Predictive Value of Intratumoral ^99mTc-Macroaggregated Albumin Uptake in Patients with Colorectal Liver Metastases Scheduled for Radioembolization with ⁹⁰Y-Microspheres

Abstract

90 Y radioembolization is a promising therapy for patients with primary and secondary liver malignancies. Pretherapeutic assessment consists of hepatic angiography and 99m Tc-macroaggregated albumin ( 99m Tc-MAA) perfusion scintigraphy to estimate the liver-to-lung shunt and exclude extrahepatic 99m Tc-MAA deposition. However, the predictive value of intratumoral 99m Tc-MAA uptake remains unclear. Methods: One hundred four patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer were treated with 90 Y radioembolization between December 2006 and December 2010. All of the patients underwent angiographic assessment and perfusion scintigraphy with 99m Tc-MAA before lobar 90 Y radioembolization. For inclusion, patients must have undergone pretherapeutic and follow-up MR imaging (6 wk and 3 mo after radioembolization, respectively). The degree of intratumoral 99m Tc-MAA uptake was rated, and liver metastases were classified according to changes in tumor diameter on both an individual and a patient basis using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response at both time points, MAA uptake, and catheter position were then statistically analyzed in a linear and generalized linear mixed model at a significance level of 0.05 (P value). Results: Sixty-six patients with a total of 435 colorectal liver metastases (mean number of lesions 6 SD, 6.6 6 2.8; mean lesion size 6 SD, 33.8 6 21.2 mm; lesion size range, 10-154 mm) were included in this analysis. According to the patient-based analysis, 3 patients had partial response, 49 stable disease, and 6 progressive disease after 6 wk. After 3 mo, 5 patients showed partial response, 26 stable disease, and 17 progressive disease. There was no association of patient-based tumor response with overall 99m Tc-MAA uptake (P 5 0.172) or with catheter position (P 5 0.6456). Furthermore, an interaction effect of 99m Tc-MAA uptake and catheter position in relation to tumor response was not found (P 5 0.512). Moreover, in lesion-based analysis according to RECIST 1.1 there was no association of tumor response with degree of 99m Tc-MAA uptake, catheter position, or interaction of 99m Tc-MAA uptake and catheter position (P 5 0.339, 0.593, and 0.658, respectively). Conclusion: Response to 90 Y radioembolization was found to be independent of the degree of 99m Tc-MAA uptake. Therefore, therapy should not be withheld from patients with colorectal liver metastases lacking intratumoral 99m Tc-MAA accumulation. Radi oembolization with 90 Y is a promising catheterbased liver-directed modality approved by the Food and Drug Administration for the treatment of patients with hepatic metastases of colorectal carcinoma (1-4). For this interventional technique, 90 Y-embedded microspheres of glass or resin are infused directly into the hepatic arteries, where they become lodged within the tumor microvasculature and irradiate the tumor by b-emission (5).Perfusion scintigraphy with 99m Tc-labeled macroaggregated albumin ( 99m Tc-MAA) is mandatory before 90 Y radioem...

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…Although it has been noted that the PM would be the preferred method of 90 Y-RE for every patient [55,56], its main drawbacks are the reliance on segmentation of tumour/non-tumour for activity determination and dosimetry purposes, and the assumption of concordance between the MAA (from which the TN ratio is calculated) and MS distribution. This assumed equivalency is a fact much disputed by recent studies, especially in liver metastases [57,58] and is described further below. In clinical scenarios, the PM and GMS equations are employed mainly in patients with hypervascular, large and numerically limited lesions, such as HCC.…”

“…In many metastatic cases, clear definition of the tumour boundaries proves difficult due to diffuse metastatic spread and differing vascularity [5], and therefor the PM proves difficult to apply. Recent work shows it cannot be recommended in general for patients with liver metastases [57,59]. This model also disregards the spatial and temporal variation of the dose, dose rate and radiobiological effects, providing a simplified picture for patient dosimetry [60].…”

“…A recent study reported on the lack of association between metastatic lesion based response (66 patients treated with RMS) and the overall MAA uptake (classified from 1 -no intratumoural uptake, to 4 -strong uptake) and that the metastatic response cannot be predicted by the degree of perfusion on 99m Tc-MAA scanning while also showing no correlation between tumour response and catheter position [57]. This work shows conflicting results with other studies, and many recent letters have discussed these results in detail [59,73,[104][105][106][107].…”

Radioembolization with 90Y-loaded microspheres: high clinical impact of treatment simulation with MAA-based dosimetry

“…First of all, their results were primarily obtained with resin microspheres in a metastatic disease context, for which several previous studies reported disappointing results [12,13], probably due to several parameters, including the disease's multifocality. This difference can be explained by the fact that Lam et al took care to only include patients with exactly identical catheter positioning between diagnostic and therapeutic angiography.…”

General Theory of Predictive Dosimetry for Yttrium-90 Radioembolization to Sites Other Than the Liver: Reply

“…Several groups have discussed discordant accumulation patterns for both substances [7][8][9]. Just recently, we have published a patient series where Tc-99m-MAA accumulation in colorectal liver lesions did not correlate with clinical response [10]. In light of these assumptions supplemented by the different morphology of lung tissue compared with liver the eligibility of the Tc99m-MAA as surrogate for radioembolization of lung malignancies must be reevaluated.…”