Radioembolization For Colorectal Liver Metastases Research Articles

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

PurposeTo 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 MethodsThis 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. ResultsMedian 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 = .028). A decrease in Ki67 was also documented (median, 73%; IQR, 70%–80% at T0 vs median, 41%; IQR, 0%–66% at T3; P = .046). 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 = .030). 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). ConclusionsPost-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.

Arterial enhancement on triphasic computed tomography scan predicts response of colorectal liver metastases to chemoembolization: A case–control study

Objectives: The arterial enhancement fraction (AEF), a simple calculation based on a standard triple-phase computed tomography (CT) scan, has been shown to predict treatment response in radioembolization of colorectal liver metastases (CRLM). The current study aims to determine if arterial enhancement also predicts treatment response in transarterial chemoembolization (TACE) of CRLM, which uses a larger particle size and exerts an ischemic effect. Materials and Methods: A retrospective analysis of our experience with TACE for CRLM between 2013 and 2022 yielded 97 TACE treatments for CRLM. The study included the first TACE treatment patients having a triple-phase CT scan before and after TACE, yielding 62 tumors treated with TACE of irinotecan drug-eluting beads in 36 patients. Tumors with complete response or partial response based on CT-based modified RECIST criteria were considered to be “responders,” whereas tumors that had progressive disease or stable disease were considered to be “non-responders.” Results: The responders differed from the non-responders in terms of arterial phase enhancement (APhE) (9.5 [interquartile range, IQR 6, 17] vs. 2 [IQR 1, 5] Hounsfield units [HUs], P < 0.001) and AEF (0.7 [IQR 0.5, 1] vs. 0.3 [IQR 0.1, 1], P = 0.01), both validated measures of hepatic arterial perfusion. Receiver operating characteristic curve analysis yielded a 5.5 HU cutoff for APhE. Those tumors with APhE >5.5 HU had a response rate of 72%, whereas those <5.5 HU had a response rate of 21%. Median overall survival for patients with tumors having APhE >5.5 HU was 22.4 months (IQR 13, 32) versus 14.5 months (IQR 10, 19) for those with APhE ≤5.5 HU, but this did not achieve statistical significance (P = 0.14). Conclusion: CRLM with greater hepatic arterial blood supply as measured by the APhE and AEF have a higher probability of TACE treatment response.

MR Imaging Volumetric Response after Yttrium-90 Radioembolization for Colorectal Liver Metastases: Predictability at Baseline and Correlation with Survival

PurposeTo prove the utility of magnetic resonance (MR) imaging response as a surrogate end point of treatment efficacy and survival after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CRLMs), and to investigate whether outcomes can be predicted at baseline using MR imaging or clinical variables. Materials and MethodsA total of 50 (135) patients with TARE for CRLMs between August 2008 and January 2020 and peri-interventional MR imaging within defined timeframes were included for tumor segmentation. Pretreatment and posttreatment target tumor volumes were measured according to the volumetric Response Evaluation Criteria In Solid Tumors (vRECIST) and the quantitative European Association for the Study of the Liver (qEASL) criteria. Cox regression models were used to analyze the impact of MR morphologic response, vascularity at baseline, and clinical variables on patient survival. Logistic regression analyses were used to evaluate the predictors of MR morphologic response at baseline. ResultsThe median survival was 337 days (95% confidence interval [CI], 243–431). As opposed to the vRECIST, the application of the qEASL criteria 3 months after the treatment allowed for a significant (P < .05) separation of the survival curves for partial response, stable disease, and progressive disease with a median survival of 412 days (95% CI, 57–767) in responders. High tumor burden and technetium-99m lung shunt significantly decreased the probability of survival. MR morphologic response was not predictable at baseline using imaging or clinical data. ConclusionsMR response according to the qEASL criteria outperformed the vRECIST in measuring the biologic impact of TARE and predicting patient survival. Baseline contrast enhancement did not predict MR response to treatment, which may reflect elevated dose requirements in tumors with a high proportion of viable tumor volume.

Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes.

Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using 90Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types of 90Y microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of 90Y microspheres selectively to treat a tumor involving 1 or 2 liver segments. This technique administers a very high radiation dose and effectively causes the ablation of tumors that are too large or are in a location considered unsafe for thermal ablation. The selective delivery spares surrounding normal liver, reducing the risk of liver failure.

PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases.

PurposeTo establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization.Materials and MethodsRetrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1). Mutation status as well as clinical, tumor, and treatment variables were recorded. These factors were evaluated in relation to time to local progression (TTLP), which was calculated from time of radioembolization to first radiographic evidence of local progression. Predictors of outcome were identified using a proportional hazards model for both univariate and multivariate analysis with death as a competing risk.ResultsSixteen patients (40%) had no mutations in either pathway, eighteen patients (45%) had mutations in the MAPK pathway, ten patients (25%) had mutations in the PI3K pathway and four patients (10%) had mutations in both pathways. The cumulative incidence of progression at 6 and 12 months was 33% and 55% for the PI3K mutated group compared with 76% and 92% in the PI3K wild type group. Mutation in the PI3K pathway was a significant predictor of longer TTLP in both univariate (p=0.031, sHR 0.31, 95% CI: 0.11-0.90) and multivariate (p=0.015, sHR=0.27, 95% CI: 0.096-0.77) analysis. MAPK pathway alterations were not associated with TTLP.ConclusionsPI3K pathway mutation predicts longer time to local progression after radioembolization of colorectal liver metastases.

Abstract No. 372 - Genomic and histopathologic biomarkers in Y90 radioembolization for colorectal liver metastases

Abstract No. 372 - Genomic and histopathologic biomarkers in Y90 radioembolization for colorectal liver metastases

Metabolic tumor volume and total lesion glycolysis on FDG-PET/CT can predict overall survival after 90Y radioembolization of colorectal liver metastases: A comparison with SUVmax, SUVpeak, and RECIST 1.0

PurposeTo compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following 90Y resin microspheres radioembolization of colorectal liver metastases (CLM). MethodsWe conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. ResultsThe study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1–5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2-16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST 1.0 (P=0.44) did not predict OS. ConclusionMetabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.

90Y Radioembolization of Colorectal Hepatic Metastases Using Glass Microspheres: Safety and Survival Outcomes from a 531-Patient Multicenter Study.

Hepatic metastases of colorectal carcinoma are a leading cause of cancer-related mortality. Most colorectal liver metastases become refractory to chemotherapy and biologic agents, at which point the median overall survival declines to 4-5 mo. Radioembolization with (90)Y has been used in the salvage setting with favorable outcomes. This study reports the survival and safety outcomes of 531 patients treated with glass-based (90)Y microspheres at 8 institutions, making it the largest (90)Y study for patients with colorectal liver metastases. Data were retrospectively compiled from 8 institutions for all (90)Y glass microsphere treatments for colorectal liver metastases. Exposure to chemotherapeutic or biologic agents, prior liver therapies, biochemical parameters before and after treatment, radiation dosimetry, and complications were recorded. Uni- and multivariate analyses for predictors of survival were performed. Survival outcomes and clinical or biochemical adverse events were recorded. In total, 531 patients received (90)Y radioembolization for colorectal liver metastases. The most common clinical adverse events were fatigue (55%), abdominal pain (34%), and nausea (19%). Grade 3 or 4 hyperbilirubinemia occurred in 13% of patients at any time. The median overall survival from the first (90)Y treatment was 10.6 mo (95% confidence interval, 8.8-12.4). Performance status, no more than 25% tumor burden, no extrahepatic metastases, albumin greater than 3 g/dL, and receipt of no more than 2 chemotherapeutic agents independently predicted better survival outcomes. This multiinstitutional review of a large cohort of patients with colorectal liver metastases treated with (90)Y radioembolization using glass microspheres has demonstrated promising survival outcomes with low toxicity and low side effects. The outcomes were reproducible and consistent with prior reports of radioembolization.

The Use of Bevacizumab Prior to Radioembolization of Colorectal Liver Metastases with Yttrium-90 Resin Microspheres

Radioembolization is one strategy for treating liver metastases from colorectal cancer. Other studies have reported on radioembolization following cytotoxic chemotherapy, but data examining radioembolization following prior anti-angiogenic therapy with bevacizumab are limited. The only previous study (Murthy et al., J Vasc Interv Radiol 2005) that directly reported the outcomes of patients with bevacizumab use prior to radioembolization did not include any patients who received the prescribed dose of microspheres.

Author reply: Radioembolization for colorectal liver metastases

Author reply: Radioembolization for colorectal liver metastases

Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.