tbuckley/cabot-search huggingface dataset:
Identifying and overcoming clinical trial enrollment barriers: Can an integrated clinical pathways tool help bridge the gap?
Authors: Mishellene McKinney, Cynthia Samborski, Nessa Stefaniak, Monica L. Murphy, Stephen B. Edge, Kristopher Attwood, Lu Liu, Stephen Lash, Wei Yu, Katherine Eakle
Journal: Journal of Clinical Oncology (2020)

2046 Background: Barriers to clinical trial (CT) enrollment continue to be a national challenge, with only about 3% of adult cancer patients treated within a CT. A key recommendation from the 2013 NCI-ASCO Cancer Trial Accrual Symposium was to use information technology to enhance identification of potentially eligible patients for CTs. We assessed if the implementation of a Clinical Oncology Pathways System (COP) with integrated CT information increased enrollment of CT’s, and categorized physician-identified reasons for non-enrollment. Methods: In 2018, Roswell Park Comprehensive Cancer Center (RP) implemented ClinicalPath pathways (formerly Via Oncology) for medical oncology. The COP software embeds interventional CTs that are open to accrual at RP in the pathway specific to a patient’s disease type, stage and biomarkers. The provider is presented with relevant CTs and must select screening for the trial or provide a reason for bypassing the CT from a drop-down list prior to being presented standard care options. CT screening requests from the COP system from 6/1/18-5/31/19 were reviewed. Screening requests and actual enrollment data were matched. The accrual-to-study ratio (ASR), defined as the number of consented accruals divided by the number of CTs open to accrual at RP at any time during the period, was calculated for the study period and the baseline from 6/1/14-6/1/18. The reasons physicians did not elect to screen for CTs were summarized. Results: There can be multiple trials presented for each pathway decision.There were 1,606 decision points with at least one embedded trial. Of these, 1,289 decision points matched 2,242 CTs that were not selected for screening. 317 trials were selected for screening. The most common reasons for not screening were patient ineligibility (41%), provider bypassing the CT by selecting treatment “off pathway” (28%), patient not interested (12%), patient already on CT (8%) and “other” (9%). Audits confirmed that the majority of ineligible patients had co-morbidities such as organ dysfunction or brain metastasis that precluded them from the CT. Among the 317 trials selected for CT screening, 108 (34%) patients enrolled in CTs. The ASR increased from the four-year historical average baseline of 4.08 to 4.33 one year post-implementation. Conclusions: The use of COP with embedded CT was associated with a modest increase in ASR. Stringent eligibility criteria was the primary barrier to enrollment. Adopting a broader set of clinical trial eligibility criteria could increase enrollment to CT.
Treatment modalities and outcomes in patients with rectal cancer (RC) in a referral center in Mexico.
Authors: Vanessa Rosas Camargo, Hector Buerba, Perla Lizeth Martinez Cruz, Luis Guillermo Anaya Sánchez, Alberto Cedro-Tanda, Rosa Caballero, Zuleyma Nieto Garcia, Mónica Isabel Meneses Medina, Christian Haydeé Flores Balcázar, Armando Gamboa Dominguez, Noel Salgado Nesme, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2020)

e16105 Background: Regarding cancer care, health system in Mexico is characterized by heterogeneous medical and technical infrastructure among institutions. Limited access to specialized surgeons, radiation therapy and medications may differ and affect survival. Our institution has surgeons, medical oncologists and radiation therapy for the treatment of uninsured low-income patients with RC. The institution does not provide chemotherapy or biologic therapy. Our aim was to describe treatment modalities and outcomes in patients (pts) with RC treated in a referral center in Mexico. Methods: A retrospective database of all consecutive pts with histological diagnosis of rectal adenocarcinoma evaluated at our institution from January 2010 to December 2016 was created. Clinical and pathological variables at diagnosis and treatment modalities were recorded. Overall survival (OS) was estimated using Kaplan-Meier method and compared by log rank test. Results: 99 pts were included, 61.6% male gender. Median age was 61 y/o (range 19 – 97). EGOG PS 0 – 1: 86%. 69% were moderately differentiated. Tumor location: lower (25%), middle (57%), and upper third (18%). Clinical stage (CS) was localized (T1-2, N0 M0) 5%, locally advanced (T3-4, or N+) 71% and advanced (M1) 24%. Treatment modalities (TM) by stage are presented in the Table. For those with advanced disease, 58% had metastasis in one site. RAS and BRAF mutation determination was performed in 21%. 5-year survival rate: 56%. Median OS (months): 25.3 for localized, 103.1 for locally advanced and 18.6 for advanced disease (P = 0.001). Conclusions: In our center, pts with local and regional RC had treatment according to international guidelines and survival was not compromised. On the contrary, limited access to systemic therapy affected patients with advanced disease and decreased survival was documented. To improve survival in patients with advanced disease, health policy adjustments to incorporate systemic treatment coverage are required. [Table: see text]
Development and validation of the PREMMplus clinical prediction model for multigene hereditary cancer risk assessment.
Authors: Matthew B. Yurgelun, Hajime Uno, C. Sloane Furniss, Chinedu I. Ukaegbu, Miki Horiguchi, Anu B. Chittenden, Tara Fehlmann, Amal Yussuf, Holly LaDuca, Judy Ellen Garber, Sapna Syngal
Journal: Journal of Clinical Oncology (2020)

1579 Background: Current clinical prediction models provide syndrome-specific numeric estimates of an individual's likelihood of having a specific hereditary cancer syndrome (e.g., PREMM 5 for Lynch syndrome; BRCAPRO for BRCA1/2). With the emergence of multigene panel testing (MGPT), there is a need to evaluate individuals' risk of carrying a pathogenic variant in a diverse array of cancer susceptibility genes in parallel. This study’s aim was to develop and validate the PREMMplus clinical prediction model for multigene cancer risk assessment. Methods: PREMMplus was developed in a cohort of 7296 individuals who had undergone germline MGPT at a single center. Logistic regression models were used to examine candidate predictive variables – including age, sex, ethnicity, and personal/family history of cancer – to provide a numeric estimate of an individual’s likelihood of carrying a pathogenic/likely pathogenic germline variant in one of 18 cancer susceptibility genes (11 high- [ APC, BRCA1/2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53] and 7 moderate-penetrance [ ATM, CDKN2A, CHEK2, PALB2, PTEN, RAD51C, and RAD51D]). Model performance was validated in an independent dataset of 14845 individuals who had undergone MGPT at a commercial laboratory. Results: Using clinical characteristics, including personal/family history of 18 cancers plus colorectal adenoma burden, PREMMplus demonstrated an excellent ability to predict pathogenic variants in high penetrance genes at 90% sensitivity. PREMMplus had acceptable performance with the addition of 7 moderate penetrance genes. PREMMplus was well-calibrated and demonstrated comparable performance in the external validation dataset. Conclusions: PREMMplus is the first validated risk assessment model to quantify an individual’s likelihood of carrying pathogenic variants in a wide diversity of cancer risk genes, and can be used to select individuals who should undergo MGPT. As expected, PREMMplus’s discriminatory capacity was reduced with the inclusion of moderate penetrance cancer risk genes. [Table: see text]
Trifluridine/tipiracil or regorafenib in refractory metastatic colorectal cancer patients: An AGEO prospective “real life” study.
Authors: Clélia Coutzac, Isabelle Trouilloud, Pascal Artru, Julie Henriques, Thérese Masson, Christelle De La Fouchardiere, Solene Doat, Olivier Bouché, Romain Coriat, Angelique Saint, Valérie Moulin, Dewi Vernerey, David Tougeron, Julien Taieb
Journal: Journal of Clinical Oncology (2020)

4036 Background: Regorafenib (R) and trifluridine/tipiracil (T) have proved their efficacy in patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy and targeted therapies. However, it remains unclear which drug should be administered first. Methods: This observational study was prospectively conducted in 13 centers between 6/2017 and 9/2019 in France. All consecutive pts with chemoresistant mCRC and receiving T and/or R were eligible. The aim of this study was to describe efficacy and tolerability of T and/or R. Overall survival (OS) and progression-free survival (PFS) of pts receiving T then R (T/R) and the opposite sequence (R/T) were also assessed. Results: A total of 237 pts (25% R and 75% T) were enrolled (109 male, median age: 67 years (32-91), mean previous lines of treatment: 2.5 (1-7)). Baseline ECOG PS was 0-1 in 77% of pts. As compared to R pts, T pts were significantly older (68 years vs 63; p = 0.033) and with &gt; 3 metastatic sites (44% vs 30%, p = 0.018). Median OS were 6.6 and 6.2. months in the T and R group, respectively (NS). Median PFS were 2.4 and 2.1 months in the T and R group, respectively (NS). After matching 46 paired pts according to primary tumor resection, age and number of metastatic sites, a trend to a longer OS (9.5 vs 6.8 months; p = 0.17) and a significantly longer PFS (2.8 vs 2 months; p = 0.048) were observed in the T group. Among the overall population, 24% of pts received R/T or T/R sequence. Median OS from first treatment were 10.7 months in the R/T group and 9.8 months in the T/R (NS). Treatment sequence was not an independent prognostic factor for OS or PFS in multivariable analysis. Tolerability profiles were similar to previously published data, but dose reductions were more frequent in the R group (44 vs 27%, p = 0.008). Conclusions: Efficacy and safety results in this real life prospective study are in line with those published phase III trials. Both treatments seem similar in term of efficacy favoring T for clinical use as shown by the higher number of patients receiving this drug.
Effect of different dox concentration with hapten and dose selection intratumoral injection on the survival time of tumor bearing mice.
Authors: Qiang Fu, Yan Han, Baofa Yu
Journal: Journal of Clinical Oncology (2020)

e15517 Background: To explore the effect of chemotherapeutic drug (Dox) with the concentration on the survival of tumor-bearing mice after intratumoral injection plus hapten. It is important to observe whether there is any difference in survival rate between the different dose of drug-administered group with hapten and the positive control group. Methods: The H22 liver tumor-bearing mice with the longest path length of tumors of 5-8 mm were selected and administered according to the tumor volume. The second dose was administered at intervals of 7 days. The death of the mice was observed daily and the time of death was recorded in order to evaluate the survival of the mice. Results: The effect on body weight, except for the negative control group, decreased in weight after the first administration, and the effect was reversible. The effect on tumor volume was significantly slower than that of the negative control group after administration. In the life extension rate study, the sustained-release drug group was compared with the corresponding positive control group, the sustained-release drug group II and the positive control group II, the sustained-release drug group IV group and the positive control group IV group, and the sustained-release drug group V and The positive control group V had significant significance (P &lt; 0.01). Therefore, the survival time of the group IV of the sustained-release drug was better than that of the positive control group IV, and the dose of the group IV of the sustained-release drug was the optimal dose. Conclusions: The reduction of doxorubicin hydrochloride concentration can prolong the survival time of mice and the survival rate of the sustained-release drug group with hapten is generally higher than that of the positive control group. By comparing the tumor inhibition rate and survival test results of the slow release drug group with hapten and the positive control group, the concentration of doxorubicin hydrochloride was initially screened at 1.0 mg/ml which is best concentration for this therapy.
Prevalence, Types, and Sources of Bullying Reported by US General Surgery Residents in 2019
Authors: Lindsey M. Zhang, Ryan J. Ellis, Meixi Ma, Elaine O. Cheung, David B. Hoyt, Karl Y. Bilimoria, Yue-Yung Hu
Journal: JAMA (2020)

Surgical resident mistreatment is concerning. 1 Bullying, one type of mistreatment, defined as persistent negative and aggressive behaviors, primarily of a psychological nature, with the effect of humiliating, intimidating, frightening, or punishing, 2 has been associated with adverse outcomes such as depression. 3However, bullying during surgical training has not been well characterized, with prior evaluations limited by low survey response rates and inclusion of few institutions. 2,4We aimed to examine the prevalence, types, sources, and factors associated with bullying reported by US general surgery residents.
Angiogenesis inhibitor plus erlotinib versus erlotinib alone as first-line for advanced non-small cell lung-cancer harboring EGFR mutation.
Authors: Thierry Landre, Gaetan Des Guetz, Kader Chouahnia, Boris Duchemann, Jean F. Morere, Alain Vergnenegre, Christos Chouaid
Journal: Journal of Clinical Oncology (2020)

9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The outcomes included overall survival (OS), progression-free survival (PFS) objective response rate (ORR), and median duration of response (DOR). A fixed-effect model was used. Results: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al), and one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p &lt; 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p &lt; 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.
Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)-Inhibitor effect on COVID-19 outcome: A Meta-analysis
Authors: Carlos J. Pirola, Silvia Sookoian
Journal: Journal of Infection (2020)

Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis.
Hypertension control incommunities:analysis of implementation of non-pharmaceutical management
Authors: zeng-wu Wang, ZHANGLin-feng, Xin Wang, Wen Wang, Wei-wei Chen, Man-lu Zhu, Sheng-shou Hu, Li-sheng Hu
Journal: BMJ (2010)

：Objective To assesseffectiveness of implementation of non-pharmaceutical treatment in a standardizedcommunity-based hypertension management program in China.Methods A protocol ofstandardized community-based hypertension management was developed based on currentguidelines for prevention and treatment of hypertension in China.Physicians in communityhealth-care service centers at the grassroots across China were trained in a standardizedway using this protocol during 2005 to 2008,and then the trainees were required to managehypertensive patients according to the protocol.Hypertensive patients eligible forcriteria of inclusion and under management for more than one year were analyzed to observechanges in their behavioral risk factors,pharmaceutical and non-pharmaceuticaltreatment,and effectiveness of blood pressure lowering.Results By the end of 2008,a totalof 29 411 hypertensive patients had been managed for one year according to the protocoland 20 077 patients with complete data (47.1％for male)withmean age of 61±11 years were eligible for analysis.After standardized management of oneyear,prevalence of smoking,alcohol drinking and proportion of patients who preferred saltydiet decreased from 17.7 percent,18.1 percent and 32.8 percent to 8.9 percent,8.7 percentand 15.8 percent,respectively(P＜0.01).Srstolic bloodpressure(BP)decreased by 11.6[95％confidenceinterval(CI)10.8-12.4]mm Hg(1 mm Hg=0.133 kPa),13.7(95％CI 13.3-14.1)mm Hg and 15.2(95％CI14.8-15.6)mmHgin the patients with non-pharmaceutical therapy,pharmaceutical therapy andboth,respectively；and diastolic BP decreased by 7.5(95％CI6.9-8.1)mmHg,8.3(95％CI8.1-8.5)mmHg and 8.0(95％CI7.8-8.2)mm Hg in the three groups,respectively.Duringthe one-year period of management,proportion of the patients with appropriatenon-pharmaceutical therapy increased continuously.By the end of one-year management,59.5percent of smoked patients were required to quit their smoking,55.5 percent of alcoholdrinkers were required to limit their drinking,52.3 percent of overweight and obesepatients were required to reduce their weight and 47.3 percent of patients with physicalexercises less than three times a week were required to increase their regular physicalactivity.However,certain proportion of the patients with risk factors did not receiveappropriate non-pharmaceutical therapy.Conclusion Guideline-oriented hypertensionmanagement succeeded in lifestyle changes among the patients,but it is a gradual processto its full implementation.

Key words: 
Hypertension;  Community health service;  Non-pharmaceuticalmanagement
Blood levels of steroid hormone precursors allow differentiation between pancreatic adenocarcinoma and neuroendocrine tumors.
Authors: Viacheslav A. Aleynov, Elena M. Frantsiyants, Valeria A. Bandovkina, Natalia D. Cheryarina, Vladimir S. Trifanov, Sergey V. Sanamyants, Mikhail A. Averkin, Oleg I. Kit, Alexander V. Shaposhnikov, Yuriy A. Fomenko, Dmitry S. Petrov
Journal: Journal of Clinical Oncology (2020)

e16692 Background: The activity of some enzymes involved in the synthesis and transformation of sex hormones changes in some tumor tissues of the pancreas, which can affect the circulating concentrations of these hormones in the blood. The purpose of the study was to determine the possibility of differential diagnosis of pancreatic cancer at primary examination. Methods: Levels of 17OHP and DHEAS were measured by RIA in the blood of 25 men with chronic pancreatitis (CP), 34 patients with pancreatic adenocarcinoma (PA) and 15 patients with pancreatic neuroendocrine tumors (PNET). The results were compared with the levels in 23 healthy donors. All patients gave voluntary informed consent for the study. Results: Men with CP did not show statistically significant changes in 17OHP and DHEAS. The levels in pancreatic cancers were lower than in donors: in PA, DHEAS was 1.6 times and 17OHP - 1.4 times lower than the norm. DHEAS in PNET was 2.4 times lower than the norm and 1.5 times lower than in PA. 17OHP in PNET was 6.4 and 4.5 times lower, respectively. Conclusions: Measuring DHEAS and 17OHP in the blood can serve as an informative laboratory test for predictor assessment of the nature of pancreatic disease.
Atezolizumab plus stereotactic ablative therapy for medically inoperable patients with early-stage non-small cell lung cancer.
Authors: Karen Kelly, Megan Eileen Daly, Amin Mirhadi, Frances Lara, Leslie A Garcia, Shuai Chen, David Eastham, Ellen Anderson Wiegner, Jonathan W. Riess, Kurt A. Schalper, Arta Monjazeb
Journal: Journal of Clinical Oncology (2020)

9011 Background: Stereotactic ablative radiation therapy (SABR) is the standard-of-care for medically inoperable, early stage non-small cell lung cancer (NSCLC), but regional and distant failures remain problematic. Based on our in vivo data showing synergy between radiation and immune checkpoint inhibitors (ICI) and the known efficacy and mild toxicity profile of ICI in NSCLC, we conducted a phase I study to determine the maximum tolerated dose of neoadjuvant, concurrent, and adjuvant atezolizumab with SABR for early stage NSCLC patients (pts). Methods: Eligible pts had histologically confirmed T1-3 NSCLC with at least one feature predictive of increased recurrence risk: diameter ≥1 cm, SUV ≥6.2 on PET, or moderately/poorly differentiated histology, were medically inoperable or refused surgery and had a Zubrod PS ≤2. Patients received 6 cycles of atezolizumab. A 3+3 dose finding design was employed with 3 dose levels: 3 mg/kg, 10 mg/kg, and 1200 mg flat dosing. SABR was delivered starting cycle 3 to 50 Gy over 4-5 fractions. Dose limiting toxicity (DLT) was assessed during the first 9 weeks. Results: 20 pts were enrolled, 15 pts in the dose finding and 5 pts at the recommended phase II dose (RP2D). Patient factors: MedIan age 77; 45% male, 85% smoking history, 85% PS 0-1 and 35% squamous. One pt on dose level 2 had a DLT – a grade 3 rash. Atezolizumab 1200 mg flat dosing was the RP2D. Grade 3 pneumonitis was not observed. Partial responses after 2 cycles were seen in 3/17 evaluable pts (18%) and 1 pt had a minor response. No patient progressed on treatment. PD-L1 expression was 0% 8/13 (62%), &gt;1% - 50% 4/13 (31%), &gt;50% 1/13 (8%) in pts with sufficient tissue. Of 5 pts with PD-L1 expression 3 (60%) were responders and 1 (12.5%) of 8 pts with 0% PD-L1 expression responded. Multi-plex Quantitative Immunofluorescence (QIF) using a T cell activation panel demonstrated to correlate with ICI response was performed on 9 samples (including 2 responders, 1 minor responder). The CD3 QIF score was &gt; two-fold higher in the responders compared to non-responders, and the levels of proliferating and activated T cells were likewise &gt; two-fold higher. Comprehensive stool and serial blood analyses have been completed. Correlative endpoints will be reported along with additional efficacy outcomes. Conclusions: Atezolizumab plus SABR is feasible, safe and shows an efficacy signal in medically inoperable early stage NSCLC. This combination will be tested in a randomized phase III trial SWOG/NRG S1914. Funding: This work was supported by the DOD CDMRP W81XWH-15-2-0063 and Genentech. Clinical trial information: NCT02599454.