Respiratory Clinical Trials

Bronchoscopy frequently precipitates intraprocedural hypoxemia. Although several recent randomized controlled trials suggest that high-flow nasal cannula oxygen (HFNO) reduces intraprocedural hypoxemia during bronchoscopy, the overall certainty of this evidence remains insufficient. Hence, we performed a systematic review and meta-analysis to compare the efficacy of HFNO with that of conventional low-flow oxygen therapy (COT) during adult bronchoscopy. MEDLINE, Embase, and trial registries were searched for randomized controlled trials (RCTs) involving adults (18y or older) undergoing bronchoscopy that compared HFNO with COT. The primary outcome was the incidence of hypoxemia during the procedure. The key secondary outcomes were total procedure time, bronchoscopy interruption, and lowest intraprocedural peripheral oxygen saturation. The pooled risk ratios (RRs) or mean differences (MDs) were calculated, and the certainty of evidence was assessed. The protocol was registered with PROSPERO (CRD420251071548). Eleven RCTs (12 study arms) comprising 1714 participants met the inclusion criteria. HFNO was found to significantly reduce the incidence of hypoxemic events compared with COT (RR: 0.39, 95% CI: 0.26-0.59) and lowered the likelihood of procedure interruption (RR: 0.39, 95% CI: 0.27-0.55). HFNO also maintained a higher nadir SpO2 (MD=4.5%, 95% CI: 3.02-5.99). No statistically significant difference was observed in the total procedure time (MD: -0.87min, 95% CI: -1.99 to 0.25). This meta-analysis showed HFNO reduces the incidence of intraprocedural hypoxemia and interruptions during bronchoscopy. Our findings support a selective approach, suggesting the benefits of HFNO are greater in high-risk patients.

Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection that primarily affects individuals with significant immunosuppression, including those receiving treatment for hematological malignancies or undergoing solid organ or hematopoietic stem cell transplantation. Additional risk factors include severe or prolonged viral infections such as influenza and COVID-19 requiring intensive care, as well as underlying conditions such as diabetes mellitus and chronic granulomatous disease. Although the clinical course could be variable, the initial presentation is often ill-defined. All three patients in this case series presented with fever and productive cough, and one developed hemoptysis during the ward stay. Diagnosis was established using a combination of radiological imaging, bronchoscopy with bronchoalveolar lavage for fungal cultures, and galactomannan antigen testing. Radiological findings were diverse, ranging from tree-in-bud nodules and cavitating consolidations to the rare occurrence of hydropneumothorax. Despite the importance of early recognition and prompt antifungal therapy, diagnosis and management remain challenging. This case series highlights the heterogeneous manifestations of invasive pulmonary aspergillosis, the diagnostic and therapeutic difficulties encountered, and the complexities of antifungal selection in the presence of organ dysfunction. Early detection and a multidisciplinary approach are essential for improving clinical outcomes. In situations where microbiological confirmation is not feasible, a high degree of clinical suspicion, characteristic radiological findings, and a favorable clinical response to empirical antifungal therapy may improve clinical outcomes.

<bold>Introduction:</bold> Iatrogenic pneumothorax (iPTX) is a heterogeneous group and is defined as a pneumothorax caused by medical procedures. There are limited data on the incidence, subtypes, pathophysiology and management of iPTX. <bold>Methods:</bold> To understand the incidence of iPTX and its subtypes, we conducted a retrospective review of all cases coded as likely iatrogenic pneumothorax in a UK hospital over the last 8-years (2016-2023). The dataset was obtained using the ICD-10 code for J93.8 for ‘other Pneumothorax’ and J95.8 for ‘other postprocedural respiratory disorders.’ A descriptive analysis of the dataset was conducted. <bold>Results:</bold> 167 unique patient episodes were identified. Of these, only 78 (46.7%) patients had correctly coded iPTX. Within the iPTX cohort, the main subtypes were post-CT-guided lung biopsy or PCTLB (42/78, 53.8%), post-lung ablation or LA (19/48, 24.4%), post-pacemaker (5/78, 6.4%), post-central-line (3/78, 3.8%) insertion and miscellaneous (9/78, 11.5%) as shown in Fig.1. The median age for post-PCTLB and post-LA pneumothorax was 71 years (IQR: 55-84). In the post-PCTLB group, 25/42 (59.5%) were treated with chest drain or ambulatory device whilst 11/19 (57.9%) were treated with chest drain in the post-LA group. The main reason for interventional management was radiologically enlarging pneumothorax but only 21/78 (26.9%) patients had symptoms of breathlessness, chest pain or hypoxia. Due to no dedicated code for iPTX, there is a high chance of missing patients which precludes true calculation of the incidence of this disease. <bold>Conclusion:</bold> This study highlights that iPTX is a common condition that is treated with invasive interventions without good evidence.

3503 Background: Despite adjuvant chemotherapy (ACT) a proportion of patients (pts) with stage III colon cancer (CC) will recur. Most at risk are those with detectable ctDNA, whereas those with undetectable ctDNA have a reduced recurrence risk. The DYNAMIC-III study explored the impact of ACT de-escalation or escalation as informed by post-surgery ctDNA results. Here, we report the primary analysis on the impact of treatment escalation in ctDNA-positive pts. Outcome data for treatment de-escalation in ctDNA-negative pts is immature. Methods: DYNAMIC-III is a multi-center, randomized, phase II/III trial. Eligible pts had resected stage III CC and were fit for ACT. Pts were randomly assigned 1:1 to ctDNA-informed or standard of care (SOC) management. Clinicians nominated the selected SOC ACT regimen prior to randomization. For ctDNA-informed management, a ctDNA-positive result at 5-6 weeks after surgery with a tumor-informed assay prompted an escalation ACT strategy (from single agent fluoropyrimidine [FP] to oxaliplatin-based doublet, from 3 months doublet to 6 months doublet or FOLFOXIRI [clinician choice], or from 6 months doublet to FOLFOXIRI). The primary efficacy endpoint for the ctDNA-positive cohort was 2-year RFS. The target sample size of 250 provided 80% power with 90% confidence to confirm superiority of ctDNA-informed treatment escalation compared to SOC with a HR of 0.746. Results: Of 961 eligible pts randomized between Oct 2017 and Apr 2023, 259 (27%) were ctDNA-positive. Of these, 113 (44%) had clinical low risk disease (non-N2 + non-T4). Median follow-up was 42.2 months (range 0.78 – 63.0). 115 (89%) of 129 ctDNA-informed pts received ACT escalation, with 65 (56%) receiving FOLFOXIRI. Of 130 SOC pts, 14 (11%) and 112 (86%) received single agent FP and oxaliplatin doublet, respectively. 2-year RFS for ctDNA-informed treatment escalation was 52% (90% CI: 44 - 59%) vs 61% (90% CI: 54 - 68%) for SOC (HR 1.11, 90% CI: 0.83 - 1.48; P = 0.6). The 3-year RFS for ctDNA-positive pts receiving FOLFOXIRI and FOLFOX/CAPOX was similar (47% vs 51%, HR 1.09, 90% CI 0.78 to 1.53; P = 0.7). In a pre-specified correlative analysis of all ctDNA positive pts, recurrence risk increased with ctDNA burden, with 3-year RFS of 78%, 63%, 36% and 22% for tumor-derived mutant molecules/mL quartiles &lt; 0.06, 0.06 – 0.17, 0.18 – 1.31, and &gt; 1.31, respectively (P &lt; 0.01). Treatment-related hospitalisation was similar for escalated and SOC pts (OR 1.21, P = 0.58). Analysis of post-ACT ctDNA is underway. Conclusions: In this first randomised study of ctDNA-informed management in stage III CC, we confirm the prognostic significance of detectable ctDNA, with the novel finding of recurrence risk increasing markedly with ctDNA burden. Treatment escalation, including to FOLFOXIRI, did not improve RFS. Future studies in ctDNA positive pts should explore other escalation strategies. Clinical trial information: ACTRN12617001566325 .

e15084 Background: Single gene assays constitute the most common modality used to detect actionable genomic biomarkers in cancer tissue in Australian clinical practice, while comprehensive genomic profiling (CGP) is not the current standard of care (SoC). This study explored the impact of the adoption of CGP on the chance of receiving matched targeted therapies in a retrospective cohort of Australian patients (recruited from July 2020 to June 2023) with advanced cholangiocarcinoma (CCA), colorectal cancer (CRC), or non-small cell lung cancer (NSCLC). Methods: A partitioned survival model was developed to compare health outcomes and medical costs between scenarios where CGP is unvailable versus the current SoC in Australia with limited CGP use. For each cancer type, the cohort was stratified into three sub-cohorts based on the therapy received: matched targeted therapy, unmatched therapy, or no therapy. Overall survival was informed by patient-level data from the Australian Molecular Screening and Therapeutics (MoST) program from patients who exhausted all lines of SoC. Outpatient healthcare costs and prescribed medicines were informed by the Medicare Benefits Schedule and Pharmaceutical Benefits Scheme (provided by Services Australia). The survival and cost inputs were stratified by the cancer type and three sub-cohorts. Quality of life was assessed using the EQ-5D-5L. Patients were assumed to equally receive unmatched therapy or no therapy before CGP was available, while the alternative scenario reflected the current distribution observed in the MoST program. Results: Patientsreceiving matched targeted therapy exhibited longer survival than those receiving unmatched therapy or no therapy (see Table). The undiscounted results showed that compared with the scenario where CGP was unavailable, the current CGP use in the MoST program led to incremental life years of 0.30 for CCA, 0.17 for CRC, and 0.15 for NSCLC and incremental quality-adjusted life years (QALYs) of 0.25 for CCA, 0.13 for CRC, and 0.12 for NSCLC. With the application of healthcare costs, these translate into incremental costs/QALY gained of $1,210 for CCA, $6,807 for CRC, and $1,248 for NSCLC. Conclusions: CGP has the potential to improve patient health outcomes and may be cost-effective for advanced solid cancers compared with single gene assays. Sub-cohort/scenario Mean survival (undiscounted, years) CCA n=163 CRC n=188 NSCLC n=61 Matched targeted therapy 3.44 2.64 1.80 Unmatched therapy 1.22 1.96 1.27 No therapy 1.17 1.04 1.08 Before CGP is available (50% unmatched therapy + 50% no therapy for all cancers) 1.20 1.50 1.18 After CGP is available 1.50 (assuming 13% matched therapy + 40% unmatched therapy + 46% no therapy 1.67 (assuming 19% matched therapy + 36% unmatched therapy + 46% no therapy 1.33 (assuming 26% matched therapy + 30% unmatched therapy + 44% no therapy

Cardiovascular disease is the leading cause of mortality not only in Australia but also worldwide. There is a high demand for a machine learning system that can predict disease risk at an early stage so that healthcare experts can provide interventions. The process of building a machine learning system requires cooperation between machine learning experts and healthcare experts who understand the data. This is both labor and computation-intensive. To make the state-of-the-art machine learning models accessible and save computation costs, we introduce a training data size prediction model called EDSPA, which is build for an automated machine learning system called Auto-Imblearn. EDSPA can predict the minimal number of training instances required for Auto-Imblearn to determine an ideal pipeline. Compared with the state-of-the-art automated machine learning systems, our system achieves the best prediction accuracy whilst saving computation costs when compared with exhaustive search.

<bold>Introduction & Background:</bold> Accurate survival prediction in patients with malignant pleural effusion (MPE) is paramount, with a need to balance the aggressiveness of management against likely survival time. The LENT and PROMISE scores have both been shown to carry predictive ability for prognosis in MPE, however they have yet to be widely adopted in clinical practice. <bold>Aims & objectives:</bold> This study aimed to assess the ability of the LENT and PROMISE scores to predict survival time in patients diagnosed with MPE at Oxford University Hospitals (OUH) between 2015-2023. <bold>Methods:</bold> A cohort of patients diagnosed with MPE was generated from the OUH pleural MDT meeting database. The medical records of these patients were reviewed to calculate the length of survival from MPE diagnosis, and LENT and clinical PROMISE scores at diagnosis. <bold>Results:</bold> 775 patients with a diagnosis of MPE made between 2015-2023 were identified and included in the study. The median (IQR) length of survival for patients in the low-, moderate- and high-risk LENT groups were 521 (319-833), 131 (62-284) and 40.5 days (20-80) respectively, while in the PROMISE categories A-D they were 302 (150-665), 87 (45-202), 52 (24-98) and 28 days (10-50). Kaplan-Meier analysis demonstrated a significant difference between survival curves for both the LENT (p < 0.0001) and PROMISE (p < 0.0001) score categories. Harrell’s C-statistic was 0.68 (95% CI: 0.66 – 0.70) and 0.70 (95% CI: 0.69 – 0.72) for LENT and PROMISE categories respectively. <bold>Conclusions:</bold> Both the LENT and PROMISE scores have predictive ability for survival time in MPE patients, however their clinical utility is limited by a lack of precision in survival estimates.

<bold>Introduction & Background:</bold> Over recent years there have been a number of new therapeutics to treat the underlying causative primary malignancies of malignant pleural effusions (MPE). However, whether these have improved survival time following the development of MPE is unknown. <bold>Aims & objectives:</bold> This study aimed to assess whether the survival length of patients diagnosed with MPE at Oxford University Hospitals (OUH) has changed between 2015-2023. <bold>Methods:</bold> A cohort of patients with MPE diagnosed between 2015-2023 was generated from the OUH pleural MDT database. Patients were split into groups of equal size based on MPE diagnosis date, and their survival time was assessed using Kaplan-Meier analysis. This was carried out for all causes of MPE, and specifically for lung cancer, mesothelioma and breast cancer patients. <bold>Results:</bold> 740 patients with MPE were identified. There were no significant differences between survival curves in either the all-cause analysis, or in the cancer-specific analyses. For the all-cause analysis, patients were split into three groups: Group 1 had MPE diagnosed between 07/2015-09/2018, Group 2 between 10/2018-03/2021, and Group 3 between 03/2021-10/2023. The median length of survival in Group 1 was 158 days, in Group 2 was 140 days and in Group 3 was 149 days. <bold>Conclusions:</bold> Our results indicate that despite the introduction of various new therapeutics for cancer types which cause MPE, there has not been a significant improvement in the length of survival from MPE diagnosis in our cohort.