g., AR mutation analysis), RECIST and PSA response. Results: By January 2020, 18 pts were dosed: 35 mg (N = 3), 70 mg (N = 4), 140 mg (N = 8), 280 mg (N = 3). 12 pts received both ENZ and ABI; 14 received prior chemotherapy. 1 of 18 pts experienced a DLT (280 mg) of Grade (Gr) 4 elevated AST/ALT followed by acute renal failure while taking rosuvastatin (ROS). A 2 nd pt had Gr 3 AST/ALT with ROS that resolved off ROS, permitting ARV-110 retreatment. ROS plasma concentrations demonstrated significant increases concurrent with AST/ALT elevations in both pts. Subsequently, ROS was prohibited without further ≥Gr 2 AST/ALT AEs. No other related Gr 3/4 AEs were reported. ARV-110 PK was generally dose proportional and at 140 mg reached levels associated with preclinical anti-tumor activity. 15 pts were evaluable for PSA response (excludes 1 pt stopped after 1 dose for early progression and 2 pts initiated 2 weeks before cutoff, all at 140 mg). Of these, 8 pts initiated dosing at ≥140 mg. 2 pts achieved confirmed PSA declines of &gt;50%, both at 140 mg. Prior therapy in both pts included ENZ and ABI, chemotherapy, bicalutamide and radium-223 plus other regimens. 1 pt had 2 AR mutations known to confer ENZ resistance. The 2nd pt also achieved an unconfirmed RECIST partial response (confirmatory scan pending). Both responses were ongoing at data cutoff (8+ and 21+ weeks of treatment). Conclusions: To date, ARV-110 has an acceptable safety profile. Concurrent ROS is now prohibited. MTD has not yet been established; determination of RP2D continues. ARV-110 demonstrates antitumor activity in mCRPC after ENZ/ABI with 2 ongoing confirmed PSA responses, one of which was associated with tumor reduction. Updated data for this first PROTAC in clinical testing will be presented. Clinical trial information: NCT03888612 .
后路椎间盘镜手术治疗老年人腰椎间盘突出症38例
Authors: 刘沂, 张爽, 陈爽, 黄载国, 于一民, 温殿学
Journal: BMJ (2006)

自2000年12月至2004年12月我院采用后路椎间盘镜手术治疗腰椎间盘突出症老年(＞60岁)患者38例,其中17例合并神经根管狭窄.平均随访18个月,优良率为89.5%.后路椎间盘镜手术具有损伤小、术后卧床时间短、恢复快等优点.镜下可以进行神经根管减压,只要严格掌握适应证,在治疗老年人腰椎间盘突出症方面有应用价值。
A phase III trial of capivasertib and paclitaxel in first-line treatment of patients with metastatic triple-negative breast cancer (CAPItello290).
Authors: Peter Schmid, Javier Cortes, Mark E. Robson, Hiroji Iwata, Roberto Hegg, Marina Nechaeva, Binghe Xu, Sunil Verma, Vincent Haddad, Esteban Rodrigo Imedio, Gaia Schiavon, Andrew Foxley, Yeon Hee Park
Journal: Journal of Clinical Oncology (2020)

TPS1109 Background: Therapeutic options for patients with metastatic triple-negative breast cancer (TNBC) are limited to sequential chemotherapy, although recent advances with novel agents have been made for specific subgroups (PD-L1 inhibitor atezolizumab in combination with nab-paclitaxel in patients with PD-L1-positive tumors and PARP inhibitors in patients with germline BRCA mutations). The PI3K/AKT/PTEN signaling pathway is often activated in TNBC, mainly through activating mutations in PIK3CA or AKT1 and/or inactivating alterations in PTEN. The phase II PAKT study (NCT02423603) demonstrated that addition of the oral AKT inhibitor capivasertib to first-line paclitaxel resulted in significantly longer progression-free survival (PFS) and overall survival (OS) in patients with advanced TNBC, especially in patients with PIK3CA/AKT1/PTEN-altered tumors (Schmid et al, 2019). This phase III trial (NCT03997123) will further evaluate the efficacy and safety of capivasertib in combination with paclitaxel in first-line treatment of patients with metastatic TNBC in an unselected population and will also explore potential predictive markers of sensitivity to the combination of paclitaxel and capivasertib. Methods: Eligible patients for this double-blind, randomized, placebo-controlled trial must have metastatic TNBC or locally advanced disease not amenable to resection with curative intent. Patients must be candidates for single-agent taxane therapy and have received no prior systemic therapy for locally advanced inoperable or metastatic disease. Prior chemotherapy in the (neo)adjuvant setting must be completed ≥12 months prior to enrollment. Patients will be randomized 1:1 to paclitaxel 80 mg/m 2 (days 1, 8 and 15) with either capivasertib 400 mg twice daily or placebo (days 2–5, 9–12 and 16–19) every 28 days, until objective radiologic disease progression as defined by RECIST 1.1, unacceptable toxicity or death. Stratification factors will be prior adjuvant chemotherapy, visceral versus non-visceral disease, and geographic region. Post-randomization central testing of tumor tissue (collected prior to enrollment) will be carried out to identify predictive markers of sensitivity to treatment. The primary endpoints of this study are PFS and OS. Secondary endpoints include safety and tolerability, time to second progression or death, objective response rate, duration of response, and clinical benefit rate. Enrollment for this study started in May 2019. Clinical trial information: NCT03997123 .
Association of rs7372209 single nucleotide polymorphism in gene for miRNA-26a-1 with tumor localization and disease outcome in patients with colorectal cancer from Bulgaria.
Authors: Galya Mihaylova, Desislava Ivanova, Oscan Tasinov, Neshe Nazifova-Tasinova, Veneta Petrova, Pavel Pavlov, Rostislav Manev, Milko Mirchev, Nikolay Vladimirov Conev, Zhasmina Mihaylova, Ivan Donev, Maria Radanova
Journal: Journal of Clinical Oncology (2020)

e13656 Background: A retrospective study was carried out to investigate the association of functional rs7372209 single nucleotide polymorphism (SNP) in the 5'- region of pri-miRNA- 26a1 gene with a risk of colorectal cancer (CRC) in a Bulgarian population, to evaluate its role as a potential prognostic or predictive biomarker for the disease and to studied its affection on the expression of miRNA-26a-1 in patients with CRC. Methods: 101 patients with colorectal metastatic disease and 90 healthy volunteers, all Caucasians from Bulgaria, were genotyped for rs7372209 SNP by qPCR method. The expression levels of miRNA-26a in sera also have been determined. U6 was used as endogenous constitutively expressed control. Relative gene expression was calculated using 2 −∆∆Ct method. Results: TT genotype in rs7372209 SNP was significantly overrepresented in CRC patients with right-sided colon cancer when compared with CRC patients with left-sided colon cancer, and rectal cancer (33% vs. 8%, OR = 6.13, 95% CI: 1.56–23.97, p = 0.009). Patients with TT genotype in rs7372209 SNP had significantly (p = 0.041) longer mean overall survival (OS) of 26 months (95% CI: 21.76–34.18) as compared to those with CT and CC genotypes – 19 months (95% CI: 16.43–22.20). Expression levels of miR-26a in sera were significantly higher in CRC patients compared to healthy volunteers. The ROC analysis revealed that miR-26a can effectively discriminate between CRC patients and the healthy volunteers (AUC = 0.830, 95% CI: 0.77–0.89, p &lt; 0.001). Patients with TT genotype in rs7372209 SNP had a numeric lower mean level of miR-26a-1 – 4.702 in comparison with patients that harboring CT or CC genotype – 6.507. Conclusions: Our data suggest that high serum levels of miR-26a-1 are potentially useful as a diagnostic biomarker for CRC. Although, that patients with ТТ genotype had often more aggressive right-sided colon cancer they had longer mean overall survival than patients harboring CT or CC genotype of rs7372209.
Gastric juice piR-1245: A promising prognostic biomarker for gastric cancer.
Authors: Wei Peng, Jianhong Liu, Xiaorong Zhou, Hong Fan, Jianwei Lu, Senqing Chen, Jifeng Feng
Journal: Journal of Clinical Oncology (2020)

e16574 Background: Emerging reports demonstrated that PIWI-interacting RNAs (piRNAs) played an indispensable role in tumorigenesis. However, it still remains elusive whether piR-1245 in gastric juice specific in stomach could be employed as a biomarker for gastric cancer (GC). The present work is aiming at exploring the possibility of piR-1245 in gastric juice as a potential marker to judge for diagnosis and prognosis of gastric cancer. Methods: Gastric juice was collected from 66 GC patients and 66 healthy individuals. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was employed to measure the levels of piR-1245 expression. Then, the pattern of piR-1245 expression in gastric juice was determined between GC patients and healthy individuals. A receiver operating characteristic (ROC) curve was constructed for distinguishing GC from healthy individuals. Results: Gastric juice piR-1245 levels in GC were higher than those of controls (P &lt; 0.0001). The value of area under ROC (AUC) was 0.885 (sensitivity, 90.9%; specificity, 74.2%; 95% confidence interval, 0.8286 to 0.9414). High gastric juice piR-1245 expression was signally correlated with tumor size (P = 0.013) and TNM stage (P = 0.001). GC patients with high piR-1245 expression in gastric juice exerted a poorer overall survival (OS) (P = 0.0152) and progression-free survival (PFS) (P = 0.013). COX regression analysis verified that gastric juice piR-1245 expression was an independent prognostic risk variable for OS (P &lt; 0.05). Conclusions: The current study suggested that piR-1245 in gastric juice had the potential to be a useful biomarker for GC detection and prognosis prediction.
Mobile apps: Breaking barriers to early cancer detection in underserved communities.
Authors: Carlos A. Munoz-Zuluaga, José David Gallo-Perez, Andres Perez-Bustos, Mavalynne Orozco-Urdaneta, Karen Druffel, Lida Patricia Cordoba-Astudillo, Luis Gabriel Parra Lara, Carolina Velez, Farah El-Sharkawy, Katherin Zambrano-Vera, Raul Hernando Erazo, Mary Caitlin King, Armando Sardi
Journal: Journal of Clinical Oncology (2020)

2065 Background: Despite being potentially curable with early detection and timely treatment, breast (BC) and cervical cancers (CC) remain leading causes of death for Colombian women. Lack of cancer screening education, tedious administrative processes, and geographical limitations hinder early cancer detection. Today, technological tools permeate all levels of society and could gather data for user risk stratification, deliver clear and customized information, and help with care coordination, tracking, and addressing communication, transportation, and financial barriers. We aimed to assess the effectiveness of a free mobile application (mApp) to reach women, understand misconceptions about cancer screening, identify users at risk for BC and CC, and coordinate screening tests in Cali, Colombia. Methods: The mApp, Ámate, was developed over 4 months and advertised to women (≥14 years) in waiting rooms of 4 healthcare facilities in Cali, Colombia for 23 months. Ámate used educational, evaluative, and risk factor questions followed by brief explanations to assess the population’s knowledge, educate users on BC and CC, and identify users in need of BC and/or CC screenings. Correct answers yielded points redeemable for cellular data. Women who required screening were subsequently navigated to a healthcare provider and enrolled in the national cancer program. Results: From August 2017-August 2019, 1,043 women from Cali downloaded Ámate and answered all questions. Misconceptions about BC included beliefs that BC can be prevented (87%), obesity does not increase the risk of BC (49%), deodorant causes BC (17%), and only women with a relative with BC can get BC (16%). For CC, misconceptions included that pap smears should not be performed while sexually active (64%), vaginal pain is an early sign of CC (44%), and only women contract HPV (33%). Overall, 31.5% (329) were identified as at-risk and needed a mammogram and/or pap smear. So far, 30% (98) were successfully navigated and completed their recommended screening test(s). Barriers to enrollment in these programs included patient unwillingness, using fake contact information, limited available appointments, and denied access due to healthcare coverage. Conclusions: Ámate is an accessible tool that identifies women at-risk for breast and cervical cancer and detects barriers to early cancer detection. Administrative obstacles exist and must be addressed to improve early cancer detection/screening. Ámate is currently being tested in other areas of Colombia and may be useful in other underserved countries.
Effect of leucovorin on radiation-induced brain injury and tumor radiosensitivity in patients of NPC: A retrospective analysis.
Authors: ZiBin Liang, Siyang Wang, Shuai Yang, Feiyu Long, Lifeng Jiang, Yanfei Zou, Jinmei Pan, Zhong Lin, Zhibin Cheng
Journal: Journal of Clinical Oncology (2020)

e18552 Background: Nasopharyngeal carcinoma (NPC) is a typical type of head and neck cancers with its high prevalence areas in Southeast of China. On account of the prolongation of life, the severe complications developed such as radiation encephalopathy (REP). Currently many methods are used to cure REP but the outcomes are limited, such as corticosteroids, hyperbaric oxygen, antiplatelet agents and so on. The aim of this study is 1) to evaluate the protective effect of Calcium leucovorin (LV), a reduced folic acid, on REP in NPC patients. 2) to investigate the progression-free survival (PFS) and overall survival (OS) in NPC treated with or without LV. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in the Fifth Affiliated Hospital of SYSU included 1075 patients diagnosed as NPC of Stage II, III, or IVa who had been treated from December 2002, through February 2014. The Leucovorin-Group (LV-Group) of 163 NPC patients were matching the preceding criteria and agreed to receive PFL chemotherapy (cisplatin 80 mg/m², 5-fluorouracil 1000 mg/m²/d, and leucovorin 120 mg/m²) every 3 weeks. The Non-leucovorin-Group (NLV-Group) of 913 patients with similar disease status who did not receive leucovorin during the same period. Histologically there were 260 patients of PF chemotherapy (PF-Group) and 653 patients of other regimen chemotherapy (NPF-Group) in NLV-Group. REP were evaluated according to MRI and CT scan imaging studies. Time to progress (TTP), the real-world local control rate (rwLCR) and OS were compared across the two cohorts using the log-rank test. REP were compared using Chi-Square and Fisher’s Exact Test. Results: The TTP of the LV-Group as compared to the NLV-Group at 3, 5, 8, 10,12 and 16 years were 98.96% vs 94.97%, 95.57% vs 90.08%, 92.01% vs 85.22%, 90.67% vs 84.39%, 88.59% vs 84.26% and 88.54% vs 81.06%, respectively. The incident of REP in LV-Group is lower than that of the NLV-Group significantly( P= 0.0413). The OS of LV-Group as compared to PF-Group at 3, 5,10 and 12 years were 97.42% vs. 91.24%, 94.61% vs. 87.44%, 88.74% vs. 81.98%和88.74% vs. 78.57%, respectively. The OS of LV-Group got higher than that of PF-Group ( P= 0.0269). The OS of LV-Group was significantly higher than that of PF-Group with 90.83% vs. 82.12% in stage I-III(P = 0.0348). The rwLCR of LV-Group as compared to PF Group were 97.06% vs. 73.91% in stage T4 ( P= 0.0133). Conclusions: Leucovorin can significantly reduce the incidence of REP of NPC combined with PF regiment. It may improve the tumor radiosensitivity in NPC patients.
骨头坏死的病因、病理和发病机制
Authors: 孙伟
Journal: BMJ (2006)

骨坏死又称缺血性骨坏死(avascular,necrosis,AVN)、无菌性骨坏死.按国际骨循环学会,ARCO,的定义,骨坏死,osteonecrosis,ON,是指由于各种原因,机械、生物等,使骨循环中断、骨的活性成分死亡及随后修复的一系列复杂病理过程.AVN可累全身许多关节,以股骨头坏死,osteonecrosis,of,the,femoral,head,ONFH,最常见,其他依次为股骨髁、肱骨头、胫骨髁,腕部月骨、舟状骨,踝部距骨、跟骨及股骨、胫骨骨干。
Tolerability of neratinib in older adults with HER2 positive or HER2 mutated metastatic breast cancer.
Authors: Jin Sun Lee, Susan Elaine Yost, Tracey Stiller, Suzette Blanchard, Simran Padam, Vani Katheria, Aileen Tang, Norma Martinez, Niki Himat Patel, Mina S. Sedrak, James Ross Waisman, Daneng Li, Shamel Sanani, Cary A. Presant, Joanne E. Mortimer, Yuan Yuan
Journal: Journal of Clinical Oncology (2020)

e13018 Background: The tolerability and efficacy of targeted therapy in older adults with cancer have not been adequately studied. Neratinib is an oral pan-HER1, HER2, and HER4 tyrosine kinase inhibitor that has been FDA approved for early stage HER 2+ breast cancer. This phase II trial is designed to evaluate the safety of neratinib in older adults (≥60 years) who have HER2 amplified or HER2 mutated metastatic breast cancer (MBC). Methods: Older adults with HER2+ or HER2 mutated MBC with any number of previous lines of therapy received neratinib at 240 mg daily in 28-day cycles. Loperamide was used for diarrhea prophylaxis: 4mg tid x 14 days followed by 4mg bid for days 15-28, and as needed after first cycle. Participants completed a pre-treatment geriatric assessment (GA) including measures of function, comorbidity, cognition, nutrition, and psychosocial status at cycle 1, cycle 4, and end of the study. Relationships between tolerability (dose reductions and number of completed courses) and log 2 risk score were assessed using t-test and linear regression. Response rate (RR), progression free survival (PFS) and overall survival (OS) were evaluated. Results: Twenty-five patients (mean age 68 [60-79]) were enrolled from 12/2016 to 03/2019, and 36% of patients (pts) were &gt;70 years old. Median number of cycles completed was 3 (0-13): 1/25 (4%) pts had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not evaluable for response. PFS was 2.6 months (95% CI [2.56-5.26]). The median OS was 17.4 months (95% CI [10.3, NA]). A total of 9/25 pts (36%) had dose modification. Of these, 3/9 had at least one dose hold, and all 9 had at least one dose reduction (diarrhea, n = 6). 20/25 participants (80%, 95% CI [59%, 93%]) had grade ≥2 toxicities, and 9/25 pts (36%, 95% CI [18%, 57%]) had grade 3 toxicities that were attributable to treatment: diarrhea (n = 5), abdominal pain (n = 2), and vomiting (n = 2). There were no grade 4 or 5 toxicities. Two pts (8%) were hospitalized due to neratinib toxicity, and two pts went off treatment due to toxicity attributed to neratinib (diarrhea and nausea). There was a trend in the difference in toxicity risk scores by whether a participant had a dose reduction (t-test: p-value = 0.054) with participants with higher risk scores being more likely to require a dose reduction; however, toxicity risk score did not predict number of cycles completed based on linear regression (slope = -1.29, se = 1.44, p = .39). Conclusions: Neratinib is safe in older adults with HER2 positive or HER2 mutated MBC. Clinical trial information: NCT02673398 .