Citations

Abstract Photon-counting detector CT (PCD-CT) represents a significant advancement in medical imaging, particularly for musculoskeletal (MSK) applications. Its primary innovation lies in enhanced spatial resolution, which facilitates improved detection of small anatomical structures such as trabecular bone, osteophytes, and subchondral cysts. PCD-CT enables high-quality imaging with reduced radiation doses, making it especially beneficial for populations requiring frequent imaging, such as paediatric patients and individuals with multiple myeloma. Additionally, PCD-CT supports advanced applications like bone quality assessment, which correlates well with gold-standard tests, and can aid in diagnosing osteoporosis and assessing fracture risk. Techniques such as spectral shaping and virtual monoenergetic imaging further optimize the technology, minimizing artefacts and enhancing material decomposition. These capabilities extend to conditions like gout and haematologic malignancies, offering improved detection and assessment. The integration of artificial intelligence could enhance PCD-CT’s performance by reducing image noise and improving quantitative assessments. Ultimately, PCD-CT’s superior resolution, reduced dose protocols, and multi-energy imaging capabilities will likely have a transformative impact on MSK imaging, improving diagnostic accuracy, patient care, and clinical outcomes.

Surgical treatment and outcomes of fibrous dysplasia (FD) in pediatric patients are areas that have not been fully studied. The authors completed a retrospective review of 20 patients who had at least one surgery for craniofacial fibrous dysplasia before 18 years of age. Surgeries were categorized into 3 groups: bone contouring only; removal of the involved bone, contouring, and replacement of the contoured bone; or en bloc resection of the involved bone and reconstruction with an alloplastic material, bone allograft, or bone autograft obtained from non-involved sites. A total of 36 distinct surgical procedures were performed in 20 patients, with a mean number of 1.9 surgeries/patient (range 1–5). The maxilla was both the bone that was most commonly affected and most commonly operated on. The most common surgical indication was visible or palpable growth in 63.9% of cases. Bone contouring only was the initial surgery in 15 patients, of whom 9 patients (55.6%) had continued bone growth requiring subsequent surgeries. Removal, contouring, and replacement wasthe initial surgery in 1 patient, who required a secondary surgery. Four patients, all with monostotic calvarial disease, initially had an en bloc resection and reconstruction; none had recurrence. Patients with subsequent surgeries had a mean time to operation of 3.7 years (range 0.24–9.8). The recurrence rate and need for secondary surgical procedures were relatively high in patients who had bone contouring only. These patients tended to be patients with facial bone involvement more than calvarial involvement.

Abstract Most myelofibrosis (MF) drug approvals by Health Authorities are based on 1 or 2 outcome measures such as spleen volume reduction and/or improved quality-of-life. This 1–2 dimensional approach fails to capture the clinical complexity of MF. A European LeukemiaNet (ELN) taskforce developed a composite endpoint which allows multiple outcomes to be simultaneously measured. The panel used the Desirability-Of-Outcome-Ranking (DOOR) method to assign 25 outcomes into 4 quartiles based on a multi-dimensional desirability score and build a 5-layer composite outcome named Desirability-of-Myelofibrosis-Outcomes (DEMYO). Outcome operational definitions were tested by Delphi consensus and correlations with survival validated by a literature review. The outcomes assigned to the first two quartiles were negatively correlated with leukemia-free survival and survival. DEMYO comprehensively captures relevant MF clinical features and meaningful endpoints. Despite DEMYO requires validation based on available trial data, it is expected to improve the quality of Health Authority approvals for new drugs for MF.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly used as a primary treatment modality for intracranial meningiomas. We aim to describe clinical outcomes after single-fraction SRS for sporadic intracranial meningiomas. METHODS: A prospectively maintained database was reviewed for patients with sporadic meningiomas who underwent SRS (Gamma Knife) as primary treatment modality from April 1997 to February 2022. Primary outcomes included progression-free survival (PFS) and treatment-related complications. RESULTS: Six hundred sixteen patients (653 tumors) underwent SRS with median follow-up of 6.3 years (interquartile range [IQR] 3.1-10.5 years). The median tumor volume was 4.5 cm 3 (IQR 2.0-8.0 cm 3 ). The median margin dose was 15.0 Gy (IQR 14.0-16.0). In-field progression was noted in 7 tumors (1.1%) and marginal progression in 2 tumors (0.3%) for a raw failure rate of 1.4%. PFS estimates at 5, 10, and 15 years were 99.8%, 99.0%, and 93.2%, respectively. Factors associated with reduced PFS on univariable analysis included older age (hazards ratio [HR] 1.14, 95% CI, 1.05-1.22, P < .001), male sex (HR 5.44, 95% CI, 1.45-20.4, P = .010), increasing tumor volume (HR 1.06, 95% CI, 0.99-1.13, P = .028), and lower tumor margin dose (HR 0.65, 95% CI, 0.43-0.97, P = .006). Treatment-related complications were noted in 56 patients (9.1%), of which 45 (7.3%) were temporary, 5 (0.8%) were minor, and 6 (1.0%) were permanent and/or required intervention. Radiosurgical parameters associated with treatment-related complications included increased number of isocenters (odds ratio [OR] 1.09, 95% CI, 1.04-1.14, P < .001), higher 12-Gy volume (OR 1.06, 95% CI, 1.03-1.09, P < .001), larger tumor volume (OR 1.06, 95% CI, 1.02-1.10, P < .001), and lower maximal dose (OR 0.90, 95% CI, 0.82-0.98, P = .11). CONCLUSION: SRS is effective as a primary treatment modality for sporadic, small-volume to medium-volume intracranial meningiomas. Pre-emptive SRS should be discussed as a safe management strategy compared with observation alone for incidentally discovered meningiomas.

Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy and the third leading cause of cancer-related death in the world. Liver transplant is a cornerstone in treating nonmetastatic disease, but a significant portion of patients miss the opportunity of upfront liver transplant given the long waiting time for donor organs. Herein, we compare the survival outcomes between upfront liver transplant, liver transplant with bridge systemic therapy, and systemic therapy only. Methods: The National Cancer Database was queried for patients diagnosed with non-metastatic hepatocellular carcinoma (HCC) between 2004 and 2017. After including only patients with clinical N0 stage who received either systemic therapy alone, liver transplant alone or liver transplant with bridge systemic therapy, we split the cohort into 3 groups: systemic therapy only (including intra-arterial chemotherapy eg, TACE) group, upfront liver transplant group and liver transplant with bridge systemic therapy group. We evaluated overall survival (OS) among the three groups. We studied the OS using Kaplan-Meier estimates and multivariate Cox regression analyses to evaluate factors associated with overall survival (OS). Results: A total of 29,691 patients with nonmetastatic HCC were included for analysis, of which 25,122 (84.6%) were treated with systemic therapy only, 2513 (8.5%) were treated with bridge systemic therapy followed by liver transplant, and 2056 (6.9%) were treated with upfront liver transplant without systemic therapy bridge. We found that patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant had a statistically significantly better OS compared to patients who were treated with systemic therapy only (mean OS was 101.9 mo and 98.2 vs. 39.4 mo, respectively, with P <0.001 for all). Whereas there was no significant difference in OS between patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant (mean OS was 101.9 vs. 98.2 months, P =0.187). On multivariate analysis, factors associated with worse OS were older age (HR: 1.011; 95% CI: 1.010-1.013; P <0.001), Male sex (HR: 1.048; 95% CI: 1.014-1.084; P =0.006), White compared with African American race (HR: 1.055; 95% CI: 1.012-1.099; P =0.011), no insurance status (HR: 1.155; 95% CI: 1.079-1.237; P <0.001), clinical T4 stage compared with T0 stage (HR: 1.366; 95% CI: 1.257-1.483, P <0.001), and systemic therapy alone compared with upfront liver transplant and liver transplant with bridge systemic therapy (HR for upfront liver transplant and transplant with bridge systemic therapy vs. systemic therapy was 0.202; 95% CI: 0.184-0.223, and HR: 0.194, 95% CI: 0.178-0.212, respectively, with P <0.001 for all). Conclusions: Patients with nonmetastatic HCC who were treated with upfront liver transplant or liver transplant with bridge systemic therapy had statistically significant improvement in OS compared with patients who were treated with systemic therapy only. While our study confirms the survival benefit of liver transplant among patients with nonmetastatic HCC, these results raise the importance of proceeding with liver transplant after intra-arterial and/or systemic treatments in patients who are not initially eligible for or missed the opportunity of upfront liver transplant.

Objective: To establish comprehensive recommendations on the management of perihilar cholangiocarcinoma (pCCA) and to identify areas in need of future investigation. Summary Background Data: The lack of consensus in management of pCCA across institutions worldwide impairs optimal patient care and best-achievable oncological outcome. A holistic and critical assessment of the body of evidence and collaborative guidance are required. Methods: The Consensus4pCCA conference developed unbiased consensus using the Zurich-Danish model. An impartial and multidisciplinary jury adopted comprehensive recommendations grounded on the work of eight expert panels answering predefined clinical questions and considering the best-quality evidence through a systematic review. The development of recommendations complied with GRADE and SIGN50 methodologies. Results: Seventy-one international experts considered 570 studies. Ten jury members concluded 71 recommendations covering definition and diagnosis, preoperative assessment and optimization, surgical resection, liver transplantation, and outcome reporting for pCCA patients. The consensus underscored that making patients amenable to high-quality curative resection and reducing its associated morbidity must be of highest priority. As such, multidisciplinary expertise and centralized care at all stages of disease management are critical to ensure both safety and oncological adequacy. To overcome the evidence-gap for rare diseases like pCCA, the jury urged large-scale registries to address open questions across the disease continuum and highlighted priorities for future investigation. Conclusion: The Consensus4pCCA represents an unprecedented commitment to collectively harmonize global treatment strategies for pCCA. This collective effort bridges the gap between expert opinions and clinical evidence and holds great promise to improve patient outcomes in the future.

Abstract INTRODUCTION Plasma biomarkers of Alzheimer's disease (AD) represent accessible alternatives to positron emission tomography (PET) and cerebrospinal fluid (CSF)‐based biomarkers in well‐characterized cohorts. It remains to be determined whether performance is maintained in outpatient clinics comprised of patients with multiple causes of cognitive impairment. METHODS Plasma phosphorylated tau217 (p‐tau217) and amyloid beta (Aβ) 42/40 were measured in 509 patients evaluated in a tertiary‐care memory clinic. Biomarker performance was compared across diagnoses, referencing established cutpoints for positive and negative biomarkers. RESULTS Plasma p‐tau217 distinguished patients with diagnoses of symptomatic AD with 95% sensitivity and 82% specificity. Integration of Aβ42 measurements (p‐tau217/Aβ42) incrementally improved specificity (86%). Plasma p‐tau217 and p‐tau217/Aβ42 concentrations closely associated with established CSF biomarkers of AD (area under the curve [AUC]: 0.94 and 0.96, respectively). Reduced kidney function associated with elevated plasma p‐tau217 and p‐tau217/Aβ42 concentrations in patients without AD (referencing CSF biomarkers). DISCUSSION Plasma p‐tau217 and p‐tau217/Aβ42 concentrations demonstrated robust diagnostic performance in a heterogeneous clinical cohort; interpretation requires consideration of kidney function. Highlights Plasma phosphorylated tau217 (p‐tau217) reliably identified clinic patients with Alzheimer's disease. A two‐cutpoint strategy yielded definitive results in 86% of patients. Integration of plasma amyloid beta (Aβ; p‐tau217/Aβ42) minimally improved diagnostic performance. Plasma p‐tau217 levels were increased in patients with kidney dysfunction.

The management of multiple myeloma (MM) in the elderly is challenging, exacerbated by age-related frailty and comorbidities. T-cell engagers (TCE) have been transformative to the treatment of relapsed MM, achieving deep and durable responses. This review evaluates the efficacy, toxicity, and other practical applications of approved and emerging TCEs in elderly MM patients. Broadly, approved monotherapy with TCEs produce overall response rates (ORR) of 60–70% in extensively treated populations. However, deeper and more durable responses have been observed with use in earlier lines of therapy or combined with conventional treatments. Cytokine release syndrome (CRS) and infection are the cardinal toxicities of TCEs. While CRS tends to be less severe than that observed with cellular immune therapies such as chimeric antigen receptor T-cell (CAR-T), the rate of severe infections appears to be higher, especially with BCMA-directed products, and strategies to mitigate this risk are being actively evaluated. TCEs offer logistical advantages over other cellular therapies, namely their off-the-shelf availability and simplified administration. TCEs are poised to redefine the care of elderly patients with MM and are being actively evaluated in this setting.