Early Determination of Prognosis by Interim 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Patients with Non-Hodgkin Lymphoma

Abstract

PET is a potentially useful modality for response analysis and prognosis prediction in patients with high-grade non-Hodgkin lymphoma (NHL). The thymidine analog 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) was recently introduced as a new tracer. 18 F-FLT uptake correlates with tumor cell proliferation and is suggested to reflect early response to treatment. We performed a prospective study to evaluate the prognostic value of early interim 18 F-FLT PET in patients with NHL. Methods: Patients with untreated NHL were enrolled between 2005 and 2007. Among them, 61 pairs of 18 F-FLT PET images were obtained at baseline (pre), after 1 cycle of chemotherapy (interim), and at the end of all scheduled first-line chemotherapy (final). All 18 F-FLT PET scans were interpreted by quantitative methods (maximum standardized uptake value [SUVmax] and mean standardized uptake value [SUVmean]). Receiver-operating-characteristic curve analysis was performed to define 18 F-FLT PET positivity using a cutoff value predicting disease progression, relapse, or death. Survival outcome was measured by progression-free survival (PFS) and overall survival (OS) rates. Results: Receiver-operating-characteristic curve analysis of SUVmax for prediction of disease progression and death showed the highest area under the curve (AUC) in interim 18 F-FLT PET scans (AUC of 0.841 for PFS and 0.834 for OS, with a cutoff of 1.86; P , 0.001), compared with pre and final 18 F-FLT PET scans. The SUVmean in interim 18 F-FLT PET scans also showed better prediction (AUC of 0.842 for PFS and 0.824 for OS, with a cutoff value of 1.65; P , 0.001) than pre and final 18 F-FLT PET scans. Patients with an interim 18 F-FLT PET SUVmax more than 1.86, who were defined as the interim PET-positive group, were associated with worse 5-y PFS and OS rates than the interim PET-negative group (for PFS: 52.0% vs. 80.7%, respectively, and P , 0.001; for OS: 56.2% vs. 81.4%, respectively, and P , 0.001). By multivariable analysis, the prognostic value of interim 18 F-FLT PET positivity by SUVmax remained significant after adjustment with other prognostic factors (for PFS: hazard ratio, 7.82, 95% confidence interval, 1.65-36.96, and P 5 0.009; for OS: hazard ratio, 5.55, 95% confidence interval, 1.47-33.77, and P 5 0.014). Conclusion: In patients with aggressive NHL, early interim 18 F-FLT PET is a significant predictor of PFS and OS. Early 18 F-FLT PET imaging also has a potential to identify patients with delayed response and nonfavorable prognosis despite achieving a clinical complete response.

Interim PET-driven strategy in de novo diffuse large B-cell lymphoma: do we trust the driver?

“…The latter highlights the high risk of iPET misinterpretation, precluding any iPET-driven strategy. In a key study challenging the validity of a positive iPET scan, Moskowitz et al 11 showed that systematic biopsy of iPET4-positive residual mass (ie, with an FDG uptake greater than the local background) after 4 cycles of dose dense rituximab plus cyclophosphamide, oncovin, prednisolone, and hydroxyadriamycine (R-CHOP) only detected active lymphoma, and a commensurate poor prognosis, in 23% of patients, 7 whereas iPETpositive patients with negative biopsy and iPET-negative patients had similar outcomes. With iPET having a false PPV in 87% of cases, they concluded that its clinical predictive value was poor and that it could not be used to drive treatment decisions.…”

“…Limited data are published about iPET1. [5][6][7] iPET4 often replaces the previously commonly used midtherapy conventional contrast-enhanced CT scan, to ensure that patients have reached at least partial response before proceeding further with treatment. Clinical interest of iPET beyond the fourth cycle is limited, as it usually comes too late to modify the treatment.…”

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

“…Additionally, 18 F-FLT uptake is well correlated with Ki-67 staining in studies of breast, brain and lung cancers [160][161][162][163]. 18 F-FLT has since been used to assess treatment response in breast cancer [164] and lymphoma [165,166], among others. Clinical reports also show that 18 F-FLT is a more reliable and sensitive tracer for evaluating treatment response than 18 F-FDG [167][168][169].…”

Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring

“…Baseline FLT uptake has been shown to be a negative predictor of response to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in DLBCL and was significantly correlated with the International Prognostic Index (18). Moreover, preliminary studies have shown that FLT PET allows noninvasive assessment of tumor grading and early response assessment (19)(20)(21)(22)(23)(24).…”