Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

In this multicentric, retrospective study, patients with newly diagnosed lung cancer admitted to ICU had acceptable ICU and hospital mortality rates of, respectively, 47 and 60%. However, mortality rates at three and 6 months remained substantially high (respectively, 67 and 71%). As expected, mortality rates rose with the severity of acute illness. Although mortality for patients who required only iMV was 60%, it reached 83% for patients with multiple organ failure. Those results were consistent with previous studies [12, 14, 15, 24] and could raise questions about the futility of intensive care for these last patients. In our study, decision to withhold or withdrawal life-sustaining therapies occurred for half of the patients with a high rate of mortality. (Seventy-two percentage of these patients died in ICU and 90% in the hospital.) Decreasing the number of unnecessary aggressive care is a major concern in this population, especially with the increasing number of patients treated for advanced cancer and therefore the number of patients with cancer-related emergencies [25]. The decisional process should include intensivists, oncologists and palliative care services. Triage criteria for this specific population of patients are still imperfect [9], and prognosis factors have been pursued to select patients who would benefit the most from intensive cares. Moreover, triage criteria should be frequently reassessed according to new treatment, and survival improvement in that setting [26].

Various factors are associated with mortality in the studies [27]. Besides organ failure related to acute disease, we found in our study two factors independently associated with hospital outcome and related to cancer characteristics. Metastatic disease was associated with mortality (p = 0.003), and the administration of chemotherapy during ICU stay was associated with survival (p = 0.020). In contrast to other previous studies [11, 13, 18], performance status was not associated with hospital mortality. This result could be related to the proportion of patients with good performance status in our cohort and to the analysis of hospital mortality only and not long-term outcome. Moreover, other prognosis factors have been described in oncology for advanced cancer patients, such as anorexia–cachexia syndrome, delirium, leukocytosis, lymphocytopenia, levels of C-reactive protein [28] or combinations of criteria, including Karnofsky index, number of metastatic sites, levels of serum albumin and lactate dehydrogenase (LDH) concentration [29]. They should be assessed for critically ill patients with inaugural diagnosis. Prospective large multicentric studies or meta-analysis is needed.

Our study added interesting data about critically ill lung cancer patients at the diagnosis of their malignancy. Studies concerning newly diagnosed lung cancer patients with life-threatening complications remained scarce [30, 31]. We defined new diagnosis as diagnosis within the month of ICU admission so that patients would not have received more than one line of treatment. Our results appear similar to recent studies on critically ill lung cancer patients, at different times of their disease [12, 18, 19].

A major strength of our study was that 17 patients were able to receive chemotherapy during their ICU stay. These patients presented mostly with SCLC. Chemotherapy was prescribed during ICU stay for 88% of patients because of cancer-related complications. Among these patients, ICU, hospital, 3- and 6-month mortality rates were, respectively, 29, 41, 53 and 59%. Receiving chemotherapy in ICU was independently associated with survival (p = 0.020). This suggested that rescue chemotherapy in ICU is feasible in selected patients and had a positive outcome. It also suggests that the tumor’s chemo-sensitivity is an important factor that should be taken into account in the decision of admitting patients in ICU. Because of their high response rate to chemotherapy [32], patients with SCLC remained good candidates for ICU admission at diagnosis. These results are consistent the study of Zerbib et al. [33] in which SCLC has been identified as an independent predictor of hospital survival for patients receiving chemotherapy in ICU for organ failure related to solid neoplasms. In another study by Chen et al. [30], ICU and hospital survival were better for patients who received either chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy compared with those receiving best supportive care. They also found that ICU survival was independently associated with the use of mechanical ventilation, which is different from our results. This difference might be explained by the particular population of the study composed by a high number of patient treated with EGFR-TKI with usually high rate of good and quick response to treatment [34]. Newly diagnosed lung cancer patients, especially those with high sensitivity to anticancer treatment admitted to the ICU for cancer-related complications, appear as a specific subgroup of patient who might benefit from invasive cares. Other studies are warranted to confirm those results, to explore the type and timing of anticancer therapy for this subpopulation, and data must be considered with caution over time since therapeutic advances in oncology are substantial. However, the increasing number of treated patients would lead to high rate of critical care admission. The decision for ICU admission, but also the assessment of the goals of care during ICU stay, should include intensivist, oncologist and palliative care physician to improve the best care for those patients [9]. Studies are needed to improve the best model of delivering care in that setting.

The present study has several limitations. First, it was retrospective, monocentric and focused on a small number of patients admitted to ICU. Although all the patients were diagnosed with lung cancer within 1 month and had a good performance status before ICU admission, the possibility of cancer treatment after complications leading to ICU admission could be small [35]. There were no details concerning triage decisions, and we could not analyze the outcome of patients who were referred, but not admitted, to the ICU. Second, the choice of the severity scores that has been made in this study can be debated. We use the SOFA and the SAPSII scores, but no differences have been clearly found between the different existing scores [36, 37] and others such as the Acute Physiology and Chronic Health Evaluation (APACHE) could have been used [38] in the specific population of cancer patients. Third, only a small number of patients received chemotherapy. There was a lack of details regarding the oncologic treatments received before ICU admission and type of chemotherapy regimens used during ICU stay, which might have an impact on the outcome. Tolerance and treatment-related toxicities of chemotherapy have not been recorded and were other important issues. Other treatments for non-small cell lung cancer (NSCLC), such as targeted therapies, were not analyzed in this study. However, some studies [30] confirmed improvements in the outcome for specific patients admitted to ICU with mutated NSCLC. Fourth, we did not describe outcome according to the metastatic stage. However, for ICU patients, number of metastatic site was not related to outcome in recent study [30]. Also, for some patients with diagnosis performed during ICU, metastatic stage was not completely known at ICU admission. Lastly, although 40% of patients were still alive at hospital discharge, we do not have any information about the quality of life and the possibilities to receive further oncologic treatments.

In conclusion, this multinational study showed that ICU management was appropriate for newly diagnosed, unresectable lung cancer patients. Nevertheless, tumor’s characteristics, number of organ dysfunctions and types of intensive interventions should be taken into account before admitting these patients in ICU. Metastatic disease and need for immediate invasive iMV were associated with mortality, and mortality rose with the severity of acute illness. The tumor’s chemo-sensitivity should also be estimated since rescue chemotherapy in ICU was associated with survival and should be proposed for selected patients, especially for those with cancer-related complications.