Short-term Local Efficacy Of Intraoperative Radiotherapy After Breast Conserving Surgery And The Mechanism Of Which Induces Apoptosis Of Breast Cancer Cells

Background and Objective:Breast conserving surgery(BCS)combined with radiotherapy is one of the standard treatment for early breast cancer.compared with the traditional modified radical mastectomy,combined breast conserving surgery with radiotherapy saves the breast look so that it can improved the quality of life of patients significantly,and treats the tumor at the same time.Radiation therapy is a significant and vital tool to improve the local control for the patients with breast conserving surgery.Articals shows that most local recurrence of tumor occurs within 3cm of the primary tumor,and intraoperative radiotherapy(IORT)has obvious advantages in local control of radiotherapy in the tumor bed of the primary tumor.The biggest advantage for intraoperative radiotherapy is that it avoids the dislocation of tumor bed by the postoperative flap displacement.Another advantage for IORT is that it can reduces the risk of tumor proliferation caused by delayed radiotherapy.It can improve the accuracy of the tumor bed boost and it is conducive to the increase of intraoperative radiotherapy on the local control of breast cancer.The possible mechanism of intraoperative radiotherapy for local control of breast conserving breast cancer patients is the focus of current research.In terms of clinical efficacy,we included 70 patients with breast conserving surgery combined with intra-operative radiotherapy(8 cases were BCS+IORT,62 cases were BCS+IORT +WBI)and matched 45 patients with conventional breast conserving surgery according to age,tumor size,pathological results and other information.The postoperative complications and local recurrence of 115 patients were followed up to evaluate the efficacy and adverse reactions of intraoperative radiotherapy.In terms of mechanism,we collected wound fluids from the breast cancer patients who took the breast conserving surgery combined with intraoperative radiotherapy and wound fluids from breast cancer patients who took breast conserving surgery only,and then co-cultured with breast cancer MDA-MB-231 cells respectively,to observe the effect of wound fluids from breast cancer patients after breast conserving surgery combined with intraoperative radiotherapy on the expression of apoptosis genes TRAIL、Bcl-2 、Bax and CASP10 in breast cancer MDA-MB-231 cells line.To explore the possible mechanism of intraoperative radiotherapy on the local control of breast cancer.Methods:We collected clinical data of 70 patients with breast conserving surgery combined with intraoperative radiotherapy(8 cases were BCS+IORT,62 cases were BCS+IORT+WBI)who were hospitalized in the Department of Breast Surgery,the Second Hospital Affiliated to Guangzhou Medical University from March 2018 to March 2020,and matched 45 patients with conventional breast conserving surgery according to general information such as patient age,tumor diameter and lymph node status.115 patients were followed up in terms of postoperative complications,local recurrence,distant metastasis,and radiotherapy related toxicity and side effects by telephone,outpatient return visit,online return visit,etc.,to evaluate the effect of intraoperative radiotherapy on the wound and postoperative local control after breast conserving surgery.In addition,24 h postoperative wound fluid of patients undergoing breast conserving surgery in the Department of Breast Surgery,the Second Hospital Affiliated to Guangzhou Medical University from March 2021 to December 2021 were collected,including 10 patients undergoing breast conserving surgery alone and10 patients undergoing breast conserving surgery combined with intraoperative radiotherapy.The wound fluid was conventionally cultured with MDA-MB-231 breast cancer cells for 24 hours,and RNA(Ribonucleic Acid)was extracted for reverse transcription.The expression of apoptosis pathway related genes TRAIL,Bcl-2,Bax and CASP10 was detected by real-time quantitative Polymerase Chain Reaction(RT-q PCR).Results:1.The clinical data of 70 patients with breast conserving surgery combined with intraoperative radiotherapy(8 cases were BCS+IORT,62 cases were BCS+IORT +WBI)were collected(IORT group),and 45 patients with conventional breast conserving surgery were matched according to the general situation of the patients(BCS group).The median follow-up was 26 months.The local recurrence rate of the breast conserving group was 4.4%,and that of the intraoperative radiotherapy group was 2.9%(P=0.65).None of the 8 case extremely low-risk patients(Meet the criteria of ASTRO for intraoperative radiotherapy: age ≥50 years,single lesion,tumor diameter ≤2cm,lymph node negative,ER receptor positive,surgical margin negative)in the intraoperative radiotherapy group who received intraoperative radiotherapy alone had recurrence during follow-up.It is suggested that intraoperative radiotherapy alone may achieve near-term local control similar to that achieved by whole breast radiotherapy in extremely low-risk patients.No distant metastasis or death occurred in the two groups during follow-up,and the survival rate was 100%.The incidence of postoperative complications was 15.4% in the breast conserving group and 18.6% in the intraoperative radiotherapy group(P=0.67).Intraoperative radiotherapy did not significantly increase the incidence of postoperative wound infection,fat necrosis and other complications.The incidence of postoperative whole breast radiotherapy was 55.5% in the breast conserving group(n=45)and 12.5% in the BCS+ only IORT group(n=8)(P=0.051),22.6% in the BCS+IORT+WBI group(n=62),There was statistical difference between this group and the breast conserving group(P=0.001).And the most toxic reactions were radioactive dermatitis(13 cases in the breast conserving group + 7 cases in the intraoperative radiotherapy group),and mainly grade I radioactive dermatitis.Intraoperative radiotherapy did not increase radiation-related toxicity.2.Compared with the breast conserving group,Wound fluids combined with intraoperative radiotherapy promoted the up-regulated expression of apoptosis gene TRAIL(IORT-WF=2.95±1.59;WF=1.36±1.02)、 Bax(IORT-WF=1.04±0.31;WF=0.47±0.18)、CASP10(IORT-WF=1.01±0.16;WF=0.36±0.08)in MDA-MB-231 breast cancer cells and suppressed the expression of Bcl-2(IORT-WF=0.54±0.4;WF= 1.27 + 0.9)(P<0.05).Intraoperative radiotherapy may achieve local control by inducing local tumor cell apoptosis in tumor bed.Conclusions:1.For highly selective breast conserving patients,only intraoperative radiotherapy can achieve short-term local control effect similar to that of whole breast radiotherapy.2.Intraoperative radiotherapy did not significantly increase the incidence of postoperative complications in breast conserving surgery,and there was no increase in radiotherapy-related toxicity.3.Wound fluid after intraoperative radiotherapy promoted the up-regulated expression of pro-apoptotic genes TRAIL,CASP10 and Bax in MDA-MB-231 breast cancer cells,and inhibited the expression of anti-apoptotic gene Bcl-2.Intraoperative radiotherapy may induce the apoptosis of tumor cells by affect the expression of apoptosis pathway related genes.