Page 54 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 3
A total of 2,411 newly diagnosed DLBCL patients from 20 studies were assessed for this analysis. Table 1 shows the main study-, patient-, and treatment characteristics of the included studies. The number of included patients per study ranged from 32 to 327 (median 112, interquartile range 70–142). Seven studies had a prospective study design. The median age of the patients ranged from 54 to 65 years, with the exception of one study with a median age of 46 [40], and 45–67% of the patients were of male gender. Most studies included patients with Ann Arbor stage I/II as well as stage III/IV; in two studies less than 50% of the patients had stage III or IV [37,45] and one study included patients with stage III and IV only [51]. First-line treatment regimens varied between and within the studies, but R-CHOP was the basic principle in all studies. Radiotherapy was given in most of the studies to selected patients (preplanned, e.g. in case of bulky disease or as a consolidation for residual lymphoma sites after treatment). Autologous stem cell transplantation had been planned upfront in three studies [44,48,50].
In Table 2 details of PET procedures, interpretation, and timing of interim PET between cycles are shown. Most studies performed an interim PET scan after two cycles of chemotherapy in all patients, one study made interim PET scans after only one course in all patients [43]; the remaining studies combined patient groups who had their interim assessment after a variable number of treatment cycles. The number of days after the previous treatment course at which the interim PET was acquired also varied between studies, mostly just before the next chemotherapy cycle, but the number of days after previous treatment was not reported by all studies. Twelve studies applied the Deauville scoring system and four the International Harmonization Project system [40,46,48,51]. The remaining studies used a custom scoring system [42,50,52,53].
The outcome measures of the included studies are shown in Table 3: 16 studies presented PFS and the other four studies reported EFS.The definitions of PFS and EFS for the different studies are presented in Supplemental Table 2. Percentages of positive interim PET scans ranged from 18.1 to 56.3%. Five original publications had reported univariate HRs, and four authors provided a (re)calculated HR upon our request. Two authors provided information about the number of events and P-values in order to use the method from Tierney et al. [28]. For one study we extracted the HR from the KM curves with numbers at risk provided by the
52