Irish national real-world analysis of the clinical and economic impact of 21-gene oncotype DX® testing in early-stage, 1-3 lymph node-positive, oestrogen receptor-positive, HER2-negative, breast cancer.

PURPOSE: The treatment landscape of Oestrogen receptor-positive (ER-positive) breast cancer is evolving, with declining chemotherapy use as a result of Oncotype DX Breast Recurrence Score® testing. Results from the SWOG S1007 RxPONDER trial suggest that adjuvant chemotherapy may benefit some premenopausal women with ER-positive, HER2-negative disease with 1-3 positive lymph nodes (N1), and a Recurrence Score® (RS) of ≤ 25. Postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. We examine the clinical and economic impact of Oncotype DX® testing on treatment decisions in patients with N1 disease in Ireland using real world data. METHODS: From March 2011 to October 2022, a retrospective, cross-sectional observational study was performed of patients with ER-positive, HER2-negative N1 breast cancer, who had Oncotype DX testing across 5 of Ireland's largest cancer centres. Patients were classified into low risk (RS 0-13), intermediate risk (RS 14-25) and high risk (RS > 25). Data were collected via electronic patient records. Information regarding costing was provided primarily by pre-published sources. RESULTS: A total of 828 N1 patients were included in this study. Post Oncotype DX testing, 480 patients (58%) were spared chemotherapy. Of the patients who had a change in chemotherapy recommendation based on Oncotype DX testing, 271 (56%), 205 (43%), 4 (1%) had a RS result of 0-13, 14-25 and > 25 respectively. Use of Oncotype DX testing was associated with a 58% reduction in chemotherapy administration overall. This resulted in estimated savings of over €6 million in treatment costs. Deducting the assay cost, estimated net savings of over €3.3 million were achieved. Changes in the ordering demographics of Oncotype DX tests were identified after RxPONDER data were presented, with increased testing in women ≥ 50 years and a reduction in proportion of tests ordered for women < 50 years. CONCLUSION: Between 2011 and 2022, assay use resulted in a 58% reduction in chemotherapy administration and net savings of over €3.3 million.

The effects of estuarine outflows on coastal marine ecosystems in New South Wales, Australia.

In the state of New South Wales (NSW), Australia, recent legislative action has focused on identifying key threats to the marine estate. We used a systematic literature review to evaluate the knowledge status of the effects of estuarine outflows on coastal marine ecosystems, within the environmental, hydrological, and physicochemical context of NSW waters. Results focussed on studies that measured outcomes for marine biota (n = 56). Trace elements and organochlorines were the most frequently studied contaminant types, with reported biological concentrations often below guideline values but detected at the highest concentrations adjacent to urban sources. Few studies measured the impacts of legacy and emerging contaminants to animal health, or the flow on effects to marine ecosystems in NSW. Our review highlights key biological and geographical data gaps in estuarine outflow research in NSW, particularly of the impact on ecosystems of exported carbon and nutrients to the oligotrophic waters of NSW.

Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Fine-scale spatial and temporal variations in diets of the pipefish Stigmatopora nigra within seagrass patches.

Diets of the pipefish Stigmatopora nigra were analysed to determine if food availability was causing S. nigra to distribute according to habitat edge effects. Gut analysis found little difference in the diets of S. nigra at the edge and interior of seagrass patches, regardless of time of day or season. Fish diets did, however, vary with seagrass density: S. nigra in denser seagrass consumed more harpacticoid copepods and fewer planktonic copepods. The lack of difference in prey eaten by S. nigra at the edge and interior of patches suggests either that food was not determining S. nigra distribution patterns within patches or that differences in fish densities across patches meant that relative fish-prey densities were similar at edge and interior positions. Alternatively, any edge effects in diet might be masked by gradients in seagrass structure.

Integrating edge effects into studies of habitat fragmentation: a test using meiofauna in seagrass.

Habitat fragmentation is thought to be an important process structuring landscapes in marine and estuarine environments, but effects on fauna are poorly understood, in part because of a focus on patchiness rather than fragmentation. Furthermore, despite concomitant increases in perimeter:area ratios with fragmentation, we have little understanding of how fauna change from patch edges to interiors during fragmentation. Densities of meiofauna were measured at different distances across the edges of four artificial seagrass treatments [continuous, fragmented, procedural control (to control for disturbance by fragmenting then restoring experimental plots), and patchy] 1 day, 1 week and 1 month after fragmentation. Experimental plots were established 1 week prior to fragmentation/disturbance. Samples were numerically dominated by harpacticoid copepods, densities of which were greater at the edge than 0.5 m into patches for continuous, procedural control and patchy treatments; densities were similar between the edge and 0.5 m in fragmented patches. For taxa that demonstrated edge effects, densities exhibited log-linear declines to 0.5 m into a patch with no differences observed between 0.5 m and 1 m into continuous treatments. In patchy treatments densities were similar at the internal and external edges for many taxa. The strong positive edge effect (higher densities at edge than interior) for taxa such as harpacticoid copepods implies some benefit of patchy landscapes. But the lack of edge effects during patch fragmentation itself demonstrates the importance of the mechanisms by which habitats become patchy.

Vulnerability of seagrass blue carbon to microbial attack following exposure to warming and oxygen.

Seagrass meadows store globally-significant quantities of organic 'blue' carbon. These blue carbon stocks are potentially vulnerable to anthropogenic stressors (e.g. coastal development, climate change). Here, we tested the impact of oxygen exposure and warming (major consequences of human disturbance) on rates of microbial carbon break-down in seagrass sediments. Active microbes occurred throughout seagrass sediment profiles, but deep, ancient sediments (~5000 yrs. old) contained only 3% of the abundance of active microbes as young, surface sediments (<2 yrs. old). Metagenomic analysis revealed that microbial community structure and function changed with depth, with a shift from proteobacteria and high levels of genes involved in sulfur cycling in the near surface samples, to a higher proportion of firmicutes and euraracheota and genes involved in methanogenesis at depth. Ancient carbon consisted almost entirely (97%) of carbon considered 'thermally recalcitrant', and therefore presumably inaccessible to microbial attack. Experimental warming had little impact on carbon; however, exposure of ancient sediments to oxygen increased microbial abundance, carbon uptake and sediment carbon turnover (34-38 fold). Overall, this study provides detailed characterization of seagrass blue carbon (chemical stability, age, associated microbes) and suggests that environmental disturbances that expose coastal sediments to oxygen (e.g. dredging) have the capacity to diminish seagrass sediment carbon stocks by facilitating microbial remineralisation.

Carbon sequestration by Australian tidal marshes.

Australia's tidal marshes have suffered significant losses but their recently recognised importance in CO2 sequestration is creating opportunities for their protection and restoration. We compiled all available data on soil organic carbon (OC) storage in Australia's tidal marshes (323 cores). OC stocks in the surface 1 m averaged 165.41 (SE 6.96) Mg OC ha-1 (range 14-963 Mg OC ha-1). The mean OC accumulation rate was 0.55 ± 0.02 Mg OC ha-1 yr-1. Geomorphology was the most important predictor of OC stocks, with fluvial sites having twice the stock of OC as seaward sites. Australia's 1.4 million hectares of tidal marshes contain an estimated 212 million tonnes of OC in the surface 1 m, with a potential CO2-equivalent value of $USD7.19 billion. Annual sequestration is 0.75 Tg OC yr-1, with a CO2-equivalent value of $USD28.02 million per annum. This study provides the most comprehensive estimates of tidal marsh blue carbon in Australia, and illustrates their importance in climate change mitigation and adaptation, acting as CO2 sinks and buffering the impacts of rising sea level. We outline potential further development of carbon offset schemes to restore the sequestration capacity and other ecosystem services provided by Australia tidal marshes.

Collecting duct carcinoma of the kidney: a case report with variable immunohistochemistry.

BACKGROUND: Collecting duct carcinoma of the kidney is a rare tumour with distinctive clinical and histopathological features. Management of this malignancy remains a challenge because of advanced stage at presentation and aggressive clinical course. AIMS: We describe a case of Collecting Duct Carcinoma with variable immunohistochemistry and review the pathology and management. RESULTS: Our patient died shortly after commencing systemic chemotherapy. CONCLUSION: Advances in immunohistochemistry have aided in diagnosis of this tumour. Early detection and nephrectomy offer the best chance of cure. Newer chemotherapeutic regimens may improve survival in more advanced disease.