tbuckley/cabot-search huggingface dataset:
Pathologic down-staging following standard (SD) MVAC (methotrexate-vinblastine-doxorubicine-cisplatin) or dose-dense MVAC (DD) neoadjuvant chemotherapy (NC) for muscle-invasive urothelial bladder cancer (UC): A retrospective multicenter cohort of the French Genitourinary Tumor Group (GETUG/AFU).
Authors: Damien Pouessel, Sylvie Chevret, Emmanuelle Bompas, Laurys Boudin, Charlotte Joly, Thomas Grellety, Safae Aarab Terrisse, Helen Jane Boyle, Guilhem Roubaud, Christine Chevreau, Jérôme Dauba, Guillaume Moriceau, Ingrid Alexandre, Gael Deplanque, Angelique Chapelle, Elodie Vauleon, Alexandre Colau, Francois Audenet, Stephane Culine
Journal: Journal of Clinical Oncology (2014)

4550 Background: The benefit of NC on survival in UC has been shown with SD and is most evident in patients (pts) who achieve a pathological complete response (ypT0). In the last decade, physicians used SD or DD. Methods: We conducted a retrospective cohort study in 246 pts who received SD or DD for NC before a planned RC for cT2-T4, cN0 or cN+, M0 UC at 16 French centers from 2004 to 2012. The primary outcome was stage ypT0 at RC. Other PDS end points were no residual muscle-invasion (< ypT2), stage < ypT3, and nodal status. Toxicities, disease-free survival (DFS) and overall survival (OS) were also evaluated. Results: A total of 246 pts (182 cN0 and 64 cN+) were identified, 208 (84.5%) were male, 56 and 190 were treated with SD and DD, respectively. Median age was 62 [range: 56.3-67.4]. The median time from start of NC to RC was 101 days [80-122]. RC has been realized in 214 pts (87.0%), 48 (85.7%) and 166 (87.6%) after SD and DD respectively. In 17 unoperated pts, concomitant chemoradiotherapy was performed, 8 (14.28%) and 9 (4.7%) after SD and DD respectively. Mean follow−up from RC was 15 months [7-28.3]. Stage ypT0 were found in 18 (40%) and 58 (36.4%) pts after SD and DD respectively (p= 0.73). PDS were reported in 27 (61%) and 81 (55%) pts after SD and DD respectively (p=0.49). The following adverse events were observed with SD and DD respectively: grade 4 neutropenia (25% and 11%), grade 3/4 anemia (63% and 36%), grade 4 thrombopenia (0% and 4%), febrile neutropenia (9% and 7%), and grade 2 peripheral neuropathy (0% and 4%). Median DFS following RC was not reached (NR) and 50.9 months (95%CI 24.2-NR, p= 0.37) after SD and DD respectively, 31 (55.3%) and 103 (54.2%) pts were still disease-free. The median OS was NR in SD versus 55 months in DD (39.3-NR, p=0.85). Conclusions: The proportion of pts whose primary tumor were downstaged was not different according to the two regimen. Toxicity was confirmed to be higher in SD than in DD. The GETUG/AFU has launched a randomized trial assessing the DD and gemcitabine-cisplatin regimens in the perioperative setting.
Improving misclassification of ICD-9 coding for bone metastases in electronic medical records (EMR) using technology-enabled abstraction.
Authors: Alexander Liede, Rohini K Hernandez, Maayan Roth, Geoffrey Calkins, Katherine Larrabee, Leo Viana Nicacio
Journal: Journal of Clinical Oncology (2015)

e12652 Background: The accuracy of bone metastases coding is unknown for most large healthcare databases commonly used for epidemiologic research. EMR hold promise in cancer research in richness of data, but often clinically-relevant data elements are found in free-text unstructured data fields. We examined validity of bone metastases coding in structured EMR and claims data, relative to a gold standard data set based on the complete (structured and unstructured) EMR using a technology-enabled abstraction process. Methods: Breast cancer patients with ≥ 1 visit on or after Nov 18, 2010 were identified from 3 community oncology practices in the US. We calculated sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) of bone metastases ICD-9 code 198.5. We evaluated effects of misclassification when studying the proportion of patients treated with bone-targeting agents (BTA: zoledronic acid, pamidronate, denosumab), BTA timing relative to diagnosis, and skeletal complications. Results: Among 8796 breast cancer patients, 524 were confirmed to have bone metastases using the technology-enabled abstraction process. Structured data and claims missed 17% of bone metastases (89 of 524); Se was 67% based on structured EMR data fields (Sp 98%, PPV 71%, NPV 98%), and 77% based on claims (Sp 98%, PPV 72%, NPV 99%). Combining structured EMR and claims increased Se to 83% (Sp 98%, PPV 70%, NPV 99%). False negatives led to an overestimation of the proportion treated with a BTA or with a skeletal complication (Table). Date of diagnosis was delayed in structured data (median 32 days) and claims (median 43 days) compared to technology-assisted EMR. Conclusions: Misclassification and low sensitivity of bone metastases can lead to underestimation of absolute risks, dilution of associations, or residual confounding. Technology-enabled chart abstraction of the structured and unstructured EMR can greatly improve data quality and minimize bias. ICD-9 code structured data or claims unstructured only N 435 89 BTA treated 89% 15% BTA within 30 days of diagnosis 52% 7% Median time to BTA start (days) 43 86 ≥ 1 skeletal complication 55% 29%
Effect of cardiac resynchronisation therapy on sleep-disorderedbreathing in patients with systolic heart failure
Authors: Tomáš Kára, Miroslav Novák, Jiří Nykodým, KA Bybee, Jaroslav Meluzín, Marek Orban, Jolana Lipoldová, Zuzana Nováková, DL Hayes, Miroslav Souček, Jiří Vítovec, VK Somers
Journal: Circulation (2004)

We evaluated the short-term effect of cardiac resynchronization
therapy (CRT) on sleep apnea in patients with systolic heart
failure. BACKGROUND: Sleep-disordered breathing is common in
patients with left ventricular systolic dysfunction.
CONCLUSIONS: CRT reduces CSA severity in the short term. This
reduction correlated significantly with the CRT-mediated
reduction of mitral regurgitation.
Longitudinal monitoring of <i>BRAF</i> V600E mutation in urinary cell-free DNA of patients with metastatic cancers.
Authors: Filip Janku, Cecile Rose T. Vibat, Gerald Steven Falchook, Sarina Anne Piha-Paul, Aung Naing, Vivek Subbiah, Veronica R. Holley, Jennifer J. Wheler, Funda Meric-Bernstam, Goran Cabrilo, Vanda M. T. Stepanek, Rajyalakshmi Luthra, Lorieta Leppin, Latifa Hassaine, Karena Kosco, Mark Erlander
Journal: Journal of Clinical Oncology (2014)

e22175 Background: Detection and monitoring of oncogenic mutations in urinary cell-free (cf) DNA opens the possibility of a new paradigm for a truly non-invasive method of individualized care for metastatic cancer patients, which would enable the quantitation of mutational tumor load and respective concordance to therapeutic responsiveness followed by detection of emerging genomic alterations underlying acquired resistance. Methods: Multiple sequential urine samples were collected >/= 4 weeks apart from patients with advanced cancers harboring BRAF V600E mutation in the tumor tissue from a CLIA-certified laboratory before and after they started on systemic therapy. Quantitative assessment of BRAF V600E mutation in urinary cfDNA was developed using droplet digital PCR methodology (RainDance, MA) with enrichment of mutation-containing DNA fragments by pre-amplification of the BRAF gene. Detection limits were established as wild-type (<0.05% of mutant copies), low-mutant (0.05%-0.107%), mutant (>0.107%). Results: Urinary cfDNA was extracted from 17 patients with advanced cancers (melanoma, n=7; non-small cell lung cancer, n=3; colorectal cancer, n=2; other, n=5) with BRAF V600E mutation in the tumor. Of these 17 patients, 15 (88%) had the same mutation in urinary cfDNA (mutant, n=11; low-mutant, n=4). Longitudinal analysis of sequentially (>/= 4 weeks) collected urine samples demonstrated that changes in the amount of BRAF V600E cfDNA correlated with response to BRAF/MEK targeted therapy defined as percentage change per RECIST 1.1 (r=0.69, p=0.002). In addition, patients with decrease in the amount of BRAF V600E cfDNA had longer median time-to-treatment failure (259 days, 95% CI 240-278 vs. 61 days, 95% CI 59-63; p=0.002). Conclusions: Our data suggest that detecting BRAF V600E mutation in cell-free DNA from urine can offer a noninvasive tool for monitoring of therapeutic efficacy in patients with cancers and BRAF V600E mutation treated with BRAF/MEK targeted therapy.
Overcoming cell size escape from tumor treating fields using a varying frequency treatment paradigm in vitro.
Authors: Rosa S. Schneiderman, Moshe Giladi, Yaara Porat, Mijal Munster, Uri Weinberg, Eilon David Kirson, Yoram Palti
Journal: Journal of Clinical Oncology (2013)

e22134 Background: TTFields Therapy at 200 kHz received FDA approval for the treatment of patients with recurrent glioblastoma (GBM) based on the results of a phase III clinical trial. Radiological responses were observed in 14% of the treated patients. The lack of radiological response in the remaining patients suggests that GBM cells may escape the effect of TTFields over time. The goals of the present study were to identify possible routes by which cancer cells can escape the antimitotic effect of TTFields and to explore ways to overcome such escape mechanisms. Methods: Measurements of cell size before and after 72 hours TTFields application revealed a significant volume increase in 10 cancer cell lines (17% - 101%). A2780 ovarian cancer cultures (cell volume 2.0+0.2 pL) exhibit maximal inhibition by TTFields at 200 kHz. Twenty four hour application of 200 kHz TTFields led to a 70+29% increase in average cell volume (p&lt;0.05). FACS analysis showed that TTFields application to A2780 cells led to a 44% increase in the G2 population due to the antimitotic effect of TTFields. However, the increase in the G2 proportion is not sufficient to explain the increase in cell volume seen after TTFields application. Furthermore, after an additional 24 hours of treatment, the fraction of cells in the G2 population returned to its original percentage (30%), while the increase in cell volume remained high (67+26%). Results: Previous publications demonstrated an inverse relationship exists between cell size and optimal TTFields frequency. Thus an increase in cell size may allow cells to avoid the maximal TTFields effect. To attempt to overcome such cell size escape we decreased the frequency of the TTFields from 200 to 150 kHz after 24 hours treatment to coincide with the increase in cell volume. We found that varying the frequency from 200 to 150 kHz increased the inhibitory effect of TTFields compared to continuous treatment at 200Khz (37+10% and 57+16% decrease in cell count, respectively; p=0.043). Conclusions: This is the first evidence of an escape mechanism from the antimitotic effect of TTFields. The results presented provide a simple way to restore treatment efficacy by varying TTFields frequency in parallel to the change in cell volume.
A review of family caregiving intervention trials in oncology
Authors: Betty Ferrell, Elaine Wittenberg
Journal: CA A Cancer Journal for Clinicians (2017)

Abstract This article contains a review of literature published from 2010 to 2016 on family caregiving in oncology. An analysis of 810 citations resulted in 50 randomized trials. These trials describe the need to prepare family caregivers for the complex role they play in cancer care. Several studies have demonstrated improved quality of life for family caregivers and improved emotional support from interventions. Several studies addressed communication and relational intimacy, which are key concerns. An additional focus of these trials was in the area of caregiving tasks and ways to diminish the burden of caregiving and preparedness for this role. Further research is needed in this area given the shift to outpatient care and as family caregivers become the primary providers of care. Future research should include expanding tested models of family caregiver support in clinical practice and in diverse populations. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:318–325. © 2017 American Cancer Society.
Phenotypic correlation of tumor uptake of exogenous glutamine radiotracer versus tumor mutational status.
Authors: Mark Dunphy, James J. Harding, Jason Stuart Lewis, Ingo K. Mellinghoff, Antonio Marcilio Padula Omuro, James Hsieh, Hanwen Zhang, Pat Zanzonico, Sriram Venneti, Sean Carlin, Anas Younes, John F. Gerecitano, Serge K. Lyashchenko, Louise Harris, Alicia Lashley, Hank Kung, Craig B. Thompson, David Paul Kelsen
Journal: Journal of Clinical Oncology (2015)

11014 Background: Fluoroglutamine (FGln) is a positron emission tomography (PET) clinical tumor imaging radiotracer now in a first in human trial. Glutamine metabolism in several cancer models has been linked both to aggressive tumor phenotype and specific oncogenic mutations. Methods: Adults with advanced solid tumors or lymphoma with adequate end organ function are eligible for this phase 1 trial. Microdose radiotracer is given by IV bolus, followed by serial PET scans over a 3-hour period. The primary endpoint is safety, pharmacokinetics, metabolism and bio-distribution of FGln, to be reported separately. Secondary endpoint analysis compares tumor uptake of exogenous glutamine tracer versus tissue-derived tumor biomarkers. Results: 20 pts: median age 75 (range 21-75); male 40%; primary tumor site: brain (6), pancreas (3), breast (3), kidney (2), stomach (2), lung (1), large bowel (1), lymph node (1), adrenal gland (1); histology: adenocarcinoma (11), neuroendocrine (2), lymphoma (1), astrocytoma/oligodedriglioma/GBM (6); mean tumor size 2.8cm (range 1.1 to 11.5). Tumor uptake of exogenous glutamine tracer varied between pts with PET-positive tumors (n = 12) and PET-negative (n = 8); tumor uptake expressed as tumor/blood ratio of tracer concentrations, ranged 0.8-4.4. Uptake did not correlate with pre FGln-injection serum glutamine levels (R2= 0.005); median serum glutamine concentration 610 (range 425-982). 14 pts with tumoral DNA sequencing available or pending were identified. Mutations in TCA cycle genes occurred in 6 of 14 pts (2 with IDH R132H, 1 with FH F402L, 3 with SDH-A/B alterations). Highest observed tumor uptake of exogenous glutamine radiotracer and the longest retention of tracer were observed in 2 pts with tricarboxylic acid (TCA) cycle mutations. Conclusions: Fluoroglutamine PET detected tumors in a variety of cancer types, including patients with known mutations affecting tumor metabolism. Clinical trial information: NCT01697930.
A Phase II Study of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Treatment of Patients with Relapsed and Refractory Mantle Cell Lymphoma (MCL).
Authors: Yasuhiro Oki, Barbara Pro, Ebrahim Delpassand, Verushka Ballaster, Peter McLaughlin, Jorge Romaguera, Michael Wang, Frederick B. Hagemeister, Anas Younes
Journal: Blood (2004)
Factors affecting the offering and enrollment of patients on clinical trials in radiation oncology.
Authors: Shayna Eliana Rich, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2013)

e17571 Background: Improvements in cancer treatment require significant patient involvement in research, which may be particularly limited for new technologies such as proton radiation therapy. Studies with biased referrals or enrollment may not be generalizable to a general population. This study examines the reasons why patients were not offered or refused enrollment in clinical trials at the University of Florida Proton Therapy Institute (UFPTI). Methods: All patients seen at UFPTI between April-October 2012 for proton therapy for tumor sites with a clinical trial available (N=463) had information collected prospectively regarding whether they were offered enrollment and consented for clinical trials, and the reasons for each decision. The majority of patients had already secured funding for proton therapy. Results: Seven percent (34/463) of patients were ineligible for an available clinical trial, due to study exclusion criteria, concerns for patient safety based on comorbidity, or concerns for data integrity (e.g., other non-skin cancer within five years). Only 3% (9/275) of eligible patients were not offered a clinical trial. Forty-four percent (99/226) of patients offered a clinical trial refused. The most common reasons for refusal included: discomfort with lack of mature data, dislike of protocol, fear that protocol is not best option for disease control, and fear of side effects. Although UFPTI treats a variety of malignancies, the overwhelming majority of those who refused consent were prostate adenocarcinoma patients, who often self-referred for proton therapy. Conclusions: Despite near universal availability of clinical trials at UFPTI, less than half of patients enroll in clinical trials. The greatest factor for non-enrollment appears to be patient acceptance. Despite the availability of non-randomized trials with fairly standard treatment approaches, 44% refused to enroll on clinical trials, suggesting discomfort for less well documented treatment approaches. Further studies should examine whether findings are similar among all US cancer patients, as patients seeking proton therapy may not resemble the general population.
REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB).
Authors: David A. Reardon, James J. Vredenburgh, Annick Desjardins, Ronald G. Steis, Erin M. Dunbar, Nitin B. Chandramouli, Olivier Rixe, Jennifer A Green, Thomas A. Davis, John Howard Sampson
Journal: Journal of Clinical Oncology (2012)

TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate use cases, Sampson 2008) suggests that rindopepimut may induce specific immune responses and regression in multifocal and bulky residual tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties (including impaired maturation of dendritic cells and disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010]) may further optimize EGFRvIII-specific immune response and antitumor activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in patients (pts) with 1 st or 2 nd relapse of EGFRvIII+ GB. BV-naïve pts will be enrolled to Group 1 (n=70: randomized 1:1 to BV plus either rindopepimut/GM-CSF or control injection [low-dose KLH]) while BV-refractory patients will enter Group 2 (n=25: to receive BV plus open-label rindopepimut/GM-CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or open-label vaccine is given in priming phase (days 1, 15 and 29), then monthly until PD. Tumor response is assessed every 8 weeks, and patients are followed for survival after PD. Objectives are PFS at 6 months (primary), objective response rate, PFS, OS, safety, immunogenicity and elimination of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).
Abstract MP036: Prevalence of American Heart Association Heart Failure Stages in African-American and White Middle Aged Adults: The CARDIA Study
Authors: Samuel S Gidding, Donald Lloyd-Jones, Joao Lima, Bharat Ambale-Venkatesh, Sanjiv Shah, Ravi Shah, Cora E Lewis, David R Jacobs, Norrina Allen
Journal: Circulation (2017)

Background: Symptomatic heart failure is increasingly recognized as a chronic and lethal condition with antecedents, earlier in life, including hypertension, obesity, and diabetes. The American Heart Association (AHA) has developed a four stage heart failure staging classification system. At the year 30 examination (and prior examinations) of the Coronary Artery Risk Determinants in Young Adulthood (CARDIA) data has been collected on a population-based cohort of 48-60 year old black and white men and women. Methods: Data on demographics and attributes for classification into a heart failure stage were retrieved from the CARDIA database. Participants were then assigned to No Risk, stage A (asymptomatic but with risk factors (hypertension, obesity, diabetes, atherosclerotic disease, metabolic syndrome, cancer), stage B (asymptomatic but prevalent cardiac structural abnormality or prevalent heart disease(prior myocardial infarction, LV hypertrophy, low LV ejection fraction, asymptomatic valve disease), or stage C/D (symptomatic, merged). Results: The Table shows the prevalence of each heart failure stage by race and gender and for the CARDIA cohort examined in Y30 without missing data. Almost half the cohort is at risk (Stage A) and about a fifth has heart failure associated co-morbidities (Stage B). Only about a fifth of African-Americans have no heart failure risk while about two fifths of whites have no risk, mostly secondary to higher prevalence of obesity and diabetes (p &lt; 0.01). There is a higher prevalence of stage C/D in African-Americans. Conclusion: Heart failure prevention should begin in young adulthood, particularly in African-Americans.
The impact of dose modification or termination of S-1 as adjuvant therapy on survival of locally advanced gastric cancer underwent curative gastrectomy.
Authors: Takeshi Kawakami, Nozomu Machida, Etsuro Bando, Kaori Hayashi, Hiromichi Shirasu, Masahiro Kawahira, Sadayuki Kawai, Yosuke Kito, Yukio Yoshida, Satoshi Hamauchi, Akiko Todaka, Takahiro Tsushima, Tomoya Yokota, Kentaro Yamazaki, Akira Fukutomi, Masanori Terashima, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2017)

193 Background: Adjuvant S-1 therapy for pStage II/III gastric cancer (GC) patients (pts) after curative resection is standard treatment in Japan, however, prognosis of pStage III is still poor. There are few reports investigating the association of treatment exposure with survival. Therefore, we investigated the impact of dose modification or termination of S-1 as adjuvant therapy on overall survival (OS). Methods: The data of locally advanced GC pts who underwent gastrectomy with D2 lymph-node dissection in Shizuoka Cancer Center between Jan 2007 and Aug 2013 were retrospectively collected. Inclusion criteria were as follows: age 20 to 80 years; ECOG PS 0 or 1; histologically proven adenocarcinoma; pStage III under TNM 7th edition; R0 resection; initiation of S-1 within 56 days after surgery. S-1 was administered for 4 weeks followed by a 2 weeks rest. We defined completion of planned S-1 therapy as continuation of S-1 one year after surgery. Results: One hundred and six pts satisfied inclusion criteria. Pts’ characteristics were as follows: median age, 67 years (range, 38-78); male/female, 77/29 pts; ECOG PS 0/1, 72/34 pts; primary tumor location EGJ/U/M/L, 1/27/45/33 pts; and pStage IIIA/IIIB/IIIC, 25/41/40 pts. Fifty-five pts (51%) needed dose modification (dose reduction and/or schedule alteration). Eighty-two pts (77%) achieved completion of planned S-1 therapy. Five year OS rate was 59.9%. Among potential prognostic factors for OS in univariate analysis (age, PS, pStage, completion of planned S-1 therapy, dose modification), completion of planned S-1 therapy (HR 0.26; 95% CI 0.13-0.51; p &lt; 0.001) and PS 0 (HR 0.52; 95% CI 0.27-0.99; p = 0.048) were good prognostic factors and dose modification was not prognostic factor (HR 1.06; 95% CI 0.53-2.12; p = 0.876) for OS. Conclusions: This study suggested that completion of planned adjuvant S-1 therapy and PS 0 were good prognostic factors for OS and appropriate dose modification might not worsen their prognosis.