Published online Mar 28, 2016. doi: 10.4329/wjr.v8.i3.308
Peer-review started: October 2, 2015
First decision: November 4, 2015
Revised: November 26, 2015
Accepted: January 8, 2016
Article in press: January 11, 2016
Published online: March 28, 2016
Processing time: 174 Days and 1.7 Hours
AIM: To investigate the angiographic and volumetric effects of mammalian target of rapamycin (mTOR) inhibitors on angiomyolipomas (AMLs) in a case series of patients with tuberous sclerosis complex.
METHODS: All patients who underwent catheter angiography prior to and following mTOR inhibitor therapy (n = 3) were evaluated. All cross-sectional imaging studies were analyzed with three-dimensional volumetrics, and tumor volume curves for all three tissue compartments (soft tissue, vascular, and fat) were generated. Segmentation analysis tools were used to automatically create a region of interest (ROI) circumscribing the AML. On magnetic resonance images, the “fat only” map calculated from the in- and opposed-phase gradient recalled echo sequences was used to quantify fat volume within tumors. Tumor vascularity was measured by applying a thresholding tool within the ROI on post-contrast subtraction images. On computed tomography images, volume histogram analysis of Hounsfield unit was performed to quantify tumor tissue composition. The angiography procedures were also reviewed, and tumor vascularity based on pre-embolization angiography was characterized in a semi-quantitative manner.
RESULTS: Patient 1 presented at the age of 15 with a 6.8 cm right lower pole AML and a 4.0 cm right upper pole AML. Embolization was performed of both tumors, and after a few years of size control, the tumors began to grow, and the patient was initiated on mTOR inhibitor therapy. There was an immediate reduction in the size of both lesions. The patient then underwent repeat embolization and discontinuation of mTOR inhibition, after which point there was a substantial regrowth in both tumors across all tissue compartments. Patient 2 presented at the age of 18 with a right renal AML. Following a brief period of tumor reduction after embolization, she was initiated on mTOR inhibitor therapy, with successful reduction in tumor size across all tissue compartments. As with patient 1, however, there was immediate rebound growth following discontinuation of inhibitor therapy, without sustained control despite repeat embolization. patient 3 presented at the age of 5 with a left renal AML and underwent two embolization procedures without lasting effect prior to starting mTOR inhibition. As with patients 1 and 2, following discontinuation of therapy, there was immediate rebound growth of the tumor. Repeat embolization, however, was notable for a substantial reduction in intratumoral aneurysms and vascularity.
CONCLUSION: AML volume reduction as well as post-treatment rebound growth due to mTOR inhibitors involves all three tissue components of the tumor.
Core tip: Pharmacologic management of tuberous sclerosis complex-associated angiomyolipomas with mammalian target of rapamycin inhibitors can provide substantial tumor volume reduction for the duration of the therapeutic course. This volume reduction impacts all three tissue compartments of the tumor. Unfortunately rebound growth involving all tissue compartments follows shortly after discontinuation of mammalian target of rapamycin (mTOR) inhibitor therapy. The addition of transarterial embolization to mTOR inhibition did not curtail the occurrence of rebound growth.