The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

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The Prognostic Significance of Minimal Residual Disease and Possibility of Its Correction in Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-118457 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5751-5751

Author(s):

Andrey Garifullin ◽

Sergei Voloshin ◽

Alexey Kuvshinov ◽

Anastasiya Kuzyaeva ◽

Alexander Sсhmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Flow Cytometry ◽

High Risk ◽

Minimal Residual Disease ◽

Induction Therapy ◽

Residual Disease ◽

Pet Ct ◽

Minimal Residual

Abstract Introduction. Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients, the optimal methodology to assess MRD is not clear. The results of previous studies demonstrated the potential of multiparameter flow cytometry (MFC) and (PET-CT) in evaluation of MRD in MM. MRD monitoring should be applied in prospective clinical trials to compare and evaluate the efficacy of different treatment strategies, particularly in the consolidation and maintenance settings. The impact of MRD negativity is important, but further studies are needed to quantify the pharmacoeconomic and quality-of-life differences between early and delayed transplant strategies. Therefore, with the currently available evidence, upfront autologous stem cell transplantation (ASCT) is standard of care regardless of MRD status. Aim. We are aiming to determine the role of MRD and role of autologous stem cells transplantation in MM. Materials and methods. We`ve recently started a prospective one-center pilot study in subjects with MM. We analyzed 18 transplant-eligible patients with MM (the median age is 57 years, a male/female ratio is 3.5:1).The induction therapy Bortezomib-based only regimens was used in 12/18 (67%) patients, combination of Bortezomib-Immunomodulator-based regimens - in 6/18 (33%). High dose therapy (Mel200) and ASCT is carried out on 100% patients. The standard risk was established on 15 patients, 1 patient has an intermediate risk and 2 patients have high risk according to mSMART 2.0 stratification. The MFC MRD status of bone marrow was evaluated after 4-6 cycles of induction therapy and after ASCT on 5-color flow cytometry with use anti- CD38, CD138, CD45, CD19, CD20, CD27, CD56 and CD117 antibodies. We were based on two levels: MFC MRD- (<10-4) and MFC MRD- (<10-5) for assessing the significance of factors that affect MRD and for identifying the prognostic potential of MRD-negative status. The evaluation of MRD was carried out by genetic (cytogenetic and FISH) analysis of bone marrow plasma cells and PET-CT with 18-FDG before ASCT and on 100 day post ASCT. The results. The MFC MRD- (<10-4) before carrying out an ASCT reached 22.2% (4/18), the MFC MRD- (<10-5) - 0% and was not depended on the variant of pre-transplantation regimen. After the ASCT had been carried out there was a tendency to decrease the tumor burden in bone marrow from 0.65% to 0.1% and to increase the frequency of MFC MRD- (<10-4) status to 44.4% (8/18), of which MFC MRD- (<10-5) was 16.7% (3/18). MRD status was determined before ASCT and after ASCT by MFC and FISH in patients with high risk. The use of maintenance therapy with bortezomib (n = 5) or lenalidomide (n = 13) did not increase the frequency of MRD status. The PFS median in MFC MRD+ (>10-4) group was 23 months, in the MFC MRD- (<10-4) was not achieved; 2-year PFS was 43% and 100%, respectively (p=.04) We compared PFC between MFC MRD+ (>10-4) before ASCT (n = 4) and MFC MRD- (<10-4) after ASCT (n = 6) to assess the effect of ASCT in MM. The median PFS was not reached in both groups; 2-year PFS was 67% and 100%, respectively. The reliable difference between PFS in MFC MRD- (10-4-10-5) group and MFC MRD- (<10-5) was absent: the median of PFS was not achieved in both groups. PET-CT has been tested on 15 patients, PET-CT- response was achieved in 53% (8/15) patients. The PFS median in PET-CT+ group and PET-CT- group was not achieved. The 2-year PFS was higher in PET-CT+ group then PET-CT- probably due to patients with MFC MRD-. The 2-year PFS in «MFC MRD-PET-CT-» group was 100% to 55% in other patients. Conclusion. Carrying out ASCT demonstrated a tendency to increase the percentage of MFC MRD negative responses and improvement of PFS. The use of MFC in evaluation of MRD should be complemented with PET-CT and genetic methods for further analysis of the MFC MRD role status on MM patients. Disclosures No relevant conflicts of interest to declare.

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