Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial.

BACKGROUND: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. METHODS: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. FINDINGS: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. INTERPRETATION: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. FUNDING: None.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.

Body position during laboratory and home polysomnography compared to habitual sleeping position at home.

STUDY OBJECTIVES: Supine-predominant obstructive sleep apnea (OSA) is highly prevalent. The proportion of time spent in the supine position may be overrepresented during polysomnography, which would impact on the apnea-hypopnea index (AHI) and have important clinical implications. We aimed to investigate the difference in body position during laboratory or home polysomnography compared to habitual sleep and estimate its effect on OSA severity. Secondary aims were to evaluate the consistency of habitual sleeping position and accuracy of self-reported sleeping position. METHODS: Patients undergoing diagnostic laboratory or home polysomnography were recruited. Body position was recorded using a neck-worn device. Habitual sleeping position was the average time spent supine over 3 consecutive nights at home. Primary outcomes were the proportion of sleep time spent supine (% time supine) and AHI adjusted for habitual sleeping position. RESULTS: Fifty-seven patients who underwent laboratory polysomnography and 56 who had home polysomnography were included. Compared to habitual sleep, % time supine was higher during laboratory polysomnography (mean difference 14.1% [95% confidence interval: 7.2-21.1]; P = .0002) and home polysomnography (7.1% [95% confidence interval 0.9-13.3]; P = .03). Among those with supine-predominant OSA, there was a trend toward lower adjusted AHI than polysomnography-derived AHI (P = .07), changing OSA severity in 31.6%. There was no significant between-night difference in % time supine during habitual sleep (P = .4). Self-reported % time supine was inaccurate (95% limits of agreement -49.2% to 53.9%). CONCLUSIONS: More time was spent in the supine position during polysomnography compared to habitual sleep, which may overestimate OSA severity for almost one-third of patients with supine-predominant OSA. CLINICAL TRIAL REGISTRATION: Registry: Australia and New Zealand Clinical Trials Registry (ANZCTR); Title: Sleeping position during sleep tests and at home; Identifier: ACTRN12618000628246; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374873&isReview=true. CITATION: Yo SW, Joosten SA, Wimaleswaran H, et al. Body position during laboratory and home polysomnography compared to habitual sleeping position at home. J Clin Sleep Med. 2022;18(9):2103-2111.

Incident pulmonary arterial hypertension associated with Bosutinib.

Pulmonary arterial hypertension is associated with tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia. Dasatinib is a known cause of drug-induced pulmonary arterial hypertension. There have been case reports linking Bosutinib with deterioration of pre-existing pulmonary arterial hypertension. Here, we present a case of a 37-year-old woman with chronic myeloid leukemia treated with Bosutinib who was diagnosed with pulmonary arterial hypertension. Prior to Bosutinib, she had received Dasatinib without documented cardiopulmonary toxicity. Withdrawal of Bosutinib led to partial reversal of pulmonary arterial hypertension, and with the addition of pulmonary arterial hypertension-targeted treatment, there was near normalization of hemodynamics.

Transition to Adult Care for Obstructive Sleep Apnea.

Obstructive sleep apnea may occur throughout the lifespan, with peak occurrences in early childhood and during middle and older age. Onset in childhood is overwhelmingly due to adeno-tonsillar hypertrophy, while in adulthood, contributors include risk factors, such as obesity, male sex, and aging. More recently, there has been a precipitous increase in the prevalence of obstructive sleep apnea in youth. Drivers of this phenomenon include both increasing obesity and the survival of children with complex medical conditions into adulthood. Appropriate treatment and long-term management of obstructive sleep apnea is critical to ensure that these youth maintain well-being unfettered by secondary comorbidities. To this end, patient engagement and seamless transition of care from pediatric to adult health care systems is of paramount importance. To date, this is an unacknowledged and unmet need in most sleep programs. This article highlights the need for guideline-driven sleep disorder transition processes and illustrates the authors' experience with the development of a program for sleep apnea.

Managing comorbid conditions in severe asthma.

Asthma care has increasingly focused on personalised management for severe asthma, and recognition of the role and importance of comorbid conditions has increased. Severe asthma can be crippling; associated comorbid conditions often play a key role in the significant disease morbidity and frequently contribute to a severe and difficult-to-treat asthma phenotype. Comorbid conditions can be broadly grouped as being either airway-related or airway-unrelated. Airway-related comorbid conditions with the greatest impact are allergic rhinitis, chronic rhinosinusitis, vocal cord dysfunction, lung fungal sensitisation and underlying structural lung disease. The most important airway-unrelated comorbid conditions are obesity, obstructive sleep apnoea, gastro-oesophageal reflux disease and anxiety and depression. A diagnostic and management algorithm for comorbid conditions in severe asthma is outlined. It concentrates initially on the group with common comorbid conditions that can be managed in primary care. If asthma remains troublesome, emphasis can shift to identifying uncommon and more complex factors. The algorithm allows for personalised diagnostic and management pathways to be implemented. Personalised diagnosis and management of comorbid conditions are essential to achieving effective and improved outcomes for patients with severe asthma.

Elective versus emergency abdominal surgery following cardiac transplantation: a Victorian state transplant service experience.

BACKGROUND: Heart transplant patients constitute a unique patient cohort with multiple risk factors predictive of poor surgical outcome. The Alfred Hospital offers the only heart transplant service in Victoria, Australia. This article presents The Alfred Hospital's experience with outcomes of abdominal operations in the heart transplant patient population. METHODS: The statewide cardiothoracic registry was cross-referenced with The Alfred Hospital's electronic hospital database to identify heart transplant patients who had undergone abdominal surgery from 2002 to November 2012. Patients who met the inclusion criteria were evaluated in two groups: elective and emergency surgical settings. In the emergency group, risk factors recorded for poor surgical outcome were high-dose immunosuppression therapy, diabetes and other conventional vascular risk factors. Outcome measures assessed in both groups were length of stay, readmission within 30 days and 1-year mortality. RESULTS: Twelve patients were identified who underwent 13 abdominal operations. Eight were elective cases and five were emergent abdominal operations. The mean length of stay was shorter in the elective group than the emergency group (2.5 days versus 21.3 days). There was one readmission within 30 days, and no mortality at 1 year following elective surgery. In the emergency surgery group, two patients were readmitted within 30 days post-operatively, and there were two deaths observed in this group. CONCLUSION: The Alfred Hospital experience demonstrates that elective abdominal surgery following heart transplantation can be performed safely. Emergent surgery in this group of patients, however, is associated with poorer outcomes.