| Part 1:The prognostic efficacy of interim 18F-FDG PET/CT,S-IPI,R-IPI and NCCN-IPI in predicting the prognosis of patients with diffuse large B-cell lymphomaObjective:The current study aims to explore the prognostic efficacy of interim 18F-FDG PET/CT,standard international prognostic index(S-IPI),revised-IPI(R-IPI)and enhanced-IPI(NCCN-IPI)in predicting the prognosis of patients with diffuse large B-cell lymphoma(DLBCL)in the rituxima era.MethodsOne hundred and eighty-five patients(116 males,69 females;average age 49(16-82)years)with pathologically confirmed DLBCL from January 2004 to January 2014 were enrolled in this retrospective study.All patients were classified of risk by S-IPI,R-IPI,NCCN-IPI and all were received 18F-FDG PET/CT scans before and after 4 cycles of chemotherapy.The risk groups of S-IPI,R-IPI and NCCN-IPI were reclassified by using interim 18F-FDG PET/CT.Interpretations were evaluated for progression-free survival(PFS)and overall survival(OS)prediction.χ2 test,Kaplan-Meier analysis and Cox regression models were used for data analysis.Results:With a median follow-up of 27(2-146)months,the 2-year PFS and OS were 60.3%and 80.8%,respectively.The 2-year PFS and OS were 82.3%and 96.3%in the I-PET/CT negative group(113 cases).In the I-PET/CT positive group(72 cases),the 2-year PFS and OS were 22.9%and 55.0%;respectively.Both PFS and OS have statistically significance(χ2=66.66,P<0.01 and χ2=33.11,P<0.01).In the S-IPI risk stratification,the 2-year PFS and OS were 73.6%and 89.8%in the low risk group(score 0-2)which had 114 patients.71 patients were in the high risk group(score 3-5)and the 2-year PFS and OS were 36.8%and 65.6%,respectively.Both PFS and OS have statistically significance(χ2=20.86,P<0.001 and χ2=13.39,P<0.01).In the S-IPI low risk group,85 patients were PET negativity,29 patients were PET positivity.The 2-year PFS were 87.8%and 30.8%,respectively(χ2=35.52,P<0.01).The 2-year OS were 97.6%and 65.0%,respectively(χ2=11.88,P<0.01).In the S-IPI high risk group,28 patients were PET negative and 43 patients were PET positive.The 2-year PFS were 65.8%and 17.8%,respectively(χ2=17.33,P<0.01).The 2-year OS were 87.2%and 48.3%,respectively(χ2=9.95,P<0.01).In the R-IPI risk stratification,there were 37 patients in the very good risk group(score 0),79 patients in the good risk group(score 1-2)and 71 patients in the poor risk group(score 3-5).Significant differences of PFS and OS were observed among these groups(χ2=27.55,P<0.01 and χ2=18.16,P<0.01,respectively).In the very good risk group,2 patients were I-PET/CT positivity and 33 patients were I-PET/CT negativity.No significant differences of PFS and OS were observed between these two groups(χ2=0.28,P=0.597 and)χ2=0.07,P=0.785,respectively).In the good risk group,52 patients were PET negativity,27 patients were PET positivity.The 2-year PFS and OS were 76.8%and 96.1%,respectively(χ2=23.15,P<0.001).In the poor risk group,28 patients were PET negative and 43 patients were PET positive.The 2-year PFS were 65.8%and 17.8%,respectively(χ2= 7.33,P<0.001).The 2-year OS were 91.8%and 48.4%,respectively(χ2=7.92,P=0.005).In the NCCN-IPI risk stratification,the 2-year PFS and OS were 69.8%and 87.6%in the low risk group(score 0-3)which had 128 patients.57 patients were in the high risk group(score 4-8)and the 2-year PFS and OS were 36.7%and 65.0%,respectively.Both PFS and OS have statistically significance(χ2=12.47,P<0.001 andχ2=12.85,P<0.001).In the low risk group,91 patients were PET negativity,37 patients were PET positivity.The 2-year PFS were 86.2%and 25.0%,respectively(χ2=57.16,P<0.001).The 2-year OS were 97.8%and 59.6%,respectively(χ2=22.36,P<0.001).In the high risk group,22 patients were PET negative and 35 patients were PET positive.The 2-year PFS were 65.5%and 22.9%,respectively(χ2=11.90,P<0.001).The 2-year OS were 89.2%and 50.9%,respectively(χ2=.13,P=0.007).ConclusionThe S-IPI,R-IPI and NCCN-IPI are three clinically useful prognostic indexes for patients with DLBCL.Our results demonstrated that interim 18F-FDG PET/CT improves the prognostic efficacy of S-IPI,R-IPI and NCCN-IPI for patients with DLBCL in the rituximab era.Part 2:Interim 18F-FDG PET/CT and molecular phenotypes in predicting the prognosis for patients with diffuse large B-cell lymphoma in the rituxima eraObjectiveIn this study,we investigated the prognostic significance of interim 18F-FDG PET/CT(I-PET/CT)and the molecular markers of BCL2,CD10,BCL6,MUM1 and the phenotypes of germinal center B-cell-like(GCB)and non-GCB for patients with diffuse large B-cell lymphoma(DLBCL)in the rituxima era.MethodsA total of 106 patients(65 males,41 females;average age 50(20-82)years)with newly diagnosed DLBCL were analyzed in this retrospective study.All patients were received PET/CT scans at baseline and a subsequent I-PET/CT after the 4th cycle of chemotherapy.I-PET/CT was analyzed using the Deauville five point score(5-DS).The prognostic value of I-PET/CT with clinical factors,BCL2,CD 10,BCL6 and MUM1 were evaluated by predicting progression-free survival(PFS)and overall survival(OS).χ2 test,Kaplan-Meier analysis and Cox regression models were used for data analysis.ResultsWith a median follow-up of 25 months,the two-year PFS and OS were 60%and 81%in the whole cases.The 2-year PFS and OS were 78%and 97%in the I-PET/CT negative group,33%and 57%for the I-PET/CT positive group(χ2=17.24,P<0.001 and χ2=15.55,P<0.001,respectively).The 2-year PFS(79%vs.52%)were significant diffenence between BCL2 negative and positive groups(χ2=9.30,P=0.002),but no significant difference of 2-year OS(84%vs.79%)was observed between BCL2 negative and positive groups(χ2=3.34,P=0.068).No significant differences of survival were observed between I-PET/CT positive and BCL2 positive or both negative.Obviously,patients with both I-PET/CT and BCL2 negativity had a significant better PFS and OS than both positivity(χ2= 19.47,P<0.001 and χ2=11.91,P<0.001,respectively).However,in the I-PET/CT positive group,no significant differences of PFS and OS were observed between BLC2 negativity and positivity(χ2=0.69,P=0.406 and χ2=0.54,P=0.461,respectively).Patients had a superior PFS in BLC2 negativity than BCL2 positivity in the I-PET/CT negative group(χ2=7.77,P=0.005),but not in OS(χ2=1.52,P=0.217).Either BCL2 negativity or positivity,patients with I-PET/CT positive results had a significant inferior outcome than I-PET/CT negative.In addition,no significant differences of PFS and OS were observed between I-PET/CT positivity BLC2 negativity and I-PET/CT negativity BCL2 positivity(χ2=0.52,P=0.471 and χ2=2.66,P=0.103,respectively).By log-rank test,age(≦ 60 years vs>60 years),lactate dehydrogenase(LDH)level(≦ upper limit of normal[ULN]vs>ULN),ann arbor stage(Ⅰ/Ⅱ vs Ⅲ/Ⅳ),higher international prognostic index(IPI)were significant associated with shorter outcome.However,no significant differences were observed between the groups of the low and high expression of CD10,BCL6 and MUM1.In multivariate analysis,I-PET/CT and BCL2 were two independent variables in assessing the outcome of PFS.Only I-PET/CT was an independent parameter in evaluating the survival of OS.ConclusionsI-PET/CT and BCL2 are two independent prognostic factors for patients with DLBCL.I-PET/CT was much better than BCL2 for the patient stratification.BCL2 showed its supplementary role for the further patient stratification when I-PET/CT was negative.The molecular markers of CD 10,BCL6 and MUM1 and the phenotypes of GCB and non-GCB might be failed to predict the outcome for patients with DLBCL.Part 3:Immunophenotypes and treatment strategies in evaluating the outcome for patients with gastrointestinal diffuse large B-cell lymphomaObjectiveIn this study,we determined to comapre the prognostic role between differnce treatment strategies and immunophenotypings for patients with gastrointestinal diffuse large B-cell lymphoma(GI-DLBCL),and to investigate the prognostic risk factors when combined with international prognostic index(IPI)and the related clinical features.MethodsA total of 99 patients[66 males,33 females;average age 48.5(11-82)years]with newly diagnosed GI-DLBCL were evaluated in this retrospective analysis from Mar,2005 to Jan,2016 in our hospital.Forty-eight patients were treated with surgery followed by chemotherapy,and 51 patients were treated with chemotherapy alone.Patients with GI-DLBCL were reclassified ino germinal center B-cell-like(GCB)and non-germinal center B-cell-like(non-GCB)phenotypes by Han’s criteria.Evaluate the prognosis for GI-DLBCL patients by international prognostic index(IPI)and its related clinical characteristics.Interpretations were evaluated by 2-year progression free survival rate(PFS)and overall survival rate(OS)prediction.Kaplan-Meier analysis and Cox regression models were used for data analysis.ResultsWith a median follow-up of 25 months,the 2-year progression free survival rates(PFS)and overall survival rates(OS)were 70.9%and 89.5%in the whole cases.The 2-year PFS and OS of surgery followed by R-CHOP and R-CHOP alone were 79.4%and 63.6%(P=0.040),94.7%and 85.0%(P=0.039),respectively.In univariate analysis,patients with age<60 years,Lugano stage Ⅰ-Ⅱ1,ECOG performance status ≦ 1,LDH concentration ≦ULN and IPI score ≦2 had a significant superior survival than those with age = 60 years,Lugano stage Ⅱ2-Ⅳ,ECOG performance status ≧ 2,serum LDH concentration>ULN and IPI score ≧ 3(P<0.05).According to immunophenotypings,no significant differences of 2-year PFS and OS were observed between the phenotypes of GCB and non-GCB GI-DLBCL patients(both P>0.05).Besides,patients with GCB phenotype who underwent surgery followed by chemotherapy had a higher 2-year PFS than those treated with chemotherapy alone(P=0.018),but not in OS.No significant differences of the 2-year PFS and OS were observed in the non-GCB group between these two treatment strategies(P>0.05).The 2-year PFS and OS were significant higher in the surgery followed by chemotherpay group than chemotherpay alone for patients’ age<60 years old.No other significant differences of survival were observed between these two treatment strategies when based on the same clinical features or molecular phenotypes.In multivariate analysis,treatment strategies were not independent prognostic factors in the whole cases or the GCB group or the patients with age<60 years group(P>0.05).ConclusionsImmunophenotypings of GCB and non-GCB might be failed to predict the survival for patients with GI-DLBCL.Even though patients treated with surgery followed by chemotherapy had a higher survival than those treated with chemotherapy alone in the whole group or the GCB group or the patients with age<60 years group,but treatment stratement strategies were not independent prognosticators in these groups.Surgery followed by R-CHOP might not be recommended as a first-line treatment strategy for patients without operation indication. |
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