18F-FDG PET/CT Associates With Disease Activity and Clinical Recurrence of AOSD Patients

Objective: The purpose of this study was to explore the value of 18F-FDG PET/CT in monitoring the disease activity and predicting the prognosis of the Adult-onset Still's disease (AOSD).Methods: We retrospectively analyzed the electronic medical records of 45 AOSD patients who underwent 18F-FDG PET/CT in the Second Xiangya Hospital. PET/CT imaging and clinical information were retrospectively reviewed and analyzed. 18F-FDG uptake was assessed by measuring standard uptake value (SUV) in the spleen, liver, bone marrow, and lymph nodes. The spleen-to-liver ratio of the SUVmax (SLRmax) and SUVmean (SLRmean), the bone-to-liver ratio of the SUVmax (BLRmax), and SUVmean (BLRmean), and the lymph nodes-to-liver ratio of the SUVmax (LyLRmax) were calculated. Clinical and laboratory information were collected and evaluated for association with metabolic parameters of 18F-FDG PET/CT. The influencing factors for recurrence within 1 year were analyzed to determine whether 18F-FDG PET/CT can predict the prognosis of AOSD patients.Results: Elevated 18F-FDG uptake could be observed in bone marrow, spleen, and lymph nodes of AOSD patients. Correlation analysis between 18F-FDG uptake of organs and laboratory examinations showed that SLRmean positively correlated with LDH, AST, ferritin, and the systemic score (r = 0.572, 0.353, 0.586, and 0.424, P < 0.05). The SLRmean had the highest correlation with ferritin (r = 0586, P < 0.001). All metabolic parameters in spleen, including SUVmax, SUVmean, SLRmax, and SLRmean, are positively correlated with LDH level (r = 0.405, 0.539, 0.481, and 0.572, P < 0.05). Bone marrow SUVmax, BLRmax, and BLRmean were correlated with C-reactive protein (CRP) level (r = 0.395, 0.437, and 0.469, P < 0.05). Analysis of the influencing factors of recurrence within 1 year showed that the spleen SUVmax, spleen SUVmean, SLRmax, SLRmean, ferritin, and the systemic score of the recurrence group was significantly higher than the non-recurrence group (P < 0.05). The SLRmean cutoff of 1.66 with a sensitivity of 72.7% and specificity of 80.0% had the highest performance in predicting recurrence.Conclusion: The glucose metabolism of the liver, spleen, and bone marrow of AOSD patients were correlated with laboratory inflammatory indicators and system score, suggesting that 18F-FDG PET/CT could be applied to evaluate disease activity. Moreover, spleen 18F-FDG uptake may be a potential biomarker for predicting clinical prognosis of AOSD patients.

Download Full-text

[18F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection

Journal of Virology ◽

10.1128/jvi.00897-17 ◽

2017 ◽

Vol 91 (21) ◽

Cited By ~ 2

Author(s):

Julie Dyall ◽

Reed F. Johnson ◽

Svetlana Chefer ◽

Christopher Leyson ◽

David Thomasson ◽

...

Keyword(s):

Bone Marrow ◽

Immune Response ◽

Lymph Nodes ◽

Metabolic Activity ◽

Fdg Pet ◽

Ct Imaging ◽

Lymphoid Tissues ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct

ABSTRACT Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.

Download Full-text

Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still’s disease

Arthritis Research & Therapy ◽

10.1186/s13075-021-02482-2 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Liyan Wan ◽

Yuting Gao ◽

Jieyu Gu ◽

Huihui Chi ◽

Zhihong Wang ◽

...

Keyword(s):

Bone Marrow ◽

Lymph Nodes ◽

Disease Severity ◽

Fdg Pet ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Lesion Volume ◽

Pet Ct ◽

Fdg Pet Ct ◽

Activation Syndrome

Abstract Background To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still’s disease (AOSD). Methods Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. Results High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. Conclusions The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.

Download Full-text

The Utility of Metabolic Parameters on Baseline F-18 FDG PET/CT in Predicting Treatment Response and Survival in Paediatric and Adolescent Hodgkin Lymphoma

Journal of Clinical Medicine ◽

10.3390/jcm10245979 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5979

Author(s):

Janet Denise Reed ◽

Andries Masenge ◽

Ane Buchner ◽

Fareed Omar ◽

David Reynders ◽

...

Keyword(s):

Positron Emission Tomography ◽

Bone Marrow ◽

Treatment Response ◽

Hodgkin Lymphoma ◽

Fdg Pet ◽

Emission Tomography ◽

Metabolic Parameters ◽

Positron Emission ◽

Pet Ct ◽

Fdg Pet Ct

Lymphoma is the third most common paediatric cancer. Early detection of high-risk patients is necessary to anticipate those who require intensive therapy and follow-up. Current literature shows that residual tumor avidity on PET (Positron Emission Tomography) following chemotherapy corresponds with decreased survival. However, the value of metabolic parameters has not been adequately investigated. In this retrospective study, we aimed to evaluate the prognostic value of metabolic and other parameters in paediatric and adolescent Hodgkin lymphoma. We recorded tMTV (total Metabolic Tumor Volume), TLG (Total Lesion Glycolysis), and SUVmax (maximum Standard Uptake Value) on baseline PET, as well the presence of bone marrow or visceral involvement. HIV (human immunodeficiency virus) status and baseline biochemistry from clinical records were noted. All patients received stage-specific standard of care therapy. Response assessment on end-of-treatment PET was evaluated according to the Deauville criteria. We found that bone marrow involvement (p = 0.028), effusion (p < 0.001), and treatment response (p < 0.001) on baseline PET, as well as HIV status (p = 0.036) and baseline haemoglobin (p = 0.039), were significantly related to progression-free survival (PFS), whereas only effusion (p = 0.017) and treatment response (p = 0.050) were predictive of overall survival (OS). Only baseline tMTV predicted treatment response (p = 0.017). This confirms the value of F-18 FDG PET/CT (Fluoro-deoxy-glucose Positron Emission Tomography/Computed Tomography) in prognostication in paediatric and adolescent Hodgkin lymphoma; however, further studies are required to define the significance of metabolic parameters.

Download Full-text

Conventionally-Defined and PET/CT-Defined Complete Response (CR) to Novel Agent-Based Induction Therapy and Autologous Stem-Cell Transplantation (ASCT) In Multiple Myeloma (MM): A Prospective Study of Clinical and Prognostic Implications

Blood ◽

10.1182/blood.v118.21.826.826 ◽

2011 ◽

Vol 118 (21) ◽

pp. 826-826

Author(s):

Elena Zamagni ◽

Cristina Nanni ◽

Francesca Patriarca ◽

Annalisa Pezzi ◽

Beatrice Anna Zannetti ◽

...

Keyword(s):

Bone Marrow ◽

Induction Therapy ◽

Fdg Pet ◽

Bone Marrow Involvement ◽

Trend Test ◽

Agent Based ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Time To Relapse

Abstract Abstract 826 Incorporation of novel agents into ASCT allowed the achievement of unprecedented high rates of CR in young MM patients, a gain which translated into extended PFS and OS. As a consequence, interest in the evaluation of the depth of CR has progressively grown. More sensitive tools, such as multiparametric flow cytometry or molecular biology, led to the demonstration of a correlation between the depth of CR and prognosis, but failed to identify the persistence of residual disease outside of the bone marrow level. 18 F-FDG PET/CT is a careful technique to detect with high sensitivity and specificity the presence of active bone lesions and/or bone marrow involvement in newly diagnosed and previously treated MM. We prospectively analysed the prognostic significance of FDG-PET/CT at diagnosis, after induction therapy and ASCT in an homogeneous population of 192 patients with newly diagnosed MM, followed for a median of 43 months. By study design, all patients were studied with FDG-PET/CT at baseline, after induction treatment, after 3 months from ASCT (single or double), once a year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FLs), as well as size and associated standardized uptake values (SUV) were recorded. Extra-medullary disease (EMD), if present, was described by location, size, number and SUV. Twenty four percent of the patients had a negative PET/CT scan at diagnosis. Among PET/CT-positive patients, 44% showed ≥3 FLs, 46% had SUV values >4.2 and in 6% EMD could be detected. These 3 variables adversely affected 4-year estimates of PFS and OS. In particular, both EMD and severe FDG uptake were significantly associated with shorter PFS and OS. Thirty seven percent of the patients were PET/CT-negative after induction. A strong correlation between conventional response and SUV max reduction was evident, the mean SUV value of patients achieving CR being significantly lower in comparison with that of patients reaching very good partial response (VGPR) or partial response (mean: 1.4 vs 3, respectively) (Cuzick's trend test, P= 0.016). Persistence of severe FDG uptake (SUV max still >4.2) after induction predicted for shorter PFS at 4 years (P= 0.004). PET/CT negativity (PET-CR) was observed in 65% of patients after 3 months from ASCT(s). A close relationship between PET/CT negativity and response to ASCT was evident, since 95% of patients with a negative PET/CT had achieved at least a VGPR (P= 0.003). Moreover, a correlation between conventional response and SUV max reduction was evident after ASCT as well (mean: 0.8 vs 1.8, respectively) (Cuzick's trend test, P= 0.001). PET-CR after ASCT conferred superior PFS and OS in comparison with persistence of FDG uptake. In particular, the 4-year estimates of PFS and OS for PET-CR patients were 66% and 89%, respectively, as compared with 45% and 65% for positive patients (P=0.02 both for PFS and OS). Notably, 23% of patients achieving CR according to conventional criteria still had positive PET/CT scans and their 4-year estimate of PFS was 30%, as compared with 61% for negative patients (P=0.02). After ASCT, patients were followed with evaluation of M protein every 3 months and of PET/CT once a year. In 44% of those who had a conventionally-defined relapse or progression, the mean time to relapse/progression was 27.6 months for PET-negative patients as compared with 18 months for positive patients (P=0.05). In PET-positive patients, the SUV max was inversely correlated to the time to relapse (correlation coefficient −0.7, P= 0.003). In multivariate analysis, both severe PET/CT involvement at diagnosis (SUV >4.2 and/or EMD) and persistence of FDG uptake after ASCT were independent predictors of worst PFS (SUV >4.2= HR: 2.0, 95%CI: 1.13–3.72; EMD= HR: 15.0, 4.0–55.8; FDG uptake after ASCT= HR: 2.12, 1.19–3.77) and OS (EMD= HR: 6.99, 2.28–21.46; FDG uptake after ASCT= HR: 3.57, 1.03–12.39). In conclusion, PET-defined CR was linked to conventionally-defined CR and was an independent prognostic factor in MM patients receiving up-front novel agent-based induction therapy and ASCT. PET/CT contributed to a more careful definition of CR, in particular after ASCT, and could be usefully incorporated into the algorithm to evaluate the depth of response in young MM patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Imaging findings of granulocyte colony-stimulating factor-producing tumors: a case series and review of the literature

Japanese Journal of Radiology ◽

10.1007/s11604-021-01130-8 ◽

2021 ◽

Author(s):

Shigeshi Kohno ◽

Akihiro Furuta ◽

Shigeki Arizono ◽

Koji Tokunaga ◽

Sei Nakao ◽

...

Keyword(s):

Bone Marrow ◽

Bone Scintigraphy ◽

Fdg Pet ◽

Imaging Findings ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct ◽

Stimulating Factor

AbstractGranulocyte colony-stimulating factor (G-CSF)-producing tumors have an aggressive clinical course. Here, we report five cases of G-CSF-producing tumors and review the literature, focusing on imaging findings related to tumor-produced G-CSF. In addition to our cases, we identified 30 previous reports of G-CSF-producing tumors on which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, bone scintigraphy, or evaluation of bone marrow MR findings was performed. White blood cell count, serum C-reactive protein, and serum interleukin-6 were elevated in all cases for which these parameters were measured. G-CSF-producing tumors presented large necrotic masses (mean diameter 83.2 mm, range 17–195 mm) with marked FDG uptake (mean maximum standardized uptake value: 20.09). Diffuse FDG uptake into the bone marrow was shown in 28 of the 31 cases in which FDG-PET/CT was performed. The signal intensity of bone marrow suggested marrow reconversion in all seven MRI-assessable cases. Bone scintigraphy demonstrated no significant uptake, except in two cases with bone metastases. Splenic FDG uptake was increased in 8 of 10 cases in which it was evaluated. These imaging findings may reflect the effects of tumor-produced G-CSF. The presence of G-CSF-producing tumors should be considered in patients with cancer who show these imaging findings and marked inflammatory features of unknown origin.

Download Full-text

Proposal for a Quantitative 18F-FDG PET/CT Metabolic Parameter to Assess the Intensity of Bone Involvement in Multiple Myeloma

Scientific Reports ◽

10.1038/s41598-019-52740-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Maria E. S. Takahashi ◽

Camila Mosci ◽

Edna M. Souza ◽

Sérgio Q. Brunetto ◽

Elba Etchebehere ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Fdg Pet ◽

Visual Analysis ◽

Hepatic Uptake ◽

Bone Involvement ◽

Whole Body ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Many efforts have been made to standardize the interpretation of 18F-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18F-FDG PET/CT considering the extent and intensity of bone 18F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00–1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p < 0.0001). There was an inverse correlation between the patients’ hemoglobin values and IBI (r = −0.248;p = 0.02). IBI score is an objective measure of bone and bone marrow involvement in MM, allowing the categorization of patients in different degrees of aggressiveness of the bone disease. The next step is to validate IBI in a larger group of patients, before and after treatment and in a multicentre setting.

Download Full-text

Clinical implications of increased uptake in bone marrow and spleen on FDG-PET in patients with bacteremia

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05071-8 ◽

2020 ◽

Author(s):

Jordy P. Pijl ◽

Thomas C. Kwee ◽

Riemer H. J. A. Slart ◽

Derya Yakar ◽

Marjan Wouthuyzen-Bakker ◽

...

Keyword(s):

Bone Marrow ◽

Glucose Level ◽

Fdg Pet ◽

C Reactive Protein ◽

Gram Negative ◽

Fdg Uptake ◽

Reactive Protein ◽

Pet Ct ◽

Focus Of Infection ◽

Fdg Pet Ct

Abstract Purpose To investigate which clinical factors and laboratory values are associated with high FDG uptake in the bone marrow and spleen on 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with bacteremia. Methods One hundred forty-five consecutive retrospective patients with bacteremia who underwent FDG-PET/CT between 2010 and 2017 were included. Mean standard uptake values (SUVmean) of FDG in bone marrow, liver, and spleen were measured. Bone marrow-to-liver SUV ratios (BLR) and spleen-to-liver SUV ratios (SLR) were calculated. Linear regression analyses were performed to examine the association of BLR and SLR with age, gender, hemoglobin, leukocyte count, platelets, glucose level, C-reactive protein (CRP), microorganism, days of antibiotic treatment before FDG-PET/CT, infection focus, use of immunosuppressive drugs, duration of hospital stay (after FDG-PET/CT), ICU admission, and mortality. Results C-reactive protein (p = 0.006), a cardiovascular or musculoskeletal focus of infection (p = 0.000 for both), and bacteremia caused by Gram-negative bacteria (p = 0.002) were independently and positively associated with BLR, while age (p = 0.000) and glucose level before FDG-PET/CT (p = 0.004) were independently and negatively associated with BLR. For SLR, CRP (p = 0.001) and a cardiovascular focus of infection (p = 0.020) were independently and positively associated with SLR, while age (p = 0.002) and glucose level before FDG-PET/CT (p = 0.016) were independently and negatively associated with SLR. Conclusion High FDG uptake in the bone marrow is associated with a higher inflammatory response and younger age in patients with bacteremia. In patients with high FDG uptake in the bone marrow, a cardiovascular or musculoskeletal focus of infection is more likely than other foci, and the infection is more often caused by Gram-negative species. High splenic FDG uptake is associated with a higher inflammatory response as well, and a cardiovascular focus of infection is also more likely in case of high splenic FDG uptake.

Download Full-text

The impact of endoscopic ultrasound-guided fine-needle aspiration of lymph nodes on subsequent positron emission tomography/computed tomography imaging: a prospective study

Endoscopy ◽

10.1055/a-0647-6824 ◽

2018 ◽

Vol 51 (02) ◽

pp. 165-168

Author(s):

Ole Bjerring ◽

Søren Hess ◽

Claus Fristrup ◽

Poul Høilund-Carlsen ◽

Michael Mortensen

Keyword(s):

Lymph Nodes ◽

Fdg Pet ◽

Needle Aspiration ◽

Emission Tomography ◽

Fine Needle ◽

Fdg Uptake ◽

Positron Emission ◽

Pet Ct ◽

Fdg Pet Ct ◽

Upper Gastrointestinal

Abstract Background Modern cancer diagnostic work-up is based on multiple modalities within a short time period. The interplay between these modalities is complex and not well known. Performing biopsy procedures prior to (18)F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is considered to pose a risk of false-positive imaging results; however, this is not based on solid scientific evidence. The use of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is commonly used in upper gastrointestinal malignancies, is proven safe, and has very little risk of complications. This study aimed to assess whether EUS-FNA induces inflammation that would increase FDG uptake on subsequent PET/CT. Methods 27 patients who were referred for upper gastrointestinal EUS for different reasons initially underwent FDG-PET/CT to detect biopsy-eligible lymph nodes with no FDG uptake. Patients then underwent EUS-FNA of the benign lymph nodes, with a minimum of three passes. Patients were re-evaluated with FDG-PET/CT 1 week later, with specific emphasis on the biopsied lymph nodes. Results None of the biopsied lymph nodes showed increased FDG uptake on follow-up FDG-PET/CT. No adverse events occurred. Conclusion EUS-FNA prior to FDG-PET/CT did not lead to false-positive FDG uptake. The interpretive impact of minor procedures prior to FDG-PET/CT needs to be re-evaluated.

Download Full-text

18F-FDG-PET/CT in Multiple Myeloma: High Intense PET Positive Lesions at Diagnosis Harbor Cytogenetic Adverse Subclones

Blood ◽

10.1182/blood.v128.22.3260.3260 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3260-3260

Author(s):

Brian Østergaard ◽

Anne L. Nielsen ◽

Hanne E.H. Møller ◽

Birgitte Preiss ◽

Jon T. Asmussen ◽

...

Keyword(s):

Bone Marrow ◽

Fdg Pet ◽

Myeloma Cell ◽

Newly Diagnosed ◽

Focal Lesions ◽

Bone Marrow Biopsies ◽

Ct Guided ◽

Fdg Uptake ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Aim:In multiple myeloma (MM), high intensity of FDG uptake in focal lesions measured as the standard uptake value (SUV) at diagnosis is associated to aggressive disease and reduced overall survival. However, the reason for high intensity FDG uptake in some focal lesions is unknown, but hypothetically such "hot" lesions could represent evolving myeloma sub-clones with particular characteristics, e.g. higher proliferative activity. We aimed to explore and characterize focal lesions with high FDG uptake and to compare the findings with random diagnostic bone marrow biopsies with lower FDG intensity or a biopsy from another lesion with lower FDG uptake. Thus, we have created a paired biopsy biobank that will be explored for molecular, biological, physiological and myeloma prognostic markers. Here we present our first data including results on morphology, immunohistochemistry, mutational, proliferative and cytogenetic status in the biopsies Material and methods: CT-guided biopsies from FDG-PET positive CT-visible focal lesions in sternum, sacrum, humerus, femoral, pubic and iliac bones were taken without complications depending on accessibility and safety in 14 newly diagnosed, untreated MM patients, 2 females and 12 males, aged 53-77 years. Patients that had received steroids or bisphosphonates were excluded. Bone marrow biopsies were taken as part of the normal diagnostic work-up, but included an extra biopsy and aspirate for research. FDG uptake in the regions of interest (ROI) at focal and random bone marrow biopsy was quantified by dedicated software (ROVER, ABX, Radeberg, Germany) to obtain the following variables: Lesion volumes, SUVmax, SUVpeak, cSUVmean (SUVmean corrected for partial volume effect). The paired biopsies were analyzed for: Myeloma plasma cells percentage (PC%), myeloma cell proliferation (Ki67 positive fraction of CD138 positive cells (Ki67/CD138%), myeloma cell MYC protein expression (MYC/CD138%), FISH aberrations in % of myeloma cells (del17p, del13q, del1p, amp1q, t(11;14), t(4;14), BRAF mutation and specific p16, p27, and p53 protein expressions by IHC in % of MM cells. Results: 13 patients were evaluable for analysis with paired datasets. One patient was excluded due to a normal bone marrow examination (multifocal myeloma). ROI SUVmax values ranged from 2.6 to 22.16 and differences in SUVmax between paired biopsies ranged from 0.4 to 17.1. First of all, we found myeloma malignancy in all PET-positive CT-guided biopsies. Comparing the findings in "hot" versus "random" biopsy groups we found significantly higher PC%s in the "hot" biopsy group (p=0.01) but this was not a consistent finding in all patients. PC proliferation rate (Ki67/CD138) was higher in some of the "hot" biopsies but this was neither a uniform observation. No difference in "primary event" chromosome 14q translocations was observed, whereas we identified subclones with typical cytogenetic secondary or late events in several "hot" biopsies that were not present in the random bone marrow biopsy: amp1q in 3 patients, del1p in 1 patient, del13q and del17p in 1 patient. MYC protein expression was higher in "hot" biopsies in 4 patients, and downregulation of p27 was evident in 2 patients. We found no unbalanced expression of p53 or p16, and in only one patient we identified a BRAF mutated subclone that was equally present in the "hot" and "random" biopsy (20% vs 30%). Few patients presented more adverse findings in the "hot" biopsies. Overall, MM adverse findings were present unbalancedly in 8 of 13 patients. Conclusion: We did not identify a mutual factor that explained the more intense FDG uptake in CT guided biopsies than in random bone marrow, e.g. a higher PC Ki67 expression. However, in 8 of 13 patients we identified 1 or more prognostic adverse, unbalanced findings in the PET positive focal lesions indicating presence of more aggressive subclones. These findings are concordant with the adverse prognostic importance of finding high-intense PET-positive focal lesions on FDG-PET/CT in newly diagnosed MM patients. Disclosures No relevant conflicts of interest to declare.

Download Full-text