bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparity in uterine cancer treatment and survival: A matter of Black women’s lives.
Authors: Balanean Alexandrina , Falkenstein Angelica , Zettler Marjorie E. , Klink Andrew J. , Savill Kristin M. Zimmerman , Kish Jonathan , Brown-Bickerstaff Cherrishe , Jeune-Smith Yolaine , Gajra Ajeet 
Published: June 2021

6550 Background: Despite similar incidence rates of uterine cancer (UC) in Black and White women, the former have worse prognosis and survival. Absence of denominator correction for UC hysterectomy (prevalence varies within the United States [US] by race/region) may underestimate incidence. The objective of this study is to compare treatment and survival of patients with UC by race in a large, contemporary, population-based study with at least 5 years of follow-up. Methods: With the latest available data from the Surveillance, Epidemiology, and End Results database, comparisons between Black and White patients were made using chi-square and Mann-Whitney tests. Cox proportional hazards regression estimated the adjusted risk of mortality by including age at diagnosis, race, US region, tumor histology/stage/grade, and receipt of hysterectomy as covariates. Results: A total of 105,036 women (11,028 Black and 94,008 White) newly diagnosed with UC in 2000-2013 and followed through 2018 were identified. Median age at diagnosis was 62 years, and more patients in the South were Black (41% vs 17%, P<.0001). Higher rates of type 2 (15% vs 6%), late-stage (44% vs 28%), and high-grade (48% vs 25%) tumors at diagnosis were also found in Black women (all Ps<.0001; Table). Compared with White women, Black women had lower 5-year survival rate (18% vs 37%, P<.0001), shorter survival (median 49 vs 78 months, P<.0001), and higher adjusted mortality risk (hazard ratio [HR]: 1.3, 95% CI: [1.3, 1.4], P<.0001). Lack or unknown status of hysterectomy was also associated with higher death risk (HR: 3.6, 95% CI: [3.4, 3.9], P<.0001). Conclusions: Correcting for hysterectomy attenuates racial disparity in incidence; however, black women have inferior outcomes primarily due to increased aggressive histology, late-stage, and high-grade tumors as well as decreased use of hysterectomy. Underestimation of at-risk populations may be misdirecting cancer control efforts, highlighting the importance of accurate reporting to inform potential treatment adaptations. Next steps are to assess cancer-specific mortality with Fine-Gray competing risk models.[Table: see text]
Characteristics of patients hospitalized through the emergency department with an oncology drug-related side effect.
Authors: Avalos-Reyes Elisea , Parke Darren , Wallace Kirsten , Freeman Allison , Johnson Kjel Andrew 
Published: June 2021

6557 Background: Recent advances in oncology treatment present an expanding spectrum of cancer-treatment-related emergencies.Many aspects of healthcare utilization, specifically emergency department (ED) visits, are not well studied in this population. The purpose of this study is to determine (1) what proportion of cancer patients visit the ED with an oncology drug-related side effect and are admitted and (2) what factors impact the probability of inpatient admission among these patients. Methods: This study evaluated ED visits by adult patients undergoing active drug treatment for cancer insured by a large commercial and Medicare health plan in the United States between January 1, 2018, and September 30, 2019. Among cancer-related ED visits, logistic regression was used to determine the marginal effect of demographic and clinical characteristics of patients on acute inpatient admission. Results: There were 39,921 total ED visits among patients undergoing drug treatment for cancer; of these, 76% presented with an oncology drug-related side-effect. 36% of all ED visits resulted in admission, 5% resulted in an observation stay. After adjusting, age was not a significant predictor of inpatient admission. Being male (p < 0.01) and living in urban (p < 0.01) or suburban (p < 0.01) zip codes significantly increased the likelihood of admission. Patients with colorectal (p = 0.019), gastrointestinal (p < 0.01), blood (p < 0.01), lung (p < 0.01), metastatic (p < 0.01) cancers, or Hodgkin’s lymphoma (p < 0.01) had significantly increased risk of admission. Patients with prostate (p < 0.01) cancer had a significantly reduced risk of admission. The primary complaint upon presentation to the ED was the most important predictor of inpatient admission; sepsis, pneumonia, medical complications, white cell disorders, metastatic cancer, and fractures were all associated with a significantly higher (all p < 0.001) risk of admission. Patients with comorbid heart failure (p < 0.001), those taking ulcer medications (p < 0.01), or inflammatory bowel disease (p = 0.03) had a significantly increased risk of admission. Results were consistent regardless of payer (Medicare or commercial health plan). Conclusions: This study identified cancer patients for whom acute inpatient admission from an ED presentation is more likely. Future studies identifying cancer patients who may be at risk of making an ED presentation based on demographic, clinical and disease-related characteristics are needed and may help inform targeted follow up of patients to mitigate potentially avoidable ED presentation and subsequent inpatient admission.
The landscape of mortality during or within 30 days after non-palliative radiotherapy across 11 major cancer types.
Authors: Xiang Michael , Raldow Ann C. , Pollom Erqi L. , Steinberg Michael L. , Kishan Amar Upadhyaya 
Published: June 2021

6570 Background: The rate of peri-RT mortality (death that occurs during or within 30 days after non-palliative radiotherapy) has not been previously characterized. Risk factors and predictors for peri-RT mortality are unknown. Methods: Adult and pediatric patients with non-metastatic cancer who received non-palliative external beam radiation between 2004-2016 were identified in the National Cancer Database for 11 cancer types: breast, prostate, genitourinary (non-prostate), bone/soft tissue, gynecological, head/neck, lymphoma, gastrointestinal, small cell lung, non-small cell lung, and central nervous system (CNS). Multivariable logistic regression was used to identify predictors of peri-RT mortality while controlling for 16 covariates, including patient, tumor, and treatment factors. Results: Approximately 1.32 million patients were identified. Peri-RT mortality was 2.8% overall but spanned 2 orders of magnitude depending on cancer type, ranging from 0.1% for breast cancer to 8.6% for CNS malignancies. Other cancers with > 5% peri-RT mortality were non-prostate genitourinary, small cell lung, and non-small cell lung. Peri-RT mortality steadily improved from 3.5% in 2004 to 2.0% in 2016 ( P <.0001). Major predictors of peri-RT mortality were cancer stage, older age, baseline comorbidity, and lack of private insurance, while male sex, Black race, and geographical region were associated with modestly increased risk (all P <.0001). Conversely, treatment at an academic center, higher patient volume at the treating facility, concurrent chemotherapy, and intensity-modulated radiotherapy were associated with modestly decreased risk (all P <.0001). Among patients receiving stereotactic radiotherapy, peri-RT mortality was 1.0% (adjusted odds ratio 0.27, 95% confidence interval 0.24-0.30, P <.0001), underscoring the excellent safety record of this treatment approach. Conclusions: Peri-RT mortality varied considerably as a function of multiple disease-specific and sociodemographic differences, which highlight potential areas of health disparities. Early recognition of patients at increased risk may facilitate closer monitoring or other prophylactic interventions.
Patient and treatment characteristics of emergency presentations due to immune-mediated toxicities.
Authors: Nahm Sharon Hyo-Eun , Heywood Richard , Callaghan Sophia , Serra-Bellver Patricio , Gupta Avinash , Cooksley Tim , Lorigan Paul 
Published: June 2021

6586 Background: The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the characteristics and treatment patterns for patients with emergency presentations due to immune-mediated toxicity are less well known. Methods: This study of all emergency presentations in patients treated with ICIs was performed at The Christie NHS Foundation Trust, Manchester, United Kingdom from May 2018-February 2020. The aims were to describe the patient and treatment characteristics of those diagnosed with an immune-mediated toxicity. Results: In total, 597 patients receiving ICIs had an emergency presentation and 191/597 (32%) were diagnosed with an immune-mediated toxicity. Of these patients, the median age was 64 years and 127/191 (67%) were male. The most common tumour types were melanoma (53%) and lung (22%) and the most common ICI received was ipilimumab + nivolumab combination immunotherapy (42%), followed by pembrolizumab monotherapy (21%) and nivolumab monotherapy (20%). The median number of cycles received was 3 (range 1-54), and 73/191 (38%) previously had ≥ grade 2 immune-mediated toxicity. The most common diagnoses were colitis (38%), hepatitis (15%), and pneumonitis (14%). The majority, 180/191 (94%) received steroids and 52/180 (29%) patients required second-line immunosuppression. The most common second-line immunosuppressants used were mycophenolate mofetil (58%) and infliximab (50%). Eleven patients (22%) required more than one second-line immunosuppressant. Conclusions: The majority of patients with emergency presentations due to immune-mediated toxicity were being treated with combination immunotherapy for melanoma. More than a third of patients had previous ≥ grade 2 immune-mediated toxicity. Over one quarter of patients treated with steroids required second-line immunosuppression. Identifying these characteristics can help inform which patients receiving ICIs seeking medical review need admission to a center with experience in managing immune-mediated toxicity.
Leveraging the electronic medical record (EMR) to predict patient reported financial hardship in cancer patients.
Authors: Voleti Sandeep Sai , Ailawadhi Sikander , Mead-Harvey Carolyn , Warsame Rahma M. , Fonseca Rafael , Griffin Joan M. , Khera Nandita 
Published: June 2021

6594 Background: Patient reported financial hardship (FH) in cancer care is a growing challenge for patients, their caregivers and healthcare providers. As treatment costs escalate, it is imperative to develop effective strategies to proactively recognize and mitigate FH within oncology practice. Using automated processes to screen and refer patients to appropriate resources is a potential option. At Mayo Clinic, screening for FH involves using a single financial strain question ‘ How hard is it for you to pay for the very basics like food, housing, medical care, and heating?’ completed by all cancer patients annually as part of the Social Determinants of Health (SDOH) assessment. In this study, we describe the prevalence and predictors for FH (denoted by the answer ‘hard and very hard’) in our patient population. Methods: Patients receiving cancer care at the three Mayo Clinic sites (Minnesota, Arizona, and Florida) who completed the FH screen at least once were included in this study. Demographics (age, gender, race/ ethnicity, insurance, employment status, marital status, and zip code) and disease state data for included patients was extracted from the EMR and Mayo Clinic Cancer Registry. Disease state was categorized by type of cancer (hematological or solid malignancy) and cancer stage. Zip code was used to derive median income, rural/urban residence and distance from the cancer center. Multivariable logistic regression models were utilized to examine factors associated with FH. Results: The final study cohort included 31,969 patients with median age 66 years (IQR 57,73), 51% females, and 76% married. Race/ethnicity composition was 93% White, 3% Black, and 4% Hispanic. 52% of patients had Medicare and 43% had commercial insurance. Other notable factors included 48% retired, 41% working/ students, 76% married, and 72% urban residents. Median time from cancer diagnosis was 1.1 year (IQR 0.1, 3.8) and median income was $64,406 (IQR 53,067, 82,038). 31% of patients had hematological malignancies, 20% of the cancers for which staging information was available were metastatic. FH was reported by 4% (n = 1194) of the patients. A significantly higher likelihood of endorsing FH (p < 0.001 for all) was noted in Hispanic (OR 1.64), Black (OR 1.84), American Indian/Alaskan native (OR 2.02), below median income (OR 1.48), rural (OR 1.17), self-pay (OR 2.77), Medicaid (OR 2.29), Medicare (OR 1.43), unemployed/disabled (OR 2.39), single (OR 2.07), or divorced (OR 2.43) patients. Older age, being retired, and living farther from the cancer center were associated with significantly less likelihood of endorsing FH. Conclusions: Our study successfully leveraged the EMR to identify key sociodemographic groups more likely to report FH. An electronic trigger to flag such patients at high-risk of FH and proactively address FH is currently being developed.
Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacitidine (Oral-AZA).
Authors: Roboz Gail J. , Wei Andrew H. , Ravandi Farhad , Pocock Christopher , Montesinos Pau , Dombret Hervé , Porkka Kimmo , La Torre Ignazia , Skikne Barry , Zhong Jianhua , Beach C. L. , Dohner Hartmut 
Published: June 2021

7014 Background: Demographic and disease factors influence outcomes for patients (pts) with AML. In the phase 3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS and RFS vs. placebo (PBO) for pts with AML in first remission after IC (Wei, NEJM, 2020). Univariate analyses showed OS and RFS benefits with Oral-AZA vs. PBO across pt subgroups defined by baseline (BL) characteristics. MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors. Methods: Pts were aged ≥55 yrs with AML in complete remission (CR) or CR with incomplete count recovery (CRi) after induction ± consolidation. Within 4 months of CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO for 14d/28d cycle. Cox proportional hazards models were used to estimate Tx effects of Oral-AZA vs. PBO on OS and RFS, adjusting for BL age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction (per investigator) and at BL (per sponsor), MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC. In a stepwise procedure, randomized Tx and BL variables were selected incrementally into a Cox model if P ≤ 0.25. After each addition, the contribution of the covariate adjusted for other covariates in the model was evaluated and retained in the model if P ≤ 0.15. Results : Oral-AZA Tx remained a significant independent predictor of improved OS (HR 0.70) and RFS (HR 0.57) vs. PBO after controlling for BL characteristics (Table). MRD status, cytogenetic risk, and pt age were each also independently predictive of OS and RFS. Response after induction (CR vs. CRi) and BL ANC were predictive of OS but not RFS, whereas prior MDS, CR/CRi at BL, and number of consolidation cycles were only predictive of RFS. Conclusions: Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. PBO independent of BL characteristics. Cytogenetic risk at Dx, MRD status, and pt age also independently predicted survival outcomes. Clinical trial information: NCT01757535. [Table: see text]
Predictive phosphoproteomic signatures for midostaurin plus chemotherapy response in FLT3 mutant positive acute myeloid leukaemia.
Authors: Dokal Arran David , Arruda Andrea , Smith Ryan , Greenhalgh Calum , Patella Francesca , Casado-Izquierdo Pedro Maria , Wrench Bela , Theaker Jane , Thompson Andrew , Minden Mark D. , Gribben John G. , Britton David James , Cutillas Pedro Rodriguez 
Published: June 2021

7019 Background: Midostaurin is approved for FLT3 mutant-positive (FLT3+) acute myeloid leukemia (AML), however efficacy has also been observed in a subpopulation of FLT3 mutant-negative AML, suggesting that FLT3 mutation is not the only determinant in conferring midostaurin sensitivity. We previously described a phosphoproteomic signature significantly elevated in primary AML blasts that responded to midostaurin ex vivo (Casado et al Leukaemia 2018). This signature includes phosphorylation sites on protein kinase C delta (a midostaurin off-target) and its substrate GSK3A. In this study, we tested whether these phospho-signatures could group FLT3+ patients based on clinical responses to midostaurin plus chemotherapy. Methods: We obtained FLT3+ bone marrow (BM) and peripheral blood (PB) diagnosis specimens (n=56 cases) from the Leukemia Tissue Bank at Princess Margaret Cancer Centre. These patients were treated with standard chemotherapy plus midostaurin. Phospho-signatures quantified using mass spectrometry were analysed with a classification machine learning algorithm to group patients based on response to treatment as a function of phospho-signature status. Other features (e.g. genetic mutations, HSC-transplant) were also analysed. Differential survival analysis was carried out with Kaplan-Meier and Log Rank test methods. Phospho-signatures for BM and PB samples were analysed independently. Results: A first ML model was developed based on the signature described in the Casado et al study. Patients positive for this signature exhibited a survival probability of 243 weeks, compared to 126 weeks in signature negative patients (averages by geometric mean, Log Rank p = 9.88e-05). As the patients in the current study received chemotherapy, in addition to midostaurin, we also identified a new signature consisting of 26 phospho-sites (model 2), which partially overlapped with the first model. Patients positive for model 2 signature showed a markedly longer survival time than negative patients (269 vs 76 weeks, Log Rank p = 1.30e-05 for PB and 241 vs 56, Log Rank p = 2.13e-09 for BM specimens, Table). No other features separated survival as clearly as model 2. Conclusions: We have identified phospho-signatures with the potential to further stratify FLT3+ AML for midostaurin treatment. The presence of PRKCD signalling components in signatures provides a rationale for midostaurin activity in sensitive cases. Analysis will also be performed on FLT3 mutant-negative cases to validate the signature in this group.[Table: see text]
High dimensional mapping of temporal evolution within the marrow microenvironment in response to FLT3 inhibitor therapy.
Authors: Newman Matthew , Joshi Sunil K. , Bottomly Daniel , McWeeney Shannon , Druker Brian J. , Lind Evan , Traer Elie A. 
Published: June 2021

7020 Background: The advent of genomic sequencing technologies has revealed underlying genetic alterations, such as FLT3 mutations, that can be targeted in acute myeloid leukemia (AML). However, development of resistance limits the durability of response. Recent data has implicated that factors from the bone marrow microenvironment mediate initial resistance to FLT3 inhibitors (FLT3i) in AML. We combined high dimensional characterization techniques, time-of-flight mass cytometry (CyTOF) and RNA sequencing, to examine sequential marrow stromal samples from a subset of patients with FLT3 mutated AML treated with the FLT3i gilteritinib. Here, we report on the heterogeneity and evolution of cell surface and secreted factors over time. Methods: RNA sequencing of primary FLT3-ITD stromal samples (N = 29) from pre-study and on-treatment patients enabled prioritization of candidate targets for CyTOF. Target-specific purified antibodies were purchased pre-conjugated to metal lanthanides or conjugated in house according to manufacturer protocols (after validation via traditional flow cytometry). Primary stromal cells were cultured ex vivo until confluent and were harvested and stained according to a standardized protocol, and subsequently run on a Helios (Fluidigm) mass cytometer. A computational approach was employed to compensate and visualize data via the CATALYST R package. A total of four pre-treatment and four post-gilteritinib timepoint isolates (N = 8) were analyzed. Results: A 36-target mass cytometry panel revealed protein level differences in patients before and after gilteritinib therapy. Dimensional reduction techniques such as MDS and UMAP showed that samples taken from later timepoints clustered together compared to their earlier counterparts with respect to global protein expression. Inflammatory mediators such as IL1-beta and MCP-1 were upregulated in patient stroma soon after gilteritinib treatment and therefore potentially contribute to early resistance. Novel markers previously implicated in early resistance to targeted therapies in AML such as FGF2 and FGFR1 similarly peaked earlier in treatment, mimicking the clinical course of expression observed in marrow stroma of patients treated with another FLT3 inhibitor quizartinib (Traer et al. Cancer Res. 2016). Conclusions: Our findings show that primary marrow stroma evolves during gilteritinib treatment, and that stromal proteins previously reported to promote early resistance to FLT3i are also upregulated during gilteritinib resistance. The heterogeneity of stromal cell isolates detected by mass cytometry highlights the utility of high dimensional tracking of disease course in patients, and may enable a better understanding of how the temporal evolution of the marrow microenvironment contributes to development of resistance to targeted therapies such as gilteritinib and other FLT3i over time.