POstmastectomy radioThErapy in Node-posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a study protocol for a multicenter prospective phase III randomized controlled trial

Background Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. Methods POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1–3 vs. 4–9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. Discussion This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. Trial registration ClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979

Postmastectomy Radiotherapy in T1–2 Female Breast Cancer Patients with 1–3 Positive Axillary Lymph Nodes: A Propensity Score Matched SEER Analysis

Purpose The application of postmastectomy radiotherapy (PMRT) in T1–2 female breast cancer patients with 1–3 positive lymph nodes has been controversial. We sought to determine the survival benefits of PMRT in the patients with T1–2 and 1–3 positive nodes. Methods A retrospective study using the Surveillance, Epidemiology, and End Results (SEER) Regs Custom Data (with additional treatment fields) from 2001 to 2011 was performed. Patients who received PMRT were matched by the propensity score with patients who did not receive PMRT. The Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed. Results We identified 56,725 female breast cancer patients with T1–2 and 1–3 positive nodes, and 18,646 patients were included in the analysis. After propensity score matching (1:1), with a median follow-up of 116 months, PMRT showed an increase in the OS (P = 0.018) but had no effect on the BCSS. The 10-year OS rates were 76.8% and 74.4%, and the 10-year BCSS rates were 82.8% and 82.2% for the patients who received and who did not receive PMRT, respectively. Only patients with 3 positive nodes could gain the benefit of PMRT for BCSS. Conclusion PMRT for patients with T1–2 and 1–3 positive lymph nodes could increase the 10-year OS, and had no effect on the 10-year BCSS. Subgroup analysis indicated that only patients with 3 positive lymph nodes could benefit from PMRT for both the OS and BCSS.

1042 The Effect of Breast Reconstruction Type on Complication Rates and Patient Satisfaction in The Setting of Postmastectomy Radiotherapy (PMRT)

Introduction The National Institute for Health and Care Excellence recommend offering post mastectomy radiotherapy (PMRT) to people with involved resection margins. With increasing evidence supporting the effectiveness of PMRT, it is important to optimise the outcomes of breast reconstruction in women receiving PMRT. Method A search was conducted in the PubMed database. The exclusion criteria were patients undergoing neoadjuvant radiotherapy and patients with metastases. The primary outcomes were patient satisfaction and complication rates. Results A meta-analysis (N = 380) found prosthetic reconstructions were 5 times more likely to develop complications than autologous reconstructions in the setting of PMRT (OR = 0.20, 95% CI = 0.1-0.4). A systematic review (N = 5437) had higher rates of total complications in prosthetic reconstructions compared to autologous reconstructions (41.3% vs 30.9%) with PMRT. Similarly, a retrospective study of PMRT patients (N = 622) had higher rates of complications with prosthetic reconstructions compared to autologous reconstructions (OR = 0.47, 95% CI = 0.27-0.82, P = 0.007). The adjusted mean satisfaction score (AMSS) of patients with autologous and prosthetic reconstructions receiving PMRT in a study (N = 54) was 4.4 and 2.8, respectively. Patient-reported satisfaction in a study (N = 622) was higher in patients with autologous (AMSS=63.5, 95% CI = 55.9-71.1) compared to prosthetic reconstructions (AMSS=47.7, 95% CI = 40.2-55.2) (all P = 0.002) with PMRT. Conclusions Existing data suggests that autologous tissue reconstructions tend to be more compatible with PMRT than prosthetic reconstructions in terms of patient satisfaction and complication rates. Although more research is needed to support these findings, current data can help patients and physicians make informed decisions regarding the type of breast reconstruction to use with PMRT.

Improvement of matching fields using coplanar field border method in postmastectomy radiotherapy

Aim: To propose a new matching method for the supraclavicular (SC) and tangential fields on three-dimensional radiotherapy (3DRT) for postmastectomy radiotherapy (PMRT). Methods: A method of matching coplanar field borders (CFB) between the tangential and SC fields was created in 3DRT. The collimator angle of the medial tangential field was calculated to coplanar the SC field. The proposed method performance was ultimately benchmarked using the half beam block (HBB) and traditional three-field monoisocenter (TTM) methods by dosimetric comparison. The decision score was then employed to clarify the performance among these methods. Results: The results show that the TTM method exhibited not only low doses on the organs at risk (OAR) but also on the matching fields. The CFB and HBB produced comparable results, but the ipsilateral lung yielded lesser amounts than the HBB. The decision score indicated a low performance level when using the TTM method, whereas the CBF method exhibited a slightly higher performance score than the HBB. Findings: The CFB exhibited good performance in terms of the dose on OARs and at the matching fields. This method offers a comparable level of performance to the HBB. Thus, the CFB offers an alternative method of significant interest in PMRT.

An Innovative VMAT Technique for Left-sided Breast Cancer Patients With Postmastectomy Radiotherapy (PMRT) Evaluated by Ratio of Heart Volume in Tangent Line (RHVTL)

For patients with left-sided breast cancer (LBC), postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival and many advanced planning techniques was adopted in PMRT. We aim to use an innovative VMAT technique to enhance the conformity of PTV and reduce the scattering dose of surrounding OARs, thereby reducing the long-term toxicity of the heart as well as ipsilateral lung (IL). The study further analyzes the more appropriate treatment planning techniques for personalized LBC patients with PMRT. 35 LBC patients were retrospectively selected undergoing PMRT. The PTV included lymph nodes, chest walls, excluding internal mammary nodes, where 95% of PTV receiving the prescription dose of 50Gy (2Gy/fraction) with three different techniques, VMAT, IMRT, Hybrid VMAT. Furthermore, the ratio of Heart Volume in Tangent line and heart volume (RHVTL) was proposed to evaluate the relative antonymy position between patient's heart and PTV, which hypothetically represents the complexity of treatment planning. The data from this study showed that for LBC patients undergoing PMRT, the CI from VMAT was 0.85 (IMRT and H-VMAT were 0.77 and 0.83), the heart D mean was 502.9cGy (IMRT and H-VMAT were 675.6cGy and 687cGy) and the V20 of IL was 21.3 as the lowest of the three techniques, but the dose of the contralateral breast (CB) and contralateral lung increased noticeably. In H-VMAT and IMRT, the mean heart dose was significantly related to RHVTL, with R-values of 0.911 and 0.892 respectively, while the values in VMAT was 0.613, thus the VMAT technique was relatively unaffected by the difficulty of treatment plan. For RHVTL values exceed than 0.06, the mean heart dose under VMAT technique raised by 98.7cGy compared to the RHVTL value of less than 0.06, but H-VMAT and IMRT increased by 233cGy and 261.58cGy individually. This study illustrates that separated fields and adjacent fields in VMAT technique obtained the optimal conformality and lowest doses of heart in three techniques for LBC with PMRT. Thus, based on the results of our preliminary study, the VMAT technique is highly recommended when RHVTL is exceeded 0.06.