tbuckley/cabot-search huggingface dataset:
Efficacy and safety of programmed death receptor-1 (PD-1) blockade in metastatic uveal melanoma (UM).
Authors: Katy K. Tsai, Alexander Noor Shoushtari, Rodrigo Ramella Munhoz, Zeynep Eroglu, Josep M. Piulats, Patrick Alexander Ott, Douglas Buckner Johnson, Jimmy Hwang, Adil Daud, Jeffrey Alan Sosman, Richard D. Carvajal, Bartosz Chmielowski, Michael Andrew Postow, Jeffrey S. Weber, Ryan J. Sullivan, Alain Patrick Algazi
Journal: Journal of Clinical Oncology (2016)

9507 Background: PD-1 pathway inhibitors have shown significant activity in the treatment of advanced cutaneous melanoma. Their role in UM has not yet been well characterized. UM has molecular, pathogenic and clinical features distinct from cutaneous melanoma, including a low overall mutation burden, rare BRAF V600 and NRAS mutations, and a propensity for liver metastasis. In this series, we further investigate the efficacy and safety of PD-1 blockade in metastatic UM patients (pts). Methods: We analyzed a multicenter retrospective series of stage IV UM pts treated with antibodies against PD-1 (pembrolizumab, nivolumab) or its ligand, PD-L1 (atezolizumab). Tumor responses were evaluated by RECIST v1.1, and adverse events by CTCAE v4.0. Survival intervals were calculated using the Kaplan-Meier method. Demographic and clinical variables associated with tumor response and survival were investigated. Results: We retrospectively identified 58 pts across 9 academic institutions. Fifty-four (93%) pts had ECOG performance status 0 or 1, and 52 (90%) had liver metastases. Seven (12%) were treatment-naïve and 36 (62%) had received prior ipilimumab. Forty (69%) received pembrolizumab, 16 (28%) received nivolumab, and 2 (3%) received atezolizumab. Objective response rate (ORR) was 3% (95% confidence interval [CI] 0-8.4%). Stable disease greater than 6 months was observed in 4 (7%) pts. Median progression-free survival (PFS) was 2.7 months (95% CI 2.4-3.3). Median overall survival (OS) was 9.5 months (95% CI 5.5-15). There was no significant association between improved PFS or OS and age, sex, metastatic site or response to prior ipilimumab. PD-1/PD-L1 blockade was well tolerated; 7 (12%) pts reported grade 3 adverse events (AEs) of colitis, fatigue, nausea, vomiting, hyperbilirubinemia or lymphopenia, and no grade 4 or 5 AEs were reported. No pts discontinued therapy due to toxicity. Conclusions: In this largest series to date of UM pts treated with PD-1/PD-L1 antibodies, treatment was safe but rarely conferred durable responses. Predictive biomarkers and other immune or targeted therapies should be further investigated to improve clinical outcomes.
Are young breast cancer patients' clinico-pathological characteristic different when comparing populations from developing countries? Analysis of two cohorts of patients from Romania and Mexico.
Authors: Saul Campos Gomez, Nicoleta Zenovia Antone, Laura Pop, Karen Angelica Campos Gomez, Andrei Stoian, Guillermo Pacheco-Cuéllar, Eleonora Dronca, Juan Valdes Andrade, Ramona DOINA Matei, Marjolijn Ligtenberg, Hicham Ouchene, Andrea Onisim, Olivia Rotaru, Rares Eniu, Alexandru E. Eniu
Journal: Journal of Clinical Oncology (2018)

e13572 Background: Breast cancer (BC) is the most common malignancy in women with 6.6% of cases diagnosed in young women below the age of 40. Although there are significant similarities in demographic and clinico-pathological characteristic between geographical areas, the striking difference is in peak age for young populations. Objetive:Comparison of two young breast cancer(YBC) patients (pts) cohorts candidates for BRCA gene testing of two Developing Countries Methods: In this retrospective study, we analyzed 2 cohorts of 70 YBC pts candidates for BRCA gene testing treated at COEI in Mexico between 2013 to 2015 and IOCN from Romania between 2015 to 2016.Patient demographic and clinico-pathological information was recorded, and included: age at diagnosis, laterality presentation, clinical stage, Scarff-Bloom-Ricardson (SBR) grading, hormone receptor (HR), HER2neu and Ki 67% status Results: The analysis of these cohorts revealed clinical stage to be statistically significant different,(p = 0.0084), the Romanian population presented more advanced loco-regional disease. Invasive ductal carcinoma was the most prevalent histopatological subtype in both groups with no statistical significance (p = 0.5239). Grade 3 was more frequent in the Romanian population, while the Mexican subgroup presented mainly grade 2( p = 0.0011), statistically significant. Regarding HR status, the Caucasian population was mainly positive, while the Hispanic cohort presented more frequent negative, statistically significant (p = 0.0040). Majority of Romanian and Mexican population were Her2 neu status negative, (p = 0.2749). The Romanian population presented more aggressive feature, ki67 > 15%, when compared with Mexican cohort (p = < 0.0001).(Table 1) Conclusions: YBC pts represent an important BC subpopulation worthy to perform systematic analysis regarding demographic and clinico-pathological characteristics, especially in populations from developing countries. Our results indicate that parameters like stage, grading, HR status and ki67% are statistical significant when comparing Romanian and Mexican YBC groups
Prolonged functional persistence of CD19CAR t cell products of defined CD4:CD8 composition and transgene expression determines durability of MRD-negative ALL remission.
Authors: Rebecca Alice Gardner, Olivia Finney, Hannah Smithers, Kasey Leger, Colleen Elizabeth Annesley, Corinne Summers, Catherine Lindgren, Stephanie Mgebroff, Christopher Brown, Karen Spratt, Assaf Oron, Marie Bleakley, Julie R. Park, Michael Jensen
Journal: Journal of Clinical Oncology (2016)

3048 Background: CD19 CAR-T cell has proven efficacy for treatment of aggressive ALL. However, limited CAR-T cell persistence and/orCD19 loss are barriers to therapeutic success. Methods: A Phase I trial (NCT02028455) of CAR-T cell products consisting of purified CD4 and CD8 T cell subsets expressing uniform levels of a 4-1BB second generation CD19-specific CAR were infused following either cyclophosphamide (Cy) or fludarabine (flu/cy). Leukemic response, B-cell aplasia (BCA) and T cell persistence were evaluated by flow cytometry. Results: Products were successfully manufactured in 39/40 consecutively enrolled patients (pts) (1-25y) despite having no screening assay of lymphocyte proliferation. The ALC at time of apheresis ranged from 140-4488/µl. Of evaluable pts, 91% (33/36) achieved MRD negative (neg) CR's in a cohort of children and young adults. The DFS and OS at 12 months are 53% and 74%. Improved disease-free survival (DFS) was observed in pts with ongoing BCA beyond day 63 (HR: 0.25 [95% CI: 0.08, 0.81], P = 0.01). For patients treated with Cy, durable engraftment of CAR T cells was positively influenced by CD19 antigen (Ag) burden (ALL + nonmalignant B cells) of > 15 % in the marrow at the time of CAR infusion (median of 4.2 v 1.4 months). This effect in 8 pts given Flu/Cy is currently under evaluation as the duration of BCA appears to also be influenced by lymphodepletion (median of 3.9 v 2.1 mo flu/cy v cy). Six patients had CD19-relapse. Conclusions: Our trial of CD19 CAR-T cell adoptive therapy has revealed a high rate of manufacturing success and MRD neg remissions. Despite high rates of MRD-neg remission, relapse is a significant etiology of treatment failure. The durability of remissions was influenced by the duration of CAR-T cell functional persistence of at least 63 days duration. Ag-driven proliferation affects the duration of B cell aplasia for pts given a Cy alone regimen. Lymphodepleting regimens also appear to influence the duration of B cell aplasia and potentially negate the effect of CD19 Ag burden. Accordingly, our program is continuing to investigate Flu/Cy conditioning regimens to improve CAR-T cell persistence. Clinical trial information: NCT02028455.
Phase II study of durvalumab (anti-PD-L1 antibody) in combination with R-CHOP or lenalidomide plus R-CHOP in previously untreated, high-risk diffuse large B-cell lymphoma.
Authors: Grzegorz S. Nowakowski, Nagesh Kalakonda, Lorenz Truemper, Hele Everaus, Pierre Fustier, Jonathan Jaeger, Oliver Manzke, Ulrich Jäger
Journal: Journal of Clinical Oncology (2017)

TPS7573 Background: The PD-1/PD-L1 pathway is an important immune checkpoint used by tumor cells and may provide an effective target for enhancing anticancer immune response. In DLBCL, high PD-L1 expression has been identified as a negative prognostic factor for overall survival. Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal Ab that selectively blocks PD-L1 binding to PD-1 and CD80, and preliminary preclinical and clinical activity support the study of durvalumab in high-risk DLBCL subtypes. The primary study objective is to explore the clinical activity of durvalumab with R-CHOP in non-activated B-cell–like (non-ABC) and durvalumab with lenalidomide + R-CHOP (R 2 -CHOP) in ABC previously untreated DLBCL; secondary objectives are to evaluate safety and identify biomarkers predictive of clinical response. Methods: This is a phase II, two-arm, open-label, global, multicenter study of durvalumab combinations in patients with previously untreated, high-risk DLBCL (MEDI4736-DLBCL-001; EUDRA CT 2015-005173-20; NCT03003520). High risk was defined as Ann Arbor stage III/IV or II with bulky disease (≥7.0 cm), along with intermediate-high/high IPI ≥3 or NCCN-IPI ≥4; patients must also have CD20+ DLBCL, ECOG PS 0-2, and no prior antilymphoma therapy. All patients receive durvalumab + R-CHOP21 in induction cycle 1 simultaneous to cell-of-origin (COO) analysis by gene expression profiling with NanoString technology. Beginning with cycle 2, Arm A (non-ABC) receives durvalumab 1125 mg IV on day 1 with 6 or 8 cycles of R-CHOP21; Arm B (ABC) receives the same durvalumab + R-CHOP21 doses with oral lenalidomide 15 mg/day on days 1-14. Both arms receive durvalumab consolidation 1500 mg IV on day 1 q28d for ≤12 months from induction cycle 1, day 1. The primary endpoint is 2-y progression-free survival (PFS); secondary endpoints include clinical response to treatment in biomarker-defined subpopulations (tumor and peripheral blood) and safety as assessed per NCI CTCAE v4.03 criteria. Exploratory endpoints include PFS at 12 mo, complete response, and PK/PD. Recruitment is ongoing, with a target enrollment of 120 patients. Clinical trial information: NCT03003520.
Phase III randomized trial of chemotherapy with or without bevacizumab (B) in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Survival analysis of E1305, an ECOG-ACRIN Cancer Research Group trial.
Authors: Athanassios Argiris, Shuli Li, Panayiotis Savvides, James Ohr, Jill Gilbert, Marshall A. Levine, Missak Haigentz, Nabil F. Saba, Arnab Chakravarti, Chukwuemeka Ikpeazu, Charles Schneider, Harlan Pinto, Arlene A. Forastiere, Barbara Burtness
Journal: Journal of Clinical Oncology (2017)

6000 Background: The addition of B, an anti-VEGF monoclonal antibody, to chemotherapy has improved outcomes in several solid tumors. Pemetrexed plus B showed promising efficacy in R/M SCCHN (Argiris et al. JCO 2011). E1305 was designed to evaluate the addition of B to a platinum doublet in R/M SCCHN. Methods: B-eligible pts with performance status 0-1, not having received chemotherapy for R/M SCCHN (prior chemotherapy for locally advanced disease allowed ≥ 4 months) and without factors predisposing to bleeding (history of bleeding due to SCCHN, anticoagulation, central cavitary lung metastasis, carotid invasion) were randomized to: A) one of 4 regimens (investigator's choice) given every 3 weeks: A1, cisplatin (C) 100 mg/m 2 , 5-FU 1000 mg/m 2 /day x 4 days; A2, carboplatin (Cb) AUC 6, 5-FU 1000 mg/m 2 /day x 4 days; A3, C 75 mg/m 2 , docetaxel (D) 75 mg/m 2 ; A4, Cb AUC 6, D 75 mg/m 2 , or B) the same regimen (B1, B2, B3, B4) plus B 15 mg/Kg IV, every 3 weeks, until progression. Chemotherapy could be stopped after 6 cycles after maximum response. All pts received prophylactic antibiotics. The primary endpoint was overall survival (OS). Control median OS of 8.5 months (mo) was projected; the addition of B was hypothesized to increase median OS to 11.5 mo with a hazard ratio (HR) of 0.74. Results: 403 pts were randomized (200 in arm A; 203 in arm B). Baseline characteristics were well balanced. 38% in arm A/42% in arm B had an oropharyngeal primary; 87% received C or Cb plus D. With a median follow-up of 23.1 mo, median OS was 11 mo in arm A and 12.6 mo in arm B; HR 0.84 (95% CI 0.67-1.05), p = 0.13. The 1-, 2-, 3-, and 4-year OS were 46% vs 51%, 18% vs 26%, 8% vs 16%, 6% vs 13%, in arm A vs B, respectively. Median PFS was 4.4 mo in arm A and 6.1 mo in arm B (HR 0.71, 95% CI 0.58-0.87; p = 0.0012). Objective response rate was 25% in arm A vs 36% in arm B (p = 0.013). Grade 3-5 bleeding occurred in 3.5% in arm A vs 7.7% in arm B (p = 0.08). Conclusions: B added to a standard platinum doublet improved response rate and PFS but not OS in first-line treatment of R/M SCCHN. The control arm in this study performed better than expected. Clinical trial information: NCT00588770.
Acute care reliance among patients with advanced cancer with or without nurse navigation.
Authors: Marc Kowalkowski, Kris Blackley, Carol J. Farhangfar
Journal: Journal of Clinical Oncology (2017)

e18303 Background: Acute care utilization is a key component of health care cost among oncology patients, particularly at advanced stages. Oncology nurse navigation (NN) was developed to improve access to quality cancer care but little is known about the impact of NN on acute care reliance (ACR) among patients with advanced cancer. Methods: A cohort study was conducted among adults (≥18) diagnosed with advanced-stage (III/IV) first primary solid tumor (10 most common solid tumors by annual incidence - bladder, breast, colon, kidney, lung, melanoma, pancreas, prostate, thyroid, uterus) from January 2013-December 2015. For inclusion, NN patients had to initiate NN services ≤30 days after diagnosis and all patients must have had ≥30 days of follow-up. The primary outcome was ACR, defined as the proportion of total health care utilization received in an acute care setting (hospital inpatient/observation, emergency department), from diagnosis through 1 year, calculated per 30-day interval to adjust for follow-up variance. To assess the effect of NN receipt on ACR, generalized linear models were fit specifying a gamma distribution and a log-link function, adjusted for patient and clinical characteristics at diagnosis. Subgroup analyses were conducted in patients surviving &lt; 6 and ≥6 months. Results: 2950 patients with advanced cancer were followed (NN = 970 [33%]). Lung (37%), prostate (13%) and breast (12%) cancers were most common. 944 (32%) patients died during the 1-year interval. Patients averaged 1.7 health care encounters per 30-day interval. Those who received NN had lower mean ACR than patients who did not, overall (0.18 vs 0.30; p &lt; 0.001) and in each individual cancer type (p &lt; 0.05) except melanoma (p = 0.4). In multivariable models, NN receipt was associated with decreased ACR (RR = 0.65 95%CI = 0.60-0.70). The effect of NN on ACR was consistent in subgroups defined by survival duration. Conclusions: Patients with advanced cancer who received NN were less reliant on acute care than patients who did not receive NN. Given the role of acute care in driving health care cost and the inverse association between increased ACR and health care quality, our findings may have important implications for improving value in oncology care.
Abstract 17754: The Impact of Postdischarge Physical Activity on Mid- and Long-Term Rehospitalization of Older Japanese Patients With Heart Failure
Authors: So Miyahara, Naoki Fujimoto, Kaoru Dohi, Emiyo Sugiura, Keishi Moriwaki, Taku Omori, Naoto Kumagai, Norikazu Yamada, Masaaki Ito
Journal: Circulation (2016)

Introduction: Regular physical activity (PA) reduces morbidity and mortality in older adults. However, the relationship between postdischarge PA and rehospitalization of older patients with heart f...
Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders: a single-centre, single-blind, randomised controlled trial
Authors: Maral Jolstedt, Tove Wahlund, Fabian Lenhard, Brjánn Ljótsson, David Mataix-Cols, Martina Nord, Lars-Göran Öst, Jens Högström, Eva Serlachius, Sarah Vigerland
Journal: The Lancet Child & Adolescent Health (2018)
Code status transitions from full code to do-not-resuscitate (DNR) among hospitalized patients with advanced cancer.
Authors: Kelsey S. Lau-Min, Ryan David Nipp, Sara D'Arpino, Samantha M.C. Moran, Ephraim Hochberg, Lara N. Traeger, Vicki Jackson, Barbara J. Cashavelly, Holly S Martinson, David P. Ryan, Joseph Greer, Jennifer Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2017)

6592 Background: Code status discussions ensure the delivery of preference-concordant care. However, the processes by which hospitalized patients with advanced cancer change their code status from full code to DNR are unknown. Methods: We conducted a mixed-methods study on a prospective cohort of patients with advanced cancer who were hospitalized from 9/14-10/15. Two physicians used a consensus-driven medical record review to characterize processes leading to code status transitions from full code to DNR. We explored factors associated with these processes using χ2 and Kruskal-Wallis tests. Results: We reviewed 1,047 hospitalizations among 728 patients. Admitting physicians did not address code status in 52.1% of these hospitalizations, leading code status orders to be presumed full. 273 patients (37.5%) transitioned from full code to DNR; 132 (48.4%) of them had erroneous presumed full code status orders on admission. We identified three additional processes leading to transitions from full code to DNR: acute clinical deterioration (15.4%), discontinuation of cancer-directed therapy (17.2%), and hypothetical discussions regarding the futility of CPR (15.4%). Among these processes, code status transitions due to acute clinical deterioration were associated with less patient involvement, shorter time to death, and higher likelihood of inpatient death. Changes due to hypothetical discussions were more likely to involve palliative care. Conclusions: Half of code status transitions among hospitalized patients with advanced cancer were due to erroneous full code orders, underscoring a greater need to discuss patient CPR preferences. Transitions due to acute clinical deterioration were associated with less patient engagement and higher likelihood of inpatient death. [Table: see text]
Sixty seconds on . . . the 100 Word Project
Authors: Abi Rimmer
Journal: BMJ (2018)

Not quite. It’s an initiative that aims to share healthcare workers’ experiences of resilience through Instagram (@100wordproject).

In a manner of speaking. The project is led by Axie Finch, a final year medical student, in collaboration with nursing students Jess Antsee and Jess Rees. They also have a presence on Facebook and Twitter.

You can indeed. Finch says …
Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel as first-line chemotherapy for patients with metastatic gastric cancer.
Authors: Rui-hua Xu, Ming-ming He, Dong-sheng Zhang, Feng Wang, Ying Jin
Journal: Journal of Clinical Oncology (2016)

4049 Background: Little was known about nanoparticle albumin-bound paclitaxel (Nab-PTX) in gastric cancer. As the first phase II trial, it aimed to evaluate the efficacy and safety of S-1 plus Nab-PTX as first-line treatment for patients with metastatic gastric cancer. Methods: A total of 73 gastric cancer patients with metastatic and measurable lesions (M/F 45/28, median age 53, ECOG 0-2) were enrolled in first-line setting from Sun Yat-sen University Cancer Center between 2011 and 2015. They were orally treated with S-1 in doses of 40 mg (BSA < 1.25 m2), 50 mg (1.25 ≤ BSA < 1.50 m2) and 60 mg (BSA ≥ 1.50 m2) b.i.d. on days 1-14 in combination with Nab-PTX (200-240 mg/m2, divided on days 1 and 8, intravenously during 30 minutes) of each 21-day cycle. Treatment was planned for 4-6 cycles, or until progression, unacceptable toxicity, and discontinuation. Primary endpoint was progression-free survival (PFS) and secondary endpoints were overall response rate (ORR), overall survival (OS), and adverse events (AEs). Results: Of the 73 patients, 4 (5.5%) had complete responses, 35 (47.9%) had partial responses (PRs), 25 (34.2%) had stable diseases, 4 (5.5%) progressed and 5 (6.8%) were not evaluable, with median number of cycles as 4 (range 1-6). The ORR and DCR were 53.4% and 87.7%, accordingly. The median PFS was 8.77 months (95% confidence interval (CI) 6.88–10.66). The median OS was 14.70 months (95% CI 9.57–19.83). Most AEs were mild without treatment-related death. Grade 3 to 4 AEs occurred in 22 patients (30.1%) and grade 4 AE (neutropenia) occurred in only one of them. Grade 3 AEs included leukopenia (13.7%), neutropenia (12.3%), anemia (5.5%), thrombocytopenia (1.4%), diarrhea (6.8%), vomiting (2.7%), stomatitis (1.4%), peripheral neuropathy (1.4%), and hand-foot syndrome (1.4%). After 2 to 6 cycles, 7 patients (6 lymph node, 1 liver) achieved good PRs and received gastrectomy plus metastasectomy. 30 (41.1%) patients had S-1 monotherapy as maintenance with median number of cycles as 4 (range 1–20). Conclusions: S-1 plus Nab-PTX is an encouraging option in first-line treatment for patients with metastatic gastric cancer, with promising efficacy, safety, and convenience. Clinical trial information: NCT02229058.