Sheth, Rahul A.

e16535 Background: RMC is a rare and highly aggressive malignancy that predominantly affects young individuals with sickle hemoglobinopathies. Due to its rarity, no validated prognostic models exist to guide clinical decision-making. We aimed to develop and internally validate a prognostic model for patients with RMC using routinely available clinical and laboratory variables. Methods: We analyzed a single-institution cohort of patients with RMC. Candidate variables were identified based on biological plausibility and represented in a directed acyclic graph. Missing data were handled via multiple imputation by chained equations ( m = 50). Variables were ranked using elastic net Cox regression ( α = 0.5, λ = λ min ) with stability selection derived from 100 bootstrap resamples per imputed dataset. Predictors achieving > 60% selection frequency were retained for a nested parsimony analysis. Bootstrap internal validation ( B = 2000) estimated optimism-corrected discrimination and calibration performance, with the calibration slope applied as global shrinkage to penalize final coefficients for overfitting. Clinical utility was evaluated via decision curve analysis (DCA) at 18- and 24-month horizons. Results: Among 180 patients (median age 29; IQR 23–37), 142 deaths occurred with a median follow-up of 12.4 months. The final model included four predictors (Table). The optimism-corrected c-index was 0.667 (optimism = 0.009), and the calibration slope was 0.964, indicating minimal overfitting. Calibration plots showed excellent predicted-observed agreement at 12, 18, 24, and 36 months. DCA showed net benefit across threshold probabilities of 10%–75% at 18 months and 10%–80% at 24 months compared to default strategies. In sensitivity analysis, inclusion of TP53 mutation status improved discrimination ( c -index 0.686) and model fit ( ΔAIC −10.6). An interactive web-based risk calculator was developed to facilitate clinical implementation. Conclusions: This study presents the first internally validated prognostic model for RMC, demonstrating acceptable discrimination and excellent calibration using routinely available variables. By stratifying patients into distinct risk groups, this model may inform treatment intensity—guiding escalation to multi-agent regimens or sequential chemotherapy cycling in high-risk patients, while identifying lower-risk patients who may benefit from de-escalation strategies such as metastasis-directed therapy for oligometastatic disease or consideration of cytoreductive nephrectomy. External validation is warranted. Variable Time Ratio 95% CI p value ECOG performance status 0.64 0.53–0.77 <0.001 Distal (non-retroperitoneal) lymph node metastases 0.69 0.52–0.92 0.011 Neutrophil-to-lymphocyte ratio 0.98 0.94–1.02 0.25 Corrected calcium (mg/dL) 0.77 0.56–1.06 0.10 Sensitivity Analysis Only TP53 Mutation 0.63 0.36-1-10 0.10

Abstract Purpose: Intratumoral injection of Clostridium novyi-nontoxic (C. novyi-NT), lacking alpha-toxin, germinates and subsequently replicates in the tumor hypoxic regions, causing cell lysis and inflammation. This phase Ib study investigated the safety and synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors. Patients and Methods: Patients with injectable solid tumors received one intratumoral C. novyi-NT injection (day 8) across four dose cohorts (3 × 104 to 100 × 104 spores) with pembrolizumab (200 mg intravenously every 3 weeks, day 0–24 months). Sixteen patients were enrolled with a median age of 62.5 years, and the most common tumor types were breast cancer and melanoma. Results: The combination therapy demonstrated a manageable safety profile, with one grade 3 dose-limiting toxicity of abscess formation and the remainder of treatment-related adverse events in ≥10% of patients being grade 1 or 2 injection site reaction (25%), pyrexia (19%), pruritus (13%), leukopenia (13%), and anemia (13%). The maximum tolerated dose was determined to be pembrolizumab intravenously at 200 mg every 3 weeks and a single dose of 100 × 104C.novyi-NT spores intratumorally on day 8. The confirmed overall objective response rate of 25% was observed among four patients with nonkeratinizing undifferentiated nasopharyngeal squamous carcinoma, human papilloma virus–positive squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma. Among these patients, we obtained three partial responses and one complete response. The median duration of the response was 10.93 months, and stable disease was observed in 69% of patients. Conclusions: This study highlights the potential of the C. novyi-NT and pembrolizumab combination as a promising therapeutic strategy for treatment-refractory solid tumors.

AbstractTissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra‐procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material‐based approaches to improve the delivery of energy and pharmacology‐based therapeutics.

Abstract Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape‐memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and affects millions worldwide. Due to the lack of effective systemic therapies for HCC, researchers have been investigating the use of locoregional tumor control with Yttrium-90 (Y90) radioembolization since the 1960s. Following the development of glass and resin Y90 microspheres in the early 1990s, Y90 radioembolization has been shown to be a safe and efficacious treatment for patients with HCC across Barcelona Clinic Liver Cancer (BCLC) stages. By demonstrating durable local control, good long term outcomes, and equivalent if not superior tumor responses and tolerability when compared to alternative therapies including transarterial chemoembolization (TACE) and sorafenib, Y90 radioembolization is being increasingly used in HCC treatment. More recently, investigations into variations in Y90 radioembolization technique including radiation segmentectomy and radiation lobectomy have further expanded its clinical utility. Here, we discuss the history and evolution of Y90 use in HCC. We outline key clinical trials that have established the safety and efficacy of Y90 radioembolization, and also summarize trials comparing its efficacy to existing HCC treatments. We conclude by reviewing the techniques of radiation segmentectomy and lobectomy, and by discussing dosimetry.

Radiogenomics is a computational discipline that identifies correlations between cross-sectional imaging features and tissue-based molecular data. These imaging phenotypic correlations can then potentially be used to longitudinally and non-invasively predict a tumor’s molecular profile. A different, but related field termed radiomics examines the extraction of quantitative data from imaging data and the subsequent combination of these data with clinical information in an attempt to provide prognostic information and guide clinical decision making. Together, these fields represent the evolution of biomedical imaging from a descriptive, qualitative specialty to a predictive, quantitative discipline. It is anticipated that radiomics and radiogenomics will not only identify pathologic processes, but also unveil their underlying pathophysiological mechanisms through clinical imaging alone. Here, we review recent studies on radiogenomics and radiomics in liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastases to the liver.

Liver cancers contribute significantly to cancer-related mortality worldwide and liver transplants remain the cornerstone of curative treatment for select, early-stage patients. Unfortunately, because of a mismatch between demand and supply of donor organs, liver cancer patients must often wait extended periods of time prior to transplant. A variety of local therapies including surgical resection, transarterial chemoembolization, and thermal ablative methods exist in order to bridge to transplant. In recent years, a number of studies have examined the role of irreversible electroporation (IRE) as a non-thermal local ablative method for liver tumors, particularly for those adjacent to critical structures such as the vasculature, gall bladder, or bile duct. In addition to proving its utility as a local treatment modality, IRE has also demonstrated promise as a technique for donor organ decellularization in the context of whole-organ engineering. Through complete non-thermal removal of living cells, IRE allows for the creation of an acellular extra cellular matrix (ECM) scaffold that could theoretically be recellularized and implanted into a living host. Here, we comprehensively review studies investigating IRE, its role in liver cancer treatment, and its utility in whole organ engineering.

Minimally invasive techniques to occlude flow within blood vessels, initially pioneered in the 1970s with autologous materials and subsequently advanced with increasingly sophisticated engineered biomaterials, are routinely performed for a variety of medical conditions. Contemporary interventional radiologists have at their disposal a wide armamentarium of occlusive agents to treat a range of disease processes through a small incision in the skin. In this review, we provide a historical perspective on endovascular embolization tools, summarize the current state-of-the-art, and highlight burgeoning technologies that promise to advance the field in the near future.