Histopathologic Changes after Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study.

PURPOSE: To evaluate the histopathologic changes and potential correlations of tumor absorbed dose (TAD) after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CLMs). MATERIALS AND METHODS: This prospective pilot study assessed 12 patients with 13 CLMs through positron emission tomography (PET)/computed tomography (CT)-guided biopsies before, immediately after TARE (T0), and 3 weeks after TARE (T3). Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin and eosin, TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3. RESULTS: Median TAD at 3 weeks after TARE was 162 Gy (interquartile range (IQR), 92-211 Gy). DSBs decreased significantly from T0 (median, 77%; IQR, 75%-100%) to T3 (median, 14%; IQR, 0%-54%; P = .03). A decrease in Ki67 was also documented (median, 73%; IQR, 70%-80% at T0 vs median, 41%; IQR, 0%-66% at T3; P = .05). There was a strong positive correlation between TAD and DSBs at T0 (r[9] = 0.68) and a strong negative correlation at T3 (r[10] = -0.855; P = .042 and P = .002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r[9] = -0.733; P = .025) and T3 (r[10] = -0.681; P = .03). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8 [88%] vs 1/5 [20%]; P = .015). CONCLUSIONS: Post-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in DSBs and proliferation index were noted after TARE. Post-TARE CC3 activation deserves further exploration.

Three-Dimensional Margin as a Predictor of Local Tumor Progression after Microwave Ablation: Intraprocedural versus 4-8-Week Postablation Assessment.

PURPOSE: To evaluate the prognostic accuracy of intraprocedural and 4-8-week (current standard) post-microwave ablation zone (AZ) and margin assessments for prediction of local tumor progression (LTP) using 3-dimensional (3D) software. MATERIALS AND METHODS: Data regarding 100 colorectal liver metastases (CLMs) in 75 patients were collected from 2 prospective fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT)-guided microwave ablation (MWA) trials. The target CLMs and theoretical 5- and 10-mm margins were segmented and registered intraprocedurally and at 4-8 weeks after MWA contrast-enhanced CT (or magnetic resonance [MR] imaging) using the same methodology and 3D software. Tumor and 5- and 10-mm minimal margin (MM) volumes not covered by the AZ were defined as volumes of insufficient coverage (VICs). The intraprocedural and 4-8-week post-MWA VICs were compared as predictors of LTP using receiver operating characteristic curve analysis. RESULTS: The median follow-up time was 19.6 months (interquartile range, 7.97-36.5 months). VICs for 5- and 10-mm MMs were predictive of LTP at both time assessments. The highest accuracy for the prediction of LTP was documented with the intra-ablation 5-mm VIC (area under the curve [AUC], 0.78; 95% confidence interval, 0.66-0.89). LTP for a VIC of 6-10-mm margin category was 11.4% compared with 4.3% for >10-mm margin category (P < .001). CONCLUSIONS: A 3D 5-mm MM is a critical endpoint of thermal ablation, whereas optimal local tumor control is noted with a 10-mm MM. Higher AUCs for prediction of LTP were achieved for intraprocedural evaluation than for the 4-8-week postablation 3D evaluation of the AZ.

Advancements and Future Outlook of PET/CT-Guided Interventions.

Advancements in minimally invasive technology, coupled with imaging breakthroughs, have empowered the field of interventional radiology to achieve unparalleled precision in image-guided diagnosis and treatment while simultaneously reducing periprocedural morbidity. Molecular imaging, which provides valuable physiological and metabolic information alongside anatomical localization, can expand the capabilities of image-guided interventions. Among various molecular imaging techniques, positron emission tomography (PET) stands out for its superior spatial resolution and ability to acquire quantitative data. PET has emerged as a crucial tool for oncologic imaging and plays a pivotal role in both staging and the assessment of treatment responses. Typically used in combination with computed tomography (CT) (PET/CT) and occasionally with magnetic resonance imaging MRI (PET/MRI), PET as a hybrid imaging approach offers enhanced insights into disease progression and response. In recent years, PET has also found its way into image-guided interventions, especially within the rapidly expanding field of interventional oncology. This review aims to explore the current and evolving role of metabolic imaging, specifically PET, in interventional oncology. By delving into the unique advantages and applications of PET in guiding oncological interventions and assessing response, we seek to highlight the increasing significance of this modality in the realm of interventional radiology.

Gradient-based Volumetric PET Parameters on Immediate Pre-ablation FDG-PET Predict Local Tumor Progression in Patients with Colorectal Liver Metastasis Treated by Microwave Ablation.

PURPOSE: This study aimed to evaluate the optimal method of segmentation of colorectal liver metastasis (CLM) on immediate pre-ablation PET scans and assess the prognostic value of quantitative pre-ablation PET parameters with regards to local tumor control. A secondary objective was to correlate the target tumor size estimation by PET methods with the tumor measurements on anatomical imaging. METHODOLOGY: A prospectively accrued cohort of 55 CLMs (46 patients) treated with real-time 18F-FDG-PET/CT-guided percutaneous microwave ablation was followed-up for a median of 10.8 months (interquartile: 5.5-20.2). Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) values of each CLM were derived from pre-ablation 18F-FDG-PET with gradient and threshold PET segmentation methodologies. The event was defined as local tumor progression (LTP). Time-dependent receiver operating characteristic (ROC) curve analyses were used to assess area under the curves (AUCs). Intraclass correlation (ICC) and 95.0% confidence interval (CI) were performed to measure the linear relationships between the continuous variables. RESULTS: AUCs for prediction of LTP obtained from time-dependent ROC analysis for the gradient technique were higher in comparison to the threshold methodologies (AUCs for TLG and volume were: 0.790 and 0.807, respectively). ICC between PET gradient-based and anatomical measurements were higher in comparison to threshold methodologies (ICC for the longest diameter: 733 (95.0% CI 0.538-0.846), ICC for the shortest diameter: .747 (95.0% CI 0.546-0.859), p-values < 0.001). CONCLUSIONS: The gradient-based technique had a higher AUC for prediction of LTP after microwave ablation of CLM and showed the highest correlation with anatomical imaging tumor measurements.

Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

PURPOSE: To evaluate the yttrium-90 (90Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure. MATERIALS AND METHODS: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after 90Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time 90Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of 90Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens' activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored. RESULTS: The mean measured 90Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal. CONCLUSIONS: Counting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing 90Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.

Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.

Real-Time Split-Dose PET/CT-Guided Ablation Improves Colorectal Liver Metastasis Detection and Ablation Zone Margin Assessments without the Need for Repeated Contrast Injection.

BACKGROUND: Real-time split-dose PET can identify the targeted colorectal liver metastasis (CLM) and eliminate the need for repeated contrast administration before and during thermal ablation (TA). This study aimed to assess the added value of pre-ablation real-time split-dose PET when combined with non-contract CT in the detection of CLM for ablation and the evaluation of the ablation zone and margins. METHODS: A total of 190 CLMs/125 participants from two IRB-approved prospective clinical trials using PET/CT-guided TA were analyzed. Based on detection on pre-TA imaging, CLMs were categorized as detectable, non-detectable, and of poor conspicuity on CT alone, and detectable, non-detectable, and low FDG-avidity on PET/CT after the initial dose. Ablation margins around the targeted CLM were evaluated using a 3D volumetric approach. RESULTS: We found that 129/190 (67.9%) CLMs were detectable on CT alone, and 61/190 CLMs (32.1%) were undetectable or of poor conspicuity, not allowing accurate depiction and targeting by CT alone. Thus, the theoretical 5- and 10-mm margins could not be defined in these tumors (32.1%) using CT alone. When TA intraprocedural PET/CT images are obtained and inspected (fused PET/CT), only 4 CLM (2.1%) remained undetectable or had a low FDG avidity. CONCLUSIONS: The addition of PET to non-contrast CT improved CLM detection for ablation targeting, margin assessments, and continuous depiction of the FDG avid CLMs during the ablation without the need for multiple intravenous contrast injections pre- and intra-procedurally.

Predictors of Major Hemorrhage After Spleen Core Biopsy in Cancer Patients.

In this retrospective study, 232 spleen biopsies from 218 patients with cancer were assessed. Biopsies resulting in hemorrhage requiring hospitalization, transfusion, or other interventions were compared with those that did not. The maximization of the Youden index helped determine the optimal systolic blood pressure (SBP) and platelet count thresholds. There were 15 (7%) major hemorrhages among 211 core biopsies. A multivariate logistic regression model showed that higher SBP, lower platelet count, and the lack of ultrasound guidance were independently associated with major hemorrhage (P < .05). The optimal SBP cutoff was 140 mm Hg, and the platelet count cutoff was 120,000 platelets/µL. In conclusion, the high major hemorrhage rate of 7% among percutaneous core spleen biopsies in patients with cancer may be mitigated by controlling SBP to <140 mm Hg and avoiding biopsy in patients with thrombocytopenia.

Biopsy and Margins Optimize Outcomes after Thermal Ablation of Colorectal Liver Metastases.

BACKGROUND: Thermal ablation is a definitive local treatment for selected colorectal liver metastases (CLM) that can be ablated with adequate margins. A critical limitation has been local tumor progression (LTP). METHODS: This prospective, single-group, phase 2 study enrolled patients with CLM < 5 cm in maximum diameter, at a tertiary cancer center between November 2009 and February 2019. Biopsy of the ablation zone center and margin was performed immediately after ablation. Viable tumor in tissue biopsy and ablation margins < 5 mm were assessed as predictors of 12-month LTP. RESULTS: We enrolled 107 patients with 182 CLMs. Mean tumor size was 2.0 (range, 0.6-4.6) cm. Microwave ablation was used in 51% and radiofrequency ablation in 49% of tumors. The 12- and 24-month cumulative incidence of LTP was 22% (95% confidence interval [CI]: 17, 29) and 29% (95% CI: 23, 36), respectively. LTP at 12 months was 7% (95% CI: 3, 14) for the biopsy tumor-negative ablation zone with margins ≥ 5 mm vs. 63% (95% CI: 35, 85) for the biopsy-positive ablation zone with margins < 5 mm (p < 0.001). CONCLUSIONS: Biopsy-proven complete tumor ablation with margins of at least 5 mm achieves optimal local tumor control for CLM, regardless of the ablation modality used.

PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.

PURPOSE: To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). MATERIALS AND METHODS: From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51 days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. RESULTS: Of the 68 post-RE scans, 6 were performed at 0-30 days, 15 at 31-60 days, 9 at 61-90 days, 13 at 91-120 days, 14 scans at 121-180 days, and 11 scans at > 180 days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15 months after the first RE administration. Highest response rates occurred at 30-90 days, with over 75% of cases demonstrating OR at that time. After 180 days, OR was seen in only 25%. There was a median TTP of 169 days among responders. CONCLUSION: In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30-90 days, with progression noted after 180 days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.