This study represents the first population-based national cohort study to investigate the pattern of care and complications among patients with breast reconstruction and PMRT between 2015 and 2020. Despite the increasing number of breast reconstructions, uncertainties persist regarding the timing and materials employed in the context of PMRT. Moreover, with advancements in radiation technology, hypofractionation has emerged as a replacement for conventional fractionation in breast cancer treatment. However, despite several randomised prospective studies, the impact and safety of hypofractionation under breast reconstruction setting was not well studied. Here, we utilised the big data from the National Health Insurance Service and reported the current status of breast reconstruction and PMRT in the South Korean population and showed comparable complication rates regardless of fractional regimens.

Our nationwide cohort study revealed that immediate reconstruction (55.4%) was the most preferred approach, followed by delayed two-stage reconstruction (36.0%). Within immediate reconstruction, autologous tissues were preferentially selected over implants. This finding aligns with the concerns regarding the elevated complications risk associated with implants compared to autologous tissue in an immediate reconstruction setting. Despite these concerns, implants remained a population choice, probably due to the shorter surgery time, faster recovery, and no donor site morbidity. Delayed two-stage reconstruction with implants was also commonly performed in our cohort. This approach is endorsed by the NCCN, as the immediate implant placement carries an increased incidence of capsular contracture, malposition, and poor cosemesis [13]. However, delayed reconstruction using autologous tissue was rarely chosen compared to the immediate reconstruction setting.

We found comparable toxicity between CF and HF in the immediate reconstruction cohort [14]. Globally, a limited number of studies have investigated the use of HF in reconstructed breasts, with heterogeneity in fractionation regimen and complication rates. Another cohort study conducted in Brazil examined the safety of hypofractionated PMRT (2.65–2.67 Gy/fraction) in reconstructed breasts. Among 35 patients who underwent implant-based immediate reconstruction, capsular contracture developed in 11.4% [14]. In contrast, a U.S. Phase II trial reported an incidence of severe complications of 35% in 43 patients receiving a dose of 36.63 Gy in 11 fractions with a daily fraction size of 3.33 Gy [15].

Beyond compatibility between fractionation regimens, our study identified several associated risk factors for reconstruction-related complications. Implant usage emerged as the sole significant prognostic factor for complications. This aligns with existing knowledge regarding the increased susceptibility of implants to radiation-induced complications. Despite the elevated risk of adverse effects such as capsular contracture associated with implants, their popularity persists due to cost-effectiveness and broader eligibility compared to autologous tissues. Consequently, further advancements in implant-based reconstruction and radiation techniques are paramount to enhancing reconstruction outcomes. While bolus application has been shown to increase toxicity in reconstructed breasts, our study did not identify a significant association between bolus usage and complication risk. This discrepancy may arise from the application of different bolus definitions in our study and the prior literature. Bolus is more likely to induce skin-related toxicity, whereas our study focused primarily on complications requiring surgical interventions [16]. However, de Sousa et al. reported an increased risk of infection (HR 10.3, CI 1.7–61.8), and reconstruction failure (HR 13.89, CI 2.24–85.98) in patients undergoing two-stage reconstructions when bolus was applied daily [17]. In contrast, alternate-day bolus usage was not associated with complication risk. Therefore, it is still important that the decision to use bolus for PMRT should be individualised considering the benefits and the risks.

A recent prospective randomised trial, the Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) study, found no significant differences in oncologic outcomes or chest wall toxicity between conventional fractionation and hypofractionation in 400 patients with immediate implant-based reconstructions [18]. The FABREC trial also reported improved quality of life in patients over 45 years old, along with reduced treatment breaks and financial toxicity in the HF group. Another pivotal study, RT CHARM (ALLIANCE A221505), is currently underway and includes both immediate and delayed reconstruction. Its results are eagerly anticipated, as they will provide valuable data on the safety of hypofractionation in the reconstruction setting.

Addressing the role of acellular dermal matrix (ADM) in immediate implant-based breast reconstruction is vital due to its widespread use and potential impact on complications. ADM is a biomaterial processed to remove cellular components while preserving extracellular matrix structure. Until now, the effect of ADM on patients undergoing PMRT is not well defined, but a few retrospective studies suggested a protective role in irradiated patients [19,20,21]. However, our study could not directly identify its actual usage because it has not been reimbursed by the government. A multi-institutional data from the South Korea Radiation Oncology Group indicated its prevalence, with over 50% utilisation in breast reconstruction and PMRT between 2015 and 2016 [22]. Considering the contemporary reliance on ADM in breast reconstruction practices, it may be reasonable to assume its significant incorporation in our study population, especially since ADM is routinely integrated into implant-based reconstruction protocols at our institution.

In addition to ADM usage, it is also important to understand the dosimetric planning and target delineation in our population. While the specific planning protocols may vary among hospitals in South Korea, it seems to follow the general principle [23]. For the hypofractionation scheme, at least 95% planning target volume was required to be covered by 95% of the prescribed dose, and the maximum point dose (D max) was limited to below 105–107%. Organ-at-risk constraints ensured that the volume of the ipsilateral lung receiving 5 Gy (V5) and 20 Gy (V20) did not surpass 45% and 20%, respectively. The mean dose to the heart was maintained be low 3 Gy and 5 Gy for right-sided tumours and left-sided tumours, respectively. The most commonly utilised RT techniques were forward IMRT (field-in-field) followed by VMAT and 3D conformal, according to a multi-institutional retrospective study conducted in South Korea [22]. In terms of target delineation, it seems that there is no specific preference between RTOG and ESTRO guidelines among radiation oncologists in South Korea [23]. Also, some institutions adopted new ESTRO-ACROP target delineation guideline which allows excluding implants from the clinical target volume [24, 25]. As there is no information on dosimetry planning and target delineations, it will be critical to interpret our results with caution.

Our study has several limitations. In our study, we excluded patients who received fewer than 14 or more than 35 fractions of radiotherapy, which could have arisen from various causes such as multiple treatment courses, treatment for metastatic lesions, or unconventional fractionation regimens. Furthermore, there may have been discrepancies between the actual number of fractions delivered and the number billed due to variations in billing practices and treatment principles across institutions. While it is challenging to derive precise radiation fractionation details from such a large-scale dataset, we believe existence of a significant difference in radiation fractions between the HF and CF groups presented, which is supported by several factors: First, the trend of increasing HF adoption in Korea since 2015 aligns with the observed pattern in our study [26]. Second, a separate analysis by Kim et al. using individual patient (N = 393) revealed comparable major breast complication rates (12.0% vs. 12.3%) following immediate reconstruction for both HF and CF groups [27]. While we recognise the inherent limitations of the nationwide database [28], we believe our study serves as a valuable step towards establishing a more robust and verifiable method for radiation fractionation assessment within national databases. Accurately filtering out such complexities from large datasets proved exceedingly challenging, necessitating an exclusion approach to maintain cohort homogeneity. Although this resulted in a reduced sample size, the enhanced treatment homogeneity within the cohort enabled us to draw more meaningful conclusions from our analysis. The radiation field or site could not be identified in the national database. Our definition of complications was limited to major events requiring capsulectomy, wound debridement, or skin graft by plastic surgeons. Other complications requiring only medical treatment were not included. Furthermore, the relatively short follow-up duration in some patients may have resulted in the failure to capture adverse events. Therefore, it is necessary to approach the interpretation of our findings with caution.