Obesity, defined as a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) greater than 30, is a chronic disease with increasing prevalence around the world, largely contributing to important health issues in most countries.¹ Alongside body fat, which is a general risk factor for serious illness (eg, metabolic syndrome), greater cardiometabolic risk has also been associated with the localization of excess fat in the visceral adipose tissue and ectopic deposits.² Several large epidemiologic studies have evaluated the association between obesity and mortality. In particular, a meta-analysis of 230 cohort studies including more than 30 million individuals³ found that both obesity and overweight were associated with an increased risk of all-cause mortality. Despite the evidence that excess mortality increases with increasing BMI, some studies have reached the conclusion that elevated BMI may improve survival in patients with cardiovascular disease, a phenomenon called the obesity paradox.⁴

Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of irAEs versus no irAEs according to fixed or random-effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. A total of 30 studies that included a total of 4324 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death [HR=0.49, 95% confidence interval (CI): 0.38–0.62; P<0.001]. Similarly, the occurrence of irAEs was associated with a reduced risk of progression (HR=0.51, 95% CI: 0.42–0.64; P<0.001). The odds of response was 4.56 (95% CI: 3.72–5.59; P<0.001). In patients treated with ICIs, irAEs predict survival and response. Although this correlation cannot be fully explained, it may be related to the strongest T-cell activation.

High level of microsatellite instability (MSI-H) is the genetic feature of a well-defined subgroup of cancers characterized by a deficient mismatch repair (dMMR) system and the resulting inability to correct damage to DNA that primarily derives from single base pair insertions or deletions that may occur during DNA replication by DNA polymerases.