Introduction: Primary resistance to immune checkpoint inhibitors (ICI) is observed in routine clinical practice. We sought to determine factors predictive of primary resistance to ICI monotherapy, defined by the Society for Immunotherapy of Cancer (SITC) as progression within 6 months of ICI treatment with patients receiving at least 6 weeks of ICI monotherapy, in patients with advanced non-small-cell lung cancer (NSCLC). Method: Patients with stage IV NSCLC treated with at least 6 weeks of single-agent ICI at two tertiary hospitals in Singapore were included. A multivariate logistic regression model was utilised to elucidate factors predictive of primary resistance to ICI. Results: Of the 108 eligible patients, 59 (54.6%) experienced primary resistance. The majority were male (65.7%), smokers (66.3%), Chinese (79.6%), had adenocarcinoma (76.9%), received Pembrolizumab (55.6%) and received immunotherapy treatment in the later line setting (≥2 lines) (61.1%). Female gender (aOR = 3.16, p = 0.041), a sixth-week neutrophil-to-lymphocyte ratio (NLR) of ≥3) (aOR = 3.454, p = 0.037) and a later line of immunotherapy treatment (≥2 lines) (aOR = 2.676, p = 0.040) were factors predictive of primary resistance to ICI monotherapy in patients with advanced NSCLC. Conclusions: Using SITC criteria, an elevated NLR (≥3) at 6 weeks, female gender and a later line of immunotherapy treatment (≥2 lines) were predictive factors of developing primary resistance to ICI monotherapy in patients with advanced NSCLC.
Endobronchial ultrasound (EBUS) combined with trans-esophageal endoscopic ultrasound bronchoscope guided fine need aspirate (EUS-B FNA) of mediastinal lymph nodes is an established procedure for diagnosis. The main barrier to a combined EBUS EUS-B FNA approach is availability of trained and accredited pulmonologist who can perform procedure safely and confidently. To address this gap, we undertook a training program for experienced EBUS bronchoscopists to train, learn, and incorporate combined EBUS EUS-B FNA into their procedural practice. Thirty-two patients were selected based on CT and or PET findings. Four experienced bronchoscopists participated by reading through learning material, observing 5 cases before performing EUS-B FNA under direct supervision. Forty-one lymph nodes and 6 non-nodal lesions were sampled. EUSAT assessment was performed by supervisor. Learning curves were derived from assessment scores. We observed that learning curve tends to plateau when participant can perform 3 or more consecutive cases with EUSAT score above 50. There were no complications. Our experience suggests that there is relative ease in transition to combined EBUS EUS-B TBNA procedures for mediastinal lymphadenopathy and lung cancer diagnosis and staging for experienced bronchoscopist using a program which incorporates direct supervision, EUSAT assessment, and extension of EUS B FNA training into daily real-world practice.
Long duty hours have been associated with significant medical errors, adverse events, and physician "burn-out". An innovative night float (NF) system has been implemented in our internal medicine program to reduce the negative effects of long duty hours associated with conventional full-call systems. However, concerns remain if this would result in inadequate training for interns. We developed a structured questionnaire to assess junior doctors' perceptions of the NF system compared to full calls, in areas of patient safety, medical training, and well-being. Ninety-seven (71%) of the 137 doctors polled responded. Ninety-one (94%) felt the NF system was superior to the full call system. A strong majority felt NF was beneficial for patient safety compared to full call (94% vs. 2%, p<0.001). The NF system was also perceived to reduce medical errors (94% vs. 2%, p<0.001) and reduce physician "burn-out" (95% vs. 5%, p<0.001). Beyond being a practical solution to duty-hour limitations, there was a significant perceived benefit of the NF system compared to the full call in terms of overall satisfaction, patient safety, reducing medical errors and physician "burn-out".
Convex probe endobronchial ultrasound transbronchial needle aspirations (CP-EBUS-TBNAs) and radial probe endobronchial ultrasound transbronchial lung biopsies (RP-EBUS-TBLBs) can be performed under moderate sedation or general anesthesia. Moderate sedation is more convenient, however patient discomfort may result in inadequate tissue sampling. General anesthesia ensures better patient cooperation but requires more logistics and also carries sedation risks. We aim to describe the diagnostic yield and safety of CP-EBUS-TBNAs and RP-EBUS-TBLBs when performed under moderate sedation at our center. All patients who underwent CP-EBUS-TBNA and/or RP-EBUS-TBLB under moderate sedation, between January 2015 and May 2017, were reviewed. Primary outcomes were defined in regard to the diagnostic yield and safety profile. A total of 336 CP-EBUS-TBNAs and 190 RP-EBUS-TBLBs were performed between January 2015 and May 2017. The mean sedation doses used were 50 mcg of intravenous fentanyl and 2.5 mg of intravenous midazolam. The diagnostic yield of the CP-EBUS-TBNAs and RP-EBUS-TBLBs were 62.5% and 71.6%, respectively. Complication rates were low with: transient bleeding 11.9%, transient hypoxia 0.5%, and pneumothorax 0.1%. None required escalation of care, post procedure. Performing CP-EBUS-TBNAs and RP-EBUS-TBLBs under moderate sedation is safe and provides good diagnostic yield. These procedures should, therefore, be considered as first-line sampling techniques.