tbuckley/cabot-search huggingface dataset:
Comparison of demographic variables related to 30-day readmission in cancers with similar risk factors: Analysis of 290,270 hospitalizations.
Authors: Suceil Sivsammye, Karthik Kailasam
Journal: Journal of Clinical Oncology (2017)

e15596 Background: There has been increasing focus on reducing hospital readmissions which are an ongoing economic challenge. This study was targeted at cancer of the esophagus (CE), stomach (CS), and pancreas (CP) which share similar risk factors to identify if these patient subsets also share risk for hospital readmission. Methods: Data was extracted from Nationwide Inpatient Sample database, which approximates 20% of U.S. community hospitals. Patients with a diagnosis CE, CS, and CP were identified by Clinical Classification Software code 11, 12, and 17, respectively. Demographic parameters associated with high readmission rates were collected for patients readmitted within 30 days over 2009-2013. Chi-square test was used to asses differences between variables. Results: We identified a total of 290,270 hospitalizations over the 5-year period of which 26.2% were readmitted within 30 days. The total number of readmissions were comparable for CS (28.0%), CP (27.89%), and CE (26.81%). Patients 45 to 64 years (28.58%, p &lt; 0.001), Medicaid insurances (33.4%, p &lt; 0.001), and metropolitan areas (26.8%, p &lt; 0.001) were associated with higher 30-day readmission rates amongst all three cancers. Males had higher readmission rates in CS (25.64%, p &lt; 0.001) and CP (28.6%, p &lt; 0.001) compared to females in CE (28.0%, p &lt; 0.001). Lowest median income for zip code patients were readmitted more often in CS (26.2%, p &lt; 0.001) vs. third median income in CP (27.78, p &lt; 0.001) and fourth (highest) median income in CE (28.38 %, p &lt; 0.001). The most common identified causes of readmission in all three cancers were complications of surgical procedures or medical care (8.51% ± 2.03%), and septicemia (6.5% ± 1.95%). Conclusions: Our analysis shows that some variables for readmission are similar however more studies are needed to further elucidate whether this is primarily due to analogous treatment techniques. If so interventions to limit readmissions related to these treatments should be taken. Differences in readmissions rate amongst income classes could be related to the ease of accessing the most endorsed treatments for each individual cancer, however further studies are needed to clarify this discrepancy.
Antipruritic effect of bezafibrate and serum autotaxin measures in patients with primary biliary cholangitis
Authors: Andreas E Kremer, Aline Le Cleac’h, Sara Lemoinne, Katharina Wolf, Luc De Chaisemartin, Sylvie Chollet-Martin, Lydie Humbert, Dominique Rainteau, Raoul Poupon, Alexandra Rousseau, Olivier Chazouillères, Christophe Corpechot
Journal: Gut (2018)

It was with great interest that we read the recent guidelines from the British Society of Gastroenterology on the treatment and management of primary biliary cholangitis (PBC).1 The authors propose a pragmatic drug approach to treat cholestatic pruritus with cholestyramine as first-line and rifampicin as second-line use, followed by naltrexone, sertraline or gabapentin as third-line options, although with concerns regarding tolerability and adverse events.

Pruritus is a characteristic, potentially agonising symptom of PBC that remains poorly cared.2 New drug options are definitively needed to relieve patients of this symptom. Bezafibrate, a pan-agonist of peroxisome proliferator-activated receptors, has been suggested to reduce itch intensity in patients with PBC.3 This beneficial effect has recently been confirmed in a placebo-controlled phase III trial Bezafibrate in Combination with Ursodeoxycholic Acid in PBC (BEZURSO).4 The mechanisms by which bezafibrate improves pruritus in PBC remain unknown. As the lysophospholipase autotaxin (ATX) and its product, lysophosphatidic acid, have been identified as potential key players in the pathogenesis of cholestatic pruritus,5 the present post-hoc analysis of the BEZURSO trial aims to investigate the role of ATX in the antipruritic effect of bezafibrate in patients with PBC.

All patients met the following criteria at inclusion: (1) PBC diagnosis and (2) …
Comparison of outcomes with PD-L1 tumor proportion score (TPS) of 50-74% vs 75-100% in patients with non-small cell lung cancer (NSCLC) treated with first-line PD-1 inhibitors.
Authors: Elizabeth Jimenez Aguilar, Hira Rizvi, Sasha Kravets, Christine A. Lydon, Anika E. Adeni, Safiya Subegdjo, Matthew David Hellmann, Mark M. Awad
Journal: Journal of Clinical Oncology (2018)

9037 Background: Among patients with NSCLC and a PD-L1 TPS ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more likely to benefit from treatment with a PD-1 inhibitor is currently unknown. We compared outcomes among NSCLC patients treated with first-line PD-1 inhibitors and different PD-L1 TPS groupings: 50-74% vs 75-100%. Methods: We retrospectively analyzed patients who received a PD-1 inhibitor as first-line treatment for NSCLC with a PD-L1 TPS of ≥50% from the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Clinicopathologic characteristics and clinical outcomes were compared among patients with a PD-L1 TPS of 50-74% vs 75-100%. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Results: 112 patients were identified for inclusion in this study: 39.3% (N = 44) had a PD-L1 TPS of 50-74%, and 60.7% (N = 68) had a TPS of 75-100%. There were no significant differences in smoking history, histology, sex, KRAS or EGFR mutation status, and age between both groups of patients. In the entire cohort, the overall response rate (ORR) was 33.9%, median progression-free survival (mPFS) was 4.2 months (95% CI: 2.8-6.2), median overall survival (mOS) was 20.3 months (95% CI: 17.7-NR). Patients with TPS 75-100% had a significantly higher ORR (13.6% vs 47.1%, P < 0.01), significantly longer mPFS (2.5 mo [95% CI: 1.8-4.5] vs 5.1 mo [95% CI: 3.8-7.4 ], P = 0.02), and higher estimated 12-month OS (76.4% vs 54.4%) compared to patients with TPS 50-74%. Conclusions: In the first-line setting for NSCLC, higher PD-L1 TPS levels of 75-100% is associated with improved clinical outcomes compared to patients with a TPS of 50-74%.
A trial of CV301 in combination with anti-PD-1 therapy versus anti-PD-1 therapy in subjects with non-small cell lung cancer.
Authors: Arun Rajan, Julius Strauss, Alanvin Orpia, Margaret Elena Gatti-Mays, Eva Wagner, Christopher Ryan Heery, Cesar Pico, James L. Gulley
Journal: Journal of Clinical Oncology (2018)

TPS9108 Background: Despite recent therapeutic advances in non-small cell lung cancer (NSCLC), an unmet medical need remains for most patients. Pembrolizumab (pembro) is approved in first-line treatment of patients with NSCLC as a single agent when PD-L1 expression is > 50% and in combination with chemotherapy when PD-L1 expression is < 50%. It is believed that a fraction of non-responders to pembro lack an adequate tumor-directed immune response. CV-301 is a poxviral-based vaccine comprising a prime-boost strategy with Modified Vaccinia Ankara (MVA) prime and fowlpox boost. The viral vectors encode 2 tumor associated antigens, CEA and MUC-1, as well as 3 costimulatory molecules (B7.1, ICAM-1 and LFA-3, called TRICOM). Current preclinical and mechanistic evidence suggests that CV-301 can generate a tumor-directed immune response in NSCLC, potentially increasing the clinical benefit associated with pembro. Methods: This open-label, multi-center trial will evaluate the combination of CV301 and pembro. The phase 1 trial, an evaluation of safety of ascending doses of CV301, has been completed. The vaccine was well tolerated with no DLTs. The phase 1b portion is currently enrolling at least 6 patients with NSCLC in the maintenance setting of pembro and will continue pembro in combination with CV301 with a goal to establish safety of the combination. Safety monitoring will occur every two weeks. If safety is established, the randomized Phase 2 portion will enroll 176 subjects, randomized 2:1 to receive maintence pembro in combination with CV301 (2) or alone (1). Maintenance setting is defined as the period following 11 weeks of initial treatment, after which chemotherapy would be complete in the < 50% PD-L1 expression group. To be eligible, patients must have stable disease or objective response at the time of radiographic evaluation (approximately 11-12 weeks after initiation of first line therapy). Preliminary efficacy will be analyzed during the Phase 2 cohort based on the Intent-to-Treat population, comprising overall survival (primary), progression-free survival and overall response rate (secondary). Clinical trial information: NCT02840994.
TCT-170 Impact of rate of recruitment on all-cause mortality: Insights from the GLOBAL LEADERS all-comers trial
Authors: Kuniaki Takahashi, Ply Chichareon, Marcello Dominici, Edouard Benit, Veselin Valkov, Christoph Liebetrau, Luc Janssens, Maurizio Ferrario, Adel Aminian, Manel Sabate, Norihiro Kogame, Rodrigo Modolo, Chun-Chin Chang, Yoshinobu Onuma, Marco Valgimigli, Stephan Windecker, Pascal Vranckx, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
TCT-593 Predicting Acute Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Replacement: Testing the Mehran Contrast Induced Nephropathy Score
Authors: Malik Murtaza, Razvan Dadu, Hasan Rehman, Colin Barker, Michael Reardon, Neal Kleiman
Journal: Journal of the American College of Cardiology (2018)
Monitoring of peripheral lymphocyte and neutrophil counts to predict efficacy of nivolumab (nivo).
Authors: Yosuke Kawashima, Shingo Nishikawa, Ryo Ariyasu, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Natsuki Takano, Tomoyo Oguri, Satoru Kitazono, Yuichi Tambo, Noriko Yanagitani, Fumiyoshi Ohyanagi, Atsushi Horiike, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2017)

e20583 Background: Programmed death-1 (PD-1) antibody is a key drug for treating non-small cell lung cancer (NSCLC), but the response rate is about 20% in non-selected populations and efficacy is difficult to predict. We examined correlations between peripheral blood tests, including counts of lymphocytes (Lym), neutrophils (Neu), and C-reactive protein (CRP), and the efficacy of nivolumab (nivo) monotherapy. Methods: Eighty NSCLC patients treated with nivo (3mg/kg every 2 weeks) in our hospital between December 2015 and September 2016 were evaluated. Peripheral blood tests on day (d) 0 (the day before 1 st nivo), d15 (the day of 2 nd nivo), d29 (the day of 3 rd nivo) were evaluated. Absolute counts and the change ratio (%) of Lym, Neu and CRP from baseline (d0) were calculated. Response to nivo was evaluated according to RECIST v1.1. Results: Response to nivo was partial response in 23 cases, stable disease in 13 and progressive disease (PD) in 44 patients (overall response rate, 28%; disease control rate, 45%). Absolute counts of Lym, Neu and CRP at baseline did not differ significantly between non-PD and PD (Lym, 1323/µl vs. 1376/µl; Neu, 4830/µl vs. 5189/µl; CRP, 3.48 mg/dl vs. 3.38 mg/dl). Neu was significantly increased from baseline to d15 and d29 in the PD population compared with the non-PD population (δNeu (d15): 25.2% vs. -6.3%, P= 0.008; δNeu (d29): 16.7% vs. -8.6%, P= 0.006). CRP was also significantly increased from baseline to d29 in the PD population compared with the non-PD population (δCRP: 60.1% vs. -21.2%, P= 0.010). In contrast, Lym was significantly increased from baseline to d29 in the non-PD population compared with the PD population (δLym: 9.6% vs. –6.7%, P= 0.010). Conclusions: Changes in peripheral blood test results after nivo differed between non-PD and PD populations. Monitoring of Neu and Lym and CRP may allow prediction of the efficacy of nivo.
Clinical efficacy and safety of apatinib combined with EGFR-TKIs in advanced non-small cell lung cancer with EGFR-TKIs resistance.
Authors: Ruifen Tian, Yi Guo, Xia Zhang, Xing Zhang, Wei Guo, Haibo Zhu, Junjun Xu, Fangfang Shen, Xia Song
Journal: Journal of Clinical Oncology (2018)

e21172 Background: Acquired resistance to EGFR-TKIs frequently occurs in advanced non-small cell lung cancer (NSCLC) patients (pts) with sensitizing EGFR mutations. Previous studies have shown that apatinib (a TKI against VEGFR-2) combined with EGFR-TKIs might improve the survival of EGFR-TKIs resistant NSCLC pts. We conducted this trial to investigate the efficacy and safety of apatinib combined with EGFR-TKIs(including erlotinib, gefitinib and icotinib) compared with traditional chemotherapy for EGFR-TKIs resistant NSCLC pts. Methods: This prospective study enrolled advanced NSCLC pts who acquired resistance to the EGFR-TKIs therapy. Pts received apatinib combined with EGFR-TKIs (apatinib in start dose of 250 mg+pior EGFR-TKIs dose) or chemotherapy ( pemetrexed or vinorelbine with platinum). Efficacy was evaluated every 6 weeks based on RECIST 1.1. Results: From Mar 2017 to Feb 2018,19 pts were enrolled, including 13 pts received apatinib combined with EGFR-TKIs,6 pts received chemotherapy, all pts had no disease progression till Feb 1, 2018. In the apatinib group, 92.31%(12/13) pts were available evaluated. The objective response rate was 25%(3/12) and the disease control rate was 100% (12/12). The most common adverse events in the apatinib group were hypertension (66.67%,8/12), proteinuria (33.33%,4/12 ), hand-foot syndrome(16.67%,2/12), diarrhea(16.67%,2/12). Main grade 3 or 4 toxicities were hypertension (25%, 3/12), hand-foot syndrome (8.33%, 1/12) and diarrhea(8.33%,1/12). Two pts with brain metastases in the apatinib group got metastases lesions decreased. Two progressive pts got lesions decreased after apatinib dose increasing to 500mg. Of the 6 pts receiving chemotherapy, 5 pts were available evaluated. The objective response rate was 20%(1/5) and the disease control rate was 100% (5/5). Major adverse reactions was hematological toxicity . Conclusions: Apatinib combined with EGFR-TKIs may provide a new therapy strategy for NSCLC pts with acquired EGFR-TKIs resistance. Further studys with lager samples are needed to validate our findings.Moreover, we will further explore the correlation between genetic mutations, biomarkers and therapeutic efficacy . Clinical trial information: ChiCTR-OIN-17012051.
Effect of Rho/ROCK pathway inhibition on metastasis-free and overall survival in biomarker selected, orthotopic, patient-derived models of pancreatic cancer.
Authors: Venessa T. Chin, Adnan Nagrial, James Conway, Claire Vennin, Lorraine A. Chantrill, Angela Chou, Angela Steinmann, Anthony J. Gill, Jeremy Humprhis, Alison Drury, Danielle Froio, Ashleigh Morgan, Andrew Biankin, Paul Timpson, Marina Pajic
Journal: Journal of Clinical Oncology (2017)

e15759 Background: PC is a highly lethal disease which metastasises early. The sequencing efforts of the Australian Pancreatic Cancer Genome Initiative (APGI) identified ROCK-1 as a target of interest. The Rho/ROCK pathway is essential in cellular movement, metastasis, vasculogenesis and stromal signaling. Fasudil (F) is a ROCK inhibitor which has been shown to be safe for human use. Using unique, patient derived models, we have previously shown that F plus gemcitabine (G) does not reduce cellular proliferation in vitro but reduces tumour size and improves overall survival (OS) in subcutaneous patient-derived xenografts (PDX). However, PDXs are critisised for not fully recapitulating the human condition. Here we aimed to generate a patient-derived orthotopic xenograft (O-PDX) which could be used to assess the effects of F + G on metastasis formation and OS. Methods: One patient-derived cell line (PDCL) was labled with firefly luciferase. This was injected into the pancreas of NOD/Shi- scid/IL-2Rγ null (NSG) mice to generate the O-PDX model. The O-PDX was imaged weekly with the IVIS imaging system. The O-PDXs were treated with saline control (S) (n = 8), gemcitabine (G) (n = 10) fasudil (F) (n = 6) or gemcitabine + fasudil (GF) (n = 10). Mice were culled once radiographic or clinical evidence of ascites was detected. Metastasis free (MFS) and OS were recorded. Vessel quantification was performed via CD-31 staining. Results: Metastases seen (spleen, liver, lung, ovary) on imaging were confirmed using GFP stains on immunohistochemistry. F prolonged MFS but not OS when compared with S. GF significantly prolonged MFS (33.5 versus 43 days; p = 0.0339) and OS (51.5 versus 64 days; p = 0.0035). CD-31 staining showed that treatment with F resulted in increased vascularity in the liver metastases and normal liver tissue but not in the pancreas tumour. Conclusions: The addition of Fasudil to gemcitabine improves MFS and OS in an orthotopic model of PC and is a promising new therapeutic option. The increase in vascularity of the metastases and normal liver tissue suggest that changes in vascularity are important and may result in improved delivery of gemcitabine.
Distinct impacts of <i>KRAS</i>, <i>NRAS</i> and <i>BRAF</i> mutations on survival of patients with metastatic colorectal cancer.
Authors: Yucai Wang, Jonathan M. Loree, Cecilia Yu, Marcella Tschautscher, Andrew M. Briggler, Michael J. Overman, Russell Broaddus, Funda Meric-Bernstam, Jeremy Clifton Jones, Jessica Balcom, Benjamin Kipp, Scott Kopetz, Axel Grothey
Journal: Journal of Clinical Oncology (2018)

3513 Background: RAS and BRAF mutations are associated with lack of response to anti-EGFR therapy and worse survival in patients with metastatic colorectal cancer (mCRC). NRAS mutations are less frequent than KRAS and BRAF mutations. While the prognostic implication of BRAF V600E mutations in mCRC is well established, the impact of NRAS mutations on outcome is unclear. Methods: Patients with mCRC who had RAS/RAF mutations tested at Mayo Clinic and MD Anderson Cancer Center between 2012 and 2016 were included in this study. Clinical information was obtained by chart review, and clinical characteristics and survival outcomes were compared among patients with different mutations. Categorical data were analyzed by Chi-square test, and time-to-event data were analyzed by Kaplan-Meier and Cox proportional hazards models. Statistical analysis was done in SPSS (v22). Results: In 2953 patients (1076 from Mayo and 1877 from MD Anderson), the mutation frequencies were: KRAS 45.6%, NRAS 3.8%, BRAF V600 8.0% and BRAF non-V600 1.3% (all wild-type [WT] 41.3%). 2282 patients with sufficient clinical information available were included for survival analysis, including 951 WT (41.7%), 1080 KRAS (47.3%), 91 NRAS (4.0%) and 160 BRAF V600 (7.0%). Compared with WT, NRAS patients were more likely female (47% vs 36%, P= 0.031) and had more right-sided cancers (30% vs 20%, P= 0.031). NRAS and KRAS patients did not differ in age, sex, sidedness, or MSI-H/dMMR. Compared with BRAF, NRAS patients were younger ( < 60, 59% vs 44%, P= 0.018), had more left-sided cancers (70% vs 29%, P< 0.001), and had less MSI-H/dMMR (1% vs 17%, P= 0.001). The median follow-up was 42.7 months. The median overall survival (OS) for WT, KRAS, NRAS and BRAF patients were 49.2, 36.2, 30.1 and 22.5 months, respectively (P< 0.001). In multivariate analysis adjusting for age, sex and sidedness, NRAS patients had worse OS than WT (HR = 1.83 [1.40-2.39], P< 0.001) and KRAS patients (HR = 1.37 [1.06-1.78], P= 0.016). The OS difference between NRAS and BRAF patients was not statistically significant (HR = 0.81 [0.57-1.14], P= 0.220). Conclusions: KRAS, NRAS and BRAF mutations have distinct impacts on survival in mCRC. NRAS mutations carry a poorer prognosis compared with KRAS.
A validated symptomatic BKV risk assessment score in patient post allogeneic stem cell transplant.
Authors: Ala Abudayyeh, Heather Y. Lin, Maen Abdelrahim, Gabriela Rondon, Borje Andersson, Charles Martinez, Jeffery Tarrand, Roy Chemaly, Dimitrios P Kontoyiannis, David Marin, Amanda Leigh Olson, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Journal of Clinical Oncology (2017)

e18536 Background: BKV, Polyomavirus hominis 1, is a member of the family Polyomaviridae, is a non-enveloped virion; in the 1980s, it emerged as an important pathogen in SCT recipients. In the absence of sufficient T-cell immunity, BKV reactivation can progress, leading to prolonged hospital stays and increased mortality secondary to late hemorrhagic cystitis, ureteral stenosis, and nephropathy. In our recently completed retrospective study of 2477 SCT patients, 38.1% had developed renal impairment, and BKV viruria was present in 25%. In addition, BKV was found to be an independent predictor of chronic kidney disease and shorter survival. Using the large cohort (2477) patients studied earlier (2004-2012) we have derived a grading system to identify patients with risk of symptomatic BKV. We hypothesize that the current grading system will identify the patients at risk of symptomatic BKV at day 30 post allogeneic stem cell transplant. Methods: We performed a retrospective chart review of all patients who underwent allogeneic SCT from 2012-2016. The data was extracted from the secured database at MD Anderson cancer Center. Using the three variables that were significant predictor for symptomatic BKV derived from our initial study (conditioning regimen, HLA donor status, &amp; underlying cancer diagnosis) we performed the analysis. Predicted cumulative incidence rate of BK infection at 30 days after transplant in 1308 patients were calculated in the presence of death as a competing risk using the “BASELINE” statement in PHREG procedure in SAS. Patients were classified into low, moderate and high risk according to the distribution of the predicted cumulative incidence of BK infection 30 days after transplant. Results: We have shown that the grading system derived from allogeneic SCT population predicted accurately the high, moderate &amp; low risk population for developing symptomatic BKV. Conclusions: We have created and validated a grading system for symptomatic BKV in a large cohort of (1308 patients) to predict risk at day 30 post allogeneic SCT. Using this grading system we would hope to identify high risk patients for BKV and intervene early with novel therapies prior to complications associated.