tbuckley/cabot-search huggingface dataset:
Association of K1505Ac IHC signal loss and response to immunotherapy in patients with metastatic cutaneous melanoma.
Authors: Daniel S. Altman, Maria Vershvovsky, Wei Jiang, Haifeng Yang, Geetha Jagannathan, Rachel Redfield, Michael J. Mastrangelo, Takami Sato, Marlana M. Orloff, Melissa Wilson
Journal: Journal of Clinical Oncology (2020)

e22049 Background: Immune checkpoint inhibitors (ICI) have become a mainstay of treatment for patients with metastatic cutaneous melanoma. Currently, there are no reliable biomarkers to predict which patients will benefit from ICI therapy. K1505Ac immunohistochemistry (IHC) signal loss is equivalent to loss of functional PBRM1 protein, which has previously been shown to predict response to ICI therapy in metastatic renal cell carcinoma. We hypothesized that loss of K1505Ac IHC expression in patients’ tumors may predict benefit to ICI therapy. Methods: An exploratory study was conducted in patients with metastatic cutaneous melanoma (n = 25) who were treated with ICI therapy at Thomas Jefferson University. Retrospective chart review was performed to determine best clinical response using RECIST 1.1 criteria. Tumor samples from these patients were tested for loss of K1505Ac IHC signals to determine the correlation to best clinical response to ICI therapy. The pathologist was blinded to clinical responses during IHC analysis. Results: The chart below demonstrates the percentage of patients with K1505Ac IHC signal loss ≥ 40% and their correlating best clinical response to ICI therapy. Four of five patients (80%) with complete or partial response displayed K1505Ac IHC signal loss ≥ 40%. Fifteen of twenty patients (75%) with stable disease or progression of disease displayed K1505Ac IHC signal loss &lt; 40%. Conclusions: Loss of K1505Ac IHC signal was associated with better clinical response to ICI therapy for patients with metastatic cutaneous melanoma. These findings suggest that K1505Ac IHC signal loss may serve as a biomarker to help determine which patients will benefit from ICI therapy. A larger cohort of patients is currently under investigation to better evaluate this association. [Table: see text]
A phase II, open-label study of tomivosertib (eFT508) added on to continued checkpoint inhibitor therapy in patients (pts) with insufficient response to single-agent treatment.
Authors: Anthony B. El-Khoueiry, Nishan Tchekmedyian, Rachel E. Sanborn, Julio Antonio Peguero, Kerry Pulver, Vikas Dembla, Jacob Stephen Thomas, Gary Gene Chiang, Mark Densel, Neil Sankar, Stephen Theodore Worland, Lyon L. Gleich, Robert S. Sikorski
Journal: Journal of Clinical Oncology (2020)

3112 Background: Despite the broad activity of checkpoint inhibitors across tumor types, primary or secondary resistance after initial response represents a major challenge. Tomivosertib (T), a potent and highly selective inhibitor of the immunosuppressive kinases MNK-1 and 2, blocks expression of checkpoint proteins PD-1, PD-L1, and LAG-3 as well as immunosuppressive cytokines IL-6 and IL-8. In preclinical models, T was shown to trigger an anti-tumor immune response and enhance the activity of checkpoint inhibitors in a T-cell dependent manner. In prior clinical studies, T had an acceptable safety profile as a single agent and in combination with anti-PD-L1 agent avelumab. Methods: Patients experiencing insufficient response (progression or stable disease for 12 weeks or more) to any FDA-approved checkpoint inhibitor in any approved indication were eligible. T at 200 mg oral (PO) BID was added to the existing checkpoint inhibitor until disease progression or unacceptable toxicity was noted. Results: 39 pts (23 male, 16 female) were enrolled across seven cancer types. Median age was 68 (range 42-85). Median prior therapies were 2 (range 1-6). The most common cancers were lung (N = 17), urothelial (N = 6), renal (N = 5) and head and neck (N = 5). 36 pts continued on anti PD-1 antibody (Pembrolizumab and Nivolumab, 18 each) and 3 on anti PD-L-1 antibody (Durvalumab 2, Atezolizumab 1) . The most common grade 3/4 treatment related adverse events occurring in more than 1 pt were alanine aminotransferase increase (2), blood creatine phosphokinase increase (2) and maculo-papular rash (2). 7 patients discontinued treatment (18%) due to adverse events attributable to either drug. Three partial responses (PR) per RECIST 1.1 were observed in pts with previous progression on checkpoint inhibitor therapy, one each in NSCLC (1/17), gastric (1/1) and renal cancer (1/5). 7 NSCLC pts (41%) were progression free for ≥ 24 weeks. All NSCLC patients entered the study with progression by RECIST 1.1 on single agent checkpoint inhibitor prior to adding T. Conclusions: The addition of T to existing checkpoint therapy was well tolerated and manifested clinical activity including objective responses in pts with progression on existing checkpoint inhibitor. A Progression Free Survival rate at 24 weeks of 41% was noted in NSCLC patients. Additional studies evaluating the addition of T to checkpoint inhibitor therapy after progression on anti PD-1 or PD-L-1 therapy are planned. Clinical trial information: NCT03616834 .
CD19-targeted chimeric antigen receptor (CAR) T cells in CNS relapsed acute lymphoblastic leukemia (ALL).
Authors: Haley Newman, Allison Emily Barz Leahy, Yimei Li, Hongyan Liu, Regina M Myers, Amanda M DiNofia, Joseph Gregory Dolan, Colleen Callahan, Kaitlin J Devine, Lisa Wray, Carl H. June, Stephan A. Grupp, Susan R. Rheingold, Shannon L. Maude
Journal: Journal of Clinical Oncology (2020)

10511 Background: CNS relapse of B-ALL is difficult to treat after cranial radiation or multiple relapses. Durable remissions of relapsed/refractory (r/r) B-ALL have been seen with CD19 CAR T cells; however, most trials excluded patients with active CNS disease. As we observed CAR trafficking into the CSF, we hypothesized that CD19 CAR T cells could control CNS B-ALL. Methods: We identified children and young adults with r/r CNS B-ALL treated on 4 clinical trials of CD19 CAR T cells, CTL019 or CTL119. NCT01626495 and NCT02435849 excluded active CNS disease, while the former in an amendment as well as NCT02374333 and NCT02906371 permitted active CNS disease controlled on therapy. All trials permitted CNS disease that cleared and excluded bulky intracranial disease that did not improve. We analyzed outcomes (CR, RFS) and safety. Results: We identified 65 patients 1-29y (median 10y) with r/r CNS B-ALL (CNS+) of 182 treated with CTL019/CTL119. There were no differences in age, sex, history of SCT or neurologic comorbidities in the CNS+ and CNS- cohorts. CNS+ patients were more likely to be in ≥2 nd relapse (74% vs 46%, p &lt; 0.01), to have received cranial radiation (58% vs 11%, p &lt; 0.01), to have detectable CNS disease (p = 0.02) and less bone marrow disease pre-infusion (p &lt; 0.01). At 1 mo post infusion, 62 (95%) CNS+ and 110 (94%) CNS- patients were in CR; 1 in each cohort died of sequelae of CRS and was inevaluable for response. All patients with CNS disease detected pre-infusion cleared by mo 3, including 9 in the CNS+ cohort [5 CNS2 ( &lt; 5 CSF WBC with blasts), 4 CNS3 ( &gt; 5 CSF WBC with blasts or exam/imaging evidence)] and 8 in the CNS- cohort (isolated CNS2 status pre-infusion). There was no difference in RFS (p = 0.28) in the CNS+ and CNS- cohorts [24-mo RFS: 61% (95% CI 46-73%) and 60% (95% CI 48-70%)]. There were 4 CNS relapses in the CNS+ cohort, and 1 in the CNS- cohort. Encephalopathy rate and grade was similar in the CNS+ and CNS- cohorts (52% vs 40% any grade; 12% vs 11% grade 3/4; p = 0.41). There were no deaths due to neurotoxicity (NT) and no statistically significant differences in incidence or severity of any NT or CRS in the CNS+ and CNS- cohorts. Conclusions: The CD19 CAR T cell therapies CTL019/CTL119 are effective at clearing CNS disease and inducing durable remissions in children and young adults with r/r CNS B-ALL. CNS relapse rates are low ( &lt; 3%). Most CD19 CAR T cell trials excluded patients with active CNS disease, primarily due to the risk of NT. We show that patients with r/r CNS B-ALL that is adequately controlled prior to infusion can be safely treated with CD19 CAR T cells, with no increased risk of NT. Clinical trial information: NCT01626495, NCT02435849, NCT02374333, NCT02906371.
Basket study of the oral progesterone antagonist onapristone ER in women with progesterone receptor positive (PR+) recurrent granulosa cell tumor (GCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC).
Authors: Rachel N. Grisham, Karen Li, Alexia Iasonos, Jeffrey Girshman, Karen Anne Cadoo, Chrisann Kyi, Vicky Makker, Seth M. Cohen, Roisin Eilish O'Cearbhaill, Paul Sabbatini, Alison M. Schram, Tiffany A. Troso-Sandoval, Viola N. Chitiyo, Maureen Kennedy, Elena N. Ngangom, Dasom N. Jang, William P. Tew, Sarah Chiang, Carol Aghajanian
Journal: Journal of Clinical Oncology (2020)

TPS6098 Background: Onapristone extended release (ER) is a type I full progesterone antagonist that inhibits progesterone mediated PR activation and stabilizes PR association with corepressors. Onapristone has shown activity across multiple preclinical models of hormonally driven cancer. A phase I dose escalation study of onapristone ER in PR+ breast, endometrial and ovarian cancer patients found all doses tested to be well tolerated, with 50mg PO BID determined to be the recommended phase 2 dose (RP2D). GCT (98% of cases PR+), LGSOC (58% of cases PR+) and EEC (67% of cases PR+) are hormonally driven cancers which generally have poor responses to chemotherapy and limited treatment options in the recurrent setting. Methods: This is an open-label, investigator-initiated basket study of onapristone ER in patients with PR+ recurrent GCT, LGSOC, or EEC currently enrolling patients at Memorial Sloan Kettering Cancer Center in NY, USA (NCT03909152). The primary objective is to evaluate the efficacy, in terms of response rate by RECIST 1.1 criteria, within 36 weeks of treatment. Eligible patients must have received at least 1 prior line of chemotherapy, have measurable disease by RECIST 1.1 criteria, and have tumor tissue collected within 3 years prior to enrollment with PR expression ≥ 1% by IHC. Patients are allowed to have unlimited additional prior lines of chemotherapy, biologic therapy, immunotherapy or hormonal therapy. Enrolled patients are treated with onapristone ER 50mg PO BID until time of progression or intolerable toxicity. The 3 disease cohorts are currently enrolling to Stage I in parallel with expansion from stage I to stage II planned when the prespecified response criteria are met for each cohort as described in the table below. Clinical trial information: NCT03909152. [Table: see text]
CTONG1104: Adjuvant gefitinib versus chemotherapy for resected N1-N2 NSCLC with EGFR mutation—Final overall survival analysis of the randomized phase III trial 1 analysis of the randomized phase III trial.
Authors: Yi-Long Wu, Wenzhao Zhong, Qun Wang, Weimin Mao, Song-Tao Xu, Lin Wu, Chun Chen, Ying Cheng, Lin Xu, Jun Wang, Xiao-Fei Li, Jian Li, Cheng Huang, Zhidong Liu, Shun Xu, Jin-Ji Yang, Hong-Hong Yan, Xue-Ning Yang, Si-yang Liu, Qing Zhou
Journal: Journal of Clinical Oncology (2020)

9005 Background: ADJUVANT-CTONG1104, a randomized phase 3 trial showed adjuvant gefitinib treatment significantly improved disease-free survival (DFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). 5-year survival rate of N1N2 were 38%-50% in IASLC staging system. Here, we present the final overall survival (OS) results from the study. Methods: From Sep 2011 to April 2014, 222 patients, aged 18-75 years, with EGFR activating mutation through completely resection and diagnosed as stage II-IIIA (N1-N2) NSCLC pathologically from 27 sites were enrolled. The enrolled patients were 1:1 randomized to receive adjuvant gefitinib (250 mg once per day) for 24 months (G, n=111) or vinorelbine (25 mg/m 2 , d1 and d8) plus cisplatin (75 mg/m2, d1) every 3 weeks for 4 cycles (C, n=111). The primary endpoint was DFS in the ITT population. Secondary endpoints included OS, 3 and 5-year DFS rate, 5-year OS rate. The subsequent therapy data were collected, including crossover from C to G, re-challenge TKI and other treatment. Data cut-off date was Jan. 13, 2020. Results: A median follow-up was 76.9 months. The median OS (mOS) was 75.5 months based on 95 (42.8%) events in ITT whole population. The mOS was 75.5m in G arm and 79.2m in C arm (HR 0.96, 95%CI 0.64-1.43, p=0.823). The 3, 5-year OS rate were 68.6%, 53.8% in G and 67.5%, 52.4% in C respectively. DFS in 3, 5-y were 40.3%, 23.4% in G and 33.2%, 23.7% in C, respectively (P 3-y =0.395, P 5-y =891). All predefined subgroups including age, gender, lymph node, EGFR mutation type had no significant difference in statistics but in favor of G arm in trend. Subsequent treatment especially targeted therapy contributed most to OS (HR = 0.46, 95% CI 0.26 – 0.83). Median OS of patients receiving subsequent target therapy was75.5m (n=35), 36.4m in other treatment (n=33; (P&lt;0.001). For G mOS were 75.5 (n=15; target therapy) and 35.0 (n=18; other, p&lt;0.001), for C 62.8m (n=20) and 46.8m (n=15; p=0.251). The RR was 26.7%, DCR 66.7%, mPFS 14.1m and mOS 19.6m for patients with rechallenged EGFR TKI in G arm (n=15). No novel unexpected SAE was observed during follow up. Conclusion The DFS survival advantage did not translate to OS difference in ADJUVANT trial. The OS with 75.5m was the best one of survival in completely resected N1N2 NSCLC comparing with historical data and sequent TKI treatment contribute to overall survival. Clinical trial information: NCT01405079.
Effect of standardized three-stage rehabilitation on activities of daily living (ADL) and complications in stroke patients with hemiplegia
Authors: 吴霜, 张继荣, 黄宇, 龙燕, 马丽, 冯丽丽, 李玫, 陈庭凤, 王莲芳, 李玲, 冯晓敏
Journal: BMJ (2005)

目的 探讨三级康复治疗对急性脑卒中患者日常生活能力及上肢并发症的影响.方法80例脑卒中患者随机分为康复组和对照组,每组各40例.在两组患者入选时、发病后1个月末、3个月末、6个月末时进行运动功能、改良Bathel指数及上肢并发症评定.结果发病后1个月末、3个月末、6个月末时运动功能及改良Bathel指数评分康复组明显高于对照组(P＜0.01);将发病后3个月末、6个月末时两组的并发症对比,对照组明显高于康复组,差异有统计学意义(P＜0.05).结论三级康复治疗对脑卒中患者运动功能及日常生活能力的提高,对上肢并发症的预防和治疗有显著意义。
Efficacy of anlotinib in advanced soft tissue sarcoma by age, gender, and ECOG performance status.
Authors: Zhiwei Fang, Yang Yao, Jianqiang Cai, Yihebali Chi, Shusen Wang, Gang Huang, Qiqing Cai, Guanning Shang, Guowen Wang, Guofan Qu, Qiong Wu, Yu Jiang, Jianmin Song, Jing Chen, Zhengdong Cai, Xia Zhu, Chunmei Bai, Yongkui Lu, Zhihua Yu, Jingnan Shen
Journal: Journal of Clinical Oncology (2020)

e23562 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. We evaluated the relationship between age, gender and ECOG performance status. Methods: Median PFS was analyzed in subgroups of age (≤40 y; &gt; 40 y), gender (male; female) and ECOG performance status score (0; 1). All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. 79 patients (50.0%) were &gt; 40 y. Median PFS was longer in patients of age &gt; 40 y than ≤40 y (7.43 vs 5.43 months, P = 0.40). In patients receiving anlotinib, 76 patients (48.1%) were female and median PFS was longer in female than male (9.80 vs 4.43 months, P = 0.002). All enrolled patients had a Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 107 patients (67.7%) were with poor PS (ECOG PS = 1). The median PFS was longer in PS of 1(8.43 vs 4.73, P = 0.53) than PS of 0. Conclusions: In patients receiving anlotinib, longer mPFS was observed in patients of age &gt; 40 y, ECOG PS = 1 and female. Clinical trial information: NCT02449343 .
Retroperitoneal laparoscopic operation for aldosterone-producing adenomas: a report of 205 cases
Authors: Kun-long Tang, Chang-hai Yang, Li-ming Li
Journal: BMJ (2011)

Two hundred and five patients with a confirmed diagnosis of aldosterone-producing adenomas underwent retroperitoneal laparoscopic operation from January 1999 to December 2009 in our hospital. All cases had hypokalemia and hypertension preoperatively. Of all the cases, 80 received total adrenalectomy and 125 received partial adrenalectomy. Operations were successfully performed in all cases. The time of operation ranged from 15 to 150 min [mean(45 ±13) min] and the volume of bleeding during operation ranged from 10 to 200 ml [mean(25 ±10) ml]. The length of hospital stay ranged from 4 to 9 d [mean(6. 8 ± 1. 2) d]. All patients were followed up for 0. 5 - 2 years (mean 1. 2 years). After operations blood potassium levels returned to normal in all cases, blood pressure returned to normal in 168 cases (82.0% ) . Results indicated that partial or total adrenalectomy with retroperitoneal laparoscopy for aldosterone-producing adenomas was safe and feasible technique.

Key words: 
Hyperaldosteronism;  Laparoscopy
Establishment of general-special integrated prevention and treatment model for chronic obstructive pulmonary disease patients in community and its preliminary effect
Authors: Xinping Wei, Jin Qiu, Zhigang Pan, Yuanlin Song, Xiwen Gao, Weigang Wang, Suhua Yang
Journal: BMJ (2019)

A general-special integrated prevention and treatment model for chronic obstructive pulmonary disease (COPD) patients in the community was preliminarily established with the joint effets of specialists from the terital hospital and general practitioners in the community health service center. During the implementation of the model the general practitioners recieved research training and participanted in the research project of COPD management; and the general-special integrated outpatient clinic greatly improved the management for COPD patients. Since the establishment of the model, the number of acute attacks of COPD patients was decreased, and the proportion of standardized medication was increased. The model also improved the research ability and clinical competency of general practitioners. The established model provides experiences for the tiered-management for COPD patients in the community.


Key words: 
Pulmonary disease, chronic obstructive; Community health services
下肢主干血管损伤31例
Authors: 潘振宇, 喻爱喜, 余国荣, 谭金海, 祝少博, 陶圣祥
Journal: BMJ (2006)

多种原因所致的下肢主干血管损伤,病情危急,处理不当易导致严重后果.因此,如何使血管再通和尽可能恢复患肢功能十分重要.我科自1998年6月至2004年12月共收治下肢主干血管损伤患者31例,疗效较好,现报告如下。
Patterns of Twitter use among trainees in hematology-oncology related areas.
Authors: Miguel Gonzalez Velez, Narjust Duma, Daniel Cabrera, Ariela L. Marshall, Deanna J. Attai, Merry Jennifer Markham, Rafael Fonseca
Journal: Journal of Clinical Oncology (2020)

11041 Background: Twitter (TW) is an essential tool in the medical community. Few studies have examined the use of TW by medical trainees. We aimed to assess its utilization among trainees in hematology-oncology related areas (HORAs). Methods: 576 training programs in HORAs were obtained. We contacted a potential pool of 3,142 trainees. A 50 item survey was distributed between 2/2019-5/2019, focusing on: demographics, professional use, attitudes toward TW, and patient interactions. Responses were analyzed using parametric descriptive statistics. Results: 442 responses (14% response rate) were received; 203 (46%) used a TW account for professional activities. See table for demographics. The most common reasons for using TW were: continuous education (73%), dissemination of information (62%), and networking (62%). &gt; 80% of users have positive views on using TW for: promoting academic discussions (92%), trainees education (89%), and conference networking (83%). 50 (25%) have used TW for collaborations, with abstracts and papers being the most common (20%). Most agreed or strongly agreed that TW: is a useful education tool (89%), and might be useful for career advancement (85%). The most common challenges were: the value of TW content can be decreased by irrelevant content and biased sources (64%), not peer-reviewed (51%), and difficulty searching information (50%). 68% considered that programs should promote the engagement of trainees, but only 21% reported instruction in the use of TW. 83% agree or strongly agree that TW is useful for physicians and patient interactions, but 82% have concerns about legal repercussions. Conclusions: Almost half of trainees in HORAs use TW for professional activities. The most common uses are for education, dissemination of information and networking. Most trainees that use TW have positive views regarding education and academic collaborations. Use of Twitter may strengthen trainees’ education, provide mentorship opportunities, and promote career advancement. Challenges on TW use should continue to be addressed. [Table: see text]
Intergration of common clinical and laboratory parameters for predictive modeling of outcome with immune checkpoint inhibitors (ICIs) in patients (pts) with Nnon-small cell lung cancer (NSCLC).
Authors: Konstantinos Rounis, Dimitrios Makrakis, Chara Papadaki, Alexia A Monastirioti, Lampros Vamvakas, Kostas Kalbakis, Krystallia Gourlia, Iordanis Xanthopoulos, Dimitrios Mavroudis, Sofia Agelaki
Journal: Journal of Clinical Oncology (2020)

e21609 Background: We prospectively recorded common clinical and laboratory parameters of pts with metastatic NSCLC treated with 2 nd line ICIs to evaluate their potential value in a clinical outcome prediction model. Methods: Data on patient (age, PS, BMI) and disease characteristics (histology, sites/number of metastases), smoking status, use/duration of co-medications [proton pump inhibitors (PPIs) inhalational/p.os steroids, antibiotics (ATB)], laboratory values [neutrophil/lymphocyte ratio (NLR), LDH] and response to previous therapy were prospectively collected. Pts were categorized as having steroids if they had received steroids &gt; 10mg for ≥10d (starting from 15d before or within the first 3 months of treatment). Prolonged ATB administration was defined as ATBs ≥14d (30d before or within the first 3 months). JAD Bio (www.jadbio.com), an Automated Machine Learning service that analyzes biological data with emphasis on feature selection was used to create predictive models. Results: 66 pts were evaluated; median follow up time was 6.37 months. 15.2% of patients had PR, 34.8% SD and 50% PD. Median PFS and OS were 3.5 and 6.77 months, respectively. Steroids had negative impact on disease stabilization (PR+SD) rates (p = 0.042) and PFS (p = 0.013) but not OS (p = 0.051). ATBs negatively affected RR (p = 0.046) only, whereas, prolonged ATB exposure was associated with lower RR (p = 0.007), PFS (p = 0.0001) and OS (p = 0.001). In multivariate analysis, steroids [HR = 2.54 (CI:1.23-5.29, p = 0.012)], prolonged ATBs [HR = 3.46 (CI:1.72-6.95, p = 0.0001)], liver HR = 2.92 (CI:1.45-5.78, p = 0.003) and bone HR = 2.06 (CI:1.041-4.10, p = 0.038) metastases independently predicted for shorter PFS. Only prolonged ATBs [HR = 2.52 (CI: 1.39-4.54, p = 0.002)] and bone metastases [HR = 2.26 (CI: 1.23-4.17, p = 0.009)] independently predicted for shorter OS. Analysis of the investigated parameters by JAD Bio predicted disease stabilization with an accuracy of 71%. Importantly, PDL-1 status was not included due to high rates of missing data. Conclusions: Our results corroborate previous evidence on the detrimental role of prolonged ATB administration on ICIs efficacy, possibly related to perturbation of the gut microbiota. Modeling, including other significant parameters from larger patient cohorts, could result in a robust estimation of outcome.