Consensus statement for cancer patients requiring intensive care support

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.
In patients with hematological or oncological malignancies, the disease itself or intensive therapy may result in critical illness in a substantial number of patients. In 1999, the American College of Critical Care Medicine stated that patients with hematological or metastasized oncological malignancies are poor candidates for ICU admission with a mortality rate of up to 90%. Thus, refusal of ICU admission of these patients was the common procedure (Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine, 1999 [bib_ref] Guidelines for intensive care unit admission, discharge, and triage. Task force of..., Tfotacocc [/bib_ref]. However, within the last 25 years, cancer and ICU treatment clearly improved. As shown in recent reports, hospital mortality decreased to less than 40% in these critically ill patients with hematologic malignancies [bib_ref] Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from..., Azoulay [/bib_ref]. Thus, criteria for ICU admission have to be adjusted. Aim of this consensus statement is to provide a review of the recent literature and the development of practical recommendations to hematologists, oncologists, and intensive care specialists. Due to a series of practice-changing investigations on proper ventilation techniques in cancer patients with acute respiratory failure, we put a special emphasis on discussing this topic.

# Methods
The consensus group was selected to represent the expertise in the field of critical care in cancer patients in Germany and Austria. Experts were sent by the German Society of Hematology and Medical Oncology (DGHO), the Austrian Society of Hematology and Oncology (OeGHO), the German Society of Internal Intensive and Emergency Medicine (DGIIN), and the Austrian Society of Medical and General Intensive Care and Emergency Medicine (OGIAIN). All authors are actively supporting the "Intensive Care Medicine in Hematologic and Oncologic Patients (iCHOP)" Initiative (info@ichop.eu).
Consensus statements are based on an in-depth PubMed literature retrieval of English as well as German language literature with last access February 01, 2017. For medical heading terms (MeSH) identifying potential relevant literature, please see Appendix. Seven working groups (a: ICU transfer criteria and goals of therapy, b: respiratory failure, c: end of live decisions, d: stem cell transplant patients, e: infections, f: coagulation, and g: miscellaneous) prepared the draft proposals in a first round of consensus development. Working groups decided on references with relevant impact on guideline development, and every group member had to approve the draft guideline subchapter. Finally, the consensus statements were approved by the assembly of the members on March 2nd and 3rd 2017 in Vienna, Austria, a meeting hosted and sponsored by the OeGHO. All statements and manuscript wording underwent voting of the consensus assembly.
This guideline follows the structure and definitions of the ESCMID Guideline on Candida diseases [bib_ref] ESCMID Fungal Infection Study Group (2012) ESCMID* guideline for the diagnosis and..., Cornely [/bib_ref]. It is in accordance with the GRADE and AGREE [bib_ref] for the AGREE Next Steps Consortium (2010) AGREE II: advancing guideline development,..., Brouwers [/bib_ref] [bib_ref] Grading quality of evidence and strength of recommendations in clinical practice guidelines..., Brozek [/bib_ref] [fig_ref] Table 1: Strength of the recommendation and quality of evidence [/fig_ref].
All recommendations are given in boldface type.

## Prognosis and icu admission criteria
Whom to admit to the ICU/eligibility and goals of therapy This statement, of course, presumes that the acute condition may be reversed by ICU measures, and that age and comorbidities of patients do not contradict such an approach. Typically, full-code management applies to patients with curative therapeutic options, those in remission of their malignancy, as well as to patients in whom cure is not likely but the expected life-span is substantial [bib_ref] Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from..., Azoulay [/bib_ref]. It has been suggested in an earlier consensus that an assumed prognosis of 1 year may be used as cutoff for clinical decision making with regard to full-code status [bib_ref] Intensive care of the cancer patient: recent achievements and remaining challenges, Azoulay [/bib_ref]. The authors of this manuscript believe this number is arbitrary and may be regarded as basis for individual considerations only.
Patients with poor performance status not eligible for further anti-cancer therapy, dying patients, as well as those rejecting critical care treatment should not be admitted to the ICU in general (A-III)
For patients not fulfilling the above-described criteria for full-code ICU management or ICU refusal, time-limited ICU trials or pre-defined do-not-escalate decisions (e.g., do-not-intubate or do-not-attempt-resuscitation) may be adequate options (B-IIu)
In a prospective trial on patients with intermediary prognosis (non-palliative, non-bedridden, non-full-code patients), those with worsening organ failure scores after days 5 of ICU therapy had a high risk of dying. The authors suggested to offer these patients a full-code ICU trial with re-evaluation of the goals of therapy after at least 6 days . We would like to point out that almost all patients who died after day 5 had treatmentlimitation decisions. Therefore, it remains unknown what their course would have been in case of further full-code management. Furthermore, data on cancer patients with poor prognosis suggest that the optimal duration of time-limited ICU trials seems to differ largely between patients with solid tumors and hematologic malignancies [bib_ref] Time-limited trials of intensive care for critically ill patients with cancer: how..., Shrime [/bib_ref]. Thus, proposing a fixed interval from admission to re-evaluation of the goals of ICU therapy in patients undergoing time-limited ICU trials may not be generally appropriate.
When to admit to the ICU, indications and screening for organ dysfunction Several observational investigations on cancer patients with septic complications and respiratory failure indicate that early ICU admissions and early interventions, respectively, are associated with improved survival [bib_ref] Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from..., Azoulay [/bib_ref] [bib_ref] Predictive factors of intensive care unit admission in patients with haematological malignancies..., Gruson [/bib_ref] [bib_ref] Intensive care unit management of patients with newly diagnosed acute myeloid leukemia..., Lengline [/bib_ref] [bib_ref] Implementation of modified early-goal directed therapy for sepsis in the emergency center..., Hanzelka [/bib_ref] [bib_ref] Delayed intensive care unit admission is associated with increased mortality in patients..., Mokart [/bib_ref] [bib_ref] Early intervention on the outcomes in critically ill cancer patients admitted to..., Song [/bib_ref]. Thus, early identification of patients at risk for critical deterioration seems crucial. Severity of illness scores can only be used for describing groups of patients and should, therefore, not be used in individual clinical decision making with regard to ICU admissions or prognostication.
Cancer patients should be considered for ICU admission in case of manifest or incipient acute organ dysfunction(s) (A-IIu)
Cancer ward patients at risk should be screened for the presence of sepsis daily (A-IIt)
Cancer ward patients at risk should be screened for the presence of acute organ dysfunction(s) daily (A-IIu)

## Recommendations for local structures and educational matters
Mortality of ICU cancer patients has markedly dropped over the last decades, presumably due to improved general ICU management, improved diagnostic and therapeutic strategies for several cancer-specific situations, as well as refined admission criteria [bib_ref] Intensive care of the cancer patient: recent achievements and remaining challenges, Azoulay [/bib_ref] [bib_ref] Managing critically Ill hematology patients: time to think differently, Azoulay [/bib_ref] [bib_ref] Critically ill patients with cancer: chances and limitations of intensive care medicine-a..., Schellongowski [/bib_ref] ]. Yet, prognostication of cancer patients and adequate patient selection remain far from perfect [bib_ref] Outcome of cancer patients considered for intensive care unit admission: a hospital-wide..., Thiery [/bib_ref].
Centers should establish local admission criteria for critically ill cancer patients as well as standardized admission procedures, such as joint assessment by cancer specialists and intensivists, if available (A-III)
A recent Brazilian investigation showed an independent correlation between daily joint rounds of cancer specialists and intensivists as well as the number of protocols with lower mortality and more efficient resource use [bib_ref] Effects of organizational characteristics on outcomes and resource use in patients with..., Soares [/bib_ref]. This is supported by Nassar and coworker stating that regular meetings may reduce possible conflicts between intensivists and oncologists [bib_ref] Oncologists' and intensivists' attitudes toward the care of critically Ill patients with..., Nassar [/bib_ref].
Centers should establish daily joint rounds of cancer specialists and intensivists as well as standard-operating procedures for the management of frequent medical conditions of critically ill cancer patients (A-IIu)
Although a recent study by Soares and colleagues failed to identify ICU volume as a prognostic marker for ICU survival [bib_ref] Effects of organizational characteristics on outcomes and resource use in patients with..., Soares [/bib_ref] , the majority of available studies demonstrate a significant association of case volume and ICU mortality in cancer patients with septic shock or acute respiratory failure [bib_ref] Case volume and mortality in haematological patients with acute respiratory failure, Lecuyer [/bib_ref] [bib_ref] Intensive care in patients with lung cancer: a multinational study, Soares [/bib_ref] [bib_ref] Impact of case volume on survival of septic shock in patients with..., Zuber [/bib_ref]. This effect might be linked to expertise and specific processes of care. However, some of the available observational studies may not have accounted for potential confounders related to ICU organization, structure, and process of care. Ultimately recognizing and developing Bcritical care of cancer patientsa s a medical subspecialty may optimally serve the needs of affected patients [bib_ref] CCC meets ICU: redefining the role of critical care of cancer patients, Bergwelt-Baildon [/bib_ref]. Nevertheless, due to the fast-growing demand for critical care for cancer patients, the major practical challenge is how to provide high-quality and affordable care for all patients. Treating all critically ill cancer patients regardless of the underlying condition in specialized centers may not be feasible after all. Therefore, managing some of the rather common cancer-specific ICU problems, such as neutropenic sepsis, should become part of routine expertise for all intensive care specialists. However, in more specific situations, such as chemotherapy administration in critically ill patients with aggressive hematologic malignancies or caring for ICU patients after allogeneic stem cell transplant, transfer to specialized centers should be discussed.

## Centers should establish joint continuous medical education of cancer specialists and intensivists (a-iii)
Basic concepts of the care of critically ill cancer patients should be included into the curricula of both cancer specialists and intensivists (A-III)
All previous statements are summarized in [fig_ref] Table 2: Admission to ICU, eligibility, and aims of therapy Full-code ICU management in... [/fig_ref].

## Acute respiratory failure (arf)

## Diagnostic work-up
With respect to the critical prognosis of ARF in cancer patients, especially in patients with ARF of unknown origin [bib_ref] The prognosis of acute respiratory failure in critically ill cancer patients, Azoulay [/bib_ref] [bib_ref] Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined..., Contejean [/bib_ref] , diagnostic procedures are of major clinical importance. A systematic diagnostic work-up may lead to a (high-probability) diagnosis in approximately 70-80% of patients with ARF [bib_ref] Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized..., Azoulay [/bib_ref] [bib_ref] Overview of current lung imaging in acute respiratory distress syndrome, Zompatori [/bib_ref]. However, diagnostic procedures should not cause a delay in the start of adequate ARF therapy including prompt antibiotic treatment (modification) in the case of a (suspected) infection (A-III).
The diagnostic strategy should encompass a comprehensive analysis of the clinical course of the underlying malignancy, including data on mechanisms of immunosuppression, antineoplastic and antimicrobial treatment, and prophylaxis [bib_ref] Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized..., Azoulay [/bib_ref] [bib_ref] Clinical assessment for identifying causes of acute respiratory failure in cancer patients, Schnell [/bib_ref].

## Independent of the clinical presentation, chest computed tomography is recommended (a-iit)
Bronchoscopy and a BAL-based diagnostic work-up including a broad range of both culture-and non-culture-based diagnostic methods should be added to noninvasive tests depending on pretest probabilities of clinical etiologies (if clinically feasible early after ICU admission and without causing clinical worsening) (A-I) [fig_ref] Table 3: Bacteriological cultures [/fig_ref] provides a summary of diagnostic procedures in cancer patients with ARF.

## Ventilatory strategies
Noninvasive ventilation (NIV) remains the first-line standard of care in acute exacerbate chronic pulmonary [bib_ref] Implementation of the German S3-guideline of non-invasive ventilation for acute respiratory failure..., Westhoff [/bib_ref]. However, the role of NIV in hypoxic ARF is far less well documented. While a historic single-center randomized controlled trial (RCT) suggested superiority of NIV over conventional oxygen therapy in immunocompromised (mainly hematologic) patients with regard to intubation and survival rates [bib_ref] Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory..., Hilbert [/bib_ref] , successive (mainly observational) studies have led to conflicting results. The 2015 BClinical Practice Guidelines on noninvasive mechanical ventilation in ARF^on behalf of the German Society of Pneumology and Ventilatory Medicine acknowledge that NIV can be attempted to avoid intubation in immunosuppressed (including hemato-oncologic) patients. In this regard, it is of particular importance to respect common contraindications and termination, i.e., intubation criteria [bib_ref] Implementation of the German S3-guideline of non-invasive ventilation for acute respiratory failure..., Westhoff [/bib_ref]. However, the respective guideline could not account for several meanwhile published investigations: First, a meta-analysis on 2380 mainly hematologic patients revealed that NIV as initial ventilator strategy was associated with lower mortality, whereas this finding is a mere association and cannot be interpreted as proof of principle. Importantly, 61% (range 40 to 78) of patients experienced NIV failure with secondary intubation, which itself was associated with increased mortality [bib_ref] Impact of initial ventilatory strategy in hematological patients with acute respiratory failure:..., Bernal [/bib_ref]. Second, in a large multicenter observational investigation in 1004 cancer patients with ARDS, NIV failure occurred in 71% of patients and was, again, independently associated with mortality, while mortality of ARDS patients undergoing IMV per se had decreased to 52% in recent years [bib_ref] Noninvasive ventilation during acute respiratory distress syndrome in patients with cancer: trends..., Neuschwander [/bib_ref]. Finally, a recent large multicenter landmark RCT compared the use of NIV to conventional oxygen in immunocompromised (mainly hematologic) patients with hypoxic ARF (acute cardiogenic pulmonary edema or hypercapnia, i.e., PaCO 2 > 50 mmHg excluded, pre-specified intubation criteria [bib_ref] Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients..., Lemiale [/bib_ref]. The trial did not show any clinical benefits or increased harms associated with NIV. However, the lower than expected mortality rate in the oxygen only group limited the power to detect significant differences, and a higher proportion of patients in the NIV group received high flow nasal oxygen intermittently, which may have limited the demonstrable effects of NIV. Risk factors for NIV failure in cancer patients are depicted in [fig_ref] Table 4: Risk factors for NIV failure in cancer patients with acute respiratory failure [/fig_ref]. High flow nasal oxygen (HFNO) has recently been shown to be associated with reduced intubation (PaO 2 /FiO 2 < 200) and mortality (PaO 2 /FiO 2 < 300) rates in elderly patients with pneumonia and hypoxic ARF when compared to conventional oxygen therapy or NIV [bib_ref] High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure, Frat [/bib_ref]. This effect was also observed in the subset of immunocompromised patients [bib_ref] Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory..., Frat [/bib_ref]. However, given conflicting data, the applicability of these findings in cancer patients, and specifically in those presenting with other etiologies than pneumonia, remains to be demonstrated [bib_ref] High-flow nasal cannula oxygenation in immunocompromised patients with acute hypoxemic respiratory failure:..., Lemiale [/bib_ref] [bib_ref] Ventilatory strategies in patients with hematologic malignancies and acute respiratory failure: new..., Schellongowski [/bib_ref].
In case a NIV or HFNO trial is initiated in cancer patients with hypoxic ARF, common contraindications and/or the occurrence of pre-specified intubation criteria should lead to intubation and invasive mechanical ventilation without delay (A-IIu)
Given the considerable failure rates of NIV and HFNO in hypoxic ARF and the lack of sufficient data on the safety of such therapies in regular wards, NIV and HFNO should not be attempted in this indication on a regular ward (B-III)

## End-of-life, palliative care
Principles in palliative care and end-of-life (EOL) management are not different in cancer patients compared to critically ill patients without a malignancy as underlying disease (A-IIt). However, (i) patient's wish, (ii) progressive (multi-) organ failure despite full-code ICU management and no chance of reversibility, or (iii) rapid progress of cancer disease without further treatment options have to be kept in mind and could change the treatment decision or treatment goals [bib_ref] End-of-life practices in European intensive care units, Sprung [/bib_ref]. These issues have to be discussed between oncologists and the intensive care team in an interdisciplinary manner. In cancer patients admitted to an ICU, current treatment state and estimated prognosis may be unknown to the ICU team. Therefore, consultation of an oncologist is highly recommended to provide valid prognostic information (A-III).
Intensive care admissions often represent an additional burden for patients and families in situations without option for cure. Good communication is essential to allow patients and families to meet their preferences regarding EOL. According to the literature, too many EOL decisions are made too late [bib_ref] Admission to intensive care unit at the end-of-life: is it an informed..., Rady [/bib_ref]. Early integration of an interdisciplinary palliative care team for hospitalized patients with life-limiting disease leads to fewer ICU admissions (A-I) [bib_ref] Impact of an inpatient palliative care team: a randomized control trial, Gade [/bib_ref]. Furthermore, integration of pro-active palliative care on ICUs, including palliative care rounds, leads to a shorter length of stay on ICU or in the hospital (A-IIt) [bib_ref] Proactive palliative care in the medical intensive care unit: effects on length..., Norton [/bib_ref] [bib_ref] Prospective study of a proactive palliative care rounding intervention in a medical..., Braus [/bib_ref].
To improve quality of EOL care in critically ill patients regarding important clinical questions, i.e., preparing for withdrawal, assessment and drug management of distress, discontinuation of treatment and monitoring, or dignity conserving care [bib_ref] Dying with dignity in the intensive care unit, Cook [/bib_ref] , the authors refer to published consensus recommendations [bib_ref] Guidelines for the withdrawal of life-sustaining measures, Downar [/bib_ref].

## Special situations
Anticancer therapy during ICU In some cases, for example pulmonary involvement due to high grade non-Hodgkin lymphoma, hyperleukocytosis, etc., despite ICU treatment initiation or completion of anticancer chemotherapy, immunochemotherapy or radiotherapy is necessary to improve patient's clinical situation. Such some decision needs intensive discussions between the responsible hemato-oncologist and intensivist. Again, we recommend joint assessments by cancer specialists and intensivists and that basic concepts of the care of critically ill cancer patients should be included into the curricula of both cancer specialists and intensivists.

## Prevention and treatment of infections in critically ill cancer patients
Published guidelines on prevention, diagnosis, and treatment of infections in cancer patients do not specifically address critically ill cancer patients. In addition, few studies and current guidelines on infections in critically ill patients specifically address the particular requirements in the treatment of cancer patients [fig_ref] Table 5: Recommendations on prevention, diagnosis, and treatment of infections in cancer patients [/fig_ref].
Resources on prevention and treatment of infections in cancer patients, which might be largely applicable to critically ill cancer patients, are guidelines on:
& Management of neutropenic patients in the intensive care unit [bib_ref] Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations..., Schnell [/bib_ref] & Prophylaxis of viral [bib_ref] Antiviral prophylaxis in patients with solid tumours and haematological malignancies-update of the..., Sandherr [/bib_ref] , bacterial [bib_ref] Infectious diseases working P et al (2013) Primary prophylaxis of bacterial infections..., Neumann [/bib_ref] , and fungal [bib_ref] Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014..., Tacke [/bib_ref] infections including Pneumocystis jirovecii pneumonia [bib_ref] Infectious diseases working P et al (2013) Primary prophylaxis of bacterial infections..., Neumann [/bib_ref] & Unexplained fever in neutropenic patients [bib_ref] Antimicrobial therapy of unexplained fever in neutropenic patients-guidelines of the Infectious Diseases..., Link [/bib_ref] (new version in progress) & Diagnosis of invasive fungal infections [bib_ref] Diagnosis of invasive fungal infections in hematology and oncology-guidelines from the Infectious..., Ruhnke [/bib_ref] (new version in progress) & Treatment of invasive fungal infections [bib_ref] Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious..., Mousset [/bib_ref] and AIIt [bib_ref] Prophylaxis of infectious complications with colonystimulating factors in adult cancer patients undergoing..., Vehreschild [/bib_ref] Allogeneic stem cell transplant setting

## Criteria for icu admission
The prognosis of allogeneic hematopoietic stem cell transplant (HSCT) patients admitted to an ICU has been significantly improved in the last years [bib_ref] Changes in intensive care for allogeneic hematopoietic stem cell transplant recipients, Lengline [/bib_ref]. It is important to note that physicians of the primary hospital have to contact the patient's transplant center immediately in case of critical illness. Allogeneic HSCT patients with early ICU admission or single organ dysfunction benefit from intensive care. However, patients with uncontrolled or refractory graft-versus-host disease (GvHD) should not be intubated for acute respiratory failure (A-III) [bib_ref] Intensive care of the cancer patient: recent achievements and remaining challenges, Azoulay [/bib_ref] [bib_ref] Critically ill allogeneic hematopoietic stem cell transplantation patients in the intensive care..., Saillard [/bib_ref]. Thus, it is important to contact immediately patient's transplant center. For further information regarding isolation procedures, specific monitoring, as well as typical complications, please see supplement.

## Coagulation
Venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in cancer patients. An increased tumor burden results in a higher risk for VTE with the highest risk in patients receiving systemic chemotherapy or being hospitalized on surgical and medical floors.
Although there are no validated data on the risk assessment in cancer patients on the ICU, according to the American Society of Clinical Oncology guidelines, risk scores (Khorana Score, revised Khorana score, Vienna score and Protecht score) are helpful tools to identify patients at highest risk for VTE [bib_ref] Development and validation of a predictive model for chemotherapy-associated thrombosis, Khorana [/bib_ref] [bib_ref] Risk stratification strategies for cancer-associated thrombosis: an update, Khorana [/bib_ref] [bib_ref] A modified Khorana risk assessment score for venous thromboembolism in cancer patients..., Verso [/bib_ref]. For further information on thromboprophylaxis in hospitalized patients with cancer, thromboprophylaxis in surgical patients with cancer, and treatment of thrombosis, please see Supplement [fig_ref] Table 3: Bacteriological cultures [/fig_ref] and accompanying text.

## Complications after new cancer drugs or cellular immunotherapy
Pharmacological and cellular treatment of cancer is changing dramatically not only with benefits for patient's outcome and comfort, but also with new toxicity profiles. The vast majority of adverse events can be classified as mild or moderate but there are also some cases of severe and life-threatening complications requiring ICU admission. Diagnosis and management of severe side effects after (monoclonal or bispecific) antibody treatment, tyrosine kinase inhibitors, immune checkpoint inhibitors, and chimeric antigen receptor-modified (CAR-) T cells were summarized recently in a concise review by the iCHOP group [bib_ref] New drugs, new toxicities: severe side effects of modern targeted and immunotherapy..., Kroschinsky [/bib_ref].

## Vaia

## Transfusions
In order to prevent the transfusion-associated graft versus host reaction (GvHR), all cellular blood products have to be irradiated with  30 Gy for patients with lymphatic diseases, autologous/allogeneic stem cell transplantation, and all patients treated with nucleoside analogues (fludarabine, cladribine) [bib_ref] The irradiation of blood and blood components to prevent graft-versus-host disease: technical..., Moroff [/bib_ref]. Generally, to prevent acute hemolysis, AB0identic transfusions should be carried out. However, after allogeneic HSCT, in exceptional cases, it is possible to transfuse major or minor incompatible blood products according to the AB0 blood group of the patient and the donor as stated in Supplement Table S1 [bib_ref] Stellungnahme der Sektion BTransplantation und Zelltherapie^zur Transplantation hamatopoetischer Stammzellen mit Blutgruppendifferenz, Cassens [/bib_ref]. Pooled platelet concentrates have a higher risk of immunization. Therefore, we recommend the transfusion of apheresis platelet concentrates.

## Cytokine storm disease/sepsis-like syndromes
Cancer patients are at risk to suffer from rare sepsis-like syndromes such as hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS), drug reaction with eosinophilia and systemic syndromes (DRESS), or capillary leak syndrome (CLS) [bib_ref] Hemophagocytic lymphohistiocytosis : a diagnostic challenge on the ICU, Lachmann [/bib_ref] [bib_ref] Drug-induced lymphadenopathy with eosinophilia and renal failure mimicking lymphoma disease: dramatic onset..., Schnetzke [/bib_ref] [bib_ref] Granulocyte colonystimulating factor-induced capillary leak syndrome confirmed by extravascular lung water measurements, Deeren [/bib_ref] [bib_ref] Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia, Frey [/bib_ref]. Infections, malignancy itself, and drugs are major triggers for these sepsis-mimicking syndromes. Diagnostic vigilance for early recognition is essential to reduce mortality. To validate diagnosis, we recommend to include blood differential (cytopenia, eosinophilia), ferritin, soluble IL2R, fibrinogen, and triglycerides in addition to the routine ICU lab admission panel in cancer patients with sepsis or sepsis-like syndromes in whom there is no apparent focus of sepsis [bib_ref] Study Group on Hemophagocytic Lymphohistiocytosis Subtypes of the Histiocyte Society (2015) Consensus..., Lehmberg [/bib_ref] (see [fig_ref] Table 6: HLH diagnostic criteria [/fig_ref] for HLH diagnostic criteria). Withholding the assumed trigger drug and immediate search for an underlying malignancy or infection are pivotal. HLH patients require immediate immunosuppression with corticosteroids to prevent further progression of organ failure . Early consultation with an HLH expert to stratify treatment according to the most likely trigger is recommended (www.hlh-registry.org).

## Summary
During the last years, outcome of patients with malignant hematological or oncological diseases requiring intensive care treatment has clearly improved. From recently published data, we conclude that the severity of the acute illness is more important with regard to short-term survival than the underlying type and stage of malignancy. Patients receiving intensive treatment of their malignancy should be considered for ICU treatment as other severely ill patients without cancer. Centers should establish local admission criteria for critically ill cancer patients as well as standardized admission procedures, such as joint assessment by cancer specialists and intensivists, allowing identification of patients and standardized transfer to the ICU. In some patients, time-limited ICU trials with pre-defined do-not-escalate decisions (e.g., do-not-intubate or do-not-attempt-resuscitation) may be an adequate option until final decision. This implements that critically ill cancer patients should be referred to experienced intensive care units. We strongly recommend establishing a local structure with daily joint rounds of cancer specialists and intensivists as well as standard-operating procedures for the management of frequent medical conditions in critically ill cancer patients.
Furthermore, centers should organize continuous medical education of cancer specialists and intensivists. Finally, basic concepts of the care of critically ill cancer patients should be included into the curricula of both cancer specialists and intensivists.
In addition, the early integration of an interdisciplinary palliative care team is an urgently necessary measure.
In order to improve the management of critically ill cancer patients, knowledge of current practices in German-speaking countries is of utmost interest. To produce more robust data, participation of treating centers in central patient registries, e.g., the iCHOP registry (info@ichop.eu), is highly recommended.

## Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
Open Access This article is distributed under the terms of the Creative Comm ons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.HLH-2004 diagnostic criteria:  5 must be fulfilled -Fever ( 38.3C) -Splenomegaly -Cytopenias in  2 lines (hb < 9 g/dL, plt < 100 /nL, neutrophils < 1.0/nL) -Ferritin  500 g/L -Hypertriglyceridemia and/or hypofibrinogenemia (fasting triglycerides  265 mg/dL, fibrinogen < 1.5 g/L) -Hemophagocytosis in bone marrow or spleen or lymph nodes -Low or absent NK activity -Soluble CD25 (soluble IL-2 receptor)  2400 U/mL
[table] Table 1: Strength of the recommendation and quality of evidence [/table]
[table] Table 2: Admission to ICU, eligibility, and aims of therapy Full-code ICU management in all critically ill cancer patients with prospect of long-term survival ICU refusal in patients with poor performance status not eligible for further anti-cancer therapy, dying patients, as well as those rejecting critical care Time-limited ICU trial and/or do-not-escalate decisions in patients neither fulfilling full code nor refusal criteria [/table]
[table] Table 3: Bacteriological cultures (quantitative or semi-quantitative) including culture media to detect Legionella spp., mycobacteria and fungi  Calcofluor white or equivalent stain (assessment of fungi)  (quantitative, if possible) PCR for Pneumocystis jirovecii  direct immunofluorescence test for Pneumocystis jirovecii  Aspergillus antigen (Galactomannan ELISA) [/table]
[table] Table 4: Risk factors for NIV failure in cancer patients with acute respiratory failure [/table]
[table] Table 5: Recommendations on prevention, diagnosis, and treatment of infections in cancer patients [/table]
[table] Table 6: HLH diagnostic criteria [/table]