bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic impact of digital tumor board software: An evaluation of cost savings using real-world data.
Authors: Hammer Richard D. , Srinivas Sharan , Rajendran Suchithra , Guo Chaohui , Prime Matthew Stewart 
Published: June 2022

e18794 Background: Multidisciplinary tumor boards (MTB) provide an interdisciplinary approach for decision-making in cancer care and are an integral part of cancer treatment plans. MTBs are widely considered the “gold standard” in cancer care delivery and are required for accreditation by the American College of Surgeons on Cancer Program. Preparing for MTBs is time-consuming and labor-intensive. We have previously published the largest real-world study of a digital solution (NAVIFY), showing significant decreases in the case preparation time compared to traditional methods.1 We now extend that study to evaluate the economic impact on costs of MTBs in an academic setting. Methods: The NAVIFY Tumor Board solution was introduced at the University of Missouri Health Care (MU) in 2018. Data was collected in three tumor boards (Breast, ENT, and GI) for pre- and post- NAVIFY implementation as previously published1 . For the current study, raw data was collected and preprocessed to obtain eight pertinent variables. A retrospective pre-post analysis was used to evaluate the economic effectiveness of NAVIFY. Using the salary data collected from publicly available sources, the average personnel cost/case (nurse navigator, radiology, pathology and genetic counseling) was analyzed for each tumor board for pre and post stable integration of NAVIFY. In addition, a system-wide cost projection study and payback analysis were also performed based on 12 tumor boards. Results: The average personnel cost/case after integration of NAVIFY showed a savings of 40% in breast MTB, 52% for ENT MTB, and 6% for GI MTB. Both Breast and ENT were considered to be the optimal use of the software after implementation. Using these two tumor boards, the average total personnel cost/case pre-NAVIFY was $93.20 and $49.55 post integration. Annual system-wide cost projections showed an annual savings of $299,614. Discounted payback period analysis showed a payback period of 0.17 years. Conclusions: Implementation of NAVIFY digital tumor board solution showed a significant impact on the total cost of tumor board preparation with overall a decrease in personnel cost/case of 53% with ideal implementation. The comparatively slight decrease in GI could be explained by an increase in cases reviewed from an average of 8 to 11 pre vs post NAVIFY requiring increased radiologist time, and poor user adoption by surgeons. In conclusion, implementation of a digital tumor board software provides significant savings in case preparation costs, second to decreased time costs of personnel. While not evaluated in this study, these cost savings do not take into account the increased potential clinical revenue that may also accompany the improved efficiency on provider time. References 1. Hammer RD, etal. Digital Tumor Board Solutions Have Significant Impact on Case Preparation. JCO Clin Cancer Inform. 2020 Aug;4:757-768.
The incidence of atrial fibrillation shortly following radiation therapy in patients with lung cancer: A population-based study.
Authors: Nikita Nikita , Lu Bo , Gandhi Krupa , Keith Scott W. , Lu-Yao Grace L. 
Published: June 2022

e18796 Background: Lung cancer is the third most common cause cancer in the US. Although radiation therapy (RT) is one of the most common treatment modalities for lung cancer. RT-induced atrial fibrillation (AFib) is understudied. We examined the relationship between different types of RT and AFib incidence. Methods: Lung cancer patients receiving RT were identified from the SEER-Medicare linked data between 2010 and 2015. Patients with 12 months continuous Part A and B coverage prior to RT were included. Patients were excluded if they lost coverage, were enrolled in HMOs, aged < 65 years old, or diagnosed at death, had malignant effusion or pre-existing AFib. RT was identified as IMRT (HCPCS: 77301, 77418, G0174, G0178, 0073T), or non-IMRT related external beam radiation (HCPCS: 77290, 76370, 77014, 77295, 77280, 77285, CPT: 77402–77416, 77427). AFib was identified within 30 days of initiating RT using ICD-10 codes. Continuous variables were summarized by mean and standard deviation; categorical variables by frequency and percentage. Student’s t-test was used to compare continuous data between groups. Pearson’s chi-square test was used to compare categorical data between groups. Results: We identified 3,499 lung cancer patients receiving radiation. Of these, 830 were diagnosed with AFib after RT. The type of RT (IMRT vs non-IMRT) and type of hilar involvement were both associated with the incidence of AFib in these patients (Table). Conclusions: This is the first population based study to identify factors associated with increased AFib incidence in lung cancer patients receiving radiation. Further studies are warranted to better understand these associations.[Table: see text]
Health outcomes modelling of RNA-based versus DNA-based detection of driver gene rearrangements in non-small cell lung cancer.
Authors: Jun Tomi , Oh William K. , Schadt Eric , Higashi Mitchell 
Published: June 2022

e18837 Background: There are several FDA-approved targeted therapies for NSCLC with driver gene rearrangements (DGRs) involving ALK, ROS1, RET, NTRK1-3, and MET exon 14. DNA-based sequencing panels miss 15-20% of DGRs compared to RNA-based methods (Benayed et al., 2019; Solomon et al., 2020). We modelled the years of life gained by using RNA- instead of DNA-based methods for DGR detection. Methods: We used the IVI-NSCLC open-source model to analyze the relationship between stable disease, progression, and death as previously described in a multi-state model. Previously reported PFS hazard ratios for targeted therapies (versus chemotherapy) treating DGRs range from 0.17 to 0.52 (Hoang et al., 2020). Therefore, we assumed that the HRs corresponding to the parameter estimates for the targeted therapy option built into the model would approximate treatment-specific relative effects of targeted therapies for DGRs (PFS = 0.3; OS = 0.8). We simulated life-years and quality-adjusted life years (QALYs) for a cohort of 1,000 patients with DGRs matched to appropriate targeted therapies over a 5-year time horizon. We used population-level prevalence data to estimate the number of patients with metastatic NSCLC and DGRs. We then estimated the number of false negatives generated by DNA-only sequencing and calculated the additional life-years gained if RNA-based methods were used instead. Results: In a simulated cohort of 1,000 patients with DGRs detected through RNA sequencing and receiving targeted therapy, median PFS and OS were 1.8 and 3.7 years, respectively. The use of targeted therapy (instead of chemotherapy) in these patients increased life-years by 3.46 years (95% CI, 3.04-3.90) and QALYs by 2.27 years (95% CI 1.91-2.71) on average per patient. There were approximately 235,768 new lung cancers in the US in 2021, 56% of which were metastatic at diagnosis (SEER). Approximately 50% of lung cancers are adenocarcinomas, and approximately 12% of adenocarcinomas have DGRs: ALK (5%) , MET (4%) , ROS1 (2%) , RET (1%) , and NTRK1-3 (< 1%). Thus, there were approximately 7,922 new metastatic NSCLC cases with DGRs in 2021. Prior studies have shown that DNA-only methods have a sensitivity of 80-85% for DGRs compared to RNA-based methods. At the level of the US population, this implies 1,188-1,584 false negative cases in 2021. The clinical impact of eliminating these false negatives by using RNA- instead of DNA-based methods to identify DGRs amounts to 4,110–5,480 life-years or 2,696–3,595 QALYs gained by appropriately matching patients with DGRs to targeted therapy over chemotherapy. Conclusions: DNA-only sequencing methods have limited sensitivity for DGRs in lung cancer, leading to false negatives and missed opportunities for targeted therapy. This modeling study suggests that the elimination of such false negatives using RNA-based detection methods would lead to meaningful gains in patient outcomes.
A phase 1b study of blinatumomab with the anti-programmed cell death (PD)-1 antibody AMG 404 in adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL).
Authors: Papayannidis Cristina , Borlenghi Erika , Yeung David , Machherndl-Spandl Sigrid , Bellido Mar , Sandhu Karamjeet , Wong Hansen , Rasmussen Erik , Zugmaier Gerhard , Markovic Ana , Gordon Paul R. , Jabbour Elias 
Published: June 2022

e19003 Background: Preclinical data indicate that anti-PD-1 agents can facilitate activity of bispecific T-cell engager (BiTE) molecules. Here we assess the combination of the anti-CD19 BiTE molecule blinatumomab with the anti-PD-1 antibody AMG 404 in adults with R/R ALL (NCT04524455). Methods: Eligible adults with R/R ALL (Ph+ disease included) received 2-5 treatment cycles. Each cycle was 42 days, consisting of 4 weeks of cIV blinatumomab and a 2-week treatment-free interval as per label. In Cohort 1, AMG 404 was dosed IV at 240 mg every 4 weeks (Q4W); first dose was Day (D) 11 of Cycle (C) 1. Primary endpoints were dose-limiting toxicities (DLTs) and other adverse events (AEs). Results: As of 20 Dec 2021, patients (pts) from Cohort 1 (n=8) had median age of 57 (range: 24-73) y, 6/8 male, 6/8 Caucasian, 1 with extramedullary disease (duodenum), 2 with prior blinatumomab, and a median of 5 (2-15) prior treatment lines. Two pts remain on study and 2 completed the study; 4 pts discontinued the study due to death (n=3) or consent withdrawn (n=1). No DLTs were reported for the 3 evaluable pts. Of the 5 pts not evaluable for DLTs, in C1, 4 had disease progression and 1 an unrelated fatal pneumonia. Treatment-related grade (Gr) ≥3 and/or serious AEs in all 8 pts included cytokine release syndrome (CRS) (1 pt Gr 2, 1 pt Gr 1 and 3), Gr 3 increases in ALT and AST, Gr 3 fever, Gr 3-4 neutropenia, Gr 4 neutropenia/Gr 3-4 thrombocytopenia (same pt), Gr 2 sensorimotor polyneuropathy, Gr 3 hypertension, Gr 3 encephalopathy, and in 1 pt Gr 3-4 decreases in white blood cells, lymphocytes, and neutrophils. One pt developed Gr 3 SARS-COV-2 pneumonia on C2D25, resolving without clinical sequelae. C3 start was delayed by 12 days but protocol treatment resumed uneventfully. All 3 DLT-evaluable pts had a complete response (CR) or CR with partial hematologic recovery (CRh), 2/3 without measurable residual disease (MRD), within 2 cycles; the 3rd pt had an MRD response at the end of C3. Preliminary pharmacokinetic results for the combination of blinatumomab and AMG 404 demonstrated that their exposures were consistent with those observed for each as monotherapy and did not indicate any drug-drug interactions. To date, all samples tested for anti-blinatumomab antibodies have been negative. Conclusions: In this ongoing phase 1b study, the combination of blinatumomab with AMG 404 was tolerated with a manageable safety profile. No DLTs were reported. Enrollment continues in Cohort 2 in which AMG 404 is dosed Q4W at 480 mg starting on C1D1, 48 hours prior to blinatumomab. Clinical trial information: NCT04524455. [Table: see text]
Evaluating asparaginase toxicity in Hispanic patients with acute lymphoblastic leukemia in a large safety-net hospital.
Authors: Abdelmeseeh Elijah , Dragon Marcin , Tomassetti Sarah 
Published: June 2022

e19012 Background: Asparaginase has been a common component of induction therapy for acute lymphoblastic leukemia (ALL) patients for decades. The use of asaparaginase in the treatment of ALL has shown significant efficacy leading to improved outcomes when used in combination with chemotherapy in children. Despite these results, this medication is not used ubiquitously due to its toxicity profile in adults that includes hepatotoxicity, thrombosis, pancreatitis, and allergic reactions. Established risk factors for increased toxicity are increased age, obesity, and higher doses. Our study aims at reviewing the toxicity profile of this medication in Hispanic patients. We suspected that our patient population will have a higher incidence of various toxicities due to the higher prevalence of obesity and liver disease in this population. Methods: We performed a retrospective chart review of all patients aged greater than 18 years who presented to Harbor-UCLA Medical Center between 2015 and 2021 and were diagnosed with ALL who were given a treatment regimen that included asparaginase. We collected information about demographics, laboratory parameters on diagnosis, treatment details, and information on complications related to the treatment. Results: A total of 14 patients diagnosed with ALL and treated with asparaginase at Harbor-UCLA Medical Center from January 2016-November 2021 were included in this study. Our cohort consists of 53% males and 46% females, with an average age of 31 (SD 9.4). Our patient population had an average of BMI of 34 (SD 8.7), with the majority, 9 out of 14, being classified as obese. The majority of the cohort was Philadelphia chromosome negative (80%). In our study, the incidence of grade 3 to 4 hyperbilirubinemia was 6 out of 14 patients (42%). Half of our patients who suffered from hyperbilirubinemia suffered from class III obesity. The incidence of grade 3 to 4 transaminitis was 13 out of 14 patients (93%). A total of 5 out of 14 patients (36%) also suffered from thrombosis. One patient (7%) had a hypersensitivity reaction. Conclusions: Our incidence of hyperbilirinemia is higher than previously published incidence values. Various studies have shown different incidence rates ranging between 14-40%. Our patient population did experience severe transaminitis in a much higher rate than previously reported rates of around 50%. The higher incidence noted in our patients with class III obesity is in line with recent expert recommendations for dose reduction of asparaginase in patients with severe obesity. We have concluded from our study that our Hispanic population is at higher risk for developing hepatotoxicity after asparaginase use but could be related to the high prevalence of obesity in our population. This is important for future patient care to appropriately select candidates for this intensive therapy and reduce the risk of severe adverse events.
Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.
Authors: Tran Valerie , Bouligny Ian Michael , Alnimer Yanal Mufeed , Zacholski Kyle , Venn Chad Michael , Ho Thuy , Maher Keri Renee 
Published: June 2022

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.
Trends in Medicare oral anticancer drug utilization among relapsed and refractory chronic myeloid leukemia patients.
Authors: McBride Kaitlyn , Snyder Sophie 
Published: June 2022

e19058 Background: The treatment landscape for patients with relapsed and refractory (RR) chronic myeloid leukemia (CML) has changed significantly in recent years, with the introduction of targeted oral anticancer therapies. Current guidelines from the National Cancer Comprehensive Network (NCCN) recommend tyrosine-kinase inhibitors (TKIs) for second line and subsequent therapy. Recent real-world data evaluating treatment patterns in RR CML is limited. Study objective was to evaluate treatment patterns and trends in utilization of oral anticancer agents among Medicare beneficiaries diagnosed with RR CML, from 2017-2019. Methods: Retrospective study using Medicare Part D Prescription Drug Event Files, which contain records on prescription drug fills among Medicare beneficiaries enrolled in Fee-for-Service and Medicare Advantage plans. Beneficiaries diagnosed with RR CML (C9212 ICD-10) and prescribed oral anti-cancer therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) were identified and followed for at least 12 months, from index diagnosis until end of study period (December 31, 2019) or death. Trends in utilization by oral therapy, by number of beneficiary utilizers and prescription drug claims, were evaluated from 2017 to 2019. Results: Overall, 327 Medicare beneficiaries with a diagnosis of RR MM were prescribed an oral TKI therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) throughout the study period (2017-2019). The number of beneficiaries prescribed at least 1 oral therapy increased between 2017 and 2019, from 154 to 212 (Table). Total utilization also increased: from 210 prescription drug claims in 2017 to 296 in 2019. Throughout the study period, Imatinib Mesylate had the largest market share among all oral therapies, however the share decreased over time (from 35.7% in 2017 to 30.7% in 2019). Nilotinib had the largest gain in market share during this period, from 15.7% to 20.9%. Conclusions: Study findings suggest utilization of oral therapies are increasing over time, and shifting from Imatinib Mesylate to newer therapeutic agents. Given the high costs for these novel therapies, future research should examine trends in patient out-of-pocket spending, as well as factors impacting patient adherence.[Table: see text]
Antibody seroprevalence against SARS-Cov-2 among chronic myeloid leukemia patients.
Authors: Miranda Marisol , Bradshaw Danielle , Farmaha Jaspreet , Patel Reeya , Jones Kimya , Singh Harmanpreet , Vashisht Ashutosh , Sahajpal Nikhil Shri , Kohle Ravindra , Cortes Jorge E. 
Published: June 2022

e19061 Background: The rapid spread of SARS-CoV-2 has elicited an equally rapid development of effective vaccines, leading to a reduction of COVID-19 severity and deaths. There is limited data on COVID-19-related immunity in chronic myeloid leukemia (CML) patients. Methods: SPARTA (SARS2 SeroPrevalence And Respiratory Tract Assessment) is an ongoing observational study for participants age ≥18 years to investigate immunity to SARS-CoV-2 after infection and/or vaccination. We included patients with CML and compared them with a non-cancer group. We collected saliva and peripheral blood to measure antigen levels by RT-PCR and antibodies (secretory IgG antibodies and neutralizing antibodies). Results: From October 1, 2021, to February 4, 2022, we prospectively enrolled 49 participants (23 CML, 26 non-cancer). Most were male (56.5%) in the CML group and female in the control group (61.5%), mean age 56.39 y vs. 51.96 y, respectively, and self-identified as white (87% vs. 76.9%). In the CML group, 11 (47.8%) had ≥1 comorbidities, vs 13 (50%) in the control group. Twenty-one (91.3%) CML patients were receiving tyrosine-kinase inhibitors; 4 (18.2%) non-cancer subjects reported taking any medication. Most participants in both groups had received at least one dose of COVID-19 vaccine (73.9% vs. 73.1%); 100% of CML patients received two doses vs. 84.2% of controls; the CML group had a higher percentage of subjects fully vaccinated (66.7% vs. 25%). The CML group had a lower percentage of patients previously diagnosed with COVID-19 (8.8% vs. 57.7%). However, there was no difference in the detection of SARS-CoV-2 antigen at the time of enrollment (0% vs. 4%). SARS-CoV-2 IgG antibodies were detected in most of the participants regardless of cancer status (78.3% in the CML cohort and 88% in the non-cancer cohort), and neutralizing antibodies were detected in 82.6% and 95.6%, respectively. The two groups had comparable IgG (mean 146.3 Ru/ml vs. 148.9 Ru/ml) and neutralizing (mean 1329.1 ng/ml vs. 1112 ng/ml) antibody levels. Conclusions: Our preliminary data comparing concomitant cohorts with similar socio-demographic characteristics and medical history indicate that a diagnosis of CML did not impact the development of antibodies against SARS-CoV-2. We are conducting continuous analysis of antibodies levels over time to assess the evolution of antibody immunity and functional studies including cellular immunity assessments.[Table: see text]