The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population.

IMPORTANCE: Immunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed. OBJECTIVE: To understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined 'older patient' as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0. MAIN OUTCOMES AND MEASURES: Study outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs. RESULTS: Our study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65-74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64-74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28-43.9, 95% CI) and 17 months (0-36.9, 95% CI) in the age <65 and age 64-74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups. CONCLUSION AND RELEVANCE: Our results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.

Ear Disease Knowledge and Otoscopy Skills Transfer to Real Patients: A Randomized Controlled Trial.

OBJECTIVE: To determine which teaching method-otoscopy simulation (OS), web-based module (WM), or standard classroom instruction (SI)-produced greater translation of knowledge and otoscopy examination skills to real patients. DESIGN: In a prospective randomized controlled nonclinical trial, medical students were randomized to 1 of 3 interventional arms: (1) OS, (2) WM, or (3) SI. Students were assessed at baseline for diagnostic accuracy and otoscopy skills on 5 volunteer patients (total of 10 ears), followed by the intervention. Testing was repeated immediately after intervention on the same patients. Student reported confidence in diagnostic accuracy and otoscopy examination were also captured. Assessors were blinded to the intervention group, and whether students were pre- or post-intervention. SETTING: Clinical Teaching Centre, Queen's University. PARTICIPANTS: Twenty-nine participants were initially randomized. Two students were unable to attend their specific intervention sessions and withdrew. Final group sizes were: OS-10, WM-9, SI-8. Five patients with external/middle ear pathologies were voluntarily recruited to participate as testing subjects. RESULTS: Baseline diagnostic accuracy and otoscopy clinical skills did not differ across the groups. Post-intervention, there were improvements in diagnostic accuracy from all groups: OS (127.78%, 2.30 ± 1.42, p = 0.0006), WM (76.40%, 1.44 ± 1.88, p = 0.0499), and SI (100.00%, 1.50 ± 1.20, p = 0.0093). For otoscopy skills, post-intervention improvements were noted from OS (77.00%, 3.85 ± 2.55, p < 0.0001) and SI (22.20%, 1.25 ± 1.20, p = 0.0011), with no significant improvement from WM (13.46%, 0.78 ± 1.92, p = 0.1050). Students across all groups reported significantly improved confidence in diagnostic accuracy (p < 0.0001) and otoscopy skill (p < 0.0001) after the intervention. CONCLUSION: All 3 teaching modalities showed an improvement in diagnostic accuracy immediately post-intervention. Otoscopy clinical skills were found to have increased only in OS and SI, with the OS group demonstrating the largest improvement. Simulation-based medical education in Otolaryngology may provide the greatest transfer of medical knowledge and technical skills when evaluated with real patients.