A mixed methods approach to developing and evaluating oncology trainee education around minimization of adverse events and improved patient quality and safety

BACKGROUND: Adverse events are a significant quality and safety issue in the hospital setting due to their direct impact on patients. Additionally, such events are often handled by junior doctors due to their direct involvement with patients. As such, it is important for health care organizations to prioritize education and training for junior doctors on identifying adverse events and handling them when they occur. The Cancer Cup Challenge is an educational program focuses on quality improvement and adverse event awareness targeting for junior oncology doctors across three international sites. METHODS: A mixed methodology was used to develop and evaluate the program. The Qstream spaced learning platform was used to disseminate information to participants, as it has been demonstrated to impact on both knowledge and behavior. Eight short case based scenarios with expert feedback were developed by a multidisciplinary advisory committee containing representatives from the international sites. At the conclusion of the course impact on participant knowledge was evaluated using analysis of the metrics collected by the Qstream platform. Additionally, an online survey and semi-structured interviews were used to evaluate engagement and perceived value by participants. RESULTS: A total of 35 junior doctors registered to undertake the Qstream program, with 31 (88.57 %) successfully completing it. Analysis of the Qstream metrics revealed 76.57 % of cases were answered correctly on first attempt. The post-program survey received 17 responses, with 76.47 % indicating cases for the course were interesting and 82.35 % feeling cases were relevant. Finally, 14 participants consented to participate in semi-structured interviews about the program, with feedback towards the course being generally very positive. CONCLUSIONS: Our study demonstrates that an online game is well accepted by junior doctors as a method to increase their quality improvement awareness. Developing effective and sustainable training for doctors is important to ensure positive patient outcomes are maintained in the hospital setting. This is particularly important for junior doctors as they are working closely with patients and learning skills and behaviors, which will influence their practice throughout their careers

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

Background Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.Methods This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).Results In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder’s TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response.Conclusions Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab