bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency and outcomes of molecularly guided off-label targeted agent prescriptions in the VA National Precision Oncology Program (NPOP).
Authors: Vashistha Vishal , Guo Aixia , Katsoulakis Evangelia , Price Meghan , Ahmed Sara , Kelley Michael J. 
Published: June 2022

e18676 Background: The increasing availability of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among cancer pts with actionable mutations. CGP has led to identification of both on-label (level 1) variants, for which TAs have known efficacy, and off-label variants with lesser strength of supporting data. We sought to evaluate real-world prescription patterns and outcomes of off-label TA prescriptions among pts who underwent CGP. Methods: The NPOP database and VA Corporate Data Warehouse were queried to identify pts who had underwent CGP between February 2019 and December 2021 and were prescribed at least 1 of 73 TAs before January 2022. TAs prescribed for FDA-approved indications not relying on CGP as a companion diagnostic were excluded. OncoKB was used to annotate gene variants and evaluated against prescriptions to select pts who received off-label TAs. The frequency of off-label TA use, and for those treated > 4 weeks, rate of pts treated for 6 months or longer, median treatment duration and overall survival (OS) were computed. Results: Of the 18686 patients who underwent CGP, 2107 (11%) were prescribed any TA, and 191 (1%) were prescribed off-label TAs, with 31 receiving multiple concurrent or sequential off-label TAs. Mean age was 65.5 years, and 88% were male. TAs were most often prescribed for cancers of unknown primary (CUP, 29), NSCLC (24), and colorectal cancer (22). Frequency of off-label prescriptions was highest for pts who completed CGP for thyroid cancer (9%), breast cancer (8%), and CUP (2%). Most common variants involved BRAF (21%), ERBB2 (18%), BRCA1/BRCA2/ATM (9%), and PIK3CA (6%). Among all 164 pts treated > 4 weeks, 40% received TAs for 6 months or longer, including 50%, 47%, and 46% of pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease, respectively. Median therapy duration and OS was 141 [78.5 – 317, IQR] days and 181 [96.5 – 304.5, IQR] days, respectively. Conclusions: Though overall use of off-label TAs following CGP is low, nearly 10% of advanced thyroid and breast cancer patients are prescribed TAs for off-label indications. Forty percent of all pts receiving off-label TAs continue for at least 6 months, with higher rates for pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease. CGP-guided off-label treatment approaches offer unique options for advanced stage cancer with amenable molecular profiles.
National claims data analysis of outcomes of hospitalized cancer patients without COVID-19 infection during versus prior to the COVID-19 pandemic.
Authors: Caswell-Jin Jennifer Lee , Nemati Shafaee Maryam , Liu Mina , Xiao Lan , John Esther M , Bondy Melissa , Kurian Allison W. 
Published: June 2022

e18679 Background: There has been growing concern regarding the impact of the COVID-19 pandemic on health care delivery and disruption of care to cancer patients. Reductions in cancer surgeries, delays in administration of life saving chemo and radiation therapies, and lower rates of cancer-related hospitalizations have been reported. While cancer patients with COVID-19 infection have poor hospitalization outcomes, less is known about the outcomes of hospitalized cancer patients without the infection. This study aimed to describe the impact of the COVID-19 pandemic on outcomes of the most common cancer-related hospital admissions for patients without COVID-19 infection at a national level using insurance claims. Given the concern for disruptions in their care, we hypothesized that hospitalized cancer patients may have worse outcomes. Methods: We used the Optum Clinformatics Data Mart, consisting of claims records linked to electronic health records, including an average of 8 million adult Americans per year enrolled for at least 6 months. We identified cancer-related hospitalizations from 02/2018-05/2021 and included patients with at least of one of these cancer types: breast, prostate, bladder, ovarian, cervical, lung, colorectal, esophageal, liver, small intestine, gastric, or gallbladder cancer. Patients with cancer-related hospitalization who had COVID-19 infection were excluded. The main outcome was “severe adverse outcome” and included at least one of the following: mortality during or within 30 days of hospitalization, mechanical ventilation during hospitalization, intensive care unit admission, or discharge to hospice. We used Poisson regression to compare the number of hospitalizations before (2/1/2018-1/30/2020) and during (2/1/2020-5/30/2021) the pandemic and a Chi-squared test to compare the proportion of cancer-related hospitalizations with severe adverse outcomes over that time period in 4-month intervals and across cancer types, gender, (male vs female) and geography (the 9 Census Bureau regions). Results: There were 82,796 cancer-related hospitalizations in the period 2/2018-05/2021. A slightly higher proportion of cancer-related hospitalizations resulted in a severe adverse outcome during the pandemic as compared to prior to the pandemic (41.8% vs 40.9%; p = 0.012). There were no differences by cancer site, gender, or geography. The number of hospitalizations was lower during vs prior to the pandemic (p < 0.0001). Conclusions: The number of cancer-related hospitalizations during the pandemic was lower compared to before the, and a slightly higher proportion of those hospitalized experienced severe adverse outcomes among insured U.S. cancer patients without COVID-19 infection. The lower number of cancer-related hospitalizations during the pandemic warrants further investigation.
Recurring event survival analyses: A methodological approach to model recurring event data in cancer patients receiving multiple lines of therapy.
Authors: Galaznik Aaron , Dudley William , Coombs Nicholas 
Published: June 2022

e18693 Background: In cancer treatment, patients often receive multiple rounds of treatment, or Lines of Therapy (LoT). The time between start of a LOT and change to a new LOT is an important outcome in clinical oncology, for understanding disease progression and anticipating response to further treatment. Research questions may focus on the associations between duration of an LOT (the dependent variable) and independent variables of interest, such as time-invariant demographic (gender, age, race) and clinical factors (comorbidities, stage of disease) as well as time-varying factors such as Patient Reported Outcomes (PRO’s), resource utilization, and adverse events. These associations can be tested empirically with traditional “survival analyses”, more generally known as time-to-event when there is a single event (such as 5-year survival). The analyses, however, may become more complex when patients experience more than one LOT. This is due to the possibility that the Time-to-Events may be correlated within an individual patient, similarly to how outcome variables are correlated in other repeated measures designs. If this correlation is not captured in the modeling, the validity of parameters estimates may be in doubt. Thus, it is important to analyze the data using methods which account for the within-person correlation among LOT durations through the use of “Recurring Event” survival analyses. Methods: This methodological presentation will report an example of a real world “Recurring Event” analysis in a study of Multiple Myeloma patients who received one or more than one LOT. The study data set was derived from users of PROmpt®, an application for remote patient reporting and provider symptom management. Patient characteristics and treatment history were assessed by survey and review of patient EMR records. 80 patients were identified, with a treatment history of receiving between 1 and 19 LOT’s (mean = 5.2). Time invariant predictors are age, gender, and frailty (employing the Modified Geriatric Assessment). Time varying variables are the incidence of hematological and non-hematological toxicities. Results: The presentation will provide: an overview of how to interpret the model parameters, a discussion of the data structure required by the modeling, and a series of results in which LOT durations are analyzed as first independent and then when modeled as a “Recurring Event” analysis. The results are examined across different modeling strategies to illustrate a model testing approach, as well as to quantitatively demonstrate the impact on survival analysis results when incorporating “recurring event” methodology. Conclusions: The intent of the presentation is to alert researchers to the need to analyze Time-To-Event models using a recurring event framework when patients experience recurring events in order to produce valid and generalizable parameters.
Hospital readmission after a breast cancer-related admission among breast cancer patients with and without heart failure.
Authors: Park Chanhyun , Lee Hyesung , Jensen Brian C. , Schonberg Mara A. 
Published: June 2022

e18717 Background: Breast cancer and heart failure (HF) are both costly conditions that lead to increased hospitalization. Little is known about hospital readmission among breast cancer patients with comorbid HF. We aimed to compare rates and causes of readmission among women hospitalized for breast cancer, between those with and without comorbid HF. Methods: This cross-sectional study, using the 2015–2018 Nationwide Readmissions Database (NRD), includes hospitalized women with a primary diagnosis code for breast cancer. The primary independent variable was the presence of comorbid HF. The dependent variables were 30-day and 90-day hospital readmission after hospital discharge. Women with HF were matched to women without HF by age group (18-49, 60-64, 65-79, ≥ 80 years). Multivariate logistic regression was used to assess the association between HF and hospital readmission rate while controlling for covariates. Subgroup analyses were conducted by age group. Results: Among 172,434 hospitalized women with breast cancer, 11.9% (n = 20,102) had HF; of which 8.8% were readmitted at 30 days and 15.9% at 90 days. Before matching, mean age (SD) of women with HF was 73.9 (SD +/-11.6) years and was 62.8 (+/-14.1) years in those without HF; after matching the mean age was 71.5 (+/-11.4) years for both groups. In multivariate analyses, comorbid HF was associated with a 14% increase in the 30-day readmission rate and a 20% increase in the 90-day readmission rate. HF was associated with an increased risk of readmission for women with breast cancer who were ≥ 65 years, but not for those < 65 years. Among those with HF who were ≥ 65 years, the most common cause of readmission was HF; among those with HF who were < 65 years, the most common cause of readmission was breast cancer. Conclusions: HF substantially increased the risk of hospital readmission for older women breast cancer. Timely inpatient and post-discharge management of HF, particularly for older women, will improve health outcomes and reduce the economic burden among patients with breast cancer.[Table: see text]
How to promote the sharing of RWS data in China's second-tier cities?
Authors: Wang Shasha , Wang Fang , Zeng Zhen , Gao Fang , Qin Haifeng 
Published: June 2022

e18719 Background: Real world studies(RWS) measure the actual effects of treatment, not the efficacy in trials, making conclusions from real world studies more extrapolative. Clinical SCI papers are primarily based on the exploration of real-world clinical practice. We investigated the status of SCI papers published by 500 front-line clinicians, hoping to find some effective ways to promote the sharing of clinical research results in the real world. Methods: From December 2021 to January 2022, 500 front-line clinicians in 26 cities completed a 20-question online survey. Results: All of respondents were attending physicians in second-tier cities, and 7% of respondents were Bachelors, 61.8% were Masters and 31.2% were Doctors. The survey indicated surprising 83.1% of the respondents had no experience in SCI paper publication. Those(56.0%) had trouble getting paper published. Among all the respondents, 29.6% did not know the grade and submission requirements of SCI journals, 27.1% have no idea how to operate it, 24.9% had insufficient knowledge of medical statistics, 7.8% were not clear about the research design requirements for papers submitted to SCI journals. The major reasons(88.2%) for the above situation was no opportunity to receive professional systematic training. In terms of expecting help, 63.2% of patients expected to receive systematic lectures from the SCI editorial board，and 25.1% expected their peers to share their experiences in turning RWS data to paper. Conclusions: The survey indicated the ability improvement of paper publication was helpful to promote the sharing of clinical research results in the real world, and further benefit more patients.
COVID-19 vaccination status and clinical outcomes in solid cancer patients treated with immune checkpoint inhibitors.
Authors: Khaddour Karam , Meeder Natalie , Kamel Josette Mary , Babwah Amaara , Nguyen Ryan Huu-Tuan , Wang Heidy , Liu Li C. , Feldman Lawrence Eric , Jain Shikha , Weinberg Frank 
Published: June 2022

e18731 Background: Immune checkpoint inhibitors (ICI) constitute the mainstay of treatment in several unresectable locally advanced and metastatic solid cancers. mRNA COVID-19 vaccines are immunogenic and can modulate intrinsic host immunostimulatory properties however the effect of COVID-19 mRNA vaccination on outcomes in patients receiving ICI is not well understood. This study examines the outcomes in cancer patients receiving ICI according to their vaccination status. Methods: From January 2021 to December 2021, we identified adult patients with locally advanced and metastatic solid tumors at the University of Illinois Hospital & Health Sciences System who had received at least one dose of ICI, either as monotherapy or in combination with chemotherapy or targeted therapy, in any line of cancer treatment. Patients were stratified by COVID-19 vaccination status and treatment type (monotherapy versus combined chemoimmunotherapy). Endpoints included immune-related adverse events (IRAEs), progression-free survival (PFS) from ICI initiation and overall survival (OS). Results: Among 89 patients meeting these inclusion criteria, the mean age at diagnosis was 66 years, patient sex was about equally split (female 50.5% to male 49.5%), most patients were minorities (including 58.4% African American), vaccinated (78.7%), had lung cancer (57.3%), were stage IV (71.1%), and had received ICI monotherapy (67.4%). There were no significant differences in the rate of IRAEs between vaccinated and non-vaccinated patients ( p= 0.53). Patients who received ICI monotherapy had higher rates of IRAEs ( p< 0.001). There was no difference in PFS between vaccinated and non-vaccinated patients ( p= 0.7) and no difference in OS between vaccinated and non-vaccinated patients ( p= 0.59). Conclusions: In this real-world sample of patients with advanced solid cancers who received ICI there were no significant differences in IRAEs, PFS or OS between vaccinated and non-vaccinated patients, which may be due to the relatively small sample size. Larger real-world datasets with long-term follow-up are needed to study the effect of mRNA COVID-19 vaccination on outcomes in advanced cancer patients receiving ICI.
Incidence of severe and febrile neutropenia in cancer patients treated with myelosuppressive chemotherapy in real clinical oncology practice: Preliminary results from the FLAME study.
Authors: Snegovoy Anton , Kononenko Inessa , Chernova Alexandra , Shepel Artem , Kaleikina Liliya , Shalina Anna , Sharov Sergey , Pavlova Elena , Goldshmidt Petr , Dergunov Alexander , Safin Rustem , Pimonova Irina , Yukalchuk Denis , Soroka Svetlana , Mikhaluk Viktorya , Vladimirova Liubov Yu , Yavorskaya Marina , Starostina Tatiyana , Tkachenko Svetlana , Sorokina Irina 
Published: June 2022

e18740 Background: Febrile neutropenia (FN) is a life-threatening complication of myelosuppressive chemotherapy (CT). It can lead to infections, subsequent hospitalizations, treatment delays, dose reductions, and additional health care costs. According to guidelines, use of granulocyte colony-stimulating factors (G-CSF) prevents FN. However, in clinical practice, the need for G-CSF use has not been defined due to the lack of national reports on neutropenic complications (NC). Methods: FLAME is the first Russian retrospective non-randomized non-interventional study designed to include 515 patients (pts) with solid tumors receiving myelosuppressive CT with or without targeting and immuno-oncology drugs. The primary objective of this study is to define the actual incidence of NC in clinical practice and to identify patients at high risk of FN. In addition, this study is intended to demonstrate the unmet need for G-CSF prophylaxis of FN. Patients who completed at least the first 2 cycles of treatment in frame of the course between the 1st’Aug 2020 till 30th’October 2021 were eligible to be included in the study. Results: Data were obtained from 492 pts recruited from cancer hospitals throughout Russia. Their characteristics were as follows: median age 56.5; male/female: 36.5%/63.5%. Among 492 pts with various malignancies, 65% had stage III or IV. Breast (68%), colorectal (10%), urogynecological cancer (10%) were the most common. The remaining were gastrointestinal cancer, lung cancer, sarcoma, and CUP. Clinically significant comorbidities were reported in 53.6% of pts. Thirty percent of patients had ≥1 risk factor for FN based on individual and CT analysis. From 29 different CT regimens, 14% had a high risk of FN. Primary prophylaxis was given only to 44.1% pts with a high risk of FN [empegfilgrastim (Extimia®) 19,1%, filgrastim 25%]. The duration of filgrastim administration was 1 to 3 days in 81% of cases. Treatment of NC with corticosteroids and others was prescribed in 12.8% of cases. Three percent (3%) and 3.8% of pts had FN and dose-limiting neutropenia, respectively. Delayed CT at the second cycle was performed in 27%. The dose of CT was reduced by 20-25% in 8.3% of patients. Conclusions: Preliminary results from this study suggest that the risk of FN is higher from the start of CT. Delaying and reducing the dose of CT is still typical for oncologists. This practice is associated with low adherence to guidelines. Further efforts are needed to decrease the risk of NC in clinical practice.
Real-world evidence on predictors of survival for hormone-positive and triple-negative advanced breast cancer by treatment and BRCA status in the United States.
Authors: Zhang Dongmu , Raskin Leon , Sebby Wendy , He Lei , Pawar Sandeep , Narod Steven A , Olopade Olufunmilayo I. , Liede Alexander 
Published: June 2022

e18754 Background: Factors that affect overall survival (OS) for women with metastatic or recurrent breast cancer (BC) and BRCA1 or BRCA2 mutations (BRCA+) are a matter of debate. We analyzed electronic health records (EHR) from centers across the US to examine the effect of bilateral salpingo oophorectomy (BSO) and other factors on OS across treatment and molecular subtypes with emphasis on hormone-positive (HR+) and triple-negative BC (TNBC). Methods: A cohort of women diagnosed with stage 3 or 4 HR+ or TNBC from 1-Jan-2015 to 31-Dec-2019 was identified from EHR (Tempus Labs, Chicago, IL). BRCA+ was confirmed from medical notes and laboratory reports. A comparator group included HR+ and TNBC with no record of BRCA testing (Non-BRCA). Kaplan-Meier and Cox proportional hazards were used to evaluate predictors of OS from earliest diagnosis in multivariate models by BRCA status and molecular phenotype; treatment exposure (any time), mastectomy and BSO were treated as time-dependent variables. Results: We identified 1227 women with median age of 53 years (range 18-89) at BC diagnosis and median follow up of 26.1 months (max > 26 years) and 358 deaths. Two-thirds had distant visceral or bone metastases, almost 60% were recurrent after original stage 1-3 BC; 302 women were stage 3 and 296 stage 4 at BC. The BRCA+ cohort included 439 women (195 BRCA1, 220 BRCA2, 24 “BRCA” mutation; 265 HR+, 142 TNBC) and median age at BC was 46 years (44 BRCA1, 47 BRCA2). Non-BRCA cohort consisted of 788 women with a median age of 57 at BC (378 HR+, 341 TNBC). BRCA+ had longer OS than non-BRCA ( P= 0.0001); HR+ had longer OS than TNBC ( P= 0.0001). For 331 TNBC, chemotherapeutic regimens were most common first line treatment; few (17%) received third line and 31% had no evidence of receiving systemic therapy. Age ≤50, BRCA+, and mastectomy were associated with increased OS in HR+; BRCA+ status and mastectomy were predictors of increased OS whereas platinum-based chemotherapy was associated with decreased OS in TNBC (Table). Across molecular subtypes, BSO was not an independent predictor of OS and most women (92%) had BSO after BC diagnosis. Conclusions: Regardless of BRCA status, women with advanced TNBC were almost exclusively treated with chemotherapy, which highlights the remaining unmet need for effective treatment options. Taking timing of BSO and other interventions into account is critical to understanding their effects of BC mortality.[Table: see text]
Review of health care access duration among cancer patients at a large health plan.
Authors: Rutter Wilbur , Cavers William , Prakash Shivaani , Avalos-Reyes Elisea , Johnson Kjel Andrew 
Published: June 2022

e18758 Background: Cancer patients have unique, long-term health care needs and access to timely and affordable care is essential. Little is known about cancer patients’ propensity to leave their health plan during and after treatment. This study aimed to examine health care access duration among cancer survivors. Methods: Adult patients diagnosed with cancer between 11/1/2015 and 10/31/2016 were identified and followed until 11/1/2021. Control patients were identified as adults with no cancer diagnosis between 11/1/2015 and 11/1/2021. Patients with skin cancer were excluded due to limited care requirements. The primary outcomes were annual patient churn and median length of health plan enrollment duration. Propensity score (PS) matching was conducted between the groups utilizing patient demographics to balance comorbidities between groups. Comorbidity was described with the National Cancer Institute comorbidity index (NCI CI). Appropriate descriptive statistics were calculated and Cox proportional hazards (CPH) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Overall, 3.2 million patients met the eligibility criteria, with 18% having cancer. Significant differences in the unmatched population were found, with the cancer group being older and having more comorbidities (p < 0.001). Following PS matching, the differences in underlying demographic variables were minimal, despite being statistically significant. Unadjusted annual churn rate, defined as the percent of cancer patients leaving the health plan per year, averaged 25.44% overall, with the non-cancer group experiencing more churn most years (Table). Median length of health plan enrollment duration was 716 days (Interquartile range (IQR) = 819) overall, with the cancer group having less median duration than the non-cancer group in the matched analysis (713 [IQR 808] vs. 717 [IQR 822], p < 0.001). After adjusting for the variables in the model, having a cancer diagnosis was associated with decreased risk of health plan disenrollment in multivariate CPH regression (HR 0.987 [95% CI 0.983 – 0.991]). Additional factors that increased the risk of disenrollment included: male gender (HR 1.011 [1.008-1.015]), Medicare eligibility (HR 1.290 [1.279-1.301]) and increasing NCI CI (1.124 [1.118-1.129]). Conclusions: Cancer patients experienced less churn from their health plan over a five-year follow-up. They were less at risk for disenrollment at any time than non-cancer patients when confounders are accounted for in multivariate modeling.[Table: see text]