Mortality In Oncology Patients Research Articles

Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, a novel ferroptosis inhibitor, is a well-described clinical drug widely used. However, its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear. In this study, we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism. A single intraperitoneal injection of DOX (15 mg/kg) was administrated to establish DOX-induced cardiotoxicity. The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe2+ and ROS overload, which resulted in ferroptosis. CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1. Interestingly, idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX. Idebenone could form stable hydrogen bonds with FSP1 protein at K355, which may influence its association with ubiquitin. The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation. In conclusion, this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1, making it a potential clinical drug for patients receiving DOX treatment.

The effect of neutrophil lymphocyte ratio and other biochemical parameters on mortality in cancer patients admitted to the emergency department

Aims: To investigate the effectiveness of the neutrophil/lymphocyte ratio and other biochemical parameters in predicting mortality in oncology patients with cancer admitted to the emergency department. Methods: This was a retrospective, observational, single-center study. The study period included a two-year period from January 2014 to December 2015. Demographic data, cancer history and blood tests, emergency department diagnoses, blood parameters evaluated in the emergency department, discharge, and mortality status of the patients were recorded in the data form. The APACHE 2 and SOFA scores of all patients were also calculated. Patients whose data could not be reached were excluded from the study. p<0.05 was considered statistically significant. Results: A total of 180 patients were included in the study. The mean age of the survivor group was 66.4±10.752 years, while the mean age of the non-survivor group was 65.18±13 years. The mean neutrophil/lymphocyte (NLR) ratio of the non-survivor group was 1.0288±11.3, while the NLR of the survivor group was 4.400±3.563. (p<0.05) The mean lactate ratio of the non-survivor group was 2.60±3.384, while the mean lactate ratio of the survivor group was 1.36±1. 090. (p<0.05) When survivor and non-survivor patient groups were compared, a statistically significant difference was observed in mean white blood cell count, neutrophil count, hemoglobin, hematocrit, and blood urea nitrogen (BUN) values. (p<0.05) Conclusion: According to the results of this study, NLR, elevated white blood cell and neutrophil values, decreased hemoglobin and hematocrit, and elevated BUN and lactate levels seem to be predictors of mortality during emergency admissions in cancer patients.

Molecular technique for precise antibiotics administration in patients with cancer.

e18749 Background: Infectious diseases are the second most common cause of mortality in oncology patients. Multiple hospital admissions and previous exposure to antibiotics are risk factors for infection with microorganisms having antibiotic resistance gene in these patients.Molecular technique helps in targeted antibiotic administration at the earliest. Methods: This was a retrospective observational study over a period of one year from November 2021 to October 2022 in Tata Memorial Hospital, Mumbai, on oncology patients with blood stream infection (BSI) whose blood sample underwent film array assay. The BioFire Blood culture Identification 2 Panel (BCID2) which identifies Imipenemases (IMP), Klebsiella pneumoniae carbapenemases (KPC), New Delhi metallo beta-lactamases (NDM), oxacillinase-48 like (OXA-48), Verona integron-encoded metallo beta-lactamase (VIM), CTX M and methicillin resistance gene like mec A/C was used. BSI was categorised according to the resistance gene and recommended antibiotics of choice as per the Infectious Disease Society of America (IDSA). CTX-M - Carbapenem  OXA-48 like/ KPC - Ceftazidime-avibactam, Polymixin  Metallo beta-lactamase (MBL) i.e VIM, IMP, NDM - Ceftazidime-avibactam plus aztreonam, polymyxin, Cefiderocol  The impact of appropriate antibiotic administration on 30-day mortality was seen. Results: A total of 79 blood samples were submitted for film array assay during the study period. The mean age of the study population was 17± 4 years. 41(51.9%) patients had acute myeloid leukemia (AML), 29 (36.7%) had acute lymphocytic leukemia (ALL), 4 (5%) patients had lymphoma and 5 (6.3%) had other malignancies. 54(68.3%) BSI had microorganism with antibiotic resistance gene, 16 (20.3%) did not carry resistance gene and in 9 (11.4%), microorganism was not identified in film array assay, though conventional culture showed contaminants. Of the 54 BSI with microorganisms having antibiotic resistance gene, 37(68.5%) had MBL gene either alone or along with CTX-M or OXA-48 like genes, 12 (22.2%) had CTX-M and 5 (9.2%) had both CTX-M and OXA -48 like genes. Empirical antibiotic did not match the antibiotic resistance pattern in 40 (74.1%), antibiotic matched the resistance pattern in 14(22.9%). Antibiotic adjustment was done in 32 (86%) of MBL, 4 (80%) of OXA-48 like with CTX-M and 9 (75%) CTX-M. The 30-day mortality was significantly less (28% vs 80%, p = 0.042) in patients who received appropriate antibiotic versus those who continued inappropriate antibiotics in MBL BSI. Conclusions: Majority of the study population had BSI with antibiotic resistance gene and underwent a change in the antibiotic after the assay. There was lesser 30-day mortality in patients who received antibiotics appropriate for the identified resistance gene. Molecular technique is helpful for precise antibiotic administration in cancer patients who have a higher risk of infection with organisms having resistance gene.

734: MORTALITY TREND FROM SEPSIS IN PEDIATRIC ONCOLOGY PATIENTS 2016-2019

Introduction: Sepsis continues to be a major cause of mortality in the pediatric oncologic population, and thus has been the subject of ongoing research. Whether improvements in chemotherapy and other advancements, especially the implementation of pediatric sepsis guidelines with early identification, has affected mortality in the pediatric cancer population is up for debate. We hypothesized that advances in chemotherapy regimens, including the introduction of immunologics, and early early identification of sepsis would decrease deaths in oncologic patients diagnosed with sepsis. Thus we aimed to identify and characterize deaths in oncologic patients who also diagnosed with sepsis. Methods: We analyzed the 2016 and 2019 Kids inpatient database (KID) data and noted the overall percentage of deaths from sepsis. We identified all patient mortalities with an oncologic as well as sepsis diagnostic code. T-test was conducted to find statistical differences between the incidence of deaths in these patients. In addition, we stratified each year into different cancer types and further characterized their demographic characteristics and identified other complications (i.e. if they developed acute renal failure) during their hospital stay. Results: In 2016, of the 1021 deaths in patients with an oncologic diagnosis, 264 (26%) had a sepsis diagnostic code. In 2019, there were 955 pediatric patients with oncologic diagnoses who died, and of those 230 (24%) had a sepsis diagnostic code. T-test revealed no statistical significance between both incidences of deaths with a P value 0.5. In both 2016 and 2019, most oncologic patients who died with a sepsis diagnosis had some form of leukemia, 59% in 2019 and 60% in 2016. Conclusions: With the stagnant mortality numbers over three years, more attention must be made to understanding and treating sepsis in this group. Are specific chemotherapies more likely to predispose certain groups to sepsis? Also, regardless of its high prevalence, the high proportion of leukemic patients does warrant further investigation. Specifically, what features of their immunologic response to infection and their chemotherapy regimens predispose them to mortality from sepsis. With the stagnation of mortality in oncologic patients from sepsis, further attention must be placed on this high-risk group.

Determinants of mortality in cancer patients with unscheduled admission to the Intensive Care Unit: A prospective multicenter study

ObjectivesTo analyze clinical features associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies. DesignAn observational study was carried out. SettingA total of 123 Intensive Care Units across Spain. PatientsAll cancer patients with unscheduled admission due to acute illness related to the background oncological disease. InterventionsNone. Main variablesDemographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed. ResultsA total of 482 patients were included: solid cancer (n=311) and hematological malignancy (n=171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064–1.143), medical admission (OR 3.587; 95% CI 1.327–9.701), lung cancer (OR 2.98; 95% CI 1.48–5.99) and mechanical ventilation after the first 24h of ICU stay (OR 2.27; 95% CI 1.09–4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09–0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as a protective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups. ConclusionsThe risk factors associated to mortality did not differ significantly between patients with solid cancers and those with hematological malignancies. Delayed intubation in patients requiring mechanical ventilation might be associated to ICU mortality.

Inpatient primary prophylaxis of cancer-associated thromboembolism (CAT)

Cancer-associated thrombosis (CAT) increases morbidity and mortality in oncology patients. The risk of CAT is increased with hospitalization for acute medical illness. The goal of this review will be to examine the available evidence for (1) risk assessment and (2) primary thromboprophylaxis, (3) international published guideline recommendations, and (4) future directions to manage oncology patients admitted for an acute medical illness. A review was performed for each subject to gather information on the available evidence and recommendations available for oncology patients hospitalized for an acute medical illness. Risk assessments for thrombosis are primarily developed and validated in the general population. There is not a risk assessment that has specifically been developed and validated in oncology patients hospitalized for an acute medical illness. Most evidence for thromboprophylaxis of oncology patients is from sub-group analysis of larger randomized-controlled trials in the general population. Evidence is conflicting and suggests an individualized approach evaluating the risk-benefit of thromboprophylaxis. The strength of recommendations of international guidelines is limited because of the available evidence. Guidelines usually recommend utilizing and/or offering thromboprophylaxis to oncology patients hospitalized for an acute medical illness barring contraindications. Future evidence needs to improve risk assessments and knowledge of the appropriate agent, dose, and duration of thromboprophylaxis if indicated. Evidence for risk assessments and primary prophylaxis for oncology patients hospitalized for acute medical illness appears limited, with many research opportunities available to improve understanding on management of this patient population.

Platelet-Lymphocyte Ratio, Circulating Tumor Cells and Circulating Tumor Microemboli as Predictors of Thrombosis in Patients with Gastric Cancer

Background: Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology patients. There are no accurate risk assessment tools to predict venous thromboembolism (VTE). Circulating tumor cells (CTCs), circulating tumor microemboli (CTM), and high platelet-lymphocyte ratio (PLR) may predispose to VTE. Objective: To evaluate correlations of CTCs, CTM, and PLR with VTE and progression-free survival (PFS) in gastric cancer patients. Methods: Patients with gastric cancer were recruited (March 2016 to April 2017). CTCs were assayed by ISET at two timepoints: before neoadjuvant treatment (CTC1) and after surgery/before adjuvant therapy (CTC2) for patients with localized disease, and before first-line chemotherapy (CTC1) and after 6 months (CTC2) for patients with metastases. VTE incidence was determined retrospectively. PFS was estimated by Kaplan-Meier analysis. Results: We studied 93 patients. According to Khorana scores, 63 (67.7%) patients were at intermediate and 30 (32.3%) were at high risk for VTE. VTE incidence was 20.4% and CTM were found in 39.8%. VTE developed in 7/37 (18.9%) CTM-positive and in 11/50 (22%) CTM-negative patients (p=0.93). When PLR >288, VTE occurred in 7/14 patients (p=0.005). PLR also associated with poor PFS (p<0.0001). CTC2 was associated with poor PFS (p<0.0001). CTC2, PLR and VTE were independent prognostic factors for PFS (p=0.005, 0.043, and <0.0001 respectively). Conclusion: PLR is a prognostic indicator for PFS and for VTE in gastric cancer. Neither CTC, nor CTM improved risk stratification for VTE in our population.

Factors associated with non-invasive ventilation failure and mortality in oncologic patients outside the intensive care unit

Introduction: New treatments have been introduced with the objective to increase the survival rate of oncologic patients. As a result of these approaches, there was an increase in the number of cases of toxicity and complications, which can lead to acute respiratory failure (ARF). One of the most frequent ways to treat ARF is non-invasive ventilation (NIV). Despite the proven benefits in several clinical conditions, NIV results in cancer patients are controversial. Objective: To evaluate risk factors associated with NIV failure and hospital mortality in oncologic patients. Methods: Retrospective cohort study including patients with solid tumors and hematological neoplasms admitted for hospitalization at National Cancer Institute between January 1, 2017 and December 31, 2019, who underwent NIV. The association between the variables of exposure and the outcome was performed by gross and adjusted logistic regression. The Kaplan-Meier method was used to analyze the length of hospital stay. Results: Sixty-three patients who underwent NIV in hospitalization were evaluated, and 26 failed NIV. The patients had a mean age of 58.5 years (±15.6), most were male (57.1%), under 60 years old (58.7%) and had comorbidities (55.5%). The patients with pulmonary infection (OR 6.53; 95% CI 1.21-35.12; p=0.02) had a higher risk of failure in NIV. In relation to hospital mortality, patients older than 60 years (OR 6.90; 95% CI, 2.12-22.45; p=0.001) had a higher risk. Conclusion: Patients who presented pulmonary infection were more likely to fail in NIV. Higher hospital mortality was observed among elderly patients.

Delays in time to antibiotics in inpatient oncologic neutropenic fever do not predict decreased overall survival.

e18765 Background: Neutropenic fever (NF) is relatively common oncologic emergency. Present expert consensus is that anti-pseudomonas gram-negative antibiotics should be administered within 60 minutes of detecting NF. To date studies investigating this relationship in neutropenic fever patients have been either limited in size, or have failed to reliably establish a relationship between time to antibiotics (TTA) and clinical outcomes.While some studies have shown an association between TTA and outcomes in NF patients admitted from the Emergency Department, such studies do not control for the time that patients may have been febrile in the community. To address these factors, we conducted a retrospective study on the effect of TTA on mortality in oncologic patients who developed NF as inpatients. Methods: We performed retrospective chart review of all cases of NF at an NCI designated Cancer Center between 7/1/2016 and 3/27/2019. NF was defined as temperature of 101˚ F on one occasion, or 100.4˚ F sustained over 60 minutes, with an absolute neutrophil count (ANC) less than 500. TTA and survival were calculated via chart abstraction; patients lost to follow up within 180 days were censored to the 180-day mortality group. Relationship between TTA and overall survival (OS) was analyzed via multivariable Cox regression. We excluded patients that had non-cancer related NF, were transferred from another institution with NF, were admitted from the ED with NF, or transitioned to hospice. Only the first instance of NF in any admission was analyzed. Results: A total of 187 eligible cases were identified during the study period, mean age was 57.6 +/- 13.6, 100 (53.5%) cases were in males, 114 (61.0%) cases in Caucasians, 53 (28.3%) in Black People. The 3 most common disease subtypes were acute leukemia (42.8%), plasma cell dyscrasias (27.8%), and lymphoma (16.6%). TTA showed no significant correlation with OS at any timeframe studied. Low Charlson Comorbidity Index ( < 3) correlated with increased survival through ̃360 days, however the effect was non-significant at longer timeframes. Immediate antibiotic treatment ( < 40 mins) correlated with poorer patient prognosis and significantly decreased OS (HR 3.08;CI: 1.30-7.28; p 0.010). Conclusions: TTA was not associated with OS in our study. For inpatients with NF, even hours long TTA may not be long enough to result in adverse clinical outcomes. Unlike NF patients presenting to the ED, where true TTA may often be many hours or even days prior to arrival, a few hours-long TTA in the hospital may not be sufficiently long enough to cause significant patient harm. Interestingly, in our cohort, those who received antibiotics quickly had adverse outcomes. It may be that in patients who were clinically unstable, TTA was shorter given the urgency of the situation. Ultimately, this study’s findings question the applicability of the 60-minute guideline when used in the inpatient setting.

Nanoformulations for Delivery of Pentacyclic Triterpenoids in Anticancer Therapies.

The search for safe and effective anticancer therapies is one of the major challenges of the 21st century. The ineffective treatment of cancers, classified as civilization diseases, contributes to a decreased quality of life, health loss, and premature mortality in oncological patients. Many natural phytochemicals have anticancer potential. Pentacyclic triterpenoids, characterized by six- and five-membered ring structures, are one of the largest class of natural metabolites sourced from the plant kingdom. Among the known natural triterpenoids, we can distinguish lupane-, oleanane-, and ursane-types. Pentacyclic triterpenoids are known to have many biological activities, e.g., anti-inflammatory, antibacterial, hepatoprotective, immunomodulatory, antioxidant, and anticancer properties. Unfortunately, they are also characterized by poor water solubility and, hence, low bioavailability. These pharmacological properties may be improved by both introducing some modifications to their native structures and developing novel delivery systems based on the latest nanotechnological achievements. The development of nanocarrier-delivery systems is aimed at increasing the transport capacity of bioactive compounds by enhancing their solubility, bioavailability, stability in vivo and ensuring tumor-targeting while their toxicity and risk of side effects are significantly reduced. Nanocarriers may vary in sizes, constituents, shapes, and surface properties, all of which affect the ultimate efficacy and safety of a given anticancer therapy, as presented in this review. The presented results demonstrate the high antitumor potential of systems for delivery of pentacyclic triterpenoids.

Acute kidney injury as a risk factor for mortality in oncological patients receiving checkpoint inhibitors.

Checkpoint inhibitors (CPIs) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated with multiple toxicities, including acute kidney injury (AKI). Data about CPI-related AKI are limited. Our aim was to determine risk factors for CPI-related AKI as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. All patients under CPI at our centre between March 2018 and May 2019 and with a follow-up through April 2020 were included. Demographic, clinical and laboratory data were collected. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. A total of 759 patients were included, with a median age of 64 years. A total of 59% were men and baseline median creatinine was 0.80 mg/dL. The most frequent malignancy was lung cancer and 56% were receiving anti-programmed death protein 1 (PD-1). About 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for CPI-related AKI. At the end of follow-up, 52.3% of patients had died. The type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not cytotoxic T-lymphocyte-associated protein 4, PD-1, programmed death-ligand 1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. A total of 15.5% of patients under immunotherapy presented with AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risk factors for the development of AKI.

Evaluating Initial Empiric Therapy for Neutropenic Fever in Vancomycin-Resistant Enterococcus-Colonized Patients.

ObjectivesVancomycin-resistant enterococcus infections impact mortality in oncology patients. Given the low rate of vancomycin-resistant enterococcus bacteremia, low virulence of vancomycin-resistant enterococcus, and advent of rapid diagnostic systems, vancomycin-resistant enterococcus-directed empiric therapy in vancomycin-resistant enterococcus-colonized patients with neutropenic fever may be unnecessary, promoting increased antimicrobial resistance, drug-related toxicity, and cost.MethodsVancomycin-resistant enterococcus-colonized adults admitted for hematopoietic stem cell transplantation or induction therapy for acute leukemia/myeloid sarcoma with neutropenic fever were stratified by vancomycin-resistant enterococcus bacteremia development and empiric vancomycin-resistant enterococcus-directed antimicrobial strategy for first neutropenic fever (Empiric Therapy vs. non-Empiric Therapy). Primary endpoints included vancomycin-resistant enterococcus-related, in-hospital, and 100-day mortality rates. Secondary outcomes included vancomycin-resistant enterococcus bacteremia incidence for first neutropenic fever and the entire hospitalization, length of stay, Clostridioides difficile infection rate, and duration and cost of vancomycin-resistant enterococcus-directed therapy.ResultsDuring first neutropenic fever, 3 of 70 eligible patients (4%) developed vancomycin-resistant enterococcus bacteremia. Although all 3 (100%) were non-Empiric Therapy, no mortality (0%) occurred. Of 67 patients not developing vancomycin-resistant enterococcus bacteremia, 42 (63%) received Empiric Therapy and 25 (37%) non-Empiric Therapy. Empiric Therapy had significantly greater median duration (3 days vs. 0 days; P<.001) and cost ($1604 vs. $0; P<.001) of vancomycin-resistant enterococcus-directed therapy but demonstrated no significant differences in clinical outcomes.ConclusionAvailable data suggest Empiric Therapy may offer no clinical benefit to this population, regardless of whether vancomycin-resistant enterococcus is identified in blood culture or no pathogen is found. Such an approach may only expose the majority of patients to unnecessary vancomycin-resistant enterococcus-directed therapy and drug-related toxicities while increasing institutional drug and monitoring costs. Even in the few patients developing vancomycin-resistant enterococcus bacteremia, waiting until the organism is identified in culture to start directed therapy likely makes no difference in mortality. This lack of benefit warrants consideration to potentially omit empiric vancomycin-resistant enterococcus-directed therapy in first neutropenic fever in many of these patients.

Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prominent cause of nosocomial infections associated with high rates of morbidity and mortality, particularly in oncological patients. The hypermucoviscous (HMV) phenotype and biofilm production are key factors for CRKP colonization and persistence in the host. This study aims at exploring the impact of CRKP virulence factors on morbidity and mortality in oncological patients. A total of 86 CRKP were collected between January 2015 and December 2019. Carbapenem resistance-associated genes, antibiotic susceptibility, the HMV phenotype, and biofilm production were evaluated. The median age of the patients was 71 years (range 40–96 years). Clinically infected patients were 53 (61.6%), while CRKP colonized individuals were 33 (38.4%). The most common infectious manifestations were sepsis (43.4%) and pneumonia (18.9%), while rectal surveillance swabs were the most common site of CRKP isolation (81.8%) in colonized patients. The leading mechanism of carbapenem resistance was sustained by the KPC gene (96.5%), followed by OXA-48 (2.3%) and VIM (1.2%). Phenotypic CRKP characterization indicated that 55.8% of the isolates were strong biofilm-producers equally distributed between infected (54.2%) and colonized (45.8%) patients. The HMV phenotype was found in 22.1% of the isolates, which showed a significant (P<0.0001) decrease in biofilm production as compared to non-HMV strains. The overall mortality rate calculated on the group of infected patients was 35.8%. In univariate analysis, pneumoniae significantly correlated with death (OR 5.09; CI 95% 1.08–24.02; P=0.04). The non-HMV phenotype (OR 4.67; CI 95% 1.13–19.24; P=0.03) and strong biofilm-producing strains (OR 5.04; CI95% 1.39–18.25; P=0.01) were also associated with increased CRKP infection-related mortality. Notably, the multivariate analysis showed that infection with strong biofilm-producing CRKP was an independent predictor of mortality (OR 6.30; CI 95% 1.392–18.248; P=0.004). CRKP infection presents a high risk of death among oncological patients, particularly when pneumoniae and sepsis are present. In infected patients, the presence of strong biofilm-producing CRKP significantly increases the risk of death. Thus, the assessment of biofilm production may provide a key element in supporting the clinical management of high-risk oncological patients with CRKP infection.

Prediction of COVID-19 Mortality in Patients with Cancer

Background: Coronavirus disease 2019 (COVID-19) is associated with an increased mortality rate in patients with cancer. Machine learning approaches have been used successfully to predict mortality in infected patients from the general population. We aimed to devise an algorithm to estimate the risk of death in the first 45 days after COVID-19 diagnosis for patients with cancer.Methods: As a first step we used the ensemble learning method random survival forests. Computations were performed with R packages randomForestSRC, ROCR and cvAUC. The cohort consisted of Memorial Sloan Kettering patients diagnosed with COVID-19 before June 12, 2020 (n=820). The primary endpoint was mortality at 45 days after diagnosis of COVID-19. Patients were included in the study regardless of whether or not they were admitted to the hospital. Predictors assessed at the time of COVID-19 diagnosis and retained for the model include: cancer type (thoracic, hematologic or other), metastatic status, age, sex, smoking, presence of a comorbidity (any of hypertension, diabetes, hyperlipidemia, chronic hepatic or renal disease, coronary artery disease, asthma, thromboembolism, chronic obstructive lung disease, congestive heart failure, valvular heart disease, stroke, HIV and peripheral arterial disease), body mass index (BMI), presence of hypoxia (defined as need to use supplemental oxygen 2 L/min or more), blood glucose, total bilirubin, total white blood count (WBC), hemoglobin, red cell distribution width (RDW), platelet count, absolute neutrophil count (ANC), absolute lymphocyte count, serum albumin, blood urea nitrogen (BUN) , creatinine, aspartate transaminase (AST), alanine transaminase (ALT), ferritin, lactate dehydrogenase (LDH), prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimers, race and smoking history. Model performance was assessed with repeated 10-fold cross-validation.Results: 11% (n=91) of patients had died by day #45 of observation. The prevalence of hematologic malignancy in the cohort at large was 26% (n=210), compared with 9% (n=74) for primary thoracic neoplasms. Metastatic solid cancer was present in 40% (n=332) of individuals. Information on cell counts and RDW was complete for 51% of patients, compared to 43% for liver function tests, 54% for renal function measurements, 23% for PT, 22% for PTT and 7% for D-dimers. Records were manually reviewed and assessed successfully in all patients for cancer type, metastatic status, presence of a comorbidity, presence of hypoxia and smoking history. Only 23% of patients were admitted at the time of COVID-19 diagnosis. The mean cross-validated area under the receiver operating characteristic (ROC) curve for a model including all available covariates was 0.81 (95% confidence interval = 0.80-0.82). The averaged ROC curve is shown in Figure A. Comorbidities, BUN, serum albumin, age, hypoxia, cancer type, RDW, hemoglobin, platelet count, metastatic status and smoking history all contributed significantly to the model, as measured with the Ishwaran-Kogalur Variable Importance (VIMP). Scaled VIMP values are reported in Figure B.Conclusions: COVID-19 is associated with substantial mortality in patients with cancer. As observed in prior reports of patients from the general population, the presence of comorbidities, age, BUN and hypoxia at presentation are highly predictive of mortality in this setting. Interestingly, serum albumin appears to be an important predictor in patients with cancer, as are cancer-specific covariates including tumor type and metastatic status. The latter suggests that optimal predictive models of COVID-19 mortality in oncology patients will differ substantially from those trained on more general medical cohorts. Additional work remains to be done in order to validate this model before its application in clinical practice.DisclosuresMantha:MJH Associates: Honoraria; Physicians Education Resource: Honoraria. Jee:MDSeq Inc.: Patents & Royalties. Soff:Bristol-Myers Squibb, Pfizer: Honoraria; Dova Pharmaceuticals: Research Funding; Amgen: Research Funding; Janssen Scientific Affairs: Research Funding; Dova Pharmaceuticals: Honoraria; Janssen Scientific Affairs: Honoraria; Amgen: Honoraria.

Impact of timing of atrial fibrillation, CHA2DS2-VASc score and cancer therapeutics on mortality in oncology patients

ObjectivesTo investigate timing and age distribution of atrial fibrillation (AF) in selected oncology patients, and the impact of AF timing, CHA2DS2-VASc score and cancer therapeutics on mortality.MethodsThis is a retrospective...

AKI as a Risk Factor for Mortality in Oncological Patients Receiving Immunotherapy

AKI as a Risk Factor for Mortality in Oncological Patients Receiving Immunotherapy

Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness.

The theory of cancer stem cells (CSCs) proposes that the different cells within a tumor, as well as metastasis deriving from it, are originated from a single subpopulation of cells with self-renewal and differentiation capacities. These cancer stem cells are supposed to be critical for tumor expansion and metastasis, tumor relapse and resistance to conventional therapies, such as chemo- and radiotherapy. The acquisition of these abilities has been attributed to the activation of alternative pathways, for instance, WNT, NOTCH, SHH, PI3K, Hippo, or NF-κB pathways, that regulate detoxification mechanisms; increase the metabolic rate; induce resistance to apoptotic, autophagic, and senescence pathways; promote the overexpression of drug transporter proteins; and activate specific stem cell transcription factors. The elimination of CSCs is an important goal in cancer therapeutic approaches because it could decrease relapses and metastatic dissemination, which are main causes of mortality in oncology patients. In this work, we discuss the role of these signaling pathways in CSCs along with their therapeutic potential.

265. Clinical Epidemiology of Invasive Fungal Infection with Aspergillus and Mucor Species in a Tertiary Children’s Hospital

BackgroundPatients undergoing hematopoietic stem cell transplantation and patients with hematologic malignancies are at increased risk for acquiring invasive fungal infection (IFI) due to immune system impairment from chemotherapy. Affected patients require prolonged antifungal therapy with the risk of associated toxicity and extended hospitalization due to delay of accurate diagnosis. There is a lack of effective serologic biomarkers and hesitancy to proceed with tissue diagnosis due to thrombocytopenia or other associated risks. Mortality in oncology patients with invasive mycoses is high, with pediatric mortality rates of 30–40% at 12 weeks following diagnosis.MethodsAll patients that were admitted to Lurie Children’s Hospital between January 2014 and December 2018 and received voriconazole, ambisome, posaconazole and isavuconazole were identified. The following data were retrospectively collected: CT chest and sinus, (1,3)-β-d-Glucan and Aspergillus galactomannan, ANC and ALC at diagnosis, blood next-generation sequencing, tissue 18s rRNA, fungal culture, duration of neutropenia and lymphopenia, site of infection, time between underlying diagnosis and development of IFI, surgical intervention and associated mortality.ResultsA total of 94 unique patients that received voriconazole were identified. There were 8 proven cases of invasive Aspergillus infection the past 5 years, 50% male, mean age 14 years. Only 25% of patients had positive serum Aspergillus galactomannan and 37.5% had positive β-d-Glucan. Seven cases were due to Aspergillus fumigatus and one case was due to Aspergillus flavus. There were 9 patients with mucormycosis and all but one were culture positive. Three patients with Mucor had mold identification in blood next-generation sequencing prior to surgery. Mucor associated mortality was 22.2%.ConclusionThe majority of pediatric patients with invasive aspergillosis did not have characteristic chest CT imaging findings and serum Aspergillus galactomannan was usually negative.The was no associated mortality in invasive Aspergillus cases, whereas the mortality rate of invasive mucormycosis was 22.2%. Although we have a small sample size, this is significantly lower compared with published literature.Disclosures All authors: No reported disclosures.

THORACIC RADIOTHERAPY AS A RISK FACTOR FOR HEART ISCHEMIA IN SUBJECTS WITH CHEST IRRADIATION AND WITHOUT CLASSIC CARDIOVASCULAR RISK FACTORS

Objective:Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in augmenting mortality in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of coronary heart disease (CAD), a cardiological scre

Impact of cardiovascular comorbidities on mortality in patients admitted for neutropenic fever in 2016.

6586 Background: Neutropenic fever (NF) remains one of the most common causes for hospitalization and mortality in oncology patients. Concomitant cardiovascular disease in patients with cancer is not uncommon. There is limited data on the impact of cardiovascular (CVS) comorbidities on mortality in cancer patients with NF. Methods: This is a retrospective cohort study using the 2016 National Inpatient Sample database (NIS) of adults ( &gt; 18 years) admitted for NF based on the ICD-10 code. Mortality was the primary outcome. Multivariate linear regression adjusted for potential confounder of age, sex, race, Charlson comorbidity index and all the CVS comorbidities of the study including atrial fibrillation (AF), heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), coronary artery disease (CAD), peripheral vascular disease (PVD), hypertension (HTN), history of smoking, history of cerebrovascular accident (CVA) or TIA and dyslipidemia. STATA 15 was used for analysis. Results: We identified 31,310 patients (mean age 44.6) (49.6% females) admitted with NF, among which 250 died during same admission. On multivariate linear regression there was a significant increase in adjusted all-cause mortality in patients with AF (OR: 2.39; 95%-CI 1.06- 5.40, P = 0.035) and HFpEF (OR: 4.30; 95%-CI 1.08- 17.17, P = 0.039). There was no significant increase in mortality in patients with HFrEF, dyslipidemia, HTN, PVD, CAD, history of CVA/TIA and smoking. Conclusions: Patients with NF and concomitant history of AF or HFpEF have an increased risk of mortality during hospitalization. Inflammation is emerging as a key player in AF pathogenesis. This may explain why AF appears to correlate with mortality, as those with more severe presentations are more likely to have a heightened state of inflammation. Patients with NF are more likely to receive fluids in the setting of infectious complications which could explain the increased mortality in CHF patients with NF. Identifying risk factors for increased mortality in patients with NF is important for risk stratification and in guiding clinicians in the management of this delicate population. [Table: see text]