Outcomes in Critically Ill Oncologic Patients
Cancer is the second leading cause of death globally, responsible for 8.8 million deaths in 2015. Globally, nearly 1 in 6 deaths is due to cancer. The introduction of new treatments for cancer and advances in the intensive care of critically ill cancer patients has improved the prognosis and survival. In recent years, classical intensive care unit (ICU) admission comorbidity criteria have been discouraging in this group of patients because the risk factors for death that have been studied, primarily the number of organ failures, allow us to understand the determinants of the prognosis inside the ICU. The number of cancer patients needing ICU care has increased both for cancer-related complications and for treatment-associated side effects. Approximately 13–22% of cancer patients will need admission to a general ICU, and only the 27% of ICU admissions are directly linked with cancer. Survival rates for patients with cancer who are admitted to the ICU have improved; therefore, admission should not be denied to patients only on the basis of their cancer diagnosis. Specialists who treat critically ill cancer patients should implement preventive measures to avoid in-hospital death of cancer patients, identifying them at an earlier stage of organ failures. ICU admission should help to prevent, detect, and treat organ dysfunction when offering full support to those cancer patients who are candidates for ICU admission to impact their final outcome. At present, treatment of these patients presents challenges for the oncologist, hematologist, surgical oncologist, and critical care specialist.
KeywordsCancer patients Oncologic patients Solid tumors Hematological malignancies Intensive care unit Critical care Outcomes
Cancer is the second leading cause of death globally, responsible for 8.8 million deaths in 2015. Globally, nearly 1 in 6 deaths is due to cancer . The introduction of new treatments for cancer and advances in the intensive care of critically ill cancer patients has improved the prognosis and survival. In recent years, classical intensive care unit (ICU) admission comorbidity criteria have been discouraging in this group of patients because the risk factors for death that have been studied, primarily the number of organ failures, allow us to understand the determinants of the prognosis inside the ICU . The number of cancer patients needing ICU care has increased both for cancer-related complications and for treatment-associated side effects . Approximately 13–22% of cancer patients will need admission to a general ICU, and only the 27% of ICU admissions are directly linked with cancer .
Outcomes of Critically Ill Patients with Solid Tumors
The reported ICU and hospital mortalies for patients with solid tumors varies from 5% to 85% and 5% to 77%, respectively . This variation reflects the substantial heterogeneity between studies and patients, with various tumors at different stages, and reasons for admission to the ICU. Patients with solid tumors are frequently admitted to the ICU for routine postoperative care after undergoing definitive surgical treatment of their underlying malignancy. Cancer patients with unplanned admission to the ICU had a hospital survival of 69% and a 180-day survival rate of 48% . The 1-year and 2-year survival rates survival rates of patients with metastatic solid cancer admitted to the ICU due to emergencies were 12% and 2.4%, respectively . The probability of leaving the hospital alive was greater for patients with solid tumors without established organ failure on admission to ICU . In a cohort study of 25,017 surgical admissions to general ICUs in the West of Scotland, cancer was a common morbidity at 21.8% of all admissions. ICU and hospital mortality were lower in the group of ICU patients with cancer [12.2%(95% CI, 11.3–13.1%) vs. 16.8% (95% CI, 16.3–17.4%) (P <0.001) and 22.9% (95% CI, 21.8–24.1%) vs. 28.1% (95% CI, 27.4–28.7%) (P <0.001)]; however, this survival advantage had reversed by 6 months . Mortality was higher in the cancer group for patients admitted to the hospital electively (14.8%, 95% CI, 13.6–16.1%; vs. 12.8%, 95% CI, 11.7–13.9%; P = 0.010) and for patients admitted to the hospital as an emergency (32.7%, 95% CI, 30.7–34.7%; vs. 29.1%, 95% CI, 28.4–29.9%; P = 0.001). The factor with the greatest association with hospital mortality was severity of illness (APACHE II score, ≥20; OR, 4.67; 95% CI, 4.34–5.01) followed by age 65 years or older (OR, 2.14; 95% CI, 2.01–2.29) and emergency hospitalization (OR, 2.86; 95% CI, 2.62–3.12) .
Outcome of Critically Ill Patients with Hematological Malignancies
The prognosis for patients with hematological malignancies (HM) admitted to the ICU is poor. Despite advances in the treatments of patients with HM [4, 7], recent reports indicated that the ICU mortality for critically ill patients with HMs ranges from 24% to 57% [2, 10, 11, 13, 17, 18, 26]. The main reasons for ICU admission in this group of patients include acute respiratory failure, sepsis or septic shock, and postoperative care. Nevertheless, the use of intensive chemotherapy protocols can lead to complications requiring ICU admission . Bone marrow transplant recipients staying in the ICU during subsequent hospitalizations have a high mortality. A study of 2653 consecutive patients undergoing bone marrow transplant over a decade in Ontario reported that ICU admission during subsequent hospitalizations is associated with high mortality (67%). Death rates at 1 year were highest among patients requiring aggressive ICU treatments including as mechanical ventilation (87%), pulmonary artery catheterization (91%), and hemodialysis (94%) . The outcomes of critically ill patients with HMs primarily depend on the number of organ failures . Taccone et al.  reported that more than 75% of cancer patients with three organs failing died compared with 50% of patients without cancer. Patients with a SOFA score ≥10 at the time of ICU admission had higher probability of dying during the hospital stay . Critically ill patients affected by HMs with acute respiratory failure who required invasive mechanical ventilation had high mortality [27, 30]. The need for vasopressors was an independent predictor of hospital mortality [15, 21, 26]. Cárdenas-Turanzas et al.  validated the performance of the SOFA score to predict death of critically ill patients with cancer. The authors reported overall ICU and in-hospital mortality rates of 11% and 17%, respectively. Medical patients had higher ICU and in-hospital mortality rates (25% and 37%, respectively) than did surgical patients (2% and 4%) . Despite advances in critical care and hematology, bone marrow transplant (BMT) recipients have not shown improved survival in the ICU. Unfortunately, the development of organ failure after BMT, especially respiratory failure and kidney failure, remains associated with a high risk of death. High mortality rates have been reported at 1 year in BMT recipients requiring advanced and aggressive organ support in the ICU, mechanical ventilation (87%), monitoring with pulmonary artery flotation catheter (91%), and hemodialysis (94%) . Patients with graft-versus-host disease requiring immunosuppression with steroids (≥0.5 mg/kg of prednisone daily), in addition to having a high risk of infectious complications, presented a higher risk of hospital death (HR: 1.60, 95% CI: 1.09–2.34, p = 0.010) . Gilbert et al.  reported 100% mortality in hematopoietic stem cell transplant recipients requiring mechanical ventilation and hemodialysis or mechanical ventilation with hepatic dysfunction (bilirubin ≥2 mg/dL). Thus, the medical team and the patient should always consider the poor prognosis of BMT recipients associated with the need for advanced organ support in the ICU. The decision to provide treatment in the ICU to this group of patients remains complex and difficult; therefore medical groups in the ICU who treat patients with HMs who are potential candidates for BMT must maintain constant and objective communication in relation to prognosis.
Admission of Patients with Cancer to the Intensive Care Unit
Cancer patients, in particular those with hematologic malignancies, are often considered poor candidates for ICU admission because of their historic high mortality rates, and their access to critical care services may be limited. The decision as to whether or not to admit a critically ill patient with cancer to the ICU should be based on already established criteria . Admission policies for ICUs should take into account improvements in the prognosis of critically ill patients with cancer over the last two decades. Admission to the ICU of critically ill cancer patients should be decided on the basis of their severity of illness and long-term prognosis, which rapidly and continuously changes, rather than on the basis of the presence of a malignancy or metastasis .
Less than three organ failures.
Recent diagnosis of hemato-oncological disease.
Treatment of medical emergencies related to cancer or its treatment; tumor lysis syndrome, pulmonary infiltrates in patients with leukemia or leukostasis as the initial manifestation of leukemia.
The likelihood of a cure or probable disease control.
Performance status (Eastern Cooperative Oncology Group scale) between 0 and 1.
Postoperative intensive care for patients undergoing complex surgical procedures who require hemodynamic monitoring and/or mechanical ventilation.
The patient or responsible family members do not accept admission to the ICU.
Patients in palliative care as the only treatment option.
Poor quality of life before the acute event.
When there is no certainty of the potential benefit of admitting the patient to the ICU, admission is suggested to ensure that the patient has a chance to recover from an acute complication .
Early ICU Admission
Overall, patients admitted late and those who are never admitted to the ICU present with higher Acute Physiology and Chronic Health disease Classification System II (APACHE II) and a higher risk of death compared to patients admitted immediately . Early intervention for physiological derangement that developed during hospitalization and led to ICU admission was independently associated with improved short-term and long-term outcomes in critically ill cancer patients . Lee et al.  reported that early intervention within 1.5 h of physiological derangement reduced the relative risk of 1-year mortality by 16% compared with late intervention after 1.5 h . Early ICU admission increased the chance of survival; in particular, a period of less than 24 h from hospital entry to ICU admission was associated with improved survival in patients with HMs (OR: 0.94, 95% CI: 0.89–0.99, p = 0.020) . These results suggest that patients with cancer should be admitted early to the ICU, with fewer resulting organ failures [1, 23, 24, 26]. Organ failure over the first hours or days of full life-support treatment could be a simple and objective tool for oncologists and intensivists group to identify patients who should be admitted earlier to the ICU .
Impact of Chemotherapy in Critically Ill Patients with HMs
Many patients with newly diagnosed HMs who have not yet received chemotherapy present with acute complications requiring ICU admission. Clinicians should consider that the administration of chemotherapy in the ICU is feasible, and the prognosis depends mainly on the number and severity of organ failures. Moreover, in patients with HMs and serious conditions such as severe sepsis or septic shock, recent treatment with chemotherapy was not associated with an increased risk of death . Furthermore, Darmon et al.  described 100 patients with newly diagnosed HMs and organ failures requiring chemotherapy to control HM, and the mortality rates at 30 and 180 days were 40% and 51%, respectively. The administration of urgently indicated CT in selected ICU cancer patients with acute organ failure was effective and was associated with considerable long-term survival, as well as long-term disease-free survival .
Patients with neutropenia are at high risk for infection. Several studies have suggested that the presence of neutropenia in patients with cancer admitted to the ICU was associated with worse outcomes [3, 19, 26]; however, it remains unclear whether neutropenia is a risk factor for death in critically ill cancer patients. A recent systematic review suggested a higher risk of death of 10% (6–14%) in neutropenic critically ill cancer patients . Nevertheless, the prognosis of patients with neutropenia and severe sepsis or septic shock has improved. Regazzoni et al.  reported the prognosis of 73 patients with cancer and septic shock and showed that neutropenia was not associated with increased mortality (56%) or longer stays in the ICU (6.6 days), compared to patients without neutropenia (52.1%, and 6.8 days). Namendys-Silva et al.  reported that neutropenia was one of the independent prognostic factors for hospital death among patients with HMs (OR: 4.24, 95% CI: 1.36–13.19, p = 0.012), and hospital mortality was 46.8%. This result was similar to that reported by Legrand et al. , who reported 43% mortality in patients with neutropenia and severe sepsis or septic shock. This improvement in survival is likely related to developments in the treatment of chemotherapy-induced neutropenia; severely ill patients with neutropenia should have the same opportunity to receive intensive care as patients with normal leukocyte counts.
Survival rates for patients with cancer who are admitted to the ICU have improved; therefore, admission should not be denied to patients only on the basis of their cancer diagnosis. Specialists who treat critically ill cancer patients should implement preventive measures to avoid in-hospital death of cancer patients, identifying them at an earlier stage of organ failures. ICU admission should help to prevent, detect, and treat organ dysfunction when offering full support to those cancer patients who are candidates for ICU admission to impact their final outcome. At present, treatment of these patients presents challenges for the oncologist, hematologist, surgical oncologist, and critical care specialist.
- 6.Bouteloup M, Perinel S, Bourmaud A, et al. Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH). Oncotarget. 2017;8(1):1860–70.CrossRefGoogle Scholar
- 11.Contejean A, Lemiale V, Resche-Rigon M, et al. Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study. Ann Intensive Care. 2016;6(1):102.CrossRefGoogle Scholar
- 13.Darmon M, Vincent F, Canet E, et al. Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie. Nephrol Dial Transplant. 2015;30(12):2006–13.CrossRefGoogle Scholar
- 39.The World Health Organization. Cancer. 2018. http://www.who.int/news-room/fact-sheets/detail/cancer Accessed 31 Oct 2018.