Page 61 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Predictive value of interim PET in DLBCL
confirm the predictive value of interim PET in DLBCL patients for PFS and EFS. Our pooled estimated HR was lower than reported in a previous meta- analysis (2013) [16] which reported a pooled estimated HR of 4.4 (95% CI 3.34– 5.81) from nine studies investigating the prediction of PFS by interim PET. They used a similar approach to extract HRs; however, they had less strict inclusion criteria with regard to the NHL types and follow-up period, both visual and semi- quantitatively assessed PET scans were included, and no subgroup analyses were performed. Despite these differences, their HR result is within the range of our calculated 95% prediction interval and the amount of statistical
heterogeneity (I2 = 39%) amongst studies was comparable. Other meta-analyses did not compare the HRs between studies [15,17,18].
We have no explanation for the statistically significant higher HR for studies (n = 5) that used both PET/CT- and PET standalone systems compared to studies that used an integrated PET/CT system.
The trend towards a higher HR for the studies with both DLBCL and PMBCL patients compared to studies with only DLBCL patients could not directly be explained by the inclusion of both lymphoma subtypes. The fact that two out of three studies with both DLBCL and PMBCL patients [52,53] used custom criteria for the interpretation of the interim PET could possibly explain this. These meta-regression results should be interpreted with caution, as the number of studies per subgroup were relatively low (Supplemental Table 3) which precludes multivariate meta-regression analysis.
Diagnostic 2 × 2 contingency tables of interim PET showed wide ranges between studies for sensitivity,specificity,and positive predictive values at 2 years.The ranges reported in other systematic reviews and meta-analyses were hard to compare as they used the complete follow-up period for their calculations, included studies with follow-up periods less than 24 months, and used other statistical methods [15,17,18]. We decided to truncate at 2 years, as most clinically relevant events occur during this period. Moreover, the widely ranging complete follow-up periods of individual studies might introduce bias.
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