Clinical Significance of Testicular FDG-PET/CT Uptake in Aggressive Lymphomas

Abstract Introduction Primary testicular lymphoma (PTL) and testicular involvement of systemic lymphoma (secondary testicular lymphoma, STL) are uncommon. Most testicular lymphomas are aggressive B-cell lymphomas and portend a high risk of extranodal relapse, including CNS relapse. As such, when testicular lymphoma is identified, the management strategy is often changed to include CNS prophylaxis. It is, therefore, essential to evaluate testicular involvement in diagnosis and staging. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a standard imaging modality to stage aggressive lymphoma. Physiologic testicular FDG activity can be challenging to distinguish from involvement by lymphoma given a wide range of normal. An imaging threshold for testicular PET uptake would be clinically relevant and would help guide management. We compare testicular FDG avidity in testicular lymphoma with physiologic testicular FDG avidity. Methods Records of patients (pts) diagnosed with PTL or STL from 2002-2018 enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource were reviewed, yielding 36 pts with testicular lymphoma. Physiologic testicular avidity by FDG PET/CT was determined from analysis of 70 randomly selected patients who received FDG PET/CT from 2013-2018 prior to treatment for non-lymphoma indications including pulmonary nodule, lung carcinoma, head & neck squamous cell carcinoma, gastrointestinal carcinomas, and metastatic melanoma, without known hematologic malignancy, testicular pathology, or history of testicular infection/surgery by medical chart review. Imaging parameters compared in this analysis were SUVmax and SUVmean. All FDG PET/CT exams were reviewed centrally by a nuclear medicine radiologist and a radiology resident. Results Of the 36 pts with testicular lymphoma, 19 had an orchiectomy prior to FDG PET/CT and 7 pts did not have a staging FDG PET/CT scan. Of the 10 pts with intact testes at the time of staging FDG PET/CT, 1 pt with low-grade lymphoma was excluded. 9 pts with aggressive lymphomas were included in this analysis: 7 pts with diffuse large B cell lymphoma (DLBCL), and 1 pt each with Burkitt lymphoma and peripheral T-cell lymphoma, not otherwise specified. Testicular lymphoma was diagnosed by orchiectomy in 3 pts, and by percutaneous biopsy in 3 pts. 3 pts did not have tissue sampling of testes or scrotal contents, but had an overtly FDG-avid testicle highly suggestive of lymphomatous involvement. These 3 pts had biopsy-proven lymphoma in parotid, bone marrow, and stomach, respectively, with mean testicular SUVmax 6.8 among the 3 pts. The median age in this analysis cohort was 62 years (range 35-88). Of the 7 analyzed DLBCL pts, 6 were non-germinal center B-cell, and 1 was germinal center B-cell. The 70 control pts had a median age of 55 years (range 18-90). In known testicular lymphoma cases and control pts, SUVmax and SUVmean were assessed from the most FDG-avid testicle. Median SUVmax for the testicular lymphoma cases was 13.3 (range 5.5-29.9), compared to a median of 3.8 (range 2.1-5.5) for controls (Wilcoxon p <0.0001). Median SUVmean for testicular lymphoma was 9.2 (range 3.3-18.6), compared to a median of 3.1 (range 1.8-4.8) for controls (Wilcoxon p <0.0001) (Figure). Based on this dataset, an SUVmax cutoff of 5.0 has a sensitivity of 100% (95% CI 66.3-100) and a specificity of 98.6% (98% CI 92.3-99.9) for the detection of testicular involvement by an aggressive lymphoma. Conclusions FDG PET/CT shows significantly greater FDG avidity for testicular aggressive lymphomas as compared with physiologic testicular FDG uptake in this single institution study with centralized radiology review of cases and controls. Testicular FDG avidity greater than an SUVmax 5.0 in staging aggressive lymphoma is highly suggestive for testicular involvement, warranting follow-up clinical exam and ultrasound, at a minimum. In addition, testicles with SUVmax <5.0 in a patient with known lymphoma but no symptoms or signs of testicular involvement should be considered negative for the purposes of staging and treatment planning. A pragmatic limitation of this study is that most patients with testicular involvement of lymphoma underwent orchiectomy prior to FDG PET/CT scan, which decreased our sample size. Larger, pooled studies would be helpful to validate these clinically relevant findings. Figure. Figure. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

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Role of FDG PET/CT to Detect Bone Marrow Involvement in the Initial Staging of Aggressive Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood-2019-128896 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2892-2892 ◽

Cited By ~ 1

Author(s):

Dominic Kaddu-Mulindwa ◽

Bettina Altmann ◽

Gerhard Held ◽

Marita Ziepert ◽

Karin Menhart ◽

...

Keyword(s):

B Cell ◽

Gold Standard ◽

Fdg Pet ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Non Hodgkin Lymphoma ◽

Pet Ct ◽

Fdg Pet Ct ◽

Initial Staging

BACKGROUND: According to the Lugano classification (Cheson et al., JCO 2014, 32: 3059-3067) fludeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for evaluation and staging of aggressive non-Hodgkin Lymphoma (NHL). It is a matter of debate whether FDG PET/CT is sufficient to determine bone marrow (BM) involvement. We performed a pooled analysis of data from the PETAL (EudraCT 2006-001641-33) and OPTIMAL>60 trials (EudraCT 2010-019587-36) as prospective, open-label, randomized, multicenter Phase-III trials to determine whether initial staging with FDG PET/CT would allow non-invasive diagnosis of BM involvement and thus could avoid established but potentially painful and unpleasant BM biopsy (BMB). PATIENTS AND METHODS: Patients treated within the trials were included if both FDG PET/CT and BMB were performed during initial staging. Only patients with a biopsy-proven, centrally confirmed diagnosis of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or follicular lymphoma grade 3b were included. FDG PET/CT images and BM findings were blinded for central review by board certified PET/CT readers. Discordant findings were documented and resolved after unblinding by interdisciplinary discussion using findings of complementary imaging and/or subsequent PET examinations. Based on literature (Berthet et al., J Nucl Med 2013), a newly defined gold standard was used to confirm BM involvement. It includes a positive BMB or a positive FDG PET confirmed by targeted biopsy, complementary CT imaging or targeted MRI, or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. RESULTS: Out of 1,976 patients a total of 930 patients met the inclusion criteria. BMB confirmed BM involvement in 85 of 930 patients (9%). According to FDG PET/CT, BM was involved in 185 out of 930 patients (20%) with 36 discordances (4%) between negative initial FDG PET/CT and positive BMB ("false negatives" with respect to previous reference standard, PRS). Discordances between positive initial FDG PET/CT and negative BMB ("false positives" by PRS) occurred in 136 patients (15%). If only BMB is used as in the PRS, the negative predictive value (NPV) of FDG PET/CT was 709/745=95% (95% confidence interval [95%CI]: 93%-97%) with a sensitivity (Sens) of 58% (95%CI: 46%-68%) and a specificity (Spec) of 84% (95%CI: 81%-86%). After discussion of these cases, 185 out of 221 cases with BM involvement were identified as true positive, resulting in a Sens of 84% for FDG PET/CT (95%CI: 78%-88%). By means of FDG PET/CT 745 cases were negative of which 709 were confirmed as true negatives, resulting in an NPV of 95% (95%CI: 93%-97%). All 185 cases with positive FDG PET/CT were evaluated as true positive for BM involvement in the unblinded synopsis of all findings, resulting in a positive predictive value (PPV) of 100% (95%CI: 98%-100%). All 709 negative FDG PET/CT findings were finally confirmed as such, so Spec was 100% (95%CI: 99%-100%). Thus, the prevalence in our total cohort analyzed was 24%, since 221 out of 930 cases had confirmed BM involvement. Diagnostic performance parameters for BMB as compared to the newly defined gold standard were Sens 85/221=38% (95%CI: 32%-45%), Spec 709/709=100% (95%CI: 99%-100%), PPV 85/85=100% (95%CI: 96%-100%) and NPV 709/845=84% (95%CI: 81%-86%), respectively. Differences between the PRS in the diagnosis of BM involvement by only BMB and the newly defined gold standard result mainly from false negative BMB due to sampling errors, which are detected by FDG PET/CT. DISCUSSION: In the majority of patients with aggressive B-cell lymphoma, routine BMB does not give any additional relevant diagnostic or prognostic information over FDG PET/CT alone and could therefore be omitted. BMB should only be performed if results would have direct therapeutic impact e.g. in patients with limited stage disease and lack of further risk factors according to the international prognostic index (IPI). Disclosures Held: MSD: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Roche: Consultancy, Other: Travel support, Research Funding; Amgen: Research Funding; Acrotech: Research Funding. Stilgenbauer:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffmann La-Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Duehrsen:Amgen: Consultancy; University Hospital Essen, Germany: Employment; Takeda: Consultancy; Novartis: Consultancy; Gilead: Honoraria; Janssen: Honoraria; Gilead: Consultancy; AbbVie: Consultancy; Celgene: Research Funding; CPT: Consultancy; Takeda: Honoraria; Novartis: Honoraria; Amgen: Research Funding; Roche: Research Funding; AbbVie: Honoraria; Amgen: Honoraria; CPT: Honoraria. Hüttmann:University Hospital Essen: Employment; Takeda: Honoraria; Gilead: Honoraria. Poeschel:Amgen: Other: Travel, accommodations, expenses; Abbvie: Other: Travel, accomodations, expenses; Roche: Other: Travel, accomodations, expenses; Hexal: Speakers Bureau.

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Clinical Utility of PET/CT Scanning in Patients with Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v120.21.3903.3903 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3903-3903

Author(s):

Michael J. Conte ◽

Deborah Bowen ◽

Kari G. Rabe ◽

Susan Schwager ◽

Susan L Slager ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Fdg Pet ◽

Research Funding ◽

Clinical Utility ◽

Lymphocytic Leukemia ◽

Ct Scans ◽

Pet Ct ◽

Fdg Pet Ct ◽

Pet Ct Scan ◽

Fdg Avidity

Abstract Abstract 3903 The clinical utility of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) scans in the management of patients with chronic lymphocytic leukemia (CLL) has not been clearly defined. CLL cells typically have low FDG avidity and the addition of the PET component has not been shown to improve the utility of CT scans in the management of patients with CLL. However, patients with CLL are at increased risk of developing FDG avid complications including more aggressive lymphomas, other second malignancies, and infections for which FDG PET-CT scans are a useful imaging modality. We hypothesized that FDG PET-CT scans are sensitive tests for evaluation of these complications in patients with CLL. Patients and Methods: This observational study was performed with IRB approval. We studied all 4030 CLL patients seen at least once in the Division of Hematology at Mayo Clinic Rochester between January 1, 2006 and December 31, 2011 using data prospectively collected into the Mayo Clinic CLL database. We reviewed the clinical and radiological records of the 272 (7%) patients who underwent 526 FDG PET-CT scans of the trunk during this time period to determine the indication for PET-CT scan, results of imaging, and the effects of the use of PET/CT scan on management. Results: Four hundred and seventy two (90%) of the 526 PET-CT scans were reported as abnormal. Of these, 78 (17%) scans were useful in directing a tissue biopsy of high FDG avidity lesions. Of the 37 (8%) positive PET-CT scans that facilitated the diagnosis of new complications of CLL, 21 (4%) scans led to a diagnosis of diffuse large B cell lymphoma and 9 (2%) scans led to a diagnosis of a solid malignancy. The FDG component of 22 PET-CT scans done because of clinical suspicion of complications of CLL were negative, and thus useful in management of these patients. PET-CT scans showed progressive CLL in 138 (29%) studies but in these patients, the PET component of the scan did not provide additional information about the status of the patients' CLL compared to the CT component alone. Conclusions: FDG PET-CT scans are not of proven value in staging CLL or determining response to treatment. However, our data suggest that they could be of considerable value in evaluation for complications, especially more aggressive lymphomas, other cancers, and infections that complicate the course of CLL. Disclosures: Off Label Use: Phase I study using PGG beta glucan in CLL. Zent:Biothera: Research Funding; Genzyme: Research Funding; Genentech: Research Funding; Novartis: Research Funding; GlaxoSmithKline: Research Funding.

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End-of-treatment 18F-FDG PET/CT in diffuse large B cell lymphoma patients: ΔSUV outperforms Deauville score

Leukemia & Lymphoma ◽

10.1080/10428194.2021.1948028 ◽

2021 ◽

pp. 1-9

Author(s):

François Allioux ◽

Damaj Gandhi ◽

Jean-Pierre Vilque ◽

Cathy Nganoa ◽

Anne-Claire Gac ◽

...

Keyword(s):

B Cell ◽

Fdg Pet ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

End Of Treatment ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct ◽

Large B Cell

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FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05348-6 ◽

2021 ◽

Author(s):

Dominic Kaddu-Mulindwa ◽

Bettina Altmann ◽

Gerhard Held ◽

Stephanie Angel ◽

Stephan Stilgenbauer ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Hodgkin Lymphoma ◽

Predictive Value ◽

Fdg Pet ◽

Bone Marrow Involvement ◽

Non Hodgkin Lymphoma ◽

Pet Ct ◽

Fdg Pet Ct ◽

Initial Staging

Abstract Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). Methods Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. Results Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32–45%) and 84% (CI: 78–88%), specificity 100% (CI: 99–100%) and 100% (CI: 99–100%), positive predictive value 100% (CI: 96–100%) and 100% (CI: 98–100%), and negative predictive value 84% (CI: 81–86%) and 95% (CI: 93–97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. Conclusion In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration NCT00554164 and NCT01478542

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Genome-Wide Transcriptome Analysis Identifies Molecular Patterns of FDG-PET/CT Biomarkers in MM Patients from the Cassiopet Study

Blood ◽

10.1182/blood-2020-140235 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-26

Author(s):

Jean-Baptiste Alberge ◽

Bastien Jamet ◽

Clement Bailly ◽

Cyrille Touzeau ◽

Jonathan Cruard ◽

...

Keyword(s):

High Risk ◽

Fdg Pet ◽

Research Funding ◽

Plasma Cells ◽

High Expression ◽

Imaging Biomarkers ◽

Rna Seq ◽

Molecular Subgroups ◽

Pet Ct ◽

Fdg Pet Ct

Background Positron emission tomography (PET) using 18Fluorodeoxyglucose (FDG) provides independent prognostic informations in newly diagnosed multiple myeloma (NDMM) patients (Moreau et al, ASH 2019; Moreau et al, JCO 2017; Zamagni et al, Blood 2011). At baseline, FDG-PET/CT characteristics such as maximum standardized uptake value (SUVmax), presence of extramedullary disease (EMD), and paramedullary disease (PMD) define high-risk NDMM patients. Similarly, the presence of negative FDG-PET/CT at baseline has been associated with favorable outcome in NDMM patients (Abe et al, EJNMMI 2019; Moreau et al, ASH 2019). The aim of the present study was to identify MM molecular features associated with these functional imaging biomarkers. Methods A group of 136 patients from CASSIOPET, a companion study of the CASSIOPEIA cohort (ClinicalTrials.gov, number NCT02541383) were subjected to whole genome expression profiling using RNA sequencing (RNA-seq) on sorted bone marrow plasma cells in addition to FDG-PET/CT imaging at baseline. RNA-seq reads were aligned to hg38 reference genome with STAR and subjected to differential expression testing with DESeq2 with sample purity treated as a model covariate. High risk group with the GEP70 signature and classification from the seven molecular subgroups (CD-1, CD-2, HY, LB, MF, MS, and PR) were determined by weighted mean value of gene expression (Zhan et al, Blood 2006). Special attention was paid to genes associated with glucose metabolism and related to plasma cells proliferation. On FDG-PET/CT, SUVmax of areas of focally increased tracer uptake on bone was determined and the presence of EMD or PMD identified. Results FDG-PET/CT was positive in 108 patients out of 136 (79,4%), with 19 (14%) and 15 (11%) of them presenting PMD and EMD disease respectively. Expression level of glucose transporter GLUT1 was independent of these three imaging biomarkers (FDG-PET/CT positivity, EMD and PMD), while HK2 was downregulated in negative scans only (Fold Change = 2.1, padj=0.02). GLUT5 expression was associated with positive FDG-PET/CT (Fold Change = 3.5, padj = 8E-4). Both GLUT1 and HK2 weakly correlated with SUVmax (r=0.26 and 0.36, respectively). Of note, negative FDG-PET/CT were enriched for the LB group of patients, consistent with the lower incidence of MRI-defined bone lesions reported in this subgroup, and it remained independent of the GEP70 signature. Furthermore, high risk GEP70 signature was associated with a SUVmax ≥ 4, and correlated with the presence of PMD (OR=3.2, CI=[0.95-10.6], p=0.03), but not with EMD (p=0.7).Conversely, there was no patient from the LB group with detected PMD on imaging, but 25% (2/8) showed EMD, suggesting that different biological features support both disease patterns. Finally, positive PET/CT profiles seemed to display two distinct signatures with either high expression of proliferation genes (MKI67, PCNA, TOP2A, STMN1), or high expression of GLUT5 and lymphocyte antigens (CD19, CD30L, and CCR2), suggesting a different phenotype for this subgroup. This finding was independent of a high SUVmax. Conclusion Our study confirmed that negative FDG-PET/CT at baseline is associated with low HK2 expression while positive exams showed increased GLUT5 expression and proliferation markers. We describe a strong correlation between two imaging biomarkers (baseline SUVmax and PMD) and high risk signature and molecular subgroup with highly proliferative disease. On the contrary, EMD appeared independent of high risk signature or molecular subgroups. Additional studies will confirm and extend the correlation between imaging and clinical features of the disease and molecular characteristics of malignant plasma cells. Disclosures Touzeau: Sanofi: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Moreau:Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria.

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