Faculty Bibliography

Aim: Standard first-line treatment of advanced urothelial cell carcinoma involves cisplatin-based chemotherapy, with carboplatin or immune checkpoint inhibitor therapy (ICI) reserved for cisplatin-ineligible individuals. Methods: Using a large de-identified electronic health record-derived database of patients with advanced urothelial cell carcinoma in the USA, we examined trends in utilization of first-line systemic therapies in cisplatin-eligible patients from 1 January 2015 to 31 March 2018. Results: Among 1181 cisplatin-eligible patients, the quarterly proportion who received first-line ICI increased from 1 to 42% (p_trend <0.001), while the proportion who received cisplatin-based chemotherapy decreased from 53 to 33% (p_trend = 0.018). Patients receiving ICI were older than those receiving cisplatin (median age: 75 vs 68). Conclusion: Our analysis suggests rising off-label ICI use in cisplatin-eligible individuals, potentially because of ICI's favorable toxicity profile.

BACKGROUND:Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown. OBJECTIVE:To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS:We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness. RESULTS AND LIMITATIONS:IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0-45.3%] vs 46.1% [95% CI 43.4-48.8%]) but higher at 36 mo (28.3% [95% CI 21.8-34.7%] vs 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding. CONCLUSIONS:In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy. PATIENT SUMMARY:To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.

Several immune checkpoint inhibitor therapies (CPIs) have been approved to treat metastatic urothelial cell carcinoma (mUC). Because of the favorable toxicity profile of CPI compared with chemotherapy, oncologists may have a low threshold to prescribe CPI to patients near the end of life. We evaluated trends in initiation of end-of-life systemic therapy in 1,637 individuals in the Flatiron Health Database who were diagnosed with mUC between 2015 and 2017 and who died. Rates of systemic therapy initiation in the last 30 and 60 days of life were 17.0% and 29.8%, respectively. The quarterly proportion of patients who initiated CPI within 60 days of death increased from 1.0% to 23% during the study period (p

BACKGROUND:There are insufficient data to make firm dietary recommendations for patients with inflammatory bowel disease (IBD). Yet patients frequently report that specific food items influence their symptoms. In this study, we describe patients' perceptions about the benefits and harms of selected foods and patients' dietary patterns. METHODS:CCFA Partners is an ongoing internet-based cohort study of patients with IBD. We used a semi-quantitative food frequency questionnaire to measure dietary consumption patterns and open-ended questions to elicit responses from patients about food items they believe ameliorate or exacerbate IBD. We categorized patients into four mutually exclusive disease categories: CD without an ostomy or pouch (CD), UC without an ostomy or pouch (UC), CD with an ostomy (CD-ostomy), and UC with a pouch (UC-pouch). RESULTS:Yogurt, rice, and bananas were more frequently reported to improve symptoms whereas non-leafy vegetables, spicy foods, fruit, nuts, leafy vegetables, fried foods, milk, red meat, soda, popcorn, dairy, alcohol, high-fiber foods, corn, fatty foods, seeds, coffee, and beans were more frequently reported to worsen symptoms. Compared to CD patients, CD-ostomy patients reported significantly greater consumption of cheese (odds ratio [OR] 1.56, 95 % CI 1.03-2.36), sweetened beverages (OR 2.14, 95 % CI 1.02-1.03), milk (OR 1.84, 95 % CI 1.35-2.52), pizza (OR 1.57, 95 % CI 1.12-2.20), and processed meats (OR 1.40; 95 % CI 1.04-1.89). CONCLUSIONS:Patients identified foods that they believe worsen symptoms and restricted their diet. Patients with ostomies ate a more liberal diet. Prospective studies are needed to determine whether diet influences disease course.

BACKGROUND:Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice. PATIENTS AND METHODS/METHODS:This retrospective study used real-world data from the Flatiron Health electronic health record-derived deidentified longitudinal database. Patients with HR+/HER2- mBC aged ≥18 years at mBC diagnosis started 1L CDK4/6i therapy (index treatment) between February 2015 and November 2023, with a potential ≥6-month follow-up. OS was defined as months from start of index treatment to death. Stabilized inverse probability of treatment weighting (sIPTW; primary analysis) was used to balance baseline patient characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis. RESULTS:Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib plus AI, ribociclib plus AI, or abemaciclib plus AI, respectively. After sIPTW, baseline characteristics were balanced between treatment groups. After sIPTW, no significant OS differences were found between treatment groups [ribociclib versus palbociclib: adjusted hazard ratio (aHR) 0.98, 95% confidence interval (CI) 0.87-1.10, P = 0.7531; abemaciclib versus palbociclib: aHR 0.95, 95% CI 0.84-1.08, P = 0.4292; abemaciclib versus ribociclib: aHR 0.97, 95% CI 0.82-1.14, P = 0.6956]. Sensitivity analysis including a subanalysis of patients who started index treatment in 2017 or later also showed no significant OS differences between treatment groups. CONCLUSIONS:This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2- mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2- mBC.

A clinical artificial intelligence (AI) system is often validated on data withheld during its development. This provides an estimate of its performance upon future deployment on data in the wild; those currently unseen but are expected to be encountered in a clinical setting. However, estimating performance on data in the wild is complicated by distribution shift between data in the wild and withheld data and the absence of ground-truth annotations. Here, we introduce SUDO, a framework for evaluating AI systems on data in the wild. Through experiments on AI systems developed for dermatology images, histopathology patches, and clinical notes, we show that SUDO can identify unreliable predictions, inform the selection of models, and allow for the previously out-of-reach assessment of algorithmic bias for data in the wild without ground-truth annotations. These capabilities can contribute to the deployment of trustworthy and ethical AI systems in medicine.