Stereotactic Body Radiation Therapy For Patients With Lung And Liver Oligometastatic Disease From Colorectal Cancer:a Phase ? Trial LncRNA And MRNA Associated With Pathologically Response After Neoadjuvant Chemoradiation Therapy Of Rectal Cancer

Part ? Stereotactic body radiation therapy for patients with lung and liver oligometastatic disease from colorectal cancer:a phase II trialObjective:To present the safety and effectiveness of SBRT for oligometastases from CRC.Materials&Methods:This is a prospective,single-arm phase ? trial.Patients who had histologically proven CRC,1-5 detectable liver or lung metastatic lesions with maximum diameter of any metastases?5cm were eligible.SBRT was delivered to all lesions.The primary endpoint was 3-year local control(LC).The secondary endpoints were treatment-related acute toxicities of grade 3 and above,1,3-year overall survival(OS)and progression-free survival(PFS).Results:Between January 2016 and December 2019,48 patients with 60 lesions were enrolled,including 37 liver lesions and 23 lung lesions.Most patients(96%)had 1-2 lesions,with median diameter of 1.3cm(range,0.6-5.0cm).The median biologically effective dose(BED10)was 100.0Gy(range,59.5-151.2Gy).Until December 2019,the median follow-up was 19.5 months(range,3-47 months)for all lesions.25 lesions developed local failure,the median LPFS was 15 months(range,1-41 months).The 1-year LC,OS and PFS was 70.2%(95%CI,63.7%-76.7%),89.0%(95%CI,84.3%-93.7%)and 40.4%(95%CI,33.0%-47.8%).The univariate analysis revealed that PTV volume(>31.7mL Vs<31.7mL,p=0.002)and total dose(<60Gy Vs?60Gy,p=0.040)were significant prognostic factors of LC.For liver and lung lesions,the 1-year LC,OS and PFS was 58.7%(95%CI,49.8%-67.6%)Vs 89.4%(95%CI,82.3%-96.5%)(p=0.015),89.3%(95%CI,83.5%-95.1%)Vs 86.5%(95%CI,77.6%-95.4%)(p=0.732),30.5%(95%CI,21.8%-39.2%)Vs 65.6%(95%CI,53%-78.2%)(p=0.024),respectively.However,liver and lung lesions differed significantly in tumor diameter(p=0.006),ITV and PTV volume(p=0.000,p=0.000),and total dose(p=0.020).No patients developed acute toxicity of grade 3 and above.Conclusions:SBRT is.safe and effective for oligometastases from CRC under respiratory motion management and robust quality assurance.Part ? LncRNA and mRNA associated with pathologically response after neoadjuvant chemoradiation therapy of rectal cancerObjective:To explore the different expression of IncRNA and mRNA and the possible mechanisms of different radiosensitivity in patients with different pathological response after neoadjuvant chemoradiation therapy of rectal cancer.Materials&Methods:(1)Pre-treatment specimens of 6 patients of locally advanced rectal cancer,with Mandard pathological grade TRG=1 and TRG=4(3 cases each)after neoadjuvant chemoradiation therapy were collected.LncRNA microarray was performed.The differentially expressed lncRNAs were screened,then were verified in the subsequent 47 sample specimens.The correlation between differential lncRNA and clinical features and their impact on survival were analyzed.We tested the expression of lncRNA in rectal cancer cell lines.(2)Pre-treatment specimens of 13 patients of locally advanced rectal cancer,6 with pathological complete response(pCR,TRG=1),7 with non-pCR(TRG=2,3,4)were collected.Then a transcriptome sequencing was performed.The differentially expressed lncRNAs and mRNAs was screened,and we searched for miRNAs that can combine with the lncRNAs and mRNAs simultaneously to build a ceRNA network(competitive endogenous RNA).Gene enrichment of differentially expressed mRNAs was done by KEGG and GO analysis.Results:The expression of lncUSP9Y-6 in the TRG=1 group was significantly lower than that in the TRG=2,3,and 4 groups,and the expression was significantly related to postoperative down-staging.However,there was no significant difference of OS,LRFS,and PFS of patients in different expression groups,patients of the low expression group had a longer survival trend.Unfortunately,in rectal cancer cell lines,the expression of lncUSP9Y-6 couldn't be detected,which limited the further exploration.Transcriptome sequencing found that in the non-pCR group,the expression of lncRNA DLX6-AS1,LINC00469 was up-regulated and may up-regulate the expression of mRNA by combining with hsa-miR-181b-5p,hsa-miR-27a-3p and hsa-let-7b-5p.In the pCR group,the expressions of LINC00707 and SOX21-AS1 were up-regulated,and possibly up-regulated the expression of mRNA by combining with hsa-miR-24-3p and hsa-miR-330-5p.The ceRNA networks were constructed in pCR and non-pCR group separately.Conclusions:There were differences in lncRNA and mRNA expression between patients of pCR and non-pCR after chemoradiation therapy of rectal cancer.Further exploration at the cellular and animal levels is required.