Genomic profiling of solid tumors by next-generation sequencing (NGS) supports personalized therapy selection, but routine clinical adoption requires robust analytical and clinical validation. The Oncomine™ Dx Express Test (ODxET) is a companion diagnostic and tumor profiling in vitro diagnostic NGS assay for detecting targeted single- and multinucleotide variants (SNVs/MNVs), insertions, deletions, copy number variations (CNVs), and RNA fusions or splice variants in formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. In a retrospective, blinded analytical study, 462 FFPE samples representing 15 tumor types and including 76 wild-type samples, were analyzed with ODxET and compared with validated orthogonal methods. Reproducibility and repeatability were evaluated across three sites, each using two operators, two sequencers, three reagent lots, and two replicates. Clinical performance for epidermal growth factor receptor (EGFR) exon 20 insertion detection was assessed using non-small cell lung cancer (NSCLC) samples from the WU-KONG1B sunvozertinib clinical trial and commercially sourced biomarker-negative specimens, with clinical effectiveness evaluated in patients treated with the approved sunvozertinib dose. The ODxET assay showed high analytical concordance for EGFR exon 20 insertions, with a positive percent agreement (PPA) of 100
Manganese-enhanced magnetic resonance imaging (MEMRI) is a functional imaging technique with several potential applications in various research fields. Manganese-enhanced magnetic resonance imaging uses paramagnetic manganese (II) ions (Mn2+) as the contrast enhancer, as they accumulate mainly in the cytosol and mitochondria, shorten the longitudinal relaxation time (T₁) and thereby increase signal intensity on T₁-weighted sequences. Most often used in preclinical neuroimaging, MEMRI is also gaining attention in cancer research, providing potentially new insights into tumour biology and treatment response monitoring. The use of MEMRI faces challenges such as the potential toxicity of free manganese and the need for chelation (mangafodipir trisodium, MnPyC3A), careful dosing below ≈25 µmol Mn2+/kg and development of new imaging protocols. Ongoing translational research aims to improve the safety profile of manganese agents and optimise imaging strategies. Early clinical studies in neurology and cardiology are exploring MEMRI; clinical oncology use remains investigational and limited. We review preclinical advances and the limited early human experience, outlining safety considerations and the potential, yet unproven, effectiveness of MEMRI in oncology. The present review also contextualises MEMRI within the broader landscape of metal-based precision imaging and neutron capture therapy approaches, including boron neutron capture therapy and gadolinium neutron capture therapy, which represent complementary strategies exploiting the tumour-selective accumulation of specific metal ions. Recent clinical and translational evidence supports the maturation of these approaches: a phase II trial of accelerator-based boron neutron capture therapy with borofalan in head and neck cancer reported acceptable safety, and a systematic review across malignant tumours confirmed favourable efficacy and safety signals for boron neutron capture therapy. Manganese-based nanotheranostics are concurrently emerging as a route to combine magnetic resonance imaging with image-guided therapy.
Achieving clear resection margins (> 5 mm) is critical during laryngeal and hypopharyngeal tumor resection, as positive margins are associated with reduced disease-specific survival. Near-infrared (NIR) fluorescence imaging has emerged as a valuable tool for intraoperative margin assessment by enabling real-time visualization of residual tumor tissue. However, current fluorescent contrast agents rely on intravenous administration, often requiring dosing hours to days before surgery. Also, targeting tumor-specific biomarkers with heterogeneous expression limits applicability. To address these limitations, we evaluated the feasibility of a topically applied pH-activatable fluorophore (PH10), which selectively fluoresces under acidic conditions. This ex vivo proof-of-concept study investigates whether topical PH10 can visualize laryngeal and hypopharyngeal tumors. Freshly resected laryngeal and hypopharyngeal squamous cell carcinoma (SCC) specimens were obtained from ten patients and topically sprayed with PH10 immediately after surgery. Following a 2-min incubation period, NIR fluorescence images were acquired before and after three sequential saline washes. Fluorescence intensity was quantified as the tumor-to-background ratio (TBR); tumor localization was confirmed on histopathology. Laryngeal tumors demonstrated tumor-specific fluorescence upon PH10 application, with significantly higher signal intensity in tumor tissue compared to adjacent normal mucosa (P < 0.05). The median TBR after the first wash was 2.3 (interquartile range 1.7–3.0), exceeding the clinically relevant threshold of 1.5 in seven of seven laryngeal SCC cases; however, this threshold was not reached in either of the two hypopharyngeal carcinoma cases included. This proof-of-concept study suggests that PH10, a sprayable pH-activatable fluorophore, can enable rapid and high-contrast visualization of laryngeal tumors, although this was not observed in the small number of hypopharyngeal cases evaluated. Given its topical application and rapid activation, PH10 may hold promise for intraoperative margin assessment, yet these preliminary findings, based on a small and heterogeneous sample, require validation in larger cohorts, including direct correlation with deep resection margins, before clinical utility can be established.
Amyloid-β (Aβ) positron emission tomography allows direct in vivo visualization of insoluble fibrillar Aβ deposition and has been used to detect Alzheimer’s disease pathology across the clinical continuum, from preclinical stages to overt dementia. Aβ tracers progressed from the prototypical [11C]Pittsburgh Compound-B ([11C]PiB), which is limited by [11C] half-life, to [18F]-labeled agents, including [18F]Florbetapir, [18F]Florbetaben, and [18F]Flutemetamol, which allowed centralized production and wide clinical use, with [18F]NAV4694 currently in development. In this narrative review, we sought to examine the principal Aβ positron emission tomography radioligands and their methodological framework, including visual reads, the standardized uptake value ratio, and the Centiloid scale, which harmonized quantitative output across tracers, scanners, and protocols and may enable cross-site comparison in multicenter studies and disease-modifying trials. The regulatory approval of lecanemab and donanemab has recently expanded the clinical use of Aβ positron emission tomography. Beyond diagnostic confirmation, the modality can currently confirm eligibility for anti-Aβ therapy, enrich trial populations, monitor target engagement through serial Centiloid measurements, and inform treatment discontinuation at predefined clearance thresholds. However, significant limitations remain, including the imperfect correlation between a high Aβ plaque burden and clinical cognitive decline that constrains its standalone diagnostic utility, tracer-specific variability, restricted accessibility, and the inability of fibril-targeted tracers to image the soluble oligomeric species most directly engaged by anti-Aβ antibodies. Probes for non-fibrillar species and computational tools for assisted interpretation are likely to shape the field in the near future.
The estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) treatment landscape continues to evolve with targeted therapy development. Estrogen receptor 1 (ESR1) testing is recommended at recurrence or each progression event to identify patients for effective therapies. However, there is limited information on testing and mutation patterns in the real world that can inform patient identification in the clinic. A retrospective observational study among patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative MBC who initiated first line (1L) therapy with aromatase inhibitors or selective estrogen receptor degraders ± CDK4/6 inhibitors from 1 January, 2020 to 31 March, 2025, using the Flatiron Health Research Database was conducted. ESR1 testing and mutation positivity rates at 1L to third line initiation, stratified by endocrine-resistant, 1L endocrine-sensitive, and endocrine-sensitive/de novo MBC were descriptively reported. Overall testing rates varied across subgroups, with one or more ESR1 test per patient in 61.2
