tbuckley/cabot-search huggingface dataset:
Barriers for access to isolated liver metastasis treatment in colon cancer in the United States.
Authors: Andre Luiz De Souza, Ritesh Rathore, Shiva Kumar Reddy Mukkamalla
Journal: Journal of Clinical Oncology (2018)

833 Background: Multidisciplinary treatment of stage IV colon cancer with isolated hepatic metastases implies patient’s access to quality healthcare. Here, we evaluate barriers for access to hepatic metastasectomy in the United States. Methods: The National Cancer Database was queried for stage IV colon cancer patients with isolated liver metastasis diagnosed from 2010-2014. Patient demographics, T and N staging, laterality and surgery were among the variables of interest. Pearson Chi square test was used for statistical analysis Results: A total of 3145 patients were identified for analysis. Moderately differentiated, T3 and N1 tumors were the most frequent tumors to be treated with perioperative and neoadjuvant chemotherapy. Neoadjuvant and perioperative chemotherapy correlated with age (p&lt;0.0001) and year of diagnosis (p=0.0289). Left sided tumors were more likely to receive perioperative and neoadjuvant chemotherapy compared to right sided or transverse tumors (p&lt;0.0001). Conclusions: With various degrees of utilization of perioperative and neoadjuvant chemotherapy based on demographic and clinical variables, there exists a great need to close the gap in access to chemotherapy and surgery for colorectal cancer isolated liver metastases. [Table: see text]
Understanding the Differences between Clinical Trial Participants and Real-World Patients with Non-Hodgkin Lymphoma
Authors: Tolulope Fatola, Sarah C. Rutherford, John N. Allan, Jia Ruan, Richard R. Furman, Chen Zhengming, Arcania Garcia, Channy Kong, Erica B Bhavsar, Joshua Falsenfeld, John P. Leonard, Peter Martin
Journal: Blood (2018)
Cost Simulation for Febrile Neutropenia Hospitalization in the US Due to Pegfilgrastim on-Body Injector Failure Compared to Single-Injection Pegfilgrastim and Daily Injections with Reference and Biosimilar Filgrastim in Non-Hodgkin Lymphoma
Authors: Ali McBride, Andriy Krendyukov, Nicola Mathieson, Kim Campbell, Sanjeev Balu, Karen MacDonald, Ivo Abraham
Journal: Blood (2018)
A phase 1 dose-escalation study of anti-HER3 monoclonal antibody LJM716 in combination with trastuzumab in patients with HER2-overexpressing metastatic breast or gastric cancer.
Authors: Seock-Ah Im, Dejan Juric, Jose Baselga, Anthony Kong, Paloma Martin, Chia-Chi Lin, Elizabeth Claire Dees, Jan H. M. Schellens, Filippo G. De Braud, Lily Delgado, Mauro Zucchetto, Xianbin Tian, Rose Fernandez, Alex Morozov, Luc Yves Dirix
Journal: Journal of Clinical Oncology (2014)

2519 Background: TheHER2-HER3 heterodimer, a key driver in HER2-positive tumors, is not completely blocked by available therapies. LJM716 is a fully human anti-HER3 monoclonal antibody (mAb) shown to enhance trastuzumab activity in HER2+ preclinical breast and gastric cancer models. Methods: This phase 1, open-label study is currently evaluating LJM716 in combination with trastuzumab in patients (pts) with HER2+ metastatic breast (MBC) or gastric (MGC) cancer who failed previous HER2-directed therapy. The objective for the dose-escalation part of the study was to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). Results: As of October 4, 2013, 35 pts (escalation, n = 17; expansion, n = 18) were enrolled (MBC, n = 29; MGC, n = 6) and treated intravenously with LJM716 at dose levels (DLs) 3, 10, 20, or 40 mg/kg once weekly (QW) in combination with trastuzumab 2 mg/kg QW. All pts had prior antineoplastic therapy, including 19 (54%) with ≥ 3 regimens. Common treatment-related adverse events (≥ 20%, all grades) were diarrhea (91%), nausea (29%), fatigue (23%), and chills (20%). Grade 3/4 events were observed in 7 pts (20%) at all DLs except 20 mg/kg QW. One dose-limiting toxicity (grade 3 diarrhea) was reported. The MTD/RDE of LJM716 in combination with trastuzumab was 40 mg/kg QW. The pharmacokinetics of LJM716 and trastuzumab was consistent with that of single agents. A reduction in pHER3 was demonstrated in 3 of 4 paired tumor biopsies. Of 30 evaluable pts, 2 partial responses (PRs) were observed: 1 each at 3 mg/kg and 10 mg/kg QW (18 and 40 weeks of exposure, respectively). Both pts with PRs had MBC and documented progression with the most recent prior regimen, which contained trastuzumab. Six additional pts (17%) with MBC demonstrated minor responses (8-27% tumor shrinkage). Twelve pts (40%) with MBC or MGC had stable disease as the best response (> 16 weeks of exposure in 3 MBC pts). Conclusions: LJM716 is the first anti-HER3 mAb to demonstrate clinical activity in combination with trastuzumab in trastuzumab-resistant pts. The safety profile of the combination was acceptable up to the highest LJM716 DL tested, 40 mg/kg QW. Clinical trial information: NCT01602406.
Deaths in Colorado Attributed to Kratom
Authors: Ken Gershman, Krista Timm, Meredith Frank, Laurissa Lampi, Jonathan Melamed, Roy Gerona, Andrew A Monte
Journal: New England Journal of Medicine (2019)

Deaths in Colorado Attributed to Kratom Kratom is an herbal drug that at high doses has opioid-like effects, but the potential for fatal overdose is unclear. This study of 15 kratom-related deaths ...
A phase II trial of the effect of perindopril on hand foot syndrome (HFSR) incidence and severity in patients receiving regorafenib with refractory metastatic colorectal carcinoma (mCRC).
Authors: Barbara L. Melosky, Howard John Lim, Janine Davies, Sharlene Gill, Christian K. Kollmannsberger, Maria Ho, Solomon A. Vandt, Daniel John Renouf
Journal: Journal of Clinical Oncology (2018)

824 Background: Regorafenib is an oral multi-kinase inhibitor (MKI), with a demonstrated overall survival benefit in mCRC refractory to standard therapy ( PMID 23177514). The most common grade 3 adverse event (AE) reported in this trial was HFSR, with 47% of patients (pts) experiencing HFSR of all grades, and 17% with grade 3 severity. The pathogenesis of regorafenib-induced HFSR is not well established, but may be related to alterations in the capillary endothelium. Perindopril is an Angiotensin Converting Enzyme (ACE) Inhibitor indicated for the treatment of hypertension, and may also play a role in preventing endothelial dysfunction ( PMID 17140552). We hypothesized that perindopril may prevent or reduce the severity of regorafenib-induced HFSR. Methods: In this single center Phase II, open label trial, 34 pts with refractory mCRC were planned to be treated with regorafenib (160 mg/day) and perindopril (4 mg/day) with both agents given 3 weeks on and 1 week off. An interim analysis was planned after 10 evaluable pts. The primary objective was to assess the proportion of pts with any grade HSFR toxicity. Secondary endpoint included time to development of worst (grade 3) HSFR toxicity, proportion of all grades of hypertension and all grade toxicities, and progression free survival. All toxicities were evaluated using CTCAE v4.03. Results: 12 pts were accrued over a 9 month time period, and 10 pts were considered evaluable as they completed one cycle of treatment. Pt characteristics included (6 M/ 6F, mean age 62, ECOG PS 0 (25%)/ 1 (75%). A planned interim analysis was performed after 10 evaluable pts had completed their first cycle of study treatment. 5/10 (50%) experienced Grade 3 HFSR, and based on the statistical plan it was deemed highly unlikely that perindopril would lead to reduced levels of regorafenib induced HSFR compared with regorafenib alone thus enrolment was stopped. The most frequent other grade 3 toxicities included hypertension (16.7%), and increased AST (16.7%). Conclusions: The addition of perindopril to regorafenib did not appear to reduce HSFR incidence and severity in pts with refractory mCRC. Clinical trial information: NCT02651415.
The CXCL12/CXCR4 pathway, bone marrow-derived myeloid cells, and survival in locally advanced cervical cancer.
Authors: Naz Chaudary, Melania Pintilie, Salomeh Jelveh, Patricia Lindsay, Rachel Glicksman, Blaise Clarke, Richard P. Hill, Michael Milosevic
Journal: Journal of Clinical Oncology (2014)

11122 Background: Cervical cancer is a global health problem. There is a need to improve standard treatment with radiotherapy (RT) and concurrent cisplatin (CT). Tumors are known to recruit myeloid cells from the bone marrow (BMDCs) via the CXCL12/CXCR4 and other chemokine pathways, which in turn influence tumor vascular function and RT response. The objective of this study was to explore the impact of the CXCL12/CXCR4-BMDC axis on clinical outcome in cervical cancer patients treated with RT, and ways of inhibiting this response. Methods: A total of 258 patients with cervical cancer (cT1b-T3b, N0-1, M0) were treated with RT +- concurrent CT. Tumor hypoxia, interstitial fluid pressure (IFP – a biomarker of abnormal vascular function) and CXCR4 expression were measured prior to treatment. The median follow-up was 5.3 years. Orthotopic cervical xenografts were developed from patient biopsies for evaluation of the chemokine inhibitor Plerixafor. Results: The pretreatment bloodpolymorphonuclear neutrophil (PMN) count was normal (<7.5X109/L) in 83% of cases.In patients treated with RT+CT, high pretreatment PMNs were associated with inferior disease-free survival (DFS) but only in the setting of high tumor IFP. This was independent of tumor stage, size and LN status, and was validated in a separate cohort of patients treated with RT alone. Patients with high PMNs displayed high peri-vascular tumor infiltration by CD11b+ or CD66b+ myeloid cells. There was 5-fold variation in CXCR4 mRNA expression by qRT-PCR, and 58% of cases showed high CXCR4 protein expression by IHC.Patient-derived orthotopic cervical tumors were treated with fractionated,image-guided RT and CT +- Plerixafor (5 mg/kg). Combined treatment with Plerixafor produced substantial tumor growth delay and prolonged survival compared to standard RT+CT alone. There was no difference in acute GI toxicity with the addition of Plerixafor to standard treatment. Conclusions: TheCXCL12/CXCR4 pathway and BMDCs influence RT response and clinical outcome in patients with cervical cancer via a vascular-dependent mechanism. Inhibition of CXCL12 signaling can mitigate this effect and should be considered for translation to phase I/II clinical trials.
Is digital mammography associated with a higher risk of false-positive results? Findings from a community setting.
Authors: Firas M Dabbous, Jenna Khan-Gates, Terry Macarol, Therese A. Dolecek, Sally Friedewald, Anne Marie Murphy, Tom Summerfelt, Garth Rauscher
Journal: Journal of Clinical Oncology (2014)

1612 Background: Compared to screen film mammography (SFM), full field digital mammography (FFDM) may improve detection of lesions in younger women with denser breasts but may also increase false positives. We compared false positive probabilities (FPP) for FFDM and SFM in a single large healthcare organization. Methods: Screening mammograms during 2001 and 2009 were linked to incident breast cancers diagnosed from 2001-2010 from a state cancer registry using probabilistic methods, and 664,342 screens without a cancer diagnosis in the subsequent 12 months were identified. False positive probability was defined as the proportion of screening mammograms without a subsequent breast cancer diagnosis that were nonetheless interpreted as abnormal. Due to the very large sample size, we focus on clinical rather than statistical significance. Results: FPP decreased from 16% in women under 50 to 9% for women aged 70 and above. FPP was lower for women with less dense vs. more dense breasts (11% vs. 14%). Non-White ethnicity (13% vs. 12%) was not associated with FPP, whereas a woman’s first screen was associated with higher FPP than subsequent screens (17% vs. 10%). In multivariable models, FPP was 1.3 percentage points lower for FFDM than SFM (p<0.001) and the difference did not vary substantially by age, race/ethnicity or breast density. Conclusions: It does not appear that FFDM as practiced in this community setting comes with a higher risk of false positive results, which should be reassuring to community-based institutions that have or are shifting away from SFM towards FFDM.
Impact of adding oxaliplatin to fluoropyrimidines in the adjuvant colon cancer: Experience in Ramon y Cajal University Hospital.
Authors: Olga Martinez Saez, Arantzazu Martínez Barquín García, Maria Villamayor Delgado, Cristina Saavedra Serrano, Elena Corral de la Fuente, Juan José Serrano Domingo, Roberto Martín Huertas, Pablo Reguera Puertas, FEDERICO LONGO, Vanessa Pachon, Mercedes Rodríguez Garrote, Carmen Guillen, Alfredo Carrato, Reyes Ferreiro Monteagudo
Journal: Journal of Clinical Oncology (2018)

815 Background: The addition of oxaliplatin to fluorouracil and leucovorin as adjuvant therapy for patients with stage II and III colon cancer (CC) has been analyzed in two large, randomized trials, MOSAIC and C-07 trials. The updated results of these studies showed that the addition of oxaliplatin enhances overall survival by approximately 5% in patients with stage III disease but has no effect in patients with stage II disease. Methods: We retrospectively included patients with stage II and III CC that were operated between 2009 and 2014 in the Ramón y Cajal University Hospital from Madrid. We perform a multivariable Cox model analysis to estimate the benefit of the chemotherapy stratifying by oxaliplatin in each stage. The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes, perforation, obstruction, grade and age. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (281 stage II and 283 stage III). 305 did not receive any chemotherapy, 61 received monotherapy with fluoropyrimidines (FP) and 198, FP and oxaliplatin. The median follow-up in the entire cohort was 49 months. Globally, adjuvant chemotherapy (either with FP alone or with the combination with oxaliplatin) showed no benefit in DFS (HR of 1.18 and 0.98, respectively). The benefit in OS was significant either for FP alone (HR: 0.46, p: 0.029) and for the combination treatment (HR: 0.41, p: 0.001). Patients with stage II treated with FP in monotherapy showed no benefit, neither in DFS nor OS (HR for DFS: 2.2, p: 0.1; HR for OS: 0.5, p: 0.22). The benefit was neither seen with the addition of oxaliplatin (HR for DFS: 2, p: 0.11; HR for OS: 0.85, p: 0.7). Stage III patients treated with FP presented a HR for DFS of 0.76 (p: 0.5) and a HR for OS of 0.42 (p: 0.087). The HR for DFS with oxaliplatin was 0.53 (p: 0.07). A significant improvement in OS was observed, with a HR of 0.22 (p &lt; 0.001). Conclusions: The addition of oxaliplatin in the adjuvant treatment of stage III patients showed a trend towards improvement in DFS and a significant benefit in OS compared to not receiving chemotherapy. On the contrary, patients with stage II did not benefit from this treatment, neither in DFS nor OS.
Prognostic significance of preoperative neutrophil-lymphocyte ratio in patients with gastric cancer treated with surgery.
Authors: Akihiro Suzuki, Ryotaro Takano, Osamu Takahashi, Takashi Taketa, Yuhsuke Shimodaira, Kazuki Sudo, Hironori Shiozaki, Keisuke Kubota, Seiji Ohigashi, Keiichiro Ohta
Journal: Journal of Clinical Oncology (2014)

e15088 Background: The neutrophil-lymphocyte ratio (NLR) is related to inflammatory status and/or cellular immunity status of patients with some cancers. We hypothesize that preoperative NLR is associated with clinical outcomes in patients with gastric adenocarcinoma. Methods: We identified 458 gastric cancer patients who had curative gastrectomy at our institute for 10 years between 2000 and 2009. All patients had baseline staging including blood test, CT scan and an endoscopic biopsy. Multiple statistical methods were used to analyze clinical outcomes. Results: More than sixty percent of patients were men and stage I was dominant (53.5%). The median follow-up time was 74.8 months (95% C.I; 69.5-80.2). The estimated overall survival (OS) and relapse-free survival (RFS) rate at 5 years were 76.1 +/- 2.1% and 78.6 +/- 2.2%, respectively. In multivariate analysis, Stage (I/II vs. III/IV), Age, Residual tumor status (R0 vs. R1) and NLR was an independent risk factor for OS and RFS, p-value of NLR were less than 0.001 for OS and 0.013 for RFS. OS and RFS of high NLR group which cut off point was 4.0 were significantly shorter than those of low NLR group (p=0.012, p=0,001 respectively). Conclusions: The data show that a higher preoperative NLR is associated with poorer prognosis in patients with gastric cancer. Upon validation, preoperative NLR may become a useful biomarker for individualizing therapy at low cost. Variables OS RFS HR (95% CI) P-value HR (95% CI) P-value Age Continuous 1.05 (1.04, 1.07) <0.01 1.05 (1.03, 1.06) <0.01 Gender Female vs. male 1.20 (0.97, 1.43) 0.43 1.32 (0.70, 1.80) 0.18 Tissue type Diffuse vs. intestinal 1.17 (0.92, 1.42) 0.53 1.07 (0.66, 1.79) 0.76 Stage Stage I/II vs. III/IV 0.17 (0.00, 0.43) <0.01 0.15 (0.00, 0.38) <0.01 Residual tumor status R0 vs. R1 0.39 (0.11, 0.66) <0.01 0.44 (0.20, 0.69) 0.01 NLR Continuous 1.05 (1.03, 1.07) 0.01 1.07 (1.05, 1.09) <0.01
Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Risk for Attention-Deficit/Hyperactivity Disorder in Offspring
Authors: Jakob Christensen, Lars Pedersen, Yuelian Sun, Julie Werenberg Dreier, Isabell Brikell, Søren Dalsgaard
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Valproate is an antiepileptic drug (AED) used in the treatment of epilepsy and many other neurological and psychiatric disorders. Its use in pregnancy is associated with increased risks of congenital malformations and adverse neurodevelopment in the offspring and may be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD). <h3>Objective</h3> To determine whether prenatal exposure to valproate and other AEDs is associated with an increased risk of ADHD in the offspring. <h3>Design, Setting, and Participants</h3> This was a population-based cohort study of all live-born singleton children in Denmark from January 1, 1997, to December 31, 2011 (N = 913 302). Information on prenatal exposure to AEDs, including valproate, was obtained from the Danish National Prescription Registry and all children with ADHD were identified (children with diagnosed ADHD in the Danish Psychiatric Central Research Register or children who redeemed a prescription for ADHD medication). The cohort was followed up from birth until the day of the ADHD diagnosis, death, emigration, or December 31, 2015, whichever came first. Data were analyzed in September 2018. <h3>Exposures</h3> Maternal use of valproate and other AEDs in pregnancy. <h3>Main Outcomes and Measures</h3> Cox regression estimates of the hazard ratio of ADHD. Estimates were adjusted for potential confounders. <h3>Results</h3> The cohort included 913 302 children (mean age at end of study, 10.1 years; median age, 9.4 years; interquartile range, 7.2-12.8 years; 468 708 [51.3%] male). A total of 580 were identified as having been exposed to valproate during pregnancy; of them, 49 (8.4%) had ADHD. Among the 912 722 children who were unexposed to valproate, 29 396 (3.2%) had ADHD. Children with prenatal valproate exposure had a 48% increased risk of ADHD (adjusted hazard ratio, 1.48; 95% CI, 1.09-2.00) compared with children with no valproate exposure. The absolute 15-year risk of ADHD was 4.6% (95% CI, 4.5%-4.6%) in children unexposed to valproate and 11.0% (95% CI, 8.2%-14.2%) in children who were exposed to valproate in pregnancy. No associations were found between other AEDs and ADHD. <h3>Conclusions and Relevance</h3> Maternal use of valproate, but not other AEDs, during pregnancy was associated with an increased risk of ADHD in the offspring. These findings have important implications for the counseling of women of childbearing potential using valproate.
Abstract 19572: Elevated PETCO2 During Cardiac Resuscitation Without Return of Spontaneous Circulation
Authors: Cameron Hypes, Dan Spaite, Tyler Vadeboncoeur, Ryan A Murphy, Chengcheng Hu, Robyn McDannold, Annemarie Silver, Bentley Bobrow
Journal: Circulation (2015)

Background: Quantitative End-Tidal CO2 (PETCO2) measurement during cardiac arrest is recommended for monitoring the CPR quality to detect ROSC. While low ETC02 can reflect suboptimal CPR quality and increases in ETC02 are often associated with ROSC the significance of high values of PETCO2 without ROSC remain unclear. Objectives: To describe the population of OHCA victims with high PETCO2 (&gt;50 mm Hg) during ongoing resuscitation including demographics, rhythm characteristics, occurrence of ROSC, the later occurrence of field termination of resuscitation and the presumed etiology. Methods: An observational analysis of adult OHCAs with available PETCO2 data occurring between Oct 2010 and Nov 2014 at two sites involved in the Save Hearts in Arizona Registry and Education (SHARE) quality improvement program. CPR and PETCO2 data were recorded using ZOLL E and X Series EMS monitors. PETCO2 is reported as the mean value for each minute. The cardiac rhythm and the presence of ROSC were determined for each minute using EMS provider reports, vital signs, ECG, and accelerometer data. The first recorded minute of PETCO2 and minutes with ROSC were excluded. Results: Study population included 654 OHCAs with PETCO2 data, 96 cases (58% male, age median 65 (IQR 54-75)) with at least 1 min of high PETCO2 in the absence of ROSC were identified. Of these, 31 (32%) had ROSC at least once during their resuscitation. Cases were of presumed cardiac etiology in 81 (84%), while 12% and 4% had presumed respiratory and other etiologies, respectively. A total of 322 minutes of PETCO2 &gt;50 mm Hg in the absence of ROSC were identified. The mean PETC02 value was 67 (IQR 54-75). Of these 296 minutes (92%) occurred during PEA. Despite high PETCO2, resuscitation was terminated in the field in 21 (22%) patients. Only one subject survived to hospital discharge. Conclusions: In this observational study, high PETCO2 was frequently found during resuscitation without ROSC and PEA was the most common cardiac rhythm. Further study is warranted to determine the significance and possible reasons for this finding.
Minimal Residual Disease in Ovarian Biopsies Collected in Patients with Bone Marrow Complete Remission of Acute Lymphoblastic Leukemia
Authors: Florian Chevillon, Jean-Hugues Dalle, Chloé Arfeuille, Céline Chalas, Marie Passet, Véronique Drouineaud, Stephanie Nguyen, Ilhem Rahal, Regis Peffault De Latour, Michael Degaud, Marion Alcantara, Aurelie Cabannes-Hamy, Nicolas Boissel, Emmanuelle Clappier, Catherine Poirot, Nathalie Dhedin
Journal: Blood (2018)
Some system characteristics of states and the types of responses to disease of patients with lung tumors.
Authors: Galina Vitalyevna Zhukova, Sergei A. Zinkovich, Elena Alekseevna Shirnina, Natalia M. Maschenko, Elena Yurievna Zlatnik, Yury Valentinovich Przhedeckyi, Anastasia Ivanovna Zhadobina, Sergey P. Pyltsin, Pavel A. Anistratov
Journal: Journal of Clinical Oncology (2014)

e20580 Background: Multifactorial etiology of tumor process, the demand for effective methods of treatment, diagnosis and prognosis of complications, as well as important role of personal features cause necessity of complex and system investigation of state of oncology patients. The aim of the research was to study the psychophysiological characteristics and indicators of hormonal and adaptation status of patients with lung tumors. Methods: It has previously been shown that the structure of the general nonspecific adaptation reactions (GNSAR) - their character and tensions - represents the activity of the neuroendocrine and immune systems (Selye Y., 1936; Garkavi L.H. et al., 1975-2006). In 37 patients with lung tumors the structure of GNSAR was determined with help of the blood count and the certified original computer program