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Prognostic significance of myeloma PET-CT focal lesions
PET-CT
Scans were performed using a standard clinical protocol follow- ing 6-8 hours of fasting and after intravenous administration of 10- 15mCi (370-555Mbq) of fluorodeoxyglucose (FDG). After 50-70 minutes of uptake, images were acquired on either a CTI-Reveal or a Biograph 6 PET/CT system (Siemens Medical Systems), both with full ring LSO crystal configurations. PET images were gener- ated by 3D iterative reconstruction on a 168x168 matrix, with a zoom of 1.0 FWHM filter of either 5.0 or 6.0 mm, and 2 iterations with 8 subsets. CT data were used for localization and attenuation correction. Images underwent a 3D region of interest (ROI) analy- sis of the axial and appendicular skeleton using the US Food and Drug Administration approved “Mirada Medical PET-CT XD Oncology Review” software (Oxford, UK). Background red mar- row was defined using a 1 cm3 ROI in the most inferior vertebral body that did not demonstrate focally increased uptake. FLs were defined as areas, measuring at least 1 cm, not otherwise demon- strated to be artefacts by comparison with co-registered CT and exhibiting a peak SUV greater than the peak SUV for the back- ground red marrow. Radiologists used a standardized approach for reporting. All data for analysis were extracted from clinical reports.
Response assessment
Clinical response assessment was performed using International Myeloma Working Group (IMWG) definitions.1 Minimal residual disease assessment was performed on BMs using an 8-color tech-
nique (CD138/CD38/CD19/CD45/CD27/CD81/CD56/CD20). A minimum of 2 million cells were analyzed, giving a sensitivity of 1 in 105.
Statistical analysis
The Kaplan-Meier method16 was used to estimate OS and PFS distributions. Cumulative incidences by GEP70 risk for complete response (CR), very good partial response (VGPR) and partial response (PR) were calculated.17 Group comparisons (overall and pairwise) for survival end points and cumulative incidence were performed using the log-rank test.18 Cox proportional hazards modeling was used to identify the association of risk factors with outcome. OS was defined as time from landmark to death from any cause. PFS was calculated as time from landmark to progres- sion, relapse, or death from any cause. Patients experiencing none of these events were censored at the date of last contact. Fisher’s exact test was used to evaluate the association between categori- cal variables. P<0.05 was considered statistically significant. Cut- off points for FL parameters were applied as previously reported.6
Results
PET-CT at presentation and outcome
The presence of more than 3 FLs detected on PET-CT scan at baseline was associated with adverse PFS (P<0.0001) and OS (P<0.0001) (Figure 1). There was no
ABC
Figure 1. Survival data according to number of focal lesions (FLs). Progression-free survival (PFS) (upper panel) and overall survival (OS) (lower panel) for patients entered into TT4-6 trials by the number of FL detected at presentation: (A) all patients, (B) GEP70 low-risk patients, and (C) GEP70 high-risk patients. A significant difference was observed for patients with FLs at baseline compared to patients with no FL at baseline for both PFS (P<0.0001) and OS (P<0.0001). These differ- ences were significant when considering separately GEP70 low-risk patients (P=0.0007 for PFS, P<0.0001 for OS) and GEP70 high-risk patients (P=0.04 for PFS, P=0.05 for OS).
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