tbuckley/cabot-search huggingface dataset:
Normal-lung uptake of fluorodeoxyglucose, patient-reported symptoms, and clinician-rated radiation pneumonitis in patients with non-small cell lung cancer treated with chemoradiation.
Authors: Jinbo Yue, Ting Xu, Tingsu Pan, Melenda Jeter, Quynh Nguyen, Lawrence B. Levy, Qiuling Shi, Ritsuko Komaki, Daniel Richard Gomez, Xin Shelley Wang, Zhongxing X. Liao
Journal: Journal of Clinical Oncology (2016)

e20028 Background: Radiation pneumonitis (RP) is an inflammatory response of normal lung tissue that causes increased uptake of fluorodeoxyglucose (FDG) on PET images and clinical symptoms. We examined potential associations between normal-lung FDG uptake, patient-reported symptoms, and clinician-rated RP in patients with non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation. Methods: Subjects were 153 patients with inoperable stage II-IIIB NSCLC from a prospective study. Patients provided FDG PET scans before, during, and at 1-3 and 4-6 months after chemoradiation. Images of both lungs (excluding tumor but including treatment related parenchymal changes) were analyzed for mean standard uptake value (SUVmean) and global lung glycolysis (GLG). Patient-reported symptoms were assessed at the same timepoints by using the lung module of the MD Anderson Symptom Inventory. Clinicians rated RP severity according to the CTCAE v3 at 1-3 months and 4-6 months after therapy. Bivariate correlation, generalized ordinal regression, and mixed effects models were used to analyze potential relationships and predictors. Results: Lung SUVmean and GLG correlated with patient-reported RP-related symptoms (coughing and shortness of breath) before, during, and after therapy (all P < 0.05). Lung SUVmean and lung GLG also correlated with clinician ratings of RP grade (all P < 0.005). At the end of therapy, patient-reported RP symptoms predicted grade ≥ 2 RP (P = 0.0078) as well as SUVmean (P = 0.0369). Tumor glycolysis and tumor SUVmean did not correlate with either clinician-rated RP or patient-reported symptoms before, during, or after therapy. Conclusions: Strong correlations were found between clinician-related RP grade, patient-reported RP symptoms, and lung FDG uptake at 1-3 and 4-6 months after therapy. We further found that patient-reported RP symptoms at the end of therapy predicted the development of grade ≥ 2 RP and increased FDG uptake on PET. Collectively, these findings established measurable markers of RP-related inflammation in patients undergoing chemoradiation for NSCLC. Clinical trial information: NCT00915005.
An evaluation of a safety improvement intervention in care homes in England: a participatory qualitative study
Authors: Martin Marshall, Nadine Pfeifer, Debi de Silva, Li Wei, James Anderson, Lesley Cruickshank, Kieran Attreed-James, Jenny Shand
Journal: Journal of the Royal Society of Medicine (2018)

A growing proportion of older people live in care homes and are at high risk of preventable harm. This study describes a participatory qualitative evaluation of a complex safety improvement intervention, comprising training, performance measurement and culture-change elements, on the safety of care provided for residents.A participatory qualitative study.Ninety care homes in one geographical locality in southern England.A purposeful sample of care home managers, front-line staff, residents, quality improvement facilitators and trainers, local government and health service commissioners, and an embedded researcher.Changes in care home culture and work processes, assessed using documentary analysis, interviews, observations and surveys and analysed using a framework-based thematic approach.Participation in the programme appears to have led to changes in the value that staff place on resident safety and to changes in their working practices, in particular in relation to their desire to proactively manage resident risk and their willingness to use data to examine established practice. The results suggest that there is a high level of commitment among care home staff to address the problem of preventable harm. Mobilisation of this commitment appears to benefit from external facilitation and the introduction of new methods and tools.An evidence-based approach to reducing preventable harm in care homes, comprising an intervention with both technical and social components, can lead to changes in staff priorities and practices which have the potential to improve outcomes for people who live in care homes.
Use of molecular testing and EGFR targeted medications for colorectal cancer at VA Hospitals.
Authors: Daniel Jacob Becker, Steve Young Lee, Kristine E. Lynch, Ji Won Chang, Scott DuVall, Julie Ann Lynch
Journal: Journal of Clinical Oncology (2018)

e18814 Background: Extended RAS testing in colorectal cancer predicts response to therapy with EGFR-directed therapies cetuximab and panitumumab (EGFR mab’s). In 2010 VA policy recommended testing of all potentially treatable metastatic colon cancer patients for KRAS mutations. We explored the uptake of RAS testing within the VA system and characterized EGFR mab use. Methods: We extracted records of VA patients with first primary colorectal cancers diagnosed 2011-2015 from the VA Central Cancer Registry (VACCR). We gathered genomic testing results from 4 commercial vendors contracted with the VA. We calculated descriptive statistics of patients, mutations, and medication use, and further characterized EGFR mab use as guideline concordant (GCC). We used multivariable logistic regression to evaluate predictors of mutations and cetuximab use. Results: Among 2315 cases of stage IV CRC diagnosed 2011-2015, RAS testing increasing from 13.4% in 2011 to 23.7% in 2015 (p < 0.0001). Younger age OR 0.65 (0.52-0.81), year of diagnosis 1.18(1.01-1.38) and US Census region 1 (NE) vs 4 (West) OR 2.94 (1.28-6.28) were associated with RAS testing. Median survival for tested patients was 21m vs 10m (logrank p < 0.0001). Among 1210 patients with evaluable test results, 485 (40.1%) had mutations, with 280(23.1%) in codon 12, and 71 (5.9%) in codon 13. There were no differences in mutation rates by age, race, ethnicity, or gender categories. A total of 216 patients received EGFRmab; 201/725 (27.7%) of KRAS wildtype and 15/485 (3.1%) of KRAS mutants . GCC (mut+/EGFR mab- or mut-/EGFR mab+) did not predict for OS (logrank p = 0.5). Across all patients with test results, increasing age (OR 0.71, 95% CI 0.60-0.85) and treatment in the NE predicted EGFR mab use (OR 2.20, CI 1.06-4.56) while race and marital status did not predict EGFR mab use. Conclusions: We found significant increase in KRAS testing between 2011 and 2015, with mutation patterns reflective of the US population. We found a low rate of inappropriate EGFR mab use among patients with RAS mutations, as well as an also low rate of EGFR mab use among RAS wild type patients among whom it may be indicated. Further study is warranted to understand patterns of appropriate and inappropriate use of targeted agents.
TCT-796 A paradox in sex-specific clinical outcomes after bioresorbable scaffold implantation: 2-year results from the AIDA trial
Authors: Laura Kerkmeijer, Ruben Tijssen, Robin Kraak, Deborah Kalkman, Sjoerd H. Hofma, Rene van der Schaaf, Karin Arkenbout, None Auke Weevers, Jan Baan, Marije Vis, Karel Koch, Jan Tijssen, Jan Piek, Jose PS. Henriques, Joanna Wykrzykowska, Robert de Winter
Journal: Journal of the American College of Cardiology (2018)
Can fit elderly patients evaluated by comprehensive geriatric assessment with intermediate or locally advanced rectal cancer receive preoperative chemoradiotherapy? An interim analysis of a multicenter phase II trial.
Authors: Wen-Yang Liu, Jing Jin, Yuan Tang, Ning Li, Jun Wang, Yun-Jie Cheng, Hui Fang, Lin Yang, Ning-Ning Lu, Shunan Qi, Yu Tang, Bo Chen, Shulian Wang, Yongwen Song, Yueping Liu, Ye-Xiong Li, Xishan Wang, Haizeng Zhang, Zhi-Xiang Zhou
Journal: Journal of Clinical Oncology (2018)

e15688 Background: Fit elderly patients evaluated by comprehensive geriatric assessment (CGA) is recommended to receive preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer. However, this strategy has never been prospectively investigated. Methods: Trial design: single arm, multicenter, phase II trial (Registered in clinicaltrials.gov with NCT02992886). Brief inclusion criteria: patients were aged 70 years above with rectal adenocarcinoma of clinical stage II/III, and fit evaluated by CGA with informed consent signed. Treatment arm: based on the decision of MDT, all patients received preCRT with Raltitrexed followed by surgery (45-50.4Gy for radiation (RT) dose, 3 mg/m2, on d1 and d22 for Raltitrexed). Sample size considerations and interim analysis prespecified: 68 patients were required for primary point testing (2-year DFS) by Brookmeyer-Crowley method. We estimated that 39 patients were required for interim analysis, if nonhematological grade 3 (G3) or higher acute toxicities was observed in 12 or more patients, the H0 hypothesis that serious toxicities rate for preCRT was equal to or less than 21% (α = 0.1,1-β = 0.8, one-sided) would be rejected. Results: From Sep. 2016 to date, 64 patients were screened by CGA, which covering functional status, cognitive capacities, emotional status, comorbidities, nutritional status, etc. In 54 fit patients, 39 were included. Median age was 75 years. There were 8 and 31 patients with tumor staged at T3 or T4 by MRI or endoscopic ultrasound, respectively. All patients except one finished RT without dose reduction. Thirty-two patients finished Raltitrexed as scheduled. There were 17/39, 11/39 and 1/39 patients developed G2, G3 and G4 acute toxicity, respectively. In 12 patients with serious toxicities, there was only 6 patients experienced nonhematological side effects. The most common serious acute toxicities were leukopenia, diarrhea and fatigue. Conclusions: In rectal cancer, the preCRT for fit elderly patients evaluated by CGA was feasible and safe, and this trial will progress as planned. Clinical trial information: NCT02992886.
The effect of prior smoking history on the molecular profile of EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC).
Authors: Hadas Sorotsky, Mor Moskovitz, Jessica Weiss, Melania Pintilie, Natasha B. Leighl, Penelope Ann Bradbury, Geoffrey Liu, Alborz Kia, Michael Cabanero, Trevor John Pugh, Dax Torti, Ming Sound Tsao, Jonathon Torchia, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2018)

8533 Background: Although EGFRm NSCLC occurs mainly in non-smoking patients, most series report 20%-35% of cases in current or previous smokers. Broad molecular profiling of EGFRm NSCLC in smokers has not been reported. Methods: Surgically resected primary EGFR exon 19 or 21 mutated NSCLC tumors from 108 patients were molecularly profiled by whole exome sequencing using the Illumina HiSeq2000 platform. Alignment and variant discovery analysis was performed according to GATK best practices workflow; 87 sequenced to a mean coverage of 65.1x. Demographics and outcomes were compared for smokers and non-smokers (non-S), and by mutation profile. Results: Of the 63 non-smokers and 24 smokers (7 current/recent within 10 years), 71% were female, 53% were non-Asian, 64.5 years was the median age and 57.5% were EGFR exon 19. Of the 87 patients, 52% were stage I, 20.5% were stage II and 27.5% were stage III+. Smoking was associated with male sex (p = 0.0028) and non-Asian ethnicity (p = 0.0006) but not with age, stage or EGFR exon 19/21 subtype. Multiple “driver” mutations occurred in tumors of 25% smokers and 23.8% non-S. TP53/EGFR co-mutation occurred in 57.9% smokers and 46.2% non-S. Total non-synonymous mutation burden (TMB) was higher in smokers: median TMB in smokers 175.35 (84.93-388.24) compared to 155.31 (56.52-414.84) in non-S (p = 0.096). The strongest prognostic factor for OS and DFS was stage (I, II, III+) (p < 0.001 for each). In univariate analysis, there was a trend to shorter OS in smokers: HR 1.9 (CI 0.98-3.67, p = 0.05). Smoking within 10 years of NSCLC diagnosis was associated with shorter DFS HR 0.37(0.13-1.09) (p = 0.06) but not OS (p = 0.34). Neither EGFRm subtype nor TP53/EGFR co-mutation was associated with DFS or OS. High TMB was associated with shorter DFS: HR above vs below the median 1.96 (CI 1.06-3.62, p = 0.028), and OS HR 2.04 (CI 1.01-4.11, p = 0.043). TMB was still significant for DFS after adjusting for smoking status (p = 0.033), but not for OS (p = 0.1). Conclusions: EGFRm NSCLC in smokers is associated with a trend to higher non-synonymous TMB. Stage remains the strongest prognostic factor, but TMB appears to have a greater effect on survival outcomes than smoking status.
Correction to: Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients
Authors: Valentine Léopold, Etienne Gayat, Romain Pirracchio, Jindrich Spinar, Jiri Parenica, Tuukka Tarvasmäki, Johan Lassus, Veli-Pekka Harjola, Sébastien Champion, Faiez Zannad, Serafina Valente, Philip Urban, Horng-Ruey Chua, Rinaldo Bellomo, Batric Popovic, Dagmar M. Ouweneel, José P. S. Henriques, Gregor Simonis, Bruno Lévy, Antoine Kimmoun, Philippe Gaudard, Mir Babar Basir, Andrej Markota, Christoph Adler, Hannes Reuter, Alexandre Mebazaa, Tahar Chouihed
Journal: Intensive Care Medicine (2018)
TCT-530 Long-term clinical outcomes in patients with coronary chronic total occlusion undergoing optimal medical therapy
Authors: Euihong Ko, Sun Hack Lee, Sangwoo Park, Tae oh Kim, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Kyusup Lee, Osung Kwon, Do-yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Stage I ovarian immature teratomas: Is there a role for chemotherapy?
Authors: John K. Chan, Emily B Rosenfeld, Austin Blake Gardner, Lejla Delic, Daniel Stuart Kapp
Journal: Journal of Clinical Oncology (2017)

5523 Background: To determine the impact of chemotherapy on survival of patients with stage I ovarian immature teratomas. Methods: Data obtained from the National Cancer Database from 2004-2013. Kaplan-Meier methods and multivariate Cox regression models were used for statistical analyses. Results: Of 888 patients (median age 24 years), 76%, 7%, 15%, 3% were stages I, II, III, and IV, respectively. 27%, 28%, 38%, and 8% had grades 1, 2, 3 and 4. The predominant racial group was White (50%) and remainder Black (19%), Hispanic (16%), Asian (6%) and other (9%). 64% had fertility sparing surgery and 55% received chemotherapy. For all patients, 5 year survival was over 90%. Chemotherapy did not change the 5 year survival for stage I or stage II disease (p = 0.35 and p = 0.69, respectively). However, chemotherapy improved 5 year survival from 59% to 76% in stages III-IV (p &lt; 0.01). When controlling for other factors, older age (HR 3.2, p &lt; 0.01), stages II and III-IV (HR 6.0, p &lt; 0.01; HR 10.6, p &lt; 0.01) and grades 3-4 (HR 15.3, p &lt; 0.01) had worse survival. In a subset analysis of stage I patients chemotherapy did not improve 5 year survival of those with stage I grade 1 (p = 0.75) but chemotherapy did improved the survival of those with stage I grade 2 disease from 85% to 99% (p = 0.04). Conclusions: The overall survival of patients with immature teratomas is excellent. In patients with stage I grade 2 or higher disease chemotherapy was associated with an improved overall survival.
A randomized doubled blind phase II study exploring the safety and efficacy of nintedanib (BIBF1120) as second line therapy for patients (pts) with differentiated thyroid carcinoma (DTC) progressing after first line therapy: EORTC 1209.
Authors: Martin Schlumberger, Kate Newbold, Baktiar Hasan, Sandrine Marreaud, Samson Assele, Lisa F. Licitra, Patrick Schoffski, Sophie Leboulleux, Laura Locati, Yann Godbert, Vincent Rohmer, Barbara Jarzab, Salvatore Domenico, Oliver Edgar Bechter, Sylvie Zanetta, Jaume Capdevila, Ellen Kapiteijn, Lars Bastholt
Journal: Journal of Clinical Oncology (2018)

6021 Background: Radioiodine refractory advanced DTC may benefit from treatment with TKI. Most DTC pts will ultimately progress after treatment with a TKI and those in good general condition are candidates for further treatment lines. Nintedanib (N) is an oral triple angiogenesis inhibitor of VEGF, FGF and PDGF receptors. We conducted a randomized phase II trial of N vs placebo (P) in pts with locally advanced or metastatic DTC who received 1 or 2 lines of prior TKI. Methods: Eligible pts had documented RECIST v1.1 progression on a prior treatment with TKI. The primary endpoint was progression free survival (PFS) using RECIST v1.1 according to local radiologist. Tumor assessment occurred every 8 weeks. With a 1-sided alpha 10%, the study was powered at 90% level to detect a Hazard Ratio (HR) of 0.6 in PFS. Results: Between July 2014 and December 2016, 70 pts were randomized 2:1 to N (45 pts starting dose 400 mg/d) or matching P (25 pts). Pt characteristics were similar in both arms. Median (med) age was 65.8 years, 56 % female, all had distant metastases, 76% received 1 prior line of TKI and 24% received 2 lines. At the time of database lock, 2 N pts and 1 P pt were still receiving study treatment. Among pts who completed treatment, med duration of treatment was 17.7 weeks (W) in N and 10.4 W in P. Med relative dose intensity was 100% in N. AEs led to decrease N treatment dose in 21 pts and to permanent discontinuation in 5 pts. Grade ≥3 AEs occurred 50% in N and 36% in P, among others hypertension (9 vs 4%), diarrhea (9 vs 4%), abdominal pain (2.3% vs 0), nausea (4.5% vs 0), anorexia (11.4% vs 0), weight loss (2.3% vs 0), fatigue (6.8 vs 4%), anemia (2.3 vs 4 %) and lymphopenia (6.8% vs 0). Based on 53 events observed in 56 per protocol population pts (37 in N and 19 in P), med PFS was significantly prolonged from 2.86 months in P to 3.71 in N (HR [80% CI]: 0.65 [0.42, 0.99], stratified logrank test p = 0.095). Conclusions: N as second line therapy for pts with DTC progressing after 1st or 2nd line therapy was well tolerated. Based on per protocol population, N slightly prolonged med PFS compared to P. Clinical trial information: NCT01788982.
P24 EARLY OVERNUTRITION IN RATS INDUCES ALTERATIONS IN THE CARDIOVASCULAR RESPONSE TO INSULIN IN ADULTHOOD
Authors: L Guerra-Menéndez, A Tejera-Muñoz, D González-Hedström, S Amor, B Martín-Carro, B Oltra, J A Paredes, R Arriazu, J Moratinos-Delgado, G Diéguez, A L García-Villalón, M Granado
Journal: Cardiovascular Research (2018)
TCT-537 Impact of concomitant anticoagulant drug on long-term thrombotic and bleeding event and after everolimus-eluting stent implantation
Authors: None Katsuya Miura, Akimune Kuwayama, Masanobu Ohya, Takenobu Shimada, Ryosuke Murai, Hidewo Amano, Shunsuke Kubo, Suguru Otsuru, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tuyoshi Goto, Kazushige Kadota
Journal: Journal of the American College of Cardiology (2018)
Gleason grade in HIV+ versus uninfected prostate cancer patients in the Veterans Aging Cohort study.
Authors: Roxanne Jimmy Wadia, Lesley S Park, Cynthia Brandt, Michal G. Rose, Herta H. Chao, Cynthia Gibert, David Rimland, Maria Rodriguez-Barradas, Amy Justice
Journal: Journal of Clinical Oncology (2016)

e16560 Background: Little is known about how the biology of prostate cancer in HIV+ men compares to that of uninfected men. The purpose of our study was to compare the Gleason grade (GL) of prostate adenocarcinoma (PrCA) in HIV+ vs uninfected patients in the combination antiretroviral therapy (ART) era (1997-present). Methods: The Veterans Aging Cohort Study (VACS) is a multi-institutional cohort of HIV+ and uninfected patients in the VA medical system matched 1:2 for age, race, sex, and clinical site; enrolling patients since 1996. We linked the VA Central Cancer Registry (VACCR) to the VACS to identify patients diagnosed with PrCA. Using the Voogo text searching tool, the electronic medical records were searched for permutations of the term “Gleason”. Text snippets containing the search terms were reviewed and GL were extracted for each patient. GL were grouped by clinical risk stratification: dysplasia (2-4), low risk (5-6), intermediate risk (7), and high risk (8-10). We performed univariate analyses comparing GL in HIV+ vs uninfected patients. Results: In the VACS (N=47,206 HIV+; 98,332 uninfected) there were 658 HIV+ and 1,839 uninfected subjects with incident PrCA diagnoses identified by VACCR. Of the 2,497 PrCA cases, 1,655 had notes that contained the term “Gleason” or a permutation of the term. Distribution of Gleason grades were similar between HIV+ and uninfected patients (p=0.63). The majority were low (44%) and intermediate (38%) risk scores. Average age and distribution of race/ethnicity and cancer diagnosis year were also similar between the HIV+ and uninfected patients. Conclusions: Our analysis demonstrates that the GL of PrCA diagnosed in HIV+ patients in the ART era is similar to the GL of PrCA diagnosed in uninfected patients matched for age and race. Future analyses will compare stage and PSA between the two groups and examine the effect of HIV viral load and CD4 count on the prognostic indicators of PrCA in HIV+ patients. Distribution of GL by HIV status. GL HIV+ (N=439) Uninfected (N=1,216) P-value N (%) N (%) Dysplasia (2-4) 7 (2) 11 (1) 0.63 Low risk (5-6) 187 (43) 549 (45) Intermediate risk (7) 169 (38) 467 (38) High risk (8-10) 71 (16) 175 (14) Not applicable 5 (1) 14 (1)
Ultra-high FRET efficiency NaGdF4: Tb3+-Rose Bengal biocompatible nanocomposite for X-ray excited photodynamic therapy application
Authors: Wenli Zhang, Xiaofeng Zhang, Yingli Shen, Feng Shi, Chaojun Song, Tianshuai Liu, Peng Gao, Bin Lan, Miao Liu, Sicheng Wang, Li Fan, Hongbing Lu
Journal: Biomaterials (2018)