Correlation between Tumor Uptake on Indium-111 Ibritumomab Tiuxetan Imaging and Size on CT to Disease Response on FDG PET/CT Scans Obtained Pre- and Post-Yttrium-90 Ibritumomab Tiuxetan Therapy for Non-Hodgkin Lymphoma.
Authors: Alexnder Jacob M. , Joyce Judith M. , McCook Barry M. , Avril Norbert , Land Stephanie R. , Begovic Mirsada , Jacobs Samuel A. 
Published: October 2019

Abstract
Background: Yttrium-90 ibritumomab tiuxetan (Zevalin, YZ), the first radioimmunotherapeutic agent approved for the treatment of relapsed or refractory B-cell non-Hodgkin Lymphoma (NHL), had an overall response rate of 80% vs 56% with rituximab alone based on CT assessment (IWRC criteria) without FDG PET correlation. Prior to the therapeutic administration of YZ, normal biodistribution must be confirmed by visual evaluation of whole-body In-111 Zevalin (IZ) images. Tumor uptake on IZ images has been noted to be variable and is not required to proceed with therapy. However, bulky lymphadenopathy has been reported to possibly predict poor response to radioimmunotherapy. We report our evaluation of the relation of tumor uptake on IZ images and size on CT scans to tumor response based on pre- and post-YZ therapy using FDG PET/CT scans.
Methods: This retrospective review includes only patients with relapsed or refractory B-cell NHL treated with YZ who had fusion PET/CT scans pre- and post-YZ therapy and fulfilled all other standard eligibility critera for YZ. PET/CT scans were performed within 4 months prior and 8 months following IZ imaging and YZ therapy. The largest tumor mass on the pre-therapy CT was measured and categorized into subgroups of < or ≥5 cm. The IZ scans were reviewed for the presence or absence of tumor uptake over background activity. Response by CT was based on the IWRC criteria (CR/CRu, PR, Stable, and PD). Response on FDG PET was based upon comparison of the intensity of uptake in relation to adjacent background (CR, PR, Mixed and PD). Response rate comparisons by patient groups were performed with Fisher exact tests.
Results: 24 patients (16M, 8F, 37–83 y.o.) fulfilled the criteria. The histologic diagnoses included: 14 follicular, 5 diffuse large B-cell, 4 mantle cell, and 1 MALT. All patients had increased FDG uptake in measurable CT lesions on the pre-therapy PET/CT scans. 14 IZ scans were positive, 10 were negative. Seven of 9 patients (78%) with lesions ≥5 cm had positive IZ versus 7 of 15 (47%) with lesions < 5 cm. The following tables display the cross-tabulation of tumor uptake on IZ, CT size, and the response to YZ. The overall response (ORR) based on FDG PET was 13/24 (54%) with a CR of 7/24 (29%) and a PR of 6/24 (25%). Excluding the patients with large cell histology, the ORR was 13/19 (68%). ORR for size ≥5 cm was 3/9 (33%) and for size <5 cm was 10/15 (66%), a suggestive but non-significant difference (p=0.2). The frequency of overall response was significantly reduced for large cell histology versus other histologies (p=0.011). The results show that those patients with tumor uptake on IZ imaging had significantly reduced overall response based on pre- and post-FDG PET/CT findings compared with patients without tumor uptake (p=0.047).
Conclusions: The presence of tumor uptake on IZ imaging, tumor size (≥5 cm) and histology (large cell) may all adversely affect response to YZ. The identification of IZ tumor uptake may be related to large tumor size rather than tumor susceptibility to therapy.
Responses (CR/CRu and PR) by PET # In+ In− CT≥5cm CT<5cm FL 9 4 5 1 8 DLBC 0 0 0 0 0 MCL 3 1 2 1 2 MALT 1 0 1 1 0 Nonresponses (Mixed and PD) by PET # In+ In− CT≥5cm CT<5cm FL 5 5 0 2 3 DLBC 5 3 2 3 2 MCL 1 1 0 1 0 MALT 0 0 0 0 0