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Monday, November 12, 2018

Chemoembolization in Conjunction with Bevacizumab: Preliminary Results


Summary


“The whole is greater than the sum of its parts” – SYNERGY! This is a concept that has been utilized a lot in oncology and modern medicine. Interventional oncology is no exception especially as new cancer treatment options continue to emerge. What we have lacked however, is the robust evidence to support this concept in our blossoming interventional oncology sphere.

In a recently published proof of concept paper, researchers from Italy and Slovenia published their preliminary results for chemoembolization in combination with Bevacizumab in colorectal liver metastasis (CR-LM). In this prospective observational single center trial, 6 patients with unresectable CR-LM that were naïve to standard chemotherapy and had good performance status (ECOG 0 and 1).

The patients received two cycles of DEB-IRI chemoembolization using the PEG embolic delivery platform loaded with 100 mg irinotecan. Bevacizumab was initiated 15 days after the first chemoembolization and then biweekly for a total of 8 cycles. OS, PFS, TTP, mRECIST tumor response, adverse effects and QoL were measured.

At 3 months: 2 pts (33%) CR, 2 pts (33 %) PR, 1 pt (17%) SD and 1 patient progressed (patient had advanced disease and on 4th line chemotherapy). Median overall survival (OS) was 10 months (range 7–15 months), median time to progression was 3 months (range 2–5 months), and median progression-free survival was 7 months (range 3–15 months). There was a reported increase in quality of life in 4 patients (66%)

There were no complications during chemoembolization but mild to moderate adverse events related to post chemoembolization syndrome were reported. Bevacizumab related adverse effects were hypertension (17%) and skins rash (33%).



Figure 1. Tumor response at 1, 3, and 6 months after first transarterial chemoembolization. CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease.

Commentary


Exploiting increased expression of VEGF post chemoembolization to create synergistic localized oncologic benefits was demonstrated with (Hepatocellular carcinoma) HCC where locoregional chemoembolization has had a very significant role over the last 3 decades. We have limited clinical data that this concept is also clinically beneficial to patients with CRC-LM.

Hepatocellular carcinoma tends to be hypervascular and largely depends on the hepatic arterial tree vs CRC - LM which are generally hypovascular and largely depend on portal venous circulation. The impact of these potential perfusion differences on the concept and ability to translate to meaningful clinical benefit or difference is still not known. This paper provides a platform and basis for us to continue to investigate this potentially beneficial option to patients and exciting frontier for interventional oncology.

The median OS of 10 months in this very small cohort is lower than previously published median OS of 14 months with DEB-IRI alone. It is important to note the study recruited technically the “worst” responders with >3 failed lines of systemic chemotherapy and attenuated expected OS. The 3 months mRECIST tumor control rates appeared comparable with previous trials of all comers. Therefore, the preliminary results suggest a very interesting trend which is potentially beneficial to patients with advanced CRC-LM.

This sets an excellent foundation for expanding this to larger multicenter cohorts to validate this concept in chemo naïve CRC-LM and also to perhaps consider trials that extend this concept to early treatment lines for CRM-LM.

The study has multiple weaknesses, not least: sample size, single center, lack of control group, no randomization to name a few. The authors do a good job to acknowledge these and many more.

Click here for the abstract

Fiorentini G, Sarti D, Aliberti C, Carandina R, Mulazzani L, Felicioli A, Guadagni S. Chemoembolization in Conjunction with Bevacizumab: Preliminary Results. J Vasc Interv Radiol. 2018 Sep;29(9):1236-1239. doi: 10.1016/j.jvir.2018.04.022. PubMed PMID: 30146190.

Post Author:
Rodrick C Zvavanjanja MD, MSc, FRCR, DABR(VIR/DR)
Assistant Professor
Department of Diagnostic and Interventional Radiology
University of Texas at Houston McGovern Medical School
@RodZvavanjanja

Thursday, November 8, 2018

Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study 


Summary


Metastatic breast cancer remains a leading cause of cancer death in women and predictors of response to hepatic metastases treated by radioembolization have not been well established.

The authors of this retrospective review sought to describe the response and survival after radioembolization with a focus on pathways affecting radiation sensitivity. They performed a retrospective review of 31 patients who had undergone radioembolization for metastatic invasive ductal carcinoma to the liver. No patient underwent external radiation to the liver or previous transarterial therapy and all but 2 patients had multifocal liver disease. In addition, all patients had received at least 3 lines of systemic therapy prior to radioembolization. Twenty-four patients underwent genetic profiling before radioembolization, with tumor tissue specimens obtained from various sites. Twenty-two patients were treated with resin spheres and 9 were treated with glass spheres with 14 patients undergoing treatment of both hepatic lobes and the remaining patients receiving unilobar or segmental treatments. Imaging response was assessed on PET/CT imaging with the changes in SUVmax evaluated. Among the 26 patients with PET/CT imaging before and after radioembolization, 18 had complete or partial imaging response and 8 did not respond. Genetic profiling was available in 24 patients with 21 patients having both genetic profiling and imaging available. Of these 21 patients, 15 had a response (complete or partial) and 6 did not respond. Radiographic response was found to be significantly associated with PI3K mutations but not MAPK/ERK or TP53 mutations or HER2 receptor status; only 5 of 11 of PI3K wild-type patients (45%) had an imaging response, but all 10 with PI3K mutations showed a response. Furthermore, complete or partial response by PET/CT at 2– 4 months was associated with significantly longer median survival (967 d) compared with patients without imaging response (291 d).



Figure 2. Kaplan–Meier survival analysis of all patients in the cohort demonstrates a median survival of 10.9 months after radioembolization.

Commentary


The researchers found that P13K pathway mutations are associated with early imaging response after radioembolization of metastatic breast cancer to the liver and that imaging response is associated with prolonged survival. While a relatively small sample size was studied, this study adds to our knowledge of genomic profiling as it relates to radioembolization outcomes. The ultimate goal is to optimize patient selection for our therapies and this work represents important progress in that direction.

Click here for abstract

Deipolyi, Amy R. et al. Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study. Journal of Vascular and Interventional Radiology, Volume 29, Issue 9, 1226–1235.

Post Author: 
Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@UTHouston_IR
@ZagumBhatti

Wednesday, November 7, 2018

Comparison of Radiofrequency Ablation and Hepatic Resection for the Treatment of Hepatocellular Carcinoma 2 cm or Less 


Summary


A retrospective analysis to compare the survival outcomes after Radiofrequency ablation (RFA) verses Surgical resection(SR) for Hepatocellular cancer(HCC) measuring ≤ 2cm was undertaken. The National Cancer Database was the source. 833 patients with tumors measuring between 5 and 20 mm who underwent either RFA or SR between 2004 and 2014 were included. 620(74.4%) received RFA and 213 (25.6%) received SR. Mean age 60, median tumor size 15mm, 70.1% males, 61% Caucasians, 42.3 with no comorbidities. Demographic and tumor characteristics between the 2 cohorts were compared using the student’s t test for continuous variables and Chi Square test for categorical variables. Log regression was used to determine variables governing choice of treatment, Kaplan Meier analysis and log rank test were used to compared overall survival (OS). A 2 sided P value of < 0.05 was considered significant.

Median follow up was 33.6 months-32.9 for RFA and 35.4 months for SR. The only factor which showed statistical significance regarding how patients were selected for RFA vs SR was a MELD score of >9. Median OS for the entire cohort was 62.7 months (95% CI 50.6-74.8).1,3 and 5-year survival RF group was 90%,64%,47% and the SR group 89%,75%,62%. SR was not associated with longer OS with HR 0.758(CI 0.538-1.068, P .113). OS was longer with multivariate regression analysis for female gender, African American or Asian ethnicity and median income ≥ $48,000 and shorter for higher MELD scores.



Figure 2. Kaplan-Meier curves of patients who received RF ablation and SR (a) before and (b) after propensity score matching. Dotted lines represent 95% confidence intervals.

Commentary


The authors have tried to address the question whether RFA and SR are comparable for small HCCs. Several studies in the past have given conflicting conclusions. The unique feature of this study is source of the data. The national database has a larger number of patients with diverse backgrounds in terms of ethnicity, etiologies and liver functions. The size criteria are stricter and there is an attempt to compare apples to apples with inclusion of just RFA and no other ablative modalities unlike previous studies. The authors used MELD score to represent liver functions and included all comers not just BCLC A patients. They did not find any difference in OS. The authors also compared the influence of gender, ethnicity, income and liver functions on OS for the entire cohort. They found better prognosis for female gender, African American or Asian ethnicity, higher socioeconomic strata and poorer prognosis for higher MELD scores. The study limitations include its retrospective nature. No information on Child Score, specific etiology, local recurrence rate, complications, recurrence free survival, effect of location of the tumor was available. Also the group studied will not meet the LIRADs criteria of LR5 for HCC due to the size criteria making the diagnosis of HCC questionable. MELD was a determining factor in choosing the treatment option and could be interpreted as the RFA cohort had poorer liver functions. Yet the survival was comparable. The effect of treating sicker patients and having comparable outcome favors RFA to SR. Overall survival is not a great end point in isolation for these small tumors and early HCC as the natural history of these tumors may not be affected by the treatment.

Click here for abstract

Huang Y, Shen Q, Bai HX, et al. Comparison of Radiofrequency Ablation and Hepatic Resection for the Treatment of Hepatocellular Carcinoma 2 cm or Less. J Vasc Interv Radiol 2018; 29:1218-25 e2.

Post Author:
Anil K Pillai, MD
Associate Professor and Section Chief,
University of Texas Health Science Center
@AnkupiMD

Thursday, November 1, 2018

One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter


Summary


Complications associated with Inferior Vena Cava (IVC) filters including Caval thrombosis, device tilting, fracture, migration, embolization, IVC perforation and death are well established and occur with increasing frequency with longer filter indwelling time. Unfortunately, despite increased awareness and filter follow up initiatives, as many as 65-80% of retrievable filters remain in place. The Sentry (Novate Medical, Galway, Ireland) IVC filter is designed to provide temporary protection against PE during transient high-risk periods and then bioconvert, avoiding the need for a second (retrieval) intervention and leaving behind a patent IVC lumen. Bioconversion occurs after approximately 60 days with hydrolysis of an absorbable filament that holds the filter arms together, allows them to retract against the IVC wall.  

This is a prospective, multi-center evaluation including 23 sites and 129 patients from the United States, Belgium and Chile. Early experience with the Sentry IVC filter, including safety and efficacy of the device and success with subsequent bioconversion were studied. Patients included were those with deep vein thrombosis or PE, or at temporary risk for venous thromboembolism and PE who could not use anticoagulation. The primary end point was clinical success, including filter deployment, freedom from new symptomatic PE before filter bioconversion at 60 days and filter related complications.  

Clinical success was achieved in 111 of 114 patients. There were no new cases of PE identified through 12 months of follow up. 2 patients developed symptomatic IVC thrombosis within the first month, which did not recur after successful intervention. There were no filter related complications through 12 months. Filter bioconversion was successful in 110/115 patients (95.7%) at 6-months and 106/100 patients (96.4%) at 12-months.



Figure 1
Photographs of the Sentry IVC filter in coronal view and representations of the axial view: (left) filtering configuration; (right) bioconverted configuration. In the filtering configuration, the 6 pairs of filter arms are held together in the center of the lumen by means of the bioabsorbable filament composed of poly-p-dioxanone. In the bioconverted configuration, the bioabsorbable filament will have been degraded via hydrolysis, allowing the filter arms to release from the cone and retract toward the IVC wall to be endothelialized, leaving an unobstructed IVC lumen.  

Commentary


This prospective, multi-center single arm evaluation of the bioconvertible Sentry filter is an interesting early experience with this device. The complications of IVC filters are widely established and even with a push towards aggressive follow up and filter retrieval, a large proportion of filters remain in place. This bioconvertible device negates the need for a second retrieval procedure in that automatic filter conversion occurs after approximately 2 months, leaving an intact IVC lumen. One potential downside of the device is that the filter does in fact remain in place in the patient’s IVC following bioconversion and so long-term patency and changes in IVC diameter at this level, as well as other potential complications will need extended evaluation. The authors reported that this will be addressed at the 24-month follow up as CT venography will be performed at that time. Additionally, patients who develop a new indication for IVC filtration following bioconversion could be an interesting point of discussion. Does the bioconverted device endothelialize to a point allowing subsequent filter placement at that level or does a new filter need to be placed above or below the bioconverted device, as was done in 2 patients in this study? Some self-reported limitations include its non-randomized, single-arm design as well as the inherent potential bias of a manufacturer funded regulatory device trial. Overall the safety and efficacy of this device appear to be acceptable and in-line with retrievable IVC filters that are available. Bioconversion rates are high and this novel IVC filtration option may prove to be ideal for some patients.   

Click here for abstract

Dake M, Murphy T, Kramer A, Darcy M, Sewall L, Curi M, Johnson M, Arena F, Swischuk J, Ansel G, Silver M, Saddekni S, Brower J, and Mendes R. One Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter. J Vasc Interv Radiol. 2018 Oct;29(10):1350-1361

Post Author:
Jordan Tasse, MD
Assistant Professor, Vascular and Interventional Radiology
Associate Program Director, Integrated VIR residency and VIR fellowship programs
Rush University Medical Center, Chicago, IL
Email: Jordan_C_Tasse@Rush.edu
Twitter: @JTassMD, @VIR_RUSH

Monday, October 29, 2018

Feasibility Study of “Snuffbox” Radial Access for Visceral Interventions


Summary


This report represents a feasibility study of the use of “snuffbox” radial access in the visceral interventions. “Snuffbox” radial access refers to access of the dorsal radial branch located on the dorsum of the hand between the first and second digits. Its use has been recently reported in cardiology literature for patients with limited mobility, operator positioning convenience, and for use as an alternative access due to radial artery limitations.

The authors retrospectively report 50 snuffbox accesses in 31 patients, the majority of which were for hepatic oncologic interventions. The access was performed under ultrasound guidance with a micropuncture set. A size cutoff of 16 mm was utilized for slender 5-F sheaths (48 accesses) and 20 mm for slender 6-F sheaths (2 accesses). 3,000 IU heparin were given after access as well as 200 µg of nitroglycerin at the beginning and end of the case.

Technical success rate was 100%, defined as ability to use the intended access for the visceral intervention, and there was one access site complication that required no intervention (2-mm pseudoaneurysm, self-resolving). The average vessel size was 2.1 mm, and there was a mean of 1.6 accesses per patient.

Overall, the authors found this access point to be successful. Intra-procedurally, it allowed for subjectively more ergonomic patient positioning, but the added length to the access did necessitate most cases be done with 110-cm length catheters. Hemostasis required more diligence due to the mobility of this anatomic region.



Figure 1
Access needle inserted under US guidance with a guide wire inserted. (Inset) US of the access site in the distal radial artery in the anatomic snuffbox over the trapezium.

Commentary


This report represents an early evaluation of the use of the dorsal radial artery branch (“snuffbox”) for use in visceral interventions. Radial access has increased in popularity and frequency with visceral interventions, piggy-backing on the large coronary literature. Its safety and efficacy are well documented, especially in anticoagulated patients and those necessitating early ambulation. 
 
The use of the snuffbox for access is relatively new in both the coronary and visceral angiography literature. The authors demonstrate its high technical success rate in this report. The advantages of this access are at this point theoretical. The dominant finding thus far has been a subjective increase in patient and operator preference for positioning, as the hand is not supinated for this access. Additional theoretical advantages are preservation of the palmar radial artery branch to the hand and sparing of direct access of the radial artery proper (and associated risks). 

At this point, snuffbox access has been demonstrated to be technically feasible and can be viewed as an alternative or bail-out option in the appropriate patient. Further research in larger cohorts will be necessary to allow for evaluation of the safety and efficacy for visceral interventions, especially given the proven safety and efficacy of traditional radial and femoral artery access.

Click here for abstract

Pua U, Sim JZT, Quek LHH et al. Feasibility Study of “Snuffbox” Radial Access for Visceral Interventions. J Vasc Interv Radiol. 2018; 29(9): 1276-1280.

Post Author:
Daniel P. Sheeran, MD
Assistant Professor
Department of Radiology and Medical Imaging
Division of Vascular and Interventional Radiology
University of Virginia

Thursday, October 25, 2018

Operator Dose Reduction during Transjugular Liver Biopsy Using a Radiation-Attenuating Drape: A Prospective, Randomized Study


Summary


Radiation protection is a critical consideration for routine as well as complex interventional radiology procedures. The authors in this study utilized disposable, heavy metal, lead-free, radiation-absorbing surgical drapes laid over the patient during transjugular liver biopsies (TJLB). The primary outcome was operator dose equivalent (ODE), measured in microSieverts (uSv). This was measured by personal dosimeters worn at the chest level outside of lead aprons. ODE was then compared between the protective drapes and standard non-protective drapes. The authors point out several similar studies comparing dose reduction with protective drapes during nephrostomy tube placements, femoral access procedures, and coronary artery interventions. This is the only known study comparing standard and protective drapes during TJLB. A total of 60 patients were included in the statistical analysis. There were no differences in mean kerma-area product (KAP), fluoroscopy time, or number of exposures between the two groups. Ultimately, mean radiation dose incident on the operator was decreased by 56% when using radiation absorbing drapes (37 uSv versus 84 uSv, p < 0.0001). Additionally, ODE corrected for KAP was reduced in the protective drape arm (p < 0.0001). The authors have shown that using radiation-absorbing drapes during TJLB reduces operator scatter radiation as measured by a chest-level personal dosimeter.



Figure 1. Drape positioning. A square split drape was positioned around the jugular access sheath. A rectangular drape was then applied to the patient’s shoulder and body wall, partially overlapping the square drape at the access site.



Figure 4. Operator exposure data per KAP. PD = protective drape; SD = standard drape.

Commentary


While continued investigation into methods of radiation dose reduction is absolutely warranted and valuable, an element of diminishing returns should not be overlooked. Most commonly in these types of studies the method of measurement is a dosimeter worn outside of conventional lead apron shielding. While this is appropriate for modeling and comparing across studies it would be difficult to extrapolate true dose reduction given that the dosimeter is outside of the lead apron. It is important to remember that typical 0.5 mm lead apron shielding provides a significant 90% reduction in equivalent dose. Therefore the actual reduction in dose to the operator in this study is presumably much lower than 56%. That said the authors report that the cost of protective drapes for each case was $60. This is a small price to pay for radiation protection and peace of mind. Additionally, over an entire career, consistent utilization of protective drapes would certainly provide a benefit. However, consistent use of protective drapes would come with consistent costs which can add up if used for a large percentage of procedures. Ultimately, this would necessitate a departmental discussion which will vary between institutions and practices based on ideology and finances.

Click here for abstract

Ryan Kohlbrenner, MD, Evan D. Lehrman, MD, Andrew G. Taylor, MD, PhD, Maureen P. Kohi, MD, Nicholas Fidelman, MD, Vishal Kumar, MD, Miles Conrad, MD, K. Pallav Kolli, MD. Operator Dose Reduction during Transjugular Liver Biopsy Using a Radiation-Attenuating Drape: A Prospective, Randomized Study. J Vasc Interv Radiol 2018; 29: 1248-1253.

Cane Hoffman, MD, PGY-5
Department of Radiology
Wake Forest Baptist Medical Center
@WakeForest_IR

Monday, October 22, 2018

Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma


Summary


Treatment planning systems (TPSs) have been used in external-beam radiation therapy to characterize three-dimensional dosimetry at the voxel level and to calculate radiation distribution. TPSs can be used during radioembolization (RE) of hepatocellular carcinoma (HCC) to assess the heterogeneity of distribution of 90Y in the liver with the hopes of identifying predictive factors related to tumor control and toxicity. In the current study, 45 90Y resin microsphere REs were performed on patients with Barcelona Clinic Liver Cancer stage B /C HCC and area under the dose-volume histograms (AUDVH) were calculated from post-therapy PET/CT scans to determine the volume of liver tumor targeting. The volume of the total liver (Virradiated liver), tumor (Vtumor), and nontumoral liver (Vnontumoral irradiated) treated was extracted from the TPS. Tumor control was assessed through routine follow-up multiphasic CT scans and progression-free survival (PFS), overall survival (OS), and toxicity were recorded.

Of the 42 included treatments, complete targeting of the tumor was achieved in 60% (n=25) of patients and the 6-month tumor control rate was 40.5% (n=17). Both univariate and multivariate analysis showed that complete tumor targeting and AUDVHtumor were significantly associated with tumor control with a dose threshold to predict tumor control of 61 Gy. The OS and PFS was significantly shorter in patients with incomplete tumor targeting (median OS = 4.5 months, mean PFS = 2.7 months) when compared to patients with complete tumor targeting (median OS = 19.2 month, median PFS = 7.9 months) (P < 0.001 and P < 0.001 respectively). Radioembolization-induced liver disease (REILD) occurred in 5 patients (11.9% of treatments), in which a mean dose of 78.9 Gy was delivered to the nontumoral liver. AUDVHtumor and tumor targeting using 3D voxel-based tumor dose provides a representative reflection of the dose received by the tumor and appears to be correlated with tumor control and responsiveness.



Figure 1. Example of TPS post-processing to obtain 3D voxel-based dosimetry and corresponding DVHs. (a) Baseline CT scan with manual segmentation of tumor (red), portal vein invasion (purple), and liver (yellow). We subtracted necrosis owing to previous ablation (blue). (b) 90Y PET/CT imaging. (c) Screenshot of 3D voxel-based dosimetry with isodose curves on TPS (complete tumor targeting). (d) DVHs for tumor (red), portal vein invasion (purple), nontumoral irradiated liver (orange), and whole liver (yellow).



Figure 4. Kaplan-Meier estimates. (a) PFS in patients with complete vs incomplete tumor targeting (P < .001). (b) OS in patients with complete vs incomplete tumor targeting (P ¼ .001). (c) PFS in patients depending on tumor targeting and a 61-Gy cutoff for AUDVH tumor (P < .001).

Commentary


Through the utilization of a 3D voxel-based TPS, the authors concluded that tumor targeting and dose delivered to the tumor are predictive of tumor control. This planning system accounts for the heterogenous deposition of 90Y microspheres within the liver, whereas the partition model used for activity calculations fails to account for varied compartmental uptake. While the proposed TPS adds to the body of literature that supports complete tumor targeting, there is still disagreement regarding the threshold dose required for tumor control. Individual patient characteristics will likely need to be incorporated into the prognostic tools used for predicting dose response. Further, while complete tumor targeting is an admirable goal, factors including difficult selective catheterization, extrahepatic blood supply, and the presence of contralateral lobar disease limit the ability to achieve complete tumor targeting. However, research regarding predictive factors related to HCC responsiveness to RE is critical to improve the PFS and OS of patients.

Click here for abstract

Allimant C, Kafrouni M, Delicque J, Ilonca D, Cassinotto C, Assenat E, et al. Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma. J Vasc Interv Radiol. 2018 Sep 11;

Post Author:
Jacob Bundy, MD, MPH
PGY-1
Department of Surgery
University of Michigan Health System
@JBundyRad