An Interventional Oncology Research Roundup
See below for summaries from selected papers published in 2016 on various interventional oncology therapies.
Study Finds No Difference Between Drug-Eluting vs Bland Microspheres for Liver Tumors
This single-center randomized trial aimed to compare the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres for patients with liver tumors. Patients were randomly assigned to embolization with microspheres alone (Bead Block [BTG], 51 patients) or microspheres loaded with doxorubicin 150 mg (LC Bead [BTG], 50 patients). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 using multiphase computed tomography 2 to 3 weeks after treatment and then at quarterly intervals. Adverse events occurred with similar frequency in both groups, with no difference in RECIST response. The authors concluded that the results bring into question the usefulness of doxorubicin-eluting beads for chemoembolization of HCC.
Brown KT, Do RK, Gonen M, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol. 2016;34(17):2046-2053.
SIRFLOX Study Evaluates SIRT With Chemotherapy for mCRC
This randomized, multicenter trial assessed the safety and efficacy of adding selective internal radiation therapy (SIRT) using yttrium-90 (Y90) resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in 530 patients with previously untreated metastatic colorectal cancer (mCRC). The control arm consisted of mFOLFOX6 (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) plus or minus bevacizumab at the investigator’s discretion. The treatment arm consisted of the control arm regimen with a single whole-liver dose of SIR-Spheres Y90 resin microspheres (Sirtex Medical Inc.) administered on day 3 or 4 of either cycle 1 or 2. Median progression-free survival (PFS) at any site was 10.2 vs 10.7 months in the control vs SIRT (HR, 0.93; 95% CI, 0.77-1.12; P=.43). Median PFS in the liver by competing risk analysis was 12.6 vs 20.5 months in control vs SIRT (HR, 0.69; 95% CI, 0.55-0.90; P=.002). The authors concluded that the addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver.
van Hazel GA, Heinemann V, Sharma NK, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;34:1723–1731.
Comparison of Criteria for Intrahepatic Cholangiocarcinoma Treated With Glass Microspheres Yttrium-90 Selective Internal Radiation Therapy
This study compared Choi criteria with RECIST for the prediction of overall survival (OS) in patients treated with glass-microspheres, Yttrium-90 selective internal radiation therapy (SIRT) for intrahepatic cholangiocarcinoma (ICC). Between 2010 and 2014, 45 adult patients with locally advanced ICC treated with SIRT were retrospectively analyzed. Computed tomography scans performed before and after treatment were analyzed using both RECIST 1.1 and Choi criteria. The response was correlated with survival. The authors concluded that Choi criteria appear more appropriate than RECIST to identify responders with long survival among patients who received SIRT for ICC.
Beuzit L, Edeline J, Brun V, et al. Comparison of Choi criteria and Response Evaluation Criteria in Solid Tumors (RECIST) for intrahepatic cholangiocarcinoma treated with glass-microspheres Yttrium-90 selective internal radiation therapy (SIRT). Eur J Radiol. 2016;85(8):1445-1452.
Liver CT for Vascular Mapping in Radioembolization Work-up
This study compared right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolization work-up between early and late arterial phase liver CT protocols. This study was conducted in 100 patients who underwent liver CT with early or late arterial phase protocol (50 in each arm; 10-second vs 20-second post-threshold delay). Origin detection rates and contrast-to-noise ratio (CNR) of the hepatic artery relative to the portal vein were compared between the protocols. The first-second rater scored the RGA origin as visible in 58% to 65% and A4 origin in 89% to 96%. Thirty-six percent of RGA origins not detectable by DSA were identified with CT. Origin detection rates were not significantly different for early or late arterial phases. Mean CNR was higher in the early arterial phase protocol (1.7 vs 1.2, P<.001). The authors concluded that a 10-second delay arterial phase CT protocol does not significantly improve detection of small intra- and extrahepatic branches, and RGA origin detection needs improvement. Origin detection for A4/MHA is adequate and has good inter-rater reproducibility. Computed tomography is still an important tool for preprocedural planning because it may reveal arterial anatomy not identified via digital subtraction angiography.
van den Hoven AF, Braat MN, Prince JF, et al. Liver CT for vascular mapping during radioembolisation workup: comparison of an early and late arterial phase protocol. Eur Radiol. 2016 Apr 23. [Epub ahead of print]
Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Prediction of Early Arterial Blood Flow Stasis in Radioembolization of Breast Cancer Liver Metastases
This study retrospectively evaluated the predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for early arterial blood flow stasis during transarterial radioembolization of liver-dominant breast metastases (LdBM). Preinterventional 1.5T DWI data were analyzed for 28 liver lobes of 18 female patients treated by resin-based radioembolization (10 bilobar and 8 unilobar treatments). Apparent diffusion coefficient and an estimation of the true diffusion coefficient and of the perfusion fraction were calculated for the 2 largest metastases. Response rate at 3 months and survival were analyzed. Procedures without full dose application because of early stasis were assigned to group A (n=15), and procedures with full dose application were assigned to group B (n=13). Overall survival did not differ significantly between group A (230 days) and B (155 days) (P=.124). The authors concluded that perfusion-sensitive IVIM parameter may predict early blood flow stasis in patients undergoing transarterial radioembolization for LdBM. Determining this parameter before intervention may provide important information to the interventionalist and increase safety of microsphere administration.
Pieper CC, Willinek WA, Meyer C, et al. Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Prediction of Early Arterial Blood Flow Stasis in Radioembolization of Breast Cancer Liver Metastases. J Vasc Interv Radiol. 2016;27(9):1320-1328.
Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Y90 Radioembolization
This study evaluated RECIST version 1.1 tumor-attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assessed interobserver variability for measuring tumor attenuation using a single 2D region of interest on a simple picture archiving and communication system workstation. A total of 25 patients with 46 target tumors were enrolled in the study. The intraclass correlation coefficient was 0.95 at baseline and 0.98 at response evaluation. More responders (i.e., partial response) were identified using EORTC PET criteria (n=14), Choi criteria (n=15), and tumor attenuation criteria (n=13) than using RECIST 1.1 (n=2). Researchers concluded that RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM.
Shady W, Sotirchos VS, Do RK, et al. Surrogate imaging biomarkers of response of colorectal liver metastases after salvage radioembolization using 90Y-loaded resin microspheres. AJR Am J Roentgenol. 2016;207(3):661-670.
Yttrium-90 Radioembolization as a Salvage Treatment Following Chemoembolization for Hepatocellular Carcinoma
This retrospective study was conducted to determine safety and efficacy of Y90 transarterial radioembolization in patients who have undergone chemoembolization for hepatocellular carcinoma. Forty patients were identified (median age 61 years; range, 44-84 years). There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1-11.6 cm). Of 40 patients, 29 (72.5%) underwent transarterial radioembolization. Median progression-free survival and overall survival were 90 days and 257 days. The results showed that transarterial radioembolization is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone >4 chemoembolizations to the Y90 target, feasibility of transarterial radioembolization tends to be decreased.
Johnson GE, Monsky WL, Valji K, et al. Yttrium-90 radioembolization as a salvage treatment following chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2016;27(8):1123-1129.
Resin vs Glass Microsphere Radioembolization for Hepatocellular Carcinoma With Portal Vein Invasion
This single-center retrospective review sought to compare outcomes of Y90 radioembolization performed with resin-based and glass-based microspheres in the treatment of hepatocellular carcinoma (HCC) with associated portal vein invasion. Ninety patients were identified, 21 treated with resin and 69 treated with glass microspheres. Grade 3/4 bilirubin and aspartate aminotransferase toxicities developed at a 2.8-fold (95% CI, 1.3-6.1) and 2.6-fold (95% CI, 1.1-6.1) greater rate in the resin microsphere group. The disease control rate was 37.5% in the resin group and 54.5% in the glass microsphere group (P=.39). The median (95% CI) time to progression was 2.8 months in the resin microsphere group and 5.9 months in the glass microsphere group (P=.48). Median (95% CI) survival was 3.7 months in the resin microsphere group and 9.4 (7.6-15.0) months in the glass microsphere group (HR, 2.6; 95% CI, 1.5-4.3, P<.001). The authors concluded that imaging response of Y90 treatment in patients with HCC and portal vein thrombosis was not significantly different between Y90 glass and Y90 resin groups. Lower toxicity and improved OS were observed in the glass microsphere group.
Biederman DM, Titano JJ, Tabori NE, et al. Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein invasion: resin versus glass microspheres. J Vasc Interv Radiol. 2016;27(6):812-821.e2.
Procedural Impact of a Dedicated Interventional Oncology Service Line in a National Cancer Institute Comprehensive Cancer Center
Researchers tested the hypothesis that establishing a dedicated interventional oncology (IO) clinical service line would increase clinic visits and procedural volumes at a single quaternary care academic medical center. From one time period to the next, clinic visits increased from 9 to 204 (P=.003, t=8.89, df=3). Procedures increased from 60 to 239 (P=.018, t=3.85, df=4). Procedural volumes increased at least 150% for each subtype. The volumes in the 5% Limited Data Set did not change significantly over the 2-year period (443 to 385, P>.05). The authors concluded that establishing a dedicated IO service significantly increased clinic visits and procedural volumes, but national trends were unchanged.
Koran ME, Lipnik AJ, Baker JC, et al. Procedural impact of a dedicated interventional oncology service line in a National Cancer Institute comprehensive cancer center. J Am Coll Radiol. 2016;13(9):1145-1150.
Sol Gel Is a Promising Material for Radioembolization
There has been recent development of spherical yttrium oxide grains obtained by a sol-gel method for production of Y90 microspheres. The authors present and discuss the results of investigations performed in the development of this new technology. The final product has the structure of spherical yttrium oxide grains with a diameter 25 μm to 100 μm, is stable, and is free from contaminants. The authors concluded that microspheres prepared by the proposed technique is a promising medical material for radioembolization of liver malignancies.
Łada W, Iller E, Wawszczak D, et al. (90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies. Mater Sci Eng C Mater Biol Appl. 2016;67:629-635.
Study of Angiogenic Response After Radioembolization
In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone or radioembolization with sorafenib. In the Y90/sorafenib arm, angiopoietin-2 and platelet-derived growth factor decreased at 2 weeks and the remainder increased. By 4 weeks, only platelet-derived growth factor remained below baseline levels. The authors concluded that radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts platelet-derived growth factor response; other factors such as vascular endothelial growth factor remain unaffected.
Lewandowski RJ, Andreoli JM, Hickey R, et al. Angiogenic response following radioembolization: results from a randomized pilot study of yttrium-90 with or without sorafenib. J Vasc Interv Radiol. 2016;27(9):1329-1336.
What Can We Learn From the SIRFLOX Trial?
In the setting of liver metastases from colorectal cancer (CRC), radioembolization with Y90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall PFS between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 vs 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 vs 12.6 months; P=.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Because radioembolization targets liver disease, lack of improvement in PFS might be explained by the fact that 40% of the SIRFLOX population had extrahepatic disease.
Sangha BS, Nimeiri H, Hickey R, et al. Radioembolization as a treatment strategy for metastatic colorectal cancer to the liver: what can we learn from the SIRFLOX trial? Curr Treat Options Oncol. 2016;17(6):26.
Hepatic Thermal Ablation: Effect of Device and Heating Parameters on Local Tissue Reactions and Distant Tumor Growth
In this study, researchers aimed to determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Rats with subcutaneous breast adenocarcinoma tumors had normal non-tumor-bearing liver treated with RFA, rapid higher-power MWA, slower lower-power MWA, or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). The authors concluded that although hepatic MWA can incite periablational inflammation and increased distant tumor growth similar to RFA in an animal tumor model, higher-power, faster heating protocols may mitigate such undesired effects.
Velez E, Goldberg SN, Kumar G, et al. Hepatic thermal ablation: effect of device and heating parameters on local tissue reactions and distant tumor growth. Radiology. 2016 Sep;207(3):661-670.
Local Tumor Control and Survival in High- vs Low-Frequency Microwave Ablation in Malignant Liver Tumors
This retrospective study included 221 patients (mean age: 61.7 years) with 356 malignant hepatic lesions. Ninety-four patients with 133 lesions underwent low-frequency microwave ablation (LF-MWA), and 127 patients with 223 lesions were treated with high-frequency microwave ablation (HF-MWA). The mean initial ablation volume of LF-MWA was nearly half of HF-MWA (19.1 mL vs 39.9 mL, P<.0001). With LF-MWA, 39/133 lesions (29.32%) progressed at follow-up while the number of lesions that progressed with HF-MWA was 10/223 (4.5%). The mean time to progression was 5.03 and 5.31 months for the lesions treated with LF-MWA and HF-MWA respectively. The difference between both systems was significant (P=.00059). The authors concluded that LF- and HF-MWA systems are effective treatment options for oligonodular liver malignant lesions, but significantly higher ablation volumes, longer time to progression and lower progression rates were observed in HF-MWA.
Vogl TJ, Hagar A, Nour-Eldin NA, et al. High frequency versus low frequency microwave ablation in malignant liver tumors: evaluation of local tumor control and survival. Int J Hyperthermia. 2016;32(8):868-875.
CT-Guided RFA for Lymph Node Oligometastases From Hepatocellular Carcinoma
The purpose of this study was to assess the effectiveness and safety of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for lymph node (LN) oligometastases from hepatocellular carcinoma (HCC). From January 2004 to December 2013, 119 consecutive patients with HCC and LN oligometastases were included in this study. A matched cohort composed of 46 patients from each group was selected after adjustment with propensity score matching. The median follow-up time was 14.0 months in the RFA group and 13.8 months in the non-RFA group. The RFA group showed higher 6-month and 1-year OS rates compared with the non-RFA group. The 3-month local control rate after RFA was 84.4%, including complete response in 71.1% of patients and partial response in 13.3%. The authors concluded that percutaneous CT-guided RFA may be a safe and effective treatment for the LN oligometastases generated by HCC.
Pan T, Xie QK, Lv N, et al. Percutaneous CT-guided radiofrequency ablation for lymph node oligometastases from hepatocellular carcinoma: a propensity score-matching analysis. Radiology. 2016 Jul 11:151807. [Epub ahead of print]
Yttrium-90 Radioembolization of Nonconventional Liver Tumors
This article systematically reviews and summarizes the current literature to assess the effects of Y90 radioembolization on nonconventional hepatic neoplasms. A few small studies have produced favorable initial results. The study limitations are heterogeneity of patient cohort, lack of standardized treatment response criteria, and difference in treatment dosage. According to the studies, a justifiable benefit (or lack thereof) from Y90 SIRT on any given patient depends on both tumor type and patient status. To improve patient outcomes, larger, multicenter studies and established clinical guidelines are necessary.
Park JK, Phyu W, Zaw T, Walsworth M, Lee HY, Lee EW. Yttrium-90 radioembolization of nonconventional liver tumors. Intervent Oncol 360. 2016;4(7):E115-E129.
US RESiN Registry for the Study and Evaluation of Patients Treated With SIR-Spheres
This study aims to describe the Radiation-Emitting SIR-Spheres in Non-resectable Liver Tumor (RESiN) registry, a national, multicenter database that will enroll patients with primary or secondary liver cancer who are scheduled for treatment with Y90 resin microspheres as part of their care plan. Patients will be included without regard to tumor type or additional therapies and followed longitudinally. For patients with colorectal or neuroendocrine tumors, subgroup analyses will be performed to identify factors that influence outcomes in order to develop personalized treatments. The RESiN registry will be a resource that will provide the oncology community with a more comprehensive understanding of the benefits and risks of Y90 resin microspheres as a localized treatment for a range of hepatic tumors and patients, including patients who would likely not be included in clinical trials. The registry will also guide future research into Y90 resin microsphere therapy, especially for conditions for which limited data currently exist.
Banovac F, Brown DB. US RESiN registry for the study and evaluation of patients treated with SIR-Spheres. Intervent Oncol 360. 2016;4(6):E101-E111.
Editor’s note: This article is reprinted with permission from Synergy Show Daily 16: Official Show Daily for Synergy 2016, published November 5, 2016.