Sonja Klebe

Molecular testing plays a critical role in guiding optimal treatment decisions for lung cancer patients across a variety of clinical settings. While guidelines for biomarker testing exist in other jurisdictions, to date no best practice guidelines have been developed for the Australian setting. To address this need, the Royal College of Pathologists of Australasia collaborated with the Thoracic Oncology Group of Australasia to identify state-based pathologists, oncologists and consumer representatives to develop consensus best practice recommendations. Sixteen recommendations were established encompassing appropriate biomarkers, lung cancer subtype, tumour stage, specimen types, assay selection and quality assurance protocols that can inform and standardise best practice in molecular testing of lung cancer. These multidisciplinary evidence-based recommendations are designed to standardise and enhance molecular testing practices for lung cancers and should help ensure laboratories provide high-quality molecular testing of lung cancer for all Australians, including those from regional or remote communities.

•We explored the neurophysiology underlying painful bladder sensations during UTI.•UTI induces significant bladder afferent hypersensitivity during distension.•Low-threshold afferents elicit exaggerated responses at normal bladder pressures.•Afferent hypersensitivity correlated with the development of bladder dysfunction.•Bladder afferents are key regulators of sensory and behavioural responses to UTI.

The use of asbestos-containing products was banned in Australia in 2003. However, the rates of new cases of mesothelioma, which has a very long latent period between exposure and disease, have continued to increase. The aim of this study was to investigate mesothelioma incidence in Australia by year of birth and age-period-cohort analysis and to develop projections of expected mesothelioma cases until 2034. Data were derived from the Australian Cancer Database which provides complete national records of mesothelioma cases notified between 1982 and 2020. Incidence rates were age-standardized to the 2001 Australian standard population to enable comparisons of the population across time. Age-period-cohort models were used to examine the temporal trends of incidence rates by age, calendar year, and birth cohort. Projections for incidence rates of mesothelioma for 2020 to 2034 were estimated using Nordpred models. Graphs of age-standardized incidence rates of mesothelioma suggest a birth cohort effect, and the age-period-cohort model confirmed this. There was a birth cohort effect in all cohorts born before 1960, strongest in cohorts born during 1920 to 1949. Projection modeling to 2034 suggested that the age-standardized rates will continue to decline whereas crude incidence rates of mesothelioma will stabilize and then gradually decline, mostly among people of 60 to 84 years of age. The findings are consistent with the greatest risk of mesothelioma in Australia occurring in cohorts with the highest levels of historical cumulative occupational exposure, showing the value of a ban on asbestos. The number of new cases of mesothelioma per year is not expected to decline until after 2030.

Background: Finding effective and curative treatment for mesothelioma remains challenging. While the introduction of immunotherapy combinations using ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have offered hope for some patients, a large proportion of mesothelioma cases, particularly the epithelial subtype, have minimal benefit from this. Methods: Our study was inspired by the results of the AdvanTG-105 phase I clinical trial, which showed partial response with anti-TIGIT/PD-1 treatment in two epithelioid mesothelioma patients. Here, we conducted a comprehensive in vivo experiment involving eight animal treatment groups administered with either PBS (control group), cisplatin/pemetrexed, anti-PD-1, anti-PD-1 + anti-CTLA-4, anti-TIGIT, anti-PD-1 + anti-TIGIT, anti-PD-1 + anti-CTLA-4 + anti-TIGIT, and cisplatin/pemetrexed + anti-PD-1 + anti-TIGIT. Results: Our results indicate that animals receiving anti-PD-1 + TIGIT exhibited a superior anti-tumour response, with 90% of the treatment group exhibiting an objective response, compared to 60%, 20% and 40% for the standard-of-care anti-PD-1 + CTLA-4, single-agent anti-PD-1 and cisplatin/pemetrexed treatment groups, respectively. Animals receiving anti-PD-1 + TIGIT displayed a significantly reduced average tumour size, with improved weight and survival rates, and fewer adverse effects than those receiving anti-PD-1 + CTLA-4 treatment. Anti-PD-1 + TIGIT-treated animals achieved complete tumour regression, with heightened effector CD8 + T cell and NK cell activity, remaining tumour-free for over 300 days without immune-related adverse events. After initial tumour elimination, anti-PD-1 + TIGIT-treated animals showed no tumour regrowth in the rechallenge experiment. Conclusions: These findings provide rationale for the development of an anti-PD-1 + TIGIT combination immunotherapy trial for mesothelioma patients.

Objective: Numerous epidemiological studies have shown increased health risks among workers and residents living near nuclear power plants exposed to radiation levels meeting regulatory dose limits. This study aimed to evaluate the association between radiation exposure and disease risks among these populations exposed to radiation levels meeting the current regulatory dose limits. Results: We searched four databases (Cochrane Library, PubMed, ScienceDirect, and Web of Science) for studies published before August 2023, screened eligible studies (inclusion and exclusion criteria based on population, exposure, comparator, and outcome framework), and collected data on exposure indicators and disease risks. We applied random-effects models of meta-analysis to estimate the pooled effects and meta-regression to assess the dose-response relationship (radiation dose rate for workers and distance for residents). We identified 47 studies, 13 with worker and 34 with resident samples, covering 175 nuclear power plants from 17 countries, encompassing samples of 480,623 workers and 7,530,886 residents. Workers had a significantly lower risk for all-cancer and a significantly higher risk for mesothelioma. Residents had significantly higher risks for all-cancer, thyroid cancer, and leukemia. Notably, children under 5 years old showed the highest risk for all-cancer. Our meta-regression showed a significantly positive dose-response relationship between cumulative dose of radiation exposure and risk for circulatory disease among workers. Our findings demonstrated higher risks for mesothelioma for workers and all-cancer, thyroid cancer, and leukemia for residents exposed to low-dose radiation from nuclear power plants. Some included studies did not adjust for cancer risk confounders, which could overestimate the association between radiation exposure and cancer risk and increase the risk of bias.