Prognostic Value Of ¹⁸F-FDG PET/CT In Diffuse Large B-cell Lymphoma

ObjectiveDiffuse large B-cell lymphoma?DLBCL?is a group of common hematological malignancy with high heterogeneity.The cure rate of DLBCL has improved with R-CHOP chemotherapy.However there are a considerable proportion of patients who are not cured either due to refractory disease or relapse.An accurate prognosis method,which can afford risk stratification and screen patients with similar prognosis,help patients achieve the best effect through personalized treatment as early as possible. With the wide use of PET/CT for patients with lymphoma in China,the establishment of a prognostic index based on the imaging is an urgent problem to be solved.In the rituximab era,our study is expected to develop a new prognostic index based on the¹⁸F-FDG PET/CT,which is performed at baseline,interim and end of the treatment.According to this index,the prognostic prediction can be improved through more meticulous risk stratification for DLBCL patientsMethodsDLBCL patients were collected from January 2008 to December 2016 in Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine,all of them having three PET/CT scans.The initial treatment for all patients was R-CHOP.The clinical data were collected including age,gender,IPI score,Ann Arbor stage,B symptoms,performance status,bulky,extra-nodal involvement,LDH,?2-microglobulin,pathological subtype.The metabolic parameters of three PET/CTs were all recorded.The end points were progression-free survival?PFS?and overall survival?OS?.Correlation analysis was used between clinical data and image metabolic parameters.The ability to assess the prognosis of DLBCL patients with PET/CT metabolic parameters was evaluated by ROC analysis.The cut-off value was also obtained.A new prognostic model was established by the combination of baseline PET/CT metabolic parameters and interim therapeutic response.The prognostic value of each index was analyzed by Kaplan-Meier method and Cox regression model.ResultsA total of 116 patients were enrolled in this study.The ratio of men and women was 1:1.32,the average age was 57.87±1.89 years,and the average follow-up time was 37.74±25.84 months.At the end of the follow-up,there were 89 cases of disease-free,27 cases of disease progression,7 cases of death.Part One:ROC analysis showed that the area under the curve?AUC?of baseline SUVmax,MTV and TLG was 0.486?p=0.848?,0.756?p=0.000?and 0.726?p=0.000?,respectively.MTV and TLG had the ability to predict the recurrence of DLBLC,and the corresponding cut-off values were 56.50 and 430.35 respectively.The MTV and TLG in the progression group were significantly higher than those in the progression free group?MTV 311.4 vs 48.9,p=0.000,TLG 2659 vs 390.6,p=0.000?,and SUVmax had no significant difference between the two groups?p=0.561?.Through the cut-off value obtained by ROC,the MTV and TLG were divided into two groups of high and low,and SUVmax was divided into high and low two groups with the median value.The probability of disease progression in high MTV and TLG groups was significantly higher than that in low MTV and TLG groups?MTV?²=18.284,p=0.000,TLG?²=16.175,p=0.000?.There was no significant difference in the incidence of disease progression and progression free between two SUVmax groups.There were significant differences in the 5 year PFS between the high and low groups of MTV and TLG?MTV 51.2%vs 91.9%,p=0.000;TLG 50.8%vs 94.1%,p=0.000?.There was no statistically significant difference in PFS and OS between the high and low groups of SUVmax.The following clinical parameters could predict prognosis effectively:the IPI score,Ann Arbor stage,B symptoms,performance status,extra-nodal involvement site,bulky,LDH,?2-microglobulin;all of above clinical parameters were significantly related to MTV and TLG.Multivariable analysis showed that baseline TLG?HR 14.191,95%CI 1.867-107.839,P=0.000?was the only independent predictor for PFS in DLBCL patients.Part Two:Metabolic parameters in two PET/CTs?interim and end of treatment?had a significant correlation.Correlation coefficients of two PET/CTs'SUVmax,MTV and TLG were 0.653?p=0.000?,0.206?p=0.027?,0.339?p=0.000?;Correlation coefficient of?SUVmax,?MTV,?TLG was 0.630?p=0.000?,0.912?p=0.000?,0.955?p=0.000?.There were 104 cases?89.7%?with the same evaluation of DS between two PET/CTs,and the correlation coefficient was 0.733?p=0.000?.Through ROC analysis,SUVmax,MTV,TLG and?SUVmax,?MTV,and?TLG of the two PET/CTs all had the ability to judge the recurrence and progress.5 years PFS and OS for CR patients evaluated by interim DS was significantly higher than that of non-CR group?PFS 83.1%vs 35.9%,p=0.000,HR 5.969,95%CI 2.753-12.939,p=0.000;OS 95.7%vs 75.5%,p=0.003,HR 8.161,95%CI 1.581-42.137,p=0.012?.Baseline TLG and interim?SUVmax were combined for further stratified analysis:The baseline TLG was divided into high and low groups with the cutoff value of 430.35,while the interim?SUVmax was divided into high and low groups with the cut-off value of 54.6%.In the low TLG group,there was no significant difference in the 5 year PFS and OS between high and low?SUVmax group?PFS90.6%vs 94.1%,p=0.981;OS 100%vs 92.9%,p=0.137?.In the high TLG group,the5 year PFS and OS of the high?SUVmax group were significantly higher than those of the lower?SUVmax group?PFS 63.7%vs 0%,p=0.000;OS 91.3%vs 64.3%,p=0.010?.The HR of high TLG and high?SUVmax group is 5.531?95%CI1.241-24.656,p=0.025?,and the HR of high TLG group and low?SUVmax group is70.205?95%CI 8.727-564.783,p=0.000?.ConclusionClinical factors such as IPI,Ann Arbor staging,B symptoms,performance status,LDH,?2-microglobulin,extra nodal involvement and bulky were effective indicators for predicting prognosis of DLBCL patients.The metabolic parameters MTV and TLG of baseline PET/CT were significantly correlated with the clinical factors with prognostic significance.MTV and TLG are more effective in predicting the prognosis of DLBCL patients than SUVmax.Baseline TLG is the only independent predictor for the prognosis of DLBCL patients.There was a significant correlation of the metabolic parameters and the DS score between interim and end of treatment PET/CTs.Interim PET/CT had the effective ability to predict the prognosis of DLBCL so that it could replace the examination after the end of the treatment.The new prognosis model can achieve more detailed risk stratification for DLBCL patients and predict prognosis accurately through the combination of baseline tumor load and interim evaluation of therapeutic response.