Page 36 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 2
Interim-PET in diffuse large B-cell lymphoma
R-CHOP is the standard therapy in DLBCL and will cure approximately 60% of patients. Standard treatment for the significant proportion of patients up to the age of 70 years with relapsed or refractory disease is platinum-based immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). However, the results of second-line immunochemotherapy are disappointing, especially for patients who relapse within one year of completing R-CHOP treatment.
Early identification of non-responders is of the utmost importance to maximize the chances of successful second-line therapy and to decrease side-effects associated with ineffective first-line therapy.
To distinguish responders from non-responders, observational studies have indicated that iPET may be an effective predictive biomarker of outcome in DLBCL, but there are inconsistencies [13,14]. It is unclear to what extent these are due to differences in the timing of PET during therapy, the choice of therapy and/or different PET reporting criteria. The current recommendation is to use DS, but earlier studies used International Harmonization Project criteria which separated PET into ‘positive’ and ‘negative’ by comparing FDG uptake with the intensity of the blood pool or nearby normal structures, if less than 2 cm, to offset partial volume effects [15].
Standardized uptake value based methods have also been used to assess response in DLBCL.Todate,moststudieshaveappliedthechangeinFDGuptakeinthepixel with the highest uptake (SUVmax) before and during/after treatment (∆SUV) [6]. Casasnovas et al. advocate ∆SUV as the most accurate criterion for response assessment. For lymphomas, in which cure is feasible and a rapid drop in SUV is common, cutoffs for a clinically relevant interim assessment of response have been reported to range from 66% to 91% [16]. Finally, metabolic tumor volume at baseline, perhaps combined with iPET response, has recently been reported as demonstrating predictive value [17]. Currently, an international consortium called PETRA (PET-Re-Analyses) is pooling clinical studies in DLBCL to perform an individual patient data meta-analysis and compare different methods in assessing interim-PET [18]. Hopefully, this will reveal the optimal time point and best visual or semi-quantitative PET-metrics to use for interim assessment.
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