Comparison Of Efficacy And Analysis Of Prognosis Of Radiotherapy Alone,PGEMOX Regimen Sequential Radiotherapy,and PGEMOX Regimen Sandwich Radiotherapy Treatment For Early Stage Extranodal Natural Killer/T Cell Lymphoma

Objective: Extranodal natural killer/T cell lymphoma,nasal type(ENKTL),is a unique pathological type of non-Hodgkin’s lymphoma(NHL)with highly aggressive,relatively shorter survival and poorer prognosis,the clinical curative effects and survival show individual differences.However,there are no standard treatment options.The early stage ENKTL patients are sensitive to radiotherapy alone with well outcomes,but easily occur to local relapse or distant metastasis,leading to poor prognosis.Combination chemotherapy could reduce the risk of distant metastasis and improve prognosis.So the majority experts are favor of radiotherapy combined chemotherapy treatment strategy.Confirmed by previous studies,resistant to the traditional CHOP or CHOP-like chemotherapy regimens,because of highly expression of P-glycoprotein(P-gP)caused the multidrug resistance(MDR).Therefore,the anti-tumor drugs which are not affected by MDR treated with ENKTL patients have been reported in succession.The domestic and overseas studies have been reported that the L-asparaginase-based regimens achieved remarkable the clinical efficacy in the treatment of ENKTL patients.However,L-asparaginase with high immunogenicity,short half-life,frequent infusion,increasing the incidence of allergic reactions,limited in clinical work.Pegaspargase retained the L-asparaginase biological activity with low immunogenicity,without skin test,very safety,long half-life,without repeatedly continuous intravenous drip and easily to use.Recently studies have confirmed that Pegaspargase-based regimens PGEMOX obviously improved clinical efficacy and long-term survival with no serious adverse reactions.However,a few patients still appear local relapse or distant metastases within a short period of time.Therefore,a novel prognostic marker used for stratification for those ENKTL patients is urgently needed.Previous researches have indicated that the inflammatory response is participating in the occurrence and development of tumor,the absolute lymphocyte count(ALC),platelet to lymphocyte ratio(PLR)are correlated with the poor survival in many kinds of solid tumors.However,there are few studies on the relationship between PLR and the prognosis of ENKTL patients.In our study,comparison of treatment response,side effects and long-term survival of radiotherapy alone,PGEMOX regimen sequential radiotherapy,and PGEMOX regimen sandwich radiotherapy for early stage extranodal NK/T cell lymphoma,and to explore the prognostic factors.Methods: 124 patients with early stage ENKTL from June 2009 to January 2016 in Sichuan Province Cancer Hospital were retrospective analyzed,comparison the treatment response of above three treatment strategies,to analyze the correlations between the clinical characteristics and prognosis.SPSS 17.0 software wasused for statistical analysis,Chi-square test was used to comparison the difference between two groups,the survival curve analysis was executed by the Kaplan-Meier method,and Univariate survival analysis was evaluated using the Log-rank test,Multivariate survival analysis was conducted by COX regression model.Results: 124 patients,male to female ratio 2.26:1,the median age was 46 years,mainly occurred to in middle aged men.For the whole patients,79.8% of patients achieved complete response(CR),partial response rate(PR)was 11.3%,the overall response rate(ORR)was 91.1%,2-year local regional control(LRC)was 80.6%,2-year overall survival(OS)was 75.8%,2-year progression free survival(PFS)was 67.7%.41 patients received radiotherapy alone,CR rate was 61.0%,PR rate was 19.5%,ORR was 80.5%,2-year LRC was 78.0%,2-year PFS was 51.2%,2-year OS was65.9%.37 patients accepted PGEMOX regimen sequential radiotherapy,CR rate was 86.5%,PR rate was 8.1%,ORR was 94.6%,2-year LRC was 81.1%,2-year PFS was 75.7%,and 2-year OS was 81.1%.46 patients were treated with PGEMOX regimen sandwich radiotherapy,CR rate was 91.3%,PR rate was 6.5%,ORR was 97.8%,2-year LRC was 82.6%,2-year PFS was 76.1%,and 2-year OS was 80.4%.There were significant differences of CR,ORR,PFS,OS among the three groups,respectively(P<0.05).there was not significantly statistical difference of LRC among the three groups(P>0.05).Further two groups comparison analysis,there were significant differences of CR,PFS between the radiotherapy alone and PGEMOX regimen sequentialradiotherapy(P<0.05),respectively.There were significant differences of CR,ORR,PFS,OS between the radiotherapy alone and PGEMOX regimen sandwich radiotherapy(P<0.05),respectively.On the contrary,there was no significant difference of CR,ORR,PFS,OS between PGEMOX regimen sequential radiotherapy and PGEMOX regimen sandwich radiotherapy(P>0.05).The major adverse reactions were leukopenia,anemia,thrombocytopenia,increased transaminases,hyperbilirubinaemia.Grade 1/2toxicities were frequent during treatment,Grade 3/4 were few occurred.Compared to the PGEMOX regimen sequential radiotherapy,PGEMOX regimen sandwich radiotherapy is more likely to happen Grade 1/2 increased transaminases(P<0.05),the rest adverse reactions are not significant differences(P>0.05).Univariate analysis showed that ECOG score(>2),B symptoms,LDH>240U/L,IPI score(>2),KPI score(>2),ALC<1x10^9/L,PLR>185,GTV≤55Gy,local tumor invasion(LTI),and treatment modalities were correlated with PFS(P<0.05).Meanwhile,the age(>60 years),ECOG score(>2),B symptoms,LDH>240U/L,IPI score(>2),KPI score(>2),PINK score(>1),ALC<1x10^9/L,PLR>185,GTV≤55Gy,LTI,underlying disease and treatment modalities were related to OS(P<0.05).Multivariate analysis revealed that ECOG score,LDH,PLR,LTI and treatment modalities were independent prognostic factors for PFS(P<0.05).ECOG score,LDH,PLR,LTI,underlying disease and treatment modalities were independent prognostic factors for OS(P<0.05).Conclusion: 124 patients,male to female ratio2.26:1,the median age was 46 years,mainly occurred to in middle aged men.The pegaspargase-based regimens PGEMOX as the first line treatment for early stage ENKTL patients is effective,no matter the treatment response or long-term survival,is better than radiotherapy alone,highly safety.There was no difference of clinical efficacy and long-term survival between PGEMOX regimen sequential radiotherapy and PGEMOX regimen sandwich radiotherapy.ECOG score,LDH,PLR,LTI and treatment modalities were independent prognostic factors for PFS.ECOG score,LDH,PLR,LTI,underlying disease and treatment modalities were independent prognostic factors for OS.