Ann Hematol (2014) 93:1629–1636 DOI 10.1007/s00277-014-2141-x
ORIGINAL PAPER
Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit Philipp Wohlfarth & Thomas Staudinger & Wolfgang R. Sperr & Andja Bojic & Oliver Robak & Alexander Hermann & Klaus Laczika & Alexander Carlström & Katharina Riss & Werner Rabitsch & Marija Bojic & Paul Knoebl & Gottfried J. Locker & Maria Obiditsch & Valentin Fuhrmann & Peter Schellongowski & Arbeitsgruppe für hämato-onkologische Intensivmedizin der Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin (ÖGIAIN)
Received: 10 March 2014 / Accepted: 11 June 2014 / Published online: 6 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Prognostic factors and outcomes of cancer patients with acute organ failure receiving chemotherapy (CT) in the intensive care unit (ICU) are still incompletely described. We therefore retrospectively studied all patients who received CT in any ICU of our institution between October 2006 and November 2013. Fifty-six patients with hematologic (n=49; 87.5 %) or solid (n=7; 12.5 %) malignancies, of which 20 (36 %) were diagnosed in the ICU, were analyzed [m/f ratio, 33:23; median age, 47 years (IQR 32 to 62); Charlson Comorbidity Index (CCI), 3 (2 to 5); Simplified Acute Physiology Score II (SAPS II), 50 (39 to 61)]. The main reasons for admission were acute respiratory failure, acute kidney failure, and septic shock. Mechanical ventilation and vasopressors were employed in 34 patients (61 %) respectively, hemofiltration in 22 (39 %), and extracorporeal life support in 7 (13 %). Twenty-seven patients (48 %) received their first CT in the ICU. Intention of therapy was cure in 46 patients
(82 %). Tumor lysis syndrome (TLS) developed in 20 patients (36 %). ICU and hospital survival was 75 and 59 %. Hospital survivors were significantly younger; had lower CCI, SAPS II, and TLS risk scores; presented less often with septic shock; were less likely to develop TLS; and received vasopressors, hemofiltration, and thrombocyte transfusions in lower proportions. After discharge, 88 % continued CT and 69 % of 1-year survivors were in complete remission. Probability of 1- and 2year survival was 41 and 38 %, respectively. Conclusively, administration of CT in selected ICU cancer patients was feasible and associated with considerable long-term survival as well as long-term disease-free survival. Keywords Chemotherapy . Acute leukemia . Lymphoma . Cancer . Intensive care unit . Tumor lysis syndrome
Introduction P. Wohlfarth : T. Staudinger : W. R. Sperr : A. Bojic : O. Robak : A. Hermann : K. Laczika : A. Carlström : K. Riss : W. Rabitsch : M. Bojic : P. Knoebl : G. J. Locker : P. Schellongowski (*) Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria e-mail: [email protected] M. Obiditsch Pharmacy Department, Vienna General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria V. Fuhrmann Department of Medicine III, Intensive Care Unit 13h1, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
Short- and long-term survival of critically ill cancer patients has improved markedly over the last decades [1–4]. For patients with both, hematological or solid malignancies, achievements have been reported in the therapy of acute respiratory failure [5–7], acute kidney failure [8, 9], and sepsis [10–12]. Moreover, quality of life after intensive care may not significantly differ in patients with hematologic malignancies when compared to the general ICU population [13]. Numerous well-established prognostic factors allowed for proposing a framework of evidence-based admission criteria [14]. Accordingly, unlimited intensive care seems to be beneficial in a significant proportion of selected patients with malignant diseases.
1630
Organ dysfunctions in cancer patients may arise from complications of the malignant disease itself as well as from toxic therapy-related effects or ensuing infections [14]. Thus, intensive care management of these patients requires specific knowledge and close cooperation between intensivists, hematologists, and oncologists [15]. Particular considerations arise when clinicians have to evaluate whether indicated chemotherapy (CT) should be administered to patients with acute organ dysfunctions. In fact, such decisions have to be taken regularly and may, in specialized centers, arise during treatment of every fourth hematologic intensive care unit (ICU) patient [1]. However, as of today, surprisingly, only three reports on moderately sized cohorts have been dedicated to the detailed description of such patients [16–18]. We report a single-center experience with critically ill ICU cancer patients and urgent indication of chemotherapy.
Materials and methods We retrospectively studied the clinical courses of all adult ICU patients (≥18 years of age) who received anti-cancer therapy at the Medical University of Vienna, General Hospital between October 2006 and November 2013. This study was conducted in accordance with Good Clinical Practice guidelines and the amended Declaration of Helsinki. The Institutional Ethical Review Board of the Medical University of Vienna approved the protocol and waved the need for informed consent due to the non-interventional retrospective design of the investigation. In our center, medical admissions to the ICU are granted to all cancer patients with one or more organ dysfunctions and life-extending therapeutic options on the discretion of the treating hemato-oncologist and the intensivist in charge. Decisions to admit a patient to the ICU are based on evidence-derived recommendations [14, 19]. Decisions on the administration of CT are made by the treating hematooncologist in cooperation with the intensivist. Interdisciplinary rounds are granted at least once a day. By analyzing the charts of the patients, we recorded the age, gender, characteristics of the underlying malignancy— including type and stage of the respective malignancy—time of diagnosis, type and timing of previous cancer specific treatments, and performance status (PS) 1 week prior to the actual hospitalization as described by the Eastern Cooperative Oncology Group scale [20], Charlson Comorbidity Index (CCI) [21], and Simplified Acute Physiology Score II (SAPS II) [22, 23] to quantify the severity of illness at ICU admission, the primary reason for ICU admission, presence and source of any documented infection, type of CT administered during the ICU stay, and intention of CT (curative vs. palliative) together with laboratory parameters (blood cell count, serum chemistry, and coagulation). Furthermore, the
Ann Hematol (2014) 93:1629–1636
need for invasive mechanical ventilation, vasopressors, renal replacement therapy (RRT), and extracorporeal life support (ECLS) were recorded as well as the occurrence of disseminated intravascular coagulation (DIC) by the definition of the International Society of Thrombosis and Hemostasis (ISTH) DIC score [24], risk for [25, 26] tumor lysis syndrome (TLS) as assessed by the stratification of Cairo et al. [26] and the TLS risk score of Darmon et al. [25], and the development of laboratory or clinically manifested TLS [26], use of blood products and coagulation factors, and medication for hyperuricemia (i.e., allopurinol and rasburicase). As follow-up, ICU and hospital survival, course of the malignancy (remission status), death date (if applicable), and date of the last visit were assessed. Continuous data are presented as median and interquartile ranges (25–75 %) unless otherwise indicated. Dichotomous data are presented as number and percentage. Data were compared between survivors and nonsurvivors by Fisher’s exact test for dichotomous variables and the Mann–Whitney U test for continuous variables, respectively. Differences were considered to be statistically significant when p was
ORIGINAL PAPER
Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit Philipp Wohlfarth & Thomas Staudinger & Wolfgang R. Sperr & Andja Bojic & Oliver Robak & Alexander Hermann & Klaus Laczika & Alexander Carlström & Katharina Riss & Werner Rabitsch & Marija Bojic & Paul Knoebl & Gottfried J. Locker & Maria Obiditsch & Valentin Fuhrmann & Peter Schellongowski & Arbeitsgruppe für hämato-onkologische Intensivmedizin der Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin (ÖGIAIN)
Received: 10 March 2014 / Accepted: 11 June 2014 / Published online: 6 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Prognostic factors and outcomes of cancer patients with acute organ failure receiving chemotherapy (CT) in the intensive care unit (ICU) are still incompletely described. We therefore retrospectively studied all patients who received CT in any ICU of our institution between October 2006 and November 2013. Fifty-six patients with hematologic (n=49; 87.5 %) or solid (n=7; 12.5 %) malignancies, of which 20 (36 %) were diagnosed in the ICU, were analyzed [m/f ratio, 33:23; median age, 47 years (IQR 32 to 62); Charlson Comorbidity Index (CCI), 3 (2 to 5); Simplified Acute Physiology Score II (SAPS II), 50 (39 to 61)]. The main reasons for admission were acute respiratory failure, acute kidney failure, and septic shock. Mechanical ventilation and vasopressors were employed in 34 patients (61 %) respectively, hemofiltration in 22 (39 %), and extracorporeal life support in 7 (13 %). Twenty-seven patients (48 %) received their first CT in the ICU. Intention of therapy was cure in 46 patients
(82 %). Tumor lysis syndrome (TLS) developed in 20 patients (36 %). ICU and hospital survival was 75 and 59 %. Hospital survivors were significantly younger; had lower CCI, SAPS II, and TLS risk scores; presented less often with septic shock; were less likely to develop TLS; and received vasopressors, hemofiltration, and thrombocyte transfusions in lower proportions. After discharge, 88 % continued CT and 69 % of 1-year survivors were in complete remission. Probability of 1- and 2year survival was 41 and 38 %, respectively. Conclusively, administration of CT in selected ICU cancer patients was feasible and associated with considerable long-term survival as well as long-term disease-free survival. Keywords Chemotherapy . Acute leukemia . Lymphoma . Cancer . Intensive care unit . Tumor lysis syndrome
Introduction P. Wohlfarth : T. Staudinger : W. R. Sperr : A. Bojic : O. Robak : A. Hermann : K. Laczika : A. Carlström : K. Riss : W. Rabitsch : M. Bojic : P. Knoebl : G. J. Locker : P. Schellongowski (*) Department of Medicine I, Intensive Care Unit 13i2, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria e-mail: [email protected] M. Obiditsch Pharmacy Department, Vienna General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria V. Fuhrmann Department of Medicine III, Intensive Care Unit 13h1, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
Short- and long-term survival of critically ill cancer patients has improved markedly over the last decades [1–4]. For patients with both, hematological or solid malignancies, achievements have been reported in the therapy of acute respiratory failure [5–7], acute kidney failure [8, 9], and sepsis [10–12]. Moreover, quality of life after intensive care may not significantly differ in patients with hematologic malignancies when compared to the general ICU population [13]. Numerous well-established prognostic factors allowed for proposing a framework of evidence-based admission criteria [14]. Accordingly, unlimited intensive care seems to be beneficial in a significant proportion of selected patients with malignant diseases.
1630
Organ dysfunctions in cancer patients may arise from complications of the malignant disease itself as well as from toxic therapy-related effects or ensuing infections [14]. Thus, intensive care management of these patients requires specific knowledge and close cooperation between intensivists, hematologists, and oncologists [15]. Particular considerations arise when clinicians have to evaluate whether indicated chemotherapy (CT) should be administered to patients with acute organ dysfunctions. In fact, such decisions have to be taken regularly and may, in specialized centers, arise during treatment of every fourth hematologic intensive care unit (ICU) patient [1]. However, as of today, surprisingly, only three reports on moderately sized cohorts have been dedicated to the detailed description of such patients [16–18]. We report a single-center experience with critically ill ICU cancer patients and urgent indication of chemotherapy.
Materials and methods We retrospectively studied the clinical courses of all adult ICU patients (≥18 years of age) who received anti-cancer therapy at the Medical University of Vienna, General Hospital between October 2006 and November 2013. This study was conducted in accordance with Good Clinical Practice guidelines and the amended Declaration of Helsinki. The Institutional Ethical Review Board of the Medical University of Vienna approved the protocol and waved the need for informed consent due to the non-interventional retrospective design of the investigation. In our center, medical admissions to the ICU are granted to all cancer patients with one or more organ dysfunctions and life-extending therapeutic options on the discretion of the treating hemato-oncologist and the intensivist in charge. Decisions to admit a patient to the ICU are based on evidence-derived recommendations [14, 19]. Decisions on the administration of CT are made by the treating hematooncologist in cooperation with the intensivist. Interdisciplinary rounds are granted at least once a day. By analyzing the charts of the patients, we recorded the age, gender, characteristics of the underlying malignancy— including type and stage of the respective malignancy—time of diagnosis, type and timing of previous cancer specific treatments, and performance status (PS) 1 week prior to the actual hospitalization as described by the Eastern Cooperative Oncology Group scale [20], Charlson Comorbidity Index (CCI) [21], and Simplified Acute Physiology Score II (SAPS II) [22, 23] to quantify the severity of illness at ICU admission, the primary reason for ICU admission, presence and source of any documented infection, type of CT administered during the ICU stay, and intention of CT (curative vs. palliative) together with laboratory parameters (blood cell count, serum chemistry, and coagulation). Furthermore, the
Ann Hematol (2014) 93:1629–1636
need for invasive mechanical ventilation, vasopressors, renal replacement therapy (RRT), and extracorporeal life support (ECLS) were recorded as well as the occurrence of disseminated intravascular coagulation (DIC) by the definition of the International Society of Thrombosis and Hemostasis (ISTH) DIC score [24], risk for [25, 26] tumor lysis syndrome (TLS) as assessed by the stratification of Cairo et al. [26] and the TLS risk score of Darmon et al. [25], and the development of laboratory or clinically manifested TLS [26], use of blood products and coagulation factors, and medication for hyperuricemia (i.e., allopurinol and rasburicase). As follow-up, ICU and hospital survival, course of the malignancy (remission status), death date (if applicable), and date of the last visit were assessed. Continuous data are presented as median and interquartile ranges (25–75 %) unless otherwise indicated. Dichotomous data are presented as number and percentage. Data were compared between survivors and nonsurvivors by Fisher’s exact test for dichotomous variables and the Mann–Whitney U test for continuous variables, respectively. Differences were considered to be statistically significant when p was
