PURPOSE Antibiotic exposure before immune checkpoint inhibitor (ICI) treatment can negatively affect outcomes through alteration in the gut microbiome, but large-scale evaluations are lacking. We performed a population-level retrospective cohort study to evaluate the impact of antibiotic exposure before starting ICI on overall survival (OS). PATIENT AND METHODS Patients with cancer, age 65 years or older, who initiated treatment with ICIs between June 2012 and October 2018 in Ontario, Canada, were identified using systemic therapy administration data. The cohort was deterministically linked to other health care databases to obtain covariates and antibiotic prescription claim data at both 1 year and 60 days before ICI therapy. Multivariable Cox models evaluated the association between exposure and OS. RESULTS Among the 2,737 patients with cancer who received ICIs, 59% and 19% of patients received antibiotics 1 year and 60 days before ICI therapy, respectively. Median OS was 306 days. Any antibiotic exposure within 1 year before ICI was associated with worse OS (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.12 to 1.23; P = .03). In antibiotic class analysis, exposure to fluoroquinolones within 1 year (aHR, 1.26; 95% CI, 1.13 to 1.40; P < .001) or 60 days before ICI (aHR, 1.20; 95% CI, 0.99 to 1.45; P = .06) was associated with worse OS, with a dose effect seen on the basis of total weeks of exposure over 1 year (aHR, 1.07 per week; 95% CI, 1.03 to 1.11; P < .001) and 60 days (aHR, 1.12 per week; 95% CI, 1.03 to 1.23; P = .01). CONCLUSION In this population-level study, exposure to antibiotics and specifically fluoroquinolones before ICI therapy was observed to be associated with worse OS among older adults with cancer. Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving ICIs with prior antibiotic exposure.

ImportanceThe surgeon-anesthesiologist teamwork and relationship is crucial to good patient outcomes. Familiarity among work team members is associated with enhanced success in multiple fields but rarely studied in the operating room.ObjectiveTo examine the association between surgeon-anesthesiologist dyad familiarity—as the number of times working together—with short-term postoperative outcomes for complex gastrointestinal cancer surgery.Design, Setting, and ParticipantsThis population-based retrospective cohort study based in Ontario, Canada, included adults undergoing esophagectomy, pancreatectomy, and hepatectomy for cancer from 2007 through 2018. The data were analyzed January 1, 2007, through December 21, 2018.ExposuresDyad familiarity captured as the annual volume of procedures of interest done by the surgeon-anesthesiologist dyad in the 4 years before the index surgery.Main Outcomes and MeasuresNinety-day major morbidity (any Clavien-Dindo grade 3 to 5). The association between exposure and outcome was examined using multivariable logistic regression.ResultsSeven thousand eight hundred ninety-three patients with a median age of 65 years (66.3% men) were included. They were cared for by 737 anesthesiologists and 163 surgeons who were also included. The median surgeon-anesthesiologist dyad volume was 1 (range, 0-12.2) procedures per year. Ninety-day major morbidity occurred in 43.0% of patients. There was a linear association between dyad volume and 90-day major morbidity. After adjustment, the annual dyad volume was independently associated with lower odds of 90-day major morbidity, with an odds ratio of 0.95 (95% CI, 0.92-0.98; P = .01) for each incremental procedure per year, per dyad. The results did not change when examining 30-day major morbidity.Conclusions and RelevanceAmong adults undergoing complex gastrointestinal cancer surgery, increasing familiarity of the surgeon-anesthesiologist dyad was associated with improved short-term patient outcomes. For each additional time that a unique surgeon-anesthesiologist dyad worked together, the odds of 90-day major morbidity decreased by 5%. These findings support organizing perioperative care to increase the familiarity of surgeon-anesthesiologist dyads.

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Objective: To examine the association of between hospital rates of high-volume anesthesiology care and of postoperative major morbidity. Background: Individual anesthesiology volume has been associated with individual patient outcomes for complex gastrointestinal cancer surgery. However, whether hospital-level anesthesiology care, where changes can be made, influences the outcomes of patients cared at this hospital is unknown. Methods: We conducted a population-based retrospective cohort study of adults undergoing esophagectomy, pancreatectomy, or hepatectomy for cancer from 2007 to 2018. The exposure was hospital-level adjusted rate of high-volume anesthesiology care. The outcome was hospital-level adjusted rate of 90-day major morbidity (Clavien-Dindo grade 3–5). Scatterplots visualized the relationship between each hospital’s adjusted rates of high-volume anesthesiology and major morbidity. Analyses at the hospital-year level examined the association with multivariable Poisson regression. Results: For 7893 patients at 17 hospitals, the rates of high-volume anesthesiology varied from 0% to 87.6%, and of major morbidity from 38.2% to 45.4%. The scatter plot revealed a weak inverse relationship between hospital rates of high-volume anesthesiology and of major morbidity (Pearson: −0.23). The adjusted hospital rate of high-volume anesthesiology was independently associated with the adjusted hospital rate of major morbidity (rate ratio: 0.96; 95% CI, 0.95–0.98; P<0.001 for each 10% increase in the high-volume rate). Conclusions: Hospitals that provided high-volume anesthesiology care to a higher proportion of patients were associated with lower rates of 90-day major morbidity. For each additional 10% patients receiving care by a high-volume anesthesiologist at a given hospital, there was an associated reduction of 4% in that hospital’s rate of major morbidity.

12002 Background: ICIs are a common therapeutic option across solid tumors. However, older adults were poorly represented in clinical trials evaluating ICIs, especially those who are very old or frail. Although ICIs are better tolerated than chemotherapy, some patients develop immune related adverse events (irAEs) that may require hospitalization. We performed a population-level retrospective cohort study to evaluate the impact of age and frailty among older adults on acute care use and irAE related hospitalizations. Methods: We used administrative data deterministically linked across databases to identify a cohort of cancer patients > 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada and obtained data on socio-demographic and clinical covariates, and acute care utilization. Acute care use was defined as an emergency department visit or hospitalization from initiation to 120 days after the last ICI dose; hospitalizations were classified as irAE related based on ICD-10 codes. Frailty was assessed using the McIsaac Frailty Index. Multivariable competing risk analyses with Fine Gray subdistribution hazards evaluated the impact of age and frailty on both acute care use and irAE hospitalizations adjusted for sex, rurality, BMI, autoimmune history, hospitalization within 60 days prior to starting ICI and comorbidity score. Results: Among 2737 patients, median age 73 (18% age > 80, 50% age 70-79); 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% had lung cancer, 34% melanoma. 70% were robust, 26% pre-frail and 4% frail. Most patients (1962; 72%) had an acute care episode during the window, while 212 (8%) had an irAE hospitalization. Older age was associated with reduced risk of being hospitalized due to an irAE when measured as a continuous variable (aHR 0.97 per year [0.95-0.99] p = 0.01). Older adults, age > 80 years were also less likely to be hospitalized due to an irAE (age 70-79 vs 65-69, aHR 0.92 [0.66-1.27] p = 0.61, age > 80 vs 65-69, aHR 0.63 [0.39-1.01] p = 0.05). Age was not associated with acute care use as a continuous or categorical variable. Increasing frailty was associated with increased risk of acute care use during ICI treatment (pre-frail vs robust, aHR 1.20 [1.07-1.36] p = 0.003; frail vs robust, aHR 1.45 [1.12-1.86] p = 0.004) but was not associated with irAE hospitalizations. When evaluating both age and frailty in the same model, the identified associations remained significant. Conclusions: Among older adults receiving ICIs, age was not associated with acute care use but may be associated with reduced risk of experiencing an irAE related hospitalization. In contrast, frailty was associated with risk of acute care use but was not associated with risk of an irAE related hospitalization. Age and frailty may need to be considered independently when evaluating their use as potential factors influencing toxicity risk among older adults receiving ICIs.