Risk factors for immune-related adverse events from anti-PD-1 or anti-PD-L1 treatment in an Asian cohort of nonsmall cell lung cancer patients.

Immune-related adverse events (IrAEs) of immune checkpoint inhibitors (ICIs) can be serious and unpredictable. We examine the incidence rate and risk factors for IrAEs in an Asian cohort of nonsmall cell lung cancer (NSCLC) patients treated with immunotherapy. Between June 2014 and August 2020, we retrospectively analysed IrAEs in NSCLC patients treated with anti-PD-1 or anti-PD-L1 inhibitors at the National University Cancer Institute, Singapore. A Poisson regression model was used to estimate the effect of risk factors on incidence rate of any grade IrAEs. One hundred and forty-one patients were enrolled. Median age was 63. Majority were male (67%) with Eastern Cooperative Oncology Group (ECOG) PS 0-1 (77%). More than half (56%) received pembrolizumab. Eleven percent harboured epidermal growth factor receptor (EGFR) mutation. Eighteen percent received concomitant chemotherapy. Median number of cycles was 4, and median duration of treatment was 2.1 months. IrAEs were seen in 71 (50.4%) patients, with an incidence rate of 99 events per 1000 person-months. Fatigue (25%), rash (10.5%) and pneumonitis (7.9%) were the most common IrAEs. Twenty out of 152 IrAEs (13.2%) were Grade 3 or higher in severity: most common being pneumonitis (5.3%), fatigue (3.3%) and transaminitis (1.3%). Multivariable analysis demonstrated that concomitant chemotherapy use, higher BMI and presence of EGFR mutation are significant predictors for IrAEs (P < .0001; P = .016; P = .007). Our findings can help guide risk stratification and monitoring of IrAEs among NSCLC patients on immunotherapy.

A systematic review and meta-analysis of the adequacy of endobronchial ultrasound transbronchial needle aspiration for next-generation sequencing in patients with non-small cell lung cancer.

OBJECTIVES: Next-generation sequencing (NGS) is able to identify targetable mutations to guide therapy and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) offers a potential route to routinely obtain specimens for analysis. However, the suitability of EBUS-TBNA samples for NGS remains uncertain. MATERIALS & METHODS: A search was conducted from inception till 28th August 2020. Pooled proportion of adequate EBUS-TBNA samples for NGS was obtained based on binomial distribution with Freeman-Tukey double-arcsine transformation. meta-analysis of means was conducted to determine mean weight of DNA extracted from EBUS-TBNA samples. meta-regression was performed to explore sources of heterogeneity. The random-effects model was used for all analyses to account for variation between studies. RESULTS: Twenty-one studies comprising 1,175 patients were included. The pooled proportion of adequate EBUS-TBNA samples for NGS (yield) was 86.5% (95%-CI: 80.9% to 91.4%). Pooled mean weight of DNA extracted from EBUS-TBNA samples was 868.7 ng (95%-CI: 446.3 ng to 1291.1 ng). However, considerable heterogeneity (I2 = 84.0%, 97.1%) was found. Meta-regression with a mixed-effects negative exponential model showed an increased proportion of adequate EBUS-TBNA samples for NGS as mean number of passes increases (ß = 0.495, 95%-CI 0.313 to 0.676, P < 0.001). Modelled yield rates were 77.3%, 86.2%, 91.6% and 94.9% at mean passes of 3, 4, 5 & 6 respectively. CONCLUSION: EBUS-TBNA was associated with a high yield for NGS and the success of EBUS-TBNA sampling for NGS was proportional to the number of passes.

Implementation and experience of the first chief residency program in singapore.

BACKGROUND: Like their counterparts in many other nations, physicians in Singapore are tasked with providing care, conducting research, and teaching and providing leadership to junior doctors. In this paper, we describe our experience implementing the first chief residency program in Singapore. INITIATIVE: A pilot of a chief residency program was initiated in the Department of Medicine at National University Hospital in July 2008, with 1 chief resident (CR) and 2 associate CR positions. The pilot used the US model for CR training as the initial framework. CRs would assist in the orientation and integration of new residents, teach residents, promote camaraderie among residents, help resolve issues, function as a liaison to senior staff, and would be developed as potential health care leaders and physician role models. RESULTS: The CRs performed a host of administrative duties and initiated several improvements in the residency, including better practices for leave scheduling, call roster planning, and a night float system. CRs attended monthly meetings with division heads and participated in departmental strategic planning as well as professional development and leadership courses. The CR position was well regarded by the other residents, and this resulted in increased interest in identifying and addressing opportunities for improvement. The introduction of a chief residency also made the department a more attractive posting for residents and contributed to a significant increase in the number of applicants for residency rotations. CONCLUSIONS: A chief residency program can benefit residents' morale and a CR's development as a leader, and it can facilitate linkage between junior and senior hospital management that promotes active involvement in problem solving and clinical and education improvement. Support from hospital administrators and senior clinicians is essential, and mentoring and succession planning are important to ensure the program's continued success.

Primary cardiac lymphoma presenting with cardiac tamponade.

Primary cardiac lymphoma (PCL) is rare and occurs more commonly in immunocompromised patients. It can present in various ways, and diagnosis is particularly challenging, especially for the unsuspecting physician. We report a case of PCL in an immunocompetent 55-year-old man who initially presented with pyrexia of unknown origin, chest pain, dyspnea, and few early clinical signs, but who was later found to have cardiac tamponade and a large cardiac mass on echocardiography and cardiovascular magnetic resonance. A high index of suspicion is needed to diagnose PCL, and echocardiogram remains an important diagnostic tool.