OBJECTIVE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS).
METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT.
RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT.
CONCLUSIONS: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.

This study aimed to identify factors associated with strut-adjusted volume implant (SAVI) displacement in accelerated partial breast irradiation (APBI) using a SAVI device.
We retrospectively analyzed computed tomography scans taken at the time of treatment planning and immediately before treatment in 61 patients (median age; 55 years, range; 40-85) treated with SAVI and determined the amount of SAVI displacement that occurred between the time from planning to the treatment. The displacement was calculated for the CT axis and SAVI axis, which is related to the SAVI structure. To investigate the cause of the displacement, multivariate analysis was performed on the calculated standard deviation and the insertion angle of SAVI with respect to the sternum in each cross-section, breast density, amount of air around the SAVI, and SAVI length inside the patient to obtain the β coefficient (p-value).
On the CT coordinate system, positive correlations were observed between the SAVI insertion angle and air volume in the lateral (β coefficient:0.255-0.483) and rotational directions (β coefficient:0.341). On the SAVI coordinate system, positive correlations were observed between the SAVI insertion angle and air volume in all lateral (β coefficient:0.270-0.354) and rotational directions (β coefficient:0.294). A negative correlation was observed between the SAVI length inside the patient and the rotational direction (β coefficient: -0.262).
SAVI insertion angle, the amount of the air outside SAVI and SAVI insertion length are factors which affect the displacement of the applicator. From the results, the applicator displacement and rotation must be <3 mm and 10o in order to meet all the dose criteria. Thus, we should be aware of these factors during insertion of the device to avoid the problem in treatment delivery for the APBI.

Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial.
At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical).
Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%.
The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

OBJECTIVE: Transforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine used as an early biomarker to develop radiation-induced fibrosis (RIF). This study aimed to compare TGF-β1 serum levels in early-stage breast cancer patients treated with whole-breast radiation therapy (WBRT) plus boost versus accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy.
METHODS: This clinical trial study was conducted on 20 women with early-stage breast cancer after breast-conserving surgery candidate for adjuvant radiotherapy in Golestan hospital, Ahvaz, in 2021. In one group APBI with high-dose-rate brachytherapy (n = 10), the other group WBRT with external beam radiation plus boost (n = 10) was performed. Serum level of TGF-β1 was evaluated before radiotherapy, immediately after the end of radiotherapy and three months after the end of radiotherapy by Enzyme-linked immunosorbent assay technique (ELISA).
RESULTS: Median serum TGF-β1 level before radiotherapy was not significantly different between the two groups (p = 0.971). In both APBI and WBRT groups, serum TGF-β1 levels significantly decreased immediately after radiotherapy compared to before treatment (p = 0.005 and p = 0.007, respectively); But three months after radiotherapy, serum TGF-β1 levels increased significantly in the WBRT group (40.50 to 77.41 pg/mL; p = 0.017), while no significant change was observed in the APBI group (24.75 to 30.50 pg/mL; p = 0.332).
CONCLUSIONS: Higher TGF-β1 values in the WBRT group after radiotherapy can be used as an early and vital biomarker in this treatment, and this data may corroborate links between TGF-beta1 and fibrosis and fibrosis rates between APBI and WBRT; It also shows the preference for using the brachytherapy technique in this group of patients. However, due to the small number of samples, definitive conclusions require further prospective studies.

UNASSIGNED: For appropriately selected patients with early-stage breast cancer (ESBC), accelerated partial breast irradiation (APBI) yields equivalent rates of ipsilateral breast tumor recurrence with mixed results in patient-rated cosmesis compared with whole-breast radiotherapy depending on the technique utilized. When utilizing external beam radiotherapy for APBI, techniques to reduce target margins and overall treatment volume are potentially important to decrease rates of long-term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is a promising technique to deliver APBI because of its increased accuracy and sparing of uninvolved breast tissue. We report the initial results of a prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of a daily five-fraction SBRT regimen for APBI.
UNASSIGNED: Twenty-three patients with ESBC after lumpectomy who met APBI suitability were enrolled. During lumpectomy, a bioabsorbable three-dimensional fixed array tissue marker (BioZorb™, Hologic, Marlborough, MA) was placed for enhanced visualization of the cavity boundaries. Clinical target volume (CTV) was defined as the delineable cavity plus a 1-cm isotropic expansion followed by a 3-mm isotropic planning target volume (PTV) expansion. Patients received 30 Gy delivered in five planned consecutive daily fractions in either prone or supine positioning depending on individual anatomy. Two patients completed the five-fraction treatments in 9-day interval and 11-day interval due to external circumstances. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans utilized 10-MV flattening filter-free beams delivered on a Varian Edge linear accelerator. Local control, toxicity, and nurse/patient-scored cosmesis at pre-treatment baseline, 1 month post-treatment, and at subsequent 6-month intervals were recorded.
UNASSIGNED: Twenty-three patients were accrued at the time of submission with median follow-up of 6 months. No patients experienced grade ≥3 acute toxicity. Of the 10 events reported probably related to SBRT, nine were grade 1 (n = 9/10, 90%). There was no evidence of difference, deterioration, or change in patient or nurse-scored cosmesis from baseline to 1 and 6 months post-treatment. One patient developed nodal failure shortly after APBI.
UNASSIGNED: Although longer follow-up is needed to assess long-term toxicity and local control, this study demonstrated a five-fraction SBRT regimen delivered over consecutive days is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering APBI in suitable women.
UNASSIGNED: https://www.clinicaltrials.gov/ct2/show/NCT03643861, NCT03643861.

BACKGROUND: Intraoperative radiotherapy (IORT) for breast cancer is used as an upfront boost or as accelerated partial breast irradiation (APBI). To date, no description of blood count changes after IORT are available. Our analysis shows blood count changes in breast cancer patients up to 5 years after IORT ± whole breast radiotherapy (WBRT).
METHODS: IORT was given as APBI in 58 patients (IORT/APBI-group) and as a boost in 198 patients (IORT/WBRT-group). A median dose of 20 Gy was given intraoperatively with low energy X-rays [INTRABEAM (TM) System] and additionally 46 Gy/2 Gy per fraction to the whole breast, if WBRT was added. Blood counts were collected preoperatively, after 90 days and through year 1-5 of follow-up. Dunnett\'s tests were used to calculate changes in blood counts over time. Additionally, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated for each time point.
RESULTS: Significantly decreases in the IORT/WBRT-group were seen for erythrocytes, hemoglobin, platelets and leucocytes and an increase for lymphocytes for the total follow-up period. In the IORT/APBI-group significantly decreases were seen for erythrocytes and hemoglobin for the total follow-up period. Regarding changes during follow-up compared to the preoperative value, much more significant changes were seen in the IORT/WBRT-group compared to IORT/APBI-group without any relevant impact of chemotherapy. Regarding PLR-, NLR- and dNLR-values the rate of patients over the range improved over time in both groups.
CONCLUSIONS: IORT/APBI seems to have a smaller effect on blood counts compared to IORT/WBRT. Furthermore, PLR-, NLR- and dNLR-values improved over time, suggesting a positive effect on outcome after IORT in general.

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with \'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)\'-in terms of equivalent local control/overall survival to the previous standard \'conventionally fractionated WBIR\'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.

BACKGROUND: Breast-conserving therapy including lumpectomy and adjuvant whole breast irradiation (WBI) has become the standard therapy for early-stage breast cancer (EBC). Without WBI, the recurrence rate is significantly increased. However, when selecting patients at a low a priori risk of local recurrence only a small breast-cancer-specific mortality benefit, but no overall survival improvement, was detected for WBI. As most recurrences occur close to the lumpectomy cavity, accelerated partial breast irradiation (APBI) delivered exclusively to a limited volume of tissue around the initial lumpectomy site, has gained increased attention and is now discussed as an alternative to WBI for selected EBC patients.
CONCLUSIONS: Numerous techniques for APBI (interstitial brachytherapy, external beam-based APBI, intraoperative radiotherapy, MR-guided radiotherapy) allow treatment delivery in a shorter period of time, and radiation oncologists expect to further reduce side effects by using these new techniques, with improvements in cosmetics and quality of life. In this review, we aim to describe the existing evidence for the feasibility and effectiveness of different APBI techniques used in modern radiotherapy.
CONCLUSIONS: APBI has provided outcomes similar to WBI combined with potentially reduced toxicity. While appropriate patient selection persists to be crucial for acceptable recurrence rates, the precise definition of patients suitable for APBI remains a matter of discussion. As long-term data are often still lacking, special attention should be paid to late side effects and long-term outcomes. Decision-making on appropriate treatment techniques should take into account not only local control rates, but also the impact on the patient\'s quality of life.

Breast conservation therapy exemplifies the tailoring of medicine in the care of patients with cancer. Akin to improvements in surgical approaches, accelerated partial breast irradiation (APBI) tailors the treatment volume and duration to the needs of well selected patients. Here, we examine the evidence supporting APBI as well as the lessons in patient selection, dose and delivery techniques. Examination of historical techniques and their associated outcomes will support more correct patient selection and treatment delivery in an era where we await the reports of several large prospective trials.

To report the clinical implementation of a novel external beam radiotherapy technique for accelerated partial breast irradiation treatments based on combined electron and photon modulated beams radiotherapy (MERT+IMRT) with conventional MLC.
A group of patients was selected to test the viability of the technique. The prescribed dose was 38.5Gy, following a hypofractionated schema, and the structures were defined following the NSABP-B39/RTOG-0413 protocol. The plans were calculated with an in-house Monte Carlo based planning system to consider explicitly the particle interactions with the MLC. An ad-hoc breast phantom was designed for a specific QA protocol. A reduced SSD was used for electron beams. Toxicity and cosmetic effects were assessed at every follow-up visit.
All the plans achieved the dosimetric objectives and fulfilled the specific quality assurance protocol. Treatment delivery did not entail additional drawbacks for the clinical routine. Moderate or severe grade of toxicity was not reported, and the cosmetic results were comparable to those obtained with other APBI techniques.
Results showed that MERT+IMRT with the MLC is a feasible and secure technique, and easy to be extended to other centers with the implementation of the adequate software for planning.