The Research Of Relationship Between Functional Dose-volume Histogram And Plasma Cytokines Markers For Predicting RP

BackgroudRadiation pneumonitis is the short-term performance of radiation-induced lung injury,generally speaking,most RP is occurred in the course or within three month after the end ofradiotherapy.On the other hand,the worse result of radiation-induced lung injury isradiation-induced pulmonary fibrosis.Even with the3D-CRT or IMRT treatmentplanning,RP remains the most serious,dose-limiting complication,finally the limitingfactors would effect the local control and Overall survival.Incidence of RP in the patientsreceiving thoracic radiotherapy is13%-37%.Objective(1)To investigate the patients’ individual clinical parameters (Age,gender,smokinghistory, pathological type,tumor location and previous lung diseases areincluded),dose-volume histogram(DVH) parameters association with RP in the patientswith lung cancer and receiving radiotherapy with or without chemotherapy.(2)With thehelp of SPECT lung perfusion, distinguish the function lung(FL) and non-functionlung(NFL),we get the functional-DVH(fDVH).Discuss weather the fDVH is a betterpredictor for RP.(3)Compare the change of the patients’ plasma cytokines level before andafter radiotherapy,cytokines include angiotensin converting enzyme(ACE), transforminggrowth factor-β1(TGF-β1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α).MethodsA total of42patients with lung cancer treated with radicial three dimensionalcomformal(3D-CRT) were prospectively recruited and analyzed.And then：(1)Single-photon emission computed tomography(SPECT) were used to provide the lungperfusion images，with the distinguished function lung we get the fDVH，the conventionalDVH we get at the same time.(2)Before the treatment and radiotherapy dose reached 40-50Gy，plasma cytokines(angiotensin converting enzyme, transforming growth factor-β1,interleukin-6, tumor necrosis factor-α.)were measured with enzyme-linked immunosorbentassay(ELISA).(3)Follow-up examination were performed at1,3,6months after completionof radiotherapy，The grade of RP was evaluated according the the NCI CommonTerminology Crteria for Advers Events.Results(1) RP did not associated with patients’ age,gender, tumor location,chemotherapy,pathological type and smoking history(P=0.74，0.28，0.83，0.28，0.52，0.63).But，previous lung diseases and tumor’s clinical stage associated with the accient ofRP.(2) Univariate analysis show numbers of radiation field,some parameters ofDVH(V10，V20，V30，V40，MLD) and fDVH parameters(V5，V10，V20，V30，MPWLD) were statistically significant relative to the development of RP.(all parameters’value of P＜0.05). Logistics regression analysis revealed numbers of radiation field，MLD，V20and fV20associated with RP（P=0.008，0.04，0.01，0.01）,these four parameterswere the independent predictive factors of RP.Receiver operator characteristicdemonstrated all fDVH parameters have larger AUC(area under curve) than the traditionalDVH,but only fV20has significant difference was abserved(P=0.03).(3) All the four plasma cytokines did not have a significant difference between beforeand after radiotherapy in “all patients group”,but they all have significant relationshipbetween before and after therapy.When we compare the plasma cytokines level of “RPGroup”and“non-RP Group” between before and after radiotherapy，which find that：beforeradiotherapy the TNF-α level of “RP Group” is much lower than the “non-RP Group”(P=0.002).After radiotherapy the TGF-β1level of “RP Group” is higher than the “non-RPGroup”（P=0.02）.The level of IL-6in plasma before and after radiotherapy and their ratio（pre-radiotherapy/post-radiotherapy），all of them in “RP Group”is higher than “non-RPGroup”(P=0.018，P＜0.001，P=0.029).Plasma ACE level of “RP Group” was significantdifferent from the “RP Group” as well in both two time points（P=0.031，P=0.002）.Conclusion(1) Because previous lung diseases and tumor’s clinical stage associated with theaccient of RP，so it’s important that lung function tests may have clinical value inpredicting theoccurrence of RP： The clinical stage of advanced patients to appropriate for radiotherapy， to prevent the occurrence of RP.(2) Numbers of radiation field,some parameters of DVH(V10，V20，V30，V40，MLD) and fDVH parameters(V5， V10，V20， V30， MPWLD) were statisticallysignificant relative to the development of RP. Moreover, forecasting performanceof fDVH on RP than traditional DVH parameters have a trend of increase.(3) Differences between the two groups of patients with various cytokines inthebefore and after radiotherapy, the cell factors between the two groups at different timepoints, have different degrees of difference.