The Role Of PET Imaging For Predicting Treatment Failure In Primary Mediastinal B-Cell Lymphoma
Authors: Nagle Sarah J. , Chong Elise A. , Chekol Seble , Shah Nirav N. , Nasta Sunita D. , Glatstein Eli , Plastaras John P. , Torigian Drew , Schuster Stephen J. , Svoboda Jakub 
Published: October 2019

Abstract

Introduction
Primary mediastinal B-cell lymphoma (PMBL) is a distinct clinicopathologic subtype of diffuse large B-cell lymphoma (DLBCL). The optimal management of PMBL remains controversial. While R-CHOP with or without radiation therapy (RT) is established as a potentially curative regimen in this setting, there have been concerns about a subgroup of PMBL patients (pts) who are refractory to R-CHOP (Soumerai et al, Leuk Lymphoma, 2013). Efforts to improve outcomes led to the use of aggressive chemotherapy regimens such as dose-adjusted R-EPOCH despite the lack of a randomized trial demonstrating benefit (Dunleavy et al, N Engl J Med., 2013). Identifying early predictors of R-CHOP treatment failure may inform risk-adapted treatment strategies in PMBL. 18F-fluorodeoxyglucose-positron-emission tomography fused with CT (PET-CT) has been used as a predictor of treatment failure in Hodgkin lymphoma and DLBCL, but the role in PMBL has not been well described.

Methods
We conducted a retrospective analysis using our institutional database of PMBL pts treated with R-CHOP with or without RT. Overall survival (OS) and progression-free survival (PFS) for the entire cohort and for those with positive versus negative interim and post-treatment PET-CT were calculated by Kaplan Meier method (STATA version 12). PET-CT scans were graded as positive or negative based on the consensus criteria from the International Harmonization Project (IHP) (Juweid et al, J Clin Oncol, 2007). We also determined positive predictive value (PPV) and negative predictive value (NPV) for interim and post-treatment PET-CTs.

Results
We identified 26 pts with PMBL treated with R-CHOP at our institution between 11/2001 and 5/2013. The median age at diagnosis was 36 years (range 18-57 years). Eight pts had stage I, 15 had stage II, 0 had stage III and 3 had stage IV PMBL. At diagnosis, IPI was low-risk in 21, low-intermediate in 2 and high-intermediate in 3 pts. LDH level was elevated in 18 pts (69%). Thirteen pts (50%) had bulky disease (> 10 cm). After R-CHOP, 19 pts (73%) underwent consolidative RT. At a median follow-up of 35.7 months, median OS was 94.7% (95%CI: 68.1-99.2%) and PFS was 75.3% (95%CI: 52.9-88.1%) for the entire cohort. The PFS and OS at 1 year was 75.3% and 100%, respectively. Six pts (23%) had progressive disease (PD): 5 progressed during or immediately following treatment with R-CHOP (prior to RT). Four pts with PD underwent high dose chemotherapy and autologous stem cell transplantation (ASCT) and all achieved complete response (CR). Only 1 of 26 pts died of progressive PMBL. Two patients required steroids for radiation pneumonitis which resolved.
Twenty-two pts (85%) underwent an interim PET-CT following 2 cycles of R-CHOP (N=12), 4 cycles of R-CHOP (N=20) or at both time points (N=10). The PFS at 1 year for pts who had a positive interim PET-CT after either cycle 2 or cycle 4 (N=17) versus pts who had negative interim PET-CT (N=5) was 68.9% vs. 100%, respectively. The NPV of interim PET-CT was 100%, but the PPV was low at 43%. Fifteen pts (58%) underwent a PET-CT at the completion of therapy. Nine (60%) had a negative scan and did not relapse. Six (40%) had a positive scan at the completion of therapy: 3 pts with PD were treated with salvage therapy, one underwent a biopsy that was negative and has not relapsed, and 2 underwent sequential PET-CT scans until resolution of the abnormality. The PFS at 1 year for pts who had a positive post-treatment PET-CT (N=6) versus pts who had a negative post-treatment PET-CT (N=9) was 50% vs. 100% respectively. The NPV for a post-treatment PET-CT was 100% and the PPV was 50%.

Conclusion
In our cohort, pts with PMBL had excellent outcomes using R-CHOP with or without RT. Those who failed primary therapy were salvaged with ASCT. There were no relapses after 6 months of completing primary therapy. Negative interim or negative post-treatment PET-CT identified patients who achieve long term remission. However, positive PET-CT in this setting is of limited clinical value in predicting treatment failure. Distinctive characteristics of this DLBCL subtype, including bulky presentation, localization to mediastinum, and necrosis, probably contribute to the high false positive rate, limiting the utility of IHP criteria. We are actively studying other factors (pathological, clinical, and radiographic) which would allow early prediction of therapeutic outcome and the ability to tailor first line therapy for PMBL.

Disclosures:
No relevant conflicts of interest to declare.