tbuckley/cabot-search huggingface dataset:
Multiple immune features based signature for predicting recurrence and survival of inoperable la-NSCLC patients.
Authors: Meiying Guo, Wanlong Li, Bingjie Fan, Bing Zou, Xindong Sun, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2020)

e21066 Background: The immune status of tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients. Methods: In this study, 100 patients who were diagnosed as inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A 5-immune feature-based signature was then constructed using the nested repeat 10-fold cross validation with LASSO Cox regression model. Nomograms were then established for predicting prognosis. Results: Immune signature combining 5 immuno-features were significantly associated with OS and PFS (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of -0.198 stratified patients into two groups with 5-year OS rates of 39.8% and 8.8%, and 2-year PFS rates of 22.2% and 5.5% for the high- and low-immune signature groups, respectively. Using immune signature, we proposed immune signature nomograms, which were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that immune signature plays a complementary role in the prognosis prediction of patients with inoperable LA-NSCLC. Conclusions: Multiple immune features based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients, and complemented the prognostic value of the TNM staging system.
Patient-reported outcomes integrated within electronic medical record in patients with head and neck cancer.
Authors: Stephanie Ossowski, Amy Kammerer, Ethan M. Basch, Jed Abraham Katzel
Journal: Journal of Clinical Oncology (2020)

e14026 Background: Patient-reported outcome (PRO) tools have been shown to improve outcomes including overall survival for cancer patients. However, routine implementation of PROs in clinical practice within the electronic medical record (EMR) remains limited. We studied the use of a PRO tool for patients with head and neck cancer (HNC) integrated in an EMR. Methods: Between August 2017 and December 2019 patients with newly diagnosed HNC were surveyed at baseline, then every 3 months using the FACT-G7 and FACT H&amp;N (Version 4). A medical assistant (MA) performed a baseline survey around the time of diagnosis and then notified patients electronically every 3 months for two years and then every 6 months until patients completed their 5 years of surveillance. Patients who did not respond to online PRO surveys could complete them via telephone appointments with MAs, or in office pre-rooming. Abnormal findings on PRO surveys were referred to appropriate members of the care team or the treating ENT physicians. Results: 290 patients received baseline surveys. Patients received up to a maximum of 8 subsequent surveys (table). Out of a total of 597 electronic surveys, 585 (97.9%) were completed. The percentage of patient completing each survey ranged from 92-100%. Conclusions: PRO tools can be effectively deployed within the EMR for HNC patients with a high completion rate provided that there is strong engagement from a dedicated member of the care team. This has important implications for designing clinical trials and symptom monitoring in clinical practices that incorporate EMRs.
Prevalence and trends of sensitisation to aeroallergens in patients with allergic rhinitis in Guangzhou, China: a 10-year retrospective study
Authors: 王玮豪, 黄雪琨, 陈壮桂, 郑瑞, 陈玉莲, 张革化, 杨钦泰
Journal: BMJ (2016)

目的
了解广州地区变应性鼻炎（AR）门诊患者中常见吸入性变应原阳性率及观察过去10年的变化趋势。


设计
回顾性分析；线性趋势检验和简单线性回归分析吸入性变应原阳性率的变化趋势。


研究设置
中国广州一家三级医疗机构。


研究对象
2005年1月至2014年12月期间来耳鼻喉科门诊就诊的鼻高反应症状患者有5 486例（男性2 997例，女性2 489例），所有患者均已接受血清变应原特异性免疫球蛋白E（sIgE）检查。其中有4 085例患者（男性2 269例，女性1 816例）诊断为AR。


主要结局测量
各种常见吸入性变应原的阳性率及10年变化趋势。


结果
AR患者中各种常见吸入性变应原的sIgE阳性率依次是：屋尘螨（HDMs）84.4%，宠物变应原组合23.4%，蟑螂21.1%，霉菌组合9.1%，树木花粉组合7.7%，草本花粉组合6.0%。鼻高反应症状患者中随着年龄增长10岁，变应原sIgE阳性率下降5.13%[95%可信区间（CI）：-7.28%~-2.98%，P<0.01]。过去10年AR患者的宠物变应原组合阳性率逐年上升1.3%（95%CI：0.85%~1.67%，P<0.01）。


结论
HDMs是广州地区最常见的吸入性变应原，变应原阳性率随年龄增加而逐渐下降。过去10年中宠物过敏情况呈上升趋势，应加强对宠物变应原预防及治疗的重视。
EndoTAG-1 plus gemcitabine versus gemcitabine alone in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas failed on FOLFIRINOX treatment (NCT03126435).
Authors: Li-Tzong Chen, Muh-Hwan Su
Journal: Journal of Clinical Oncology (2020)

TPS4669 Background: Pancreatic cancer (PC) is the 3 rd deadliest cancer in the United State surpassing breast cancer in 2016, with the overall survival rate of - 9% for those newly diagnosed individuals. The notorious disease is set to become the 2 nd leading cause of death from cancer by 2020 in US (National Cancer Institute, NIH). FOLFIRINOX regimen is one of the standard 1 st -line treatments for PC patients with good performance status; however, there is currently no standard of care in 2 nd -line therapy after FOLFIRINOX failure. EndoTAG-1 is a novel formulation of cationic liposomes embedded with Paclitaxel, which specifically displays antivascular and antiangiogenic activities. By binding and internalizing at tumor endothelial cells after intravenous administration, the cytostatic activity of paclitaxel will be targeted to the activated tumor endothelial cells. Methods: Eligible patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas failed on FILFIRINOX treatment will be screened and randomized (1:1) into one of the two arms in the study (n=218). The primary endpoint of the study is overall survival (OS), with secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and quality of life (QoL). Arm A: EndoTAG-1 plus Gemcitabine: Patients will receive intravenous injection with EndoTAG-1 (22 mg/m 2 ) twice weekly plus gemcitabine (1,000 mg/m 2 ) once weekly for consecutively 3 weeks followed by 1 week rest. The treatment will be repeated every 4 weeks, with 8 weeks per cycle. The treatment will be kept until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent. Arm B: Gemcitabine: Patients will receive gemcitabine (1,000 mg/m 2 ) once weekly for consecutive 3 weeks followed by 1 week rest. The treatment will be repeated every 4 weeks, with 8 weeks per cycle. The treatment will be kept until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent. The phase III trial began enrollment since November 2018. The trial will continue as planned from the last review in January 2020. Clinical trial information: NCT03126435 .
A phase III randomized study of neoadjuvant chemotherapy (NAC) alone or in combination with nivolumab (NIVO) ± linrodostat mesylate, followed by adjuvant postsurgical NIVO ± linrodostat, in cisplatin-eligible muscle invasive bladder cancer (MIBC).
Authors: Guru Sonpavde, Andrea Necchi, Shilpa Gupta, Gary D. Steinberg, Juergen Gschwend, Michiel Simon Van Der Heijden, Audrey Richiero, Alexandre Lambert, Bradley Raybold, Srikanth Gajavelli, Dimitrios Zardavas, Matt D. Galsky
Journal: Journal of Clinical Oncology (2020)

TPS5091 Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible, muscle invasive BC (MIBC), the recommended tx is cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, supporting the therapeutic pursuit of the PD-1/PD-L1 axis. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. Linrodostat mesylate, a selective, potent, once-daily oral IDO1 inhibitor that works to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + linrodostat in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± linrodostat followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + linrodostat (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320 .
Study on policies to implement proper technology of traditional Chinese medicine in communities in central city of Shanghai
Authors: Zhao-hui Du, Hui-zhen Peng
Journal: BMJ (2010)

We studied policies of traditional Chinese medicine (TCM) on four levels ( national,Shanghai city, Pudong New District and community health services (CHS)) from 2008 to 2009 with the method of literature review,questionnaire survey and group interview. 18 national, 5 Shanghai's, 4 Pudong New District's and 87 CHS' TCM related policies were identified. By defining the development target,financial capability, human resource and proper technology of TCM care, those policies ensured and prompted the progression of community TCM services. Yet TCM policy fulfill in community remained lagged,and talent cultivating, medical insurance support and TCM participating in public health needed to be improved.

Key words: 
Community health services;  Health policy;  Proper technology of traditional Chinese Medicine
ctDNA from ascites as an alternative to tumor sampling for HRD (homologous recombination deficiency) testing in ovarian cancer (OC).
Authors: Alexandra Leary, Reda el Hazzaz, Audrey Le Formal, Elodie Lecerf, Chloé Brizais, Emeline Colomba Blameble, Sebastien Gouy, Amandine Maulard, Yannick Boursin, Patricia Pautier
Journal: Journal of Clinical Oncology (2020)

6066 Background: Knowledge regarding HRD status is becoming crucial to guide maintenance strategies for patients with newly diagnosed OC. Unfortunately, for patients (pts) treated with neoadjuvant chemotherapy (NACT), HRD testing on small biopsies from diagnostic laparoscopies (Dx Lap) or interval debulking has a high failure rate. At relapse, biopsies may not be feasible. Aim: Evaluate the feasibility and usefulness of HRD testing on cfDNA from ascites Methods: Pts enrolled in a prospective biological study (OvBIOMark) consented to analysis of biological samples obtained as part of routine diagnosis. cfDNA was extracted from 1-2ml of double-centrifuged fresh ascites and subjected to 1) targeted NGS including the most common somatic mutations in high grade ovarian cancer ( TP53) to confirm presence of tumor cfDNA and 2) SNParray for copy number (CN) analyses to calculate a genomic instability score (GIS) for HRD. Results: Thirty four ascites samples were collected from 25 pts with suspected or confirmed OC. For 15/25 pts samples were obtained at Dx Lap, and for 10 pts samples were obtained at relapse. Seven pts underwent repeat ascitic drains during treatment or at relapse. 97% (33/34) of ascitic samples had detectable cfDNA (median = 980ng, range:80-5730ng) even when obtained during chemotherapy. A deleterious mutation was identified in 87% (29/33) of samples with high allelic frequencies (median allelic frequency, AF = 60%; 3.3-87%), confirming that most of detected cfDNA was tumoral. The most common mutation was a TP53m (86%; 25/29). We have performed CN analysis on cfDNA from ascites on 17 of these patients to evaluate their HRD status. Ten pts had a high GIS (HRD+), and 7 pts a low GIS (HRD-). The 4 pts with confirmed BRCAm included in this study had a high GIS on ascites. When available from the same patient, the CN profiles derived from ascites cfDNA and tumor sampling were superimposable. Conclusions: Ascites yields large amounts of cfDNA, which can be confirmed as tumoral based on TP53 mutation detection. CN analysis on ascitic cfDNA is feasible and can be used to detect the same HRD scar as tumor testing. Ascites is frequent at diagnosis, especially in pts with inoperable disease planned for NACT and could provide a useful alternative to tumor for HRD and BRCA testing.
Low rates of <i>BRCA1</i> and <i>BRCA2</i> testing for patients with ovarian cancer in ASCO's CancerLinQ, a real-world database.
Authors: Summer Dewdney, Danielle Potter, Joy Larsen Haidle, Peter J Hulick, Mark Riffon, Federico A. Monzon, Sameer R. Keole, Robert S. Miller
Journal: Journal of Clinical Oncology (2020)

6041 Background: Ovarian cancer is the deadliest gynecological cancer and has limited screening options for early stage diagnosis. Genetic mutations in genes such as BRCA1 and BRCA2 increase the risk of ovarian cancer, and if identified, patients can undergo risk-reducing surgery. It is recommended and well accepted to test any new ovarian cancer patient for genetic mutations, particulary BRCA1 and BRCA2. If a BRCA1/2 mutation is found in a patient (somatic or germ line), this information can be used to guide therapy. We sought to analyze the characteristics of genetic testing in a real-world database, ASCO’s CancerLinQ. Methods: We performed a retrospective cohort study using the CancerLinQ Discovery database. Women with ovarian, fallopian tube, or primary peritoneal cancer were identified using ICD9 and ICD10 codes. We included patients diagnosed between 1/1/11 to 12/31/18 and age &gt;18. We included all epithelial histologies including carcinosarcomas and excluded patients without a known histology. Results: Of the 2654 patients meeting inclusion criteria, 600 had been tested for a BRCA1/2 mutation (22.6%). Of those tested, 63% were stage III/IV, 14% stage I/II, and 21.8% an unknown stage. The majority of the histologies were serous (76%), followed by undifferentiated (21.2%). The majority of patients tested were white (69.9%), with 18.8% unknown, and 9.9% black. The rate of a positive BRCA1 or BRCA2 mutation in this population was 17.2%. Of the patients with a BRCA1/2 mutation, the majority had serous histology (87%), followed by 18.5% undifferentiated, and 3.9% transitional cell. The majority of the patients found to have a BRCA1/2 mutation were age &gt;50 (57.3%). Conclusions: Since 2008 evidence-based guidelines have recommended that all ovarian cancer patients be tested for BRCA1 and BRCA2 mutations, but in this real-world database only 22.6% have a recorded test. Of those tested, we found a BRCA1 or BRCA2 mutation rate of 17.2%. Our data is limited by what is recorded in the database and may not represent the true number of patients tested because of data missing from the EHR; however, these percentages appear similar to previous studies. Not only is testing important for cancer prevention for family members of patients, it now impacts the type of treatments for which these patients are eligible. Since genetic testing remains low at only 22.6% in this population, significant opportunities exist to impact cancer prevention and treatment.
小儿胃食管反流病461例临床和内镜分析
Authors: 游洁玉, 赵红梅, 唐硕, 刘莉, 段柏萍
Journal: BMJ (2011)

回顾分析2003年7月至2009年9月湖南省儿童医院诊治的461例胃食管反流病((GERD)患儿的临床资料,以进一步了解儿童反流性食管炎(RE)的临床和内镜检查特点. 一、临床资料 1.一般资料:2003年7月至2009年9月本院对1866例患儿行食管下段24 h pH值监测确诊GERD 573例,对其中461例患儿行电子胃镜检查.461例中男282例,女179例,年龄6个月～16岁,平均(8±3)岁,病程7 d～12年,平均(21±9)个月.临床表现:呕吐361例,反复呼吸道感染76例,腹痛43例,酸反流42例,呕血 104例,胸部不适及胸骨后疼痛29例.另外诊断食道裂孔疝57例,幽门螺杆菌(HP)感染93例。
Phase I dose-finding study of oral ERK1/2 inhibitor LTT462 in patients (pts) with advanced solid tumors harboring MAPK pathway alterations.
Authors: Filip Janku, Elena Elez, Gopa Iyer, Noboru Yamamoto, Daniel Shao-Weng Tan, Anastasios Stathis, Uz M. Stammberger, Helen Evans, Abdelkader Seroutou, Anna Mais, Martin H. Schuler
Journal: Journal of Clinical Oncology (2020)

3640 Background: LTT462 is an investigational small molecule inhibitor of ERK1/2, which has demonstrated preclinical activity in multiple MAPK activated cancer cells and xenograft models. This first-in-human study was designed to evaluate the safety and tolerability of LTT462 in advanced solid tumors harboring MAPK pathway alterations (NCT02711345). Methods: The dose-escalation part of this Phase I, open-label study, enrolled adult and adolescent pts with advanced solid tumors harboring ≥1 documented MAPK pathway alteration with progressive disease (PD) despite standard therapy, or for whom there is no effective standard treatment. Oral LTT462 was given once daily (QD) at 45–600 mg or twice daily (BID) at 150 mg or 200 mg. Objectives were to determine the maximum tolerated dose (MTD) using a Bayesian hierarchical logistic regression model guided by escalation with overdose control, and characterize safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of LTT462. Results: Sixty-five pts (median age 60 years) including 1 pt aged 15 were enrolled in the dose-escalation; most pts (22%) had 3 prior therapies. Most common primary sites for cancer were in the colon (n = 21; 32%), ovary (n = 9; 14%), and pancreas (n = 7; 11%). All pts discontinued, the majority due to PD (n = 44; 68%). Eleven pts experienced DLTs; 6 pts experienced Grade 3 eye disorder DLTs (4 pts retinopathy, 2 pts chorioretinopathy). Treatment-related adverse events (TRAEs) were reported for 89% of pts, most commonly ( &gt; 30%) diarrhea (n = 25; 38%) and nausea (n = 22; 34%). Grade 3/4 TRAEs were reported in 29% of pts; most common was retinopathy (n = 4; 6%). MTD of LTT462 was 400 mg QD and 150 mg BID. Overall, 8 pts (12%) had stable disease (SD) and 35 pts (54%) had PD. An unconfirmed partial response was reported in a pt with cholangiocarcinoma with BRAF mutation; best change in sum of target lesions per RECIST 1.1 was -33.9%. LTT462 increased plasma peak drug concentration and drug exposure at increasing doses between 45–450 mg QD. Exposure at LTT462 600 mg QD was lower than anticipated, indicating potential saturation of absorption at this dose. LTT462 inhibited ERK1/2 and reduced DUSP6 expression relative to baseline in most pts evaluated. Conclusions: LTT462 is well tolerated. Limited clinical activity was reported with single agent LTT462; best overall response was SD. An ongoing study is investigating LTT462 in combination with the RAF inhibitor, LXH254, in NSCLC and melanoma. Clinical trial information: NCT02711345 .
Immunotherapy in patients with advanced stage non-squamous (non-Sq) non-small cell lung cancer (NSCLC) with activating genetic mutations: Single institution retrospective study.
Authors: Leila Khaddour, Sunny R K Singh, Igor I. Rybkin
Journal: Journal of Clinical Oncology (2020)

e21577 Background: Immunotherapy has dramatically changed the landscape of lung cancer management. However, its efficacy remains controversial in patients with activating mutations. We report retrospective analysis of clinical outcomes of advanced stage NSCLC patients with activating mutations treated with immune checkpoint inhibitors throughout their disease course. Methods: We analyze all adult patients diagnosed with advanced NSCLC in our institution between January 2014 and January 2018, and who had activating mutations in EGFR, MET, or BRAF genes or ALK rearrangement. Patients in both arms must be treated with at least one line of tyrosine kinase inhibitors (TKI). The investigation arm were patients who received immunotherapy at any time during their disease course. The control arm were patients who did not receive immunotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate (ORR) and disease control rate (DCR) in the investigation arm. Results: A total of 47 patients met the inclusion criteria: 27 patients received immunotherapy after or before TKI failure, while 20 patients did not receive immunotherapy. Baseline characteristics were similar in both groups. The average age at diagnosis was 65 years and 40% were males. 68% of patients were at stage IV at the time of diagnosis, 43% were never smokers, and 40% had brain metastases. EGFR mutations accounted for 76.6% of alterations, while ALK rearrangement was demonstrated in 17%, MET and BRAF mutations in 4.3% and 2.1% respectively. Among 27 patients in the immunotherapy group, 3 received chemotherapy simultaneously, 11 patients had received prior chemotherapy, while 13 patients were chemotherapy naive. Complete response was achieved in one case. The ORR was 22.2% and DCR was 37%. Targeted therapy was re-introduced in 9 patients after discontinuation of immunotherapy, of whom 3 responded. The median OS was 44 months (95%CI 28.9-59.4) in immunotherapy group versus 35.7 months (95% CI 23.9-47.4) in control group (P-value 0.34). Conclusions: Immunotherapy, as single agent or in combination with chemotherapy, is associated with better OS trend in patients with advanced NSCLC who harbor activation mutations and failed TKI. This effect was not statistically significant. The prospective data in this population is also limited and controversial. More trials are warranted to evaluate the efficacy of immunotherapy in this group.