1. Patients
We collected data on lymphoma patients, who underwent 18F-FDG PET-CT imaging at the Shanghai Chest Hospital, Shanghai Changzheng Hospital and Dongfang Hospital from January 2015 to February 2020. According to the criteria for inclusion and exclusion, 97 patients with NHL were enrolled in this study, including 50 males and 47 females, aged 18–85 (54.3 ± 16.9) years. A total of 5 cases were Hodgkin’s lymphoma (HL), and the remaining were non-Hodgkin’s lymphoma (NHL). Among non-Hodgkin’s lymphoma, 57 cases were diffused large B-cell lymphoma (DLBCL), 8 were follicular lymphomas (FL), 7 were natural killer (NK)/T-cell lymphomas, 8 were peripheral T-cell lymphomas (PTCL), 4 were mucosa-associated lymphoid tissue (MALT), 4 were mantle cell lymphomas (MCL), and the remaining 4 were diagnosed as NHLs but the specific pathological type not clarified. According to the result of pathology, all the patients were enrolled according to the following criteria: (1) diagnosed by pathology, and detailed immunohistochemical results were included in the diagnosis; (2) untreated; (3) PET- CT imaging and pathological examination did not exceed 4 weeks as assessed by the same method; (4) the highest FDG uptake area in the lesion was coherent to that in the biopsy or operation area. Patients, who had undergone surgery or received chemotherapy, were excluded. Table 1 summarizes the characteristics of all included patients.
2. 18F-FDG PET/CT imaging and interpretation
2.1 Imaging method
All patients underwent staging 18F-FDG PET/CT before any treatment (local surgery or chemotherapy). In both hospitals, Philips GXL 16 PET-CT (Philips Medical Systems, Inc., Cleveland, OH, USA) was used as the imaging device. The imaging agent 18F-FDG was provided by Shanghai Atomic Kexing Pharmaceutical Co., Ltd. with radiochemical purity >95%. 18F-FDG was injected after at least 6 h fasting and the glucose level <10 mmol/L. The dose of 18F-FDG was 3.70–5.18 MBq/kg, and the images were acquired at 60±10 min after the injection. Written consent was obtained from all hospitals before the study.
2.2 Detection of metabolism activity of lymphoma
The SUVmax of lymphoma was obtained by the average of 4–8 consecutive layers of lesions on PET images. For every layer, a manual region of interest (ROI) over the area of maximum activity was drawn, and SUVmax was estimated as the highest SUV of the pixels within the ROI. In the case of single lesions, the SUVmax was measured directly, while for multiple lesions, the highest SUVmax value in the whole body was considered as the SUVmax value of the patient, and if the intake was negative value, the SUVmax value of the largest lesion in the whole body was considered as the SUVmax value of the patient.
2.3 Immunophenotype, clinical information, and gene information
Immunohistochemistry was used for detecting the samples. The specimens were fixed in 10% neutral buffer formaldehyde solution, embedded in paraffin, and sliced into 4-μm-thick sections. The staining was performed for molecules Bcl-6, Bcl-2, CD10, CD23, Mum-1, Pax-5, Ki67, CD2, CD3, CD5, EMA, CD138, CD30, and ALK, and the results were determined based on the number of positively stained cells recorded. The results were recorded as follows: negative (-): <10%; weakly positive (+): 10–30%; moderately positive (++): 30–75%; strongly positive (+++): >75%; an expression of ≥10% is considered positive. The clinical characteristics of the patients, including age (according to the age division regulation of WHO, the patients were divided into youth group with age <44 years, middle-age group with age 45–59 years, and elderly group with age >60 years), gender (male and female), tumor clinical grade stage (stage I/II was divided into low-grade group and stage III/IV was classified into the high-grade group), presence of bone metastasis, and IPI score (low-risk, IPI 0–2 or aaipi 0-1 and high-risk, IPI 3–5 or aaipi≥2) were assimilated. Consecutively, the genotype of the patients was assessed (GCB or non-GCB).
2.4 Statistical analysis
All statistical analyses were conducted using SAS 9.2 software (SAS Institute, Carey, NC). The statistical significance of SUVmax between pathological subtype groups, different levels of molecule expression groups and different gene expression groups was analyzed by Fisher’s exact test or Student’s t-test and Wilcoxon two-sample test. The correlation between SUVmax and Ki-67 was evaluated by Pearson’s correlation test. p<0.05 was considered statistically significant.