bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes
Authors: Barnell Erica K. , Waalkes Adam , Mosior Matt C. , Penewit Kelsi , Cotto Kelsy C. , Danos Arpad M. , Sheta Lana M. , Campbell Katie M. , Krysiak Kilannin , Rieke Damian , Spies Nicholas C. , Skidmore Zachary L. , Pritchard Colin C. , Fehniger Todd A. , Uppaluri Ravindra , Govindan Ramaswamy , Griffith Malachi , Salipante Stephen J. , Griffith Obi L. 
Published: October 2019

PURPOSE Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology. MATERIALS AND METHODS We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 cancer samples from 5 tumor types. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants (61.5 kb of genomic space). RESULTS When compared with orthogonal sequencing, CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61 of 64 variants). Variant allele frequencies for variants identified on both sequencing platforms were highly concordant (Pearson’s r = 0.885; n = 61 variants). Moreover, for individuals with paired tumor and normal samples (n = 12), 182 clinically relevant variants missed by orthogonal sequencing were discovered by CIViC smMIP sequencing. CONCLUSION The OpenCAP design paradigm demonstrates the utility of an open-source and open-access database built on attendant community contributions with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant interpretation provides a transparent approach to build dynamic next-generation sequencing–based oncology panels.
Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
Authors: Argiris Athanassios , Li Shuli , Savvides Panayiotis , Ohr James P. , Gilbert Jill , Levine Marshall A. , Chakravarti Arnab , Haigentz Jr Missak , Saba Nabil F. , Ikpeazu Chukwuemeka V. , Schneider Charles J. , Pinto Harlan A. , Forastiere Arlene A. , Burtness Barbara 
Published: October 2019

PURPOSE We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy ( P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy ( P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.
Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer
Authors: Sjöström Martin , Chang S. Laura , Fishbane Nick , Davicioni Elai , Zhao Shuang G. , Hartman Linda , Holmberg Erik , Feng Felix Y. , Speers Corey W. , Pierce Lori J. , Malmström Per , Fernö Mårten , Karlsson Per 
Published: October 2019

PURPOSE Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy. METHODS We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT. RESULTS ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit ( Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT. CONCLUSION ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
Implementation and efficacy of a large-scale radiation oncology case-based peer-review quality program across a multinational cancer network.
Authors: Ludmir Ethan B. , Hoffman Karen E. , Jhingran Anuja , Ip Mee-Chung Puscilla , Frey Seth D. , Ning Matthew S. , Minsky Bruce D. , McAleer Mary Frances , Chronowski Gregory , Arzu Isidora , Reed Valerie Klairisa , Garg Amit K. , Roberts Terence , Ashish Patel , Olson Michael R. , Selek Ugur , Gabel Molly , Koong Albert , Herman Joseph M. , Kuban Deborah A. 
Published: October 2019

1 Background: With rapid community expansion of academic cancer centers, ensuring high-quality delivery of care across all affiliated network sites is critical. Here we report the results of a radiation oncology peer-review system implemented across a large multinational cancer network. Methods: Weekly radiation oncology peer-review conferences were held between network centers and the main campus of a major cancer system; results of standardized peer-review for each case were recorded. Peer-review resulted in each case being scored as concordant or nonconcordant on initial review; nonconcordance was based on institutional guidelines, national standards, and/or expert opinion. Results: Between 2014 and 2018, 28,730 patient radiation treatment plans underwent peer-review at 10 network centers. The peer-review case volume increased over this study period, from 1,420 cases in 2014 to 9,112 in 2018, concomitant with network expansion. Examining cases reviewed in 2018 (N = 9,112), the most-commonly reviewed cases by disease site were breast (28.9%), head and neck (HN; 13.9%), and lung (12.6%). Of all cases in 2018, 452 (5.0%) were deemed nonconcordant. Higher nonconcordance rates were noted for HN cases (14.0%), and lower rates for lung cases (2.3%; p < 0.001). Of nonconcordant HN cases, the majority (69.5%) were deemed nonconcordant based on target volume delineation. Of nonconcordant breast cases, most (67.1%) were nonconcordant based on radiation field design. For centers added to the network during the study period, we observed a significant decrease in the nonconcordance rate over time after joining the network (average annual decrease of 5.4% in nonconcordant cases; p < 0.001). Conclusions: These data demonstrate the feasibility and efficacy of a large-scale multinational cancer network radiation oncology weekly peer-review program. Nonconcordance rates were highest for HN cases, primarily due to target volume delineation. With improved nonconcordance rates for newly-added network centers, these results offer the promise of improving the quality of radiotherapy delivery across an extensive cancer network with a major academic center as the nucleus.
Reducing ED visits by “closing the loop” for symptomatic patients.
Authors: Arrowsmith Edward , Suits Lenes , Anz Bertrand Marquess , Geren Gina , Vasta Leslie , Lyss Aaron J. 
Published: October 2019

100 Background: Improving the value provided to patients and payers in our system of cancer care relies on reduction of avoidable hospital and emergency department (ED) utilization. Furthermore, recent payer pressures on community oncology practices (COPs) have resulted in an increased focus on improving care coordination (CC) under strict resource constraints. As part of the ASCO Quality Training Program, we tested several low-cost CC interventions, leveraging workflow redesign, already employed care team members, and technology already implemented, to reduce ED visits (EDV) in a single large COP clinic where more than 3,200 cancer patients were treated during 2016. Methods: Baseline EDV rates were obtained through nurse chart review during Jan.-Jun. 2016. The following CC interventions were implemented: Initiated after hours call process with access to EMR and patient access to bidirectional real-time messaging with care team members; Implemented new in-office process to “close the loop” on patient evaluations by creating follow up guidelines for symptomatic telephone triage and in-clinic patient evaluations; Implemented a standard 48 hour follow up process for all EDV and hospital admissions; Increased patient awareness of telephone triage services during and after clinic hours by: augmenting new patient education by staff, developing a magnetic reminder to call the office for non-emergent and emergency situations, and instructions for use of afterhours call system. Nurse chart reviews were conducted throughout implementation to observe effects of new CC processes on EDV. Results: We observed a 30% reduction in EDV from baseline measurement. No new FTEs added and no new technology licenses acquired for this initiative. Conclusions: Low-cost CC interventions can be implemented in COPs to avoid ED utilization. Limitations of this analysis included manual chart abstraction that could not account for EDV outside the partnering health system, illustrating data access for hospital utilization remains a major challenge for quality improvement efforts for COPs. Additional challenges have been experienced in expanding these process improvements from a single large clinic to the broader Tennessee Oncology network of more than 30 clinics.
Implementation of the quality training program in Spain.
Authors: Lopez Rafael , Anton Antonio , Aranda Enrique , Carrato Alfredo , Constenla Manuel , Cruz Juan Jesús , Diaz-Rubio Eduardo , Feyjoo Margarita , Garcia-Foncillas Jesus , Gascon Pedro , Guillem Vicente , Lugo Ilse , Camps Carlos 
Published: October 2019

11 Background: The ECO Foundation is a collaboration of experts representing the major Spanish hospitals in the pursuit of excellence in cancer treatment. Since 2015, ECO has been collaborating with ASCO (American Society of Clinical Oncology) in quality initiatives in cancer care, like the QOPI (Quality Oncology Practice Initiative) program and the QOPI Certification Program (QCP). The Quality Training Program (QTP) is a 6-month course with 3 in-person learning sessions that prepares oncology teams to design, implement and lead successful quality improvement activities in their practices. In 2018, ECO reached a new agreement with ASCO to implement this program in Spain. Methods: The QTP was developed in Spain by ECO in collaboration with ASCO, following the same methodology and contents of ASCO’s program. The first session was carried out in October 2018, with 12 Spanish teams participating with diverse quality improvement projects. The program counted with ASCO and ECO faculty, constituted by experts in the quality and oncology field. Results: Each QTP Spanish team counted with 2-3 representatives from their hospitals and developed an improvement project, following the methodology of the course, including a problem statement, process map, cause and effect diagram, diagnostic data, aim statement, measures, baseline data, priority/pay-off matrix of possible changes/interventions, change data, next steps/plan for sustainability, among others. The projects were mainly focused on the waiting time reduction in the Emergency Area and from the patient’s visit to the oncologist until treatment administration, burnout reduction on oncology professionals, improvement of the identification and management of complications for cancer patients receiving immunotherapy, improvement of the uniformity in the medical records registry, among others. QTP participants presented their projects’ results on the third and last session of the program in April 2019 with positive outcomes. Conclusions: The QTP’s quality improvement approach allows Spanish teams and the ECO Foundation to enhance the goal of a quality-oriented health care system. ECO will continue pursuing excellence and quality with further initiatives like the QOPI program, the QCP and the QTP.
Impact of brain metastases on end-of-life health care utilization.
Authors: Ray Emily Miller , Dunham Lisette , Reeder-Hayes Katherine Elizabeth , Sanoff Hanna Kelly 
Published: October 2019

116 Background: Patients with brain metastases (BMets) represent a subset of cancer patients who may experience high costs and frequent healthcare utilization. This study aims to assess whether patients with BMets have higher likelihood of healthcare utilization at the end of life (EOL) compared to other patients with metastatic cancer. Methods: Using the Cancer Information and Population Health Resource, linking North Carolina Medicare, Medicaid, and private payer claims with state cancer registry data, we conducted an observational cohort study of decedents with metastatic melanoma, renal cell carcinoma, breast cancer, or lung cancer (diagnosed 2003-2014) with or without BMets. Multivariate logistic regression, adjusting for demographics, cancer type, systemic treatment, comorbidity, frailty, and hospice use, was used to examine the impact of BMets on use of the emergency department (ED), hospital, and intensive care unit (ICU) in the 30 days prior to death. Results: Patients with BMets are hospitalized at EOL more often than patients without BMets (44% vs 38%, p < 0.001), but experience no difference in ED or ICU use. BMets patients receiving systemic treatment were particularly high risk for hospital and ICU use (odds ratios in Table). Black race and Charlson comorbidity score 3+ increased risk of hospitalization and ICU use. Utilization did not vary by cancer type. Hospice care significantly reduced all utilization. Conclusions: Patients with BMets are high risk for hospitalization at the end of life. Further study is needed to determine if targeted health system interventions can decrease hospitalizations in this patient group. [Table: see text]
Expanding access to genetic evaluations in a large community oncology practice through a collaborative service delivery model.
Authors: Patel Gayle , Nichols Trisha , Bunnell Ann , Principe Kate , Sandbach John F. , Toth Sara , White Monica , Long Christine L. , Jones Megan , Sperl Ryan , Wilfong Lalan S. 
Published: October 2019

123 Background: Identifying individuals with inherited cancer susceptibility is critical to cancer treatment and prevention in patients and families. While the identification and management of inherited susceptibility to cancer is the standard of care, genetic testing rates are low; 1.2 million women with breast and/or ovarian cancer who qualify have yet to undergo genetic testing (Childers et al 2017). The Genetic Risk Evaluation and Testing Program (GREAT) formed to improve access to genetic evaluations and testing in Texas Oncology, a large, state-wide community oncology practice. Methods: The GREAT program is a collaborative service delivery model, utilizing 4 certified genetic counselors (CGC) to lead advanced practice providers and physicians in offering pre and post-test evaluations to oncology patients in their own community. Training involves 8-12 weeks of didactic lectures, precepting, and ongoing education and support. GREAT-trained providers then offer comprehensive genetic evaluations and testing to established oncology patients as well as at-risk individuals from the surrounding community. Results: The GREAT program has trained 72 providers at 52 cancer centers. Rates of genetic evaluations increased each year from 2012 to 2018. Overall findings: 19,129 unique patients received an evaluation; 17,305 genetic tests were completed; 2,597 pathogenic/likely pathogenic variants (P/VLP) have been identified. Conclusions: Despite guidelines recommending genetic evaluations for hereditary cancer syndromes, most patients are not receiving this service. A hybrid service delivery model utilizing regional CGCs to train providers in community oncology offices can significantly increase access to genetic services. The model described is an effective and expansive mechanism for the delivery of high-quality cancer genetics care. The GREAT program plans to hire additional CGCs to train more providers across Texas Oncology with the goal of expanding access. [Table: see text]
Utilizing volunteer, nonclinical navigators (NCN) as extenders of the breast nurse navigator (BNN) to provide patient education and support.
Authors: Koutlas Judy B , Mascarenhas Debra C 
Published: October 2019

128 Background: The role of the BNN during the treatment phase of the care continuum involves educating patients and families and assisting them with overcoming barriers to care by linking them to appropriate resources. Our BNN provides education to approximately 15 new patients per month. Additional navigation services are provided to 114 patients per month with an annual caseload of 580. The caseload volume limits the number of patients she can see in one day. With our existing volunteer NCN program, we decided to conduct a 3-month pilot project utilizing NCN in our breast clinic to provide navigation services while the BNN was on medical leave. Methods: Three NCN were trained by BNN to provide breast navigation services. Each NCN received a minimum of 10 hours of training, which included education regarding breast cancer, common barriers to care, and resources. The BNN created a navigation tool indicating the education to be provided at diagnosis, pre-and post-surgery, and systemic therapy. NCN provided education by utilizing videos and written materials. Patient medical questions were deferred to nursing staff and physicians. BNN provided training and resource guide to aide NCN to identify and link patients with appropriate resources and support staff. Results: NCN provided services to 78 patients including approximately 10 new patients per month. A total of 24 surveys were completed by healthcare team and patients. Results revealed 94% of patients agreed/strongly agreed NCN helped them feel better and reduced fears, 100% reported helpfulness in linking to resources and support programs, and 50% viewed a video and reported better understanding. Healthcare team overwhelmingly reported the emotional support provided was beneficial and that NCN were helpful in providing resources and recommended continuing. Conclusions: NCN are effective in providing additional navigation services. Our breast navigation program had a 29% increase in new patient encounters and 27% increase in returning patient encounters compared to the previous year prior to the addition of NCN. We plan to expand this model into other multidisciplinary clinics.
Small cell lung cancer: Sociodemographic factors in patients’ decisions for treatment.
Authors: Ho Thanh P. , Duma Narjust , Durani Urshila , Funni Shealeigh , Inselman Jonathan , Molina Julian R. , Mansfield Aaron Scott 
Published: October 2019

144 Background: Small cell lung cancer (SCLC) is highly responsive to cytotoxic therapy and can be cured in early stages of disease. In this setting, disparities in patient refusal despite provider recommendations are unknown. Methods: All incident limited stage (LS)-SCLC cases from the National Cancer Database were identified from 2004 to 2014. Logistic regression was used to determine factors associated with treatment refusal. Results: 65,664 patients (pts) were identified with LS-SCLC: 44% male, median age 68 years. 3.4% of pts refused radiation and 3.8% refused chemotherapy. The proportion of chemotherapy refusal increased over the study period: 3% in 2004-2006 compared to 5.4% in 2013-2014 [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.55-2.01]; this was not observed for radiation. In multivariate analysis, women were more likely to refuse radiation (OR 1.18, 95% CI 1.06-1.32) and chemotherapy (OR 1.30, 95% CI 1.19-1.43) than men. Women who accepted treatment had higher overall survival compared to those who refused radiation (19.8 vs 5.2 months) or chemotherapy (17.4 vs 3.9 months) (both p < 0.001). Hispanic, Black, and Asian pts were not more likely to refuse treatment than White pts. Older pts were more likely to refuse radiation (OR 1.09 per year, 95% CI 1.08-1.09) and chemotherapy (OR 1.10 per year, 95% CI 1.09-1.11). Charlson comorbidity index (CCI) of 2 was associated with more frequent treatment refusal compared to CCI of 0 (radiation OR 1.96, 95% CI 1.68-2.30; chemotherapy OR 1.54, 95% CI 1.34-1.76). Medicaid as primary insurance predicted a higher risk of refusal compared to private insurance for radiation (OR 2.36, 95% CI 1.81-3.07) and chemotherapy (OR 2.23, 95% CI 1.78-2.80). Treatment at an academic facility predicted a lower risk of radiation refusal (OR 0.71, 95% CI 0.59-0.84) but not chemotherapy refusal. Conclusions: Female sex, comorbidities, and Medicaid insurance were predictors of treatment refusal in LS-SCLC, suggesting that socioeconomic and sex disparities may affect treatment decisions in this life-threatening disease. Further research to identify reasons for refusal via patient and provider interviews can improve care of vulnerable populations with potentially curable cancer.