tbuckley/cabot-search huggingface dataset:
Prospective study of work limitations in cancer patients (pts) undergoing curative chemotherapy (CT).
Authors: Amye Tevaarwerk, Kevin A Buhr, William A. Conkright, Adedayo A. Onitilo, Emily G. Robinson, Robert B. Hegeman, Harish G. Ahuja, Roger W. Kwong, Ranveer Nanad, Alexandra Dennee, Mark E. Burkard, Douglas Wiegmann, Kari Braun Wisinski, Mary E Sesto
Journal: Journal of Clinical Oncology (2017)

18 Background: Impaired work performance that when significant leads to decreased productivity (work limitations) contribute to the “financial toxicity” of cancer treatment. Factors influencing work limitations and employment outcomes are poorly understood for cancer pts. We prospectively examined the proportion of cancer pts with significant increases in work limitations during curative treatment (co-primary endpoint). Methods: Eligible pts were ≥ 18 years, employed, intended to work during or after end of treatment (EOT), and had received ≤ 1 CT cycle. The Work Limitations Questionnaire (WLQ) survey was administered (baseline [BL], EOT, 3 and 6-months post EOT) to determine change in work limitations (WLQ index scale: 0 = no limitations to 28.6 = limited all of the time). “Significantly affected” pts had &gt; 5-point increase in WLQ - an increase associated with decreased work productivity. Descriptive statistics (estimates with 95% confidence intervals [CI]; means with standard deviations [SD]) were calculated. A two-factor ANOVA (pt, timepoint) was used for analysis of WLQ changes over time. Results: 120 pts enrolled 5/2013 - 10/2015 at 8 sites (85 breast, 16 colon, 19 other). 110 took 1+ surveys: median age 50 (range 24-69), 92 (84%) female, 105 (96%) White; 93 (85%) had surgery, 110 (100%) CT, 57 (52%) RT. The mean increase in WLQ index from BL to EOT was +4.4 (95% CI [+2.1,+6.8], p &lt; 0.001). A total of 44% were “significantly affected” by treatment (37/85, 95% CI [33%,55%]). WLQ index decreased at 3 and 6-mos (as compared to BL or EOT, see table). Conclusions: Among largely White pts getting CT, 44% experienced a significant increase in work limitations from BL to EOT. An improvement in group WLQ scores was noted after EOT. Analysis of factors (e.g., job type, education, symptoms) most associated with work limitations is underway to assist in prospectively identifying at-risk pts. [Table: see text]
Women know, and men wish they knew, prognostic information in advanced cancer.
Authors: Kalen M Fletcher, Holly Gwen Prigerson, Paul K Maciejewski
Journal: Journal of Clinical Oncology (2012)

9037 Background: Little is known about gender differences in advanced cancer patient communication with oncologists. The few studies conducted have explored differences in preferences for prognostic disclosure. Our data allow us to test for gender differences in actual rates of audio-recorded, patient and oncologist reported, prognostic disclosures. We studied a group of advanced cancer patients to determine whether gender disparities exist in: a.) reported rates of prognostic disclosures from physicians and b.) willingness to estimate (versus not) one’s prognosis (i.e., amount of time left to live). Among patients who report never receiving a prognosis from their physician, we also tested for gender difference in wishing that this had been discussed. Methods: Coping with Cancer II is an NCI -funded multi-site, prospective longitudinal study of advanced cancer patients. Patients were interviewed after receiving scan results and asked if they have received a prognosis from their oncologist either at their most recent visit or at any time in the course of their disease. They are also asked if they would be willing to estimate their prognosis. Patients who state that they have not received a prognosis are asked if they wish that they had. Results: Among the advanced cancer patients studied (N=51; men=23, women=28), male cancer patients were significantly more likely to state never receiving a prognosis from their physician than female patients (OR=3.5; χ 2 =4.49, df=1, p=0.034). Male cancer patients were also significantly less willing to provide a life-expectancy estimate (OR=5.6; χ 2 =5.06, df=1, p=0.025). Among patients who stated never receiving a prognosis (N=27; men=16, women=11), male patients tended to be more likely than female patients to wish that their prognosis had been discussed (OR=7.8; χ 2 =3.11, df=1, p=0.078). Conclusions: Male advanced cancer patients are less likely than female cancer patients to state that they have received prognostic information and less willing to provide a life-expectancy estimate. Although male patients receive less open prognostic disclosure than female patients, male patients tend to be more likely than female patients to want prognostic information.
Incorporating genomic testing using next-generation sequencing (NGS) into clinical practice: Genetic counselors’ (GC) experience, knowledge, and perceived competence.
Authors: Michael J. Hall, Patrick McKay Boland, Karen Ruth, Jennifer Madeline Matro, Kim Rainey, Carolyn Y Fang, Yu-Ning Wong, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2014)

e17624 Background: NGS genomic testing technologies are rapidly entering routine oncology practice. GC are critical to bridging the gap between genomic medicine and patient care, but may be inadequately prepared to support NGS genomic testing (NGSGT) in the clinic. Methods: National Society of Genetic Counselors members were recruited by list-serv postings (n=340) and email (n=353/690, 51% opened emails) from 4/13-6/13. Overall response was 693/2,589 (26.8%). GC completed a survey assessing NGSGT experience, objective knowledge, and perceptions of personal competence related to NGSGT, including understanding of: advantages/disadvantages (AD), clinical barriers (CB), clinical availability (CA), perceived ability to interpret (AI) NGSGT results, perceived role in supporting patients undergoing NGSGT, and perceived education needs. Scales were evaluated with Cronbach’s α (0.74-0.82), and responses were compared using chi-square and ANOVA. Results: Participants were primarily female (96%) and White (92%). Over half (52%) had practiced >5 yrs, and 35% spent >75% in cancer care. Few (13%) had counseled for NGSGT. Perceived understanding of AD, CB and CA were each strongly associated with prior education about NGSGT, more time spent in cancer-related counseling, previous experience with NGSGT counseling, lower perceived need for NGSGT education, greater perceived importance of NGSGT to routine clinical care, and higher knowledge (all p<0.0001). Perceived confidence in interpreting NGSGT results was lower for tumor compared to germ-line panels (p<0.001). Nearly all (97%) perceived a role for GC in supporting germ-line panel NGSGT while only 46% agreed GC had a role in tumor panel NGSGT (p<0.001). The majority agreed to needing more education about NGSGT in tumors (84%) and germ-line (87%). Conclusions: GCs lack experience with NGSGT and desire more education. While NGSGT of tumors is rapidly entering the clinic, GC feel unprepared and uncertain of their professional role. Lack of experience and knowledge deficits may adversely impact GC perceived clinical competence to help patients make important decisions using this new technology.
Short-Term and Long-Term Economic Burden Following Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in Adult Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Richard T. Maziarz, Yanni Hao, Annie Guerin, Genevieve Gauthier, Marjolaine Gauthier-Loiselle, Simu K Thomas, Lamis K Eldjerou
Journal: Blood (2016)
A phase II study of erlotinib monotherpay in patients with previously treated advanced non-small cell lung cancer (NSCLC) without EGFR gene mutation who have never/light smoking history: NEJ006/TCOG0903.
Authors: Yoshiki Ishii, Makoto Maemondo, Koichi Okudera, Kei Takamura, Yoshiki Demura, Kunihiko Kobayashi, Naoto Morikawa, Akihiko Gemma, Osamu Ishimoto, Masao Harada, Satoru Miura, Yuka Fujita, Kazuhiro Usui, Yasuo Saijo
Journal: Journal of Clinical Oncology (2012)

7561 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated good response in NSCLC harboring EGFR gene mutation. However, survival benefit from erlotinib was observed also in NSCLC patients with wild type (wt) EGFR gene in subsets of several phase III trials. Additionally, smoking status could be a predictive factor of erlotinib efficacy, This study aimed to evaluate the efficacy of erlotinib in Japanese NSCLC patients with wt-EGFR and find a biomarker that predicts the efficacy of erlotinib other than EGFR gene mutation. Methods: The primary endpoint was an objective response rate. Secondary endpoints included disease control rate, overall survival, and safety. Advanced NSCLC patients without EGFR gene mutation who had received one to three prior chemotherapy regimens and who had never smoked or light smoked (Brinkman Index: less than200) were eligible in this study. EGFR gene status was evaluated by the PNA-LNA PCR clamp method. Erlotinib was administered daily (150mg/day) until disease progression or unacceptable toxicities. Results: Forty seven patients were enrolled between March 2010 and November 2011. One patient was excluded for evaluation because having mutation of EGFR. Efficacy and safety were evaluated among 46 patients. Best responses were PR 7 (15.2%), SD 12 (26.1%), PD 26 (46.4%), NE 1 (2.2%). Response rate and disease control rate were 15.2% (95%CI: 4.9-25.5%) and 41.3 % (95%CI 27.1-55.5%) respectively. Grade 3 or 4 adverse events were anorexia (4), skin rash (2), neutropenia (1), leukopenia (1), anemia (2), elevation of AST/ALT (1), rectal ulcer (1), and cerebral infarction (1).Two patients suffered grade 3 interstitial lung disease. Conclusions: This is the first report to evaluate Erlotinib efficacy in selected NSCLC who do not possess EGFR gene mutation. Erlotinib showed significant anti-tumor activity in pretreated never or light smoked Japanese NSCLC patients without EGFR gene mutation. The results of biomakr analysis will be presented at the meeting.
Identification of real-time PCR-negative EGFR mutations by direct sequencing test.
Authors: Tao-Yeuan Wang, Chi-Kuan Chen
Journal: Journal of Clinical Oncology (2013)

e22118 Background: High percentage of patients with non-small cell lung cancer (NSCLC) has EGFR activating mutations in Taiwan and responses to EGFR inhibitors such as Tarceva (1, 2, 3). Timely molecular diagnosis is critical and molecular testing should be performed before treatment for the individual patient. It is important to develop an effective molecular diagnostic method for accurately detecting mutations and preventing false positive results. Therefore, we used a universal genetic detecting method (FemtoPath) to increase sensitivity of gene mutation detection and improve the sensitivity limitation (0.1%). Our previous reports indicated that FemtoPath/direct sequencing test is more sensitive, accurate and inexpensive than Cobas KRAS real- time PCR mutation test. Methods: In this study, we compared two molecular testing methods for the detection of EGFR mutation; the direct sequencing and the real-time PCR. Results: FemtoPath EGFR direct sequencing test identified mutations in 57 of the 73 tumors (77.03%) and Cobas EGFR mutation test identifies mutations in 53 of the 73 tumors (72.97%). Six negative results obtained by Real-Time PCR test were re-confirmed to be positive by direct sequencing test. From the results above, FemtoPath/direct sequencing test not only accurately detected all of the mutations, but also identified mutations adjacent toexons 18, 19, 20 and 21 of the EGFR gene. In 52 consensus cases of EGFR mutation obtained from both methods, there were 10 major discrepancies including two S768, four Exon 19 deletion, one L858, five T790, and one exon 20 insertion in this experiment. Conclusions: FemtoPath/direct sequencing test has lower invalid rate than Real-Time PCR test while fewer sample amount was required with increased detection efficiency of unknown mutation site.
High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death
Authors: Petra Niederberger, Emilie Farine, Maria Arnold, Rahel K. Wyss, Maria N. Sanz, Natalia Méndez-Carmona, Brigitta Gahl, Georg M. Fiedler, Thierry P. Carrel, Hendrik T. Tevaearai Stahel, Sarah L. Longnus
Journal: Metabolism (2017)
A second-generation DNA-binding pyrrole-imidazole polyamide with antitumor activity.
Authors: Nicholas George Nickols, Fei Yang, Benjamin C Li, Jerzy O Szablowski, Chieh-Mei Wang, Peter Brendan Dervan
Journal: Journal of Clinical Oncology (2013)

e13588 Background: Pyrrole-imidazole polyamides are synthetic minor groove binders with programmable sequence recognition. A polyamide that targets the DNA sequence 5’-WGWWCW-3’ (W=A/T) found in the Androgen Receptor (AR) response element inhibits a subset of AR driven transcripts and is cytotoxic in a number of cancer cell lines including LNCaP (prostate cancer), without evidence of DNA damage. Pharmacokinetic studies show bioavailability after intravenous or subcutaneous injection. This polyamide suppressed growth of LNCaP tumor xenografts in mice. However, escalated dosing resulted in significant weight loss that could deter further development. We now report a second-generation polyamide with decreased systemic toxicity that retains efficacy towards LNCaP xenografts. Methods: We investigated the toxicity of our lead polyamide in normal (C57BL/6)mice by necropsy. We then synthesized a focused library of four polyamides that retain the DNA-recognition sequence of our lead molecule, but with chemical substitutions at non-recognition elements. We treated groups of normal male mice (n=4 each) with escalating doses up to 10 mg/kg and observed them for 10 days or until signs of significant distress, after which mice were necropsied. The least toxic polyamide was then tested for suppression of LNCaP xenograft growth (n=14 per treatment arm: 1 mg/kg polyamide versus saline vehicle alone). Tumors were allowed to grow to 200 mm3 prior to treatment by subcutaneous injection every three days for a cycle of six injections. Tumors were then resected and measured. Results: The primary target organ of toxicity for our lead polyamide was the liver, which demonstrated toxicity at 3 mg/kg and dose-limiting toxicity at less than 10 mg/kg. One polyamide in our library demonstrated no evidence of toxicity by necropsy and serum analysis up to 10 mg/kg. This polyamide also suppressed growth of established LNCaP xenografts (T/C: 51%, p=0.0073) at a dose of 1 mg/kg. The other polyamides demonstrated greater toxicity and were not tested further. Conclusions: We report a second-generation polyamide with minimal systemic toxicity in rodents that retains in vivo antitumor activity in prostate cancer xenografts.
Outcomes in the second line treatment of metastatic colorectal cancer (mCRC): Findings from 6,462 patients (pts) in the ARCAD database.
Authors: Alexis Diane Leal, Fang-Shu Ou, Aimery De Gramont, Levi Pederson, Alberto F. Sobrero, Marc Peeters, Dirk Arnold, Henry C. Pitot, Mace L. Rothenberg, Bruce J. Giantonio, Eric Van Cutsem, Daniel J. Sargent, Axel Grothey
Journal: Journal of Clinical Oncology (2017)

757 Background: Progression free survival (PFS) and overall survival (OS) appear to differ across trials, even when pts receive the same regimen (REG). This analysis aimed to benchmark the clinical outcomes in the 2 nd line treatment of metastatic colorectal cancer (mCRC). Methods: Individual patient (pt) data was available on 6,462 pts with mCRC enrolled in 7 2 nd line clinical trials (8 REGs) in the ARCAD database. Regimens used in at least two trials included FOLFIRI +/- an EGFR inhibitor (EGFRi), FOLFOX +/- a VEGF inhibitor (VEGFi), and irinotecan (IRI). Descriptive statistics were used to describe pt demographics. Multivariable Cox models were used to assess differences (DIFFs) in PFS and OS, while p-value &lt;0.05 were considered statistically significant (SS). Results: 500-1400 pts received each REG (see Table). Median OS and PFS differed by 0.2 to 4.6 months (mo) and 0.8 to 2.5 mo across trials within the same REG. These DIFFs were SS except for PFS in REGs containing FOLFIRI +/- EGFRi. After multivariable adjustment, all DIFFs in OS were attenuated and non-significant. DIFFs in PFS attenuated for most REGs but remained SS for FOLFOX and IRI. Conclusions: After multivariable adjustment, there were no SS DIFFs in outcomes across trials within the same REG, with the exception of PFS in FOLFOX and IRI. The initial observed DIFFs in outcomes could be due to confounding factors and the remaining SS DIFFs in PFS in FOLFOX and IRI may be due to variation in definition of progression across trials. Therefore, caution is warranted when using historical data to design future trials.[Table: see text]
Gut Microbiota in Cardiovascular Health and Disease
Authors: W.H. Wilson Tang, Takeshi Kitai, Stanley L. Hazen
Journal: Circulation Research (2017)

Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine
Retrospective review of capecitabine as adjuvant therapy in high risk or recurrent squamous cell carcinoma of head and neck (SCCHN).
Authors: Poorni Manohar, Eli Sapir, Avraham Eisbruch, Mathew E Spector, Mark E Prince, Andrew G Shuman, Carol Rossier Bradford, Douglas Brian Chepeha, Gregory T. Wolf, Jeffrey Moyer, Kelly M Malloy, Scott A McLean, Erin Lynn McKean, Emily Light Bellile, David A Hanauer, Francis P. Worden
Journal: Journal of Clinical Oncology (2015)

e17043 Background:For patients with recurrent SCCHN there are currently no evidence- based, approved adjuvant treatment options (following surgery and/or chemoradiotherapy for recurrent disease). Roughly 40-75% of these high-risk patients recur after treatment, with median survival rates up to 10 months. Capecitabine, an oral 5FU pro-drug, has documented efficacy in the treatment of metastatic and locally advanced SCCHN. In this retrospective analysis, we hypothesize that prolonged exposure to capecitabine may offer benefit to patients with recurrent/high disease when given adjunctively. Methods: We identified 17 patients with either locally advanced SCCHN with multiple high-risk features or recurrent SCCHN that were treated with adjuvant capecitabine post chemo-radiation or surgery for 1 year. The data was extracted from a database of patients treated for SCCHN at the University of Michigan Comprehensive Cancer Center from 2003 through 2015 and matched with 17 control patients by age, sex, and clinical stage to evaluate disease free survival benefit of adjunctive therapy. Results: Nine patients with stage III-IVA disease with multiple high-risk features and 8 patients with at least one prior recurrence received capecitabine 1,500 mg/day for 12 months. 15 were male and 2 were female; median age was 57 years; 9 patients had oropharyngeal primaries, 4 with hypopharyngeal primaries, and 4 with oral cavity primaries. 11/17 patients were able to complete prescribed treatment and tolerated it with acceptable toxicity. With a median follow up of 39 months, no significant difference was observed in disease free survival [HR 0.670 (95% CI 0.245, 1.832)] when compared with control group of patients. Clinical stage appears to be the only significant predictor of DFS (p-value for stage = 0.04). More specifically, it appears that N stage mattered most (p-value for N stage < 0.0001). Conclusions: Adjuvant capecitabine does not appear to offer a benefit to SCCNH patients with recurrent/high risk disease. However, given the small number of patients in our study, future prospective trials are needed to explore the utility of adjunctive therapy in this patient population.
Prospective analysis of serial FLT-PET scanning to discriminate between true and pseudoprogression in glioblastoma.
Authors: Martha W. den Hollander, Roelien H. Enting, Jan Cees de Groot, Millad A. Solouki, Wilfred F.A. den Dunnen, Wim J. Sluiter, Martinus A.A.M. Heesters, Michiel Wagemakers, Jourik A. Gietema, Elisabeth De Vries, Jan Pruim, Anna Maria Elisabeth Walenkamp
Journal: Journal of Clinical Oncology (2014)

2009 Background: Response evaluation in glioblastoma (GBM) patients after concomitant radiotherapy and temozolomide (TMZ) is hampered by the occurrence of progressive contrast enhancing lesions on MRI that do not reflect true tumor progression. 18F-fluorothymidine (FLT) is a Positron Emission Tomography (PET) tracer that is taken up by proliferating cells. The goal of this study was to prospectively assess the value of FLT-PET in discriminating between true progression and pseudoprogression in patients with primary GBM treated with radiotherapy and TMZ (NTR3680). Methods: FLT-PET scans were performed before start and 4 weeks after radiochemotherapy. MRI scans were performed at these time points and after 3 cycles of adjuvant TMZ. Macdonald criteria were used for response evaluation on MRI. Pseudoprogression was defined as progressive disease on MRI after radiochemotherapy, with stabilization or improvement of enhancing lesions after 3 cycles of adjuvant TMZ. Changes in SUVmax and tumor to normal brain tissue ratios were calculated for FLT-PET and compared between patients with true progression and pseudoprogression. In case of multiple lesions, the mean of the SUVmaxof lesions was calculated. Ki67 staining in the primary tumor and overall survival data were analyzed. Results: Thirty patients, 28 patients with GBM and two with gliosarcoma (WHO grade IV), were included. Of the 19 patients assessed for pseudoprogression, 6 showed pseudoprogression and 6 showed true progression. There was no difference in (changes in) SUVmax and tumor to normal brain tissue ratios on FLT-PET between patients with true progression and pseudoprogression. Baseline FLT uptake correlated with overall survival (P = 0.002) but not with Ki67. Conclusions: FLT-PET scans do not discriminate between true progression and pseudoprogression in patients with GBM, but baseline FLT uptake does correlate with overall survival. Clinical trial information: NTR3680.
A rare etiology of idiopathic recurrent acute pancreatitis
Authors: Malay Sharma, Piyush Somani, Rajendra Prasad, Saurabh Jindal
Journal: Endoscopy (2017)

A 30-year-old Indian woman was referred with recurrent episodes of acute pancreatitis; she had experienced four episodes in the previous 7 months. There was no history of alcohol or drug intake. She was diagnosed with idiopathic recurrent acute pancreatitis (IRAP), as results of blood investigations, ultrasonography, computed tomography (abdomen), and magnetic resonance cholangiopancreatography were normal. Linear endoscopic ultrasound (EUS) was performed to diagnose the etiology of IRAP.