bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of clonal hematopoiesis to tumor-targeted liquid biopsy in a Chinese pan-cancer cohort.
Authors: Xu Enwu , Zhou Yang , Yi Zhao , Gong Longlong 
Published: June 2021

e18700 Background: Somatic mutations through detecting circulating cell-free DNA (cfDNA) in plasma samples have been used to diagnose tumor, administer drugs and monitor tumor recurrence. However, cfDNA is not only derived from tumor, but also from clonal hematopoiesis. Thus, the mutations from clonal hematopoiesis impact accuracy of somatic mutation detection using plasma cfDNA in tumor patients. Methods: We screened clonal hematopoiesis using a bioinformatics pipeline in 11,725 Chinese pan-cancer cohort. To evaluate the impact of clonal hematopoiesis for somatic mutations, Fisher’s exact test was used. Results: In this study, we identified clonal hematopoiesis mutations using a bioinformatics pipeline in a Chinese cohort included 11,725 pan-cancer patients. In order to enhance the detection accuracy of clonal hematopoiesis mutations, we performed a statistical framework to compare the distribution of alteration-supporting reads in cfDNA and matched peripheral blood lymphocyte (PBL) samples. The result indicated that 5,933 clonal hematopoiesis mutations in 301 genes for 5,100 patients. In particularly, 48 of 5,933 clonal hematopoiesis mutations carried by 92 of 5,100 tumor patients were actionable somatic mutations. Seven oncogenes (including EGFR, ERBB2, FGFR3, IDH1, KIT, KRAS and NRAS) and 10 tumor suppressor genes (including BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, PTEN, RB1, SMAD4 and TP53) were contained in the 48 clonal hematopoiesis mutations. The frequency of TP53 gene was 32.6% (30 of 92 tumor patients) and KRAS which was considered as targeted therapy was 16.3% (15 of 92 tumor patients). Conclusions: Taken together, we exhibited characteristic of clonal hematopoiesis mutations in a Chinese pan-cancer cohort and explored effect of clonal hematopoiesis mutations on liquid biopsy for tumor patients.
Patterns and costs of hospital-based cancer care in the last year of life: A national data linkage study in Scotland.
Authors: Diernberger Katharina , Bowden Joanna , Fallon Marie T. , Luta Xhyljeta , Droney Joanne , Lemmon Elizabeth , Gray Ewan , Ennis Holly , Marti Joachim , Hall Peter S 
Published: June 2021

e18732 Background: Approximately thirty thousand people in Scotland are diagnosed with cancer each year, of whom 10,000 live less than one year. Hospital is the most common place of death for people with cancer, despite most expressing a preference for community-based care. There is inadequate understanding of the nature and value of hospital-based care for people with advanced cancer. This study aimed to describe patterns of hospital-based healthcare use and associated costs for cancer decedents in their last year of life. Methods: A population-wide administrative data linkage study of hospital-based healthcare use for cancer decedents aged 60+ at death who died between 2012 and 2017 was conducted in Scotland. Linkage was established between the Scottish Morbidity Record, Scottish Cancer Registry and the National Records of Scotland. Hospital admissions, length of stay (LoS), number and nature of outpatient and day case appointments were extracted. Associated costs were estimated using generalised linear models, adjusted for age, gender, primary cause of death, socioeconomic deprivation status, rural-urban (RU) status and comorbidity. Results: The study population included 85,732 decedents with a cancer diagnosis, for whom 64,553 (75.3%) cancer was the underlying cause of death. Mean age at death was 84 years. The mean number of inpatient stays in the last year of life was 5.88 (SD 5.68), with a mean LoS of 7 days. Mean total 1-year inpatient, outpatient and day-case costs per patient were £10,261, £1,275 and £977 respectively. People who died of haematological cancers had the most hospital admissions (mean 11.8). Admission rates rose sharply in the last month of life and were most common in those who died of haematological and lung cancers. One year adjusted and unadjusted costs decreased with increasing age. Unadjusted costs for the youngest group (60-64) were £15,895, double the cost for those aged 90+. People dying of haematological cancers had the highest hospital-based costs (mean £24,772) followed by those with ovarian cancer (mean £17,556). The largest single contributor to hospital-based costs in the last year of life was unscheduled admissions. Conclusions: People in Scotland in their last year of life with cancer use substantial hospital-based care. Unscheduled admission rates are high, particularly in the last month of life when the value of acute intervention may be uncertain. Further research is needed to examine triggers for hospitalisation and to assess the value of hospital-based care to people living with advanced cancer.
Do differences in baseline clinical severity of ovarian cancer patients with thrombosis predict treatment with rivaroxaban versus low molecular-weight heparin?
Authors: Kohn Christine G. , Caranfa Jonathan T. , Brewer Molly , Singh Meghana , Coleman Craig I. , Costa Olivia S. 
Published: June 2021

e18748 Background: Prescribers use direct oral anticoagulants and low molecular-weight heparin (LMWH) for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT). We sought to identify predictors impacting the use rivaroxaban versus LMWH for CAT in patients with ovarian cancer. Methods: Using US Surveillance, Epidemiology and End Result-Medicare linked data from 2013-2016, we evaluated adults with ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Univariate analysis was performed to examine the association between covariates and clinicians’ choice to use rivaroxaban or LMWH. Variables with a p-value < 0.20 upon univariate analysis were deemed significant and subsequently included into a stepwise, backwards multivariable logistic regression model to obtain adjusted odd ratios (ORs) of treatment assignment. Results: Of the 125 ovarian cancer patients included in our analysis, 26% received rivaroxaban and 74% LMWH. All patients had stage 3 or 4 ovarian cancer, 36% were ≥75 years-of-age, 78% were white, and 18% were below the poverty line (p ≥ 0.25). Upon univariate analysis, rural community, time between cancer diagnosis and VTE ≥ 1 year, index VTE without evidence of pulmonary embolism, and CKD ≥ stage 3 were found to be significant predictors of rivaroxaban use when compared to LMWH (p ≤ 0.14 for all). Upon multivariable regression, CKD ≥ stage 3 (OR = 3.13) was shown to be independently associated with rivaroxaban versus LMWH use (p≤0.01). Conclusions: In routine practice, patients were more likely to receive rivaroxaban if they had CKD and lived in a rural area. These differences in prescribing practices may be due to less availability of LMWH in rural areas and less tolerance of injections in CKD patients. Univariate analysis also suggest that low VTE burden (i.e., DVT only) and VTE event ≥ 1 year after cancer diagnosis were also associated with rivaroxaban use over LMWH, which may be due to LMWH therapy as the long-established standard of care for patients with cancer. Large observational studies are needed to confirm these results. [Table: see text]
Effect of influenza vaccination on immune-related adverse events in patients receiving single-agent immune checkpoint inhibitors for the treatment of cancer.
Authors: Vutukuri Naga Malleswari , Corcoran Calette , Comeau Jill , Stephenson Elizabeth , Beedupalli Kavitha , Shi Runhua 
Published: June 2021

e18763 Background: Recent single-center, retrospective reviews have evaluated the effect of influenza vaccinations on the incidence and severity of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI). Methods and outcomes in these studies vary. The most common medication investigated was ipilimumab, an Anti-CTLA-4 monoclonal antibody. There is limited data evaluating the incidence of irAEs in those receiving the specific ICIs, program death-1 (PD-1) and program death ligand-1 (PD-L1) inhibitors. Methods: A retrospective chart review was conducted including patients 18 to 89 years old who received single-agent pembrolizumab, nivolumab, atezolizumab, or durvalumab at an academic medical center from August 2015 to August 2019. The primary objective was to evaluate the incidence of irAEs in those who received an influenza vaccine compared to those who did not. Electronic health records, and the Louisiana Immunization Network for Kids (LINKS), which now collects adult information, were utilized for data collection. Chi-square tests were used to evaluate all endpoints. Results: Of the 217 charts screened, 133 were included in this study Fifty-three patients were included in the influenza vaccination group and 80 patients in the group that did not receive influenza vaccinations. The median age in those who received an influenza vaccine and in those who did not were 61 years and 62 years, respectively. The most common cancer diagnoses were lung cancer and melanoma. Ninety-one percent of patients in the vaccination group versus 81% in the group who did not receive an influenza vaccine received either nivolumab or pembrolizumab (PD-1 inhibitors). There was no statistical difference in irAEs in those who received an influenza vaccine versus those who did not (30% versus 45%, p = 0.15). The only significant secondary outcome found was the rate of irAEs in patients receiving a PD-1 inhibitor versus a PD-L1 inhibitor regardless of vaccination (42.2% versus 11.1%, p = 0.03). The majority of irAEs were grade 1 or 2. Conclusions: Based on this study, receiving an influenza vaccine does not have an influence on the risk of irAEs in those receiving ICI, specifically PD-1 and PD-L1 inhibitors. These outcomes may have been affected by adherence issues with yearly influenza vaccinations, inaccurate vaccine records, and receiving vaccines out of state. The statistically significant secondary outcome may have been affected by the disproportionate number of patients who were receiving a PD-1 inhibitor in this study. Larger population studies are needed to validate these findings and identify both the risk and benefit of patients receiving their yearly influenza vaccine while receiving ICI.
The impact of COVID-19 pandemic on access to new patient cancer care as evaluated in the Integra Connect Database (ICD).
Authors: Gart Mike , Varughese Prateesh , Gordan Lucio N. , Heritage Trevor , Brown Greg , Botts Elizabeth , Keni Dakshesh , Blanc Simon , Scott Jeffrey A. , Smith Robert E. 
Published: June 2021

e18792 Background: The Covid-19 pandemic has affected all aspects of life. Integra Connect sought to assess its impact on new visits for cancer care by querying its Electronic Medical Record and Claims database as a surrogate for understanding Covid’s impact on cancer care in the larger United States population. Methods: Using Real World Data (RWD) from over 1200 oncology providers in 14 large practice settings, comprising 250 plus care sites in the ICD, we measured new patient (Pt) and established Pt visits from 2018 through 2020. Centers for Medicare & Medicaid Services (CMS) codes for new and established Pt’s were applied to define cohorts. Disease states were defined using CMS Oncology Care Model (OCM) mapping to diagnosis codes. Because the ICD is heavily based in the Eastern US, we conducted a geographic analysis by segmenting providers by Northeast (NE) with 506 providers from NY, NJ, PA, and VA and Southeast (SE) with 578 providers from FL, GA, SC, and AL. We looked at visits across all tumor types and identified breast cancer (BC) and colorectal cancer (CC) as likely to be most affected by decreased screening, and multiple myeloma (MM) and advanced prostate cancer (APC) as likely to be vulnerable to delay in initiation of first treatment since treatment often trails diagnosis. Results: We found a decline in new patient volume (NPV) in ‘20 of -1% compared to ‘19; this compared to an anticipated increase of +7% based on growth in NPV in the ICD from ‘18 to ‘19. In the NE we saw NPV decrease in ‘20 by -7% vs. ‘19 but increase by +6% in the SE compared to ‘19. In comparing NPV ‘20 to ’19 and ’19 to ‘18, we saw a smaller increase for BC of +4% vs. +6% and for CC of +5% vs. +7%, respectively. Whereas in MM it was -7% vs. +3% and APC -6% vs. +8%. (See Table). Conclusions: Covid-19 has negatively impacted cancer care access. This RWD shows the number of both newly diagnosed Pts and those with initial oncologic intervention in established Pts, where symptoms traditionally have determined initiation of treatment, has declined year-over-year. The American Cancer Society projected new Pt cases to increase +2% in ‘20 to 1.806 million ( ACS, Cancer Facts and Figures 2020), whereas in the ICD, that figure was projected +7% but resulted in -1%. This suggests a major expected reduction of new Pt cases in the US at large. The drop in cases during Covid-19 in our data was greater in the NE compared to the SE. In addition, the drop in the NE in our data was earlier and more prolonged than SE. While recovery occurred in both regions, after an initial overshoot following lockdowns, volumes plateaued at levels lower than pre-pandemic.[Table: see text]
Real-world trends in costs of next generation sequencing (NGS) testing in U.S. setting.
Authors: Desai Kaushal , Hooker Gillian , Gilbert Katri , Cropper Caiqian , Metcalf Rob , Kachroo Sumesh 
Published: June 2021

e18824 Background: Recent advances in NGS testing have revolutionized the scope for personalized medicine. The goal of this study was to describe historic trends in the average allowed cost for NGS testing. Methods: This was a retrospective database study evaluating biomarker testing claims in patients undergoing tumor and/or germline sequencing tests between 2016-2019. Molecular testing claims data and marketplace data of tests currently sold in the U.S. were analyzed in the proprietary Concert Genetics Medical Claims Data Warehouse. Results: Analysis of data highlighted high variability in utilization rates as well as allowed amounts for NGS testing. The average allowed amounts for NGS Tests varied from $1269 to $2058 per test during the study period. Higher variability in billing codes and price was also observed when analysis was done for subgroups, which included region, age, gender and cancer type. Similar trends were also observed for panels containing NGS-derived tests such as Tumor Mutation Burden (TMB), an upcoming biomarker. Average allowed amounts for NGS tests that included TMB testing varied from $438 to $3700 per test. To gain a better perspective on evolution of coding, utilization and pricing trends, additional analyses were done in hereditary cancer, given longer availability of these tests in the US Market. For Hereditary cancers, the average allowed amounts varied from $1722 to $2249 per test during the study period. Greater consistency in price was observed in hereditary cancer. Utilization is also more consistent over time and price showed a gradual decreasing trend over time. Coding was also less variable per claim for hereditary cancer and showed a converging trend. Conclusions: Understanding and quantifying the trends in cost of NGS testing for novel biomarkers is critical to predict evolution of testing costs and provide insights essential for minimizing barriers to availability and affordability of these tests. NGS testing can play an important role in improving quality of care and making the clinical decision-making process more efficient. Currently, coverage and reimbursement of NGS tests is one of the key policy challenges that needs to be addressed. Hence, development and adoption of policies is needed to ensure efficient integration of NGS testing in the US health care system.
Comprehensive genomic profiling in advanced/metastatic colorectal cancer: Number needed to test and budget impact of expanded first-line use.
Authors: Proudman David , DeVito Nicholas C. , Belinson Suzanne , Alsaraf Allo Mina , Morris Eric D. , Signorovitch James , Patel Anuj K. 
Published: June 2021

e18834 Background: A growing number of genomic alterations inform treatment of advanced/metastatic colorectal cancer (mCRC). However, use of comprehensive genomic profiling (CGP) is limited in the first-line (1L) setting. Based on the Tempus xT next-generation sequencing assay, we estimated the impact of expanded 1L CGP on the detection of currently actionable alterations in mCRC and associated diagnostic testing costs in a modeled US health plan setting. Methods: A decision analytic model was used to compare testing scenarios over a two-year time horizon: current 1L testing with a mix of CGP and non-CGP diagnostics vs. replacing 20% of usual testing with Tempus CGP. The incidence of 1L mCRC, current testing rates, prevalence of actionable alterations, and test sensitivity were drawn from a literature review and clinical expert input. Currently actionable alterations included KRAS, NRAS, RAF, BRAF, dMMR/MSI, NTRK, RET, EGFR, HER2, MET, PIK3CA and POLE1. Cost components included initial and repeat testing, physician-associated and administrative costs. Opportunities for genomically-informed therapy or clinical trials were assessed under each testing scenario. A forward looking scenario, with additional informative alterations, was also explored. Results: In a hypothetical five million-member health plan, with 50% Medicare and 50% commercial insurance, 1,112 incident cases of mCRC (22 per 100,000 patients) are expected in a typical year. Among these cases, 566 (51%) are expected to undergo 1L molecular diagnostic testing, with 55 projected to undergo repeat testing upon progression within the next year. Based on current real-world testing rates, there are an expected 521 missed opportunities for genomically informed treatment (47% of the incident mCRC population), with 442 missed due to lack of testing and 79 due to testing without CGP. Replacing 20% of usual testing with Tempus CGP in the modeled scenario was associated with up to a $0.003 per member per month (PMPM) testing cost increase and an additional 15.5 patients with an opportunity for genomically-informed care (12.7 patients for guideline-recommended treatment and 2.8 for a clinical trial). The number needed to test (NNT) with Tempus CGP versus the usual mix of testing was 7.8 1L patients to identify one actionable alteration. Scenario analyses projecting the advent of additional genomically-informed treatments and clinical trials resulted in smaller numbers needed to test. Conclusions: Replacing 20% of usual testing with Tempus CGP is associated with a small incremental testing cost but can identify actionable alterations for a meaningful number of patients. For every eight 1L mCRC patients tested with Tempus CGP rather than the usual mix of molecular testing, one additional patient is expected to be identified as having currently actionable alterations.
Cost-effectiveness analysis of p53 immunohistochemical testing in stage I and II high-risk endometrial cancer.
Authors: Orellana Taylor , Berger Jessica L. , Boisen Michelle M. , Buckanovich Ronald J. , Coffman Lan Gardner , Courtney-Brooks Madeleine , Edwards Robert P. , Mahdi Haider , Olawaiye Alexander , Sukumvanich Paniti , Vargo John , Bhargava Rohit , Beriwal Sushil , Taylor Sarah E. , Smith Kenneth , Lesnock Jamie Lee 
Published: June 2021

e18838 Background: PORTEC-3, a phase III clinical trial comparing adjuvant radiation alone (RT) to combined chemoradiation therapy (CTRT) in patients with high-risk endometrial cancer (EC), demonstrated no benefit with CTRT compared to RT for patients with stage I and II EC. However, a subsequent tumor molecular analysis revealed that individuals with stage I and II high-risk EC with p53 mutations had statistically significantly improved progression-free survival (PFS) and clinically significantly improved overall survival (OS) with combined CTRT. As p53 immunohistochemical (IHC) testing and CTRT adds to cost and toxicity, we sought to evaluate the cost-effectiveness of p53 IHC tumor testing in patients with stage I and II high-risk EC. Methods: A Markov decision model was developed to compare two testing strategies in patients with stage I and II high-risk EC: p53 IHC testing vs. no IHC testing. IHC staining for p53 is an accurate and validated surrogate for TP53 mutational status. As a result, p53 IHC testing alone was used in the decision analysis. Data from PORTEC-3 and the subsequent molecular analysis were used for the base case model parameters, including treatment regimen, PFS, OS, and incidence of p53-mutated tumors. Cost and utility data were derived from the Federal Supply Schedule, the Centers for Medicare and Medicaid Services (CMS) Fee Schedules, the Tufts CEA registry, peer-reviewed literature, and expert input. Data analysis was performed using TreeAge Pro Software, 2021. Effectiveness outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed in order to identify the influence of individual variables on the overall model. Results: When compared to no testing, p53 IHC testing resulted in a cost savings of $471 per patient while providing an additional 0.310 QALYs. Therefore, p53 IHC testing was less expensive and more effective than no IHC testing and was a dominant strategy in this model. In one-way sensitivity analyses, CTRT and RT costs, discount rate, and percentage of p53 mutations detected had the most impact on the model; however, p53 IHC testing remained a cost-saving strategy over all parameter ranges examined. Conclusions: For patients with high-risk stage I and II EC, this analysis suggests that p53 IHC testing is cost-effective compared to no testing in determining the costs and benefits of adjuvant chemotherapy. Although additional studies are warranted, this data provides further support for the role of molecular-based treatment decisions for high-risk stage I and II endometrial cancer.