Role of Radiomics-Based Baseline PET/CT Imaging in Lymphoma: Diagnosis, Prognosis, and Response Assessment

Abstract Introduction Marginal Zone Lymphoma (MZL) is an indolent lymphoma in which the use of PET/CT is poorly explored and also controversial due to the heterogeneous 18F- FDG avidity described in these types of lymphoma. Our aim in the present study is to evaluate the role of 18F-FDG-PET/ CT (PET/CT) in comparison to CT with intravenous contrast enhancement at initial staging and response assessment to chemotherapy in these patients. Methods and Materials A retrospective single-center study that included 34 patients, diagnosed of MZL between 1998 and 2012, with at least one PET/CT available. A total of 55 PET/ CT were performed: 25 at initial diagnosis, 19 for first- line response assessment, 6 in relapse and 5 after relapse- treatment. Locations of involved areas were registered comparing staging CT and PET/CT and were classified as discrepancy or not. Results Patients´ baseline characteristics are shown in table 1. At diagnosis, all patients presented with at least one abnormal focal FDG uptake except for one, which reflected a sensitivity of 96%. Median SUVmax was higher in nodal marginal zone lymphoma (NMZL) and extranodal marginal zone lymphoma (ENMZL): 6,1 (4- 8,4) and 6,9 (2- 13,8) respectively, in comparison to splenic marginal zone lymphoma (SMZL) 3,4 (3,2- 3,6) p=0,3. SUVmax was much higher in a patient with histological transformation to a DLBCL (SUVmax 37). Among 17 patients with both radiological imaging at the time of diagnosis, there were 8 patients (47%) with more involved areas demonstrated by PET/ CT than by CT alone, 75% of them were extranodal lesions. PET/CT upstaged 5 patients but in only 2 of them entailed a change in therapeutic management. Four patients did not show FDG avidity by PET/CT in some areas suspected to be involved by CT, what generated a CT sensitivity of 76%. Overall, CR was attained in 24 patients (66%) with 5-y OS 78%. Among 19 patients with a PET/CT available for first-line response assessment, responses were: 12 CR, 2 PR, 1PD and isolated residual lesions in 4 patients. Progression was documented in 2 of the 4 patients with residual lesions which were considered positive, and in 2 patients who maintained remission, the image was interpreted as a false positive (FP). The response assessment was performed by both radiological imaging in 13 patients. Discrepancies were found in 4 cases: CT showed CR in 3 patients while PET/CT detected localized residual disease and in another patient, CT showed stable disease whereas PET/CT demonstrated CR. Overall, none of the patients in CR by PET/CT relapsed. Five-year OS was 100% in contrast to 64% for those patients with a positive PET/CT after completing treatment (p=0,2), with a mean follow-up of 50 months (10-152). The NPV was 100% and PPV was 71% (5/7). Relapse was detected in 9 patients (37.5%). Six patients had PET/CT for re-staging and 5 for response assessment. All re-staging PET/CT had FDG-avidity with a median SUVmax of 9.9 (4.6-17.2). PET/CT for response after salvage treatment demonstrated 3 CR and 2 localized residual lesions. The NPV and PPV was 100% and 50%, respectively. Conclusions MZL shows higher 18F- FDG avidity in NMZL y ENMZL subtypes. PET/CT is more sensitive than CT at initial staging, chiefly in identifying extranodal involvement. Response assessment PET/CT had a NPV of 100% and PPV of 71 and 50% after first and second-line treatment, respectively. Disclosures: No relevant conflicts of interest to declare.

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Role of PET/CT As a Measure of Minimal Residual Disease (MRD) Negativity Among Patients with Myeloma Post Autologous Stem Cell Transplant (ASCT)

Blood ◽

10.1182/blood.v126.23.4202.4202 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4202-4202

Author(s):

Ajay K. Nooka ◽

Jonathan L. Kaufman ◽

A. Tuba Karagulle Kendi ◽

Yan Li ◽

Chikaodili O Obidike ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Residual Disease ◽

Standardized Uptake Value ◽

Response Assessment ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Pet Ct ◽

Lytic Lesions

Abstract Background: In the context of improved novel therapeutic anti-myeloma regimens using combinations of antibodies and other small molecules, measuring the efficacy of therapy is an ongoing challenge. Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC), polymerase chain reaction (ASO-PCR), next-generation sequencing are sensitive tests that are becoming more significant as improved therapies result in deeper responses, however challenges remain, such as standardizing these testing methods. 18F Fluorodeoxglucose Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that can provide essential information in diagnosis and management of MM. PET/CT has high sensitivity (80-90%) and specificity (80-100%) to detect MM lesions. PET/CT also has a recently acknowledged role in prognostic information. Standardized uptake value maximum (SUVmax) is a widely used PET/CT parameter for assessment of therapy response in a variety of cancers. Recent publication by Zamagni et al showed that in addition to the presence of three or more focal lesions, a maximum standardized uptake value (SUVmax) of over 4.2 and presence of extramedullary disease were negative prognostic factors. Our aim in this study was to evaluate the prognostic role of PET/CT in MM patients post ASCT at day 100 restaging. Methods: We have identified 130 myeloma patients that underwent autologous stem cell transplant (ASCT) from 09/2014 until 04/2015. Along with their hematologic restaging post-ASCT for response assessment per International Myeloma Working Group (IMWG) criteria, patients also underwent PET/CT for MRD assessment. After excluding 3 patients that underwent tandem transplants, and one patient that received stem cell boost, 102 patients were evaluable for the current analysis (24 patients did not undergo PET/CTs). We have done an exploratory analysis with previously described SUVmax cut off of <2.0 (Waheed S) and <4.2 (Zamagni E). Results: The median age of the patients that underwent ASCT was 64 years (range: 38-76 years). 77 pts (75%) received melphalan 200 mg/m2, 22 pts (22%) received melphalan 140 mg/m2, 2 pts received melphalan+bortezomib and 1 pt received BEAM regimen as conditioning regimen. Median time from day 0 to response assessment is 98 days (range: 55-189 days). Hematological restaging shows that 89% of patients achieved ≥VGPR (SCR: 46% and CR: 11%). 13 pts did not have prior lytic lesions while 89% had lytic lesions (one lesion: 4%, two lesions: 2% and multiple (≥3): 82%). PET/CT negativity was achieved among 63% of the patients. At SUV cut off of <2.0 and <4.2, PET/CT negativity was achieved among 64% of the patients and 83% of the patients respectively. Taking the patients that have achieved SCR, for the same cut offs, PET/CT negativity rates were 59% and 76% respectively (Table 1). Conclusions: Negative PET/CT rates post-ASCT are in accordance with previously published studies. With taking SUVmax as sole criteria for assessing MRD negativity, false positive PET/CT results will continue to remain a challenge. Although SUVmax is the most widely used PET/CT parameter, it has limitations. There are other PET/CT parameters mean or peak standardized uptake values (SUVmean, SUVpeak); metabolic tumor volume (MTV); total lesion glycolysis (TLG); standardized added metabolic activity (SAM); and, normalized standardized added metabolic activity (NSAM) used in clinical practice and research. These PET/CT parameters may have role as prognostic imaging probes in MM patients post ASCT. With longer follow up to assess PFS and OS, we can evaluate the prognostic impact of using PET/CT as MRD measure. Table 1. PET parameters and hematological responses Response Response rates PET positive PET negative PET positive (≥SUV 2.0) PET negative (<SUV 2.0) PET positive (≥SUV 4.2) PET negative (<SUV 4.2) SCR 46 19 27 19 27 11 35 CR 11 7 4 6 5 3 8 VGPR 34 9 25 9 25 3 31 PR 10 2 8 2 8 0 10 PD 1 1 0 1 0 1 0 ≥CR 57 26 31 25 32 14 43 ≥VGPR 91 35 56 34 57 17 74 Disclosures Nooka: Onyx Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Gleason:Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Lonial:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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