Efficacy,Complications,and Cosmetic Outcomes Of Intrabeam Intraoperative Radiotherapy System In Breast-conserving Surgery For Breast Cancer

Breast cancer is one of the most common malignancies in women,accounting for about 10%of all malignancies in women,and more than 1.4 million women are diagnosed with breast cancer every year worldwide.With the continuous application of breast X-ray screening technology,about 60%of patients are diagnosed in the early stage of breast cancer,and breast conserving surgery plus postoperative whole breast external beam radiotherapy(EBRT)has become the main treatment for these patients.At present,EBRT with single dose of 1.8-2.0Gy and total dose of 45-50Gy is usually adopted after breast-conserving surgery for early breast cancer.Most patients need tumor bed boost of 10-16gy depending on whether there are risk factors and the total treatment time is 5-7 weeks.However,many studies have found that 90%of breast cancer recurrence after breast-conserving surgery is concentrated in the focus quadrant with or without EBRT,and the recurrence rate of breast cancer outside the ipsilateral breast tumor bed is similar to the incidence of the second primary breast cancer on the opposite side.Therefore,more and more scholars began to question the necessity of EBRT after breast-conserving surgery,and the concept of accelerated partial breast irradiation(APBI)came into being.APBI adopts the large fraction radiotherapy technique and only irradiate the tumor bed and its surrounding area of 1-2cm,which shortens the duration of the whole radiotherapy and reduces the volume of exposed breast.APBI technologies include multi-catheter interstitial brachytherapy,balloon catheter brachytherapy,three-dimensional conformal radiation therapy,and intraoperative radiotherapy.Compared with other technologies,intraoperative radiotherapy is able to perform single high-dose irradiation on tumor bed under direct vision during surgery,which reduces the risk of tumor proliferation caused by delayed radiotherapy,ensures the accuracy of tumor bed dose,and reduces the dose of surrounding organs by avoiding various errors such as patient movement and tumor bed definition.As a way of APBI,targeted intraoperative radiotherapy(TARGIT)uses Intrabeam system(Carl Zeiss Meditec,Oberkochen,Germany)produced by Zeiss in Germany to generate low-energy X-ray,which can give all the required radiation dose at one time under direct vision during surgery and only illuminate tumor bed.Compared with EBRT,it greatly shortens the treatment time and reduces the volume of exposed breast.As the most widely used mobile intraoperative radiotherapy technique,it is also the focus of research in recent years.The multicentre,large-cohort,randomized controlled TARGIT-A trial conducted in 2013 found that TARGIT may replace EBRT in some patients with early breast cancer.Patients in TARGIT group were not worse than those in EBRT group in overall survival rate and overall toxicity,and the incidence of high-level toxic and side effects was lower than those in EBRT group.However,the follow-up time of this study was short,and the local recurrence rate was higher than that of the EBRT group.We also noted that no Asian patients were involved in the study.Toxicity of TARGIT in Asian women is also of concern,given that the mammary glands of Asian women are smaller than those of western women.In addition,although high-level complications are rare,TARGIT may cause a variety of low-level side effects,which may cause some discomfort to patients and may reduce the satisfaction of treatment.There are few reports on TARGIT in Asia,and no study on the risk factors of TARGIT complications in Asian population has been seen.China was late to introduce this technology.Currently,the Chinese Society of Clinical Oncology recommends the application of APBI based on the recommendation of the American Society for Radiation Oncology.There is no high-level evidence that TARGIT is suitable for Chinese breast cancer patients.This study retrospectively analyzed the clinical data of breast cancer patients who received breast-conserving surgery combined with TARGIT in our center,observed the clinical efficacy,complications and cosmetic effects,and discussed the risk factors affecting the complications.Meanwhile,it compared the efficacy of TARGIT and traditional EBRT for breast cancer,hoping to provide some reference for clinical decision-making.Part ? Observation on efficacy,late complications,and cosmetic outcomes of targeted radiotherapy in breast conserving surgery for early stage breast cancerMethodsBetween September 2014 and May 2017,breast cancer patients undergoing TARGIT at our facility were recruited for this study.Intraoperative radiotherapy was performed with a 5 0-kV X-ray source in an Intrabeam system.The one-time prescribed irradiation dose to the tumour bed was 20 Gy after breast-conserving surgery.Clinical data and treatment parameters of all patients were documented.Recurrence,death,late complications,and cosmetic outcomes were recorded.Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group(RTOG).Cosmetic outcomes were assessed by patients or the same physicians according to the difference between the treated and untreated breast.ResultsA total of 82 patients were recruited,including 77 subjects(93.9%)who were treated with TARGIT only.The cohort had a mean age of 57 years(23 to 85 years);the median follow-up duration was 40 months(4 to 52 months);there were 2 cases of recurrence and 2 cases of death.The 1-,2-,and 3-year recurrence rates were 1.2%,1.3%,and 1.5%,respectively;the 1-,2-,and 3-year survival rates were 98.8%,97.5%,and 97.0%,respectively.There were no cases of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above.The main complications were seroma(17.1%),breast oedema(17.1%),chromatosis(11.0%),induration(7.3%),pain(4.9%),skin depression(2.4%),mild dry cough(2.4%),delayed wound healing(1.2%),and wound infection(1.2%).Last,78 patients participated in the cosmetic outcome evaluation,which yielded an excellent or good rate of 96.2%.ConclusionsWith low recurrence rates,no high-grade late radiotoxicity,and excellent cosmetic outcomes,TARGIT may be a suitable treatment for select early-stage breast cancer patients in China.Part II Risk factors of complications after targeted intraoperative radiotherapy in breast-conserving surgery for breast cancerMethodsA retrospective study was conducted on 82 breast cancer patients who received breast-conserving surgery combined with TARGIT in our hospital from September 2014 to May 2017.Wound-related complications and late radiotoxicities were recorded.Univariate analysis and multivariate logistic regression models were used to analyze the influence of variables on the overall complications and major complications.ResultsThe 82 patients had an average age of 57 years.The median follow-up time was 3.3 years.37 patients(45.1%)had complications.There was no case of RTOG 3-4 grade radiotoxicity.Univariate analysis showed that perioperative use of anticoagulants,applicator size,time of intraoperative radiotherapy and chemotherapy were the possible risk factors for overall complications(P<0.1).Multivariate logistic regression analysis showed that perioperative use of anticoagulants and applicator size were independent risk factors for overall complications(P=0.039,0.002),and perioperative use of anticoagulants and age were independent risk factors for skin edema and pigmentation,respectively(P=0.032,0.005).ConclusionsBreast-conserving surgery combined with TARGIT is safe and feasible in Chinese breast cancer patients.Perioperative use of anticoagulants and applicator size may predict overall complications.Part ? Comparison of efficacy of TARGIT and traditional EBRT in Chinese breast cancer patients with breast-conserving surgeryMethodsA total of 281 patients with breast cancer who underwent breast conserving surgery in our hospital from April 2009 to October 2017 were retrospectively selected.According to radiotherapy methods,they were divided into TARGIT group and EBRT group.Intrabeam system was used for TARGIT with a prescribed dose of 20Gy on the adapter surface.One to one propensity score matching was performed to balance the covariance between TARGIT group and EBRT group.Kaplan-meier method was used to calculate the locoregional recurrence(LR),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups of patients.The treatment effect of the two groups before and after matching was compared by log-rank test.ResultsThe median follow-up of 281 patients was 43 months.There were 82 cases in TARGIT group and 199 cases in EBRT group.Before matching,the cumulative 3-year LR of TARGIT group and EBRT group was 1.2%and 1.6%(P=0.694),the 3-year DMFS was 100%and 97.8%(P=0.157),the 3-year DFS was 98.8%and 96.7%(P=0.604),and the 3-year OS was 97.6%and 97.8%(P=0.862),respectively.There was no significant difference between the two group's.After matching,the baseline characteristics were balanced,and a total of 128 patients were included in the analysis.There was no significant difference in LR,DMFS,DFS and OS between the TARGIT group and the EBRT group at 3 years(P=0.659,0.313,0.659 and 0.987).Univariate analysis showed that ER,Ki67 and endocrine therapy were significantly correlated with LR,N staging was significantly correlated with DMFS,Ki67 was significantly correlated with DFS,and N staging was significantly correlated with OS(all P<0.05).Cox multivariate analysis found that endocrine therapy was an independent factor affecting LR,andKi67 was an independent factor affecting DFS.ConclusionsTARGIT is not inferior to EBRT in specific breast cancer patients in China and can be an effective alternative to standard therapy.The long-term results need to be confirmed with extended follow-up time.