tbuckley/cabot-search huggingface dataset:
Final overall survival (OS) analysis of an international randomized trial evaluating bevacizumab (BEV) in the primary treatment of advanced ovarian cancer: A NRG oncology/Gynecologic Oncology Group (GOG) study.
Authors: Robert Allen Burger, Danielle Enserro, Krishnansu Sujata Tewari, Mark F. Brady, Michael A. Bookman, Gini F. Fleming, Helen Q Huang, Howard D. Homesley, Jeffrey Fowler, Matthew Boente, Leslie M. Randall, John K. Chan, James Stuart Ferris, Philip J. DiSaia, Larry J. Copeland, Robert S. Mannel, Michael J. Birrer, Bradley J. Monk
Journal: Journal of Clinical Oncology (2018)

5517 Background: GOG 0218 is a double-blind, placebo-controlled, phase 3 randomized trial studying chemotherapy with and without concurrent BEV, and with concurrent BEV followed by maintenance BEV for advanced stage ovarian carcinoma. In 2010, at a median follow-up of 17.4 months (m), the trial met its primary endpoint demonstrating improvement in progression-free survival (PFS) for patients receiving BEV with and following chemotherapy compared to chemotherapy alone: median PFS 14.1 vs 10.3m, respectively; HR 0.717; 95% CI, 0.625-0.824; p < 0.001 [Burger RA, et al N Engl J Med 2011]. With extended follow-up, we report on the key secondary endpoint, final OS. Methods: 1,873 women with newly diagnosed, incompletely resected stage III or stage IV ovarian cancer received six 21-day cycles of carboplatin (AUC 6) IV and paclitaxel (175 mg/m2 BSA) IV chemotherapy alone (control) vs chemotherapy plus BEV (15 mg/kg body weight) IV cycles 2-6 (BEV-initiation) vs chemotherapy plus BEV cycles 2-22 (BEV-throughout). OS was analyzed in the intention-to-treat (ITT) population. The database was locked on Jan. 17, 2018 at a median follow-up of 102.9m. Results: After 1,491 (79.6%) deaths, 204 patients (10.9%) are alive with a progression event, and 178 (9.5%) are alive without progression. Comparing BEV-throughout to control, the hazard of death (HR) is 0.96; 95% CI, 0.85-1.09; p = 0.53. For BEV-initiation vs control, HR is 1.06; 95% CI, 0.94-1.20; p = 0.34. The relative HR for stage IV patients was reduced for BEV-throughout compared to control (HR 0.774). While the median survival times for stage IV control and stage IV bevacizumab-initiation were 32.6 and 34.5 mos., respectively, the median OS (42.8m) for stage IV BEV-throughout patients was similar to the median OS (control, 44.3m; BEV-initiation, 42.9m; BEV-throughout, 44.2m) of stage III patients. Conclusions: In the ITT analysis, there were no survival differences between patients receiving BEV compared to chemotherapy alone. Patients with FIGO stage IV disease may derive a survival advantage from BEV when administered with and following front-line chemotherapy. Clinical trial information: NCT00262847.
In acute myeloid leukemia patients CpG-methylation changes associate with resistance to induction chemotherapy.
Authors: Christian Dietger Niederwieser, Christian Rohde, Hubert Serve, Wolfgang E. Berdel, Gerhard Ehninger, Stefanie Göllner, Sebastian Schwind, Lutz P. Müller, Carsten Müller-Tidow
Journal: Journal of Clinical Oncology (2018)

7036 Background: Acute myeloid leukemia (AML) is a heterogeneous disease associated with epigenetic alterations targetable with demethylating agents. However, predictive response markers are missing. Here we analyzed the methylation changes of transcription factor (TF) binding motifs in resistant patients after treatment with or without azacytidine (Aza) followed by induction chemotherapy. Methods: Twenty refractory patients from the AML-AZA trial of the Study Alliance Leukemia receiving Aza followed by induction chemotherapy (n = 16/105) or chemotherapy alone (n = 4/109) were selected to perform genome wide DNA methylation analyzes using a 450K Illumina array (Illumina, San Diego, USA) before and on day 15 after therapy start. Methylation changes from day 0 to 15 corrected for %blasts were identified and motifs detected using HOMER software (Salk institute, San Diego, USA). Methylation variation was analyzed according to treatment with Aza and/or chemotherapy. Results: In the Aza/chemotherapy group, a total of 389 differentially methylated regions (DMRs), most of them single CpGs, were identified, 176 hyper- and 213 hypomethylated. In methylation clustering analyses, patients with a reduction/increase of blasts clustered separately together. Those with blast reduction were more likely female and FLT3-ITD mutated. The most highly represented de novo motifs (differential enrichment between 2 sets of sequences) were associated with 5 (hypermethylation) and 10 TFs (hypomethylation). The chemotherapy only group had 7181 DMRs, 5752 hyper- and 1429 hypomethylated. We found 24 and 12 TFs for the hyper- and hypomethylated loci in these patients, respectively. The known motifs (based on listing of motifs from previous data) in the Aza/chemotherapy group of the enriched TFs were analyzed [hyper-: 17 TFs (Jun-AP1 (p = 1e-7); hypomethylated: 4 TFs, GATA (p = 1e-2)]. For the chemotherapy group we found 90 TFs [EHF (p = 1e-126)] and 43 TFs [RUNX1 (p = 1e-18)] for hyper- and hypomethylated sites, respectively. Conclusions: DNA methylation of specific TF binding motifs may be associated with therapy resistance and could be used for response prediction of therapy with Aza and/or chemotherapy. Clinical trial information: NCT00915252.
TCT-163 The analysis of safety and effectiveness of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension which has indication for surgical therapy.
Authors: Shun Minatsuki, Arihiro Kiyosue, Akihito Saito, Hisataka Maki, Satoshi Kodera, Masaru Hatano, Issei Komuro
Journal: Journal of the American College of Cardiology (2018)
Association of <i>ATM</i> mutation and unmutated IGHV status with shorter time to first treatment (TTFT): An analysis of multigene mutation profiling and standard prognostic clinical markers in 384 treatment-naive (TN) chronic lymphocytic leukemia (CLL).
Authors: Boyu Hu, Keyur Patel, Hsiang-Chun Chen, Xuemei Wang, Rajyalakshmi Luthra, Mark Routbort, Rashmi Kanagal-Shamanna, L Jeffrey Medeiros, Cameron C. Yin, Zhuang Zuo, Chi Ok, Sanam Loghavi, Philip A. Thompson, Michael J. Keating, Jan Andreas Burger, Nitin Jain, Alessandra Ferrajoli, Prithviraj Bose, Zeev Estrov, William G. Wierda
Journal: Journal of Clinical Oncology (2018)

7523 Background: Somatic mutations (MUTs) in CLL play important roles in leukemogenesis and affect both response to treatment and survival outcomes. Correlation of somatic MUTs with TTFT remains limited. In this study, we associated somatic MUT results from a 29-gene panel and known prognostic factors with TTFT. Methods: DNA from either peripheral blood or bone marrow that contained > 10% CLL cells from 384 TN pts underwent next generation targeted sequencing of a 29-gene panel. Concurrent clinical characteristics such as Rai/Binet staging, FISH abnormalities, cytogenetics and IGHV MUT were analyzed in univariable (UA) and multivariable (MVA) analyses with MUT data. TTFT was defined as time from diagnosis to initial treatment; untreated pts were censored at last follow up. Results: With a median follow up of 24.3 months (m), the median TTFT for all pts was 61.7m (95% CI 47-74.5m). Compared to pts with no MUTs, pts with a single MUT in ATM (p < 0.001), BIRC3 (p < 0.001), CXCR4 (p < 0.001), NOTCH1 (p < 0.001), SF3B1 (p = 0.02) and SPEN (p = 0.04) had shorter TTFT. Pts with 2-5 MUTs also had shorter TTFT by 39m compared to pts with 0-1 MUT (p < 0.001). Location of the MUT in various domains of TP53 gene along with “hotspot” MUTs in SF3B1 and NOTCH1 were not associated with differences in TTFT. Additionally, del(17p) was not associated with shorter TTFT. In UA, MUT in ATM (p < 0.001), NOTCH1 (p < 0.001) and SF3B1 (p = 0.002) as well as unmutated IGHV (p < 0.001), del(11q) (p < 0.001) and trisomy 12 (p < 0.001) and advanced Rai (p = 0.05) and Binet (p < 0.001) stages were associated with shorter TTFT. In MVA, ATM MUT (p < 0.001), unmutated IGHV (p < 0.001) and advanced Binet stage (p = 0.01) remained significant; del(11q) was not significant in the model. Conclusions: Somatic MUT in ATM and unmutated IGHV are important independent prognostic factors for shorter TTFT. Other somatic MUTs, like CXCR4 and SPEN whose clinical significance have not been fully elucidated, correlated to shorter TTFT although not independently. Somatic gene MUTs, especially ATM, are associated with disease progression in TN pts.
Does oncologist productivity impact goals of care discussions?
Authors: Sofya Pintova, Cardinale B. Smith, Kerin B. Adelson, Jason Parker Gonsky, Natalia Egorova, Rebeca Franco, Nina A. Bickell
Journal: Journal of Clinical Oncology (2017)

e21675 Background: Oncologists are pressed to care for higher volumes of advanced cancer patients. Interviews with oncologists revealed their concern that goals of care (GoC) discussions take time. We studied the impact of oncologists’ productivity on their conduct of meaningful GOC discussions with patients. Methods: At academic, municipal and rural hospitals, we recruited &amp; randomized solid tumor oncologists &amp; their newly diagnosed advanced cancer patients with &lt;2 year prognosis to participate in a RCT testing a coaching model of communication skills training. All oncologists were encouraged to have GoC discussions at the visit after imaging to restage. Patients are surveyed after that post-imaging visit. We define GoC discussions as patient report that their doctor talked about preferences for cancer treatment and clarified things most important to them given their illness. We measure quality of GoC discussions by patients’ rating. Productivity was measured by work revenue value units (wRVUs) per hour for the day each oncologist saw the study patient post-imaging. Results: We enrolled 22/25 oncologists (88%); to date 77 patients completed surveys. Productivity did not vary significantly by hospital though oncologists generated greater wRVUs at the municipal hospital (p=0.2203). Overall, 36% of patients report having a high quality GoC discussion. There was no significant relationship between level of productivity and conduct of high quality GoC discussion. Multivariate model controlling for hospital and intervention found no relationship between productivity and conduct of high quality GoC discussion. Conclusions: Despite concerns about the time required to conduct GoC discussions, we found that productivity did not affect oncologists’ ability to conduct high quality GoC discussions nor did conduct of a GoC reduce productivity. The prevalence of high quality GoC discussions was low. [Table: see text]
FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab for patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction as second-line therapy: The RAMIRIS study.
Authors: Sylvie Lorenzen, Peter C. Thuss-Patience, Claudia Pauligk, Eray Goekkurt, Thomas Jens Ettrich, Florian Lordick, Peter Reichardt, Michael Stahl, Hans-Georg Kopp, Susanna Hegewisch-Becker, Alexander Reichart, Hana Alguel, Dmitry Bichev, Angelika Kestler, Ulrich Hacker, Nicolas Stephan Ziegenhagen, Christian Mueller, Barbara Hermes, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2018)

TPS4132 Background: The majority of patients with gastroesophageal cancer present with inoperable or metastatic disease. After failure of first-line chemotherapy, ramucirumab is a proven option as monotherapy and in combination with paclitaxel as second line treatment in advanced gastric cancer. Irinotecan has shown significant improvement of overall survival compared to best supportive care (BSC) in the second line setting and is an accepted safe and efficient standard chemotherapeutic treatment for patients with refractory gastroesophageal cancer. More and more patients get treated with taxanes in the perioperative or 1st line metastatic setting. For those patients the benefit of a combination of ramucirumab and paclitaxel is unclear, and many physicians would choose an irinotecan based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a prospective, multicenter, randomized, investigator initiated phase II trial. Patients with advanced gastric or esophagogastric junction cancer will be randomized 2:1 to FOLFIRI (irinotecan 180 mg/m²; 5-FU 400 mg/m²; leucovorin 400 mg/m²; 5-FU 2400 mg/m² on day 1 and 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m² (days 1, 8, 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm B). Primary endpoint of the trial is OS rate after 6 months, based on the ITT population. The experimental therapy (FOLFIRI + Ramucirumab; n = 67) is considered to be a highly promising candidate for further development (e.g. in a phase III trial), if the true OS rate amounts to 65% or more, as this corresponds to the efficacy of the standard ramucirumab-paclitaxel regimen according to the RAINBOW study in the western population. Secondary endpoints are progression-free survival, response rate, safety and tolerability. Currently (Jan 2017) 40 of planned 111 patients are randomized. Clinical trial information: NCT03081143.
Exploring outcomes of <i>RAS</i>-mutant (<i>RAS</i> mut) advanced colorectal cancer (aCRC) treated with chemotherapy: Analysis from 2254 patients (pts) in randomised clinical trials (RCTs).
Authors: Jenny F. Seligmann, David Fisher, Christopher G. Smith, Faye Elliott, Susan Richman, Philip Quirke, Tim Maughan, Jeremy Cheadle, Richard A. Adams, Matthew T. Seymour, Gary William Middleton
Journal: Journal of Clinical Oncology (2016)

3561 Background: RAS mut status predicts lack of benefit from anti-EGFR agents in aCRC, but its impact on prognosis and chemotherapy outcomes is less clear. Previously we have reported that the poor outcomes of BRAF mut cancer aCRC are due to accelerated decline following 1st-line progression, not chemoresistance. In the same dataset we perform a detailed analysis of outcomes of RAS mut pts throughout the aCRC treatment pathway to help guide clinical decision-making in this underserved population. Methods: RAS was assessed in tumors of 2254 BRAF wild-type (wt) pts in 3 RCTs: COIN (n = 1158), FOCUS (n = 706, KRAS only) and PICCOLO (n = 390). End-points were progression free survival (PFS), response rate (RR), and OS. Treatments received were 1st line OxFU (COIN), 1st line OxFU or IrFU (FOCUS) or 2nd line Irinotecan (Ir) (PICCOLO). Analyses were adjusted for known negative prognostic markers: poor performance status, primary tumour in-situ, right tumour location, peritoneal mets and high platelet count, and were performed using Cox proportional hazards models and logistic regression. Results: 1101 pts (48.8%) were RAS mut. RAS mut status conferred worse OS in both 1st-line studies (COIN adj HR = 1.38, p < 0.001; FOCUS adj HR = 1.33, p < 0.001), and at the point of starting 2nd-line treatment (adj HR = 1.33, p = 0.014). Compared with wt, RAS mut pts treated with 1st-line combination chemotherapy had inferior treatment outcomes (RR 42.2% vs 51.7%; adj OR = 0.69,p < 0.001) and PFS (6.4 vs 8.0 mths, adj HR = 1.24, p < 0.001). RAS mut pts were just as likely as wt to receive 2nd-line treatment after 1st-line progression in COIN (51.4% vs 51.7%) and were well represented in PICCOLO (53.6%). RAS-mut pts treated with 2nd-line Ir had inferior outcomes than wt (RR 7.7% vs 12.7%; PFS 3.1 vs 4.9 months) but neither were statistically significant (p = 0.10 and p = 0.42, respectively). Conclusions: RAS-mut status is an independent poor prognostic marker in aCRC. This is partly driven by relative chemoresistance in both the 1st and 2nd-line settings, observed following adjustment for known poor prognostic factors. New approaches in treating RAS mut aCRC are urgently required.
Implementing the patient reported outcomes measurement information system (PROMIS) global health scale in the adolescent and young adult (AYA) oncology population.
Authors: Joseph R. Henderson, Elizabeth Kiernan, Jennifer Lynn McNeer, Angie Mae Rodday, Tara O. Henderson, Katherine Spencer, Susan K. Parsons
Journal: Journal of Clinical Oncology (2016)

6565 Background: Advances in quality of life (QOL) measurement, including improved precision and brevity, greatly enhance the incorporation of QOL assessment at the point-of-care. In this study we report the novel incorporation of the PROMIS Global Health Scale to the AYA oncology population. Methods: Patients 18-39 years old, who presented for routine care at Tufts Medical Center’s Reid R. Sacco AYA Cancer Program and The University of Chicago’s AYA Oncology Program/Childhood and AYA Cancer Survivor Center were invited to complete the 10-question PROMIS Global Health Scale upon check-in. Responses form two subscales of physical and mental health, with scores standardized to a mean of 50 (SD, 10). Patient consent allowed us to link scores with medical records information including diagnosis, treatment status and select patient characteristics. Results: Out of 147 eligible patients, 142 (96.6%) provided informed consent to release their scores for research purposes. The mean age was 24.6 ± 5.3 years; 53.5% were male; 75.4% were White, non-Hispanic; 61.3% were diagnosed with hematologic malignancies; 23.9% were currently on-therapy and 43.0% had therapy-related complications. While the mean Global Physical Health (GPH) and Global Mental Health (GMH) scores did not differ statistically from the standardized population mean of 50 (GPH, 49.7 ± 8.8, p = 0.73; GMH, 50.5 ± 9.3, p = 0.55), 35.9% of GPH and 26.1% of GMH scores were < 45, which has been previously defined as clinically meaningful. Factors associated with GPH scores < 45 included being on-therapy (p = < 0.001), diagnosed at ≥ 15 years of age (p = 0.005), < 10 years since diagnosis (p = 0.02), therapy-related complications (p = 0.01), and unemployment (p = 0.03). No statistically significant associations were identified for GMH scores < 45. Conclusions: It is feasible to implement QOL measures in the AYA oncology population with minimal burden and high acceptance. Factors associated with lower GPH scores identified in this study may guide interventions in future studies. Further research is needed to understand factors associated with lower GMH scores in this clinical population.
Factors impacting time to engraftment in patients with high-risk neuroblastoma following autologous stem cell transplant.
Authors: Kirsty Hillier, Robert Krance, Jennifer Haunani Foster
Journal: Journal of Clinical Oncology (2017)

e22008 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood, with overall survival for high-risk patients (HRNBL) near 50%. The outcomes of HRNBL have improved significantly with high dose chemotherapy followed by autologous stem cell rescue (ABMT). Data about factors influencing the rate of hematopoietic recovery following ABMT in HRNBL is lacking in the literature. Methods: This is a retrospective chart review of patients with HRNBL treated at Texas Children’s Hospital from October 2011 - November 2016. Neutrophil engraftment was considered the first of three consecutive days with post-transplant neutrophil count &gt; 500 cells/uL. Red blood cell and platelet engraftment were considered at a hemoglobin &gt; 8g/dL and platelets &gt; 20,000/uL three days after the last transfusion. Race and conditioning regimen were analyzed using one-way ANOVA; amount of infused cells was analyzed using Pearson correlation coefficients; chemotherapy delay and bone marrow (BM) involvement after cycle 2 of induction chemotherapy were analyzed using independent sample t-tests. Results: The study included 17 males and 8 females with a median age at diagnosis of 3 years. 15 patients were Caucasian, 4 African-American, 5 Hispanic, and 1 Asian. The mean dose of infused CD34+ cells was 3.44x10 8 cells/kg. 16 patients received conditioning therapy with carboplatin/etoposide/melphalan, 7 received busulfan/melphalan, and 2 received thiotepa/cyclophosphamide. Race was found to be significant for hemoglobin engraftment (p &lt; 0.001). There were trends toward significance for conditioning regimen and neutrophil engraftment (p = 0.079), presence of delays in induction chemotherapy due to hematologic toxicity for platelet engraftment (p = 0.069) and BM involvement after cycle 2 of induction chemotherapy for hemoglobin engraftment (p = 0.12). Conclusions: Knowing the barriers for timely engraftment may help develop interventions for future patients. Race significantly impacted hemoglobin engraftment. Conditioning regimen, delays in induction chemotherapy, and BM involvement after cycle 2 of induction chemotherapy trended towards significance and need to be validated in a larger dataset.
Radiosurgery and immune checkpoint inhibition in the treatment of brain metastases: A meta-analysis of patient-level data.
Authors: Eric J Lehrer, Jennifer Layton Peterson, Paul D. Brown, Jason Sheehan, Alfredo Quinones-Hinojosa, Nicholas George Zaorsky, Daniel Michael Trifiletti
Journal: Journal of Clinical Oncology (2018)

e14009 Background: Many studies have reported on the use of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) for the treatment of brain metastases (BMs). The generalizability of these studies is limited, as they are largely retrospective and were conducted at single institutions. A meta-analysis was therefore performed to pool data on this topic while clinicians eagerly await the results of prospective clinical trials. Methods: The primary outcome measure was overall survival (OS) at 1-year. Secondary outcomes measures were 1-year local control (LC), 1-year regional brain control, and incidence of radionecrosis. Guidelines from PICOS/PRISMA/MOOSE were utilized to identify studies where patients with BMs: (1) at least the primary or one of the secondary outcomes measures were reported; (2) were treated with SRS and ICI; (3) SRS and ICI were delivered concurrently or non-concurrently. Weighted random effects meta-analyses were conducted for each outcomes measure using the Dersimonian and Laird method. Kaplan-Meier curves were compared using the log-rank test. Results: elanoma was the most common primary tumor. Median patient age was 61.7 years, the most common ICI agent used was ipilimumab, and the median dose was 20 Gy (range: 18-24 Gy) administered to the tumor margin. At 1-year, OS for all studies was 58% (95% confidence interval [CI]: 51.9-63.8%) with improved survival for concurrent versus non-concurrent (p < .01) therapy. 1-year LC for all studies was 82.2% (95% CI: 66.8-90.2%); and was 89.2% (95% CI: 79.9-94.5%) for concurrent and 67.8% (95% CI: 40.2-86.8%) (p = .09) for non-concurrent therapy. 1-year regional brain control was 33.2% (95% CI: 18.3-50.0%) for all studies; and was 38.1% (95% CI: 20.1-60.1%) for concurrent therapy and 12.3% (95% CI: 4.0-31.9%) for non-concurrent therapy (p < .05). The incidence of radionecrosis for all studies was 5.3% (95% CI: 0.3-15.7%). Conclusions: Combination SRS and ICI is safe and may confer a survival advantage with an improved abscopal-like effect when administered concurrently in a select group of patients.
TCT-848 Comparison between Conventional Access Site Approach and Fully Trans-Wrist Approach for Chronic Total Occlusion Percutaneous Coronary Intervention: the Minimalistic Hybrid Approach
Authors: Lorenzo Azzalini, Enrico Poletti, Carlo Zivelonghi, Ozan Demir, Susanna Benincasa, Barbara Bellini, Davide Maccagni, Mauro Carlino, Antonio Colombo, Pierfrancesco Agostoni
Journal: Journal of the American College of Cardiology (2018)