In-vivo proliferation imaging for early response assessment in patients with aggressive non-Hodgkins lymphoma

Objectives To evaluate the in-vivo proliferation marker [18F]fluorodeoxythymidine (FLT) as surrogate marker for early prediction of response to CHOP-based chemotherapy and outcome in patients with aggressive Non-Hodgkins Lymphoma (NHL).

Methods 56 patients (27 male, 29 female) with proven aggressive NHL were recruited into this prospective study. FLT-PET scans were performed prior to and 1 week after start of (R-)-CHOP chemotherapy. FLT-PET and image analysis was performed according to a standardized protocol (45 min p.i., 300-370 MBq FLT, 1.5 cm diameter 2D-standard ROI). Mean and max FLT-SUVs and changes of SUV were correlated with response and survival. Treatment response was classified after completion of six cycles of chemotherapy (n=54; 2 patients were lost to follow-up). Mean follow-up was 23.2 months (median: 18.8 months).

Results Reduction of SUVmean and SUVmax was higher for patients achieving CR (n=48) as compared to patients achieving PR or PD (n=6). To date, this difference did not reach statistical significance (p=0.071 and p=0.051, respectively). Martingale-residual analysis was performed for all six death events and revealed a significant correlation between survival and change of SUV. The corresponding estimated hazard ratio per one-point increment of FLT-SUVmean was at least or above 4.88 (95%CI: 4.88 - 1000, p=0.02).

Conclusions Our results show that early response assessment with FLT-PET allows stratification of risk to death already 1 week after initiation of treatment. Complete responders show a higher decrease in SUVmean than patients in PR/PD. Due to the low incidence of non-responders and death associated with standard chemotherapy in the selected patient cohort this difference did not reach statistical significance yet.

Research Support This work was supported by the collaborative research center SFB 824, project C3, German Research Foundation (DFG)