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A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) Abstract: BACKGROUND: In patients with advanced triple negative breast cancer (TNBC), immunotherapy has shown acceptable safety and efficacy in a PD-L1 (programmed death-ligand 1) positive population. Pre-clinical evidence has demonstrated that SABR can prime a more effective systemic anti-tumor response in combination with checkpoint inhibition. It is currently unknown if single or multi-fraction SABR scheduling synergises best with atezolizumab therapy. METHODS: This was a multi-centre, open label, phase 2 randomised trial of patients with advanced TNBC, unselected for (PD-L1) status, who had recurred at least 6 months post completion of (neo) adjuvant chemotherapy and received less than 2 lines of treatment in the metastatic setting. Participants were randomised to 20Gy SABR in 1 fraction or 24Gy SABR in 3 fractions to 1-4 sites of disease, with at least one metastasis left unirradiated. Within 5 days following the final fraction of radiotherapy atezolizumab was commenced at a dose of 1200 mg every 21 days and continued for up to 24 months, or until progression or intolerable toxicity. The primary endpoint is progression- free survival (PFS). Secondary endpoints include efficacy according to PD-L1 IHC status (positive: SP142 ≥1%) and TIL (tumour infiltrating lymphocyte) quantity, response assessment, overall survival and safety. Results presented are from interim analysis performed 18 weeks after the last patient commenced treatment. RESULTS: Fifty evaluable patients were recruited and randomised between 20th November 2018 and 12thApril 2021 with a median age of 57 [35 - 79] yrs. Thirty (60%) and 20 (40%) patients had received none or one previous line of chemotherapy in the metastatic setting, respectively. 14/40 (35%) patients were PD-L1 positive at baseline and 26/42 (62%) had TIL≥5%. Median follow-up was 17 months. The median PFS for the 20 Gy arm was 2.5 (90% CI: 1.7-4.5) months, 3.1 (90% CI: 1.8-3.9) months for the 24 Gy arm. For both arms combined, the PFS was 3.1 (90% CI: 1.8-3.9) months, with no difference between the arms, HR 1.2 (95% CI: 0.6-2.1), p=0.64. PFS by PD-L1 IHC status and TIL CONCLUSIONS: The efficacy between single and multi-fraction SABR in combination with Atezolizumab was similar and toxicity was acceptable. Efficacy was seen in PD-L1 positive and negative patients. Longer follow-up is required to assess the effect on OS.. (Research support and funding provided by the imCORE Network on behalf of F. Hoffmann-La Roche; AZTEC ClinicalTrials.gov Identifier: NCT03464942) Table 1.Response AssessmentResponse, n (%)All patients (n = 50)Patients with measurable disease (n = 32)Best objective response (non-SABR lesion)CR3 (6)2 (6)PR2 (4)2(6)NCR/NPD8 (16)0SD13 (26)13 (41)PD24 (48)15 (47)ORR (CR + PR)5 (10); 95% CI: 3-224 (12%); 95% CI: 4-29DCR (CR + PR + SD + non-CR/non-PD ≥24 weeks)a11 (22%); 95% CI: 12-377 (23%); 95% CI: 10-41aOne patient withdrew at 8 weeks and was not assessable for DCR. Citation Format: Steven David, Peter Savas, Shankar Siva, Michelle White, Michael W Neeson, Shane White, Gavin Marx, Robyn Cheuk, Michelle Grogan, Maria Farrell, Jessica Foudoulis, Annette Dempsey, Paul J Neeson, Mathias Bressel, Sherene Loi. A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-02.

Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT.We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed.In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cmThese data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.

Oncology patients who are migrants or refugees face worse outcomes due to language and communication barriers impacting care. Interventions such as consultation audio-recordings and question prompt lists may prove beneficial in mediating communication challenges. However, designing robust research inclusive of patients who do not speak English is challenging. This study therefore aimed to: a) pilot test and assess the appropriateness of the proposed research design and methods for engaging migrant populations, and b) determine whether a multi-site RCT efficacy assessment of the communication intervention utilising these methods is feasible.This study is a mixed-methods parallel-group, randomised controlled feasibility pilot trial. Feasibility outcomes comprised assessment of: i) screening and recruitment processes, ii) design and procedures, and iii) research time and costing. The communication intervention comprised audio-recordings of a key medical consultation with an interpreter, and question prompt lists and cancer information translated into Arabic, Greek, Traditional, and Simplified Chinese.Assessment of feasibility parameters revealed that despite barriers, methods utilised in this study supported the inclusion of migrant oncology patients in research. A future multi-site RCT efficacy assessment of the INFORM communication intervention using these methods is feasible if recommendations to strengthen screening and recruitment are adopted. Importantly, hiring of bilingual research assistants, and engagement with community and consumer advocates is essential. Early involvement of clinical and interpreting staff as key stakeholders is likewise recommended.Results from this feasibility RCT help us better understand and overcome the challenges and misconceptions about including migrant patients in clinical research.

Coastal agricultural practices are often located in catchments upstream of ecologically important aquatic systems. Here, we investigate the occurrence of pesticides in a coastal creek flowing into a habitat-protected area within the Solitary Islands Marine Park, Australia. Water samples were collected from six sites along a creek transect during three sampling periods. Samples were analysed for 171 pesticide analytes, including organochlorines, organophosphates, herbicides, and fungicides. Five insecticides, two herbicides, and two fungicides were detected. The neonicotinoid imidacloprid was detected at 5 out of 6 sites, with concentrations reaching 294 μg L

Ongoing land-use intensification in subtropical catchments is expected to release more inorganic nitrogen to downstream coastal waters similar to historical changes in temperate ecosystems. Here, we examined spatial and temporal drivers of stream nitrogen loads across a subtropical land-use gradient using the isotopic compositions of nitrate (NO