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Cancer and Sepsis: Adding Insult to Injury—As if Either Alone Were Not Enough?*

Parker, Robert I. MD

doi: 10.1097/CCM.0000000000003950
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Department of Pediatrics, Pediatric Hematology/Oncology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY

*See also p. 1310.

Dr. Parker has disclosed that he does not have any potential conflicts of interest.

Both sepsis and cancer are common diagnoses associated with admission to an ICU, and patients with both cancer and sepsis have generally been shown to carry an increased risk of mortality when compared with ICU sepsis patients without cancer (1–4). There is some variability in ICU cancer outcome with some studies demonstrating no increased mortality in ICU cancer patients and others finding increased mortality from cancer only in subsets of patients (e.g., elderly, those with advanced disease, those requiring mechanical ventilation, those having received a transplant) (5–9). Although the survival of cancer patients admitted to the ICU over the past 2–3 decades has improved, there are little data comparing outcome of those ICU patients with both conditions to ICU patients with neither. In this issue of Critical Care Medicine, Hensley et al (10) report the national experience with these patients. Using the National Readmissions Database for the years 2013–2014 comprised of 1,104,363 hospital admissions for sepsis and containing all-payer claims for 49% of U.S. population, the authors compared outcome for cancer patients with sepsis versus those with sepsis but no cancer diagnosis. Multiple clinical and outcome characteristics were compared between the groups, and several subgroup analyses were performed. Overall, in-hospital mortality for sepsis alone was 19.5% while that for cancer-related sepsis was 27.9%, a 43% increase in sepsis mortality in cancer patients compared with noncancer related sepsis. This excess sepsis mortality was noted across all age groups; however, the absolute difference was greatest for the young adult patients (age 18–44 yr). For this age group, the risk ratio (RR) of sepsis mortality ranged from 3.2 to 3.9 with the absolute increase in mortality approximately 15%. Excess mortality risk subsequently declined as age increased and was negligible (0.1%) for that group of patients greater than 85 years old. This is not too surprising given the high baseline mortality seen in the geriatric population. The youngest patients (those < 18 yr old) also demonstrated an absolute increase in sepsis mortality, although less than that found in the young adult population, with an increase in mortality of approximately 5% and a RR of 1.6–1.8. The reason(s) for this age effect on sepsis was not elucidated in the study by Hensley et al (10), but this is an important finding for the pediatric and young adult populations. Although the occurrence of organ dysfunction/failure was not appreciably different in cancer-related sepsis patients, the likelihood of readmission was higher following sepsis in cancer patients suggesting that these patients may be at higher risk for occult organ dysfunction having developed as a consequence of their acute critical illness. Although the authors noted some differences in outcome based on tumor type, the data available did not allow for further analysis regarding the validity or cause for this possible association. Probably the most important finding raised by the study by Hensley et al (10) is the marked increase in sepsis-related mortality in the young adult population who generally have a significantly better outcome than older adults. Indeed, this finding should alert intensivists to the need for aggressive management in these patients. The Adolescent and Young Adult (AYA) population of cancer patients, generally defined as those between the ages of 15 and 39 years old, has largely not been studied adequately in the oncology community as these patients are less likely to be enrolled in clinical cancer studies than are younger patients, and also generally represent a small minority of patients enrolled in adult oncology studies (11–13). As a consequence, there is often not the same clinical data on disease and treatment-related comorbidities from which to gain insights into the cause and pathophysiology of critical illness in these patients that may help guide treatment of sepsis.

The findings by Hensley et al (10) of an increase in sepsis-related mortality confirm findings of previously published studies comprised of smaller patient numbers and serves to alert clinicians to the seriousness of sepsis in these high-risk patients (14–17). Although the cause of increased mortality in cancer patients has not been identified, there are some data to suggest that an altered immune response in cancer patients is, at a minimum, a contributing cause (1617). The current study by Hensley et al (10) as well as each of these prior studies suggests possible causes for the increased mortality including “active” cancer, ongoing chemotherapy, critical neutropenia, and type of cancer. As each of these studies relied on retrospective analysis of clinical data, there is not the granularity of data that allowed investigators to parse out the relationship of each of these possible confounding factors. Let this report by Hensley et al (10) be a clarion call for collaborative research between the Critical Care and Oncology communities to design and implement robust studies investigating the effect cancer and cancer therapy has on critical illness in cancer patients, particularly the AYA population.

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Keywords:

adolescent and young adult; cancer; mortality; sepsis; young adult patients

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