End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making

Christopher Melani, Ranjana Advani, Mark Roschewski, Kelsey M Walters, Clara C Chen, Lucia Baratto, Mark A Ahlman, Milos D Miljkovic, Seth M Steinberg, Jessica Lam, Margaret Shovlin, Kieron Dunleavy, Stefania Pittaluga, Elaine S Jaffe, Wyndham H Wilson, Christopher Melani, Ranjana Advani, Mark Roschewski, Kelsey M Walters, Clara C Chen, Lucia Baratto, Mark A Ahlman, Milos D Miljkovic, Seth M Steinberg, Jessica Lam, Margaret Shovlin, Kieron Dunleavy, Stefania Pittaluga, Elaine S Jaffe, Wyndham H Wilson

Abstract

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (clinicaltrials.gov identifier 00001337).

Trial registration: ClinicalTrials.gov NCT00001337.

Copyright© 2018 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of event-free and overall survival of all patients and by study group. DA-EPOCH-R was administered to a total of 93 patients; 59 treated on the NCI prospective study and 34 treated on the retrospective Stanford study. (A). Event-free survival 90.6% (95% CI, 81.8-95.2) at 8-years for the total cohort. (B). Overall survival 94.7% (95% CI, 86.3-98.0) at 8-years for the total cohort. (C). Event-free survival 90.6% (95% CI, 78.8-96.0) for the NCI cohort and 91.0% (95% CI, 74.6-97.0) for the Stanford cohort (P=0.71) at 8-years. (D). Overall survival 95.6% (95% CI, 83.5-98.8) for the NCI cohort and 93.8% (95% CI, 77.5-98.4) for the Stanford cohort (P=0.30) at 8-years.
Figure 2.
Figure 2.
Kaplan–Meier estimates of event-free and overall survival by Deauville group. Event-free survival and overall survival according to EOT FDG-PET Deauville group. (A). Event-free survival 96.0% (95% CI, 84.8-99.0) vs. 71.1% (95% CI, 43.6-86.9) (P=0.0010) for Deauville 1-3 (blue curve) and Deauville 4-5 (red curve), respectively, at 8-years. (B). Overall survival 97.7% (95% CI, 84.6-99.7) vs. 84.3% (95% CI, 56.5-95.0) (P=0.0115) for Deauville 1-3 (blue curve) and Deauville 4-5 (red curve), respectively, at 8-years. (C). Event-free survival 93.3% (95% CI, 82.8-97.5) vs. 50.0% (95% CI, 15.2-77.5) (P=0.0003) for Deauville 1-4 (blue curve) and Deauville 5 (red curve), respectively, at 8-years. (D). Overall survival 95.9% (95% CI, 84.5-99.0) vs. 75.0% (95% CI, 31.5-93.1) (P=0.029) for Deauville 1-4 (blue curve) and Deauville 5 (red curve), respectively, at 8-years.
Figure 3.
Figure 3.
Tumor reduction by end-of-treatment CT. Reduction of the bi-dimensional product of the largest mediastinal mass for the 89 patients with complete tumor measurements by EOT CT. All patients had reduction in tumor bi-dimensional product and there was no relationship between EOT tumor reduction and EOT FDG-PET Deauville score. No difference in tumor reduction was demonstrated between patients with (N=6, red arrows) and without (N=83) treatment failure; Median reduction 92% (range, 65-99) vs. 93% (range, 62-100), respectively.
Figure 4.
Figure 4.
Evolution of serial FDG-PET imaging. Heatmap depiction of (A). SUVmax, and (B). Deauville score, over time in the 20 non-progressing patients with a positive EOT FDG-PET scan. Heatmap depiction of (C). SUVmax, and (D). Deauville score, over time in the 6 patients with treatment failure. FDG-PET scans performed prior to the EOT FDG-PET are listed as negative numbers with those following the EOT FDG-PET listed as positive numbers. The EOT FDG-PET scan is bordered by black dashed lines. FDG-PET scans performed following salvage intervention are shaded in black.

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