Dosimetric characteristics of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free‐hand implantation in the treatment of early breast cancer

Abstract Introduction The aim of this study is to evaluate the characteristics of the dosimetry and the skin dose of interstitial brachytherapy by the use of the free‐hand implantation technique toward the treatment of early breast cancer. Materials & Methods Seventeen patients diagnosed with early breast cancer were selected for the study. The implantation of the catheters for postoperative interstitial brachytherapy was performed using the free‐hand technique. The total tumor dose to the tumor cavity plus 2 cm margin was 3400 cGy, twice daily for 10 fractions in 5 days. The dosage to the target and the organ at risk (OAR) were recorded for analysis. The skin dose of the patient and the phantom were measured with Gafchromic film (EBT3) and the results were compared with the skin dose calculated by the brachytherapy treatment planning system. Results The median conformal index is 94% (range 89%–99%), and the median homogeneity index is 71%. The median skin dose measured from the skin of the patients was 20.1% lower than the skin dose calculated from the treatment planning system and consistent with the phantom surface measurement experiment. There were no grade 3 or above acute toxicity recorded. Conclusions Interstitial brachytherapy by the use of the free‐hand implantation technique for early breast cancer is feasible and avoids the need for a second surgical intervention. The calculated skin dose was overestimated by at least 20%. The results of this study may help in building a modification model for the prediction of skin toxicity in any future study.

effects, and positive cosmetic results. 4,5 However, conventional WBI after BCS is a time-consuming treatment that requires a course of 5-6 weeks until completion of the treatment. The difficulties involve transportation, and the adverse effects during radiation therapy may prohibit the patients' ability to work for their livelihood. Additionally, a significant portion of the normal organs, particularly the lung and heart, are irradiated within the radiation field during conventional WBI. 6,7 The acute side effects may prohibit the patient from working, while some of the serious late side effects may even cause premature death from heart disease in certain patients. 8 Accelerated partial breast irradiation (APBI) offers a high dose to the target while reducing risk in a significant portion of normal organs at risk due to the prescribed doses. 9 APBI increases the quality of life of the patient by reducing the volume of breast irradiated to the tumor cavity plus a 1-2 cm margin, while also shortening the radiation treatment duration to 4-5 days. 10 The results of recent clinical trials involving APBI revealed that APBI can be an alternative treatment modality to conventional WBI in the treatment of early breast cancer. 11 APBI has been suggested as one of the treatment options for low-risk breast cancer patients after BCS in many treatment guidelines. 12,13 APBI can be performed using interstitial brachytherapy, intraoperative radiotherapy, or external beam irradiation. [14][15][16] Interstitial brachytherapy for the treatment of early breast cancer has been under investigation for more than 20 years and has been found to be noninferior in terms of local control, overall survival, and disease-free survival. 11 Although interstitial brachytherapy is an attractive method of APBI for the treatment of early breast cancer, the high learning curve due to the difficulty of the technique and the lack of recommendations for target delineation and treatment workflow are the reasons for its infrequent utilization in our country.
Most of the interstitial brachytherapy cases which have been reported were performed using a sonography-guided or computed tomography (CT)-guided multicatheter implantation after the BCS, which in turn required a second operation. The present study reports on our dosimetry analysis of the treatment plans for patients enrolled in interstitial brachytherapy involving intraoperative freehand multicatheter implantation at our institution. The intraoperative free-hand multicatheter implantation technique is a one-step procedure that allows for the avoidance of a second surgical intervention.
Because the skin dose is closely related to the cosmetic results after interstitial brachytherapy, the dosimetry analysis on the comparison of the measured skin dose, the treatment planning system calculated skin doses, and the phantom measured surface doses are also reported in this study. This study was reviewed and approved by our Institutional Review Board (IRB CF17213B). Informed consent has been obtained from all patients in the written form.

| MATERIALS AND METHODS
Seventeen patients diagnosed with early breast cancer who had matched our inclusion criteria for multicatheter high dose rate (HDR) interstitial brachytherapy were selected for the study. The intraoperative implant of the catheters was performed using the open tumor cavity free-hand technique. For localization of the tumor bed after lumpectomy, surgical findings are incorporated with physician palpation, preoperative sonography, and CT scan. In the surgery, the tumor bed was visualized directly and the extent of the tumor cavity was marked by four surgical clips at the superior, inferior, medial, and lateral sites. The skin projections of the tumor bed [inner blue circle in Fig. 1 The CT scan slice thickness was 2.5 mm and the CT image was acquired with the patient in a supine position after the insertion of the radio-opaque dummy source (Fig. 2). The CT images were then transferred to our treatment planning system (TPS). The target contouring followed the definition recommended by the International Commission on Radiation Units and Measurements (ICRU) Report 50. 17 The tumor bed cavity was identified by the surgical clips with or without the seroma. The clinical target volume (CTV) was contoured at a distance of 2 cm from the tumor cavity. The planned target volume (PTV) is defined by the CTV plus a 0.5 cm margin. The ipsilateral breast, the skin, and nearby ribs, as well as the ipsilateral lung and the heart, were also contoured. The treatment planning was designed by the Oncentra Brachy V4.5.3 planning system from the same company. The treatment was initiated on the fourth day after surgery. All patients were treated with the Elekta microSelectron HDR afterloader. A 1 cm × 1 cm Gafchromic EBT3 film was placed on the marked skin area during CT simulation for the skin dose measurement 18 prior to the initiation of brachytherapy.
The delivered dose was 340 cGy per fraction, twice daily at 6 h apart, for a total of 10 fractions in 5 days, making for a total tumor dose of 3400cGy. The dose constraints were 95% of the target volume covered by 95% of the prescribed dose. The definitions of the involved skin region for dose calculation by TPS are previously described in the first paragraph of the method section [ Fig. 1 The dose constraints for the previously defined skin region was kept at 0.2 cm 3 volume (D 0.2 cm 3 ) less than 100% of the prescribed dose and 1 cm 3 volume (D 1 cm 3) less than 90% of the prescribed dose.
The involved ribs are defined as the rib volume just beneath the previously defined skin region. The dose constraints for the involved rib was kept at 0.1 cm 3 volume (D 0.1 cm 3 ) less than 90% of the prescribed dose and 1 cm 3 volume (D 1 cm 3 ) less than 80% of the prescribed dose. For the ipsilateral nontarget breast, 90% of the volume was covered by less than 10% of the prescribed dose; heart doses were constrained to a mean heart dose less than 8% of the prescribed dose and 0.1 cm 3 of the heart < 50% of the prescribed dose.
The ipsilateral lung was constrained by the mean lung dose < 8% of the prescribed dose and 0.1 cm 3 of the volume < 60% of the prescribed dose.
The definitions of the key dose-volume parameters for the target are described below. The coverage index (CI) 19 is defined as the fraction of the PTV receiving the prescribed dose. The conformal index (COIN) 19 is calculated using the equation: where PTV PD refers to the volume in PTV received the prescribed dose; V PTV refers to the volume of the PTV; V PD refers to the absolute volume irradiated by the prescribed dose.
The homogeneity index (HI) 20 is calculated using the equation: where V PD refers to the absolute volume irradiated by the pre- films were kept in a dry, dark area at room temperature for at least 24 h before reading. The optical density was found using the Epson Expression 10000XL scanner and then converted into the dosage using a calibration curve by green channel. 21 All measured doses were expressed as a percentage of the prescribed doses.

| RESULTS
The intraoperative free-hand multicatheter implantations were performed smoothly for all of our patients. The patient characteristics are shown in Table 1. Due to the small breast size of Asian women, the use of a double plane arrangement for the catheters was enough to cover the tumor cavity plus 2 cm margins for all of the patients. The dosimetric characteristics of the target parameters and the OAR are shown in Table 2 and Table 3 apy. The measured skin dose was overestimated by the TPS. 22 The median skin point dose measured from the skin surface of the patients was 20.1% lower (range 15%-33%) than the skin doses calculated from the treatment planning system (Fig. 4). The phantom

| DISCUSSION
Interstitial multicatheter brachytherapy is a less common approach in Asian countries than it is in Western countries. There were only a few studies from Asian countries that reported their treatment results in 2017. 23  , absolute dose given to exposed xxcm 3 of organ.
F I G . 4. The overestimation ratio of skin dose between the calculated dose by TPS and the measured dose by EBT3 film on the patients. The horizontal line at 20.1% indicates a median percent difference between the calculated dose and the measured dose. respectively, which is less than the suggested European Society for Therapeutic Radiology and Oncology (ESTRO) recommendation. 12 Model-based dose calculation algorithms (MBDCAs) have been developed for resolving the problems with the tissue heterogeneities. 25,26 Radioactive source for HDR brachytherapy requires detailed measurement of dosimetric parameters to improve the accuracy of the TPS. Hence, the dosimetric parameters of several radioactive sources are well investigated and compared by Monte Carlo calculations and experimental measurements. [27][28][29][30][31][32][33] In these radioactive sources, iridium-192 is the most common radioisotope for HDR brachytherapy due to low average energy of 0.38 MeV and needs less shielding for personnel protection. In previous literature for the dosimetric parameters of iridium-192, there is a negligible difference (less than 6%) between the dose calculated by TPS and that measured by Gafchromic film. 32

| CONCLUSION
The dosimetric characteristics of interstitial brachytherapy using the intraoperative free-hand catheter implantation technique are comparable to the recommendation of some major clinical trials previously performed. This procedure prevents a second surgical intervention.
The skin dose is overestimated by TPS around 20%. This result is consistent with the data from the phantom skin dose measurement experiment. The result of this study may help to build a modification model for the prediction of skin toxicity in further dosimetric or clinical studies.

ETH ICAL APPROVAL
This study was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (ethical approval number: IRB CF17213B). Informed consent has been obtained from all patients in the written form. F I G . 5. The dose difference ratios between the TPS-calculated dose and the measured dose by EBT3 film on the phantom.

DECLARATIONS OF IN TE REST
none.

ACKNOWLEDGMENTS
This study was supported by Taichung Veterans General Hospital.