Peiman Habibollahi

Objective: To assess the long-term oncologic and survival outcomes of percutaneous cryoablation (PCA) for patients with solitary de novo T1a renal cell carcinoma (RCC). Methods: This retrospective study was conducted following the STROBE guidelines. We included patients with a single, biopsy-confirmed, treatment-naïve T1a RCC (<4 cm) who underwent PCA between January 2008 and December 2021. Patient demographics, tumor characteristics, and procedural details were collected. Survival analyses were performed using the Kaplan–Meier estimator. Results: Eighty-six patients (57 men and 29 women) with a median age of 69 years met the inclusion criteria. Fifty patients (58%) had a history of an additional non-renal malignancy. In total, 86 renal tumors were treated using PCA, with a median tumor diameter of 2.7 cm. Clear cell RCC accounted for 67.4% of the tumors. Procedural complications classified as Clavien–Dindo grade III or higher occurred in 4.6% of cases. Local tumor recurrence at the ablation site was observed in five patients (5.8%), and four patients (4.6%) developed new lesions elsewhere within the kidney. The estimated median overall survival was 10.34 years. The 10-year local recurrence-free and disease-free survival rates were 93.5% and 84.0%, respectively. Both metastasis-free survival and cancer-specific survival rates at 10 years were 100%. Conclusions: Percutaneous cryoablation provided durable local tumor control with low major morbidity and favorable long-term oncologic outcomes in this selected cohort of patients with solitary cT1a renal tumors.

Supplementary Figure S2: GPC3 expression in HCC samples and normal adjacent liver. Sample images from immunostaining showing nearly absent GPC3 expression in normal adjacent liver (n=41) (A, B) and high GPC3 expression in HCC tumors (n=47) (C,D). 79% of the tumors (79%) stained strongly positive for GPC3 expression (Grade 3 and 4) (E). Within normal adjacent liver samples only 2 (5%) had grade 3/4 GPC3 expression compared to 79% among HCC tumor samples (F).

Supplementary Figure S3: GPC3-specific targeting peptide has a similar binding pattern to HCC samples compared to immunostaining with GPC3 antibody. (A-D) Representative contiguous slides from HCC samples stained with GPC3 antibody (A, B) and GPC3-specific peptide (C, D) demonstrate similar staining patterns. HCC, hepatocellular carcinoma.

Supplementary Figure 4: In-Vivo treatment schedule of injections and imaging. After i.p. injection of saline or T-cells, tumors were injected with saline, scGPC3/CD3, or the GPC3/CD3 bispecific antibody every 12 hours for a total of five injections. This serial injection sequence was repeated on the fourth day following the first injection. Mice were euthanized on day 14 with tumor tissues preserved for histology.

Supplementary Figure S1: Expression and Purification of TRAB Recombinant Protein. Synthesized TRAB gene fragments (IDT DNA, Coralville, IA), as specified in figure above (A), were inserted into a pTXB1 (New England Biolabs) vector using standard restriction enzyme based cloning techniques. Insertion of the TRAB sequence was verified by DNA sequencing using the T7 promoter as the sequencing primer. The TRAB-pTXB1 plasmids were then transformed into a competent E coli expression cell line (Origami 2 Cells, Novagen). Bacterial cell cultures were initially grown overnight in an air shaker (225 rpm) at 37°C in 3 mL of lysogeny broth (LB) media, eventually inoculated into scaled up 1 L LB media containing 50 mg/L of ampicillin. At optical density (OD) 600 nm = 0.6, Isopropyl β-D-1-thiogalactopyranoside (IPTG) was added to a final concentration of 0.5 mM to induce T7 RNA polymerase-based expression. Cultures were allowed to express for 2 h at 37°C. Bacterial cultures were centrifugally pelleted at 10,000 g for 30 min, resuspended in 5 mL of column buffer (20 mM Na-HEPES, 0.5 M NaCl, 1 mM EDTA, pH 8.5) containing 0.75 g/L lysozyme and 50 mM phenylmethylsulfonyl fluoride. Cells were lysed by pulse sonication on ice. Cell lysate was centrifuged at 15,000 g for 30 min at 4°C. Supernatant was then loaded and incubated in Poly-Prep chromatography column (Bio-Rad, Hercules, CA) packed with Talon metal affinity resin (Clontech, Mountain View, CA). Supernatant was then allowed to pass through the column and resin beads were washed with multiple rounds of column buffer (0.1 M Tris-HCl, pH 8.5). Bound and washed TRAB protein (sequence shown in panel B) was then released from metal resin via the addition of 200 mM imidazole-containing elution buffer. Purification and concentration of the final product was performed using a 3 kDa molecular weight cutoff (MWCO) filter (Amicon Ultra, Milipore, Temecula, CA). The final product was analyzed on SDS-PAGE protein gel (Figure 2), with confirmation of the protein band at the expected molecular weight.

This invited review discusses recent advancements and prospects in locoregional therapy (LRT) for hepatocellular carcinoma (HCC), a leading cause of cancer mortality globally. The epidemiology of HCC is shifting toward nonviral etiologies, prompting a focus on early surveillance and personalized treatment approaches. Updated international guidelines, such as the Barcelona Clinic Liver Cancer (BCLC) staging system, American Association for Study of Liver Disease (AASLD) guideline, and European Association for the Study of the Liver (EASL) now recognize LRT—including transarterial embolization, ablation, and radiotherapy—as cornerstone therapies in curative and downstaging strategies for HCC at multiple stages. The article reviews novel transarterial and ablative technologies, including advanced dosimetry for radioembolization, innovative embolic agents, and emerging nonthermal ablation modalities like irreversible electroporation and pulsed electric field ablation, all aimed at increasing precision, local delivery, minimizing systemic exposure. Additionally, combination approaches integrating LRT with immunotherapy are highlighted, reflecting the evolving understanding of HCC’s tumor-immune microenvironment. Progress in robotic guidance, fusion imaging, and imageable radioembolics is also explored. Ongoing and future clinical trials will further define the optimal use of these evolving modalities. Overall, LRT continues to expand as a minimally invasive, indispensable backbone in multidisciplinary HCC management.

Objective: To assess the safety and diagnostic outcomes of image-guided, non-target renal biopsies performed in cancer patients. Materials and Methods: We retrospectively identified patients who underwent percutaneous, image-guided, non-target renal biopsy between January 2017 and December 2020 in our institution. We recorded demographics, clinical, procedural, and pathologic details. Univariate and multivariable logistic regression models were used to assess the association between various variables and diagnostic yield or development of adverse events. Results: A total of 318 biopsies were performed in 318 patients (178 male, 140 female) with a median BMI of 28.4 kg/m². Median systolic and diastolic BP at the time of biopsy were 133 mmHg and 74 mmHg, respectively. Tissue was obtained using 18-gauge needles (99%). Adverse events were documented in 57 cases (18%), with 12 cases (3.8%) classified as grade 2 or higher per SIR classification. Diagnosis was achieved in 310 biopsies (97%). The median number of the glomeruli identified by light microscopy, immunofluorescence, and electron microscopy was 25, 8, and 3, respectively, and a higher number of identified glomeruli was associated with diagnostic yield in univariate analysis, although not in multivariable analysis. Diastolic BP higher than 80 mmHg and CT imaging guidance were associated with the development of adverse events in univariate analysis, and CT use remained so in the final multivariable analysis (p < 0.001). No other variables, including pre-biopsy anticancer or immunotherapy medications, were associated with increased risk of adverse events. Conclusions: Percutaneous, image-guided, non-target renal biopsy in cancer patients using an 18-gauge needle has a high diagnostic yield and safety profile.

Purpose: To describe the safety and efficacy of Yttrium-90 transarterial radioembolization (Y90-TARE) in patients with fibrolamellar hepatocellular carcinoma (FL-HCC). Patients and Methods: This is a retrospective study of patients with FL-HCC treated with Y90-TARE in a single tertiary cancer center. Y90-TARE was performed using Y90 glass or resin microspheres. Treatment response was evaluated at 1, 3, and 6 months using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Electronic medical records were retrospectively reviewed to evaluate clinical outcomes, complications, tumor response on imaging, overall survival (OS), and progression-free survival (PFS). MIM Software (v7.1, Cleveland, OH) was used for dosimetry analysis and contouring. Results: Seven patients (5 females, 2 males; median age at the time of Y90-TARE: 24, range: 16– 77 years) with FL-HCC underwent nine Y90-TARE procedures. The median progression-free survival (PFS) was 9.0 months, and the median overall survival (OS) was 15.8 months. Partial response (PR) was observed in 86% of patients at 3 months and 100% of evaluable patients at 6 months. One patient underwent successful liver transplantation, and another received hepatectomy after treatment. No adverse events grade 3 or greater were reported within 30 days. One patient developed a hepatic abscess two months post-procedure, and another developed a tumor to duodenum fistula three months after Y90-TARE. The median absorbed tumor dose was 405 Gy (mean: 579 ± 442 Gy; range: 109– 1362 Gy), and the median absorbed dose to perfused normal liver was 83 Gy (mean: 96 ± 41 Gy; range: 63.5– 190 Gy). The median administered activity was 3.85 GBq, with a median lung shunt fraction of 4.59% and a median lung dose of 6.4 Gy. The study is limited by its retrospective design and small sample size in this rare tumor cohort. Conclusion: Treatment of FL-HCC patients with unresectable tumors with 90Y-TARE is safe and shows a favorable response to treatment. Plain Language Summary: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of liver cancer that usually affects young people without underlying liver disease. Because it is rare, there is limited information on multidisciplinary treatment approaches, especially when surgery is not feasible. In this study, we report seven patients with FL-HCC who were treated with Yttrium-90 transarterial radioembolization (Y90-TARE). The treatment delivers radiation directly to liver tumors through the hepatic arteries, which can help control tumor growth with acceptable side effects. The study found that the treatment was generally safe and well-tolerated and induced promising anti-tumor effects and survival outcomes. In two cases, the treatment allowed patients to undergo surgery for treatment. These findings suggest that Y90-TARE may be a valuable multidisciplinary treatment option for select patients with FL-HCC, particularly those with unresectable disease. Our study warrants further investigation through future multicenter studies to validate this approach in patients with FL-HCC.

Interventional radiology (IR) is a rapidly evolving medical field that combines advanced imaging with minimally invasive techniques for both diagnosis and treatment. Interventional oncology (IO), a subspecialty of IR, focuses on the minimally invasive, image‐guided intervention for cancer and cancer‐related conditions. IR plays an important and increasingly recognized role within the multidisciplinary care of patients with cancer, contributing meaningfully to diagnosis, therapy, and palliation. IO therapies, particularly tumor ablation and transarterial embolization, aim to target tumors directly while preserving surrounding healthy tissue. These therapies are increasingly supported by clinical guidelines and have shown favorable outcomes in cancers such as hepatocellular carcinoma, renal cell carcinoma, and metastatic colorectal cancer. This review focuses on the role of minimally invasive, image‐guided, locoregional IR therapies for patients who have cancer.