Prospective International Cohort Study Demonstrates Inability of Interim PET to Predict Treatment Failure in Diffuse Large B-Cell Lymphoma

Abstract

The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.

Protocol for qRT-PCR analysis from formalin fixed paraffin embedded tissue sections from diffuse large b-cell lymphoma: Validation of the six-gene predictor score

“…This method and markers are accepted as gold standard and reliable for the subclassification. These patients were a subset of the cohort of a Coordinated Research Project funded by the IAEA where the use of interim PET was investigated in order to risk stratify patients [9]. CD20 immunohistochemistry was performed for all of the cases for indication of anti CD20 therapy.…”

Retrospective Analysis of a New Prognostic Score for Diffuse Large B-Cell Lymphoma Based on Interim Positron Emission Tomography-Computed Tomography

“…However, Mamot et al [26] analyzed 92 patients with DLBCL and reported a recurrence rate of 39.1% in patients with a negative interim PET-CT, which is similar to the recurrence rate of 30%-40% observed after treatment [27, 28]. In contrast, Carr et al [29] reported a recurrence rate of only 10% if the interim the PET-CT was negative. These differences may be attributed to different treatments, sensitivities of the tumor cells, histologies, stages, and completion times of the interim PET-CT examination [30] as completion of interim PET-CT in an interval of at least 3 weeks may reduce the proportion of false-negative results [31].…”

Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for Early Interim Response Assessment in Advanced-Stage B-Cell Lymphoma

“…In some studies, iPET provided meaningful prognostic information (3,5,8,9), but in other studies, the end of treatment scan proved more informative (6,7,20). We previously (4) reported a low PPV of FDG iPET, at least in part resulting from rituximab-induced inflammation in the R-CHOP regimen (10) and from the use of iPET interpretation criteria that are now obsolete (12,21).…”