Objective.Phase-contrast computed tomography (PCT) of the breast has previously been shown to produce higher-quality images at lower radiation doses without the need for breast compression. The present study is aimed at further reduction of the radiation dose in PCT, while preserving or further increasing the image quality, by applying supervised deep learning denoising of reconstructed PCT images. This work was carried out in preparation for live patient PCT breast cancer imaging, initially at specialised synchrotron facilities.Approach.PCT scans of 34 fresh full mastectomy samples were acquired using propagation-based phase-contrast imaging with 32 keV monochromatic parallel x-rays at mean glandular doses of 4 mGy and 24 mGy. All scans were reconstructed using Filtered Back Projection algorithm with Paganin's phase retrieval. A supervised U-Net-based deep learning denoising model was trained on 28 pairs of 4 mGy and 24 mGy scans and then applied to denoise the remaining 6 stacks of reconstructed 4 mGy images. Denoised PCT images were quantitatively evaluated using signal-to-noise ratio (SNR), spatial resolution, structural similarity index measure (SSIM) and peak-SNR (PSNR). The images were also visually compared and systematically assessed by experienced medical imaging specialists and radiologists.Main results.Deep learning denoising increased SNR by a factor of four while spatial resolution remained unchanged. SSIM and PSNR improved from 0.89 and 37 dB to 0.96 and 42 dB, respectively. Visual assessors significantly preferred the denoised images over the original 4 mGy images, and visual assessment indicated no increase in perceived artefacts in denoised images compared with the original 4 mGy images.Significance.Deep learning-based image denoising can further improve image quality in PCT without increasing radiation dose in imaging of mastectomies, supporting the feasibility of lower-dose PCT protocols or improved image quality for future clinical applications.

Background RNA-based fusion panels using targeted next-generation sequencing of formalin-fixed paraffin-embedded tumour tissue specimens are used for various tumour types to detect rearrangements/fusions. Using bioinformatic approaches, the data obtained from RNA sequencing (RNA-Seq) can also be used for small nucleotide variants analysis (single nucleotide variants and indels).Methods The performance characteristics of applying Small nucleotide variant analysis Using RNA Fusion panel (SMURF) analysis to RNA-Seq (RNA sequencing) data obtained from an RNA-based fusion panel was evaluated and compared to results obtained from a dedicated DNA-based panel.Results This demonstrated that an RNA fusion panel can be enhanced to identify small nucleotide variants to maximise the utility of this panel. Although coverage depth across various genes, based on gene expression, was found to be quite variable, which is expected, there were certain genes found to consistently display coverage depth suitable for variant identification, such as GNAS, GNAQ, NRAS, and CTNNB1.Conclusion This analysis suggests that the variants in these genes can be confidently reported from RNA-Seq data obtained from an RNA-based fusion panel.

Abstract Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germline defects in DNA mismatch repair (MMR) genes, resulting in microsatellite instability and a high tumour mutational burden (TMB). While classically associated with colorectal and endometrial cancers, high-grade glioma represents a rare but clinically significant manifestation within the Lynch syndrome spectrum. These tumours frequently arise in childhood or adolescence, exhibit marked hypermutation, and may demonstrate limited sensitivity to conventional alkylating chemotherapy, creating significant therapeutic challenges. However, their biological profile provides a strong rationale for immune checkpoint inhibition, underscoring the importance of accurate molecular diagnosis. We report the case of a 14-year-old male who presented with a short history of headaches and right-sided focal seizures. Neuroimaging revealed a large high-grade parietal lesion. He underwent two-stage surgical debulking, and histopathological assessment confirmed a non-H3 K27M mutant, IDH-wildtype high-grade glioma. The patient was enrolled in the ZERO2.0 precision oncology program and registered with the International Replication Repair Deficiency Consortium, enabling comprehensive molecular and immune profiling, including LOGIC assay analysis. Molecular testing identified a heterozygous likely pathogenic germline MSH6 missense variant alongside a heterozygous somatic MSH6 alteration, consistent with Lynch syndrome. The tumour demonstrated microsatellite instability, a mismatch repair–deficiency mutational signature, and high TMB (21.65 mutations/Mb; 298 SNVs/exome). LOGIC assay classification placed the tumour within the priMMRD-2 subgroup with additional CTLA4 expression. Based on these findings, immune checkpoint inhibition was recommended. The patient commenced nivolumab monotherapy, which was well tolerated with no grade ≥3 toxicities, and demonstrated moderate clinical and radiological improvement. Persistently detectable cerebrospinal fluid circulating tumour DNA supported escalation to combination nivolumab and ipilimumab therapy. This case illustrates the critical role of comprehensive molecular analysis in guiding diagnosis and treatment selection in rare, therapeutically challenging paediatric gliomas, and highlights the value of multidisciplinary and international collaboration in delivering precision oncology care.

Breast cancer is among the most prevalent cancers worldwide. Despite screening with digital mammography and digital breast tomosynthesis, many cancers remain undetected, and both modalities require breast compression. Breast computed tomography (BCT) is an alternative modality providing isotropic resolution without compression, but achieving sufficient image quality requires higher X-ray doses than current screening practice. Phase-contrast propagation-based computed tomography (PBCT) can provide enhanced image quality compared to absorption-based computed tomography (ABCT) at equivalent doses. In the present work, we compare supervised deep learning denoising models trained on ABCT and PBCT scans of 27 fresh mastectomies and tested on 6. U-Net models were trained to denoise 2 mGy mean glandular dose scans against 4 mGy targets. We measured structural similarity (SSIM) and peak-signal-to-noise (PSNR), as well as no-reference signal-to-noise (SNR), spatial resolution and contrast-to-noise (CNR). PBCT models yielded higher PSNR and SSIM than ABCT. Spatial resolution was 140 mu m in all input, target and denoised images. Gains in SNR due to phase contrast alone were 2.9-fold, and denoising yielded 2-fold SNR gains for both ABCT and PBCT, with similar gains in CNR. The overall gain in SNR due to phase contrast and deep denoising was 5.8-fold. With spatial resolution unchanged and X-ray dose proportional to SNR2, this improvement was equivalent to a 34-fold dose reduction. The results demonstrate significant image quality improvement achieved by PBCT combined with deep denoising at doses comparable to DM and DBT screening, using training data collected at doses lower than current average BCT doses.

Background Patients with indeterminate thyroid nodules continue to be a challenge to clinicians. Molecular testing on fine needle aspirates (FNA) is well established in the United States, but its access is limited elsewhere. We aimed to explore the utility of a pre-existing Next Generation Sequencing (NGS) platform, and the role of BRAF mutation in patient selection for preoperative molecular testing. Methods Patients were recruited from the Monash University Endocrine Surgery Database for BRAF immunohistochemistry status on histopathological samples; and prospectively for NGS testing of preoperative FNA samples, using the Archer DX VariantPlex (31 genes) and FusionPlex (40 genes) Comprehensive Thyroid and Lung panels. Results The mean age of 90 patients (103 nodules) for NGS testing was 53, with 58 % female. Most of the nodules (n = 72, 70 %) had indeterminate cytology. Histology showed malignancy in 52 (50 %) nodules; of these, 45 had pathogenic DNA mutations and 3 had pathogenic RNA fusions on NGS testing of needle aspirates. The NGS panels were able to detect malignancy in indeterminate nodules with 75 % sensitivity, 85 % specificity, 80 % positive predictive value, and 81 % negative predictive value. 74 % of the papillary thyroid cancer population had BRAF mutations on immunohistochemistry, which showed 88 % concordance with the NGS results. Conclusion This is the first Australian study to demonstrate that pre-existing, non-proprietary NGS mutation and fusion panels can achieve high diagnostic specificity and positive predictive value for malignancy in indeterminate thyroid nodules. Furthermore, we propose exploration of using BRAF V600E testing to select patients for full NGS analysis.

For 2 decades, the American Society of Clinial Oncology-College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing criteria have included 0 and 1+ scores, but this distinction was inconsequential. Now, based on the DESTINY Breast-04 Trial (DB-04) results, for patients with metastatic breast cancer it underpins eligibility for trastuzumab-deruxtecan treatment. Discerning 0 from 1+ immunohistochemistry (IHC) staining is challenging, as HER2 low is not a biologically distinct cancer subset, there are no reference standards or controls, and second-tier tests (eg, in situ hybridization) do not apply. Prior reports cast doubt on the reliability of pathologists' IHC scoring, with resulting treatment misalignments. With institutional review board approval, our group of 9 breast pathologists from 8 Australian laboratories had previously established HER2-low-focused scoring conventions, based on the American Society of Clinial Oncology- College of American Pathologists 2018 HER2 guidelines, and specifying common staining pitfalls. We reported the results of the first set of 60 breast cancers evaluated with these methods. After a 5month washout, for the present validation study, we have compiled a second set of 64 HER2negative invasive breast cancer core biopsies, all assessed with the Ventana 4B5 HER2 assay. We have each scored digitized images of HER2 IHC slides of the cases. Using the majority opinion as the target score, we have calculated our performance metrics. We have compared the results of our performance in set 1 and set 2 to assess the effectiveness of our approach and learning retention. The cases in this validation set included 40 (62.5%) HER2 low, 10 (17.2%) ultralow (UL), and 13 (18.8%) null cancers. Concordance was not achieved in 1 case. For distinguishing HER2 low from other cancers (UL and null combined) the mean values of our performance metrics were accuracy 89.58%, sensitivity 90.83%, specificity 87.50%, positive predictive value 95.63%, negative predictive value 83.59%, and Cohen kappa score 0.81. Comparing these results with our initial study, we have maintained our high level of performance across these parameters. Our mean kappa score is now in the excellent range for concordance. Maintaining high performance across a range of measures in 2 separate data sets validates the effectiveness of our HER2-low-focused scoring conventions. Having validated our approach, we will use these reference case sets with expert-level consensus scores for peer training and updating our national HER2 IHC external quality assurance program. In our ongoing studies, we are also assessing the performance of software algorithms to determine their suitability for the prescreening of HER2 IHC slides. (c) 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Breast cancer is the most frequently diagnosed human cancer in the United States at present. Early detection is crucial for its successful treatment. X-ray mammography and digital breast tomosynthesis are currently the main methods for breast cancer screening. However, both have known limitations in terms of their sensitivity and specificity to breast cancers, while also frequently causing patient discomfort due to the requirement for breast compression. Breast computed tomography is a promising alternative, however, to obtain high-quality images, the X-ray dose needs to be sufficiently high. As the breast is highly radiosensitive, dose reduction is particularly important. Phase-contrast computed tomography (PCT) has been shown to produce higher-quality images at lower doses and has no need for breast compression. It is demonstrated in the present study that, when imaging full fresh mastectomy samples with PCT, deep learning-based image denoising can further reduce the radiation dose by a factor of 16 or more, without any loss of image quality. The image quality has been assessed both in terms of objective metrics, such as spatial resolution and contrast-to-noise ratio, as well as in an observer study by experienced medical imaging specialists and radiologists. This work was carried out in preparation for live patient PCT breast cancer imaging, initially at specialized synchrotron facilities.

Most mesothelioma patients either have primary refractory disease or develop acquired resistance to immune checkpoint inhibitors (ICIs). A more sophisticated understanding of the tissue microenvironment (TME) and intercellular communication will enable opportunities for overcoming ICI resistance. Here, we utilize the Visium 10x spatial transcriptomics (ST) technology to address this question. We conducted ST on a cohort of 12 mesothelioma patients (28 samples) treated with ICIs (Table 1). Nine patients had a response to ICIs with a median response duration of 9 months and three had primary ICI resistant disease. We show the transition from the immune infiltrated tumor in a pre-treatment sample transition to immune exclusion in the post-treatment (ICI-resistant) sample. In addition, we were able to map the immune cell sub-types in relation to cancer cells. In a responder, we identified CXCL12-CXCR4 mediated communication at the mesothelial-immune interface. We mapped a 48-gene prognostic signature to generate spatial heat maps showing specific regions within tissue with elevated poor prognosis signatures in treatment naïve samples that expanded in matched relapsed samples. We also identified remarkable heterogeneity showing pre- and post-ICI treatment samples to be transcriptionally diverse. In another patient, we assessed four samples from the primary tumor prior to treatment, two from PET-positive and two from PET-negative areas. Moreover, we complemented spatial transcriptomics with multi-region whole genome sequencing. This revealed that these sites are genomically stable but transcriptionally distinct. Further deconvolutional analysis to approximate cell composition, cell co-localization, and cell evolution/plasticity measures are underway. Together, this deep spatial investigation provides a key understanding of oncogenic communication in TME, before and after ICI therapy. Table 1. Patient No Sex Histological Subtype Treatment Pre-Treatment samples Post Treatment samples Response Response duration 1 M Sarcomatoid PD-1 5 - Yes 6 2 M Epithelioid PD-1 3 - No - 3 M Biphasic PD-1/CTLA-4 4 - Yes 87 4 F Biphasic PD-1/CTLA-4 1 - No - 5 M Epithelioid PD-1/CTLA-4 2 1 Yes 12 6 F Sarcomatoid PD-1 1 - Yes 52 7 M Epithelioid PD-1 1 1 Yes 17 8 M Sarcomatoid PD-1/CTLA-4 2 - Yes 75 9 M Epithelioid PD-1/CTLA-4 1 1 No - 10 M Biphasic PD-1 1 1 Yes 18 11 M Sarcomatoid PD-1/CTLA-4 1 1 Yes 22 12 M Epithelioid PD-1/CTLA-4 - 1 Yes 16 Muhammad Alamgeer, Daniel Gough, Vinvent Xue, Beena Kumar, Adrian Pick, Fathima Sharafath Yoosuf, Surein Arulananda, Jhoseph Marquez, Vinod Ganju. Illuminating mesothelioma immune microenvironment in response to immune checkpoint inhibitors using spatial transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3977.

BACKGROUND:Homologous recombination repair (HRR) is the preferred pathway for repairing double-strand DNA breaks, using proteins like BRCA1 and BRCA2, among others, while the PARP-mediated repair pathway is primarily used for single-strand breaks. When a tumour becomes HRR-deficient (HRD), then those tumour cells become reliant on PARP-mediated repair. Poly ADP-ribose polymerase inhibitors, olaparib and niraparib, have been approved in Australia for advanced (FIGO III-IV), high-grade serous or other high-grade ovarian, fallopian tube or primary peritoneal carcinoma with homologous recombination deficiency (HRD). METHODS:HRDsig (Roche Inc) is a new HRD biomarker that is part of the AVENIO Tumor Tissue CGP Kit V2. We have studied the performance of HRDsig against two NATA (National Association of Testing Authorities, Australia) accredited HRD assays in the cases of high-grade ovarian carcinomas. We have evaluated the performance of HRDsig using a total 40 HRD results against the two accredited HRD assays, as well as against commercial controls and inter-laboratory comparison samples. RESULTS:HRDsig has demonstrated a high concordance rate for HRD by comparing it with two different locally accredited HRD assays in cases of ovarian cancers. CONCLUSION:These findings provide real-world evidence of the performance of a new HRD assay (HRDsig) in ovarian carcinomas.

Haematological malignancies are being increasingly defined by gene rearrangements, which have traditionally been detected by karyotype, fluorescent in situ hybridisation (FISH) or reverse-transcriptase polymerase chain reaction (RT-PCR). However, these traditional methods may miss cryptic gene rearrangements and are limited by the number of gene rearrangements screened at any one time. A next-generation sequencing (NGS) RNA fusion panel is an evolving technology that can identify multiple fusion transcripts in a single molecular assay, even without prior knowledge of breakpoints or fusion partners. We explored the utility of the Illumina TruSight RNA Fusion Panel for use in haematological malignancies by sequencing 30 peripheral blood or bone marrow aspirate samples. Secondary and tertiary analyses were performed using the Illumina DRAGEN RNA pipeline and PierianDx Clinical Genomics Workspace platform. Our RNA fusion panel was able to reliably detect known fusion transcripts, such as BCR::ABL1, ETV6::RUNX1 and KMT2A::AFF1, in acute lymphoblastic leukaemia (ALL), KMT2A::MLLT3, KMT2A::MLLT6, PML::RARA and CBFB::MYH11 in acute myeloid leukaemia (AML), and FIP1L1::PDGFRA in myeloid/lymphoid neoplasm with eosinophilia (MLN-Eo). In addition, it was able to detect rare KAT6A::CREBBP and CHIC2::ETV6 fusions, which could not be confirmed by traditional methods. The assay had a transcript limit of detection of approximately 5-10% of positive controls. These findings confirm the unique utility of the NGS-based RNA fusion panel as a diagnostic tool to identify gene rearrangements that drive haematological malignancies. It can identify novel and rare gene rearrangements to assist with diagnosis, prognostication and treatment decisions.

BACKGROUND:Phase-contrast breast CT imaging holds promise for improved diagnostic accuracy, but an optimal reconstruction algorithm must balance objective image quality metrics with subjective radiologist preferences. PURPOSE:This study systematically compares three reconstruction algorithms-filtered back projection (FBP), unified tomographic reconstruction (UTR), and customized simultaneous algebraic reconstruction technique (cSART)-to identify the most suitable approach for phase-contrast breast CT imaging. METHODS:Fresh mastectomy samples were scanned at the Australian synchrotron using monochromatic 32 keV X-rays, a mean glandular dose of 2 mGy, flat-panel detectors with 0.1 mm pixels, and 6-m distance between the rotation stage and the detector. Paganin's phase retrieval method was used in conjunction with all three CT reconstruction algorithms. Objective metrics, including spatial resolution, contrast, signal-to-noise, and contrast-to-noise, were evaluated alongside subjective assessments by seven experienced radiologists. Ratings included perceptible contrast, sharpness, noise, calcification visibility, and overall quality. RESULTS:cSART excelled in objective metrics, outperforming UTR and FBP. However, subjective evaluations favored FBP due to its higher image contrast, revealing a discrepancy between objective and subjective assessments. CONCLUSIONS:The findings highlight the contrast-focused nature of radiologists' subjective assessments and the potential of cSART for delivering superior objective image quality. These insights inform the development of hybrid evaluation tools and guide clinical translation for future live patient imaging studies.

Three different computed tomography (CT) reconstruction algorithms: Filtered Back Projection (FBP), Unified Tomographic Reconstruction (UTR) and customized Simultaneous Algebraic Reconstruction Technique (cSART), have been systematically compared and evaluated using experimental data from CT scans of ten fresh mastectomy samples collected at the Imaging and Medical beamline of the Australian Synchrotron. All the scans were collected at the mean glandular dose of 2 mGy, using monochromatic X-rays with 32 keV energy, flat-panel detectors with 0.1 mm pixels and 6 meter distance between the rotation stage and the detector. Paganin's phase retrieval method was used in conjunction with all three CT reconstruction algorithms. The reconstructed images were compared in terms of the objective image quality characteristics, including spatial resolution, contrast, signal-to-noise, and contrast-to-noise ratios. The images were also evaluated by seven experienced medical imaging specialists, rating perceptible contrast, sharpness of tissue interfaces, image noise, calcification visibility and overall image quality. Of the three compared algorithms, cSART was clearly superior to UTR and FBP in terms of most measured objective image quality characteristics. At the same time, the results of the subjective quality evaluation consistently favoured the images reconstructed by FBP, followed by UTR, with cSART receiving lower scores on average. We argue that this apparent disagreement between the objective and subjective assessments of image quality can be explained by the importance assigned to image contrast in the subjective assessment, while the signal-to-noise ratio seemed to receive relatively low weighting. This study was conducted in preparation for phase-contrast breast CT imaging of live patients at Australian Synchrotron (Melbourne, Australia).

The DESTINY Breast-04 trial revealed survival advantages of trastuzumab deruxtecan for women with metastatic HER2-low breast cancer (1+ or 2+ immunohistochemistry [IHC], without amplification). Although this trial applied the 2018 Americal Society of Clinial Oncology (ASCO)/College of American Pathologists (CAP) HER2 IHC scoring criteria, the subjectivity and imprecision in IHC scoring have raised concerns that patients' treatment may be misaligned. Our group of 9 experienced breast pathologists collated a deidentified set of 60 breast cancer core biopsies from 3 laboratories, evaluated with the Ventana 4B5 HER2 assay and mostly scored locally as HER2 0 or 1+. Based on ASCO/CAP 2018 criteria and our extensive experience of reporting HER2 IHC, we specified scoring conventions for cancers with low levels of HER2 protein expression, articulating specific scoring pitfalls. Each pathologist then reviewed digitized whole slide images of the IHC slides and scored the HER2 expression for each case. At a subsequent consensus workshop, we reviewed the cases jointly to establish consensus scores for each case and determine the percentage of HER2 expressing tumor cells. Consensus was reached on all cases, with 40 classified as 1+ and 3 as 2+ (not amplified), totaling 43 (71.7%) HER2-low cancers. The remaining cases were HER2 0. In 93.3% of cases (56/60), the consensus score matched with the majority opinion of pathologists' independent scores. Seven (41.2%) of the 17 cases reported locally as HER2 0 were classified as HER2 low. Conversely, among 32 cases with local scores of 1+, 7 (21.8%) were reclassified as ultralow or null. Individual pathologists' accuracy in matching the consensus scores ranged from 73.3% to 91.67% (mean, 80.74%). Among HER2-low cancers those in which <20% of the tumor cells expressed HER2 had the lowest concordance levels. Observers Cohen's κ coefficients for concordance were excellent for 4, good in 1, and moderate in the 4 observers. This reference set of cases with expert consensus HER2 scores will be invaluable for peer training and development of our national external quality assurance program for HER2-low cancers. For assessing breast cancers at the low end of HER2 protein expression, our targeted scoring criteria and explicit instruction on pitfalls improved pathologists' accuracy and concordance.

Background: Indolent T cell lymphoproliferation of the gastrointestinal tract is a novel entity recently added to the 2016 WHO classification of lymphoid neoplasms. Classically, these patients demonstrate an immunophenotype consistent with T cell proliferation and can be either CD4-positive or CD8-positive but with a low Ki67 index, highlighting the indolent nature of this disease compared to its more aggressive T cell lymphoma counterparts such as enteropathy-associated T cell lymphoma and monomorphic epitheliotropic intestinal T cell lymphoma. Methods: Here, we describe one rare case of such a neoplasm under our care, initially presenting with non-specific signs and symptoms and requiring extensive investigations to diagnose. Available cases in the literature reflect a wide variety of ages and ethnicities affected, and any part of the gastrointestinal sites can be affected, which makes diagnosis difficult and prolonged; however, progression beyond lymph nodes is rare, and prognosis is otherwise favourable, particularly if CD8-positive. The optimal management of these patients remains yet to be defined, given the paucity of available cases currently. The current evidence suggests the utility of steroids, cyclosporine, radiotherapy, and a potential role for JAK inhibitors. Conclusions: Our case showed an excellent response to the initial course of steroids, with a subsequent successful transition to cyclosporine, keeping symptoms at bay with ongoing stable disease.

Abstract Background Precise nodal staging is critical in guiding systemic and regional treatments including surgery in the management of breast cancer. Regional nodal assessment includes axillary imaging (mostly by ultrasound) and lymph node sampling. Since imaging findings suggestive of nodal metastasis are based on size and morphologic changes and not specific to tumor type, pathologic confirmation through either biopsy or removal of sentinel lymph node (SLN) remains the gold standard. Imagion is developing the MagSense® HER2 Imaging Agent (MSH2IA), an anti-human epidermal growth factor receptor 2 (HER2) conjugated with iron oxide nanoparticles, for the detection of nodal metastasis in HER2+ breast cancer patients. MSH2IA is currently being investigated in a first-in-human phase 1 study (ACTRN12621000126819) in HER2+ breast cancer patients who are diagnosed to have suspicious nodes by conventional imaging. Methods The key objectives of the phase 1 study are safety and tolerability of MSH2IA and confirmation that MSH2IA drains to the axillary lymph nodes. The study also explores MSH2IA’s ability to detect metastatic nodes when used with magnetic resonance imaging (MRI), with tumor status assessed by standard tissue histopathology. All eligible subjects receive a 22.5 mg (iron equivalent) subareolar or peritumoral injection of MSH2IA. MRI of the axilla are obtained before and 24 to 72 hours after MSH2IA injection. Core biopsy or dissection of a node suspicious by ultrasound is obtained for histopathology assessments. After completing the first cohort of 6 subjects, the protocol was amended to include the insertion of an MRI compatible clip in a node suspicious by ultrasound to localize the suspicious node for core biopsy and postdose MRI scan. Review of MRI scans and histopathology are performed in respective central laboratories. Results Thirteen participants with HER2+ breast cancer have completed the study. MSH2IA appears safe and well tolerated. The imaging agent, as administered, is detectable by MRI and pathology, confirming that MSH2IA drains to the lymph nodes via the chosen route of administration. In postdose MRI scans, study central radiologists reported distinct and differentiable MRI appearance in morphologically normal and suspicious nodes. The presence of a distinct postdose MR image appearance was confirmed by a group of independent radiologists in a separate blinded review. While normal nodes appeared with homogeneous hypointensity, morphologically suspicious nodes showed partial irregular darkening and/or speckled heterogeneous hypointensity. In evaluable subjects, histopathology of the core biopsies obtained from the clipped nodes confirmed the presence of HER2+ nodal metastasis, providing preliminary evidence for node-level concordance between MRI vs pathology observations. Safety, imaging, and pathology results from all available subjects will be presented. This phase 1 study in Australia will be closing enrollment by July 31, 2023. A phase 2 study in the United States and elsewhere is being planned with the objectives of optimizing dose, schedule, and imaging parameters for best diagnostic performance for clinical utility. Conclusion Available data from the ongoing phase 1 study show that MSH2IA appears safe and drains to the axillary lymph nodes. MSH2IA displays a distinct and differentiable MRI appearance in nodes morphologically highly suspicious for tumor, which is confirmed to be HER2+ metastasis by histopathology by node level concordance. This data provides preliminary proof of principle for the mechanism of molecularly targeted MR imaging and suggests that MSH2IA has the potential to provide tumor-specific MR imaging not currently available in conventional axillary imaging. Citation Format: Jane Fox, Shanta Velaiutham, Natalie Yang, Eddie lau, Kowsi Murugappan, Beena Kumar, Alex Laslowski, Koushik Govindarajan, Steven Reich, Stephen Thomas, Nitika Neha, Marie Zhang, Isaac Bright. MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-03.

BACKGROUND:Endoscopic ultrasound-guided fine needle biopsy (FNB) is the gold standard in tissue acquisition of pancreatic ductal adenocarcinoma (PDAC). There is a paucity of evidence of the impact of needle type or size on the genetic yield and quality. METHODS:Patients 18 years and older with PDAC who underwent FNB were retrospectively identified from a single database from 2016 to 2021. Genetic quantity is measured in micrograms (µg) and quality defined by RNA or DNA integrity number (RIN and DIN). FNB needles examined were Acquire 22 gauge (Boston Scientific, Marlborough, MA, USA) and ProCore 22 and 20 gauges (Cook Medical, Bloomington, IN, USA). RESULTS:Two hundred seventy-seven patients were identified. ProCore 20G needle procured higher RNA quantity (4125.8µg, IQR: 2003.8, 5954.8, p = 0.012) compared to ProCore 22G (2050µg IQR: 966.4, 3181.6) and Acquire 22G (2310.6µg, IQR: 1439.3, 4312). Median DNA quantity was 3340.5µg (Acquire 22G), 2610.4µg (ProCore 22G) and 3499.7µg (ProCore 20G) (p = 0.763). Median DIN was 7.3 (Acquire 22G and ProCore 22G) and 7.4 (ProCore 20G) (p = 0.449). Median RIN was 3.0 (Acquire 22G and ProCore 22G) and 2.7 (ProCore 20G) (p = 0.886). CONCLUSION:ProCore 20G was associated with higher quantity of RNA. There were no differences in the quality acquired by different needles.