Extra-stent vascular remodeling in in-stent restenosis after ¹⁸⁸Re-MAG₃ radiation therapy

Background: The effect of β-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received β-radiation therapy as well as conventional therapy has also not been studied. Methods: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a β-radiation therapy patient group ( ¹⁸⁸Re-MAG₃, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. Results: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4±3.3 mm ² post-intervention to 17.1±3.3 mm² at follow-up, P=0.001 in the radiation therapy group, and 16.8±4.0 mm² post-intervention to 17.4±4.1 mm² at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Δ EEM area between the two groups: 0.7±0.4 mm² in the radiation therapy group vs. 0.6±0.4 mm² in the control group, P=0.389. The Δ IH area correlated with the Δ EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). Conclusions: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.