Prognostic values of interim and post-therapy ¹⁸F-FDG PET/CT scanning in adult patients with Burkitt’s lymphoma

Burkitt’s lymphoma is a rare and highly aggressive type of B-cell non-Hodgkin’s lymphoma (NHL). It is divided into endemic, sporadic, and immunodeficiency-associated variants [1–3] and has an intimate relationship with Epstein-Barr virus infection [4, 5]. Burkitt’s lymphoma accounts for 40% of pediatric lymphomas and less than 5% of adult lymphoma cases [6]. Highly aggressive neoplasms are potentially curable with short and intensive treatment schedules, with survival rates of up to 90% [2, 7, 8].

Fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) are used to stage and monitor the response of most lymphomas to therapy during clinical treatment, and their use has become increasingly prevalent [9–11]. Recent studies have demonstrated the prognostic value of interim PET or PET/CT performed after 1–4 cycles of chemotherapy for some subtypes of lymphoma. A positive early interim ¹⁸F-FDG PET was shown to identify poor responders in patients suffering from advanced-stage or extranodal disease [12]. In a prospective study of patients with high-risk diffuse large B-cell lymphoma (DLBCL), the reduction in the maximum standardized uptake values (∆SUVmax) between the baseline measurement and the measurements after 2 and 4 cycles of treatment was feasible for high-risk DLBCL and more accurately predicted the patient’s outcome than visual analysis [13]. In a recent report regarding patients with mature T-cell and natural killer (NK) cell lymphomas, both interim and post-therapy PET/CT SUVmax were independent prognostic predictors [14]. However, studies of the prognostic value of PET or PET/CT in patients with Burkitt’s lymphoma have been limited [15–17]. The purpose of this study was to explore the prognostic value of interim and post-therapy PET/CT in adult patients with Burkitt’s lymphoma.

Whole-body scans were performed on a combined PET/CT system (Discovery ST, with a 16-slice CT component; GE Healthcare Bio-Sciences Corp, Piscataway, NJ, USA). All patients were instructed to fast for at least 6 h before the administration of 5.55 MBq/kg ¹⁸F-FDG. Whole-body acquisition began 45–60 min after ¹⁸F-FDG injection, and the patient was scanned from the groin up to the head at the mid-thigh level with a 5-min acquisition per bed position. The CT acquisition was obtained at 140 kV and 150–160 mA with a 5-mm section thickness. An Entegra or Xeleris (GE Healthcare, NJ, USA) workstation was used for the registration and fusion of the acquired images from the PET and CT scans. Corrections were applied for random effects, geometry, attenuation, and scatter.

Burkitt’s lymphoma is usually indicated by intense ¹⁸F-FDG uptake in untreated lymphomatous lesions due to a high glycolytic rate. Accurate initial staging plays an important role in the selection and duration of treatment. The roles of ¹⁸F-FDG PET-PET/CT in staging, treatment response evaluation, and prognostic prediction for many types of lymphomas have been explored [12–14]. However, there are very limited data available on the role and prognostic value of interim and post-therapy ¹⁸F-FDG PET/CT in adult Burkitt’s lymphoma patients.

Almost all studies of PET/CT in Burkitt’s lymphomas have involved individual cases. The prognostic value of mid-therapy and post-therapy PET/CT has rarely been reported. Barrington et al. [20] reported that a 32-year-old Burkitt’s lymphoma patient presented with intense ¹⁸F-FDG uptake in the bone marrow, bowel, and peritoneum on PET-only scan. A repeat PET scan was negative 6 days after the commencement of chemotherapy [20]. Chander et al. [21] reported a 34-year-old male patient with PET-positive head and neck Burkitt’s lymphoma who underwent a slight decrease in SUVmax at the post-therapy follow-up PET, suggesting a PR to the chemotherapy. Ford et al. [22] demonstrated a false-positive restaging PET scan in the spleen of a 58-year-old man with Burkitt’s lymphoma. Wang et al. [23] reported a 7-year-old boy with ¹⁸F-FDG-avid lesions in the pleura that were identified by PET/CT, lesions in the peritoneum, mesentery, and omentum with marked ascites, and mesenteric nodules and renal involvement as demonstrated by CT.

In the present study, 23 patients received baseline PET/CT examinations, and these patients were highly ¹⁸F-FDG-avid at initial presentation, with a median SUVmax of 18.3. The highly aggressive nature of Burkitt’s lymphoma leads to intense ¹⁸F-FDG uptake during the initial stage. These results are consistent with those of Schöder et al. [24], who suggested that the intensity of ¹⁸F-FDG uptake was generally higher in aggressive lymphoma than in indolent lymphoma. After 2–8 cycles of chemotherapy with the main CODOXM/IVAC regimen, more than 90% of patients achieved a good response, reflecting the chemosensitivity of the disease. ¹⁸F-FDG uptake was decreased or even negative during remission after chemotherapy. Karantanis et al. [25] reported that ¹⁸F-FDG PET examinations in most Burkitt’s lymphoma patients were negative during or immediately after therapy, which is consistent with our findings. Many previous studies have revealed the value of mid-therapy and post-therapy PET/CT in predicting disease progression. In a retrospective study of 85 patients, Hutchings et al. [26] showed that ¹⁸F-FDG PET after 2–3 cycles of chemotherapy had a high negative predictive value in the early-stage diseases and a high positive predictive value in the advanced-stage disease, independent of other known prognostic factors. Hutchings et al. [12] demonstrated that early interim ¹⁸F-FDG PET was a stronger predictor of patient outcome than the known prognostic factors and that a positive early interim ¹⁸F-FDG PET was highly predictive of progression in patients with advanced-stage or extranodal disease. A study of 85 patients with high-risk DLBCL revealed that the outcomes did not significantly differ for PET2 and PET4 scans that were visually positive or negative [13]. According to our data on the relationship between PET/CT and survival, patients with positive post-therapy PET/CT results tended to have poorer outcomes than patients with negative post-therapy PET/CT results, but this difference was not significant. However, these studies had limited sample sizes, and more definitive answers to this question could be obtained through large-scale studies.

We investigated the relationships between PET/CT results and prognostic factors. The results showed different ECOG scores in patients were significantly associated with the baseline PET/CT SUVmax, which is consistent with the results by Chihara et al. [27].

Various factors are related to the scan quality. Effective control should be mandatory, and the injection-to-scanning time should be fixed. To a lesser extent, SUVmax analysis can generate false-positive results because ¹⁸F-FDG uptake is not only specific for tumor cells but also observed in inflammatory and infectious processes or after bone marrow stimulation. Quantitative assessment is likely a more objective and effective way to interpret PET/CT results. Numerous previous studies have emphasized the percentage of SUVmax reduction. Itti et al. [28] proposed that an optimal cutoff of 72.9% SUVmax reduction from the baseline to the end of therapy yielded a higher estimated 2-year event-free survival rate in patients with a reduction of more than 72.9% (79% vs. 32%). Casasnovas et al. [13] and Lin et al. [29] regarded ∆SUVmax (between the baseline PET and mid-therapy PET) analysis as a feasibly better predictor of outcome than visual analysis for high-risk DLBCL. Previous studies have established several cutoff points for predicting survival using receiver-operating characteristic analysis. It was found that a ∆SUVmax ≤91.8% was the best cutoff point [30], whereas a ∆SUVmax of >70% prompted favorable prognosis [31]. Combined with previous studies, we defined ∆SUVmax of 25%, 50%, and 75% as cutoff points. In the ∆SUVmax analysis, a 50% ∆SUVmax from the baseline to the end of therapy was an optimal cutoff point. ∆SUVmax of greater than 50% led to a favorable predictive value for OS compared with that of 50% or less. The OS tended to be longer in patients with ∆SUVmax >75% than in those with ∆SUVmax ≤75% although the difference was not significant. Due to the limited survey samples, a long-term and further study should be conducted to help us understand the subject comprehensively and objectively.

In conclusion, our results indicated that ¹⁸F-FDG uptake was intense in Burkitt’s lymphoma, and the ∆SUVmax was significantly different between the interim and post treatment. The patient’s ECOG score was significantly associated with the patient’s baseline PET/CT SUVmax. A post-therapy PET/CT ∆SUVmax of 50% was an optimal cutoff for predicting OS. Longer follow-up time and an analysis of a larger cohort are warranted to confirm the prognostic value of mid-therapy and post-therapy PET/CT in Burkitt’s lymphoma patients. Furthermore, further work should be perform to unify the response criteria and further research is needed to assess the prognostic value.