Comparison of Efficacy and Safety Between Hypofractionated and Conventional Fractionated Radiotherapy After Breast Reconstruction in Breast Cancer Patients: A Phase III Randomized Controlled Clinical Trial

Breast cancer is one of the most common malignant tumors among women worldwide. For high-risk patients who undergo total mastectomy, postoperative radiotherapy can significantly reduce the local recurrence rate and improve survival rates. With the advancement of treatment and the increasing demands of patients for quality of life, breast reconstruction surgery has become increasingly popular, which greatly improves the psychological and social status of patients.

Currently, post-reconstruction radiotherapy for breast cancer is mostly carried out using a conventional fractionation scheme (such as 50 Gy/25 times, lasting 5 weeks), which is long in duration and burdensome, affecting patient compliance and occupying a large amount of medical resources. Large fractionation radiotherapy can significantly shorten the treatment course by increasing the single dose and reducing the number of treatments (such as 43.5 Gy/15 times, lasting 3 weeks). Its application has a solid theoretical basis: breast cancer has a relatively low α/β value (about 3-4 Gy), and moderately increasing the single dose may enhance the killing effect on the tumor. In patients after breast-conserving surgery and modified radical mastectomy, large-scale phase III clinical trials (such as START, Wang SL, etc.) have confirmed that the long-term efficacy and safety of large fractionation radiotherapy are comparable to those of conventional fractionation, so the international authoritative consensus (such as ESTRO) has supported its use for chest wall irradiation.

However, when radiotherapy is combined with breast reconstruction, the situation is more complex. Radiotherapy may affect tissue healing, increasing risks such as capsular contracture, infection, prosthesis exposure, and reconstruction failure. Currently, high-level evidence is mostly derived from patients without reconstruction. Although retrospective studies suggest that the complication rate after using a large fractionation scheme (such as 40 Gy/15 times) in patients after reconstruction may be comparable to or even lower than that of conventional fractionation, and the radiotherapy dose and complication risk may have a positive correlation, these conclusions are not consistent and lack conclusive evidence from prospective randomized controlled trials. This is the current key evidence gap in clinical practice.

In addition, post-reconstruction radiotherapy requires high technical requirements and needs to follow specific consensus on target area delineation (such as the ESTRO guidelines) to ensure coverage of common recurrence sites such as skin and subcutaneous tissues, and the use of intensity-modulated radiotherapy and other technologies to ensure uniform and sufficient target doses while strictly protecting vital organs such as the heart and lungs.

In conclusion, although large fractionation radiotherapy shows advantages in a wide population of breast cancer patients, its long-term efficacy and safety in patients after breast reconstruction, especially its impact on the reconstruction outcome, have not been clearly verified through phase III randomized controlled trials. Therefore, conducting a head-to-head comparison III phase clinical trial is crucial to provide an efficient and safe optimized radiotherapy scheme for this growing patient group, fill the evidence gap in evidence-based medicine, and provide direct evidence for clinical guidelines.