| 1 BackgroundLung cancer is a major public health problem worldwide and it can be categorized into small cell(SCLC)and non-small cell carcinoma(NSCLC).NSCLC accounts for approximately over 80%of all patients with lung cancer.Surgery is an important curative treatment for NSCLC,however,many of patients were diagnosed at advanced stages(ⅢB or Ⅳ)of the disease and fewer than 20%of tumors can be radically resected.For those patients who cannot be helped surgically,chemotherapy is one of the main treatments at present,but chemotherapy can make damage to normal cells while killing tumor cells.At the meantime,intravenous chemotherapy can cause some adverse reactions such as nausea and vomiting,which can reduce the tolerance of patients and affect the efficacy.Radiotherapy is another effective treatment for non-small-cell lung cancer,but the radiation dose is strictly controlled due to the radiation damage to normal tissue.Radiotherapy can cause complications such as bone marrow suppression and radioactive pneumonia.Recently,with the help of image guidance,brachytherapy has been proposed as a strategy to treat inoperable large cancers which has several advantages over conventional external beam radiotherapy and other therapeutic modalities.Iodine-125(125I)seed implantation brachytherapy was applied initially to cancer of the prostate gland and achieved good local control with few complications.125I radioactive seeds has been increasingly practiced in the clinical treatment of non-small cell lung cancer since the 1980s.125I seeds implantation treatment can increase the local tumor control rate and survival rate of lung cancer patients,reduce the suffering of the patients while not increase other serious complications.2 ObjectiveThe objective of this study is to evaluate the efficacy of CT-guided implantation of radioactive 125I seed for the treatment of lung cancers.At present,there are lany studies about the efficacy of 125I brachytherapy,but the outcome variables are usually grouped according to WHO or RECIST 1.1 solid tumor evaluation.This study focuses on the trends of tumor size and tumor markers over time,in order to explore the factors influencing the efficacy and the prognosis of NSCLC patients after 125I brachytherapy.3 Methods and materials3.1 MaterialsOur study included 85 NSCLC patients who were treated with 125I brachytherapy in Cancer Therapy and Research Center,Shandong Provincial Hospital.We designed a questionnaire to collect information of patients including:characteristics of patients,characteristics of tumors,prior treatment,diagnosis of patients,laboratory examination and treatment status of patients,the follow-up information etc.3.2 Statistical analysisSPSS 24.0 and R software were used to conduct statistical analysis.The main analytical methods include descriptive analysis,chi-square test,ANOVA for repeated measurements,linear mixed-effects model,logistic regression analysis and cox proportional hazard regression model.4 Results4.1 The efficacy of the treatmentAccording to RECIST 1.1,15 patients(17.6%)were complete response(CR),26 patients(30.6%)were partial response(PR),42 patients(49.4%)were stable disease(SD),2 patients(2.4%)were progressive disease(PD).The overall response rate(CR+PR)was 48.2%,the disease control rate(CR+PR+SD)was 97.6%.4.2 Trends of tumor sizeAfter six months,we measured the tumor volume in 85 NSCLC patients.There were 79 patients(92.9%)whose tumor volume reduced after 125I brachytherapy.Among the patients,fifty-six(65.9%)patients’ tumors shrank over 50%,seventeen(20%)patients’tumors shrank over 80%,six(7.1%)patients’ tumors enlarged.The average change of tumor volume was-50.96%(± 40.70%).According to the changes in tumor volume changes over time,patients’ tumors shrank rapidly in the first two months,then the tumors shrank at a slower speed until 7.5 months,then the tumors no longer changed.4.3 The comparison before and after brachytherapy and the trends of tumor markersCancer embryo antigen(CEA)and Carbohydrate antigen 125(CA125)were reduced after 125I brachytherapy,but the difference was not statistically significant.Cytokeratin 19 fragment antigen(CYFRA21-1)was significantly reduced after 125I brachytherapy and there was statistical difference(before 7.8 ± 11.1,after 4.9 ± 4.7,F=8.712,P=0.04).There were 41 patients in the effective group,and the cyfra21-1 was significantly reduced after 125I brachytherapy(before 8.9± 13.3,after 5.4±5.1,F=4.694,P=0.036).There was no statistical difference before and after 125I brachytherapy in CEA and CA125.The ineffective group included 44 patients and there were no statistically significant differences in CEA,CA125 and cyfra21-1.The tumor markers trends showed that,CEA decreased significantly during the first six months after 125I brachytherapy,then kept at a normal range after six months.CA125 had a downward trend within 7.5 months after 125I brachytherapy,but the change is not significant.CYFRA21-1 had an obvious downtrend within 3 months after 121I brachytherapy and then kept at a stable level.4.4 Risk factors that affect short-term efficacyThe results of Logistic regression model showed that tumor type is the risk factor of the short-term efficacy(Squamous carcinoma compared to adenocarcinoma:OR=3.53,95%CI:1.36-9.19,P=0.01).4.5 Risk factors that affect the outcome and prognosis of patientsCox proportional hazard regression model showed that age(HR=1.03,95%CI:1.01-1.04,P=0.002),tumor stage(HR=2.31,95%CI:1.31-4.07,P=0.004),and accompanying by pulmonary diseases including pneumonia,atelectasis,pulmonary abscess and pleural effusion(HR=3.06,95%CI:1.21-7.72,P=0.018)were the main factor affecting the prognosis of patients.5 Conclusions(1)CT guided radioactive 125I seed implantation for non-small cell lung caneer is an effective and minimally invasive treatment which had good local control rate.(2)The tumors shrank rapidly in two months after 125I brachytherapy,then the tumor shrank at a slower rate after two months.(3)125I brachytherapy for non-small cell lung cancer can effectively reduce the level of multiple tumor markers.The level of tumor markers with different therapeutic effects is significantly different.(4)Tumor type is a risk factor that affects the therapeutic effect of 125I brachytherapy,squamous cell carcinoma is more effective than adenocarcinoma.(5)Age,tumor stage and accompanying by pulmonary diseases including pneumonia,atelectasis,pulmonary abscess and pleural effusion are the factors affecting the prognosis of patients after 125I brachytherapy. |
