18F-FDG and 11C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers

11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.

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P-013: Development of a new risk stratification system for patients with newly diagnosed multiple myeloma using R-ISS and 18F-FDG PET/CT

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(21)02147-9 ◽

2021 ◽

Vol 21 ◽

pp. S46

Author(s):

Juhyung Kim ◽

Jung Min Lee ◽

Hee Jeong Cho ◽

Sung-Hoon Jung ◽

Ho-Jin Shin ◽

...

Keyword(s):

Multiple Myeloma ◽

Risk Stratification ◽

Fdg Pet ◽

Newly Diagnosed ◽

Pet Ct ◽

18F Fdg ◽

Stratification System ◽

Fdg Pet Ct ◽

Risk Stratification System

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Clinical Impact of 18f-FDG PET/CT As a Valuable Prognostic Tool for the Newly Diagnosed Multiple Myeloma with Extramedullary Disease

Blood ◽

10.1182/blood-2019-129831 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3142-3142

Author(s):

Dong Won Baek ◽

Hee Jeong Cho ◽

Sang Kyun Sohn ◽

Sung-Hoon Jung ◽

Hong chae Moon ◽

...

Keyword(s):

Multiple Myeloma ◽

Fdg Pet ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Prognostic Tool ◽

Pet Ct ◽

National University ◽

18F Fdg ◽

Fdg Pet Ct

Purpose 18F-FDG PET/CT (PET/CT) could be a valuable tool to predict long-term survival outcomes in patients with newly diagnosed multiple myeloma (MM). It has ability to distinguish metabolically active sites such as extramedullary disease (EMD) as well as bone damage with relatively high sensitivity and specificity. In this study, we attempted to evaluate the role of PET-CT as a novel prognostic tool for patients with newly diagnosed MM who have EMD. Patients and Methods This study included 211 patients who were newly diagnosed with multiple myeloma from Kyunpook National University Hospital and Chonnam National University Hwasun Hospital. We retrospectively analyzed the medical records of enrolled patients. PET/CT was performed at the diagnosis and EMD was identified in 36 patients (17.1%). Results With a median follow-up duration of 21.5 months (range 1.4-67.7), the estimated 2-year PFS and OS rates were 46.1% and 79.6%, respectively. The presence of PET/CT positive EMD and high maximum standardized uptake value (SUVmax) on baseline PET/CT were significantly associated with inferior long-term survivals in terms of PFS (p=0.013, p=0.007) and OS (p=0.002, p=0.004). In addition, patients who underwent autologous stem cell transplantation (auto-SCT) showed superior PFS (p=0.005) and OS (p=0.022) in PET/CT positive EMD group. Meanwhile, Revised-International Staging System (R-ISS) successfully predicted the prognosis in this study. When we modified R-ISS with the presence of EMD, survival outcomes of the R-ISS stage III patients who didn't have EMD were similar to R-ISS II, while patients with PET/CT positive EMD showed even worse prognosis than the R-ISS stage III group. In the multivariate survival analysis, the presence of EMD (hazard ratio (HR), 2.397; 95% confidence internal (CI), 1.281-4.483; p=0.006) and auto-SCT (HR, 0.326; 95% CI, 0.194-0.549; p<0.001) were related to PFS, while LDH (HR, 2.56; 95% CI, 1.221-5.366; p=0.013) level and auto-SCT (HR, 0.398; 95% CI, 0.167-0.953; p=0.039) were independent prognostic factors of OS. Conclusion In conclusion, PET/CT positive EMD was a poor prognostic factor in patients with newly diagnosed MM. In addition, PET/CT could be a valuable tool to make better risk-adapted treatment strategies with R-ISS in EMD positive MM patients. Above all, patients with PET/CT positive EMD should be considered auto-SCT to improve long-term survivals. Figure Disclosures No relevant conflicts of interest to declare.

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99mTc-sestamibi SPECT/CT and 18F-FDG-PET/CT have similar performance but different imaging patterns in newly diagnosed multiple myeloma

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000001259 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1081-1088

Author(s):

Camila Mosci ◽

Fernando V. Pericole ◽

Gislaine B. Oliveira ◽

Marcia T. Delamain ◽

Maria E.S. Takahashi ◽

...

Keyword(s):

Multiple Myeloma ◽

Fdg Pet ◽

Newly Diagnosed ◽

Similar Performance ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct ◽

99Mtc Sestamibi

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Bortezomib-Based Chemotherapy Regimens Can Inmprove The Complete Remission In Newly Diagnosed Multiple Myeloma Patients With Bcl-2 and Survivin Overexpression

Blood ◽

10.1182/blood.v122.21.5349.5349 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5349-5349

Author(s):

Zeng Wen ◽

Huang Lifang ◽

Yicheng Zhang ◽

Sun Hanying ◽

Liu Wenli ◽

...

Keyword(s):

Multiple Myeloma ◽

Complete Remission ◽

Conflicts Of Interest ◽

Clinical Manifestations ◽

Staging System ◽

Chemotherapeutic Agents ◽

Tumor Burden ◽

Newly Diagnosed ◽

Double Positive ◽

Research Fields

Abstract Compared with the traditional chemotherapeutic agents, Bortezomib-based chemotherapy regimens can increase the complete remission and improve the prognosis significantly in the newly diagnosed multiple myeloma patients. Molecular markers which can predict the chemotherapeutic efficacy and safety could help the physicians to make the right decisions and benefit the patients, and it has been one of most interesting research fields in MM. It has been reported that Survivin and Bcl-2 was involved in the adverse clinical events and therapeutic resistance, respectively. In order to investigate the relationship between the Survivin and Bcl-2 expression and the different regimens therapeutic efficacy, we retrospectively studied the proteins expression in the bone marrow biopsy specimens by inmmunohistochemistry and the efficacy of different chemotherapy regimens in the newly diagnosed MM in a single center of Tongji Hospital. Total 59 newly diagnosed MM were admitted into this study. The positive expression rate for Survivin and Bcl-2 was 35.3%（n=21）and 73.5%（n=43）, respectively. The protein expression had no relationship with the Durie-Salmon and International Staging System stratification, which suggested that Survivin and Bcl-2 were not responsible for the clinical manifestations. Bortezomib-based regimens (n=22) could effectively decrease the tumor burden and achieve response (CR+PR: 67.5% ). The non-bortezomib regimens (n=37), containing VAD(T), MP(T), TAD, were effective in the absent of Survivn and Bcl-2 expression(n=7; CR+PR 62.5% ). When Survivin and Bcl-2 were single or double positive (n=30), the newly diagnosed MM patients had no response for non-bortezomib regimens with none reaching complete remission or partial remission (p=0.0088). According to this study, we recommend the newly diagnosed MM which were Survivin and Bcl-2 single or double positive by inmmunohistochemistry received the regimens containing bortezomib for anti-myeloma therapy. Disclosures: No relevant conflicts of interest to declare.

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Development of a new risk stratification system for patients with newly diagnosed multiple myeloma using R-ISS and 18F-FDG PET/CT

Blood Cancer Journal ◽

10.1038/s41408-021-00577-2 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Hee Jeong Cho ◽

Sung-Hoon Jung ◽

Jae-Cheol Jo ◽

Yoo Jin Lee ◽

Sang Eun Yoon ◽

...

Keyword(s):

Multiple Myeloma ◽

Risk Stratification ◽

Fdg Pet ◽

Survival Rates ◽

Newly Diagnosed ◽

Focal Lesions ◽

Pet Ct ◽

Stratification System ◽

Fdg Pet Ct ◽

Risk Stratification System

AbstractIn multiple myeloma (MM), a high number of focal lesions (FL) detected using positron emission tomography/computed tomography (PET/CT) was found to be associated with adverse prognosis. To design a new risk stratification system that combines the Revised International Staging System (R-ISS) with FL, we analyzed the data of 380 patients with newly diagnosed MM (NDMM) who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis. The K-adaptive partitioning algorithm was adopted to define subgroups with homogeneous survival. The combined R-ISS with PET/CT classified NDMM patients into four groups: R-ISS/PET stage I (n = 31; R-ISS I with FL ≤ 3), stage II (n = 156; R-ISS I with FL > 3 and R-ISS II with FL ≤ 3), stage III (n = 162; R-ISS II with FL > 3 and R-ISS III with FL ≤ 3), and stage IV (n = 31; R-ISS III with FL > 3). The 2-year overall survival rates for stages I, II, III, and IV were 96.7%, 89.8%, 74.7%, and 50.3%. The 2-year progression-free survival rates were 84.1%, 64.7%, 40.8%, and 17.1%, respectively. The new R-ISS/PET was successfully validated in an external cohort. This new system had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.

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18f-FDG PET/CT and the Revised International Staging System Are More Discriminating of Survival Outcomes in Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-112354 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4483-4483

Author(s):

Sung-Hoon Jung ◽

Seong Young Kwon ◽

Jung-Joon Min ◽

Hee Seung Bom ◽

Seo-Yeon Ahn ◽

...

Keyword(s):

Fdg Pet ◽

Conflicts Of Interest ◽

Independent Predictor ◽

Staging System ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Pet Ct ◽

International Staging System ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Purpose : This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS). Method: We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to induction therapy in patients with newly diagnosed MM. A Focal lesions (FL) at diagnosis was defined as focally increased FDG uptake greater than the physiologic bone marrow or liver uptake, with or without any underlying lesion. Extramedullary disease (EMD) was defined as FDG-avid soft tissue that was not contiguous to bone. Results: A total of 102 patients (61.1%) had at least one FL at diagnosis, and 44.9% had more than three FLs. EMD was present in 13.2% of all patients. In the total cohort, the presence of more than three hypermetabolic FLs or EMD on baseline PET/CT was associated with significantly inferior progression free survival (PFS) and overall survival (OS) than other patients. Because most patients (91%) with EMD had more than three FLs, PET/CT positivity was defined as the presence of more than three FLs or the presence of EMD. The C-reactive protein level was higher (0.550 vs. 0.245 mg/L, P = 0.004) and the serum albumin level was lower in the PET/CT-positive group (3.5 vs. 3.6 g/dL, P = 0.040). Patients who were PET/CT-positive had a significantly lower complete response rate after first-line therapy compared with those who were PET/CT-negative (15.6% vs. 34.4%, P = 0.007). In multivariate analyses, PET/CT positivity was an independent predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS II were PET/CT-positive at baseline and had significantly shorter PFS and OS. PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS III. Conclusion : 18F-FDG PET/CT was an independent predictor of survival outcomes in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at diagnosis may be useful for determining the survival outcomes of MM patients with R-ISS II and III. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas

Diagnostics ◽

10.3390/diagnostics11040605 ◽

2021 ◽

Vol 11 (4) ◽

pp. 605

Author(s):

Alexander Weich ◽

Rudolf A. Werner ◽

Andreas K. Buck ◽

Philipp E. Hartrampf ◽

Sebastian E. Serfling ◽

...

Keyword(s):

Fdg Pet ◽

Cxcr4 Expression ◽

Reference Standard ◽

Diagnostic Potential ◽

Pet Tracer ◽

Standardized Uptake Values ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct ◽

Neuroendocrine Carcinomas

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer 68Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard 18F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent 18F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. 68Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while18F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, 18F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to 68Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard 18F-FDG PET/CT.

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Evaluation of Whole-Body MRI (WB-MRI) in Smoldering Multiple Myeloma (SMM)

Blood ◽

10.1182/blood-2020-136185 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 19-20

Author(s):

Elizabeth Hill ◽

Baris Turkbey ◽

Evrim Turkbey ◽

Candis Morrison ◽

Peter Choyke ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Fdg Pet ◽

High Sensitivity ◽

Focal Lesions ◽

Pet Ct ◽

18F Fdg ◽

Whole Spine ◽

Fdg Pet Ct ◽

Spine Mri

Introduction Whole-body magnetic resonance imaging (WB-MRI), including multiplanar multisequence technique with diffusion weighted images, is a novel imaging technique being evaluated for patients with multiple myeloma (MM). WB-MRI is ideal for this population due to its high sensitivity for bone marrow signal changes and full anatomic coverage from vertex to mid-thighs. It is well established that patients with unequivocal focal lesions on MRI have worse outcomes. Currently the IMWG recommends that all patients with smoldering multiple myeloma (SMM) undergo WB-MRI (or whole spine MRI if WB-MRI is not available) to rule out two or more focal lesions which would classify the patient as having symptomatic myeloma requiring treatment. There is a clear benefit of using MRI for the detection of early focal myeloma lesions however less is known about findings in the SMM population. Detection of subtle findings such as one small focal lesion or heterogeneous bone marrow in WB-MRI has unknown clinical significance that needs to be further evaluated. This study aimed to evaluate the sensitivity of WB-MRI compared to other highly sensitive functional imaging modalities in patients with SMM both at baseline and after treatment. Methods Imaging of patients with WB-MRI performed at the National Institutes of Health Clinical Center Myeloma Program were reviewed and compared to whole spine MRI and 18F-FDG PET/CT completed at the same timepoint. The majority of patients were being evaluated for enrollment on clinical trials. Patients had undergone a WB-MRI with a 3-Tesla system either as a baseline study, after completion of induction treatment, or during follow up determined by the time DWI became available at our institution. The imaging protocol included sagittalT1 weighted (W) and Short tau inversion recovery (STIR) for spine and coronal, axial T1W and axial T2 TSE pulse sequences. The functional component included diffusion weighted imaging in the axial plane (b=0 and 900sec/mm2). Radiological interpretation was performed by two readers using myeloma response assessment and diagnosis system (My-RADS) {Messiou, 2019 #340}. WB-MRIs were categorized as positive if focal lesions or diffuse/heterogenous pattern of bone marrow infiltration were present. Similarly, 18F-FDG PET/CTs and whole spine MRIs were classified as positive if focal lesions or diffuse/heterogenous pattern of bone marrow were present. Results A total of 34 patients with SMM and 5 patients with relapsed refractory multiple myeloma (RRMM) had sequential WB-MRI and 18F-FDG PET/CT. Figure 1 summarizes the radiological data of the SMM population. Eleven of these patients had PET/CT, whole spine MRI, and WB-MRI at baseline. Twenty-five patients had PET/CT and WB-MRI completed after at least 8 cycles of treatment. Thirteen patients had consistently negative imaging at baseline, 7 of which also had negative imaging after treatment, while 2 patients were found to have new lesions seen on WB-MRI after treatment. Six patients had resolution of positive imaging seen at baseline after treatment. Among the 17 patients with a positive WB-MRI, 12 (71%; 95% CI 47% - 87%) had a negative correlating PET/CT. Among 5 patients with positive PET/CT at the same time point as a WB-MRI, only 1 (20%; 95% CI 2% - 64%) correlated to a negative WB-MRI. Figure 2 depicts findings from patients with RRMM for comparison. All imaging modalities showed multiple focal findings in all 5 patients. Conclusions This study depicts the high sensitivity of WB-MRI in the SMM population. Such a high sensitivity is especially needed in SMM and early myeloma when disease burden is lower and the decision for treatment is being considered. In comparison to the RRMM population where all three imaging modalities easily detect multiple focal lesions, WB-MRI tends to identify myeloma involvement in the SMM patients more than the other imaging techniques. This suggests the importance of utilizing WB-MRI when diagnosing SMM. In the SMM population, the prognostic significance of lesions that are discrepant between MRI and FDG PET/CT is not yet known. Further follow up is needed to evaluate any difference in hard endpoints such as progression free survival between patients with positive findings described by WB-MRI. Disclosures No relevant conflicts of interest to declare.

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