tbuckley/cabot-search huggingface dataset:
Impact of a pilot patient navigator program on pediatric cancer outcomes in a low resource setting.
Authors: Kristin Schroeder, Fatima Alvi, Hartlee Johnston, Nestory Andrew Masalu, Nelson Jen An Chao
Journal: Journal of Clinical Oncology (2019)

e18152 Background: Oncology patient navigation programs have been successfully implemented at hospitals throughout the U.S., enhancing the quality of canceer care. In low resource settings, the barriers to receiving cancer care are increased and a patient navigator in this setting has the potential to significantly impact outcomes. However, research on efficacy is limited. Methods: At Bugando Medical Centre (BMC) in Mwanza, Tanzania, semi-structured qualitative interviews of 15 key stakeholders in the oncology department and 15 families of patient with pediatric cancer diagnoses were completed to identify health system delivery and patient related barriers to timeliness of diagnosis, treatment initiation, and treatment completion. Based on identified barriers, a pilot patient navigation program was established to assist patients and their families with care coordination throughout the diagnosis and treatment process. A retrospective analysis of hospital records was conducted of all pediatric oncology patients seen at BMC from 2010-2016, separated by presentation date before or after establishment of navigation program. Collected data includes demographics, diagnosis, time from presentation to oncology evaluation and diagnosis, and treatment completion. Results: Identified patient related barriers included patient diagnosis and treatment knowledge, and complexity of care. Health system delivery barriers included limited provider capacity, and poor care coordination between the oncology providers, other health care services and patient families. A total of 238 patient files were reviewed, with 169 pre- and 69 post- program initiation. Patient groups did not differ by age or gender (p = 0.329 and 0.744), or diagnosis distribution. The average time to oncology evaluation decreased from 49.7 to 16.6 days (p = 0.015), and time to diagnosis decreased from 49.1 to 23.6 days (p = 0.07). Treatment abandonment decreased from 50% to 38% (p &lt; 0.001). Conclusions: In pediatric oncology, early diagnosis is critical to the initiation of chemotherapy and improving outcomes. These data suggest that a patient navigation program is feasible in a LMIC and can impact both health system inefficiency and treatment abandonment, with the potential to improve pediatric cancer outcomes.
SP0043 MY IDEAL TRANSITION
Authors: Indra Beer
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> In my lecture I will present the barriers of transition from the young patient"s point of view and show possible solutions. Every year 2.000 young people aged between 16 and 19 arrive at the transition phase in Germany. One third of these young rheumatic patients stop or interrupt their therapy when they have to change from the paediatric rheumatologist to the adult rheumatologist. In my talk I will focus on significant changes in the lives of young people. This includes e.g. the changes due to education and training, the first partnership or just moving out of the parents' house. Especially in the difficult phase of transition young people should be strengthened and be made aware of the differences between the doctors treating them and the barriers they will be facing. They should learn to manage themselves and be made sensitive that long-term damage can be avoided. So, based on my experience I will outline the various support services that are necessary to prepare and accompany young people in that transition phase. Only then, in addition to evidence-based medical care, young people with a rheumatic disease can achieve a successful long-term healthcare outcome that will enable full participation in life. <h3>Disclosure of Interests:</h3> None declared
Abstract 14760: Right Ventricular Function in Preterm Neonates: Reference Values for Longitudinal Strain by Two-dimensional Speckle Tracking Echocardiography From Birth to One Year of Life
Authors: Philip T Levy, Meghna D Patel, Mark R Holland, Timothy J Sekarski, Amit Mathur, Caroline Lee, Aaron Hamvas, Gautam K Singh
Journal: Circulation (2015)

Introduction: Right ventricle (RV) systolic function is an important determinant of cardiopulmonary outcomes in premature infants. Two-dimensional speckle tracking echocardiography (2DSTE) derived myocardial strain is a reliable measure of RV systolic function in premature infants, but lacks reference values for clinical application in premature infants. We aimed to determine the maturational (age- and weight- related) changes in RV strain to establish reference values in preterm infants from birth to one year corrected age (CA). Methods: RV peak global longitudinal strain (pGLS) and RV free wall longitudinal strain (FWLS) were measured in a prospective longitudinal study in 115 preterm infants (&lt; 29 weeks at birth) at 24 and 72 hours of age (HOA), 32 and 36 weeks postmenstrual age (PMA), and one year (CA) by 2DTSE (GE EchoPac) from a RV-focus apical 4-chamber view using a validated protocol. Premature infants that developed chronic lung disease or had a hemodynamically significant PDA were excluded (n=65) from analysis for the reference values. Results: RV pGLS ranged from -16% at birth to -26% by one year CA and RV FWLS ranged from -18% at birth to -27% to one year CA in healthy preterm infants. RV pGLS and FWLS strain correlated with increasing weight (r=0.87, p &lt; 0.001), PMA in weeks (r=0.85, p &lt; 0.001; r=0.83, p &lt; 0.001), but were independent of gestational age at birth (r=0.4, p=0.38; r=0.3, p=0.5). RV strain was significantly lower in preterm infants with bronchopulmonary dysplasia (p=0.004) at 32 and 36 weeks PMA, and one year CA (Figure). RV strain was independent of gender or need for mechanical ventilation. Conclusions: This study establishes reference values of RV global and free wall longitudinal strain and tracks their postnatal maturational changes in preterm infants. These measures increase from birth to one year CA and are linearly associated with increasing weight reflecting the postnatal cardiac growth as a contributor to the maturation of RV function.
BRCA1 genetic variant to predict survival in metastatic colorectal cancer (mCRC) patients (pts) treated with FOLFIRI/bevacizumab (bev): Results from phase III TRIBE and FIRE-3 trials.
Authors: Madiha Naseem, Shu Cao, Sebastian Stintzing, Fotios Loupakis, Martin D. Berger, Alberto Puccini, Ryuma Tokunaga, Francesca Battaglin, Afsaneh Barzi, Shivani Soni, Joshua Millstein, Mohamed E. Salem, Chiara Cremolini, Wu Zhang, Volker Heinemann, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

3145 Background: BRCA muts in CRC are associated with a higher tumor mutation burden irrespective of microsatellite instability, which highlights the possibility of using PARP-inhibitors(i) in CRC in the future. Early phase studies have shown that combination of PARP-i with oxaliplatin or irinotecan enhances tumor lysis in CRC. In this study, we investigated the influence of mutations in the Homologous Repair Pathway genes on survival outcomes among mCRC pts treated with oxaliplatin or irinotecan-based regimens. Methods: The impact of selected SNPs within 4 genes (BRCA1, BRCA2, RAD51, BARD1) on OS/PFS was analyzed through the OncoArray, a custom array manufactured by Illumina, on genomic DNA from blood samples of 431 pts enrolled in 2 randomized trials. TRIBE FOLFIRI/bev arm (n = 215, mPFS/OS: 9.7/26.2 mo) served as discovery cohort, FIRE-3 FOLFIRI/bev arm (n = 107, mPFS/OS: 11.5/31.4 mo) as validation and TRIBE FOLFOX/bev arm (n = 109, mPFS/OS: 10.8/26 mo) as control. Results: Significant associations were found among carriers of BRCA1 rs8176318 SNP, where C &gt; A base change is known to reduce BRCA1 expression among CRC cells. In the discovery cohort, pts with A/A had shorter OS (22.4 vs 27.3 mo, P = .009) and PFS (7.5 vs 10.5 mo, P = .0006) compared to carriers of any C allele in both univariate and multivariate analysis. Same results were observed in pts with left-sided CRCs (PFS-7.5 vs 11 mo, P = .005; OS- 25.6 vs 32.3, P = .034) and among males (PFS- 7.5 vs 10.3 mo, P = .008; OS- 25.7 vs 31.3 mo, P = .008) in both uni and multivariate analysis. These results were also seen in the validation cohort: A/A carriers in left-sided CRCs had poor OS (26.1 vs 36.0 mo, P = .027) and PFS (9.5 vs 11.7 mo, P = .002. Males with A/A genotype also had poor OS (24.7 vs 32.5 mo, P = .028) and PFS 96.9 vs 12.2 mo; P = .0002). In the control cohort, A/A genotype carriers had poor tumor response in overall (P = .011) and left-sided disease (P = .034). These outcomes were independent of KRAS mutation status. No significant relationship was observed among females with mCRC. Conclusions: This is the first study to report that BRCA1 mut influence survival outcomes among mCRC pts, particularly among males and those with left-sided disease. Prospective trials are warranted to assess the utility of routine BRCA mut testing and the role of PARP-i in improving survival outcomes in this pt population.
Cumulative benefit of multiple agents and drug classes for adjuvant therapy (adj rx) of HER2+ early breast cancer (EBC).
Authors: Frankie Ann Holmes, Melissa Brammer, Renard Dubois, Feng Xu, Bin Yao, Deepa Lalla
Journal: Journal of Clinical Oncology (2019)

e12037 Background: Disease-free survival (DFS) in patients with EBC has improved over time. Trials of systemic agents for adj rx of HER2+ BC, including chemotherapies (CT), endocrine, and HER2-targeted agents have reported improved DFS. This review is a high-level overview describing DFS improvements in adj rx HER2+ BC. Methods: Therapeutic agents listed in NCCN guidelines for adj rx HER2+ BC were evaluated for relative and absolute improvements in DFS. Information was derived from US product labels and publications. Hazard ratios, 95% CI, p-values, and DFS differences at 2 and 5 years (if available) are reported. Results: At 2−3 years, adj rx of HER2+ BC with CT and HER2 treatments reported DFS improvements of 4−5% and 0.9−11.3%, respectively. For hormone receptor positive (HR+) BC, unselected by HER2 status, extended adj letrozole had a 1.9% DFS improvement at 2 years; in HR+ HER2+ BC, extended adj neratinib had 4.5% DFS at 2 years. Conclusions: Relative and absolute improvements in DFS in the adj rx BC setting have been largely incremental and cumulative. Absolute improvements in DFS were 0.9−11.3% with CT, HER2 agents, and AIs. In the subset of HR+ / HER2-positive patients, neratinib showed higher DFS improvement compared to non-steroidal AIs. Similar hazard ratios did not always correspond to similar DFS improvements, possibly reflecting differences in baseline risks in the study populations. [Table: see text]
A single-center retrospective analysis to evaluate the prognostic role of lymph node density in patients with lymph node-positive cervical cancer.
Authors: Arkadius A. Polasik, Wolfgang Janni, Christoph Scholz, Nikolaus De Gregorio, Fabienne Schochter, Thomas W. P. Friedl, Peter Widschwendter
Journal: Journal of Clinical Oncology (2019)

e17013 Background: The aim of this retrospective analysis is to evaluate the prognostic role of lymph node density (LND), i.e. the ratio of positive lymph nodes to the total number of lymph nodes removed during surgery, in nodal-positive cervical cancer patients. Methods: Out of 266 patients with cervical cancer that underwent surgery including lymphonodectomy between 2000 and 2017 at the Department for Gynecology and Obstetrics of the University Hospital Ulm, 86 patients with positive lymph nodes were included in the analysis. According to former study results, patients were divided into two groups with LND &lt; 10% vs. ≥ 10%. Univariable and multivariable cox-regression models (adjusted for age, histological subtype, grading, body mass index, R-status, lymphangiosis, histologically confirmed FIGO-status and chemotherapy) were used to evaluate the association between LND and both overall survival (OS) and disease-free survival (DFS). Results: In the 86 patients, a median of 42 lymph nodes were removed (range 11 – 107), and a median of 2 lymph nodes (range 1 – 25) were found positive. 57 (66.3%) patients had a LND &lt; 10% and 29 (33.7%) patients had a LND ≥ 10%. There was no significant association between LND (≥ 10% vs. &lt; 10%) and OS in both univariable (hazard ratio[HR] 1.49, 95% CI 0.72 – 3.07, p = 0.280) and multivariable survival analysis (HR 1.46, 95% CI 0.64 – 3.32, p = 0.372), respectively. However, LND was significantly associated with DFS in univariable analysis (HR 2.11, 95% CI 1.10 – 4.03, p = 0.024) and was found to be an independent predictor for DFS in adjusted multivariable analysis (HR 2.30, 95% CI 1.08 – 4.91, p = 0.031). Conclusions: LND ≥ 10% in patients with lymph node-positive cervical cancer is associated with a worsened DFS compared to patients with a LND &lt; 10%. Thus, LND may be used as an independent prognostic marker and/or for risk stratification in these patients.
Next-generation genome annotation: we still struggle to get it right
Authors: Steven L. Salzberg
Journal: Genome biology (2019)

While the genome sequencing revolution has led to the sequencing and assembly of many thousands of new genomes, genome annotation still uses very nearly the same technology that we have used for the past two decades. The sheer number of genomes necessitates the use of fully automated procedures for annotation, but errors in annotation are just as prevalent as they were in the past, if not more so. How are we to solve this growing problem?
Use of a modified Delphi panel to define value of combination therapy in oncology.
Authors: Michael Broder, Harshali Patel, Zac Wessler, Sarah Gibbs, Irina Yermilov, Jeffrey Lemay
Journal: Journal of Clinical Oncology (2019)

e18369 Background: Treatment regimens involving 2+ novel oncologics have improved health outcomes in several tumor types. These regimens have significantly higher costs than single agents and older treatments (e.g., chemotherapies), which are still widely used to treat different cancers. Our goal was to determine if current concepts of “value,” such as those described by ICER and other frameworks, adequately capture the value of combination therapies. Methods: Using a RAND/UCLA modified Delphi panel, 8 experts from various backgrounds were provided with a review of current concepts of value and asked to rate them on measurability, relevance, and necessity to determine a combination therapy’s value from 4 perspectives (patient, physician, payer, society). After the first round of ratings, panelists met in person and discussed areas of disagreement. Ratings were repeated, and results used to quantitatively summarize group opinion on concepts recommended for inclusion in a value definition. Results: In both rating rounds, experts agreed treatment, clinical evidence, and health outcomes as important domains in determining value. Experts disagreed on whether societal/cultural beliefs, disease factors (i.e., rarity of cancer, unmet need, burden of disease), and other elements of value (e.g., insurance value, reduction in uncertainty, treatment affordability) needed to be incorporated into value assessments of combinations. Responses differed by perspective. Concepts on which there was disagreement decreased post-meeting (23% to 9%). Conclusions: Experts agreed that “value” for 2+ novel oncologics would have a similar definition to value for all high cost oncology therapies. Four key research opportunities to characterize the value of combination therapy emerged: societal context and patient preference may affect value assessments but are not widely considered in current models; some important benefits are not recognized by patients and may be missed by traditional value assessments; given typical patient and societal preferences, cancer treatments may be systematically undervalued vis a vis other health conditions; and combination therapies may present challenges for recently promulgated value frameworks.
Time to surgery (TTS) in renal cell carcinoma (RCC): Predictors and association with overall survival (OS).
Authors: Anuhya Kommalapati, Sri Harsha Tella, Pavankumar Tandra
Journal: Journal of Clinical Oncology (2019)

e16107 Background: Guidelines recommend surgical resection of primary tumor in stages 1-3 RCC. TTS refers to the time frame from the initial diagnosis to surgical resection of primary tumor. Shorter TTS has shown OS benefit in breast, head and neck cancers whereas longer TSS was shown to be acceptable in colon cancer. However, no such data exists for RCC. Using National Cancer Data Base (NCDB), we sought to determine the factors associated with TTS and its effect on OS. Methods: Patients with RCC who underwent partial or total nephrectomy were included, excluding those received neoadjuvant therapy. Logistic regression model was utilized to evaluate relative risk of delayed TTS. OS in association with TTS was estimated using the Kaplan-Meier method and Cox multivariate analysis (MVA). Results: A total of 60,198 RCC patients met the inclusion criteria. In contrast to a prior study that showed a median TTS of 41 days our study showed a median TTS of 35 days. We dichotomized the TTS as ≤ 35 days or ≥ 36 days. On MVA, TSS ≥ 36 days had significantly better OS (HR: 0.95 [CI:0.92-0.99], p &lt; 0.01). Factors associated with TSS ≥ 36 days were race, insurance, higher Charlson score, lower grade, and getting managed at academic facilities and Pacific region (p &lt; 0.01) (Table). Conclusions: A longer TTS with RCC is understandably associated with greater comorbidity, and non-private insurance, but questionably so in race, ethnicity, and facility related factors. However, given that TTS ≥ 36 days was not associated with higher risk of death, it may indicate that a reasonable delay could be pursued in certain cases for more accurate preoperative evaluation. [Table: see text]
A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.
Authors: Maria M Rubinstein, Imogen Caird, Qin Zhou, Alexia Iasonos, Claire Frances Friedman, Karen Anne Cadoo, Jason A. Konner, Roisin Eilish O'Cearbhaill, William P. Tew, Dmitriy Zamarin, Rachel N. Grisham, Chrisann Kyi, Krysten Soldan, Stuart M. Lichtman, Louise Ligresti, Sarah J. Schweber, Jasmeet Chadha Singh, Tiffany A. Troso-Sandoval, Carol Aghajanian, Vicky Makker
Journal: Journal of Clinical Oncology (2019)

5582 Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS 24wks ) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS 24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS 24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129.
Salvage therapy after failure from anti-PD-1 single agent treatment: A Study by the German ADOReg melanoma registry.
Authors: Michael Weichenthal, Selma Ugurel, Ulrike M. Leiter, Imke Satzger, Katharina C. Kähler, Julia Welzel, Claudia Pföhler, Ingrid Feldmann-Böddeker, Friedegund Elke Meier, Patrick Terheyden, Sebastian Haferkamp, Rudolf Herbst, Jens Ulrich, Jochen Utikal, Alexander Kreuter, Ralf Gutzmer, Dirk Schadendorf, Peter Mohr
Journal: Journal of Clinical Oncology (2019)

9505 Background: In melanoma, potential benefits of therapies after PD-1 inhibitor failure, including those BRAF positive patients who have already received combined BRAF-/MEK inhibitors before anti PD-1 are poorly defined. We therefore analyzed the treatment patterns and outcome of systemic therapies for patients after anti-PD-1 failure. Methods: From the ADOReg registry, patients fulfilling the following inclusion criteria were consecutively included until a number of 200 cases was reached. 1) Ipilimumab naive patients with unresectable metastatic cutaneous or mucosal melanoma. 2) Failure from treatment with a single agent anti PD-1 antibody. 3) Known BRAF status and, in case of BRAF-V600 mutation, BRAF-/MEK-inhibitor treatment prior to anti PD-1 treatment. 4) Consecutive systemic treatment started within a maximum of 6 months after anti PD-1 failure. Objectives: Rate of objective remissions (ORR), disease control (DCR), survival (OS), tolerability and disease patterns correlated to the use of different treatments after PD-1 treatment failure in real-life conditions in Germany. Results: In total 23.5 % of the patients received ipilimumab single agent, 38.5 % received the combination of ipilimumab and nivolumab (Ipi/Nivo), and the remaining various regimens. (Table) Ipi/Nivo resulted in an ORR significantly higher than for Ipi alone (p=0.02). In 18 patients receiving BRAF-/MEK inhibitor re-challenge, ORR was comparable to Ipi/Nivo. Conventional Chemotherapy was still in frequent use (dacarbazine n =33; other n=17), but response rates were low (ORR 6%). Some remission were also achieved by use of talimogene laherparepvec (n=2 out of 4). Conclusions: Treatment patterns of patients after anti-PD-1 failure differ remarkably. Although lower than reported in treatment naive patients, the combination of Ipilimumab and Nivolumab appeared favorable as compared to all other regimens, except for BRAF-/MEK inhibitor re-challenge which produced similar remission rates. Still, chemotherapies including dacarbazine are in clinical practice, though giving only poor outcome. [Table: see text]
Abstract 16928: Fragmented Care Following Transcatheter Aortic Valve Replacement is Associated With Increased 1-year Mortality and Readmission
Authors: Alice Wang, Babatunde Yerokun, Zhuokai Li, Andrzej Kosinski, Morgan L Cox, Brian C Gulack, Matthew W Sherwood, Renato D Lopes, Vinod Thourani, Ajay J Kirtane, David Holmes, G. Chad Hughes, J. Kevin Harrison, Peter K Smith, Sreekanth Vemulapalli
Journal: Circulation (2017)

Background: Postoperative fragmented care following elective surgery has been associated with poor outcome. The association between fragmented care and outcomes among patients undergoing transcathe...