Quantification Of Early, Intermediate And Late Volumetric And Metabolic Response During Fractionated Radiation Therapy For Non-Hodgkin'S Lymphoma

To quantify early, intermediate, and late volumetric and metabolic response to fractionated radiation therapy using weekly 18F-FDG PET imaging for 10 non-Hodgkin lymphoma (NHL) patients and correlate them to clinical outcome. Ten patients with chemotherapy-refractory NHL (5 DLBCL, 1 FL, 2 FL transformed to DLBCL, 1 NK/T lymphoma, 1 Grey Zone lymphoma) planned for radical RT were prospectively entered into an IRB-approved study. PET/CT scans were acquired prior to RT (scan PT), and repeated weekly during the 3-4 week course of RT (scans T1w to T4w, delivered dose 35-40 Gy), and at 1 and 3 months afterwards (scans F1m and F3m). Patients received 5-6 scans on average. Four patients had more than one tumor treated and analyzed. For the analysis of the images, GTVs were contoured on all CT scans (total 14) and the maximum standard-uptake values to body weight (SUV) were determined in the coregistered PET images. Clinical outcome (local tumor response) at time of last clinical follow-up was quantified as local control (LC), stable disease (SD), and relapsed/progressive disease (PD). All SUV and volumetric response measures were defined as relative change per gray delivered dose. Early response was assessed between PT and T1w, intermediate response between T1w and T2w, and late response between F1m and F3m (where available). 4 patients showed clinical LC, 1 patient SD, and 5 patients PD. The early and intermediate responses (SUV and volumetric) were not correlated to clinical outcome. Treatment failure (SD and PD) was associated with significantly larger initial tumor volumes (Wilcoxon rank sum test, p = 0.03). High initial FDG uptake was not associated with treatment failure. Despite a gap between planning and start of the delivery, the early responses were larger than the intermediate responses, significant for the SUV (Wilcoxon paired signed rank test, p = 0.02, medians - 0.034 Gy-1 and - 0.017 Gy-1), and a trend for the volumes (p = 0.24, medians - 0.035 Gy-1 and - 0.019 Gy-1). The early and intermediate volume responses also showed some degree of negative correlation (Spearman's rho = - 0.33) whereas they did not for the SUV responses (rho = - 0.02). For late response assessment (F1m - F3m), all SD and PD patients showed increasing SUV and volumes, whereas for the CR patients these values were continuing to decrease. The difference between these two groups was significant (Wilcoxon rank sum test, p = 0.01 for SUV, p = 0.03 for volumes). These data in a small number of patients suggest that early and intermediate metabolic response during RT does not predict eventual local control, whereas a lack of a late metabolic and volumetric response between F1m and F3m, as well as large initial tumor bulk are associated with treatment failure.