Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring

Abstract

Purpose To compare the performance characteristics of interim fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (after two cycles of chemotherapy) by using the most prominent standardized interpretive criteria (including International Harmonization Project [IHP] criteria, European Organization for Research and Treatment of Cancer [EORTC] criteria, and PET Response Criteria in Solid Tumors (PERCIST) versus those of interim (18)F fluorothymidine (FLT) PET/CT and simple visual interpretation. Materials and Methods This HIPAA-compliant prospective study was approved by the institutional review boards, and written informed consent was obtained. Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) underwent both FLT and FDG PET/CT 18-24 days after two cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. For FDG PET/CT interpretation, IHP criteria, EORTC criteria, PERCIST, Deauville criteria, standardized uptake value, total lesion glycolysis, and metabolic tumor volume were used. FLT PET/CT images were interpreted with visual assessment by two reviewers in consensus. The interim (after cycle 2) FDG and FLT PET/CT studies were then compared with the end-of-treatment FDG PET/CT studies to determine which interim examination and/or criteria best predicted the result after six cycles of chemotherapy. Results From November 2011 to May 2014, there were 60 potential patients for inclusion, of whom 46 patients (24 men [mean age, 60.9 years ± 13.7; range, 28-78 years] and 22 women [mean age, 57.2 years ± 13.4; range, 25-76 years]) fulfilled the criteria. Thirty-four patients had complete response, and 12 had residual disease at the end of treatment. FLT PET/CT had a significantly higher positive predictive value (PPV) (91%) in predicting residual disease than did any FDG PET/CT interpretation method (42%-46%). No difference in negative predictive value (NPV) was found between FLT PET/CT (94%) and FDG PET/CT (82%-95%), regardless of the interpretive criteria used. FLT PET/CT showed statistically higher (P < .001-.008) or similar NPVs than did FDG PET/CT. Conclusion Early interim FLT PET/CT had a significantly higher PPV than standardized FDG PET/CT-based interpretation for therapeutic response assessment in DLBCL. (©) RSNA, 2016 Online supplemental material is available for this article.

Figure 1a:

Images in 50-year-old man. (a) Baseline FDG PET maximum intensity projection shows intense FDG uptake in a bulky mass within the left pelvis (arrow). (b) Interim FDG PET maximum intensity projection shows decreased activity, but the lesion remained positive (arrow). (c) Interim FLT PET image shows photopenic tracer uptake in this lesion, which was reported as negative for disease. (d) End-of-treatment FDG PET maximum intensity projection shows substantial reduction in FDG activity; this patient was classified as having CR on the basis of both imaging findings and clinical outcome, confirming the FLT PET/CT result.

Figure 1b:

Images in 50-year-old man. (a) Baseline FDG PET maximum intensity projection shows intense FDG uptake in a bulky mass within the left pelvis (arrow). (b) Interim FDG PET maximum intensity projection shows decreased activity, but the lesion remained positive (arrow). (c) Interim FLT PET image shows photopenic tracer uptake in this lesion, which was reported as negative for disease. (d) End-of-treatment FDG PET maximum intensity projection shows substantial reduction in FDG activity; this patient was classified as having CR on the basis of both imaging findings and clinical outcome, confirming the FLT PET/CT result.

Figure 1c:

Images in 50-year-old man. (a) Baseline FDG PET maximum intensity projection shows intense FDG uptake in a bulky mass within the left pelvis (arrow). (b) Interim FDG PET maximum intensity projection shows decreased activity, but the lesion remained positive (arrow). (c) Interim FLT PET image shows photopenic tracer uptake in this lesion, which was reported as negative for disease. (d) End-of-treatment FDG PET maximum intensity projection shows substantial reduction in FDG activity; this patient was classified as having CR on the basis of both imaging findings and clinical outcome, confirming the FLT PET/CT result.

Figure 1d:

Images in 50-year-old man. (a) Baseline FDG PET maximum intensity projection shows intense FDG uptake in a bulky mass within the left pelvis (arrow). (b) Interim FDG PET maximum intensity projection shows decreased activity, but the lesion remained positive (arrow). (c) Interim FLT PET image shows photopenic tracer uptake in this lesion, which was reported as negative for disease. (d) End-of-treatment FDG PET maximum intensity projection shows substantial reduction in FDG activity; this patient was classified as having CR on the basis of both imaging findings and clinical outcome, confirming the FLT PET/CT result.

Figure 2a:

Images in 60-year-old woman. (a) Baseline coronal FDG PET image shows FDG-avid lesions in the right clavicle (arrow) and mesentery (arrowhead). (b) Interim coronal FDG PET image shows residual abnormal activity in the clavicle (arrow) and mesentery (arrowhead). (c) Interim coronal FLT PET image also shows persistent tracer activity in the clavicle (arrow) and mesentery (arrowhead). (d) Posttherapy coronal FDG PET image shows complete resolution of these foci, and the patient was classified as having CR on the basis of clinical evaluation with 3 months of follow-up, refuting both the interim FDG and FLT PET/CT results.

Figure 2b:

Images in 60-year-old woman. (a) Baseline coronal FDG PET image shows FDG-avid lesions in the right clavicle (arrow) and mesentery (arrowhead). (b) Interim coronal FDG PET image shows residual abnormal activity in the clavicle (arrow) and mesentery (arrowhead). (c) Interim coronal FLT PET image also shows persistent tracer activity in the clavicle (arrow) and mesentery (arrowhead). (d) Posttherapy coronal FDG PET image shows complete resolution of these foci, and the patient was classified as having CR on the basis of clinical evaluation with 3 months of follow-up, refuting both the interim FDG and FLT PET/CT results.

Figure 2c:

Images in 60-year-old woman. (a) Baseline coronal FDG PET image shows FDG-avid lesions in the right clavicle (arrow) and mesentery (arrowhead). (b) Interim coronal FDG PET image shows residual abnormal activity in the clavicle (arrow) and mesentery (arrowhead). (c) Interim coronal FLT PET image also shows persistent tracer activity in the clavicle (arrow) and mesentery (arrowhead). (d) Posttherapy coronal FDG PET image shows complete resolution of these foci, and the patient was classified as having CR on the basis of clinical evaluation with 3 months of follow-up, refuting both the interim FDG and FLT PET/CT results.

Figure 2d:

Images in 60-year-old woman. (a) Baseline coronal FDG PET image shows FDG-avid lesions in the right clavicle (arrow) and mesentery (arrowhead). (b) Interim coronal FDG PET image shows residual abnormal activity in the clavicle (arrow) and mesentery (arrowhead). (c) Interim coronal FLT PET image also shows persistent tracer activity in the clavicle (arrow) and mesentery (arrowhead). (d) Posttherapy coronal FDG PET image shows complete resolution of these foci, and the patient was classified as having CR on the basis of clinical evaluation with 3 months of follow-up, refuting both the interim FDG and FLT PET/CT results.