Chemotherapy-associated Febrile Neutropenia Research Articles

2153P Circulating biomarkers to predict severe complications in cancer patients with low-risk chemotherapy-associated febrile neutropenia

2153P Circulating biomarkers to predict severe complications in cancer patients with low-risk chemotherapy-associated febrile neutropenia

Pharmacokinetics of Vancomycin among Patients with Chemotherapy-Associated Febrile Neutropenia: Which Would Be the Best Dosing to Obtain Appropriate Exposure?

Previous research has determined that the required doses for treating febrile neutropenia with vancomycin are higher than the doses used conventionally. These recommendations have been made considering pharmacotherapeutic goals based on minimum concentration (Cmin) between 15-20 mg/L. This study was developed to evaluate dose recommendations based on the achievement of a target consisting of ratio of area under the curve over minimum inhibitory concentration (AUC24h/MIC) ≥400 in this population of individuals. This study was conducted in a referral hospital for cancer treatment, study participants received vancomycin doses of 1g every 12 h in 2-4-h infusions. Vancomycin was described by a two-compartment pharmacokinetic model with clearance dependent on the estimated glomerular filtration rate. Simulations were performed taking into account a reduced version of the model to establish the influence of controllable and non-controllable variables on the probability of achieving several PK-PD targets. A dose of 2.5g/day in patients with estimated glomerular filtration rate (eGFR) between 80 and 122mL/min/1.73m2 was adequate to achieve the pharmacotherapeutic target. A discrepancy was found between AUC-based and Cmin-based PK/PD indices, the former being affected by the dose and creatinine clearance while the latter highly influenced by the interval between doses.

Granulocyte colony-stimulating factor-associated aortitis in a woman with breast cancer: a case report

BackgroundGranulocyte colony-stimulating factor (G-CSF) is increasingly used to prevent chemotherapy-associated febrile neutropenia. Generally, aortitis is not considered a side effect of G-CSF and is thought to be extremely rare. Aortitis is an inflammation of the aorta and occurs mainly in connective tissue diseases (Takayasu arteritis, giant cell arteritis, etc.) and infectious diseases (bacterial endocarditis, syphilis, etc.). We report herein a rare case of G-CSF associated with aortitis in a woman with breast cancer.Case presentationHere, we present a case involving a 63-year-old woman with luminal type stage IIa breast cancer. The patient’s treatment was initiated with docetaxel and cyclophosphamide, with pegfilgrastim (PEG-G) as support. After PEG-G administration on day 3, the patient developed an intermittent fever of up to 39.4 °C on day 10 and visited our outpatient clinic on day 13 with persistent high fever. Laboratory tests revealed a high neutrophil count (14,000/μL) and a high C-reactive protein (CRP) level (42.8 mg/dL) without any other abnormalities. Contrast-enhanced computed tomography scanning revealed soft tissue thickening with weak enhancement around the wall of the thoraco-abdominal aorta, aortic arch and left subclavian artery. The patient did not respond to antimicrobial agents. On the basis of these observations, the patient was diagnosed with PEG-G-induced aortitis, and her condition rapidly improved without corticosteroids.ConclusionsClinicians should be aware of aortitis as a potential complication in patients undergoing G-CSF chemotherapy. In cases with persistent high fever after PEG-G administration, and in the absence of infection, aortitis should be suspected.

Application of veno-venous extracorporeal membrane oxygenation in lymphoma patients with severe acute respiratory distress syndrome

Aim: To report the clinical courses of two patients, one with Hodgkin’s lymphoma (HL) and one with Non-Hodgkin’s lymphoma (NHL), who developed severe refractory acute respiratory distress syndrome (ARDS) and were treated with veno-venous extracorporeal membrane oxygenation (VV ECMO). Case report: Both patients developed chemotherapy-associated febrile neutropenia followed by pneumonia and ARDS, after which they were transferred to the intensive care unit. Their respiratory failure deteriorated despite endotracheal intubation with protective mechanical ventilation, at which point a decision for VV ECMO initiation was made. Both patients had complicated treatment courses and developed severe ECMO-associated complications. The most important complications of ECMO support in our HL patient were cardiac arrest; right atrial laceration with pericardial tamponade which needed surgical treatment; right leg ischemia which required transfemoral amputation; thrombosis within the membrane oxygenator; several septic episodes with severe hemodynamic instability; and right sided tension pneumothorax. Despite all difficulties, the patient was successfully weaned from ECMO. Unfortunately, he died prior to hospital discharge as a result of sepsis with multiple organ failure. The most significant ECMO-induced complications in our NHL patient were severe bleeding incidents, most notably diffuse oropharyngeal and continuous bilateral pulmonary hemorrhage; superimposed bacterial pneumonia; extensive pneumomediastinum and subcutaneous emphysema. Despite all therapeutic efforts, the patient died during ECMO treatment because of respiratory decompensation. Conclusions: The patients with hematologic malignancies (HMs) undergoing ECMO support have poor outcomes, with high rates of severe ECMO-induced complications. Further studies focusing on patient selection and issues concerning prevention, diagnosis and treatment of ECMO-associated complications are needed.

Adjuvant chemotherapy-associated febrile neutropenia in a patient with breast malignancy: A case report

Adjuvant chemotherapy has been widely applied in patients with breast malignancy after surgery to prevent its recurrence and to improve survival comprehensively. Febrile neutropenia is one of the most life-threatening chemotherapy-associated toxicities. A 66 years old woman came to an emergency department of a secondary healthcare facility one week after her final chemotherapy with dose regimen of docetaxel and epirubicin, followed by having nausea, vomitus, and general fatigue with a fever of 38.2°C. Based on her medical record, she had experienced breast malignancy for almost two years and had already conducted mastectomy three months after her diagnosis. Her leukocyte number was only 300 cells per mm3, with 23% neutrophil, hypoalbuminemia, and hypokalaemia. She was then treated in an internal ward and was given intravenous ceftazidime, fluid, granulocyte colony-stimulating factor, albumin transfusion, intravenous potassium replacement, and symptomatic medication. After two days of inpatient care, she was referred to an oncology team in a tertiary healthcare facility. Febrile neutropenia is considered as a fever with a low neutrophil number as a result of bone marrow suppression. The neutrophil plays an essential role as the body’s first line of defence. This condition could make the patient more vulnerable to infections. The Patient was given broad-spectrum antibiotics and typically hospitalized to allow close monitoring until the neutropenia was resolved. Febrile neutropenia possesses a serious threat to patients with breast malignancy who are on cytotoxic chemotherapy. Urgent full blood count and immediate broad-spectrum antibiotic administration are significant to reduce morbidity and mortality.

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department.

IntroductionCancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score.Materials and methodsData were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively.ResultsA serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively.ConclusionA single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

Integrative omics to detect bacteremia in patients with febrile neutropenia.

BackgroundCancer chemotherapy-associated febrile neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients.MethodsWe classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors.ResultsFor metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed.ConclusionsClassifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development.

Outpatient management of febrile neutropenia associated with cancer chemotherapy: risk stratification and treatment review.

Strategies for the management of chemotherapy-induced febrile neutropenia (FN), including assessment tools for determining which patients are at low risk for FN complications and can be treated in the outpatient setting, are discussed. Due to the potential for life-threatening complications, the development of FN in patients receiving cancer chemotherapy traditionally prompted hospitalization and i.v. antimicrobial therapy, but there is convincing published evidence that an identifiable subset of patients can be safely treated as outpatients. Two validated assessment tools recommended for identifying patients at low risk for FN complications are the Talcott classification system and the Multinational Association for Supportive Care in Cancer (MASCC) risk index; the MASCC index is superior in terms of sensitivity and negative predictive value but has lower specificity. In low-risk FN cases, outpatient oral antimicrobial therapy has been shown to be a safe and effective alternative to i.v. therapy for both inpatients and outpatients; current practice guidelines recommend an oral fluoroquinolone (e.g., ciprofloxacin) in combination with oral amoxicillin-clavulanate. The guidelines emphasize that in certain cases of FN (e.g., those involving prolonged or pronounced neutropenia or serious comorbidities), inpatient i.v. therapy is required. Pharmacists can play an important role in the management of chemotherapy-associated FN through involvement in risk assessment to identify candidates for outpatient oral antimicrobial therapy, selection of appropriate pharmacotherapy, drug therapy monitoring, and development of institutional guidelines or pathways.

P1-21-4 - Acute Myeloid Leukemia with Extensive Bone Marrow Necrosis

Background: Bone marrow necrosis, a rare condition, characterized by necrosis of the medullary stroma and myeloid tissues of the bone marrow. The etiology is diverse, including hematopoietic malignancies.Case report: A 54-year-old male arrived by ambulance with collapse and high fever. On clinical examination, he had numerous petechiae and ecchymoses in the mouth and on the limbs. Laboratory findings revealed anemia and thrombocytopenia (WBC 15,140/μl, Hb 4.7g/dl, Plt 3.8X104/μl). A blood culture was positive for Staphylococcus aureus, diagnosed as septic shock, complicated by disseminated intravascular coagulation (DIC). When his medical condition was improved after treatment, blood examination showed pancytopenia (WBC 2,170/μl, blast 1.5%, Hb 9.2g/dl, Plt 1.1X104/μl). Multiple bone marrow aspiration displayed only small amount of the cells, which were difficult to be classified and were negative for peroxidase. Bone marrow biopsy showed marked bone marrow necrosis. During being treated for DIC, the abnormal cells were appeared in the peripheral blood, which were analyzed by flow cytometry and cytogenetics and eventually he was diagnosed as AML (M0, FAB classification). The sudden appearance of consolidation in the lungs by chest X-ray indicated leukemic cells infiltration into the lungs. His physical status was allowed chemotherapy consisting of cytarabine and aclarubicin only for the first four days of the standard protocol. Laboratory findings were improved, however, he suffered from repeated hemoptysis. Thoracic CT scan demonstrated diffuse alveolar damage and possible pneumonia. Despite of supportive treatment, his condition was complicated with chemotherapy associated-febrile neutropenia and he expired four weeks after admission.Conclusion: Bone marrow necrosis prognosis is related to underlying diseases and is generally poor. Therefore, multiple bone marrow aspirations and biopsies are needed to achieve appropriate diagnosis.

Impairment of thrombin generation in the early phases of the host response of sepsis

PurposeThe purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock. Material and MethodsTwenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis. ResultsThe rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis. ConclusionsPatients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not necessarily translate into a clinically relevant systemic hypercoagulable state. These findings could help explain why treatment with systemic anticoagulants did not translate to clinical benefits in human sepsis and highlight the need for a better understanding of the hemostatic alterations in sepsis before new treatments targeting coagulation activation are developed.

Pegfilgrastim prophylaxis in patients at different levels of risk for chemotherapy-associated febrile neutropenia: an observational study

Background:Guidelines for using granulocyte colony-stimulating factor (G-CSF) in patients receiving chemotherapies with 10–20% (intermediate) risk for febrile neutropenia (FN) recommend additional assessment of patient-related FN risk factors.Objective:The current study evaluated adherence to guideline recommendations and analysed modalities of pegfilgrastim use.Methods:Adult cancer patients scheduled to receive a chemotherapy regimen assessed by the investigators as intermediate FN risk and who received pegfilgrastim were prospectively enrolled in this observational study from 2007–2010. Risk factors at study entry, treatment modalities and FN assessment were documented by investigators, whereas guideline adherence was centrally checked in a post-hoc analysis, according to guideline categorizations.Results:Thirty-seven centres enrolled 335 evaluable patients with solid and hematologic neoplasias. Although physicians initially rated the FN risk of all chemotherapies as intermediate, after central re-assessment this applied only to 63.9% of regimens; 21.2% were reassessed as low risk and 14.9% as high risk. Pegfilgrastim was used as primary prophylaxis in 80.3% of all patients. The most frequent FN risk factors considered by physicians when deciding to use pegfilgrastim were female gender, advanced disease, age ≥65 years, and anaemia. FN incidence was higher in patients with ≥4 FN risk factors than those with <4 risk factors (10% vs. 4.3%; p = 0.055) and in patients with severe comorbidity than those without (13.6% vs. 4.5%; p = 0.014). Overall FN rate was 5.7%.Limitations:Due to the observational design of the study, findings are descriptive in nature. Post-hoc assessment of chemotherapy FN risk was determined by author’s opinion in some cases.Conclusions:Overall, there was good adherence of Austrian physicians to guideline recommendations; however, there are chemotherapy regimens and clinical settings in which FN risk assignment is unclear in the literature. FN incidence with pegfilgrastim prophylaxis was similar to that reported in other observational and randomized studies.

A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia

IntroductionEndothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN.MethodsThis was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome.ResultsA total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality.ConclusionsA high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.

A High Angiopoietin-2/Angiopoietin-1 Ratio Independently Predicts Septic Shock Development in Patients with Chemotherapy-Associated Febrile Neutropenia and Hematological Malignancies.

AbstractAbstract 2154 Introduction:Febrile neutropenia (FN) patients with hematologic malignancies present a high risk of septic shock. Clinical scores such as MASCC can identify low-risk patients with FN, mainly in the outpatient setting, but are not very informative for high-risk patients (MASCC<21), which is the category that most patients with hematologic malignancies fit in. Endothelial barrier breakdown is a key element in septic shock, so that proteins involved in this process are currently considered among the most promising biomarkers and therapeutic targets in sepsis. Notably, angiopoietins (Ang) 1 and 2 are key elements of embryonic vascular development, with vessel-stabilizing and -destabilizing properties respectively. In an exploratory study, we previously demonstrated that levels of these proteins are increased in neutropenic patients with septic shock. Materials and Methods: here we prospectively evaluated the significance of VEGF-A, sFlt-1, Ang-1 and Ang-2 levels as biomarkers of septic shock progression in an independent population of patients with chemotherapy-associated FN and hematological malignancies. The study was deliberately designed to mimic real-life conditions in which a sepsis biomarker would be ordered. All patients admitted to the Hematology or BMT wards of our Institution for the treatment of FN between April 2011 and March 2012 were invited to participate. Blood samples were collected in the morning after enrollment, along with the routine blood work-up, by non-study staff. Biomarker levels were obtained by commercially-available ELISA. Primary clinical endpoints were septic shock development or mortality from infection, in 30 days from fever onset. Results: Of the 99 patients that fulfilled the inclusion criteria, 20 (19.8%) developed septic shock and 17 (16.8%) died from infection. Of these, 78 (78.8%) were classified as high-risk according to the MASCC score, a distribution characteristic of hematological malignancies. There were no significant clinical and demographic differences between patients with non-complicated FN and septic shock. No significant difference could be detected in VEGF-A or sFlt-1 levels between outcome groups either. In contrast, Ang-2 concentrations were increased in patients with septic shock (6,494 pg/ml, range 1,730–49,611 pg/ml) compared to non-complicated FN (4,467 pg/ml, range 1,289–37,318 pg/ml; P=0.02), whereas an inverse finding was observed for Ang-1 concentrations, which were lower in patients that developed septic shock (898.8 pg/ml, range 77.87–5,420 pg/ml) than in patients with non-complicated FN (1,220 pg/ml, range 32.55–47,924 pg/ml; P=0.07). Because imbalances between Ang-1 and Ang-2 could be more informative than each isolated biomarker, we calculated the Ang-2/Ang-1 ratio, which was much higher in patients with septic shock (5.29, range 0.58–57.14) than in non-complicated FN (1.99, range 0.06–64.62; P = 0.01). When analyzed as a continuous variable, the Ang-2/Ang-1 ratio proved to be an independent factor for shock septic development. The presence of a threshold level of Ang-2/Ang-1 ratio for an increase in the risk of shock septic could be demonstrated by dichotomizing the ratio by the median and by the optimal cut-off value identified using a ROC procedure (Ang-2/Ang-1=5.0). After adjustment for confounding factors, the multivariate risk for septic shock development was RR=5.47 (CI95% 1.93–15.53) for values above 5.0 and RR=2.99 (CI95%1.02–8.42) for values above the median. Similar results were obtained for 30-day mortality from infection. Conclusion: the prognostic impact of a high Ang-2/Ang-1 ratio as a biomarker for septic shock development was demonstrated in an independent and representative population of high-risk FN patients. The persistence of statistical significance of this association in a much less controlled context than in exploratory studies of biomarker research highlights the strength of the association between this important modulator of endothelial barrier integrity and progression to septic shock. This information has important implications for the clinical management of patients with FN and hematological malignancies, for whom no validated sepsis biomarkers are used in clinical practice, as well as for the development of new therapeutic strategies for the treatment of septic shock. Disclosures:No relevant conflicts of interest to declare.

Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study

The soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is a useful marker of infection in patients with sepsis, but has not been adequately evaluated in patients with chemotherapy-associated febrile neutropenia (FN). The value of sTREM-1 in this setting has been tested in a retrospective, pilot study using stored serum from 48 cancer patients with documented FN. On presentation, patients were categorized according to the Talcott risk-index clinical score. Circulating soluble sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an immunoluminescence-based assay and Bio-Plex® suspension bead array system, respectively. Circulating concentrations of both sTREM-1 and PCT were significantly (P < 0.05) elevated in patients at high risk for complications or death, as predicted by the Talcott score and were significantly lower in patients who responded to empiric antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications in patients with FN. These observations, albeit from a pilot study, demonstrate that sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to predict their clinical course, either together with, or as an alternative to PCT.

Changes in medical oncology admissions for the management of breast cancer complications: An Australian institution's experience

There is a scarcity of data regarding medical hospitalizations for breast cancer. The aim was to determine whether the burden of inpatient care for breast cancer was declining. A retrospective study was conducted of all admissions to a single medical oncology inpatient unit in 1996 and 2006 related to the treatment of breast cancer. The total number of hospitalizations, patients' length of stay in hospital, clinical indications for hospitalization and utilization of inpatient services were determined. Data analysis involved pairwise comparisons between the cohorts. The total number of breast cancer hospitalizations was similar in 1996 and 2006. However, the number of hospitalizations for adjuvant treatment complications was 50% lower in 2006, attributable to a lower rate of chemotherapy-associated febrile neutropenia. Acute clinical problems necessitating inpatient care differed between 1996 and 2006. Fewer hospitalizations for symptomatic hypercalcemia, uncontrolled pain and chemotherapy toxicity were required in 2006 but a significant increase was seen in central nervous system complications. Recent practice involved greater inpatient consultation of other medical and surgical teams. There was a trend towards a shorter duration of admissions in 2006 in both adjuvant and metastatic patients. Although total annual breast cancer admission numbers and length of stay did not change significantly, hospitalization for treatment-related complications was less frequent in 2006. The clinical manifestations of metastatic breast cancer appear to be changing, and in our institution are being managed with broader multidisciplinary care.

Cancer-Associated Neutropenic Fever: Clinical Outcome and Economic Costs of Emergency Department Care

Purpose. Febrile neutropenia (FN) is a common, costly, and potentially fatal complication in oncology. While FN in the inpatient setting has been extensively studied, only one study has evaluated emergency department (ED) care for FN cancer patients. That study found that 96% of patients survived the complication. We evaluated clinical and economic outcomes for cancer patients with chemotherapy-associated FN treated in an ED. Methods. ED records for consecutive oncology patients with FN were reviewed for information on death, intensive care unit (ICU) use, blood cultures, and costs. Results. Forty-eight patients (n = 57 visits) were evaluated. Six patients died from FN (12%) and four received ICU care within 2 weeks and survived (8%). Blood cultures were positive for 37% of the ED visits. The median ED time was 3.3 hours. In 91% of visits, i.v. antibiotics were administered in the ED, ordered at a median of 1.7 hours from triage (interquartile range [IQR], 1.2-2.8 hours). All patients with death or ICU in 2 weeks and all but one patient with positive blood cultures received antibiotics. The median per patient ED costs were $1,455 (IQR, $1,300-$1,579)-42.4% for hospital/nursing, 23.5% for radiology, 20.8% for physician services, 10.9% for diagnostic tests, and 2.4% for antibiotics. Conclusions. Cancer patients with FN in this sample presenting to the ED frequently had no identified source of infection. One third of the patients had positive ED blood cultures and one fifth died or required ICU care within 2 weeks. Costs of ED care were similar to the cost of a single day of inpatient care. Disclosure of potential conflicts of interest is found at the end of this article.

Uncompensated costs associated with the outpatient management of cancer chemotherapy-associated febrile neutropenia

Uncompensated costs associated with the outpatient management of cancer chemotherapy-associated febrile neutropenia

Granulocyte Colony-Stimulating Factor for Chemotherapy-Induced Neutropenia in Patients with Small Cell Lung Cancer

Recombinant granulocyte colony-stimulating factor (G-CSF) [filgrastim and lenograstim] and pegylated G-CSF (pegfilgrastim) have been shown to reduce the severity and duration of chemotherapy-associated febrile neutropenia (FN) when administered prophylactically to cancer patients receiving chemotherapeutic regimens. The American Society of Clinical Oncology (ASCO) evidence-based clinical guidelines published in 1994, 1996 and 1997 recommended primary prophylaxis with G-CSF for cancer patients. The 2000 ASCO update, with the same recommendation, highlights the importance of economic considerations in decision making for CSFs. This paper reviews the available cost-effectiveness evidence on the use of G-CSF as primary prophylaxis against FN in patients with small cell lung cancer (SCLC).Cost-effectiveness ratios from a healthcare payer perspective supported the use of filgrastim as primary prophylaxis for people with SCLC, on the basis of both clinical and economic benefits, treated with chemotherapeutic regimens that have an FN rate in the range of 40-60%. However, when indirect and patient out-of-pocket costs attributable to severe FN are included, available evidence suggests that the risk threshold may be reduced by more than half. Given that FN rates associated with chemotherapeutic regimens for SCLC are generally <40%, then few circumstances would warrant the use of G-CSFs (filgrastim and lenograstim) under the current rule. However, inclusion of indirect costs would lower the cost-effectiveness threshold. Future cost-effectiveness studies of medications such as pegfilgrastim should attempt to capture the societal perspective by incorporating productivity-related costs and using base-case rates of FN reported in the literature.

The uncompensated costs associated with the evaluation and treatment of neutropenia

6120 Background: Febrile neutropenia is a serous complication of chemotherapy which is frequently managed in the outpatient setting. Health care personnel provide many uncompensated services as they coordinate outpatient and home care services for this treatment-related complication. We performed a time and motion study designed to evaluate time spent and associated costs of uncompensated care provided by physicians, nurses, phlebotomists, and medical assistants for outpatient management of cancer chemotherapy-associated febrile neutropenia. Methods: Over a three month period, cancer chemotherapy-associated febrile neutropenia management activities of a small community medical practice were monitored. Tasks were categorized as: consultation/education, documentation, medication administration, test or medication ordering, phone calls, nursing, procedures, after hours follow-up, and miscellaneous. Unit costs were estimated using 2003 practice-specific salary and fringe benefit rates. Results: The results presented represent the time spent on the evaluation and management of neutropenia and related activities over the course of a 5 day work week. Conclusions: Based on the results of this observational study, the time required for coordination of chemotherapy-associated neutropenia management can be considerable, and the associated uncompensated costs to a small community practice can be substantial. For one community oncology practice, treatment and management of neutropenia and related care costs $88,832 of lost time per year. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen; Medimmune Amgen