Title: Admission of critically ill patients with cancer to the ICU: many uncertainties remain
Abstract: With the beginning of the 21st century, development in the early detection and management of patients with cancer has led to a significant increase in the survival rates of these patients.1.Brenner H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis.Lancet. 2002; 360: 1131-1135doi:10.1016/S0140-6736(02)11199-8Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar As a result, an increased number of patients with cancer are requiring admission to the intensive care unit (ICU) either for cancer-related complications or for treatment-associated side effects. Until recently, admission of patients with cancer to the ICU has been discouraged2.Guidelines for intensive care unit admission, discharge, and triage.Crit Care Med. 1999; 27: 633-638doi:10.1097/00003246-199903000-00048Crossref PubMed Scopus (489) Google Scholar because of the risk of unfavourable outcome.3.Schuster D.P. Everything that should be done—not everything that can be done.Am Rev Respir Dis. 1992; 145: 508-509doi:10.1164/ajrccm/145.3.508Crossref PubMed Scopus (40) Google Scholar4.Schapira D.V. Intensive care, survival, and expense of treating critically III cancer patients.JAMA. 1993; 269: 783doi:10.1001/jama.1993.03500060083036Crossref PubMed Scopus (193) Google Scholar According to the current literature, however, the number of patients with cancer who may benefit from ICU support has increased,5.Taccone F. Artigas A.A. Sprung C.L. et al.Characteristics and outcomes of cancer patients in European ICUs.Crit Care. 2009; 13: R15doi:10.1186/cc7713Crossref PubMed Scopus (282) Google Scholar, 6.Azoulay E. Alberti C. Bornstain C. et al.Improved survival in cancer patients requiring mechanical ventilatory support: impact of noninvasive mechanical ventilatory support.Crit Care Med. 2001; 29: 519-525doi:10.1097/00003246-200103000-00009Crossref PubMed Scopus (312) Google Scholar, 7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar, 8.Peigne V. Rusinová K. Karlin L. et al.Continued survival gains in recent years among critically ill myeloma patients.Intensive Care Med. 2009; 35: 512-518doi:10.1007/s00134-008-1320-4Crossref PubMed Scopus (96) Google Scholar, 9.Mokart D. Pastores S.M. Darmon M. Has survival increased in cancer patients admitted to the ICU? Yes.Intensive Care Med. 2014; 40: 1570-1572doi:10.1007/s00134-014-3433-2Crossref PubMed Scopus (45) Google Scholar while improved survival rates have been reported in various subgroups of patients previously supposed to be of adverse outcome, such as patients after haematopoietic stem cell transplantation, patients with acute respiratory failure, acute renal failure, even patients who received urgent chemotherapy while in the ICU.10.Azoulay E. Afessa B. The intensive care support of patients with malignancy: do everything that can be done.Intensive Care Med. 2006; 32: 3-5doi:10.1007/s00134-005-2835-6Crossref PubMed Scopus (111) Google Scholar11.Azoulay E. Lemiale V. Mokart D. et al.Acute respiratory distress syndrome in patients with malignancies.Intensive Care Med. 2014; 40: 1106-1114doi:10.1007/s00134-014-3354-0Crossref PubMed Scopus (195) Google Scholar These new data prompt the need for reappraisal of the policies regarding ICU admission in critically ill patients with cancer. The decision as to whether or not to admit a critically ill patient with cancer to the ICU is quite often challenging. Their medical problems along with their baseline disease underscore a need for an individual approach to this patient population. The decision to apply life-sustaining technology in these patients involves weighing the potential benefit against a futile care. Identification of factors associated with outcomes would help physicians, patients and families in determining the goals of treatment. Risk factors for adverse outcome have been defined repeatedly. Reasons of admission, type of malignancy, number of organ failures on ICU admission, need for mechanical ventilation, presence of invasive fungal infection and septic shock are, among others, factors that may influence the short-term outcome of these patients.10.Azoulay E. Afessa B. The intensive care support of patients with malignancy: do everything that can be done.Intensive Care Med. 2006; 32: 3-5doi:10.1007/s00134-005-2835-6Crossref PubMed Scopus (111) Google Scholar, 11.Azoulay E. Lemiale V. Mokart D. et al.Acute respiratory distress syndrome in patients with malignancies.Intensive Care Med. 2014; 40: 1106-1114doi:10.1007/s00134-014-3354-0Crossref PubMed Scopus (195) Google Scholar, 12.Wohlfarth P. Staudinger T. Sperr W.R. et al.Prognostic factors, long-term survival and outcome of cancer patients receiving chemotherapy in the intensive care unit.Ann Hematol. 2014; 93: 1629-1636doi:10.1007/s00277-014-2141-xCrossref PubMed Scopus (39) Google Scholar, 13.Staudinger T. Stoiser B. Mullner M. et al.Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.Crit Care Med. 2000; 28: 1322-1328doi:10.1097/00003246-200005000-00011Crossref PubMed Scopus (265) Google Scholar, 14.Kostakou E. Rovina N. Kyriakopoulou M. et al.Critically ill cancer patient in intensive care unit: issues that arise.J Crit Care. 2014; 29: 817-822doi:10.1016/j.jcrc.2014.04.007Crossref PubMed Scopus (48) Google Scholar Even though there are several publications focusing on the decision-making criteria for appropriate ICU utilisation,5.Taccone F. Artigas A.A. Sprung C.L. et al.Characteristics and outcomes of cancer patients in European ICUs.Crit Care. 2009; 13: R15doi:10.1186/cc7713Crossref PubMed Scopus (282) Google Scholar7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar15.Benoit D.D. Soares M. Azoulay E. Has survival increased in cancer patients admitted to the ICU? We are not sure.Intensive Care Med. 2014; 40: 1576-1579doi:10.1007/s00134-014-3480-8Crossref PubMed Scopus (32) Google Scholar, 16.Darmon M. Thiery G. Ciroldi M. et al.Intensive care in patients with newly diagnosed malignancies and a need for cancer chemotherapy.Crit Care Med. 2005; 33: 2488-2493doi:10.1097/01.CCM.0000181728.13354.0ACrossref PubMed Scopus (139) Google Scholar, 17.Azoulay E. Soares M. Darmon M. et al.Intensive care of the cancer patient: recent achievements and remaining challenges.Ann Intensive Care. 2011; 1: 5doi:10.1186/2110-5820-1-5Crossref PubMed Scopus (215) Google Scholar, 18.McGrath S. Chatterjee F. Whiteley C. et al.ICU and 6-month outcome of oncology patients in the intensive care unit.QJM. 2010; 103: 397-403doi:10.1093/qjmed/hcq032Crossref PubMed Scopus (51) Google Scholar the validity of these criteria has not been documented in different patient groups and thus, uncertainty still remains on the precise indications for ICU admission and/or continuation of treatment. It should be emphasised that precision in prognosis is crucially important in ensuring that patients with a reasonable prospect of recovery will not be deprived of ICU admission, but also that patients along with their families will not undergo any unnecessary suffering should there be a low chance of recovery. Emphasis should be given to the fact that the current prognostic models used for all ICU patients have been found to be inaccurate in predicting outcome in patients with cancer,19.Soares M. Fontes F. Dantas J. et al.Performance of six severity-of-illness scores in cancer patients requiring admission to the intensive care unit: a prospective observational study.Crit Care. 2004; 8: R194doi:10.1186/cc2870Crossref PubMed Google Scholar whereas clinical judgement alone fails to predict an accurate prognosis.20.Thiéry G. Azoulay E. Darmon M. et al.Outcome of cancer patients considered for intensive care unit admission: a hospital-wide prospective study.J Clin Oncol. 2005; 23: 4406-4413Crossref PubMed Scopus (233) Google Scholar In fact, the absence of reliable predictors of outcome at the time of ICU admission has led some investigators to suggest an 'ICU trial' consisted of an unrestricted ICU admission policy with full code management, for a limited period of time, followed by a reappraisal of the level of care afterwards.21.Lecuyer L. Chevret S. Thiery G. et al.The ICU trial: a new admission policy for cancer patients requiring mechanical ventilation.Crit Care Med. 2007; 35: 808-814doi:10.1097/01.CCM.0000256846.27192.7ACrossref PubMed Scopus (242) Google Scholar In a comprehensive narrative review published in the current issue of ESMO Open Journal—Cancer Horizons, Schellongowski et al22.Schellongowski P. Sperr W. Wohlfarth P. et al.Critically ill cancer patients: chances and limitations of intensive care medicine—a narrative review.ESMO Open. 2016; (▪▪▪)Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar highlight evidence-based knowledge on the issues concerning critically ill patients with cancer. In this valuable contribution to the existing literature, independent factors associated with short-term and long-term prognosis of critically ill patients with cancer are extensively presented. Although these outcome predictors could be used as reliable tools to help clinicians in determining which patients should be admitted to the ICU, the authors emphasise that 'an individual patient's prognosis is far from perfect' and that 'employing these criteria requires thorough evaluations of the applicability in the individual patient'. Both statements imply that there is still a high degree of uncertainty in this subject. Many factors appear to be associated with our persistent inability to determine admission criteria with accuracy: heterogeneity of the populations studied, the lack of information regarding long-term outcomes, the diverseness in patients approach by different specialities (oncologists and intensivists) and the fact that most studies on the topic are based on patient groups that may not be representative of that particular population are, among others, the main ones. Most of the studies published on the definition of mortality risk factors comprise inhomogeneous populations of patients with regard to type and stage of cancer, cause of ICU need, comorbidities and physical status of patients, time to ICU admission as well as admission and discharge policies.5.Taccone F. Artigas A.A. Sprung C.L. et al.Characteristics and outcomes of cancer patients in European ICUs.Crit Care. 2009; 13: R15doi:10.1186/cc7713Crossref PubMed Scopus (282) Google Scholar7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar8.Peigne V. Rusinová K. Karlin L. et al.Continued survival gains in recent years among critically ill myeloma patients.Intensive Care Med. 2009; 35: 512-518doi:10.1007/s00134-008-1320-4Crossref PubMed Scopus (96) Google Scholar14.Kostakou E. Rovina N. Kyriakopoulou M. et al.Critically ill cancer patient in intensive care unit: issues that arise.J Crit Care. 2014; 29: 817-822doi:10.1016/j.jcrc.2014.04.007Crossref PubMed Scopus (48) Google Scholar, 15.Benoit D.D. Soares M. Azoulay E. Has survival increased in cancer patients admitted to the ICU? We are not sure.Intensive Care Med. 2014; 40: 1576-1579doi:10.1007/s00134-014-3480-8Crossref PubMed Scopus (32) Google Scholar, 16.Darmon M. Thiery G. Ciroldi M. et al.Intensive care in patients with newly diagnosed malignancies and a need for cancer chemotherapy.Crit Care Med. 2005; 33: 2488-2493doi:10.1097/01.CCM.0000181728.13354.0ACrossref PubMed Scopus (139) Google Scholar18.McGrath S. Chatterjee F. Whiteley C. et al.ICU and 6-month outcome of oncology patients in the intensive care unit.QJM. 2010; 103: 397-403doi:10.1093/qjmed/hcq032Crossref PubMed Scopus (51) Google Scholar23.Soares M. Caruso P. Silva E. et al.Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study.Crit Care Med. 2010; 38: 9-15doi:10.1097/CCM.0b013e3181c0349eCrossref PubMed Scopus (255) Google Scholar Different prognostic criteria might be expected to apply to different groups of patients with cancer. Current clinical research on critically ill patients with cancer is focused on factors predicting short-term (ICU or hospital) mortality,5.Taccone F. Artigas A.A. Sprung C.L. et al.Characteristics and outcomes of cancer patients in European ICUs.Crit Care. 2009; 13: R15doi:10.1186/cc7713Crossref PubMed Scopus (282) Google Scholar6.Azoulay E. Alberti C. Bornstain C. et al.Improved survival in cancer patients requiring mechanical ventilatory support: impact of noninvasive mechanical ventilatory support.Crit Care Med. 2001; 29: 519-525doi:10.1097/00003246-200103000-00009Crossref PubMed Scopus (312) Google Scholar19.Soares M. Fontes F. Dantas J. et al.Performance of six severity-of-illness scores in cancer patients requiring admission to the intensive care unit: a prospective observational study.Crit Care. 2004; 8: R194doi:10.1186/cc2870Crossref PubMed Google Scholar23.Soares M. Caruso P. Silva E. et al.Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study.Crit Care Med. 2010; 38: 9-15doi:10.1097/CCM.0b013e3181c0349eCrossref PubMed Scopus (255) Google Scholar, 24.Azevedo L.C. Caruso P. Silva U.V. et al.Outcomes for patients with cancer admitted to the ICU requiring ventilatory support.Chest. 2014; 146: 257-266doi:10.1378/chest.13-1870Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 25.Maschmeyer G. Bertschat F. Moesta K.T. et al.Outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period.Eur J Cancer. 2003; 39: 783-792doi:10.1016/S0959-8049(03)00004-2Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar whereas studies on long-term outcomes have been mainly restricted to specific subgroups of patients.7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar12.Wohlfarth P. Staudinger T. Sperr W.R. et al.Prognostic factors, long-term survival and outcome of cancer patients receiving chemotherapy in the intensive care unit.Ann Hematol. 2014; 93: 1629-1636doi:10.1007/s00277-014-2141-xCrossref PubMed Scopus (39) Google Scholar26.Shih C.Y. Hung M.C. Lu H.M. et al.Incidence, life expectancy and prognostic factors in cancer patients under prolonged mechanical ventilation: a nationwide analysis of 5,138 cases during 1998–2007.Crit Care. 2013; 17: R144doi:10.1186/cc12823Crossref PubMed Scopus (28) Google Scholar, 27.van Vliet M. van den Boogaard M. Donnelly P. Long-term health related quality of life following intensive care during treatment for haematological malignancies.PLoS ONE. 2014; 9: e87779doi:10.1371/journal.pone.0087779Crossref PubMed Scopus (18) Google Scholar, 28.Schellongowski P. Staudinger T. Kundi M. et al.Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience.Haematologica. 2011; 96: 231-237doi:10.3324/haematol.2010.031583Crossref PubMed Scopus (91) Google Scholar Although in the majority of studies, short-term survival after ICU treatment has been reported to be higher than 50%,5.Taccone F. Artigas A.A. Sprung C.L. et al.Characteristics and outcomes of cancer patients in European ICUs.Crit Care. 2009; 13: R15doi:10.1186/cc7713Crossref PubMed Scopus (282) Google Scholar7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar8.Peigne V. Rusinová K. Karlin L. et al.Continued survival gains in recent years among critically ill myeloma patients.Intensive Care Med. 2009; 35: 512-518doi:10.1007/s00134-008-1320-4Crossref PubMed Scopus (96) Google Scholar15.Benoit D.D. Soares M. Azoulay E. Has survival increased in cancer patients admitted to the ICU? We are not sure.Intensive Care Med. 2014; 40: 1576-1579doi:10.1007/s00134-014-3480-8Crossref PubMed Scopus (32) Google Scholar18.McGrath S. Chatterjee F. Whiteley C. et al.ICU and 6-month outcome of oncology patients in the intensive care unit.QJM. 2010; 103: 397-403doi:10.1093/qjmed/hcq032Crossref PubMed Scopus (51) Google Scholar23.Soares M. Caruso P. Silva E. et al.Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study.Crit Care Med. 2010; 38: 9-15doi:10.1097/CCM.0b013e3181c0349eCrossref PubMed Scopus (255) Google Scholar25.Maschmeyer G. Bertschat F. Moesta K.T. et al.Outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period.Eur J Cancer. 2003; 39: 783-792doi:10.1016/S0959-8049(03)00004-2Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar long-term survival, quality of life and quality-adjusted life year expectancy have been reported to be limited.7.Azoulay E. Mokart D. Pène F. et al.Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study.J Clin Oncol. 2013; 31: 2810-2818doi:10.1200/JCO.2012.47.2365Crossref PubMed Scopus (404) Google Scholar15.Benoit D.D. Soares M. Azoulay E. Has survival increased in cancer patients admitted to the ICU? We are not sure.Intensive Care Med. 2014; 40: 1576-1579doi:10.1007/s00134-014-3480-8Crossref PubMed Scopus (32) Google Scholar18.McGrath S. Chatterjee F. Whiteley C. et al.ICU and 6-month outcome of oncology patients in the intensive care unit.QJM. 2010; 103: 397-403doi:10.1093/qjmed/hcq032Crossref PubMed Scopus (51) Google Scholar29.Normilio-Silva K. de Figueiredo A.C. Pedroso-de-Lima A.C. et al.Long-term survival, quality of life, and quality-adjusted survival in critically ill patients with cancer.Crit Care Med. 2016; 44: 1327-1337doi:10.1097/CCM.0000000000001648Crossref PubMed Scopus (34) Google Scholar30.Soares M. Salluh J.I.F. Torres V.B.L. et al.Short- and long-term outcomes of critically ill patients with cancer and prolonged ICU length of stay.Chest. 2008; 134: 520-526doi:10.1378/chest.08-0359Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar In fact, in an unselected population of patients with cancer, Normilio-Silva et al29.Normilio-Silva K. de Figueiredo A.C. Pedroso-de-Lima A.C. et al.Long-term survival, quality of life, and quality-adjusted survival in critically ill patients with cancer.Crit Care Med. 2016; 44: 1327-1337doi:10.1097/CCM.0000000000001648Crossref PubMed Scopus (34) Google Scholar have recently shown that the probabilities for attaining 12 and 18 months of quality-adjusted survival were 30.1% and 19.1%, respectively, while a wide variability of these outcomes was detected among patients. Factors associated with an acceptable short-term survival may be not relevant for long-term outcome, which seems to be poor, and thus additional doubts regarding the accuracy of our assessment arise. Uncertainties on the admission policies may also exist because the two main specialities that are usually asked to assess these patients and determine the indications for potential admission to the ICU, that is, oncologists and intensivists, are frequently distinct types of physicians and thus may have quite different perspectives for patients' situation and prospects.31.Von Bergwelt-Baildon M. Hallek M.J. Shimabukuro-Vornhagen A. et al.CCC meets ICU: redefining the role of critical care of cancer patients.BMC Cancer. 2010; 10: 612doi:10.1186/1471-2407-10-612Crossref PubMed Scopus (28) Google Scholar Furthermore, uncertainties may originate from the fact that most studies on predictive factors refer only to patients admitted to the ICU and not in all critically ill patients with cancer for whom an ICU admission was requested. Selection bias may impose limitations to the validity of the results of these studies. In fact, in a prospective 1-year study of all cancer and haematological patients for whom admission to ICU was requested, regardless of whether admission was granted or not, it was found that 20% of patients who were not admitted because they were considered 'too well' died and 25% of the patients who were not admitted because they were considered 'too sick' survived.20.Thiéry G. Azoulay E. Darmon M. et al.Outcome of cancer patients considered for intensive care unit admission: a hospital-wide prospective study.J Clin Oncol. 2005; 23: 4406-4413Crossref PubMed Scopus (233) Google Scholar These findings imply that physicians' judgement can be an unreliable predictor of the outcome, as well as that different admission criteria among centres may provide different results. Finally, although decisions about life-sustaining therapies should be based first on patients' preferences,32.U.S. Supreme Court Cruzan v. Director, Missouri Department of Health.Wests Supreme Court Report. 1990; 110: 2841-2892PubMed Google Scholar the majority of critically ill patients are unable to express their own decisions.33.Prendergast T.J. Luce J.M. Increasing incidence of withholding and withdrawal of life support from the critically ill.Am J Respir Crit Care Med. 1997; 155: 15-20doi:10.1164/ajrccm.155.1.9001282Crossref PubMed Scopus (550) Google Scholar A possible intensive care treatment has rarely been addressed in previous discussions,34.Nelson J.E. Gay E.B. Berman A.R. et al.Patients rate physician communication about lung cancer.Cancer. 2011; 117: 5212-5220doi:10.1002/cncr.26152Crossref PubMed Scopus (68) Google Scholar while the relatives are unable to precisely express patient's preferences.35.Shalowitz D.I. Garrett-Mayer E. Wendler D. The accuracy of surrogate decision makers. A systematic review.Arch Intern Med. 2006; 166: 493-497doi:10.1001/archinte.166.5.493Crossref PubMed Scopus (728) Google Scholar Our doubts as to whether our decisions about advanced ICU support are against patients' desires create additional concerns regarding the appropriateness of our choices. Although it is possible that prediction of mortality in an individual patient will remain an unrealistic goal, we need to minimise uncertainties on appropriate triage decisions in order to improve outcome of these patients without prolonging a painful dying process. To do so, we need large multicentre studies with homogenised inclusion and exclusion criteria as well as studies on long-term survival, disease-free survival and quality of life. In the mean time, enhancing interdisciplinary communication and collaboration of the ICU team with oncologists and palliative care specialists remains the best way to make a decision in a context of uncertainty.15.Benoit D.D. Soares M. Azoulay E. Has survival increased in cancer patients admitted to the ICU? We are not sure.Intensive Care Med. 2014; 40: 1576-1579doi:10.1007/s00134-014-3480-8Crossref PubMed Scopus (32) Google Scholar