Management and outcome of oncological patients under immune checkpoint inhibitors presenting at the emergency department.

INTRODUCTION: With the rising use of immune checkpoint inhibitors (ICIs) in oncology, emergency physicians are increasingly confronted with their immune-related adverse events (irAEs). We described the types of irAEs presenting to the ED of a Belgian cancer centre and determined associations with the development of an irAE and other patient's characteristics. Secondary objectives describe the therapeutic management and determine 7 and 30-day mortality. METHODS: A retrospective chart review of ED visits of patients on ICI from 15 December 2016 to 6 December 2020 was performed. Clinical presentation, cancer characteristics and type of ICI were extracted by a single abstractor. We recorded any suspicion of irAE in the ED and confirmation of an irAE was based on the patient's oncologist report. Outcome was based on mortality at date of last follow-up. RESULTS: 227 patients on ICI presented to the ED, with a total of 451 visits. 54 (12%) of the visits resulted in a diagnosis of irAE. Four clinical features were associated with an irAE: gastrointestinal complaints (p=0.01), skin rashes (p=0.02), acute renal failure (p=0.002) and abnormal liver function (p=0.04). An irAE was also associated with three different factors: a cancer status in remission (OR=5.33, 95% CI 2.57 to 11.04), a combination of two ICIs (OR=4.43, 95% CI 2.09 to 9.42) and a medical history of irAE (OR=2.44, 95% CI 1.27 to 4.68). 30-day mortality was lower in the irAE group (0%) than in the non-irAE group (13%, 95% CI 9% to 19%). CONCLUSIONS: Oncological patients under ICI presenting in the ED are more likely to have an irAE if they present with gastrointestinal and dermatological complaints, acute renal failure and abnormal liver function. This is also true for patients with any history of irAE, a concomitant use of two ICIs and with a cancer status in remission.

p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial.

In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression signature identified patients with a good prognosis irrespective of the luminal subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer.

Are Intensive Cares Worthwhile for Breast Cancer Patients: The Experience of an Oncological ICU.

PURPOSE: One among seven women will present with breast cancer for which major therapeutic advances led to a significant increase in survival and cure rates. During or after cancer treatment, severe complications may occur requiring admission in intensive care unit (ICU). Intensivists could be reluctant for accepting cancer patients in the ICU, and there are very few data about causes of admission and prognosis of patients with breast cancer admitted in the ICU for an acute complication. Our study seeks to determine, in a population of patients with breast cancer, the main causes for ICU admission and the predictors of death during hospital stay and prognostic factors for survival after hospital discharge. METHODS: This retrospective study includes all unplanned ICU admissions of patients with breast cancer in a cancer hospital from January 1, 2009 to December 31, 2014. To search for predictive factors of death during hospitalization, Mann-Whitney or Fisher Exact (or chi-square) tests were used for continuous variables or categorical variables, respectively. A logistic regression model was applied for multivariate analysis. Multivariate analysis of prognostic factors for survival after hospital discharge was performed with a Cox's proportional hazards model. RESULTS: Of 1586 ICU admissions during the study period, 282 (18%) concerned breast cancer of which 175 met the inclusion criteria. The main causes of admission were of cardiovascular (26%), respiratory (19%), neurologic (19%), or infectious (14%) origin. ICU death rate was 15% and, overall, 28% of the patients died during hospitalization. The median survival time after hospitalization was 12.8 months (95% CI: 8.2-20.7). Independent predictors of death during hospitalization were the sequential organ failure assessment (SOFA) score (OR 1.36, 95% CI 1.15-1.60), high GPT values (OR 3.70, 95% CI: 1.52-9.03), and cardiovascular disease (OR 0.23, 95% CI: 0.06-0.86). Independent predictors of death after hospital discharge were metastatic disease (HR 7.90, 95% CI 3.69-16.92), high GOT value (HR 3.22 95% CI: 1.93-5.36), simplified acute physiology score (SAPS) (HR 1.95 95% CI: 1.21-3.16), and therapeutic limitations during the first 24 h after ICU admission (HR 8.52 95% CI: 3.66-19.87). CONCLUSION: Independent predictors of death during hospitalization were related to the acute complications (SOFA score, GPT level and cardiovascular-related admission) while cancer parameters retained their prognostic significance for survival after hospital discharge (metastatic disease, therapeutic limitations).