Background: Closed-loop oxygen titration devices have been developed to avoid periods of hypoxemia and hyperoxemia, both detrimental to patients hospitalized for respiratory failure and requiring supplemental oxygen. However, their clinical impact remains unknown. Objective: To compare the effect of automatic versus manual oxygen titration on clinical outcomes in pediatric and adult patients requiring supplemental oxygen in the hospital. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched MEDLINE, EMBASE, and CENTRAL electronic databases (from inception to August 2018), and conference proceedings of major societies in respiratory medicine (2015–2018). Randomized controlled trials were included if they compared automatic to manual oxygen titration in hypoxemic inpatients and if they assessed at least one of the following: length of hospital stay (primary outcome), length of oxygen therapy, need and duration of mechanical ventilation, mortality, percentage of time within, above, and below the oxygen saturation target range, as well as the percentage of time spent in hypoxemia and hyperoxemia. Results: We included 9 trials (354 patients, adults and preterm infants, with or without ventilatory assistance). Eight of these trials were at high risk of bias due to lack of blinding and selective reporting. Automatic titration was associated with a significant decrease in the length of hospital stay (mean difference: –2.2 days; 95% CI: –3.8 to –0.6; p = 0.009; I² = 0%; n = 237, 2 trials), and a decrease in the length of oxygen therapy (mean difference: –1.6 days; 95% CI: –3.1 to 0.0; p = 0.05; I² = 0%; n = 237; 2 trials). We did not observe a reduction in the need for ventilatory assistance or in mortality in the automatic titration period. An increase in the percentage of time spent within target (mean difference: 18.23%; 95% CI: 10.93–25.52; I² = 81%; n = 351, 7 trials) and a significant reduction in the percentage of time spent in both hypoxemia and hyperoxemia with automatic compared to manual oxygen titration were, however, observed. Conclusions: In patients requiring supplemental oxygen in the hospital, automatic oxygen titration was associated with a reduction in length of both hospital stay and oxygen therapy, as well as a greater percentage of time spent within the saturation target range. However, it was not associated with a significant difference in the need for mechanical ventilation or in mortality. Results should be interpreted with caution due to the small number of included trials and their high risk of bias.

Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the following four sections: single-agent immunotherapy, immunotherapy and chemotherapy, dual immunotherapy, and dual immunotherapy and chemotherapy. The results are summarized and tabulated. Finally, application of the trial data is illustrated in four clinical scenarios depending on the programmed death-ligand 1 (PD-L1) expression levels. Single checkpoint inhibitors have become an easy and excellent treatment in patients whose tumors have high PD-L1 expression. Adding chemotherapy to immunotherapy benefits our patients. Immunotherapy, with or without chemotherapy, is now the standard of care in the first-line setting in patients without EGFR, ALK, or ROS driver mutations.

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.

Chemoradiotherapy (CRT) followed by durvalumab (CRT → durvalumab) is standard of care to treat patients with unresectable, stage III non-small cell lung cancer (NSCLC). The RELEVANCE study was designed to provide real-world effectiveness and safety data for CRT → durvalumab in Canadian settings. RELEVANCE was a retrospective, observational, multicenter chart review that included adult patients with unresectable, stage III NSCLC treated with CRT alone or CRT → durvalumab at 5 Canadian cancer centers. Key outcomes included treatment patterns, adverse events of special interest (AESI), and overall survival (OS). 487 patients were included (144 CRT alone; 343 CRT → durvalumab). Median follow-up was 43.1 and 35.8 months for the CRT alone and CRT → durvalumab groups, respectively. The most frequently observed regimen included radiotherapy dose 54-66 Gy and radiosensitizing carboplatin. Median treatment duration was 1.5 months (CRT alone) and 13.4 months (CRT → durvalumab), and 47 % of patients completed a full course of durvalumab. Median OS and 3-year OS rate were 21.3 months and 32 % for CRT alone and 44.6 months and 56 % for CRT → durvalumab. Exploratory analysis by programmed cell death-ligand 1 (PD-L1) expression status of the CRT → durvalumab group noted 3-year OS rates of 69 %, 44 %, and 39 % in the PD-L1 ≥ 50 % (high), 1 %-49 % (intermediate), and < 1 % (negative) populations, respectively (32 %, 38 %, and 24 % for CRT alone, respectively). PD-L1 high expression was associated with lower risk of death vs. PD-L1 negative expression (P < 0.05). The most common AESI with CRT → durvalumab was pneumonitis. Median OS for patients who completed durvalumab was not reached and was 41.3 months among patients who discontinued durvalumab due to AEs. Results validate the treatment benefit and safety of the PACIFIC regimen in real-world Canadian settings. Among patients who received CRT → durvalumab, there was a correlation between increasing PD-L1 status and improved OS; however, shorter OS was observed in patients discontinuing durvalumab early due to AEs. Real-world Canadian RELEVANCE study validates effectiveness and safety of durvalumab in patients with unresectable, stage III NSCLC.

Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42–0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34–0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44–1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.