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.

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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

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.

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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

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.   

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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