| Background and ObjectiveExtranodal Natural Killer/T-cell Lymphoma(ENKL)is the most common subtype of peripheral T-cell lymphoma.Due to its high aggressiveness and resistance to multiple drugs,its clinical prognosis is poor.The malignant degree of ENKL is high,but the incidence of ENKL has been on the rise in recent years.ENKL has regional and ethnic differences.It is rare in European and American countries,with an incidence rate of less than 1%,while the incidence rate is higher in Asia and South America,of which the incidence rate is.about 15%in our country.The common sites of ENKL invasion are the nose,nasopharynx,oropharynx,and Webster’s ring,and a few involve the upper respiratory tract,digestive tract,and skin.Traditional imaging methods are difficult to accurately assess the size of the lesion,anatomical structure,and tumor metabolism intensity.Positron emission tomography/computed tomography(PET/CT)is an imaging examination method that combines functional metabolism imaging and anatomical structure imaging.PET/CT can accurately display systemic tumor lesions by using the high uptake capacity of 18F-2-fluoro-2-deoxy-D-glucose(18F-FDG)in tumor cells.Studies have shown that 18F-FDG is a good imaging agent for ENKL,and its PET/CT results have a certain correlation with the prognosis of ENKL.However,due to the complex anatomical structure of the nasal cavity,the shape of the lesion formed by ENKL at this site is irregular,making it difficult to measure the size of the lesion.In addition,the lesions of the nasal cavity,nasopharynx and sinuses in ENKL patients are often accompanied by inflammation,which interferes with 18F-FDG PET/CT and makes it difficult to judge the location of the lesions and evaluate the therapeutic effect.In the efficacy evaluation of ENKL,there are many analysis methods for PET/CT results,including the International Harmonization Project(IHP)standard visual judgment method,the Deauville 5-point scale(DS),the maximum standard Standardized uptake value maximum(△SUVmax)method,etc.However,several studies have reported that there are high false positive rates in IHP standard and DS,and at present,there is no recognized best method for efficacy evaluation.Therefore,it is urgent to find more accurate efficacy evaluation methods based on PET/CT to guide clinical decision-making.In this study,the efficacy of IHP standard,DS,ΔSUVmax method and ΔSUVmax%method in the mid-term efficacy evaluation of ENKL treatment and their correlation with prognosis were compared and analyzed,so as to guide the clinical treatment decision.Materials and Methods1.The clinical data of 68 ENKL patients who were admitted and pathologically confirmed to The First Affiliated Hospital of Zhengzhou University from February 2014 to December 2019 were collected.18F-FDG PET/CT was performed before and in mid-term treatment which was of first-line treatment.2.18F-FDG PET/CT images before and in mid-term treatment of 68 patients were collected and analyzed.IHP standard visual judgment(hereinafter referred to as IHP standard),DS,ΔSUVmax method and ΔSUVmax%method were used to evaluate the mid-term treatment response,besides,the efficacy of the four methods were compared.3.Patients were grouped according to the efficacy evaluation results with the four methods,survival analysis was conducted in different groups,and the correlation between the efficacy evaluation results of the four methods and prognosis was discussed.4.Univariate analysis was carried out with gender,age,stage,SUVmax in mid-term treatment,ΔSUVmax,ΔSUVmax%,EB virus encoded RNA(EBER),EB-DNA,prognostic index of natural killer cell lymphoma with epstein-barr virus DNA(PINK-E)score,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin,lactate dehydrogenase,DS results,IHP standard results,Ki-67,etc.Statistically significant factors were performed in Cox model multivariate regression analysis to analyze the independent prognostic factors of ENKL patients.Statistical approachSPSS 22.0,Medcalc19.3.1 and GraphPad Prism 8.0 software were used for analysis and mapping.χ2 test or corrected χ2 test,McNemar test and Kappa test were used for efficacy evaluation results of four methods.The receive operating characteristic(ROC)curves of four PET/CT interpretation methods were drawn by Medcalc 19.3.1 software,Z test was used in the overall effectiveness of the four methods.The critical values of ΔSUVmax and ΔSUVmax%were obtained in ROC curves.Using GraphPad Prism 8.0 software,the efficacy evaluation results of the four methods were grouped for Kaplan-Meier survival analysis,and Log-rank test was performed.The difference was statistically significant(P<0.05).Results1.Characteristics and survival of patients:The median age of 68 ENKL patients was 45 years old,the ratio of male to female was 2.5:1,57.4%of patients were stage III-IV,38.2%patients had PINK-E score of 3-5 points,44.2%of patients had EB-DNA≥500,23.5%of patients had elevated β2-MG,39.7%had elevated LDH,79.4%had Ki-67≥60%,98.5%were EBER positive,32.4%patients had ECOG score>2 points,54.4%of patients had B symptoms;55.9%of patients had distant lymph node metastasis.Among the 68 patients,the 1-year,3-year,and 5-year progression free survival rates were 68.8%,57.2%and 52.4%,respectively.The 1-,3-,and 5-year overall survival rates were 86.4%,78.2%and 82.7%,respectively.Among the 68 patients,51 were alive,15 died and 2 were missed follow-up.2.The cut-off values of △SUVmax and △SUVmax%method:The △SUVmax and △SUVmax%of each patient were obtained.The cutoff values of △SUVmax andΔSUVmax%were 5.90 and 52.63%in ROC curves,respectively.3.Efficacy evaluation results of four methods in 18F-FDG PET/CT images at the mid-term treatment:45 cases(66.2%)were IHP positive,and 23(33.8%)cases were negative in the middle stage of treatment,and the misappraisal rate was 42.6%.According to DS,28 cases(41.2%)were negative with 1～3 points,and 40 cases(58.8%)were positive with 4-5 points,and the misappraisal rate was 29.4%.49 cases(72.0%)were negative with ΔSUVmax>5.90,19 cases(28.0%)were positive withΔSUVmax<5.90,and the misappraisal rate was 13.2%.47 cases(69.1%)were negative with ΔSUVmax%≥52.63%,21 cases(30.9%)were positive group with△SUVmax%<52.63%,and the misappraisal rate was 10.3%.4.The efficacy of four methods in the evaluation of curative effect:The AUC values of IHP standard,DS,ΔSUVmax criterion and ΔSUVmax%criterion were 0.669,0.792,0.837 and 0.935,respectively.The efficacy of DS,ΔSUVmax criterion and △SUVmax%criterion were higher than IHP standard(P<0.05).There were differences in the efficacy of the four methods for efficacy evaluation(P<0.05).Among the four methods,the positive predictive value of ΔSUVmax criterion andΔSUVmax%criterion were higher,which were 78.9%and 81.0%respectively.The negative predictive value of DS and ΔSUVmax%criterion were higher,which were 100.0%and 93.6%respectively.The sensitivity of DS was the highest,which was 100.0%.The specificity of ΔSUVmax criterion and ΔSUVmax%criterion were higher,which were both 91.7%.The accuracy of ΔSUVmax%criterion was the highest,which was 87.1%,respectively(P<0.05).5.Correlation between the results of four methods and prognosis:There was no significant difference in 3-year PFS rate between IHP negative group and IHP positive group,which was respectively 59.0%vs.55.7%(x2=0.180,P=0.671),3-year OS rate was 82.0%vs.76.5%(χ2=0.047,P=0.829).There was no significant difference in 3-year PFS rate between DS negative group and positive group,which was respectively 70.4%vs.48.1%(χ2=3.579,P=0.059),and the 3-year OS rate of DS negative group was higher than DS positive group,which was 92.3%vs.68.6%(X2=3.952,P=0.048).Of the ΔSUVmax≥5.90 group and ΔSUVmax<5.90 group,the 3-year PFS rate was 75.0%vs.15.0%(x2=18.94,P<0.001),and the 3-year OS rate was 87.2%vs.53.3%(χ2=7.868,P=0.005<0.05).Of the ΔSUVmax%≥52.63%group and<52.63%group 3-year PFS rate was 76.5%vs.15.2%(x2=29.33,P<0.001),3-year OS rate was 88.9%vs.52.7%(χ2=11.01,P<0.001),the difference was statistically significant.6.Analysis of prognostic factors:Univariate analysis showed that patients with high ΔSUVmax,high Δ SUVmax%,low SUVmax in the mid-term of treatment,1～3 points of DS and low Ki-67 had a longer progression free survival,and the difference was statistically significant(P=0.010,P<0.001,P<0.001,P=0.026,P=0.033).High △SUVmax%,low SUVmax in the mid-term of treatment and 1-3 points of DS had a longer overall survival(P<0.001,P=0.001,P=0.030).Conclusions1.The Deauville 5-point method,ΔSUVmax and ΔSUVmax%of PET/CT in the mid-term treatment are more effective than the IHP standard visual judgment in evaluating the efficacy of ENKL patients.2.The results of the ΔSUVmax method and ΔSUVmax%method in mid-term treatment show advantages in predicting the prognosis of ENKL patients.3.In the analysis of prognostic factors of ENKL,the patients with highΔSUVmax,high ΔSUVmax%and 1-3 points in DS had better prognosis. |
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