Imaging Considerations before and after Liver-Directed Locoregional Treatments for Metastatic Colorectal Cancer.

Colorectal cancer is a leading cause of cancer-related death. Liver metastases will develop in over one-third of patients with colorectal cancer and are a major cause of morbidity and mortality. Even though surgical resection has been considered the mainstay of treatment, only approximately 20% of the patients are surgical candidates. Liver-directed locoregional therapies such as thermal ablation, Yttrium-90 transarterial radioembolization, and stereotactic body radiation therapy are pivotal in managing colorectal liver metastatic disease. Comprehensive pre- and post-intervention imaging, encompassing both anatomic and metabolic assessments, is invaluable for precise treatment planning, staging, treatment response assessment, and the prompt identification of local or distant tumor progression. This review outlines the value of imaging for colorectal liver metastatic disease and offers insights into imaging follow-up after locoregional liver-directed therapy.

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.

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver.

PURPOSE: To assess whether yttrium-90 transarterial radioembolization (TARE) is safe and effective in the treatment of primary lung cancer metastases to the liver (LCML). METHODS AND METHODS: This retrospective study included 57 patients with LCML who were treated with 79 TARE treatments. Histology included non-small cell lung cancer (NSCLC) (n = 27), small cell lung cancer (SCLC) (n = 17), and lung carcinoid (LC) (n = 13). Survival was calculated using Kaplan-Meier method; differences between groups were estimated using log rank test. Cox proportional hazards model was used to determine factors influencing survival. Adverse events were graded using the Society of Interventional Radiology Adverse Events Classification. RESULTS: Median overall survival (OS) was as follows: NSCLC, 8.3 months (95% confidence interval [CI], 6.3-16.4 months); SCLC, 4.1 months (95% CI, 1.9-6.6 months); and LC, 43.5 months (95% CI, 7.8-61.4 months). For NSCLC, presence of bilobar vs unilobar disease (hazard ratio [HR], 5.24; 95% CI, 1.64-16.79; P = .002); more tumors, 2-5 vs 1 (HR, 4.88; 95% CI, 1.17-20.37; P = .003) and >5 vs 1 (HR, 3.75; 95% CI, 0.95-6.92; P = .05); and lobar vs segmental treatment (HR, 2.56; 95% CI, 0-NA; P = .002) were negative predictors of OS. For SCLC, receipt of >2 lines of chemotherapy vs ≤2 lines (HR, 3.16; 95% CI, 0.95-10.47; P = .05) was a negative predictor of OS. For LC, tumor involvement of >50% was a negative predictor of OS (HR, 3.77 × 1015; 95% CI, 0-NA; P = .002). There were 11 of 79 severe or life-threatening adverse events within 30 days (abdominal pain, altered mental status, nausea/vomiting, acalculous/aseptic cholecystitis, hyponatremia, pancreatitis, renal failure, and death from pneumonia). CONCLUSIONS: TARE has an acceptable safety profile for the treatment of LCML, with survival benefits best seen in LC tumors.

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.

The Importance of Optimal Thermal Ablation Margins in Colorectal Liver Metastases: A Systematic Review and Meta-Analysis of 21 Studies.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the US. Thermal ablation (TA) can be a comparable alternative to partial hepatectomy for selected cases when eradication of all visible tumor with an ablative margin of greater than 5 mm is achieved. This systematic review and meta-analysis aimed to encapsulate the current clinical evidence concerning the optimal TA margin for local cure in patients with colorectal liver metastases (CLM). METHODS: MEDLINE, EMBASE, and the CENTRAL databases were systematically searched from inception until 1 May 2023, in accordance with the PRISMA Guidelines. Measure of effect included the risk ratio (RR) with 95% confidence interval (CI) using the random-effects model. RESULTS: Overall, 21 studies were included, comprising 2005 participants and 2873 ablated CLMs. TA with margins less than 5 mm were associated with a 3.6 times higher risk for LTP (n = 21 studies, RR: 3.60; 95% CI: 2.58-5.03; p-value < 0.001). When margins less than 5 mm were additionally confirmed by using 3D software, a 5.1 times higher risk for LTP (n = 4 studies, RR: 5.10; 95% CI: 1.45-17.90; p-value < 0.001) was recorded. Moreover, a thermal ablation margin of less than 10 mm but over 5 mm remained significantly associated with 3.64 times higher risk for LTP vs. minimal margin larger than 10 mm (n = 7 studies, RR: 3.64; 95% CI: 1.31-10.10; p-value < 0.001). CONCLUSIONS: This meta-analysis solidifies that a minimal ablation margin over 5 mm is the minimum critical endpoint required, whereas a minimal margin of at least 10 mm yields optimal local tumor control after TA of CLMs.

Percutaneous image-guided ablation for hepatic metastases.

The presence of hepatic metastases indicates advanced disease and is associated with significant morbidity and mortality, especially when the hepatic disease is not amenable to locoregional treatments. The primary tumour of origin, the distribution and extent of metastatic disease, the underlying liver reserve, the patient performance status and the presence of comorbidities are factors that determine whether a patient will benefit from hepatectomy or local curative-intent treatments. For patients with metastatic colorectal cancer, the most common primary cancer that spreads to the liver, several studies have demonstrated a survival benefit for patients who can be treated with hepatectomy and/or percutaneous ablation, compared to those treated with chemotherapy alone. Despite advances in surgical techniques increasing the percentage of patients eligible for surgery, most patients have unresectable disease or are poor surgical candidates. Percutaneous ablation can be used to provide local disease control and prolong survival for both surgical and non-surgical candidates. This is typically offered to patients with small hepatic metastases that can be ablated with optimal (≥10 mm) or at least adequate minimum ablation margins (≥5 mm), as high local tumour control rates can be achieved for these patients which are comparable to surgical resection. This review summarizes available evidence and outcomes following percutaneous ablation of the most frequently encountered types of hepatic metastases in the clinical practice of interventional oncology. Patient selection, technical considerations, follow-up protocols and oncologic outcomes are presented and discussed.

Safety and Efficacy of Hepatic Artery Embolization in Heavily Treated Patients with Intrahepatic Cholangiocarcinoma: Analysis of Clinicopathological and Radiographic Parameters Associated with Better Overall Survival.

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4-18.5) and 4 months (CI = 95%, 2.09-5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC.

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.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma.

PURPOSE: Transarterial radioembolization (TARE) is a liver-directed treatment for unresectable intrahepatic cholangiocarcinoma (ICC). The aim of this study is to evaluate factors affecting outcomes of TARE in heavily pretreated ICC patients. METHODS: We evaluated pretreated ICC patients who received TARE from January 2013 to December 2021. Prior treatments included systemic therapy, hepatic resection, and liver-directed therapies, including hepatic arterial infusion chemotherapy, external beam radiation, transarterial embolization, and thermal ablation. Patients were classified based on history of hepatic resection and genomic status based on next-generation sequencing (NGS). The primary endpoint was overall survival (OS) after TARE. RESULTS: Fourteen patients with median age 66.1 years (range, 52.4-87.5), 11 females and 3 males, were included. Prior therapies included systemic in 13/14 patients (93%), liver resection in 6/14 (43%), and liver-directed therapy in 6/14 (43%). Median OS was 11.9 months (range, 2.8-81.0). Resected patients had significantly longer median OS compared to unresected patients (16.6 versus 7.9 months; p = 0.038). Prior liver-directed therapy (p = 0.043), largest tumor diameter > 4 cm (p = 0.014), and > 2 hepatic segments involvement (p = 0.001) were associated with worse OS. Nine patients underwent NGS; 3/9 (33.3%) and had a high-risk gene signature (HRGS), defined as alterations in TP53, KRAS, or CDKN2A. Patients with a HRGS had worse median OS (10.0 versus 17.8 months; p = 0.024). CONCLUSIONS: TARE may be used as salvage therapy in heavily treated ICC patients. Presence of a HRGS may predict worse OS after TARE. Further investigation with more patients is recommended to validate these results.

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.

Colorectal Cancer Liver Metastases: Genomics and Biomarkers with Focus on Local Therapies.

Molecular cancer biomarkers help personalize treatment, predict oncologic outcomes, and identify patients who can benefit from specific targeted therapies. Colorectal cancer (CRC) is the third-most common cancer, with the liver being the most frequent visceral metastatic site. KRAS, NRAS, BRAF V600E Mutations, DNA Mismatch Repair Deficiency/Microsatellite Instability Status, HER2 Amplification, and NTRK Fusions are NCCN approved and actionable molecular biomarkers for colorectal cancer. Additional biomarkers are also described and can be helpful in different image-guided hepatic directed therapies specifically for CRLM. For example, tumors maintaining the Ki-67 proliferation marker after thermal ablation have been particularly resilient to ablation. Ablation margin was also shown to be an important factor in predicting local recurrence, with a ≥10 mm minimal ablation margin being required to attain local tumor control, especially for patients with mutant KRAS CRLM.

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.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.