National Health and Medical Research Council

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

Bangladesh, a lower-middle-income country in South Asia, faces a rapidly rising cancer burden. In the absence of a population-based cancer registry (PBCR), monitoring national patterns remains challenging and constrains evidence-informed policymaking. We analyzed temporal trends in cancer distribution at the country's largest national cancer hospital to inform priorities for a cancer control strategy. We conducted a retrospective analysis of 82,209 histologically and/or clinically confirmed cancer cases diagnosed or treated at the National Institute of Cancer Research & Hospital, between January 2014 and December 2020. Demographic and clinical data were extracted from hospital records, and cancers were grouped according to their primary anatomic site. Annual distributions and sex-specific patters of the 10 most common cancers were examined, and temporal changes were illustrated using trend diagrams. Over 7 years, the most common cancers were of the respiratory system (19.6%-22.5%), digestive organs (18.8%-22.8%), and breast (12%-14.9%). Comparison between 2014 and 2020 revealed notable increases in the proportion of digestive organ cancers (+3.6%), hematopoietic and reticuloendothelial malignancies (+1%), and breast cancer (+0.8%), whereas respiratory cancers (-2.3%), lymph node cancers (-1.1%), and bone and cartilage cancers (-1%) decreased. A marked spike in female genital cancers was observed in 2015 (11.84% v 9.9% average across other years). Findings should be interpreted in the context of hospital-based case mix and referral patterns. In this large tertiary cancer hospital in Bangladesh, respiratory system, digestive organ, and breast cancers represented the highest burden, with rising proportions of proportional increases in digestive, hematopoietic, and breast cancers and declines in respiratory and lymph node cancers, provide early signals of an evolving cancer landscape. While not population-representative, these trends highlight the urgent need to establish government-supported PBCRs in well-defined subnational regions to inform effective cancer control strategies for Bangladesh.

The paucity of diagnostic tests for isoniazid-resistant tuberculosis is concerning, given its status as the most common form of drug-resistant tuberculosis and a gateway to multidrug-resistant diseases. Molecular drug-susceptibility testing has improved access to timely diagnosis of rifampicin-resistant tuberculosis, but testing for isoniazid-resistant tuberculosis still remains rare. In this Review, we assessed the characteristics of molecular drug-susceptibility testing for detection of isoniazid-resistant tuberculosis, referencing the WHO target product profiles. 9243 citations were screened to select 238 studies published between 2000 and 2024. The diagnostics options have expanded rapidly since 2020, with 27 nucleic acid amplification tests, eight line probe assays, five DNA microarrays, two targeted next-generation sequencing platforms, and two whole-genome sequencing platforms. Most of the evaluated molecular drug-susceptibility tests met diagnostic performance targets but were often complex and costly. Although a few low-complexity nucleic acid amplification tests met key target product profile criteria, additional field validation and greater efforts are needed to ensure optimal feasibility and affordability for low-resource settings.

The immune system protects against invading pathogens and helps maintain homeostasis. Other pivotal roles include the regulation of tissue health through interactions with the nervous system. Understanding how these neuroimmune interactions may go awry in musculoskeletal conditions and how they can be targeted therapeutically may optimise patient care. We conducted a clinically focused narrative review of the role of the immune and nervous systems in musculoskeletal health and conditions such as neck pain, back pain and osteoarthritis and how psychosocial and behavioural factors impact these conditions via interacting with neuroimmune functioning. The interplay between the immune and nervous system is involved in both the physiology and pathology of musculoskeletal tissues, including bone, joint, nerve, muscle and tendon. We describe this at the local tissue, whole nervous system, and systemic (blood) level and how psychosocial and behavioural factors impact immune activity and influence outcomes. We also highlight recent advances in medical imaging and multi-omics that shed new light on the interplay between the immune and nervous systems in musculoskeletal conditions. Advances in understanding these relationships provide promising new treatment avenues for musculoskeletal conditions and important insights into how psychosocial- and behavioural-based therapies such as exercise and cognitive behavioural therapy work and can be optimised to improve outcomes. This review provides clinicians with a foundation in the neuroimmunology of musculoskeletal conditions. It also explores how the immune and nervous systems, and their interplay can be modulated to improve prevention and management strategies.

ABSTRACTPreventing pressure injuries among nursing home residents is a significant challenge that necessitates understanding the barriers and facilitators from the perspective of staff. This qualitative study aimed to describe these factors within Sri Lankan nursing homes. Semi‐structured interviews were conducted with 15 nursing home staff members from nine nursing homes in and near the Colombo district, Sri Lanka. The study was informed by the capability, opportunity, motivation, and behaviour model that guided both data collection and analysis. Data were analysed using content analysis. Using deductive coding based on capability, opportunity, and motivation, followed by inductive analysis, four primary categories emerged: focusing on skincare is foundational for pressure injury prevention, pressure injury knowledge is critical for prevention, pressure injury prevention is a low organisational priority, and overcoming challenges to enact pressure injury prevention. Key facilitators included access to skincare products, maintaining clean and dry skin, recognising risk factors, proactively managing risks, and understanding the broader implications of pressure injuries on residents and their families. Conversely, barriers encompassed limited training, varying staff support, inadequate resources, and the complexities of managing multiple tasks. This research highlights that enhancing knowledge and allocating resources effectively can improve the implementation of pressure injury prevention strategies in Sri Lankan nursing homes.

Adjuvant immunotherapy improved patient outcomes in two trials in completely resected non-small cell lung cancer (NSCLC), but with conflicting primary end point results. The Canadian Cancer Trials Group BR.31 trial evaluated adjuvant durvalumab in completely resected early-stage NSCLC. Following resection of stage IB (≥4 cm) to IIIA NSCLC (American Joint Committee on Cancer 7th Edition) and optional adjuvant chemotherapy, patients were randomly assigned 2:1 to durvalumab 20 mg/kg or placebo 20 mg/kg once every 4 weeks for 12 cycles. Random assignment was stratified by stage, extent of nodal dissection, tumor cell (TC) PD-L1 expression, adjuvant chemotherapy use, and center. The primary end point was investigator-assessed disease-free survival (DFS). Secondary outcomes included overall survival (OS), adverse events, and quality of life. The primary analysis was in the subgroup with cancers that had a PD-L1 TC expression ≥25%, no common activating EGFR mutations (EGFR-), and no ALK gene rearrangements (ALK-). Secondary analyses in hierarchical order included DFS in the subgroup whose tumors were EGFR-/ALK- with PD-L1 TC ≥1%, followed by all patients whose tumors were EGFR-/ALK-, followed by OS in the same primary and secondary subgroups in the same hierarchical order. Of 1,415 patients randomly assigned, 1,219 (86%) had EGFR-/ALK- tumors: 815 randomly assigned to durvalumab and 404 to placebo. With a median follow-up of 60 months, there were no differences in DFS between patients assigned durvalumab (316) versus placebo (161) in the primary population (stratified hazard ratio [HR], 0.93 [95% CI, 0.71 to 1.25]; P = .64) or in the secondary populations. Grade 3 to 4 adverse events were higher in durvalumab-treated patients (D = 26% v P = 20%). Adjuvant durvalumab following complete resection was not associated with improvement in DFS compared with placebo in EGFR-/ALK- NSCLC, regardless of PD-L1 status.

BackgroundModerate-late preterm infants born at 32–35 completed weeks’ gestation constitute a large proportion of all preterm births (< 37-week gestation), yet they are not well represented in the newborn resuscitation literature. Preterm infants often receive respiratory support in the delivery room, and recommendations exist to guide the use of supplemental oxygen when providing this support. However, there are minimal data regarding the best initial supplementary oxygen concentration for moderate-late preterm infants requiring respiratory support at birth, resulting in practice variation. The aim of this trial is to compare initial supplementary oxygen concentrations of 30% and 21% (air) in preterm infants of 32–35 weeks’ gestation who require respiratory support in the delivery room, with a primary outcome of the need for ongoing respiratory support upon leaving the delivery room.MethodsThis is a prospective, unblinded, multicenter, cluster-randomized, crossover trial in Australian maternity hospitals comparing initial supplementary oxygen concentrations of 30% and 21% (air) in moderate-late preterm infants who require respiratory support at birth. Eligible infants are those born from 32 + 0 to 35 + 6 weeks’ gestation without major cardiorespiratory or craniofacial anomalies, who are receiving active care, and who receive respiratory support in the delivery room within the first three minutes after birth. The primary outcome is the need for ongoing respiratory support upon leaving the delivery room. The trial will recruit a minimum of 1200 infants from at least 20 study sites in Australia using a waiver of consent process.DiscussionThe AIROPLANE trial is a pragmatic study in an underrepresented population using a novel study design. It will be the first randomized study of initial supplementary oxygen concentration during respiratory support in the delivery room to exclusively recruit moderate-late preterm infants. The results will address an important evidence gap and will inform future international guidelines.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12621001267842. Registered on 20th September 2021.

Previous stage I-III colon cancer trials demonstrated improved peri-operative and similar long-term oncological outcomes with minimally invasive approaches compared with open surgery. Subsequent technical developments, including intracorporeal anastomosis, complete mesocolic excision (CME), refined pathologic grading systems and robotic approaches are increasingly used despite minimal supporting evidence. This international phase II trial aims to assess patient, surgical and pathological outcomes following robotic (RRHC) with laparoscopic right hemicolectomy (LRHC) for right sided colon cancer. Prospective, international multicentre pilot randomised phase II trial for patients with right colon adenocarcinoma, randomised 2:1 to robotic (RRHC) or laparoscopic (LRHC) surgery performed by accredited surgeons. Primary outcome was 90-day surgical morbidity measured using the Comprehensive Complication Index (CCI). Standardised pathology reviews, patient reported quality of life and surgeon task load index data was captured. RRHC vs. LRHC surgery allocation was 19 vs. 10, mean operative time 3.8 vs. 3.1 h with no operative mortality, all had R0 resection, CME rate 53 vs. 50% and intact mesocolon 94 v 100%. CCI was significantly lower at 30 and 90 days after RRHC (median (Q1, Q3): 0 (0, 9) vs. 21 (21, 26); median difference: 21; 95% CI 9-26; p = 0.005 at 30 days; p = 0.008 at 90 days). No significant differences in pathological nor quality of life data was observed. Surgeons task load data tended to favour robotic procedures. Median follow-up was 6 months. Limited funding led to early study closure. RRHC improved short-term surgical morbidity and surgeon physical demand and performance whilst obtaining similar quality of life and pathological specimen quality compared to LRHC for right sided colon cancer, supporting the case for larger randomised trials. ACTRN12620001378910.

Abstract BACKGROUND CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) gene alterations are integral to the diagnosis and prognostication of IDH-mutant gliomas. CDKN2A/B status is commonly assessed by next generation sequencing (NGS) or inferred from loss of the surrogate marker MTAP (5’-methylthioadenosine phosphorylase) by immunohistochemistry, since the MTAP gene (located adjacent to the CDKN2A/B locus on chromosome 9p21) is often presumed deleted when CDKN2A/B is deleted. However, with MTAP deletion emerging as a therapeutic target in gliomas, directly characterising its incidence and implications is essential. METHODS The incidence of CDKN2A/B and MTAP deletions was evaluated by NGS multigene panels across glioma subtypes within the Australian national Molecular Screening and Therapeutics (MoST) and Cancer Screening Programs (CaSP). All patients with glioma (glioblastoma, astrocytoma, oligodendroglioma) enrolled between June 2017 and April 2025 were reviewed. Sequencing was performed using FoundationOne CDx, TruSight Oncology 500, TruSight Tumor 170, or AVENIO. For panels not directly assessing MTAP, a bioinformatic algorithm was used to predict deletion based on copy number variation in non-targeted regions. RESULTS Of 785 gliomas, 328 (41.8%) had CDKN2A deletion and 271 (34.5%) had CDKN2A/B codeletion. MTAP homozygous deletion, whether predicted or directly measured, was observed in 230 (70.1%) with CDKN2A deletion and in 200 (73.8%) with CDKN2A/B codeletion. MTAP deletion was not identified in the absence of CDKN2A deletion. An additional 19 patients harboured CDKN2A/B mutations without associated MTAP deletion. When stratified by IDH mutation status, CDKN2A deletion occurred in 40 of 200 IDH-mutant gliomas (20%), with co-occurring MTAP deletion in 31 cases (77.5%); and in 288 of 585 IDH-wildtype gliomas (49.2%), with co-occurring MTAP deletion in 199 (69.1%). CONCLUSIONS MTAP deletions can no longer be inferred from CDKN2A/B status alone. Beyond NGS, evaluating other methods of determining MTAP deletion status such as immunohistochemistry would be worthwhile as a cost-effective method for screening and/or validation.