-Author name in bold denotes the presenting author
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5134 PET/CT Enables Appropriate Staging in Extranodal Marginal Zone Lymphoma

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Lymphomas, Clinical Research, health outcomes research, Diseases, indolent lymphoma, Lymphoid Malignancies, Technology and Procedures, imaging
Monday, December 11, 2023, 6:00 PM-8:00 PM

Juan Pablo Alderuccio, MD1, Michele D. Stanchina, DO, MS2, Jean L. Koff, MD, MSc3, Isildinha M. Reis, PhD4*, Eduardo Edelman Saul, MD5*, Melissa C. Larson, MS6*, Dai Chihara, MD, PhD7, Wei Zhao, MD, MS8*, Thomas M. Habermann, MD9, Peter Martin, MD10, Loretta J. Nastoupil, MD11, Jennifer R. Chapman-Fredricks, MD12*, Andrew L. Feldman, MD13, Brian K. Link, MD14*, Brad S. Kahl, MD15, Jonathon B. Cohen, MD, MS16, Mark K Polar, MD17*, Rafael Henneman Sassi, MD18*, Craig H. Moskowitz, MD19, Jonathan W. Friedberg, MD, MMSc20, James R. Cerhan, MD, PhD21, Russ Kuker, MD22*, Christopher R. Flowers, MD, MS7 and Izidore S. Lossos, MD23

1Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
2Sylvester Comprehensive Cancer Center, Division of Hematology, University of Miami, Miller School of Medicine, Miami
3Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA
4Department of Public Health Sciences and Biostatistics and Bioinformatics Shared Resource, University of Miami Miller School of Medicine, Miami, FL
5Sylvester Comprehensive Cancer Center, Miami
6Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, Rochester, MN
7Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
8Sylvester Comprehensive Cancer Center, Department of Public Health Sciences, Miami
9Division of Hematology, Mayo Clinic, Rochester, MN
10Weill Cornell Medicine, New York
11MD Anderson Cancer Center, Houston, TX
12University of Miami Miller School of Medicine, Miami, FL
13Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN
14Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA
15Siteman Cancer Center, Division of Oncology, Washington University School of Medicine in St. Louis, Saint Louis, MO
16Winship Cancer Institute, Emory University, Atlanta, GA
17Department of Radiology, Division of Nuclear Medicine, University of Miami Miller School of Medicine, Miami
18Sylvester Comprehensive Cancer Center, Department of Medicine, Miami
19Sylvester Comprehensive Cancer Center, University of Miami, Coral Gables, FL
20Wilmot Cancer Center, University of Rochester, Rochester, NY
21Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
22Department of Radiology, Division of Nuclear Medicine, University of Miami, Miller School of Medicine, Miami, FL
23Sylvester Comprehensive Cancer Center, Division of Hematology, University of Miami School of Medicine, Miami, FL

Introduction: PET/CT is the standard-of-care for staging and therapy response assessment in lymphoma. Fluorodeoxyglucose (FDG)-avidity in extranodal marginal zone lymphoma (EMZL) remains controversial with some variability by extranodal location. The current Lugano classification recommends the use of CT scans only in staging and follow-up for EMZL. However, emerging data from small studies have challenged this suggestion. In this study we aimed to determine the ability of PET/CT to detect FDG-avid EMZL during staging work-up.

Methods: First, we retrospectively analyzed the University of Miami (UM) MZL database (period 2/2016-1/2023) searching for patients who underwent staging PET/CT. Images were reviewed by expert radiologists to ascertain avidity of tumor and not surrounding tissue, with specific attention to ocular and GI locations; if scans were not available (n=15), we retrieved data from reports (results presented in part at ICML2023). Next, we aimed to validate the initial UM results additionally analyzing data from imaging reports for patients prospectively enrolled in the Lymphoma Epidemiology of Outcomes (LEO) MZL cohort (period 7/2015-5/2020), excluding LEO patients from Miami to avoid overlap. Patients with high-grade transformation at diagnosis were excluded. For patients with >1 extranodal site, each location was counted independently. We considered FDG-avid disease if SUVmax was ≥2 as this value is commonly observed between mediastinal blood pool (BP) and liver background. To normalize data, we calculated ratios of lymphoma SUVmax versus both BP and liver background, as available. Patients without measurable disease were excluded from analysis.

Results: Among 210 patients with EMZL in the UM cohort, 152 had staging PET/CT and were analyzed. Twenty-two patients demonstrated >1 extranodal site providing a total of 187 locations. The LEO cohort included 411 patients from 7 centers, with 235 having available imaging reports. Fifty-two patients in this cohort demonstrated >1 extranodal site providing a total of 306 locations. Disease distribution is depicted in Table 1. Among 187 EMZL locations in the UM cohort, the most common were gastric (n=33, 17.6%), ocular (n=31, 16.6%), lung (n=30, 16%), skin and soft tissue (n=16, 8.6%, each). Similarly, lung (n=63; 20.6%), soft tissue (n=46; 15%), gastric and ocular (n=34 each; 11%) were common locations in the LEO cohort. EMZL demonstrated FDG-avidity (SUVmax ≥2) across all locations with identical values in both cohorts (UM= 78.1% & LEO= 76.5%). FDG-avidity by location is shown in Table 1A & B with salivary gland (100% & 100%), lung (93.3% & 95.2%), soft tissue (93.8% & 100%), and airways (90.9% & 100%) demonstrating high avidity in both cohorts. Contrarily, skin was commonly non-FDG avid (93.8% & 81%). The median size of FDG-avid lesions was 2.4cm (range, 0.7-17.4) in UM and 2.9cm (range, 0.1-12) in LEO cohorts. In patients with >1 extranodal site FDG-avidity was nearly universal across sites (UM=93% & LEO=100%). We observed a significant correlation between lymphoma size and FDG-avidity for UM (r=0.33; P=0.001), and for LEO (r=0.55; P<0.0001). In patients with background FDG-avidity data in the UM cohort (n=150), a BP index and liver index ≥1 detected lymphoma in 79.3% & 71.5% cases, respectively. We were unable to calculate indexes in LEO cohort since only limited data on BP (n=26) and liver (n=19) background was available in imaging reports.

Conclusions: This study represents the largest analysis evaluating accuracy of PET/CT to determine initial tumor burden in 387 patients with EMZL. We demonstrate that EMZL is largely an FDG-avid disease across two cohorts, and PET/CT should be included in the staging of these patients while acknowledging possible limited sensitivity in GI locations due to physiologic uptake. Furthermore, we observed that patients with multiple extranodal locations demonstrate uniform FDG-avidity across all sites except for skin involvement. Based on our results we recommend the incorporation of PET/CT into standard staging of EMZL in planned revised Lugano classification guidelines. In those demonstrating initial FDG-avidity, a lower SUVmax threshold of SUVmax ≥2, comparison to mediastinal BP rather than to liver background activity and evaluating for resolution of focal FDG-avidity should be considered to assess treatment response in routine care and clinical trials.

Disclosures: Alderuccio: Genmab: Research Funding; Abbvie: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Research Funding; Regeneron: Consultancy. Koff: Viracta Therapeutics: Research Funding; BeiGene: Consultancy. Habermann: BMS: Research Funding; Genentech: Research Funding; sorrento: Research Funding. Martin: AbbVie, AstraZeneca, Beigene, Epizyme, Genentech, Gilead, Janssen, Pepromene, Daiichi Sankyo: Consultancy. Nastoupil: AbbVie: Honoraria; ADC Therapeutics: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Caribou Biosciences: Honoraria, Research Funding; DeNovo: Honoraria; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; Regeneron: Honoraria; AstraZeneca: Honoraria; Gilead Sciences/Kite Pharma: Honoraria, Research Funding. Cohen: Lam Therapeutics: Research Funding; BMS/Celgene: Research Funding; BioInvent: Research Funding; Novartis: Research Funding; Takeda,: Research Funding; Genentech: Research Funding; ADCT: Consultancy; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy; Janssen: Consultancy; BeiGene: Consultancy; Loxo/Lilly: Consultancy, Research Funding. Cerhan: NanoString: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Research Funding; Protagonist: Other: Safety Monitoring Committee; Genentech: Research Funding. Flowers: TG Therapeutics: Research Funding; V Foundation: Research Funding; Kite: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; 4D: Research Funding; Genentech Roche: Consultancy, Research Funding; National Cancer Institute: Research Funding; Ziopharm: Research Funding; Jannsen Pharmaceuticals: Research Funding; Acerta: Research Funding; Xencor: Research Funding; Allogene: Research Funding; Adaptimmune: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; CPRIT Scholar in Cancer Research: Research Funding; Beigene: Consultancy; Celgene: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Burroghs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Guardant: Research Funding; Cellectis: Research Funding; Spectrum: Consultancy; Genmab: Consultancy; Sanofi: Research Funding; Pharmacyclics: Research Funding; Novartis: Research Funding; Nektar: Research Funding; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Iovance: Research Funding; SeaGen: Consultancy; Pharmacyclics Jansen: Consultancy; Morphosys: Research Funding; Abbvie: Consultancy, Research Funding; Bayer: Consultancy, Research Funding. Lossos: LRF: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; NCI: Research Funding; University of Miami: Current Employment; NCI: Research Funding; BeiGene: Consultancy.

*signifies non-member of ASH