Carmen Beato

Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study

PURPOSE To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. PATIENTS AND METHODS We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. RESULTS We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CONCLUSION CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.

Clinical features and short-term outcomes of cancer patients with suspected and unsuspected pulmonary embolism: the EPIPHANY study

The study aimed to identify predictors of overall 30-day mortality in cancer patients with pulmonary embolism including suspected pulmonary embolism (SPE) and unsuspected pulmonary embolism (UPE) events. Secondary outcomes included 30- and 90-day major bleeding and venous thromboembolism (VTE) recurrence. The study cohort included 1033 consecutive patients with pulmonary embolism from the multicentre observational ambispective EPIPHANY study (March 2006–October 2014). A subgroup of 497 patients prospectively assessed for the study were subclassified into three work-up scenarios (SPE, truly asymptomatic UPE and UPE with symptoms) to assess outcomes. The overall 30-day mortality rate was 14%. The following variables were associated with the overall 30-day mortality on multivariate analysis: VTE history, upper gastrointestinal cancers, metastatic disease, cancer progression, performance status, arterial hypotension <100 mmHg, heart rate >110 beats·min−1, basal oxygen saturation <90% and SPE (versus overall UPE). The overall 30-day mortality was significantly lower in patients with truly asymptomatic UPE events (3%) compared with those with UPE-S (20%) and SPE (21%) (p<0.0001). Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups. In conclusion, variables associated with the severity of cancer and pulmonary embolism were associated with short-term mortality. Our findings may help to develop pulmonary embolism risk-assessment models in this setting. Predictors of 30-day mortality in cancer patients with suspected and unsuspected pulmonary embolism http://ow.ly/Nu0k305t5KD

Predicting serious complications in patients with cancer and pulmonary embolism using decision tree modelling: the EPIPHANY Index

Background:Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days.Methods:The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold cross-validation to predict development of serious complications following PE diagnosis.Results:About 208 patients (19.3%, 95% confidence interval (CI), 17.1–21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4–12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs ⩾2), O2 saturation (<90 vs ⩾90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e.=0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717–0.840).Conclusions:We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia

Background:We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN).Patients and methods:The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups.Results:The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm3, and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value.Conclusions:We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.

Embolia pulmonar en el paciente oncológico: bases para el estudio EPIPHANY

Pulmonary thromboembolism (PE) is a common cause of morbidity and mortality in patients with cancer. Having cancer is an independent risk factor for death in the general series of patients with PE and is included as a variable in the prognostic scales of acute symptomatic PE. This fact limits the discriminatory power of these general scales for patients with cancer and has prompted the development of specific prognostic tools: POMPE-C and a scale derived from the RIETE registry. Whether the increased risk of death by PE in patients with cancer is due to complications related to the neoplasm or to a greater severity of the thromboembolic episode in this population has not been well studied. Moreover, the introduction of computed multidetector tomography in recent years has led to a growing diagnosis of incidental PE, which currently represents up to half of pulmonary embolisms in patients with cancer. The EPIPHANY study attempts to further the understanding of the characteristics of pulmonary embolisms in patients with cancer by including incidental and symptomatic events. Its primary objectives are a) to understand the clinical and epidemiological patterns of pulmonary embolism associated with cancer and b) to develop and validate a specific prognosis model for PE in this population. The registry includes variables of interest to oncology (cancer type and extent, oncospecific treatments, patients functional condition, cancer progression), radiological variables (thrombotic burden, signs of ventricular overload and other findings), location of treatment (hospital or outpatient), acute complications and causes of death in patients with PE associated with cancer.Resumen La tromboembolia pulmonar (TEP) constituye una causa frecuente de morbimortalidad en los pacientes oncologicos. Tener cancer es un factor de riesgo de muerte independiente en las series generales de pacientes con TEP y se incluye como variable en las escalas pronosticas de TEP aguda sintomatica. Este hecho limita el poder discriminatorio de estas escalas generales en los pacientes con cancer y ha motivado el desarrollo de herramientas pronosticas especificas: POMPE- C y una escala derivada del registro RIETE. No esta bien estudiado si el mayor riesgo de muerte por TEP en los pacientes con cancer se debe a complicaciones relacionadas con la neoplasia o a una mayor gravedad del episodio tromboembolico en esta poblacion. Por otro lado, la introduccion de la tomografia computarizada multidetector en los ultimos anos ha comportado un diagnostico creciente de TEP incidental, que en la actualidad representa hasta la mitad de las embolias pulmonares en los pacientes oncologicos. El estudio EPIPHANY pretende profundizar en las caracteristicas propias de la embolia pulmonar en el paciente oncologico incluyendo TEP incidental y sintomatica. Sus objetivos principales son: a) conocer los patrones clinicoepidemiologicos de la embolia pulmonar asociada al cancer; b) desarrollar y validar un modelo pronostico especifico de TEP en esta poblacion. Incluye el registro de variables de interes en oncologia (tipo y extension del cancer, tratamientos oncoespecificos, estado funcional del paciente, progresion del cancer), variables radiologicas (carga trombotica, signos de sobrecarga ventricular y otros hallazgos adicionales), lugar de tratamiento (hospitalizacion o ambulatorio), complicaciones agudas y causas de muerte en los pacientes con TEP asociado al cancer.

Prognostic value of computed tomography pulmonary angiography indices in patients with cancer-related pulmonary embolism: Data from a multicenter cohort study

OBJECTIVE To analyze the prognostic value of pulmonary artery obstruction versus right-ventricle (RV) dysfunction radiologic indices in cancer-related pulmonary embolism (PE). METHODS We enrolled 303 consecutive patients with paraneoplastic PE, evaluated by computed tomography pulmonary angiography (CTPA) between 2013 and 2014. The primary outcome measure was serious complications at 15days. Multivariate analyses were conducted by using binary logistic and robust regressions. Radiological features such as the Qanadli index (QI) and RV dysfunction signs were analyzed with Spearmans partial rank correlations. RESULTS RV diameter was the only radiological variable associated with an adverse outcome. Subjects with enlarged RV (diameter>45mm) had more 15-day complications (58% versus 40%, p=0.001). The QI correlated with the RV diameter (r=0.28, p<0.001), left ventricle diameter (r=-0.19, p<0.001), right ventricular-to-left ventricular diameter ratio (r=0.39, p<0.001), pulmonary artery diameter (r=0.22, p<0.001), and pulmonary artery/ascending aorta ratio (r=0.27, p<0.001). A QI≥50% was only associated with 15-day complications in subjects with enlarged RV, inverted intraventricular septum, or chronic cardiopulmonary diseases. The central or peripheral PE location did not affect the correlations among radiological variables and was not associated with clinical outcomes. CONCLUSIONS Right ventricular dysfunction signs in CTPA are more useful than QI in predicting cancer-related PE outcome.

A nomogram for predicting serious complications in patients with solid tumors and apparently stable febrile neutropenia: Prospective data on 781 consecutive episodes from the FINITE study.

165 Background: An accurate estimate of the likelihood of serious complications in patients with otherwise apparently stable febrile neutropenia (FN) may assist in decision-making regarding individualized therapy. Our group has developed a prognostic score for predicting complications in patients with solid tumors and apparently stable episodes called CISNE (Clinical Index for Stable Febrile Neutropenia). The purpose of this study is to present a nomogram based on the previously mentioned index in a broader dataset of patients. METHODS FINITE is a prospective and multicenter study which aims to investigate prognostic factors and outcomes of FN episodes with clinical stability at first assessment, defined as events without acute organ dysfunction, vital signs abnormalities or major infections. We performed a nomogram based on the CISNE score which includes the following prognostic variables: ECOG PS≥2, chronic obstructive pulmonary disease, cardiovascular disease, mucositis NCI grade ≥2, monocytes <200/mm3 and stress-induced hyperglycemia. A calibration plot was used to analyze the accuracy of this multivariate nomogram. RESULTS From October 2012 to December 2013, 781 patients with apparently stable FN were recruited in 21 Spanish hospitals. The rate of infection-related complications and death was 15.6% (95% confidence interval [CI], 12.9-18.6%) and 1.7% (95% CI, 0.98%-3.01%). A nomogram was designed according to the CISNE score. The area under the ROC curve was 0.836 (95% CI, 0.808-0.861). The observed and predicted probabilities also matched closely. CONCLUSIONS Our group has developed a user-friendly nomogram for predicting complications in patients with apparently stable FN. This nomogram may be particularly useful to prevent premature discharges of cancer patients starting inpatient management.

1485PDOUTPATIENT MANAGEMENT OF CANCER-RELATED PULMONARY EMBOLISM: A PROPENSITY SCORE-MATCHED ANALYSIS OF 803 PATIENTS FROM THE EPIPHANY STUDY

ABSTRACT Aim: Outpatient management of ‘low-risk’ pulmonary embolism (PE) is suggested in clinical guidelines (Evidence 2B) although the definition of ‘low-risk’ varies according to different authors. We aimed here to assess whether home versus hospital management were equivalent to treat ‘low-risk’ cancer-related PE. Methods: EPIPHANY is an observational, multicenter study to assess prognostic factors and patterns of care on cancer-related PE. The definition of low risk used in this study comprised: systolic blood pressure ? 100 mmHg, arterial oxygen saturation≥90%, respiratory rate ?30 breaths/min, pulse ?110 beats/min, no sudden or progressive dyspnea and absence of a clinically relevant hemorrhage. We used propensity score matching to compare the efficacy and safety of outpatient versus inpatient therapy. Results: We included 803 consecutive patients, 390 (48%) of whom were classified as low risk. Ambulatory management was used in 201 (51%) of them, whereas 189 (49%) were treated in hospital. Unadjusted rates of acute complications, 30- and 90- mortality were significantly lower in outpatients (Table 1). However, incidental detection, previous ambulatory status, absence of symptoms and oxygen saturation ≥96% were significantly more frequent in patients treated at home. After adjusting for imbalances, absolute difference estimates for 30- and 90 days mortality were: -0.6% (95% CI, -3.7 to+2.5%) and -2.7% (95% CI, -9.4% to +3.9%), respectively. Rates of venous rethrombosis and major bleeding events were also similar. Table 1. Outpatients (95% CI) Inpatients (95% CI) Short-term complications 2.5% (1- 5.7%) 6.3% (3.7- 10.7%) 30 days mortality 1.4% (0.5- 4.2%) 8.5% (5.2- 13.3%) 90 days mortality 7.4% (4.5- 11.9%) 20.1% (15- 26.3%) 30 days major bleeding 1.8% (0.7- 4.5%) 1.8% (0.7- 4.6%) Venous retrombosis 5.9% (3.4- 9.8%) 6.7% (4.1- 11%) Conclusions: Outpatient management of low-risk cancer-related PE appears to be safe and effective. A randomized trial is needed to confirm these data and assess outcomes in specific subgroups. Disclosure: All authors have declared no conflicts of interest.

Complexity and uncertainty in the critical care of cancer patients in the era of immunotherapy and targeted therapies

We have carefully read the letter from Illescas-Vacas et al. regarding SEOM-SEMICYUC’s commitment to optimize the care of cancer patients admitted to Intensive Care Units.1,2 We agree with the authors that radiotherapy has evolved with important technological advances in recent years, with more precise, effective and less toxic treatments that contribute to improve survival. Likewise, radiotherapy, in general, is associated with low acute potential toxicity if administered in monotherapy, without concomitant systemic treatment. On the contrary, systemic cancer treatments, chemotherapy, anti-target agents and immunotherapy, among others, have made it possible for a group of patients with advanced disease becoming longterm survivors. Nevertheless, these drugs not only bring new opportunities for patients, but also new challenges and toxicities, creating greater complexity and uncertainty in the field of critical care. In the previous decade, when the prognosis was universally bleak, decision-making was simple, the only solution often being palliative care. However, admission and support in the Intensive Care Unit of a patient with metastatic cancer may currently be justified if it is known that his tumor expresses a target for which specific treatment is available. In addition, a patient with advanced cancer who develops severe toxicity while receiving immunotherapy may require advanced supportive care if a tumor response has been confirmed. These oncological situations and emergencies, which are increasingly common nowadays, have led the SEOM-SEMICYUC team to develop an informative document in which they comment on the oncological scenarios and treatments that

Psychometric properties of the Shared Decision-Making Questionnaire (SDM-Q-9) in oncology practice

Background/Objective: This study sought to assess the psychometric properties of the 9-item Shared Decision-Making Questionnaire (SDM-Q-9) in patients with resected, non-metastatic cancer and eligible for adjuvant chemotherapy. Method: A total of 568 patients were recruited from a multi-institutional, prospective, transversal study. Patients answered the SDM-Q-9 after visiting their medical oncologist who, in turn, completed the SDM-Q–Physician version. Reliability, factorial structures [exploratory factor analysis (EFA), confirmatory factor analysis (CFA)], and convergent validity of the SDM-Q-9 scores were explored. Results: SDM-Q-9 showed a clear factorial structure, compatible with a strong and replicable general factor and a secondary group factor, in patients with resected, non-metastatic cancer. Total sum scores derived from the general factor showed good reliability in terms of omega coefficient: .90. The association between patient and physician perception of SDM was weak and failed to reach statistical significance. Males and patients over 60 years of age displayed the greatest satisfaction with SDM. Conclusions: SDM-Q-9 can aid in evaluating SDM from the cancer patients’ perspective. SDM-Q-9 is helpful in studies examining patient perspectives of SDM and as an indicator of the degree of quality and satisfaction with health care and patient-physician relationship.