| 1.Background and objectiveQuality of life（QOL）is a concept of one’s status of body,feeling and social functions from the view of patients.Concerning humanself more,it received more and more attention and there are more and more researches that take QOL as endpoints of treatment trial.As one of the several malignant tumors with the greatest incidence rate in Southern China,the primary treatment of nasopharygeal carcinoma（NPC）is radiotherapy alone or chemoradiotherapy and its overall survival rate of 3 years has been above 90%.As more and more patients may survive long time,it’s getting more and more important to research the QOL of NPC patients during and after radiotherapy treatment.The radiotherapy fields of definitive radiation therapy for NPC patients are rather large and more than 90%patients may suffer acute radiation-induced mucositis with QOL worsened.Thus radiation therapy may be interrupted and the treatment outcome affected.And about 27%NPC patients experienced late injury in 5 years after conventional radiation therapy while so did 35%NPC patients treated by chemoradiotherapy including swallowing dysfunction,vision loss,hearing loss and brain necrosis,with great impact in QOL long time.It has been widely accepted that the inflammatory reaction is triggered by radiation-induced damage with induction of cytokinese cascade which being shown as the activation of proinflammatory and anti-inflammatory cytokinese net.There was a pilot study showing that there is positive correlation between IL-6 serum levels and severity of mucositis and dysphagia in head and neck patients receiving combined chemo-radiation therapy.There are also studies about radiotherapy patients suffered with breast cancer,prostate cancer,non small cell lung cancer and cervical cancer etc.,showing QOL of patients are related with serum cytokines level.There have also been some studies trying to find the cytokines changing modules in the radiation therapy treatment.And there is finding that the prognosis of some cancer is correlated with serum cytokines level.So to research the relationship between QOL and serum cytokines level among NPC patients during and after radiotherapy will help us to understand deeply the impact of radiation on local tissues and whole body and may also help to find some factors that may promote or inhibit the development of early or late injury and improve QOL during and after treatment.2.MethodsNPC patients hospitalized in oncology department of our hospital during January 2011 to December 2012 were enrolled of cancer stage Ⅰ～Ⅳb（according by nasopharygeal carcinoma 2008 staging standard）treated by primary definitive conventional radiation therapy or chemoradiotherapy.Cases with metastasis in the treatment or follow-up and those with local residual tumors were eliminated.All enrolled patients finished QOL questionaire of EORTC QLQ-C30 and QLQ-H&N35.At the same time blood samples were collected of 3ml and stored at-80℃ until assayed.Levels of IL-1β,IL-6,IL-8,IL-10,TNF-α and CRP were measured by enzyme-linked immunosorbent assay（ELISA）.Mean scores of each scale of QLQ before,in and after radiotherapy were compared using ANOVA.To assess the relationship of mean scores of different scales of QLQ in the same time,Pearson correlation was used.To compare the cytokine levels of before,in and after radiotherapy,ANOVA was used.The correlation between cytokine and mean score of each scale was checked with Pearson correlation test and so did correlation of different cytokine levels.Microsoft SPSS 13.0 software was used for data processing and P value of less than 0.05 was considered significant.3.Results3.1 Outcome of QOL of NPC patients treated with conventional radiotherapy.One hundred and twenty-three NPC patients were enrolled in this study,having finished EORTC QLQ-C30 and QLQ-H&N35.Five patients were eliminated because of metastasis or residual tumors and other one hundred and eighteen patients finished definitive radiotherapy or chemoradiotherapy.There were nineteen questionnaires before treatment,thirty-seven in the treatment and sisxty-two after treatment.There were no differences among mean scores before treatment,in treatment and after treatment of global health status,physical functioning,role functiong,emotional functioning,cognitive functioning and social functioning（P>0.05）.In the nine symptom scales of QLQ-C30,there were only two scales（pain and appetite loss）of which mean scores changing（F=2.108,P =0.041;F=4.081,P<0.001）,showing higher in the treatment and reduced to pretreatment levels 3-6 months postreatment.In the eighteen symptom scales of QLQ-H&N35,there were eight scales of which mean scores changed including pain（F=4.807,P<0.001）,swallowing（F=3.380,P=0.020）,sense problems（F=2.818,P=0.007）,trouble with social eating（F =2.690,P =0.010）,opening mouth（F=3.380,P=0.02）,dry mouth（F=3.380,P =0.020）,pain killers（F=3.380,P=0.020）。During radiation therapy or chemoradiotherapy there were correlations between mean score of pain and that of several scales,including physical functioning（r =-0.454,P = 0.005）,role functiong（r =-0.400,P = 0.014）,emotional functioning（r =-0.373,P = 0.023）,fatigue（r =0.643,P<0.001）,appetite loss（r =0.643,P<0.001）.There were also correlations between mean score of swallowing and that of physical functioning（r =-0.526,P = 0.001）and appetite loss（r =-0.396,P = 0.015）;The mean scores of financial difficulties of patients showed correlation with that of emotional functioning（r =-0.482,P = 0.003）,fatigue（r=0.440,P = 0.006）and appetite loss（r =0.532,P = 0.001）.After treatment there were still correlations between mean score of pain and that of several scales,including physical functioning（r =0.302,P = 0.019）,role functiong（r =-0.267,P=0.039）,emotional functioning（r =-0.305,P = 0.018）,fatigue（r=0.392,P=-0.002）,insomnia（r=0.327,P = 0.011）,appetite loss（r=0.460,P<0.001）.The mean scores postreatment of opening mouth were correlated that of physical functioning（r =-0.291,P= 0.025）,role functiong（r =0.-329,P = 0.011）.The mean scores of financial difficulties of patients postreatment also statistically correlated with that of physical functioning（r =-0.318,P =0.012）,emotional functioning（r =-0.362,P = 0.004）,fatigue（r =0.592,P<0.001）and appetite loss（r =0.335,P＝0.008）.3.2 Outcome of serum cytokines levels of NPC patients treated with conventional radiotherapy.One hundred and thirty-four patients were enrolled in this study,whose blood samples having been collected.Five patients were eliminated because of metastasis or residual tumors and other one hundred and twenty nine patients finished definitive radiotherapy or chemoradiotherapy.Their blood samples were assayed for levels of IL-6,IL-8,IL-1β,IL-10,TNF-α and CRP by ELISA.Comparing all the levels of cytokines and patients’ clinical characteristics,there were negative relation found between IL-6 level and patients’age（r =-0.510,P = 0.026）,also negative relation between IL-8 level and tumors pathological differentiation（r=-0.458,P = 0.048）and positive relation between IL-1βlevel and EB virus VCA-IgA（r =0.503,P = 0.028）.Comparing all the levels of cytokines and CRP,there were correlation found between IL-6 level IL-8 level（r=0.409,P<0.001）and correlation between IL-6 level IL-1βlevel（r=0.203,P =0.021）.There were also correlation between IL-6 level TNF-α level（r=0.321,P<0.001）.All one hundred and twenty nine patients were divided into three groups with 19 cases before treatment,5 casese in the treatment and 74 casese after the treatment.There were no statistical differences among levels of IL-6,IL-10,TNF-α,CRP of three groups.The IL-8 level of the patients after two years postreatment showed higher than other patients,but with no significance statistically.The IL-1βlevel of the patients after two years postreatment showed higher than other patients with significance statistically（F=2.724,P =0.047）.There were no correlation between cytokine levels and mean score of any scale of 19 patients before treatment（P>0.05）.In the course of treatment of 36 patients there were negative relation between IL-6 levels and mean scores of global health status（r=-0.473,P =0.030）,positive relation between IL-6 levels and mean scores of pain（r=0.520,P =0.016）and positive relation between IL-6 levels and mean scores of coughing（r=0.514,P=0.020）.There were also negative relation between IL-10 levels and mean scores of insomnia（r=-0.486,P =0.025）,and negative relation between TNF-alevels and mean scores of speech problems（r=-0.446,P =0.049）.For the seventy-four NPC patients after treatment,there were relations between IL-10 levels and mean scores of several scales.The IL-10 levels were found negtively correlated with mean scores of swallowing postreatment（r=-0.423,P=0.011）,also with that of speech problems（r=-0.395,P =0.019）and with that trouble of social eating（r=-0.479,P =0.004）.The IL-8 levels were found negtively correlated with mean scores of dry mouth（r=-0.366,P =0.030）and that of weight loss（r=0.466,P<0.001）.And the mean scores of weight loss were also related with IL-6 levels（r=0.398,P<0.001）.4.ConclusionsNPC patients treated with conventional radiation therapy experienced changes of many scales of quality of life in the treatment and after the treatment.In the treatment patients’ pain symptom and swallowing symptom affect QOL most.After the treatment patients’ pain symptom and opening mouth symptom affect QOL most.And financial difficulties affect widely many scales both in the treatment and after the treatment.Serum levels of IL-6,IL-8,IL-1β and TNF-a of NPC patients interact each other.IL-6 may mainly promote acute radiation-induced injury that worsen QOL of NPC patients during conventional radiationtherapy.While IL-8 may mainly inhibit the progress of dry mouth and IL-10 also plays a role in inhibition of late damage that affect patients’ QOL after treatment. |
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