In Patients with Aggressive Non-Hodgkin Lymphoma Treated with CHOP Therapy the Rapidity of Early Response, as Determined by Residual FDG Uptake, Does Not Impact on the Overall Prognosis.
Authors: Dann Eldad J. , Fuchs Eyal , Tamir Ada , Avivi Irit , Gaitini Diana , Israel Ora , Rowe Jacob M. , Bar-Shalom Rachel 
Published: April 2020

The role of interim FDG PET/CT for the evaluation of response and prediction of prognosis during the treatment of Hodgkin lymphoma has been demonstrated in several studies; however, its function in aggressive non-Hodgkin lymphoma has not been established. This study assesses the value of interim FDG-PET/CT performed after 2 cycles of chemotherapy for predicting response to CHOP-like regimen and prognosis of these patients. There was no change of therapy based on interim PET results. 85 patients (51 males, 34 females; median age 47, range 19–69 years) diagnosed and treated between 2001 and 2006 at the Rambam Medical Center with aggressive lymphoma were evaluated. Patients were treated either with standard CHOP or high-dose cyclophosphamide (3g/m2) CHOP with (n=52) or without (n=33) rituximab. All patients had PET/CT scan after 2 cycles and at the end of therapy. Results of interim PET/CT were considered negative or positive for active disease in the absence or presence of any abnormal FDG uptake. Positive pre-treatment PET/CT study was available in 71 patients. Baseline Gallium67 scan was performed in 9 patients and 5 patients had no baseline study. Only patients with a baseline scintigraphy were included in this analysis. Patients with a negative interim study were defined as negative (group A - 51 patients). Patients with positive interim study showing a decrease in the number or intensity of pre-therapy FDG abnormalities (≤50% of the initial visual uptake) were defined as having improved PET/CT (group B - 27 patients). PET/CT results after 2 cycles and at the end of therapy were assessed for overall (OS) and progression-free survival (PFS), estimated at 30 months. Median follow-up was 22 months (range 4–56 months). 61/85 patients (72%) achieved complete remission and 9/85 patients (10%) achieved partial remission after therapy. Twenty eight patients relapsed or had disease progression within 30 months, with PFS of 61% and OS of 88%. Interim PET was negative in 51 and improved in 27 patients. Tumor progression or relapse occurred in 14/51 (27%) and 9/27 (33%) of these patients, respectively. Thirty month PFS for low risk international prognostic index (IPI), intermediate risk (2) and high risk IPI (3–5) were 82%, 80% and 42%, respectively. Interim PET/CT after 2 cycles of therapy did not correlate with a difference in PFS or OS for patients with improved compared to those with a complete negative study outcome, treated by standard CHOP or CHOP-like protocol (Table). At the end of therapy PET/CT remained positive in 12 patients and became negative in 67 patients in groups A and B. In these two cohorts PFS was 64% and 70% and OS was 81% and 92%, respectively. These data suggest that, in contrast to Hodgkin Disease, an early PET/CT demonstrating residual FDG uptake may not have impact on the long-term outcome. Whether this is due to the different biology of these diseases needs to be determined.

30 month PFS 30 month OS Predictive value of study Interim PET with baseline PET or Gallium 67 scan (n=78) n % % % *NPV - negative predictive value; **PPV - positive predictive value Negative study: Group A (n=51) 37/51 68% 90% *NPV=73% Improved study: Group B (n=27) 18/27 60% 88% **PPV=33%