¹⁸F-FDG or 3′-Deoxy-3′-¹⁸F-Fluorothymidine to Detect Transformation of Follicular Lymphoma

Abstract

Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that 18 F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) might be superior to 18 F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a headto-head comparison of 18 F-FDG and 18 F-FLT in patients with FL and TF. Methods: 18 F-FDG and 18 F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUV max ), defined as the lymph node with the highest uptake per patient, and SUV range , defined as the difference between the SUV max of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm 3 (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of 18 F-FDG or 18 F-FLT. To determine the discriminative ability of SUV max and SUV range of both tracers for TF, receiver-operatingcharacteristic curve analysis was performed. Results: The highest SUV max was significantly higher for TF than FL for both 18 F-FDG and 18 F-FLT (P , 0.001). SUV range was significantly higher for TF than FL for 18 F-FDG (P 5 0.029) but not for 18 F-FLT (P 5 0.075). The ability of 18 F-FDG to discriminate between FL and TF was superior to that of 18 F-FLT for both the highest SUV max (P 5 0.039) and the SUV range (P 5 0.012). The cutoff value for the highest SUV max of 18 F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For 18 F-FLT, these values were 5.1 and 18%, respectively. When the same method was applied to SUV range , the cutoff values were 5.8 for 18 F-FDG (specificity, 71%) and 1.5 for 18 F-FLT (specificity, 36%). Conclusion: Our data suggest that 18 F-FDG PET is a better biomarker for TF than 18 F-FLT PET. The proposed thresholds of highest SUV max and SUV range should be prospectively validated.

Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma

“…70,71 Identifying biomarkers that predict risk of transformation or that can facilitate the early diagnosis of transformation may aid in management. 72 Of interest, chronic lymphocytic leukemia can also transform into secondary DLBCL. Unlike secondary DLBCL arising from FL, secondary DLBCL arising from chronic lymphocytic leukemia does not respond to treatment with the immune modulator lenalidomide.…”

Can histologic transformation of follicular lymphoma be predicted and prevented?

“…Correlates of an acceleration of proliferation kinetics can be found, for example, in increased expression of Ki67 within the tumor 18 or high levels of maximum standardized uptake value (.12-14) on positron emission tomography scanning. [19][20][21][22][23] On the molecular level, transformed FL (TFL) differs from preceding indolent FL by higher numbers of single-nucleotide mutations, small insertions and deletions, copy-number changes, and structural rearrangements. [24][25][26] Transformation occurs via the activation of known or putative oncogenes (MYC, CCND3) and inactivation of known or putative tumor suppressor genes (TP53, CDKN2A/B, B2M).…”

PET Scan in Hodgkin Lymphoma

“…Finally, technological progress on the webbased imaging exchange and the availability of the web platform WIDEN® to upload and download images [ 95 ] have rendered BICR and the consequent treatment decision by the local clinical investigator possible and timely. In the HD0607 trial the median scan uploading and downloading times were 1 min, 25 s, and 1 min 55 s, respectively; the average and median times for central review were 47 h, 53 m, and 37 h, 43 m, respectively.…”

“…Although there is lack of consistency for defining an exact SUV max cutoff, a transformation is suggested at a SUV max of 10-15 [91][92][93][94][95][96]. The value of FDG-PET/CT diagnosing transformation has been well established for guiding lymph node biopsy when transformation is suspected.…”