Management and outcome of oncological patients under immune checkpoint inhibitors presenting at the emergency department.

INTRODUCTION: With the rising use of immune checkpoint inhibitors (ICIs) in oncology, emergency physicians are increasingly confronted with their immune-related adverse events (irAEs). We described the types of irAEs presenting to the ED of a Belgian cancer centre and determined associations with the development of an irAE and other patient's characteristics. Secondary objectives describe the therapeutic management and determine 7 and 30-day mortality. METHODS: A retrospective chart review of ED visits of patients on ICI from 15 December 2016 to 6 December 2020 was performed. Clinical presentation, cancer characteristics and type of ICI were extracted by a single abstractor. We recorded any suspicion of irAE in the ED and confirmation of an irAE was based on the patient's oncologist report. Outcome was based on mortality at date of last follow-up. RESULTS: 227 patients on ICI presented to the ED, with a total of 451 visits. 54 (12%) of the visits resulted in a diagnosis of irAE. Four clinical features were associated with an irAE: gastrointestinal complaints (p=0.01), skin rashes (p=0.02), acute renal failure (p=0.002) and abnormal liver function (p=0.04). An irAE was also associated with three different factors: a cancer status in remission (OR=5.33, 95% CI 2.57 to 11.04), a combination of two ICIs (OR=4.43, 95% CI 2.09 to 9.42) and a medical history of irAE (OR=2.44, 95% CI 1.27 to 4.68). 30-day mortality was lower in the irAE group (0%) than in the non-irAE group (13%, 95% CI 9% to 19%). CONCLUSIONS: Oncological patients under ICI presenting in the ED are more likely to have an irAE if they present with gastrointestinal and dermatological complaints, acute renal failure and abnormal liver function. This is also true for patients with any history of irAE, a concomitant use of two ICIs and with a cancer status in remission.

European Respiratory Society guideline on various aspects of quality in lung cancer care.

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

PARIS score for evaluation of probability of SARS-CoV-2 infection in cancer patients.

Control of transmissible diseases as COVID-19 needs a testing and an isolation strategy. The PARIS score developed by Torjdman et al. was aimed at improving patient selection for testing and quarantining but was derived from a general population. We performed a retrospective analysis of the validity of the PARIS score in a cancer patient population. We included 164 patients counting for 181 visits at the emergency department of the Jules Bordet Institute between March 10th and May 18th which had a SARS-CoV-2 RT-PCR test at admission. Twenty-six cases (14.3%) were tested positive with a higher proportion of positive tests among hematological patients compared to those with solid tumors (26% vs 11% p = 0.02). No clinical symptoms were associated with a positive SARS-CoV-2 PCR. No association between anticancer treatment and SARS-CoV-2 infection was found. The PARIS score failed to differentiate SARS-CoV-2-positive and SARS-CoV-2-negative groups (AUC 0.61 95% CI 0.48-0.73). The negative predictive value of a low probability PARIS score was 0.89 but this concerned only 11% of the patients. A high probability PARIS score concerned 49% patients but the positive predictive value was 0.18. CT scan had a sensitivity of 0.77, specificity 0.51, a positive predictive value of 0.24, and a negative predictive value of 0.92. The performance of the PARIS score is thus very poor in this cancer population. A low-risk score can be of some utility but this concerns a minority of patients.

Sepsis and Septic Shock Definitions in Patients With Cancer Admitted in ICU.

INTRODUCTION: In 2016, a new definition of sepsis and septic shock was adopted. Some studies based on the general population demonstrated that the Sequential Organ Failure Assessment (SOFA) score is more accurate than the systemic inflammatory response syndrome (SIRS) criteria to predict hospital mortality of infected patients requiring intensive care. PATIENTS AND METHOD: We have analyzed all the records of patients with cancer admitted for a suspected infection between January 1, 2013, and December 31, 2016, in our oncological intensive care unit (ICU). Sequential Organ Failure Assessment score and quick SOFA (qSOFA) score as well as SIRS criteria were calculated. We analyzed the accuracy of each score to predict hospital mortality in the setting of the new and old definitions of septic shock. RESULTS: Our study includes 241 patients with a solid tumor and 112 with a hematological malignancy. The hospital mortality rate is 37% (68% in patients with septic shock according to the new definition and 60% according to old definition) between 2013 and 2016. To predict hospital mortality, the SOFA score has an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.68-0.79), the qSOFA of 0.65 (95% CI, 0.59-0.70), and the SIRS criteria of 0.58 (95% CI, 0.52-0.63). In multivariate analysis, a higher SOFA score or a higher qSOFA score indicates poor prognosis: odds ratio (OR) per 1-point increase by 1.28 (95% CI, 1.18-1.39) and 1.48 (95% CI, 1.04-2.11), respectively. Complete remission is a good prognostic factor for hospital mortality: OR 0.39 (95% CI, 0.22-0.67). CONCLUSION: The new definition of sepsis and septic shock is applicable in an ICU oncological population with the same reliability as in the general population. The SOFA score is more accurate than qSOFA and SIRS criteria to predict hospital mortality.

Factors associated with SARS-CoV-2 infection and outcome in patients with solid tumors or hematological malignancies: a single-center study.

BACKGROUND: Immunocompromised cancer patients are presumed to be at high risk of developing COVID-19 infection. Predisposing factors to contracting COVID-19 and to severe outcomes have been described in registries but were not compared between solid tumors and hematological malignancies. METHOD: This retrospective single oncologic center study included adults with solid tumors or hematological malignancies referred to testing by naso-pharyngeal swab for a SARS-CoV-2 RT-PCR from March 10 to May 18, 2020. RESULTS: A total of 212 patients were included in the study. Forty-five (21%) were tested positive with SARS-CoV-2. The univariate analysis with positive SARS-CoV-2 PCR as a dependent variable reveals significant odds ratios (ORs) for age-with a mean of 62.5 years-(OR: 1.05, 95% CI: 1.02-1.08), performance status ≥2 (OR: 2.38, 95% CI: 1.22-4.70), inpatient status (OR: 2.36, 95%CI: 1.11-4.91), and hematological malignancies (OR: 2.48, 95% CI: 1.23-4.96). In contrast, OR for solid tumors reveals a negative association (OR: 0.40, 95% CI: 0.20-0.81). When integrating severe outcome (ICU admission or COVID-19-related death) as a dependent variable, the univariate logistic regression model shows significant ORs for pre-existing lymphopenia (OR: 4.0, 95% CI: 1.17-15.04), hematological malignancies (OR: 3.73, 95% CI: 1.09-13.80), and a negative association for solid tumors (OR: 0.27; 95% CI: 0.07-0.92). CONCLUSION: In patients referred for SARS-CoV-2 testing, hematological malignancies were associated with a higher risk of COVID-19 infection and severe outcomes. Other factors were age and inpatient status.

Drug-related problems and risk factors related to unplanned hospital readmission among cancer patients in Belgium.

INTRODUCTION: There are about 60,000 diagnoses of cancer per year in Belgium. After hospital care, about 12-13% of cancer patients are readmitted within 30 days after discharge. These readmissions are partly related to drug-related problems (DRP), such as interactions or adverse drug effects (ADE). OBJECTIVES: The aim of this study is to quantify and to classify DRP readmissions within 30 days for cancer patients and to highlight risk factors potentially correlated to readmissions. METHODS: This study is a 6-month observational retrospective study in two care facilities in Brussels: an academic general hospital and an academic oncology center. Patients readmitted within 30 days after their last hospital care for a potential DRP were included. Patient files were evaluated with an intermediate medication review that included interactions analysis (Lexicomp®). The probability of DRP readmission was assessed using the World Health Organization's Uppsala Monitoring Centre (WHO-UMC) system. RESULTS: The final population included 299 patients; among them, 123 (41.1%) were readmitted due to DRP (certain DRP (4.9%), probable DRP (49.6%), and possible DRP (45.5%)). Risks factors linked to these DRP were a low Charlson Comorbidity Index, polypharmacy, the kind of hospital, and some chemotherapies (platinum preparations). Among all readmitted patients, the D-type interactions were the most common (44.8%), which suggest a possible therapy modification. However, around 10% of interactions were X-type (drug combination to avoid). CONCLUSION: Almost 10% of patient readmitted within 30 days were potentially related to a DRP, most of them from adverse drug effects. Four risk factors (low Charlson Comorbidity Index, polypharmacy, the hospital, and some chemotherapies) were highlighted to prevent these readmissions.

Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients.

OBJECTIVES: To assess the response to initial oxygenation strategy according to clinical variables available at admission. DESIGN: Multicenter cohort study. SETTING: Thirty French and Belgium medical ICU. SUBJECTS: Immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03-2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07-3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23-10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73-4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27-3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10-4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11-11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35-4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26-3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates. CONCLUSIONS: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.

Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVES: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. DATA SOURCE: Seven European ICUs. STUDY SELECTION: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. DATA EXTRACTION: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). DATA SYNTHESIS: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. CONCLUSIONS: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

Management of Acute Complications of Targeted Therapy in Patients With Cancer: A Review of Cases Managed in ICU.

INTRODUCTION: Targeted therapies, molecules in full expansion, are not free of side effects that can lead patients to intensive care. We performed an extensive review of the published evidence and propose a management strategy for acute complications of targeted therapy in critically ill patients with cancer. METHODS: The literature search was performed in August 2017 using the Ovid Medline system by a scientific librarian and physicians. We made a review of cases admitted in intensive care unit (ICU) and a review of toxicities of grades greater or equal to 3. RESULTS: Our search selected 59 articles. The main cardiovascular side effects requiring ICU are heart failure, which is generally reversible, severe hypertension, thrombotic and ischemic events, and rhythm disturbances. The main pulmonary side effects are interstitial lung disease essentially caused by crizotinib, respiratory infections, pneumothorax, and alveolar hemorrhage. The main gastrointestinal side effects are fulminant hepatitis that may be fatal, colitis that may be complicated by hemorrhage, and perforation. The main neurological side effect is posterior reversible encephalopathy syndrome essentially caused by bevacizumab. The main other side effects are Steven-Johnson syndrome, necrotizing fasciitis, and anaphylactic reactions. CONCLUSIONS: The side effects induced by targeted therapies may be fatal but are generally potentially reversible. The main treatment includes stopping current therapy and symptomatic management. Treatment rechallenge should be discussed on a case-by-case basis.

Immunotherapy: a new standard of care in thoracic malignancies? A summary of the European Respiratory Society research seminar of the Thoracic Oncology Assembly.

In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events. The need for biological selection, currently based on immunohistochemistry testing to identify the tumour expression of programmed death ligand (PD-L)1, was stressed, as well as the need to harmonise PD-L1 testing and techniques. Finally, sessions were dedicated to the combination of ICIs and radiotherapy and the place of ICIs in nonsmall cell lung cancer with oncogenic addictions. Finally, an important presentation was dedicated to the future of antitumour vaccination and of all ongoing trials in thoracic oncology.

ERS statement on harmonised standards for lung cancer registration and lung cancer services in Europe.

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration.

Endothelial Cell-Specific Molecule-1 in Critically Ill Patients With Hematologic Malignancy.

OBJECTIVES: To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients. DESIGN: Prospective multicenter cohort study. SETTING: Seventeen ICUs in France and Belgium. PATIENTS: Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Median total endocan concentrations were 4.46 (2.7-7.8) ng/mL. Endocan concentrations were higher in patients who had received chemotherapy before ICU admission (4.7 [2.8-8.1] ng/mL vs. 3.7 [2.5-6.3] ng/mL [p = 0.002]). In patients with acute respiratory failure, endocan levels were increased in patients with drug-induced pulmonary toxicity compared with other etiologies (p = 0.038). Total endocan levels higher than 4.46 ng/mL were associated with a higher cumulative probability of renal replacement therapy requirement (p = 0.006), a higher requirement of mechanical ventilation (p = 0.01) and a higher requirement of vasopressors throughout ICU stay (p < 0.0001). By multivariate analysis, total endocan levels at admission were independently associated with ICU mortality (odds ratios, 1.39; 95% CI, 1.06-1.83; p = 0.018). The predictive value of endocan peptide fragments of 14 kDa in terms of mortality and life-sustaining therapies requirement was inferior to that of total endocan. Endocan levels were higher in critically ill hematology patients compared with healthy subjects (p < 0.0001) but lower than endocan values in critically ill septic patients without hematologic malignancy (p = 0.005) CONCLUSIONS:: Serum concentrations of endocan at admission are associated with the use of ICU resources and mortality in critically ill hematology patients. Studies to risk-stratify patients in the emergency department or in the hematology wards based on endocan concentrations to identify those likely to benefit from early ICU management are warranted.

Intensive care in thoracic oncology.

The admission of lung cancer patients to intensive care is related to postprocedural/postoperative care and medical complications due to cancer or its treatment, but is also related to acute organ failure not directly related to cancer.Despite careful preoperative risk management and the use of modern surgical and anaesthetic techniques, thoracic surgery remains associated with high morbidity, related to the extent of resection and specific comorbidities. Fast-tracking processes with timely recognition and treatment of complications favourably influence patient outcome. Postoperative preventive and therapeutic management has to be carefully planned in order to reduce postoperative morbidity and mortality.For patients with severe complications, intensive care unit (ICU) mortality rate ranges from 13% to 47%, and hospital mortality ranges from 24% to 65%. Common predictors of in-hospital mortality are severity scores, number of failing organs, general condition, respiratory distress and the need for mechanical ventilation or vasopressors. When considering long-term survival after discharge, cancer-related parameters retain their prognostic value.Thoracic surgeons, anesthesiologists, pneumologists, intensivists and oncologists need to develop close and confident partnerships aimed at implementing evidence-based patient care, securing clinical pathways for patient management while promoting education, research and innovation. The final decision on admitting a patient with lung to the ICU should be taken in close partnership between this medical team and the patient and his or her relatives.

High-Flow Nasal Cannula Oxygenation in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

OBJECTIVE: In immunocompromised patients with acute respiratory failure, invasive mechanical ventilation remains associated with high mortality. Choosing the adequate oxygenation strategy is of the utmost importance in that setting. High-flow nasal oxygen has recently shown survival benefits in unselected patients with acute respiratory failure. The objective was to assess outcomes of immunocompromised patients with hypoxemic acute respiratory failure treated with high-flow nasal oxygen. DESIGN: We performed a post hoc analysis of a randomized controlled trial of noninvasive ventilation in critically ill immunocompromised patients with hypoxemic acute respiratory failure. SETTING: Twenty-nine ICUs in France and Belgium. PATIENTS: Critically ill immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTION: A propensity score-based approach was used to assess the impact of high-flow nasal oxygen compared with standard oxygen on day 28 mortality. MEASUREMENTS AND MAIN RESULTS: Among 374 patients included in the study, 353 met inclusion criteria. Underlying disease included mostly malignancies (n = 296; 84%). Acute respiratory failure etiologies were mostly pneumonia (n = 157; 44.4%) or opportunistic infection (n = 76; 21.5%). Noninvasive ventilation was administered to 180 patients (51%). Invasive mechanical ventilation was ultimately needed in 142 patients (40.2%). Day 28 mortality was 22.6% (80 deaths). Throughout the ICU stay, 127 patients (36%) received high-flow nasal oxygen whereas 226 patients received standard oxygen. Ninety patients in each group (high-flow nasal oxygen or standard oxygen) were matched according to the propensity score, including 91 of 180 (51%) who received noninvasive ventilation. High-flow nasal oxygen was neither associated with a lower intubation rate (hazard ratio, 0.42; 95% CI, 0.11-1.61; p = 0.2) nor day 28 mortality (hazard ratio, 0.80; 95% CI, 0.45-1.42; p = 0.45). CONCLUSIONS: In immunocompromised patients with hypoxemic acute respiratory failure, high-flow nasal oxygen when compared with standard oxygen did not reduce intubation or survival rates. However, these results could be due to low statistical power or unknown confounders associated with the subgroup analysis. A randomized trial is needed.

Inequalities in lung cancer: a world of EGFR.

Epidermal growth factor receptor gene (EGFR) mutation status has emerged as a crucial issue in lung cancer management. Availability and cost of tests and tyrosine kinase inhibitors (TKIs) may vary as a function of country development.We conducted a prospective specialist opinion survey to map EGFR test and EGFR-TKI availability and detect associations with the Human Development Index (HDI). A questionnaire was sent to specialists in thoracic oncology in all United Nations Member States.We obtained responses from 74 countries, comprising 78% of the worldwide population. Nonresponding countries had significantly lower HDI rank than responding countries. EGFR mutation analysis was routinely available in 57 countries (70% of the worldwide population). The cost of the test was

Management of EGFR mutated nonsmall cell lung carcinoma patients.

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI. To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.

Systematic qualitative review of randomised trials conducted in nonsmall cell lung cancer with a noninferiority or equivalence design.

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10-15 years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects. All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracted a priori defined methodological information. A qualitative analysis was then performed. We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors' conclusions. CONSORT guidelines were better followed for general items than for specific items (p<0.001). Improvement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable.

Primary tumour standardised uptake value is prognostic in nonsmall cell lung cancer: a multivariate pooled analysis of individual data.

(18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I-II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22-1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I-III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27-1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I-III NSCLC, for squamous cell carcinoma and for adenocarcinoma.