The Outcome of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab-CHOP (R-CHOP) Is Not Predicted by 18-FDG-Positron Emission Tomography/Computerized Tomography (PET) Performed at Intermediate In-Course Evaluation, but Only by PET Assessed at the End of Therapy.
Authors: Vitolo Umberto , Chiappella Annalisa , Bellò Marilena , Passera Roberto , Botto Barbara , Castellano Giancarlo , Ciochetto Chiara , Ferrero Simone , Frairia Chiara , Franceschetti Silvia , Giunta Francesca , Ladetto Marco , Menga Massimo , Nicolosi Maura , Priolo Giorgio , Puccini Benedetta , Rigacci Luigi , Salvi Flavia , Vaggelli Luca , Pregno Patrizia , Bisi Gianni 
Published: October 2019

Abstract
Abstract 2819

Background.
Whilst positron emission tomography has a clear role in the evaluation of the final response to therapy in DLBCL, its predictive value at an interim time-point in this setting is controversial. Criteria of interpretation of Interim PET are yet to be standardized and the visual analysis of PET results by dichotomous evaluation is difficult to apply. Aim of the study was to determine the predictive value of interim (I-PET) and final PET (F-PET) on Progression Free Survival (PFS) in a cohort of DLBCL patients treated with R-CHOP.

Patients and Methods.
From April 2004 to October 2009, 88 DLBCL patients at diagnosis, at five Hematology Departments were included. All patients were treated with standard chemo-immunotherapy R-CHOP for 6 or 8 courses; therapy was performed as planned and never modified by I-PET results. Thirty-one patients received R-CHOP21, 57 R-CHOP14. Involved Field radiotherapy (IF-RT) for areas of bulky disease was delivered to 14 patients regardless of PET results. G-CSF was given to 21/31 R-CHOP21 patients and in all 57 R-CHOP14. PET scan was performed in all patients at diagnosis, during and at the end of therapy: all results were centrally reviewed and defined as positive or negative by visual dichotomous response criteria according to the First Consensus Conference (Deauville 2009). PFS and overall survival (OS) were analyzed by the Cox proportional hazards model, comparing the two arms by the Wald test with 95% CI. Due to small number of events, the Cox proportional hazards model was used in two independent bivariate analyses to assess the effect of different prognostic factors on PFS.

Results.
Clinical features were: median age 55 years (18-80); males/females 41/47; stages I-II/III-IV 29/59; Low/Low Intermediate International Prognostic Index score (IPI 0–2) 53 and Intermediate/Intermediate High/High IPI score (IPI 3–5) 35. I-PET was performed after two R-CHOP in 58 patients, after 3 or 4 in 30. At the end of therapy, 79 patients (90%) achieved a complete response (CR) and nine (10%) were non responders. Sixty-three patients (72%) were negative and 25 (28%) positive at I-PET; 77 patients (88%) were negative and 11 (12%) positive at F-PET; 15/25 (60%) I-PET positive patients converted at F-PET, while only 1/63 (2%) I-PET negative case had a positive F-PET (Table 1). The concordance between clinical CR and F-PET negativity was 97%: two patients, whilst in CR, had false positive final scans due to parotid and colorectal carcinoma (histologically confirmed) respectively. We evaluated the prognostic impact of PET results on the outcome. With a median follow-up of 26.2 months, 2-year OS and 2-year PFS were 91% and 77% respectively. There was a weak correlation between PFS and I-PET results: rates were 85% in negative and 72% in positive patients (p.05) (Figure 1A). Conversely F-PET strongly predicted PFS (p <.001): 83% in negative and 64% in positive patients. (Figure 1B). In univariate analysis for PFS, elevated LDH value, ≥ 2 extranodal sites, bone marrow involvement, 3–5 IPI score, I-PET and F-PET positivity were predictors of lower PFS rates. Use of G-CSF or number of R-CHOP courses before I-PET did not influence PFS rates. Two independent bivariate analyses by Cox models were performed to properly evaluate the prognostic role of I-PET and F-PET results. In model 1, only F-PET retained its prognostic value compared to I-PET with an adjusted HR of 5.03 (95% CI 1.37–18.43, p=.015) vs 1.27 (95% CI 0.40–4.03, p=.691). In model 2, both Final-PET (HR 4.54, 95% CI 1.68–12.31) and IPI score (HR 5.36, 95% CI 1.91–15.05, p=.001) remained independent prognostic factors for PFS. (Table 2).

Conclusions.
Our results indicate that in DLBCL patients treated with first-line R-CHOP, a positive I-PET does not predict a worse outcome: indeed the majority of I-PET positive patients achieved CR at the end of therapy. Conversely, F-PET results strongly correlate with PFS. Larger prospective studies and standardization of criteria for interim PET evaluation are needed to better assess the prognostic value of interim PET in DLBCL patients.

Disclosures:
No relevant conflicts of interest to declare.