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

Xueying Zhao ,Yuan Tang,Chen Hu,Yueping Liu ,Yexiong Li ,Zhihui Hu ,Shunan Qi ,Xingchen Yan ,Yang Song ,Ningning Liu ,Yuhui Zhang ,Lin Liang,Ning Li,Hao Jing,Hui Fang,Yu Tang,Bo Chen,Kuo Men,Jing Jin,Shulian Wang

doi:10.1186/s12885-021-08852-y

Abstract

BackgroundVarious 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.MethodsPOTENTIAL 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.DiscussionThis 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 registrationClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979

Highlights

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
Historical surgical series have demonstrated that the incidence of internal mammary node (IMN) metastasis was 15.5% in patients after extended radical mastectomy [5] and IMN metastasis was more often observed in patients with positive axillary nodes or medial tumors compared with those without [6]
The value of IMN irradiation (IMNI) in the era of modern systemic treatment and radiation techniques is still unclear; the present study aims to investigate whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with pathological positive axillary nodes after mastectomy

Summary

Introduction

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. The survival benefits of postmastectomy radiation therapy (PMRT) in axillary node-positive breast cancer have been confirmed by prospective randomized trials and meta-analyses [1,2,3,4]. In all these studies, the treatment volume included the chest wall plus comprehensive regional nodal areas. A French randomized trial showed no overall survival benefit associated with IMNI in patients with node-positive or high-risk node-negative breast cancer after mastectomy [10]. Improvements in radiation techniques, such as computed tomography (CT)-based target delineation, three-dimensional (3D) conformal radiotherapy (RT), and cardiac-sparing techniques [15], have allowed for increased target conformality and minimized heart dose, which might make IMNI safe for most patients

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