Predictive Value Of Serum MiR-345 In Locally Advanced Rectal Cancer Undergoing Preoperative Concurrent Chemoradiotherapy And The Outcomes After Stereotactic Body Radiotherapy For Colorectal Cancer Oligometastases

Part Ⅰ:Circulating Serum MicroRNA-345 Correlates with Unfavorable Pathological Response to Preoperative Chemoradiotherapy in Locally Advanced Rectal CancerPurpose:Preoperative chemoradiotherapy(pre-CRT)has been represented as the standard treatment for locally advanced rectal cancer(LARC),but large variations of tumor radiation response to CRT have been reported in the clinic.The aim of the study was to explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC.Patients and Methods:We analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment.MiR-345 was significantly elevated in the CRT-resistant group.Therefore,miR-345 was selected as a candidate for further analysis.We assessed the correlation between the miRNA signatures and the chemoradiotherapeutic response in 20 randomly selected LARC tissue samples(Validation set)and 87 serum samples(Training set)by qRT-PCR.Further,we validated the results in 42 randomly selected LARC serum samples(Validation set).Result:High miR-345 expression was significantly correlated with unfavorable pre-CRT pathological response in tissue and serum.Moreover,low miR-345 levels predicted superior 3-year local recurrence free survival(LRFS).Conclusion:Circulating serum miR-345 correlates with unfavorable pre-CRT response and poor locoregional control in LARC.It might be a promising biomarker to facilitate patient stratification for personalized treatment.Part Ⅱ:the Outcomes after Stereotactic Body Radiotherapy for Colorectal Cancer OligometastasesPurpose:Stereotactic body radiotherapy(SBRT)has been emerged as a treatment recommendation for recurrent or metastastic diseases.The purpose of the study was to assess the optimal dose,the safety and efficacy of SBRT in oligometastases of colorectal cancers.Methods and Materials:From 2009 to 2014,52 patients with 92 single metastases were included for the clinical review.We used the dfmacox(degrees of freedom inmultivariate additive Cox models)function in smoothHR to assess the relationship between BED and the risk of local recurrence.LC and overall survival(OS)were compared by the Kaplan-Meier and log-rank test.Result:The median follow-up time was 15 months(range,0-82 months),the 2-year LC was 70.8%,with nine patients developed local progression.We found a non-linear relationship between BED and the hazard ratio(HR)of local relapse.The risk of local progression decreased continuously since the BED>90 Gy.Patients receiving higher dose SBRT(BED ≥100 Gy)were associated with significantly better 2-year LC and OS,compared with those treated with low dose(BED<100 Gy)(LC:82.2%vs 54.9%;OS:74.9%vs 48.1%).Introduction CT did not provide additional survival benefit.No grade≥ 3 early-or late-adverse events were observed,exception that one patient who underwent long-term anti angiogenic treatment and multiple cycles CT died of acute intestine massive hemorrhage.Conclusion:SBRT achieved a favorable outcome with acceptable toxicities in oligometastases of colorectal cancers.Higher dose SBRT(BED>100 Gy)might be recommended.The role of introduction CT needs to further concern.