Northern Health

Abstract Introduction: Abemaciclib, a CDK4/6 inhibitor, reduces the risk of recurrence in patients (pts) with high-risk HR+/HER2- early breast cancer; use is associated with toxicities, particularly diarrhea, which can impact pts’ ability to maintain dose and/or remain on therapy. TRADE (NCT06001762) is a phase 2, investigator-initiated single-arm trial designed to evaluate whether an initial dose-escalation strategy improves adjuvant abemaciclib tolerability. The study met its primary endpoint, showing the dose escalation strategy reduced treatment discontinuation and improved ability to reach/maintain the target dose of 150 mg BID at 12 weeks (wks), compared to historical controls. Here, we present 6-month follow-up results from TRADE. Methods: Pts with HR+/HER2- early breast cancer eligible for abemaciclib with adjuvant endocrine therapy were enrolled. All pts initiated abemaciclib at 50 mg BID for 2 wks, escalated to 100 mg BID for 2 wks, and then to 150 mg BID onward for a planned 2-year course. Dose escalation required the absence of ongoing grade 3/4 or persistent grade 2 adverse events (AEs). Management of AEs and dose reductions beyond 12 wks was per standard of care. Data on adherence to oral therapy and ctDNA dynamics were collected. Results: Ninety pts were enrolled; median age was 58 years (range 24-78), and the majority were White (80.0%). 51.1% had stage II disease and 48.9% stage III disease. 73.3% had received chemotherapy in the neo/adjuvant setting. All pts received an adjuvant aromatase inhibitor (AI), 17.8% with ovarian function suppression. One pt had progression within 24 wks of treatment, hence was excluded from dose-related analyses. Out of 89 evaluable pts, 72 (80.9%) remained on treatment at 24 wks; 46 (63.9%) were receiving abemaciclib at 150 mg BID, 18 (25.0%) at 100 mg BID and 8 (11.1%) at 50 mg BID. Abemaciclib discontinuation occurred in 6 pts (6.7%) during the first 12 wks and in an additional 11 pts (12.4%) between wks 12 and 24, resulting in a cumulative discontinuation rate of 19.1% (n=17) over the initial 24 wks of exposure. The most common reasons for discontinuation were AEs (7, 7.9%) and withdrawal of consent/patient preference (6, 6.7%). Specific AEs contributing to discontinuation included diarrhea (2, 2.2%), pneumonitis (2, 2.2%), transaminitis (1, 1.1%), allergic reaction (1, 1.1%), and other (1, 1.1%). Of those who discontinued for patient preference, 5 of the 6 had reached target dose, of whom 3 did not have a dose reduction. A total of 12 pts (13.5%) did not reach target dose, and 29 (32.6%) required dose reductions within 24 wks, primarily due to gastrointestinal or hematologic toxicities, 22 (24.7%) with reductions from 150 mg dosing. The most frequently reported AEs overall were diarrhea (grade ≥2 32.2%, grade 3 5.6%), neutropenia (31.1%, grade ≥3 4.4%), and fatigue (25.6%, no grade ≥3). When analyzed by 4-wk intervals, rates of grade >2 diarrhea were 8.9% (wks 1-4), 19.1% (wks 5-8), 16.5% (wks 9-12), 12.0% (wks 13-16), 8.9% (wks 17-20), and 9.5% (wks 21-24), showing an early peak and gradual decline over time. Patient-reported outcomes, measured by FACT-B assessments, indicated that quality of life remained stable throughout the study period. Additional analyses, including evaluation of adherence and ctDNA, are ongoing. Conclusions: In the TRADE study, after initial dose escalation, abemaciclib was generally well tolerated, with a cumulative discontinuation rate of 19.1% at 24 wks, 7.9% for AE. The incidence of grade >2 diarrhea peaked at month 2 and declined over time. The majority of pts maintained quality of life and were able to remain on therapy with manageable and expected toxicities. These updated findings continue to support the feasibility of an initial abemaciclib dose-escalation approach to optimize drug exposure and reduce early discontinuation, while preserving therapeutic intensity. Citation Format: I. Schlam, D. Trapani, S. Kim, M. Faggen, N. Sinclair, P. Sanz-Altamira, C. Battelli, S. Berwick, S. Lo, J. Acevedo, S. Sinclair, A. Malcom, L. Varella, S. L. Sammons, S. T. Schumer, P. D. Poorvu, E. P. Wallace, E. Pasternak, N. Tayob, S. M. Tolaney, E. L. Mayer. Trade: 6-month abemaciclib tolerability after initial dose escalation in early HR+/HER2- breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD1-08.

Abstract Introduction: Neoadjuvant chemotherapy (CT) with pembrolizumab (P) is standard for most patients (pts) with high-risk early TNBC. Biomarkers for the addition of P to CT are lacking. The prognostic and predictive value of TILs in pts who receive neoadjuvant CT+P vs CT alone and the significance of change in TILs from pre- to post-treatment samples remains unclear. Methods: From the prospective DFCI Multicenter TNBC Registry, pts with stage I-III TNBC who received neoadjuvant CT or CT+P were identified. Stromal TILs were scored in tumor samples at baseline (BL) and surgery (if residual disease, RD). TILs were evaluated as a continuous and binary variable using a threshold selected based on BL distribution. Fisher’s exact test was used to compare TILs between CT and CT+P, and between RCB groups. Association with pathologic complete response (pCR) and with recurrence-free (RFS), distant recurrence-free (DRFS) and overall survival (OS) were evaluated using logistic regression and Cox proportional hazards models, respectively, adjusting for clinical stage and neoadjuvant treatment. All statistical tests were two-sided (significance p < 0.05). Results: Between 5/2019-1/2024, 121 TNBC pts were identified; 18 (14.9%) stage I, 49 (40.5%) stage II, 52 (43.0%) stage III, 2 (1.7%) unknown. 19 (15.7%) had germline BRCA1/2 mutations. 49 (40.5%) received CT and 72 (59.5%) CT+P, with anthracycline-based CT in 40 (81.6%) and 62 (86.1%) pts, respectively. The pCR rate was 51.0% (25/49; 95% CI 36.3-65.6%) with CT alone and 58.3% (42/72; 95% CI 46.1-69.8%) with CT+P. Median follow-up was 2.2 years (interquartile range [IQR] 1.4-3.9): CT, 4.2 years (IQR 3.4-5.1); CT+P, 1.7 years (IQR 1.2-2.2). 115 pts had TILs scored at BL and 41 at RD, of whom 35 had paired samples. BL TILs (range 0-90%) were categorized by quartiles (5%, 10%, 30%) with 10% used for primary analysis. Both BL and RD TILs did not differ between CT vs CT+P as a continuous variable (BL p=0.11; RD p=0.56) or ≥10% cutoff (BL p=0.62; RD p=0.56). High BL TILs (≥ 10%) were significantly associated with pCR and this did not differ by treatment (interaction p=0.36). No association was observed between TILs (at BL or RD) and RCB class (TILs as continuous variable: BL p=0.36, RD p=0.84; or 10% cutoff: BL p=0.31, RD p=0.86). High BL TILs (≥ 10%) were associated with longer RFS (aHR 0.15, p=0.01), DRFS (aHR 0.17, p=0.01) and OS (aHR 0.19, p=0.05; or as a continuous variable, aHR per 5-unit increase 0.46, p=0.05). Neither TILs in RD nor increase from BL to RD (in 14/35 pts, 40%) were associated with RFS, DRFS or OS. Conclusion: In this multicenter TNBC cohort, BL TILs were reinforced as a prognostic marker for pCR, regardless of the addition of P to CT. TILs at RD and changes during neoadjuvant therapy were not prognostic. Additional follow-up for survival outcomes is ongoing. Citation Format: R. S. Lee, Q. Jin, B. Binboga Kurt, B. Koca, J. Gomez Tejeda Zanudo, A. Patel, A. Barkell, J. Baginska, O. M. Cunningham, C. E. Stever, T. S. Parker, T. Rahman, M. Luo, I. G. Martino, B. M. Drummey, S. A. Virani, K. Santos, J. Bsat, C. Snow, N. Tung, S. Lo, M. G. Faggen, N. Sinclair, N. Ahmad, M. Constantinou, S. Sinclair, J. L. Meisel, S. A. Kirschner, T. A. King, R. Salgado, E. A. Mittendorf, N. U. Lin, N. Tayob, E. P. Winer, E. C. de Bruin, S. M. Tolaney, A. Moeini, A. C. Garrido-Castro. Association of tumor-infiltrating lymphocytes (TILs) with outcomes in patients with early TNBC treated with neoadjuvant chemotherapy with or without pembrolizumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-18.

A woman in her late twenties presented to an Australian tertiary hospital with syncope following 3 days of melena and pre-syncopal symptoms. Her social history was notable for illicit methamphetamine, cannabis and benzodiazepine use. Furthermore, she reported tobacco and alcohol use. She was not

Benzodiazepines have been established as a safe and efficacious treatment option for Alcohol Withdrawal Syndrome (AWS). The applicability of current evidence for the management of AWS in the acute hospital setting with benzodiazepines is not clear. This review sought to capture efficacy and safety outcomes for benzodiazepine use within acute hospital settings in those experiencing moderate-severe AWS symptoms. Cochrane Registry, Medline, Embase and APA PsycInfo were searched for studies published between 2000 and 2025. Adult patients experiencing at least moderate severity AWS symptoms and treated with benzodiazepines in an acute hospital setting were included. Efficacy and safety outcomes were extracted and subsequently analysed. There were 603 articles imported for screening, of which 24 met inclusion criteria for data extraction. There was significant heterogeneity between studies. The most common efficacy outcomes assessed were total cumulative benzodiazepine dose (20 studies); length of stay (ED, hospital admission or equivalent) (19 studies) and use of adjunct medication(s) (12 studies). The most common safety outcomes assessed were need for intubation/respiratory failure (12 studies); Occurrence of seizure (11 studies); need for ICU/higher level care (nine studies) and occurrence of delirium/DT (nine studies). Current evidence lacks uniformity in reported outcomes and inclusion/exclusion criteria such that there is insufficient data to readily apply current evidence to the acute hospital setting for the selected population. Higher level evidence is required for future research. Prospective studies in this area should be in the form of randomised-controlled trials with pre-defined cohorts and treatment parameters.

BackgroundMobile stroke units (MSUs) accelerate prehospital acute stroke care and improve outcomes. Both onboard and telemedicine neurologist models of care are used but have not been directly compared.MethodsMSU-TELEMED was a randomized, open-label, blinded-endpoint trial comparing onboard neurologist care to a telemedicine care model for people presenting to an MSU with suspected stroke. MSU care was prospectively randomized by day to onboard versus telemedicine care. The primary outcome was a hierarchical composite outcome using a win-odds approach that prioritized: (1) safety, (2) scene-to-treatment-decision time, and (3) percentage of the total case time the neurologist spent in direct care (higher values denote better resource use). Every participant in each group was compared to those in the other, resulting in a “win/tie/loss” distribution for telemedicine compared to onboard.ResultsA total of 275 participants were assigned to telemedicine (n=135) or onboard (n=140) neurologist care groups. The primary outcome of win/tie/loss distribution favored the telemedicine model (76%/4%/20%) with an adjusted win odds of 3.5 (95% confidence interval [CI], 2.4–5.1). Safety events were similar (13% telemedicine vs. 12% onboard, risk ratio 0.9; 95% CI, 0.5–1.8). Median scene-to-treatment-decision time was 19 minutes in the telemedicine group and 13 minutes in the onboard group (adjusted difference in median time 4 minutes; 95% CI, 1.9–5.9). The median percentage of the neurologist’s time directly involved in patient care was 100% in the telemedicine group and 33% in the onboard group (adjusted difference in median percentage 63 percentage points; 95% CI, 53–74).ConclusionsCompared to an onboard model, an MSU telemedicine model of care was superior based on a composite hierarchical outcome of safety, scene-to-treatment-decision time, and percentage of the neurologist’s time spent in direct care. (Funded by the Sylvia and Charles Viertel Charitable Foundation and the Medical Research Future Fund “Golden Hour”; ClinicalTrials.gov number, NCT05991310.)

Postoperative pancreatic fistula (POPF) is the primary cause of morbidity after distal pancreatectomy (DP). This trial investigated the application of a combined polyethylene glycol (PEG) and recombinant human albumin sealant gel to the stapled, transected pancreatic margin to reduce clinically significant POPF. A multicenter randomised controlled trial in patient candidates for DP with stapled transection was conducted. Participants were randomised to receive DP with or without PEG sealant applied to the stapled margin. The primary outcome was clinically significant POPF. Secondary outcomes included other complications, length of hospital stay and 90-day mortality. Seventy-eight patients with completed DP were included, 38 of whom underwent stapled DP combined with the use of PEG sealant (PEG group). No significant differences between the two groups were observed with respect to pathology type, operative approach or operative time. The PEG group exhibited significantly fewer complications (18% vs. 50% in the control group; p = 0.003), and a lower rate of POPF (11% vs. 28%; p = 0.08, respectively). Multivariate analysis revealed a significant association between spleen preservation and the rate of clinically significant fistula (OR 4.4; 95% CI 1.1-18.0; p = 0.038). The rate of POPF was lower in the PEG group but did not reach statistical significance (OR 0.3; 95% CI 0.1-1.2; p = 0.091). Stapled DP combined with PEG application was associated with reduced complications. There was a lower rate of POPF in the PEG sealant group that did not reach statistical significance. ACTRN12620001336976p.

BackgroundSmall and ground glass pulmonary nodules pose a surgical and diagnostic challenge, with an increase in identification expected with the roll-out of lung cancer screening in Australia. Accurate preoperative localisation of small pulmonary nodules can be a useful adjunct to lung resection in nodules that are not palpable. Various methods have been trialled including methylene blue dye injection and hook-wire placement; however, these are limited by dye diffusion, wire dislodgement, and patient discomfort. CT-guided insertion of a microcoil is a technique of localisation that provides a stable and visible marker on X-ray, improving intraoperative identification. This study reports an Australian institutional experience with this technique and evaluates its safety and efficacy.MethodsA retrospective review of all patients undergoing CT-guided pulmonary microcoil localisation followed by video-assisted thoracoscopic surgery (VATS) was conducted at the Alfred Hospital, Melbourne. A case series of 19 patients from 2021 - 2025 was identified and data on technical success, complications, operative outcomes, and pathology were collected.ResultsThe mean patient age was 63.5 years, with a slight male predominance (n=11, 57.8%). Indications for lung resection included pulmonary metastasectomy (n=12, 63.2%) and primary lung adenocarcinoma (n=7, 36.8%). The indication for microcoil guidance was a deep nodule in 36.8% (n=7) of cases and in 63.1% (n=12) of cases an impalpable nodule due to small size or ground glass appearance. The technical success of microcoil placement was 94.3% (n=18), with one displaced microcoil early in the series. No pneumothorax requiring intervention occurred and no major radiological complications from microcoil placement seen in the series. All lesions were successfully resected, with clear histologic margins and no major surgical complications. The mean chest drain duration was 3.4 days and mean hospital stay 4.6 days.ConclusionsCT-guided pulmonary microcoil insertion is a safe, reliable, and reproducible technique for intraoperative identification of small or impalpable pulmonary nodules. It addresses some of the limitations of previous localisation methods and demonstrates excellent outcomes in an Australian setting. Future developments may include indocyanine green-coated microcoils for fluorescence guidance during robotic-assisted thoracic surgery.

Despite significant advances in the availability and quality of palliative care globally, health economics research to understand the value of palliative care in Australian settings remains scarce. To address knowledge gaps and foster evidence-informed policy, funding and practice, this paper presents a consensus-driven research agenda for the health economics of palliative care in Australia. A panel of 27 Australian experts was convened, including health economists, palliative care clinicians/researchers, policy makers/government officials, and representatives from the national peak body for palliative care. Panel members completed a survey, participated in a forum and collectively drafted the research agenda. The panel recommended 16 health economics research priorities across four key areas: (1) person-centred outcomes; (2) costs; (3) economic evaluation; and (4) data and metrics. Specific priorities included: comprehensively capturing the benefits of palliative care for people with life-limiting illnesses and their informal carers; understanding the diversity of preferences for palliative care across the population; capturing informal caring costs within economic evaluations; embedding economic evaluation within clinical trials and health services studies; and quantifying the extent and location of unmet palliative care needs. This paper outlines high-priority research actions to generate the economic evidence required for appropriate funding and resource allocation in palliative care. The research agenda serves as a strategic tool to help researchers address gaps without duplicating efforts. By focusing on these priorities, we aim to support the development of more effective, equitable and sustainable palliative care services across Australia.