Mahati Mokkarala, Washington University School of Medicine, 2019

Editor: Justin Foster, MD, PGY-4 Rochester Regional Health, Rochester, NY

Introduction:  

Multiple studies have shown that breast cancer genomic profile can affect metastatic breast cancer treatment effectiveness. Breast cancer gene mutations have been linked towards increased radiation therapy resistance. This JVIR retrospective study determined what genetic prognosticators might influence breast cancer liver metastasis radioembolization treatment.

Materials/Methods:

This study is a retrospective single center study of 31 patients with metastatic invasive breast ductal carcinoma treated with radioembolization for hepatic metastasis. Study members needed to be 1) 18 years of age, 2) have measurable liver metastasis, 3) have Eastern Cooperative Oncology Group (ECOG) status of 0/1, and 4) have a serum creatinine less than or equal to 2.0 mg/dL, total bilirubin level less than 1.2 times the upper limit of normal, and albumin level greater than or equal to 2.0. Patients excluded from the study included those with tumor replacing >70% of the liver. Other exclusion criteria included patients with a contraindication to radioembolization such as patients with bleeding and clotting difficulties, had an allergy to contrast agent, or patients with clinically significant pulmonary/hepatic disease including hepatic encephalopathy and ascites. All 31 patients in the study were female with an average age of 52.2 plus or minus 11.4 years. All the patients received at least 3 lines of systemic therapy.  All but 2 patients had multifocal liver metastasis. Approximately three quarters of patients had ER-positive disease and 1/4 had HER-2 positive documented disease. Out of the 31 patients, 24 patients had tumor genome profiling prior to radioembolization searching for common breast cancer genes using Sequenom Mass Array system or MSK-IMPACT. Radioembolization outcomes were evaluated via chart review of key factors implicated in patient survival. Examples included bilirubin, complete blood count levels before and after radiation, hormone receptor status, and radiation dosage used in radioembolization. Liver tumor burden was determined by preprocedural computed tomography (CT) imaging, and 26 patients had Positron emission tomography–computed tomography (PET/CT) imaging available to document response to treatment. Complete response was defined as when standardized uptake values on PET/CT was >80%  from baseline, partial response at 30-80%, and progressive disease when uptake increased by 30%.

Results:

Out of the 31 patients, 14 were still alive at time of study with a median survival of 10.9 months (95% CI- 9.5-31.8 months). 18 of the 26 patients had an imaging response with 7 having a complete response and 11 having a partial response. Three major adverse events occurred after radioembolization. One event was liver failure with subsequent mortality and the other two were gastric ulcers, confirmed with endoscopic biopsy, and later resolved.

Univariate analysis found that PET/CT imaging response was associated with PI3K pathway mutation but not mutations in gene TP53, MAPK/ERK and HER2 signaling pathways. While complete or partial response on PET/CT was associated with longer median survival, no genetic variables including PI3K mutation status, as well as pre procedure bilirubin values, and tumor burden significantly predicted survival.

Discussion/Conclusion:

The study results showed that patients with certain PI3Kpathway mutations potentially have better imaging response after radioembolization. Study authors were interested in understanding the mechanism behind why these patients responded to radioembolization so effectively. Study authors did acknowledge that results could be skewed by having only 13 patients in thePI3K pathwaymutation pool. Larger prospective studies could further explain what patient populations would benefit from radioembolization. Improved gene sequencing assays for PI3K pathwaymutations could further determine if PI3K pathwaymutation patients have improved imaging and treatment response after radioembolization.  Finally, the study authors acknowledged needing to factor in how intertumoral mutational heterogeneity could affect survival.

Importance for IR:

By having more personalized treatments, IR could propose interventional oncology treatments that can promise improved treatment response and overall survival.  This study adds to the distant possibility of an interventional radiologist that uses specific patient genetic information when deciding  the appropriate treatment that works best for their particular patient.

References:

1. Deipolyi AR., Riedl CC., Bromberg JB, 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. J Vasc Interv Radiol 2018; 29:1226-1235.