tbuckley/cabot-search huggingface dataset:
Rapid, real-time central pathology review for E1412: A novel and successful paradigm for future National Clinical Trials Network diffuse large B cell lymphoma studies.
Authors: Rebecca L. King, Grzegorz S. Nowakowski, Thomas E. Witzig, David W. Scott, Richard F. Little, Fangxin Hong, Randy D. Gascoyne, Brad S. Kahl, William R Macon
Journal: Journal of Clinical Oncology (2017)

7547 Background: E1412 statistical design is based on results of lenalidomide/RCHOP (R2CHOP) vs RCHOP in ABC-DLBCL as determined by NanoString gene expression profiling (GEP). Central pathology review (CPR) was conducted to confirm diagnosis and to ensure adequate tissue for GEP. Initially, CPR occurred after randomization and treatment initiation. Due to high ineligibility rate (IR), the protocol was amended to include real-time CPR to determine patient eligibility prior to study enrollment. We describe the revision and how it affected the IR. Methods: Pre-amendment, CPR was done retrospectively. Post-amendment, CPR was done prior to enrollment, in real time, on a submitted tissue block, H&amp;E, and CD20 slides. Based on CPR, if a diagnosis of DLBCL was confirmed, and sufficient tissue remained for GEP, a patient was deemed eligible and the submitter was notified by fax. Protocol goal was notification within 2 working days (WD) of receipt of materials at the CPR site. Results: Pre-amendment, 219 patients were enrolled. Material was typically received at the CPR site 6-9 months after patient registration. The IR with CPR was 36% for all those enrolled, and 26% for patients with adequate tissue for GEP. Post-amendment, 218 patients were submitted for CPR: 145 (67%) were eligible; 73 (33%) were ineligible. Reasons for ineligibility included insufficient tissue (n=27) or a diagnosis other than de novo DLBCL (n=46). Notification of eligibility occurred in a median of 2 WD (Mean 2 WD; Range 1-5 WD). 90% were notified within the protocol goal of 2 WD. GEP for all enrolled was completed within 6 weeks of CPR. Conclusions: The success of this novel, real-time CPR serves as a model for the future of NCTN DLBCL trials. When CPR is performed rapidly prior to enrollment, study slots may more accurately reflect the target population and eliminate excess costs. In the precision medicine era, rapid collection of relevant pathology and biomarker data is essential to trial success. Study Coordinated by ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs), supported by NCI grant # CA180820, CA180794, CA180790, CA180799, CA180833.
TCT-350 Safety and Performance of the Resorbable Magnesium Scaffold, Magmaris in a Real World Setting - First 400 Subjects at 12-month Follow-up of the BIOSOLVE-IV Registry
Authors: Michael Lee, Adrian Wlodarczak, Johan Bennett, Jan Torzewski, Michael Haude, Mathias Vrolix, Thomas Buck, Adel Aminian, Rene van der Schaaf, Amin Ariff Nuruddin, Marcus Wiemer, Bryan Yan, Jan van der Heyden, Ralph Toelg, Bela Merkely, Andrejs Erglis, Johannes Brachmann, Didier Carrié, Robert Zweiker, Stephan Achenbach, Sebastian Philipp, Huay Cheem Tan, Mark Webster, Nigel Jepson, Michael Nguyen, Eric Eeckhout, Hans-Heinrich Minden, Christian Valina, Manel Sabate, Thomas Schmitz, Rafael Jose Ruiz-Salmeron, Christoph Liebetrau, Fabrizio Tomai, Holger Nef, Christopher Zeitz, Gillian A. Jessurun, Jean Fajadet, Madhav Menon, David Erlinge, Angel Cequier, Ulf Landmesser, Stephan Kische, Marco Moccetti, Constantin von zur Mühlen, Jochen Wöhrle, Franz Eberli, Peter Barlis, Hüseyin Ince, None victor legrand, Dougal Mcclean, Abid Assali, Henning Ebelt, Evald Christiansen, Guy Friedrich, Werner Jung, Kristof Graf, Graham Cassel, Helge Möllmann, Irene Lang, Alexander Schmeisser, Dirk Westermann, Florim Cuculi, Iftikhar Ebrahim, None Carlo Trani, Lisette Okkels Jensen, Martin Winterhalter, Harald Darius, Michael Magro, Stefan Verheye
Journal: Journal of the American College of Cardiology (2018)
Addressing advance directive completion rates on an inpatient oncology unit.
Authors: Susan McInnes, Navin Dhingra
Journal: Journal of Clinical Oncology (2018)

147 Background: Advanced directives (ADs), particularly heath care power of attorney (HC-POA), are not always obtained or documented for patients with cancer. Hospitalized cancer patients may become too ill to complete them, making treatment decisions difficult. Understanding patients’ end-of-life preferences and providing care congruent with their values is fundamental to quality care. Completing ADs is an important aspect of this process. However, AD rates for oncology patients are typically under 40%. Our team sought to measure and increase our oncology inpatient AD rates. Methods: An interdisciplinary group including oncology and palliative medicine physicians, nurses, social workers, care managers and quality leaders convened to address ADs on our inpatient oncology services as a quality improvement project. We completed a current state analysis, evaluated areas of wasted or redundant workflow and performed a root cause analysis, identifying 4 countermeasures: 1) educating patients and staff re the value of completing HC-POAs, 2) clarifying the role of each team member, 3) implementing a discussion script for HC-POA conversations and 4) tracking and reviewing HC-POA completion in daily multidisciplinary rounds. AD completion rate by discharge was collected weekly through the 12-week project (325 discharges) then monthly for 6 months (709 discharges.) Results: Our baseline HC-POA rate was 30% for hospitalized oncology patients. Completion increased to 39% with education, role clarification and use of a discussion script. When daily tracking was initiated with the entire care team, including medical oncology staff, fellow and residents, the AD rate increased as high as 65%. This model was implemented as a best practice and has been sustained with AD completion rates of 45-60% in the subsequent 6 months. Conclusions: Our interventions successfully and sustainably increased HC-POA completion rate by engaging the entire interdisciplinary oncology team around the need for HC-POA documentation. We standardized team communication about ADs into daily workflow in interdisciplinary rounds. This increased the comfort level of the entire team and normalized discussion of HC-POAs, contributing to increased AD completion.
Mutation of the DNA damage gene signature to predict for better outcome in malignant melanoma.
Authors: Mahesh Y. Iddawela, Arun Azad, Gail Risbridger
Journal: Journal of Clinical Oncology (2017)

e21036 Background: DNA damage response is a fundamental cellular pathway with an important role in maintaining genomic integrity. As Malignant Melanoma (MM) is associated with high mutation rates, and we postulated that mm is likely to have abnormal DNA repair pathway aberrations that could have prognostic and/or therapeutic significance. Methods: We conducted an unbiased assessment of genes involved in the DNA damage response through a comprehensive survey of established public data repositories and published literature and abstracts in all cancers. This survey was used to generate a 6-gene DNA Damage Signature (DDS). The DDS was then applied to 287 mm samples in The Cancer Genome Atlas. Results: The DDS was altered in 25% (72/287) of patients with mutations being present in all 6 genes including ATM (6%), TP53BP1 (7%), MDC1 (7%), BRCA1 (5%), PRKDC (8%) and RAD50 (1.4%). The DDS was more commonly altered in mm harboring alterations in BRAF (78%, 112/143), NRAS (89%, 73/82) or NF1 (75%, 5/20) than in triple wild type tumors (60%,19/32). The correlation between alteration in BRAF/NRAS/NF1 and DDS (p = 0.02) reached significance, as did the tendency for DDS and NF1 altered subtype to co-occur (p &lt; 0.05). Importantly, alteration in the DDS was associated with significantly longer disease free (88 vs. 44 months, p = 0.02) and overall survival (152 vs. 66 months, P = 0.02). The mutations in ATM and BRCA1, shown to be targets in other cancers for PARP inhibition were seen in these patients as well as other oncogenic or hot-spot mutations. Conclusions: The improved survival associated with alteration of the DDS implicate DNA damage response signaling as favorably modulating the immune system, and propose a possible role for PARP inhibition as a therapeutic strategy in melanoma.
Geriatric assessment (GA) and treatment (Tx) outcomes in older adults with cancer receiving immunotherapy (IO).
Authors: Karim Welaya, Susan Messing, Emily Szuba, Ronald John Maggiore
Journal: Journal of Clinical Oncology (2018)

e22023 Background: Older adults age ≥65 years are the majority of patients (pts) with cancer in the US, yet remain under-represented in clinical trials. Outcomes of older adults with cancer receiving IO are not well defined. We evaluated the role of GA in older patients with solid tumors who received IO at our institution. Methods: We performed a retrospective chart review of pts diagnosed with any solid tumor age ≥65 years who had received IO and had a GA from January 2011 to April 2017. Patient-, cancer-, and GA-related data were collected. In addition, prior chemo, duration of tx, toxicities, and best response were assessed. GA domains were evaluated for association with key tx-related outcomes: duration of tx, toxicity, and hospitalization during tx. Chi square or Fisher’s exact tests were used for categorical variables; t-test and Spearman’s correlation coefficients were used for continuous variables where appropriate. Results: Cohort N = 28 pts. Median age at IO tx = 78 years (range, 66-93). Most pts were ECOG PS ≥2 (N = 17; 60%); had lung cancer (N = 11; 39%); were stage IV (N = 25; 89%); and received pembrolizumab (N = 14; 50%). 15 pts (53%) had GA prior to first-line IO. Of 24 pts, 50% had 1+ baseline IADL impairment. Mean no. of IO cycles = 8.5 (+/- 11). Best response was associated with no. of IO cycles (P < 0.01). ADL impairment (r = -0.53, P = 0.05), IADL impairment (r = -0.39, P = 0.06), weight loss (r = -0.37, P = 0.08) and no. of comorbidities (r = -0.39, P = 0.09) trended with fewer IO cycles. 57% (N = 16) were hospitalized during tx. IADL impairment tended to be associated with increased hospitalization risk during tx (P = 0.07). 11 pts (39%) had any-grade irAE, mostly dermatitis (45%). IO was discontinued for toxicity in 10 pts (36%). ADL (P = 0.01) and IADL (P = 0.03) impairments, higher depression scores (P = 0.04), cognitive impairment (P < 0.01), and lower self-rated physical health scores (P < 0.01) were associated with higher rates of IO discontinuation due to non-disease progression. Neither age nor GA measures were associated with any-grade or Grade 3-4 IO toxicity. Conclusions: GA impairments and not age were shown to be associated with select tx outcomes; however, prospective data are needed to further define these relationships.
Vincristine/irinotecan upfront window treatment of high-risk hepatoblastoma: A report from the Children’s Oncology Group (COG) AHEP0731 study committee.
Authors: Howard M. Katzenstein, Wayne Lee Furman, Marcio Malogolowkin, Mark D. Krailo, Mary B McCarville, Alexander Towbin, Greg Tiao, Milton Finegold, Sarangarajan Ranganathan, Stephen Dunn, Max Langham, Eugene McGahren, Carlos Rodriguez-Galindo, Rebecka Meyers
Journal: Journal of Clinical Oncology (2016)

10516 Background: The identification of new therapies for high-risk (HR) hepatoblastoma (HB) is challenging. Children's Oncology Group Study AHEP0731 included a HR stratum to explore novel agents. We report the response rate to vincristine/irinotecan and the outcome of high-risk HB patients. Methods: Patients with newly diagnosed metastatic HB or those with a serum alpha-fetoprotein (AFP) < 100 ng/ml were eligible. Patients received 2 cycles of vincristine (V) 1.5 mg/m2/day intravenously, on days 1 and 8 and irinotecan (I) 50 mg/m2/day, intravenously, on days 1-5. Patients were defined as responders if they had either a 30% decrease in tumor burden according to RECIST criteria or a 90% (> 1 log10 ) decline in the AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Non-responders were to receive 6 cycles of C5VD alone. Results: Thirty-two patients (median age at diagnosis, 26 months, range: 11-159) were enrolled on study between September 2009 and February 2012. Fourteen of 30 evaluable patients were responders (RECIST and AFP = 6, RECIST only = 3, AFP only = 5). The median AFP decline following 2 cycles of VI was 345,565 ng/ml or 85% of the initial AFP. Three-year event-free and overall survival was 49% (95% confidence interval-CI: 30-65%) and 62% (CI: 42-77%) respectively. VI was well tolerated with the most common grade 3 and 4 toxicities during the first two cycles being diarrhea (n=8 patients, 26%); anorexia and febrile neutropenia (n=7 patients, 23%); nausea (n=6 patients, 19%); and a documented infection (n=4, 13%). Neuropathy was only reported in one patient (3%). Conclusions: The combination of vincristine and irinotecan has substantial activity against HR hepatoblastoma. AFP response may be a more sensitive predictor of activity than RECIST. The ultimate impact of this regimen in improving outcomes of children with HR hepatoblastoma remains to be determined. Clinical trial information: NCT00980460.
Lorazepam as an adjuvant to haloperidol for agitated delirium at the end of life: A double-blind randomized controlled trial.
Authors: David Hui, Susan Frisbee-Hume, Annie Wilson, Seyedeh Dibaj, Thuc Nguyen, Maxine Grace Jaucian De La Cruz, Paul Walker, Marvin Delgado-Guay, Marieberta Vidal, Donna S. Zhukovsky, Daniel E. Epner, Akhila Sunkepally Reddy, Kimberson Tanco, Janet L. Williams, Stacy Hall, Diane D Liu, Kenneth R. Hess, Sapna R. Amin, William Breitbart, Eduardo Bruera
Journal: Journal of Clinical Oncology (2017)

10003 Background: Agitated delirium is a highly distressing neuropsychiatric syndrome common in the last days of life. The use of benzodiazepines for agitated delirium is highly controversial. We compared the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitated delirium. Methods: In this double-blind trial, we randomly assigned patients with advanced cancer admitted to an acute palliative care unit with agitated delirium despite scheduled haloperidol to either lorazepam 3 mg IV or placebo, in addition to haloperidol 2 mg IV upon the onset of agitation. The primary outcome was the Richmond Agitation Sedation Scale (RASS) over the first 8 hours, ranging from -5 (unarousable) to +4 (combative). Secondary endpoints were rescue neuroleptic use, perceived comfort, delirium-related distress, adverse effects and overall survival. 26 patients per arm provided 80% power to detect a between arm difference of 0.5 effect size in mean RASS with a=5%. We used the Wilcoxon Rank Sum test for primary comparison. Results: 52 of 58 (90%) patients who received the medications completed 8 h of observation. RASS decreased significantly within 30 min of treatment in both arms (Table). The lorazepam arm was associated with significantly greater reduction of RASS (Table), less rescue neuroleptics (mean haloperidol equivalent dose 1 mg v. 3 mg, P=0.02), and greater comfort as perceived by blinded caregivers (84% v. 37%, P=0.007) and nurses (77% v. 30%, P=0.005) compared to placebo. We found no significant between-group differences in delirium-related distress, adverse effects and overall survival (median 68 v. 73 h, P=0.56). Conclusions: The combination of lorazepam/haloperidol resulted in rapid and significant reduction of agitation compared to haloperidol alone. Our study supports the judicious use of single dose lorazepam/haloperidol for persistent agitated delirium. Clinical trial information: NCT01670097. [Table: see text]
Concordance rates of provider selected pathway decisions to actual delivered therapy.
Authors: Corey J. Shamah
Journal: Journal of Clinical Oncology (2017)

e18220 Background: In November 2014, Aurora Cancer Care (ACC) adopted a new software package called Via Oncology (Via). It is a software driven, algorithmic, decision support tool. Via's goal is to help providers make the best decision in the treatment plan for patient care. Eligible clinical trials are the preferred therapy choice. If not available, treatment choices are then ranked by efficacy, toxicity, then cost. Its use has been mandated for every patIent visit in the department of Medical Oncology. ACC has 19 sites of service. While our current electronic medical record (EMR) and Via do communicate, it is limited to demographics and sending a link of the selected pathway from Via to the EMR. However, this link does not need to be selected in the EMR and another treatment could be selected. Our group does not penalize for off-pathway decisions, but it is possible that providers are selecting one protocol in Via to count as "on-pathway", and entering another treatment plan in the EMR. The goal of this study was to determine the concordance of stated pathway on Via and the actual ordered therapy in the EMR. Methods: One month of pathway decisions for a large, hospital based, multisite oncology group were obtained. Those decisions in Via that were recorded as new "on-pathway" treatment decisions were manually audited in the EMR to determine if there was concordance. If discordant decisions were corrected on a subsequent visit, it was felt that there was likely a mitigating circumstance and these decisions were not included in the final analysis. Results: Over one month, our 39 oncologist made 1534 new decisions for patients. Of these, 368 were "on-pathway" in Via. There was concordance of 319 (87%) to our EMR. The discordant charts were mostly due to differing drugs (19), dosing schedule (8), drug omitted (7), never given (7), additional drug (2). Conclusions: Despite the mandated use to two mostly independent software systems, agreement was high among patient records. Further integration of these systems will likely result in even greater concordance.
Long-term survival outcomes of a placebo-controlled phase 3 trial with NGR-hTNF in combination with best investigator choice in relapsed malignant pleural mesothelioma (MPM).
Authors: Vanesa Gregorc, Chiara Lazzari, Alessandra Bulotta, Maria Grazia Viganò, Domenico Ghio, Floriana Fontana, Giulia Salini, Antonio Lambiase
Journal: Journal of Clinical Oncology (2018)

8567 Background: NGR-hTNF is a vascular-targeting agent able to increase intratumoral chemotherapy penetration and T-cell infiltration by modifying tumor microenvironment. MPM patients failing first-line therapy have limited treatment options. Methods: In the phase 3 trial NGR015 (ASCO 2015; abs 7501), 400 patients received single-agent gemcitabine, vinorelbine or doxorubicin ± NGR-hTNF as second-line therapy. By ITT analysis, overall survival (OS) did not differ between arms (median follow-up 18.7 months; data maturity 75%). In subgroup analyses, there was a significant interaction only between treatment and treatment-free interval (TFI) after first-line therapy. NGR-hTNF improved OS and PFS in the short TFI subset ( < median: 4.8 months; n = 198). We assessed long-term outcomes in patients with short TFI and prognostic TFI value after adjusting for baseline covariates (age, sex, PS, histology, EORTC score, NLR, response to prior therapy and selected chemotherapy). Results: At a median follow-up of 33.8 months (data maturity 86%), a treatment-by-TFI interaction for OS persisted in univariate (p = 0.004) and multivariable models (p = 0.002). In the short TFI subset, median OS was 9.2 months (95% CI 6.6-11.8) for NGR-hTNF vs 6.3 months (5.7-7.0) for placebo (HR 0.67; 0.48-0.93; p = 0.02; adjusted HR 0.64; 0.45-0.89; p = 0.008). Survival rates were 39% (29-50) vs 24% (16-32) at 1 year and 18% (9-26) vs 9% (3-15) at 2 years. The 25% survival rate occurred 7 months later with NGR-hTNF than with placebo (17.3 months vs 10.2 months). NGR-hTNF treatment was associated also with improved PFS (median 3.4 vs 1.9 months; HR 0.66; 0.48-0.91; p = 0.01; adjusted HR 0.65; 0.47-0.90; p = 0.009). In sensitivity analyses, consistent results were found using a 6-month TFI cutoff. The prognostic TFI value was assessed in the control group to avoid confounding effects of experimental treatment. A short TFI independently correlated with worse OS (HR 1.79; 1.29-2.50; p = 0.0006). Conclusions: Benefit with NGR-hTNF treatment in the short TFI subgroup was maintained after a 3-year follow-up, deserving a confirmatory randomized trial as these MPM patients have a poor prognosis. Clinical trial information: NCT01098266.
Genomic and transcriptomic profiling of localized sarcomatoid carcinoma of the lung to reveal association between immune activation and a lower risk of recurrence.
Authors: Sahil Seth, Won-Chul Lee, Jianhua Zhang, Junya Fujimoto, Carmen Behrens, Christina McDowell, Neda Kalhor, Annikka Weissferdt, Vassiliki Papadimitrakopoulou, John Heymach, Don Lynn Gibbons, Andrew Futreal, Ignacio Ivan Wistuba, Moran Amit, Humam Kadara, Jianjun Zhang
Journal: Journal of Clinical Oncology (2017)

e20058 Background: The sarcomatoid carcinoma of the lung (SCL) is a rare subtype of non-small cell lung cancers (NSCLC). The prognosis of SCL is poor with 5-year survival of ~20%. There have been only a few studies on genomic landscape of SCL. Comprehensive genomic and transcriptomic profiles of SCL have not been systematically studied. Methods: In this study, we performed whole-exome sequencing and ultra-deep targeted sequencing of 400 cancer genes on 21 resected localized SCLs and matched normal lung tissues. RNA sequencing (RNA-seq) was also performed to 17 SCLs and matched normal lung tissues for those with materials available. Results: On average, 688 mutations including 503 non-synonymous mutations were identified per tumor. Canonical cancer gene analysis demonstrated that the most frequently mutated gene in this cohort was TP53 (detected in 11 out of the 21 tumors) followed by KRAS (detected in 6 out of the 21 patients). The recently discovered potentially targetable MET exon 14-skipping mutation was also detected in 3 patients in our cohort. For the 17 tumors, for, whom RNA-seq was conducted, unsupervised clustering analysis using non-negative matrix factorization (NMF) led to two stable clusters of patients in our cohort. Of particular interest, all patients (7/7) in Cluster 1 have relapsed, while only 3 of 10 patients in Cluster 2 relapsed (p-value &lt; 0.01). Further pathway analyses demonstrated that immune activation pathways are significantly up regulated in tumors from Cluster 2 compared to Cluster 1. Conclusions: SCLs seem to have similar genomic landscape and canonical cancer gene mutations compared to other types of NSCLCs such as squamous cell carcinoma and adenocarcinomas. Immune pathway activation may be associated with lower risk of postsurgical recurrence in patients with localized SCL.