tbuckley/cabot-search huggingface dataset:
Abstract 12023: The Effectiveness Teaching Continuous Chest Compression CPR Using a Combined Program of Watching a Brief Video, Seeing a Live CPR Demonstration Performed on a Mannequin and Using the Celtic Cell Phone Application for Real Time Feedback
Authors: Srishti Nayak, Tomas Nuno, Whitney Burns, Daniel L Beskind
Journal: Circulation (2016)

Introduction: CPR training via cell phone application is an effective way to train laypersons in CPR. However, it is unclear whether using a combination of watching a brief video and live demonstration of CPR as well as receiving real time feedback via a cell phone application improves CPR quality, responsiveness and confidence. Objective: To determine if viewing a brief chest compression only (CCO) CPR video, watching a live demonstration and receiving real time feedback via the Celtic cell phone app. is an effective modality in training laypersons CCO-CPR leading to improved performance, responsiveness, and confidence. Methods: This was a prospective cohort control analysis from June 2014 till January 2016. Participants had little or no previous CPR training. Participants were consented and filled out an 8-question survey regarding baseline confidence in performing CPR. A CPR content quiz was answered to determine fluency in CPR. All participants then performed CPR on a mannequin while receiving real time feedback via the Celtic cell phone app. Finally they received formal “verbal” and “visual” training on CCO-CPR. Compression rate was categorized as very good if their compressions per minute (cpm) were &gt;90, Ok if CPM was 80-89 and poor if CPM was &lt;80. Compression depth categories were: Excellent: &gt;2.0 inches, Good: 1.5-2.0 inches and Poor: &lt;1.5 inches. Results: There were statistically significant improvements in percentage of participants (N=67) with very good compression rates (OR=49.1; 95% CI: 17.8, 135.0) and excellent compression depth (OR=26.5; 95% CI: 7.3, 96.1) from before to after the training and feedback using the Celtic app. Average score for confidence questions (difference=4.34; 95% CI: 3.67, 5.00); willingness to perform CPR in cardiac arrest patients (OR=6.83; 95% CI: 2.75, 17.01); and percent of content knowledge (difference=30.2; 95% CI: 25.0, 35.4) were significantly improved. Conclusions: CCO-CPR training via a combined program of watching a brief CCO video and live demonstration as well as getting real-time feedback via the Celtic cell phone application demonstrated statistically significant improvements in both target compression rate and depth as well as confidence in laypersons attempting to perform CCO-CPR.
What is the benefit from second- and third-line (2L and 3L) therapy for extensive disease small cell lung cancer (ED-SCLC)? A prospective study of patterns, discontinuation, and survival in US community practices.
Authors: Donald A. Richards, Maen A. Hussein, Steven L. McCune, Brian Kent Ulrich, Bijoy PanKaj Telivala, Marc Monte, Mark D. Danese, Michelle L. Gleeson, Deborah P. Lubeck, Jenine Sanzari, John R. Penrod, Yong Yuan, Pranav Abraham, Beata Korytowsky, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

e20567 Background: Limited 2L therapy options and no established 3L standard of care make treating relapsed ED-SCLC challenging. This study explores current treatment and outcomes in patients receiving 2L and 3L therapy in community practice. Methods: CA209-118, a prospective observational study of adult lung cancer patients in 70 US community practices, enrolled ED-SCLC patients on or before initiating 2L therapy from April 2014 to September 2017; they were followed until death, end of follow-up, or study withdrawal. Study sites reported therapy start and end dates and reasons for discontinuation. Platinum-refractory (PT-ref) was defined as a gap of ≤90 days between the end of 1L and start of 2L; platinum sensitive (PT-sen) was a > 90-day gap. Results: 165 ED-SCLC patients were enrolled prior to initiating 2L. The most common 2L therapies were topotecan (TOP, n = 89), PT + etoposide or irinotecan (ETOP or IRI, n = 30), paclitaxel monotherapy (PAC, n = 12), or nivolumab (n = 9). Mean age was 65 years, 53% were male, 96% were white, 94% were current or former smokers, and 17% had ECOG scores ≥2. At database (DB) lock, 26 (16%) completed 2L, 26 (16%) were still receiving 2L therapy, 78 (47%) discontinued 2L due to progression or death, 18 (11%) due to adverse events, and 17 (10%) for other reasons. In 2L, median OS was 5.1 months (95% CI: 4.6, 6.3) overall, 4.4 months (95% CI: 3.7, 5.8) for PT-ref patients (n = 69) and 6.3 months (95% CI: 5.1,7.8) for PT-sen patients (n = 96). Median time to discontinuation or death was 1.9 months (95% CI: 1.6, 2.3). The 91 3L patients most commonly received PAC (n = 24), TOP (n = 18), and PT + ETOP or IRI (n = 10). At DB lock, 13 (14%) completed 3L, 11 (12%) were still receiving 3L therapy, 45 (49%) discontinued due to progression or death and 22 (24%) due to AEs or other reasons. In 3L, median OS was 5.8 months (95% CI: 4.3, 7.1) and time to discontinuation was 2.1 months (95% CI: 1.4, 2.8). Conclusions: Treatment patterns in community practice for 2L and 3L appear largely limited to historical agents. Median survival and duration of therapy were short, highlighting the need for more effective and tolerable treatments in ED-SCLC.
Target-based therapeutic matching of phase I trials in patients with advanced breast cancer (BC pts) in the Royal Marsden Hospital Drug Development Unit (RMH DDU).
Authors: Brent O'Carrigan, Awais Jalil, Dionysios Papadatos-Pastos, Samuel John Harris, Juanita Suzanne Lopez, Udai Banerji, Johann S. De Bono, Timothy Anthony Yap
Journal: Journal of Clinical Oncology (2016)

11508 Background: Advanced BC pts are often referred to phase I units for treatment with novel antitumor agents after exhausting conventional therapies. Such pts are heterogeneous, with discordant responses to molecularly targeted agents (MTA). This study assessed outcomes after rational pt stratification in BC pts. Methods: Retrospective study of BC pts treated in RMH DDU (2009-2015). Baseline data included pt demographics, prognostic variables, targeted next generation sequencing (NGS) data and trial allocation as matched to a MTA or un-matched. Endpoints included response rates, overall (OS) and progression free survival (PFS). Results: 97 pts with 113 trial encounters (ECOG PS 0/1 43/70; median age 51y, median sites of disease 3 [1-7]) were included in this study. 14 pts participated in ≥ 2 trials. BC subtypes included ER+/PR+/HER2- (46%), TNBC (35%) and HER2+ (18%). Median 3 (0-8) prior lines of chemotherapy; median 2 (0-4) prior lines of endocrine therapy for ER/PR+; median 2 (1-4) prior lines of anti-HER2 therapy for HER2+ pts. 32/113 (28%) pts harbored germline BRCA1/2 mutations. Common NGS somatic aberrations included TP53 (15%), PIK3CA (14%), PTEN (6%) and ATM (4%) mutations. Antitumor pathways targeted included PI3K (39%), PARP (27%), androgen receptor (AR) (12%) and others (22%). Overall median PFS was 3 months (m, range 0-14) and median OS 7m (0-58). 59/113 (52%) pts accrued to matched trials (BRCA1/2mutant pts + PARP inhibitors (24/59); ER+ and/or AR+ pts + AR inhibitors (16/59); PI3K aberrations + PI3K/mTOR inhibitors (7/59) and HER2+ pts + HER2 antibody drug conjugates (4/59). Pts on matched vs unmatched trials had superior PFS 4m vs 3m (HR 0.56, 0.28-0.65, p = 0.001). In 107 evaluable pts, clinical benefit rates (RECIST partial response or stable disease) were significantly higher for matched vs unmatched trials (34/56, 60% vs 17/51, 33%; p = 0.004). Treatments were well tolerated; 9/113 (8%) pts discontinued trials for toxicity. Conclusions: Phase I trials are well tolerated with meaningful clinical benefit in BC pts. These data also indicate that efforts to rationally match novel treatments to actionable aberrations are feasible and improves outcomes.
Is there an optimal time to initiate adjuvant chemotherapy in order to predict the benefit of survival in NSCLC?
Authors: Xiaoyu Zhai, Ziping Wang
Journal: Journal of Clinical Oncology (2016)

e20012 Background: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC). However, few studies have reported the possible correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: Clinical data of 925 NSCLC patients who received curative resection and postoperative AC in the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were analyzed retrospectively. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The survival curve of DFS was estimated by Kaplan-Meier method, and Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cutoff value of TTAC was set at day 35 after curative resection, based on which the patients were assigned to two groups: group A ( ≤ 35 days) and group B ( > 35 days). Unfortunately, there was no significant difference in DFS between the two groups (P = 0.246), indicating that TTAC was not an independent prognostic factor of DFS. Further comparison still showed no significant difference in DFS in 258 PSM pairs (P = 0.283). Conclusions: There was no significant correlation between TTAC and DFS in NSCLC patients. Larger-sample studies are needed to further verify this conclusion.
P05.29 Improvement of stereotactic radiosurgery plan quality with multiple non-coplanar VMAT beams
Authors: J Zindler, D Hartgerink, A Swinnen, M Guckenberger, N Andratschke, M Zamburlini, D de Ruysscher, R Popple
Journal: Neuro-Oncology (2018)

Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Optimal SRS plan quality is important to minimize the risk of severe side effects such as radionecrosis.1,2 We studied if multiple non-coplanar VMAT beams are beneficial over one non-coplonar VMAT beam in terms of SRS plan quality. Three artificially contoured scenarios of brain metastases on an anonymized cerebral planning-CT were used. The first case had 10 BM, the second case 5 BM, and the third case 7 BM. Treatment plans were made in 3 institutions: a single non-coplanar SRS VMAT plan (MAASTRO Clinic=M), HyperArc (multiple non-coplonar beams, Zuerich=Z), and HyperArc (Birmingham, Alabama=A). MAASTRO Clinic and Zuerich used 1 mm GTV-PTV margin, and Alabama 0 mm GTV-PTV margin. The presciption dose was 21 Gy in a single fraction for case 1 and 18 Gy in a single fraction for case 2 and case 3. All plans were normalized that 99% of the comulative planning target volumes (PTVsum) were covered with 100% of the prescription dose. Multiple non-coplanar VMAT beams (e.g. HyperArc) and avoidance of a GTV-PTV margin resulted in better conformity in the high dose region. For case 1 the Paddick GI was 7.2 (M), 3.5 (Z), and 3.8 (A) respectively. For case 2 the Paddick GI was 4.1 (M), 2.9 (Z), and 3.0 (A). For case 3 the Paddick GI was 5.5 (M), 3.2 (Z), and 3.1 (A). The mean brain dose for case 1 was 6.5 Gy (M), 4.8 Gy (Z), and 4.0 Gy (A). The mean brain dose for case 2 was 2.8 Gy (M), 2.2 Gy (Z), and 2.0 Gy (A). The mean brain dose for case 3 was 4.7 Gy (M), 2.8 Gy (Z), and 2.6 Gy (A). The cumulative V12Gy for case 1 was 133 cc (M), 54 cc (Z), and 35 cc (A). The cumulative V12Gy for case 2 was 25 cc (M), 18 cc (Z), and 12 cc (A). The cumulative V12Gy for case 3 was 71 cc (M), 30 cc (Z), 20 cc (A). Optimal SRS plan quality with sparing of healthy brain tissue was achieved with usage of multiple non-coplanar beams (e.g. HyperArc) and avoidance of a GTV-PTV margin. 1) Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs. Gamma Knife. Liu H et al. Front Oncol. 2016 Feb 11;6:26 2) Comparison of plan quality and delivery time between volumetric arc therapy (RapidArc) and Gamma Knife radiosurgery for multiple cranial metastases. Thomas E et al. Neurosurgery. 2014 Oct;75(4):409–17
Feasibility of implementing the G8 screening tool in geriatric patients in oncology clinics across multiple institutions.
Authors: Rashida Haq, Camilla Wong, Pauline Gulasingam, Amy Kong, Youmna Ahmed, Jarred Rosenberg
Journal: Journal of Clinical Oncology (2018)

e22026 Background: Geriatric patients often experience more toxicity from cancer treatments due to their age and co-morbidities. The Comprehensive Geriatric Assessment (CGA) identifies patients at higher risk of adverse events, functional decline and treatment toxicity, which allows directed interventions to attain therapeutic harmonization. However, CGAs are time consuming and resource intensive. Validated geriatric screening tools such as the G8 may be more feasible to identify patients who require further assessments and close monitoring. Methods: The feasibility of using the G8 screening tool to better identify patients with geriatric impairments in oncology clinics was assessed. Patients ≥70 years of age, diagnosed with a solid or hematological malignancy, considering systemic therapy, and attending clinics at two academic institutions (St. Michael’s Hospital (SMH) and Sunnybrook Health Sciences Centre (SHSC)) and one community hospital (Michael Garron Hospital (MGH)) were eligible to participate. Medical staff administered a paper-based G8 tool to consented patients at SMH and SHSC, and an electronic medical record (EMR) embedded G8 tool at MGH. Feasibility was defined as the proportion of eligible patients with a completed G8 tool and the cut-off of ≤14 indicated an abnormal score. Results: The proportions of eligible patients that completed the G8 were 0.84 (83/99), 0.65 (60/92) and 0.47 (9/19) at SMH, SHSC and MGH respectively. Common reasons for not completing the G8 were lack of time, clinicians’ opinion on patient suitability and undecided treatment plans at the first visit. Overall, 87.5% had a solid cancer and the most common tumor sites were lung, breast and colorectal. Among the 152 completed G8 tools, a proportion of 0.52 (90/152) had an abnormal score. Poly-pharmacy and weight loss contributed to majority of the lower scores. Conclusions: The feasibility of G8 implementation varied across the three institutions with sub optimal uptake. EMR embedded G8 did not improve the uptake. Institutions need to adopt site specific strategies to facilitate and promote the use of the G8 tool. Barriers and facilitators to implementation are being assessed at SMH.
An examination of the BET bromodomain inhibitor JQ1 in comparison with histone deacetylase and aurora kinase inhibitors in human cancers.
Authors: Robert Alan Nagourney, Paula J Bernard, Federico Francisco, Ryan Wexler, Eknath A. Deo, Milan Rohit Sheth, Nilesh L. Vora, Steven Evans
Journal: Journal of Clinical Oncology (2016)

e14114 Background: Up to 70% of human cancers overexpress MYC oncogenes, many via mutation, amplification or translocation, yet MYC has remained a challenging target for therapeutic intervention. MYC activation is associated with altered histone acetylation (HDAC) and the upregulation of aurora kinases (AK) (Gabay, Cold Spring Harbor, 2014). The BET bromodomain (BD) inhibitor JQ1 has been shown to downregulate MYC activity. Methods: We used a phenotypic platform to examine human tumor primary culture microspheroids isolated directly from patient surgical specimens to examine JQ1 activity in comparison with the activity of the HDACi, SAHA, & 2 AKi's, Alisertib & Tozasertib. Dose response curves generated by Ex Vivo Analysis of Programmed Cell Death (EVA/PCD) (Nagourney, Anticancer Res. 2012) were interpolated to provide LC50 values for comparison by Pearson Moment. Results: JQ1 reveals activity in human tumors with NSCLC, bladder cancer and Ewing's Sarcoma falling in the sensitive range and a heavily pretreated Wilms tumor and several ovarian cancers falling in the more resistant range. Pearson Moment correlations, though preliminary, revealed the strongest correlation between JQ1 and SAHA (r = 0.92) followed by Alisertib (r = 0.54) and Tozasertib(r = 0.24). Conclusions: BD inhibitors reveal activity in human tumors. Activity appears to differ by tumor type and between individual specimens within the same tumor types. Evidence of correlation with SAHA a pan-HDACi as well as the AKi's suggests modes of action for JQ1 and may also offer potential strategies for future therapeutic interventions. Phenotypic platforms provide the opportunity to examine operative cellular signaling events in the presence or absence of detectable genomic alterations. As several HDACi's are FDA approved and the AKi's are in late stage clinical development, the entry of BD inhibitors into clinical therapy could offer the development of novel combinations and/or sequences of these drug classes. Additional studies are underway, as will be reported. Supported by the Memorial Medical Center Foundation and the Vanguard Cancer Foundation
<i>Clostridium difficile</i> carriage and its implications in preoperative colorectal cancer patients.
Authors: Yi Zheng, Peng Zhao, Weiqin Jiang, Lulu Liu, Zhou Tong, Dazhi Jin, Weijia Jia Fang
Journal: Journal of Clinical Oncology (2016)

e15084 Background: Clostridium difficile (C. difficile) colonizes the large intestine, with toxigenic strains causing infection resulting in serious morbidity and mortality, which has emerged as a worldwide health-care threat. Cancer is a known risk factor for C. difficile infection. Although the whole process of colonization to infection takes place in the large intestine, the real carriage pattern of C. difficile in preoperative colorectal cancer (CRC) patients has not been studied. Herein, we conduct this pilot study in order to reveal the potential relationship between C. difficile carriage and CRC patients who were scheduled to accept surgical resection. Methods: Stool samples from 206 preoperative CRC patients were collected in this study. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. The clinical and pathology results of CRC patients were then collected for further analysis. Results: Thirty-three (16.0%) samples from preoperative CRC patients were confirmed to be C. difficile positive. CRC patients over 60 years old had a C. difficile positive rate as high as 18.2%. In contrast, patients who were younger than 60 years old had a C. difficile positive rate of only 12.2% (p = 0.02). Strikingly, the C. difficile positive rate for T4 and non-T4 CRC patients was 23.6% and 13.2% (p = 0.01), while C. difficile positive rate for lymph nodes (LN) positive and LN negative patients was 22.3% and 10.7%, respectively (p = 0.02). Meanwhile, stool occult blood (OB) negative CRC patients had a higher C. difficile positive rate than OB positive patients (24.0% to 11.5%, p = 0.02). No association was found between C. difficile carriage and cancer sites, macroscopic morphology, differentiation, and days of hospitalization. Conclusions: T4 or LN positive preoperative CRC patients have higher risk of C. difficile carriage. Since these patients inevitably need adjuvant chemotherapy, the call for sustained monitoring of C. difficile carriage is apparently urgent in order to avoid discontinuation of chemotherapy. Besides, elderly or OB negative preoperative CRC patients should also be noticed for potential C. difficile carriage.
Metastatic neuroendocrine neoplasia treatments in patients over 70 years of age: A retrospective outcome analysis.
Authors: Alberto Bongiovanni, Federica Recine, Flavia Foca, Valentina Fausti, Nada Riva, Sebastiano Calpona, Stefano Severi, Chiara Liverani, Alessandro De Vita, Chiara Spadazzi, Giacomo Miserocchi, Greta Fabbri, Laura Mercatali, Dino Amadori, Toni Ibrahim
Journal: Journal of Clinical Oncology (2018)

e16181 Background: Neuroendocrine Neoplasia (NEN) incidence increases with age above all at 70 years-old. This population is usually underestimated in clinical trials and because of co-morbidities and low performance status (PS), prognosis’ informations of this subgroup are lacking. Aim of the study was to retrospective analyse the outcome of elderly mNEN patients (pts) with multimodality therapies Methods: From June 2007 to march 2016 we collected data from pts ≥70 y with mNEN. Comorbidities were summarized by the Charlson Comorbidity Index (CCI). Kaplan-Meier method was used to estimate overall survival (OS), Cox’s proportional hazard model to assess the impact of prognostic factors. Adjusted hazard ratios (HR) were calculated with 95% confidence interval (95% CI). Results: We identified 145 pts (86 male/59 female) ≥70 y with mNEN. Median age was 74 y (70-87); 56 pts (38.6%) were 75 y or older. ECOG PS was 0 in 45.7%, 1 in 46.5% and ≥ 2 in 7.8% pts. According to the CCI, 57 (41.0%) had 0, 52 (37.4%) 1; 19 (13.7%) 2 and 11 pts (7.9%) a score ≥ 3. Hepatic or extra-hepatic metastases were identified in 58 (40%) and 29 (20%) respectively, both in 58 (40%) pts. G1-G2 NEN were found in 95 (75.4%), and G3 NEN in 31 pts (24.6%). Octreoscan/Gallium and FDG PET were positive in 130 (94.2%) and 77 (70.3%) pts respectively. Median follow up was 72.3 (53.2-85.1) months . First Line treatment was : Somatostatin analog (SSA) in 79 pts, peptide radionuclide therapy (PRRT) in 23, chemotherapy (CHT) in 36 pts. 7 didn’t receive first line treatment and 102 pts received more than 1 line. PS ECOG and FDG PET results were identified as independent prognostic factors for OS, with an higher risk for patients with PS ECOG ≥0 and with positive FDG PET, while age at diagnosis showed an hazard ratio of 1.10 (95%CI:0.99-1.26). Median OS was 5.1 (3.4-6.6) y. No difference in mOS were seen according to CCI. G1/G2 NEN Patients who underwent PRRT as first line had a mOS of 6.5 y (3.3-NE) , SSA 5.7 y (4.2-7) and CHT 5.9 y (0.4-NE). G3NEN pts treated with CHT had a mOS of 1.5 y (1.0-2.5) Conclusions: Our results show that in clinical practice treatment has a positive impact on OS of elderly pts included patients with age > 80 y. FDG PET and PS ECOG remain independent prognostic factors