tbuckley/cabot-search huggingface dataset:
National population-based study of racial variation in characteristics and outcomes of young breast cancer patients: Analysis of temporal trends.
Authors: James Thompson McClain, Catalina Mosquera, Praveen Namireddy, Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2017)

e18068 Background: Breast cancer outcomes correlate with racial and socioeconomic status. Efforts to reduce disparities in breast cancer among vulnerable populations has had limited success. We sought to examine trends of racial and socioeconomic factors and its impact on outcome in young breast cancer patients. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified female patients aged 20-35 with invasive breast cancer diagnosed from 1990-2012. We performed univariate, multivariate and survival analysis. Variables included patient age, race, stage, receptor status, surgery type and year of diagnosis. Results: A total of 18,999 women were identified. Mean age was 31.7. 80.8% were white and 19.1% were black. A higher percentage of blacks had stage III/IV disease (34% v 27%) and ≥ 4 positive nodes (19% v 16%) compared to whites. 54% of whites were ER receptor positive while 46% of blacks were ER receptor positive (p&lt;0.0001). Analysis of American Community Survey attributes indicated white patents were more likely to live in counties where ≤15% of households were below the poverty line (64% v 45%) and where ≤15% of the population had less than a high school education (35% v 28%) compared to blacks. 31.2% were diagnosed in 1990-2000 while 68.7% were diagnosed in 2001-2012. 5 year disease specific survival (DSS) was 79.1% among all patients diagnosed from 1990-2000 and 84.2% among patients diagnosed from 2001-2012 (p&lt;0.0001). In each time period, white patients had significant difference in 5 year DSS compared to black patients. While the 5 year DSS for white patients improved from 80.9% to 86.3% (p&lt;0.0001), the 5 year DSS improvement for black patients from 1990-2000 to 2001-2012 did not reach statistical significance (71.3% vs 75.7%, p=0.24). Conclusions: Demographic and economic factors are associated with outcomes in young breast cancer patients. Absolute DSS has improved over consecutive time periods, but the improvement was not significant among blacks. More effort is needed to evaluate and address disparity in these patients. [Table: see text]
Getting the most out of follow-up: A prospective study using the Measure of Ovarian Symptoms and Treatment concerns (MOST) symptom index to evaluate and track adverse effects (AEs) and detect symptoms of recurrence in patients with ovarian cancer (OC) following first line chemotherapy (1LT).
Authors: Michael Friedlander, Madeleine King, Christina Nagle, Andreas Obermair, Peter T. Grant, Anna deFazio, Penelope M Webb
Journal: Journal of Clinical Oncology (2018)

10062 Background: Patients with OC are followed clinically every 3 months (m) after 1LT with the aim of managing symptoms/late AEs and diagnosing recurrence. Studies report that clinicians are unaware of up to half the symptoms patients experience. We developed and validated the MOST in patients with recurrent OC. We hypothesized that patient self-reporting of symptoms could complement clinical follow-up by identifying patients who experience significant late effects and also detect abdominal symptoms of recurrence. Methods: Women with OC participating in a prospective study (OPAL) completed MOST every 3m after 1LT for up to 3 years. We analysed MOST subscales representing abdominal, (MOST-Abdo), chemotherapy-related (MOST-Chemo) and psychological (MOST_Psych) symptoms (scales range 0-100, higher scores = greater symptoms). Results: 812 patients who received ≥3 cycles and did not progress within 3m of completing 1LT were evaluable. MOST completion rate was 81%. MOST-Chemo revealed high symptom burden just before or < 7 days after the last cycle .Trajectory analyses showed that the symptoms improve significantly/resolve in many patients by 6 months. However, 40% reported persisting moderate symptoms and ~10% had severe symptoms to > 2 years. Patients who scored > 30/100 on MOST-Chemo at the end of chemotherapy were likely to have persistent symptoms and the ~10% who scored > 50/100 reported ongoing severe symptoms to > 2 years. Among ~400 women with recurrence detected during follow-up, the MOST-Abdo symptom scores increased 2-3 months before the clinical diagnosis of progression. Conclusions: MOST is a brief patient-reported symptom index that complements clinical surveillance after 1LT. It was well accepted with high compliance rates. It can quantify and track symptoms and AEs experienced post 1LT and can detect the re-emergence of abdominal symptoms associated with recurrence. MOST could help triage the subset of patients likely to experience ongoing moderate-severe symptoms following 1LT for appropriate interventions.
ATIM-35. VXM01 PHASE I STUDY IN PATIENTS WITH PROGRESSIVE GLIOBLASTOMA – FINAL RESULTS
Authors: Wolfgang Wick, Antje Wick, Felix Sahm, Dennis Riehl, Andreas von Deimling, Martin Bendszus, Philipp Kickingereder, Philipp Beckhove, Friedrich Hubertus Schmitz Winnenthal, Christine Jungk, Sébastien Wieckowski, Anne-Valérie Keller, LIlli Podola, Christel Herold-Mende, Heinz Lubenau, Andreas Unterberg, Michael Platten
Journal: Neuro-Oncology (2018)

BACKGROUND. VXM01 consists of the attenuated Salmonella Typhi Ty21a delivering a plasmid encoding vascular endothelial growth factor receptor 2 (VEGFR2) into the Peyer's patches via the oral route of administration. The vaccine elicits a systemic T-cell response targeting VEGFR2. This trial examined safety and tolerability, clinical and immunogenic responses to VXM01 after at least four vaccinations at 106 or 107 colony-forming units in patients with progressive glioblastoma who have failed at least radiochemotherapy with temozolomide. METHODS. Patients with progressive operable glioblastoma were subjected to VXM01 in one oral administration each on day 1, 3, 5, and 7, and 4-weekly single doses during the tumor follow-up period after surgery. Follow-up was done by safety laboratories and physical examinations, MRI, T-cell immunomonitoring in the peripheral blood, and brain tumor immunohistochemistry. RESULTS. Fourteen patients have been treated with VXM01, three out of them with additional nivolumab. Surgery has been performed in eight patients. Under VXM01 treatment 129 adverse events, mostly unrelated to VXM01, were observed after a median of 7.5 doses per patient. IFN-γ ELISpot analysis showed a detectable VEGFR2–specific T–cell response in 7 out 12 patients measured. In the observation period up to 2 years, seven patients are alive and survived for more than 12 months. Survival correlated with a higher CD8/Treg ratio in progressive and primary tumor, which further increased after VXM01 treatment. In patients with prolonged survival a decrease in intratumoral PD-L1 was measured. In one patient, a strong partial response was observed under VXM01 monotherapy, and a complete response after addition of nivolumab. CONCLUSION: VXM01 was safe, produces detectable specific peripheral immune responses and increased T-cell infiltration in post-vaccine tumor tissue, with a favorable course of disease in five patients. A combination study of VXM01 and anti-PD-L1 avelumab in 30 patients with relapsed glioblastoma has been launched.
TCT-334 Treatment of degenerated aortic bioprostheses: a comparison between valve-in-valve transfemoral transcatheter aortic valve replacement and conventional reoperation
Authors: Norman Mangner, Georg Stachel, David Holzhey, Felix Woitek, Philipp Kiefer, Stephan Haussig, Sergey Leontyev, Florian Schlotter, Jennifer Adam, Lisa Crusius, Aileen Spindler, Holger Thiele, Michael Borger, Axel Linke
Journal: Journal of the American College of Cardiology (2018)
Ramucirumab (ram), immune checkpoint inhibitors (ICIs), and single-agent chemotherapy (chemo) usage in real-world advanced non-small cell lung cancer (aNSCLC) patients (pts) after rapid disease progression (RDP) on platinum (Pt).
Authors: Marta Batus, Cliff Molife, Rebecca A. Miksad, Jeffrey Melson Clarke, Victoria Jennifer Stefaniak, Rebekah Foster, Katherine B. Winfree, Anala Gossai, Zhanglin Lin Cui, Aracelis Z. Torres, Dana Feuchtbaum, Mahesh K Tawney, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2018)

e21162 Background: This retrospective study described treatment patterns of pts with RDP using ram, ICIs, or chemo in the US. As RDP pts (progression ≤ 12 weeks after Pt start) in REVEL benefited from ram/docetaxel, outcomes were analyzed for pts treated with ram after RDP on 1L/2L Pt. Methods: aNSCLC pts receiving ram, ICI or chemo in 2L or 3L between March 2015 - May 2017 after Pt, with ≥ 3 months of potential follow-up, were identified in the Flatiron Health EHR-derived database. Overall survival (OS) was indexed to 1L start and real-world progression-free survival (rwPFS) was indexed to start of 2L/3L ram. Unadjusted hazard ratios (HR) were calculated using Cox models. Results: Of 591 eligible pts, 105 (18%) had RDP on Pt, of whom 48%, 24%, and 28% were treated with ram, ICIs, or chemo, respectively. Table shows baseline factors and treatment patterns for RDP pts. RDP pts more often used ram in 2L. Ram pts with RDP were younger and more likely had non-squamous NSCLC, stage IV at diagnosis, and 2+ ECOG status than pts without RDP. For ram pts, RDP was associated with shorter median OS (12.66 v 17.51 months; HR = 0.56, 95% CI: 0.36 - 0.87). Median rwPFS was similar between ram pts with RDP (reference) and those without RDP (2.9 v 3.0 months; HR = 1.25, 95% CI: 0.83 - 1.91). Conclusions: In this real-world cohort, pts with RDP on Pt were more often treated with ram than ICIs or chemo. This differential use suggests that RDP may influence the choice of subsequent therapy. In ram pts, RDP correlated with poorer OS as seen in REVEL, further suggesting RDP as a potential negative prognostic factor for OS. Further research on RDP risk factors and optimal treatment sequence is urgently needed given the poor clinical outcomes. Ram (n = 50) ICI (n = 25) Chemo (n = 30) Demographics (%) > 65 years 50 60 53 Male 50 52 57 Race White 72 60 73 Black 6 16 3 Prior smoker 92 92 97 Region Northeast 22 32 10 Midwest 26 12 33 South 34 32 43 Treatment patterns Prior Pt (%) Cisplatin/carboplatin + bevacizumab 22 24 17 Cisplatin 22 8 7 Carboplatin 56 68 77 Treated at academic site (%) 6 12 7 Therapy duration (median months, 95% CI) 2.1 (1.4, 3.5) 3.0 (2.4, 6.9) 1.4 (1.3, 2.1)
TCT-444 Comparison of transthoracic echocardiogram with quantitative assessment of aortic regurgitation after TAVI with videodensitometry in a large real-world population: sub-analysis of the RESPOND registry.
Authors: Rodrigo Modolo, Patrick Serruys, Jochen Wöhrle, David Hildick-Smith, Daniel Blackman, Mohamed Abdel-Wahab, Ian Meredith, Yoshinobu Onuma, Nicolas Van Mieghem, Osama Soliman
Journal: Journal of the American College of Cardiology (2018)
An improvement in the method used to assess discriminatory ability when predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation
Authors: David J McLernon, Ewout W Steyerberg, Egbert R te Velde, Amanda J Lee, Siladitya Bhattacharya
Journal: BMJ (2018)

Our paper presents two clinical prediction models that estimate the chance of having a baby over multiple complete cycles of in vitro fertilisation (IVF)—that is, cumulative live birth.1 The pretreatment model predicts the chance of cumulative live birth before treatment starts, and the post-treatment model predicts the chance of cumulative live birth just after the first embryo transfer. Through a collaboration with researchers from the University of Utrecht, who have externally validated these models, we have decided to revise the method used to assess the discriminatory ability of our models in the original study. In time to event models, such as ours, discrimination indicates the proportion of all pairs of women who can be ordered such that the woman with the lower predicted chance of live birth is the one who either did not have a live birth or had more complete cycles of IVF to have a live …
R-CHOP preceded by blood-brain barrier permeabilization (BBBp) by NGR-tumor necrosis factor (NGR-hTNF) in patients with relapsed or refractory primary CNS lymphoma (rrPCNSL): First results of the “INGRID” phase II trial.
Authors: Andres J. Ferreri, Teresa Calimeri, Gian Marco Conte, Paolo Lopedote, Marco Foppoli, Stefania Girlanda, Angelo Corti, Dario Cattaneo, Federico Fallanca, Alessandro Nonis, Maurilio Ponzoni, Giovanni Citterio, Letterio Politi, Marianna Sassone, Salvatore Perrone, Caterina Cecchetti, Fabio Ciceri, Claudio Bordignon, Nicoletta Anzalone
Journal: Journal of Clinical Oncology (2018)

7575 Background: PCNSL pts are treated with HDMTX-based chemo, which requires hospitalization and extensive expertise to manage toxicity. R-CHOP could overcome these troubles, but CNS access of related drugs is poor. TNF induces BBBp and improves CNS access of anticancer drugs. The addition of NGR peptide enhances biological properties of TNF without major toxicity. The hypothesis that NGR-hTNF can improve CNS availability and activity of R-CHOP in pts with rrPCNSL is being evaluated in a phase II trial. Herein, we report results of a per-protocol exploratory analysis. Methods: HIV-neg pts (age 18-80 y; PS ≤3) with PCNSL failed after HDMTX-based chemo were enrolled. Pts received 6 cycles of R-CHOP, preceded by NGR-hTNF 0.8 μg/m² in 1-hr inf in cycles 2-6. Response, microvasculature and vessel permeability were assessed by DCE- and DSC-MRI. Permeability was assessed in enhanced lesions and perilesional areas; results were expressed as Ktrans values normalized using contralateral white matter. R-CHOP drugs levels were assessed on matched CSF and serum/plasma samples. Results: The first 10 registered pts (median age 61 yo, range 41-68; 7 males) were analyzed. Pts were heavily pretreated: 7 had received ASCT, WBRT or both; 6 had refractory disease. Response to NGR-hTNF R-CHOP was complete in 5 pts and partial in 2; 3 pts experienced PD. All responding pts received consolidation (WBRT or ASCT); DoR was > 6 months in 6 pts, only one responding pt died. Treatment was well tolerated; no cases of g≥3 non-hematol toxicity, dose reduction or interruption were recorded. Neutropenia (54% of courses) and thrombocytopenia (15%) were the only g4 toxicities. NGR-hTNF delivery increased permeability as median (range) Ktrans of enhanced and perilesional areas raised from baseline values of 23.5 (6.8-98.8) and 2.5 (0.4-3.9) to 35.3 (23.9-887.7; p = 0.39) and 4.7 (2.2-37.7; p = 0.01), respectively. PK and perfusion data will be presented at the meeting. Conclusions: This exploratory study suggests that NGR-hTNF increases vascular permeability in pts with rrPCNSL. R-CHOP preceded by NGR-hTNF is safe and active in these pts. Clinical trial information: 201400153211.
Prognostic factor for third-line chemotherapy in patients with advanced gastric cancer.
Authors: Jonggwon Choi
Journal: Journal of Clinical Oncology (2017)

e15702 Background: To evaluate prognostic factors for patients with advanced gastric cancer treated by Third-line chemotherapy, and to identify the characteristics of long-term survivors. Methods: Eighty seven advanced gastric adenocarcinoma patients, who received third-line chemotherapy, were enrolled in this retrospective study from January 2010 until December 2014. Univariate and multivariate analyses were created using log-rank tests and Cox’s proportional hazard model, respectively. Results: In univariate and multivariate analyses, poor prognostic factor were investigated and four independent factors were found to be associated with poor overall survival: time-to progression under first-line chemotherapy≤6 months (HR, 1.64; 95% CI, 1.18–2.25; P ≤ 0.01), CA 19-9 level &gt; 50 ng/ml (HR, 1.78; 95% CI, 1.32–2.67; P ≤0.007), the presence of ascites (HR, 1.67; 95% CI 1.295– 2.37, P ≤0.001), the presence of greater than or equal to three metastatic sites of disease (HR, 1.45; 95% CI 1.19– 2.19, P ≤0.004). 87 patients were classified as low-risk group( no risk factor), intermediate-risk group (one to two risk factors), high- risk group (three to four risk factor), and median survival times for each groups were 14.3 months, 12.1 months, and 7.4 months, respectively (P ≤0.01). Conclusions: This model will help in selecting the patients with advanced gastric cancer who could benefit from proceeding with third-line chemotherapy.
Characterization of clinically aggressive meningiomas by mutational signatures associated with DNA mismatch repair and aging.
Authors: Sylvia Christine Kurz, Stephen Kelly, Varshini Vasudevaraja, Benjamin Liechty, Ramona Bledea, Peter Wu, Jonathan Serrano, Leah M. Katz, Joshua Seth Silverman, Donato Pacione, Stephen Russel, Chandra Sen, John Golfinos, Andrew S. Chi, Matija Snuderl
Journal: Journal of Clinical Oncology (2018)

e14044 Background: Up to 20% of meningiomas behave aggressively with high recurrence rates and reduced survival. There is a lack of biomarkers predicting the risk of an unfavorable clinical course although aberrations in NF2, increased copy number variations (CNV) and a hypermethylated phenotype have been associated with more aggressive behavior. Mutational signatures are characteristic patterns of somatic mutations seen in cancer genomes that have been associated with aging, exposure to certain mutagens, or defective DNA repair. We aimed to identify mutational patterns in clinically aggressive meningiomas with early recurrence. Methods: We performed whole exome sequencing (WES) of 17 de novo meningiomas, locally invasive and recurrent WHO I n = 6, atypical WHO II n = 4, anaplastic WHO III n = 7. Median PFS was 18.9 months. Copy numbers were assessed by DNA methylation array analysis. Mutational signatures were identified using published signature algorithms (COSMIC). Results: We detected a high prevalence of mutational signatures (MS) associated with defective DNA mismatch repair (MMR): MS20 and MS26 were detected in all 17 (100%) and MS6 in 2 (12%) meningiomas. MS1 which is associated with age of diagnosis was present in all 17 (100%) and MS12 (unknown etiology) in 14 (82%) cases. Despite the universal prevalence of MMR mutation signatures, WES analysis identified only 2 (12%) somatic mutations in MMR genes: 1 (6%) meningioma had a MLH1 mutation and 1 (6%) meningioma had a MSH6 mutation. Mutations in other DNA repair pathways (BER/NER/HR) were not detected. WES analysis also identified NF2 mutations in 9 (53%), a SMARCB1 mutation in 1 (6%) and an AKT1 mutation in 3 (18%) meningiomas. Sonic-hedgehog (SHH) pathway mutations were present in 3 (18%) samples (PTCH1 n = 1, SMO n = 2). CNV analysis revealed loss of chr1p in 9 (53%), chr14q in 5 (29%), chr6q in 3 (18%), and chr10q in 2 (12%), and chr22 in 8 (47%) meningiomas. Conclusions: In this set of clinically aggressive meningiomas, we identified a universal prevalence of mutational signatures associated with defective DNA MMR and age of diagnosis. However, only 2 meningiomas had MMR gene mutations (MLH1 and MSH6).
Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis
Authors: Jared Klarquist, Alisha Chitrakar, Nathan D. Pennock, Augustus M. Kilgore, Trevor Blain, Connie Zheng, Thomas Danhorn, Kendra Walton, Li Jiang, Jie Sun, Christopher A. Hunter, Angelo D’Alessandro, Ross M. Kedl
Journal: Science Immunology (2018)

T cell responses to subunit vaccination require both IL-27 and IL-15 to support an aerobic glycolysis–independent metabolic program.
Patient-reported outcomes (PROs) in the randomized, phase III IMpower150 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous metastatic NSCLC (mNSCLC).
Authors: Martin Reck, Tom Karagiannis, Thomas Wehler, Mikhail Shtivelband, Jose-Luis Gonzalez-Larriba, Jeffrey Rothenstein, Martin Frueh, Yu Deng, Ariel Lopez-Chavez, Alan Sandler, Mark A. Socinski
Journal: Journal of Clinical Oncology (2018)

9047 Background: Atezo (anti–PD-L1) + bev (anti-VEGF) + chemo prolonged PFS vs bev + chemo in patients (pts) with 1L nonsquamous mNSCLC in the randomized, Phase III IMpower150 study. PRO data, including symptom burden, functioning and health-related quality of life (HRQoL), were evaluated to assess overall clinical benefit in each treatment (Tx) arm. Methods: Pts received atezo 1200 mg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator decision, then maintenance atezo, atezo + bev, or bev, respectively. PRO data were collected using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Prespecified analyses included the mean change from baseline in symptoms, functioning and HRQoL and time to deterioration (TTD) in lung cancer symptoms. Clinically meaningful change was defined as a ≥10-point change in score from baseline. Results: PRO completion rates were high (≥70% through cycle 23 for all arms). Mean changes from baseline indicated that a clinically meaningful worsening (≥10-point change) was not observed in any arm through cycle 13 (≈25% of pts remain in Arm C); HRQoL and physical functioning scores minimally decreased (Arm A: −2.83 and −3.39; Arm B: −1.8 and −3.98; Arm C: −1.92 and −2.6) with concurrent numerical worsening in Tx-related symptom scores (e.g., fatigue, constipation, nausea/vomiting). Following chemo completion, scores returned to baseline or numerically improved. HRQoL, physical functioning and Tx-related symptoms were comparable between Arms B and C. No difference was observed between arms in the TTD in lung cancer symptoms assessed. All arms reported numerical improvement in multiple lung cancer symptoms while on Tx. Conclusions: These data suggest that prolonged PFS in Arm B was achieved without compromising HRQoL or physical functioning despite higher Tx-related AEs than Arm C. PRO data reflected a minimal Tx burden across arms, further reduced following chemo discontinuation. Overall, PRO data support the positive benefit:risk of the clinical data with atezo + bev + chemo in 1L nonsquamous mNSCLC. Clinical trial information: NCT02366143.