Alberto Carmona-Bayonas

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

PURPOSEnTo 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.nnnPATIENTS AND METHODSnWe 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.nnnRESULTSnWe 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).nnnCONCLUSIONnCISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.

Geriatric Assessment Predicts Survival and Competing Mortality in Elderly Patients with Early Colorectal Cancer: Can It Help in Adjuvant Therapy Decision‐Making?

BACKGROUNDnThe challenge when selecting elderly patients with colorectal cancer (CRC) for adjuvant therapy is to estimate the likelihood that death from other causes will preclude cancer events from occurring. The aim of this paper is to evaluate whether comprehensive geriatric assessment (CGA) can predict survival and cancer-specific mortality in elderly CRC patients candidates for adjuvant therapy.nnnMATERIAL AND METHODSnOne hundred ninety-five consecutive patients aged ≥75 with high-risk stage II and stage III CRC were prospectively included from May 2008 to May 2015. All patients underwent CGA, which evaluated comorbidity, polypharmacy, functional status, geriatric syndromes, mood, cognition, and social support. According to CGA results, patients were classified into three groups-fit, medium-fit, and unfit-to receive standard therapy, adjusted treatment, and best supportive care, respectively. We recorded survival and cause of death and used the Fine-Gray regression model to analyze competing causes of death.nnnRESULTSnFollowing CGA, 85 (43%) participants were classified as fit, 57 (29%) as medium-fit, and 53 (28%) as unfit. The univariate 5-year survival rates were 74%, 52%, and 27%. Sixty-one (31%) patients died due to cancer progression (53%), non-cancer-related cause (46%), and unknown reasons (1%); there were no toxicity-related deaths. Fit and medium-fit participants were more likely to die due to cancer progression, whereas patients classified as unfit were at significantly greater risk of non-cancer-related death.nnnCONCLUSIONnCGA showed efficacy in predicting survival and discriminating between causes of death in elderly patients with high-risk stage II and stage III resected CRC, with potential implications for shaping the decision-making process for adjuvant therapies.nnnIMPLICATIONS FOR PRACTICEnAdjuvant therapy in elderly patients with colorectal cancer is controversial due to the high risk for competing events among these patients. In order to effectively select older patients for adjuvant therapy, we have to weigh the risk of cancer-related mortality and the potential survival benefits with treatment against the patients life expectancy, irrespective of cancer. This prospective study focused on the prognostic value of geriatric assessment for survival using a competing-risk analysis approach, providing an important contribution on the treatment decision-making process and helping clinicians to identify elderly patients who might benefit from adjuvant chemotherapy among those who will not.

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 <100u2005mmHg, heart rate >110u2005beats·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

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.

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer

BackgroundTrastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC.MethodsThis Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression.ResultsThe rate of HER2 testing increased steadily over time, from 58.3xa0% in 2008 to 92.9xa0% in 2016. HER2 was positive in 194 tumors (21.3xa0%). In the stratified Cox PH regression, each 1xa0% increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3xa0% increase in the risk of death: hazard ratio, 1.0035 (CI 95xa0%, 1.001–1.005), Pxa0=xa00.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2.ConclusionPatients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: a Spanish multicenter experience

BACKGROUND & METHODSnCapecitabine and temozolomide chemotherapy was used in 65 patients with gradexa01/2 neuroendocrine tumors (NETs). 46 patients (70.8%) had pancreatic NETs (pNETs).nnnRESULTSnResponse rate was 47.7%, with two complete responses (3.1%), 29 partial responses (44.6%) and 27 patients (41.5%) achieved stable disease. Median progression-free survival was 16.1 months (95% CI: 10.7-21.6) and overall survival was 38.3 months (95% CI: 24.6-51.9). Differences in progression-free survival and overall survival between pNETs and non-pNETs were not found. Nine (13.8%) patients experienced grade 3/4 toxicities, mainly thrombocytopenia (10.8%) and neutropenia (7.7%).nnnCONCLUSIONnThis is the largest reported series of NETs treated with capecitabine and temozolomide in daily practice and shows that this combination is a promising treatment option for both grade 1/2 pNETs and non-pNETs.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Background:The choice of chemotherapy in HER2-negative gastric cancer is based on centre’s preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).Methods:We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2–3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of ‘treatment-by-histology’ interaction, was used to estimate treatment effect.Results:Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525–0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054–1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49–0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50–0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46–0.88), P=0.046.Conclusions:As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Tapentadol for Cancer Pain Management: A Narrative Review

Pain is one of the most common symptoms in patients with cancer. The aim of this review is to summarize the most recent literature regarding tapentadol use in oncology patients and moderate or severe pain.

Performance of the clinical index of stable febrile neutropenia (CISNE) in different types of infections and tumors

PurposeThe clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients.MethodsWe prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots.Results171 patients had a serious complication (12.3xa0%, 95xa0% confidence interval 10.7–14.2xa0%). The most common initial assumptive diagnoses were: fever without focus (34.5xa0%), upper respiratory infection (14.9xa0%), enteritis (12.7xa0%), stomatitis (11.8xa0%), and acute bronchitis (10.7xa0%). Lung and breast were the most common tumors, accounting for approximately 56xa0% of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes.ConclusionDespite FN’s clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in 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.