Dataset Information

Effect of Elective Internal Mammary Node Irradiation on Disease-Free Survival in Women With Node-Positive Breast Cancer: A Randomized Phase 3 Clinical Trial.

ABSTRACT:

Importance

The benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.

Objective

To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer.

Design, setting, and participants

This multicenter, phase 3 randomized clinical trial was conducted from June 1, 2008, to February 29, 2020, at 13 hospitals in South Korea. Women with pathologically confirmed, node-positive breast cancer after breast-conservation surgery or mastectomy with axillary lymph node dissection were eligible and enrolled between November 19, 2008, and January 14, 2013. Patients with distant metastasis and those who had received neoadjuvant treatment were excluded. Data analyses were performed according to the intention-to-treat principle.

Interventions

All patients underwent regional nodal irradiation along with breast or chest wall irradiation. They were randomized 1:1 to receive radiotherapy either with IMNI or without IMNI.

Main outcomes and measures

The primary end point was the 7-year DFS. Secondary end points included the rates of overall survival, breast cancer-specific survival, and toxic effects.

Results

A total of 735 women (mean [SD] age, 49.0 [9.1] years) were included in the analyses, of whom 373 received regional nodal irradiation without IMNI and 362 received regional nodal irradiation with IMNI. Nearly all patients underwent taxane-based adjuvant systemic treatment. The median (IQR) follow-up was 100.4 (89.7-112.1) months. The 7-year DFS rates did not significantly differ between the groups treated without IMNI and with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14; log-rank P = .22). However, an ad hoc subgroup analysis showed significantly higher DFS rates with IMNI among patients with mediocentrally located tumors. In this subgroup, the 7-year DFS rates were 81.6% without IMNI vs 91.8% with IMNI (HR, 0.42; 95% CI, 0.22-0.82; log-rank P = .008), and the 7-year breast cancer mortality rates were 10.2% without IMNI vs 4.9% with IMNI (HR, 0.41; 95% CI, 0.17-0.99; log-rank P = .04). No differences were found between the 2 groups in the incidence of adverse effects, including cardiac toxic effects and radiation pneumonitis.

Conclusions and relevance

This randomized clinical trial found that including IMNI in regional nodal irradiation did not significantly improve the DFS in patients with node-positive breast cancer. However, patients with medially or centrally located tumors may benefit from the use of IMNI.

Trial registration

ClinicalTrials.gov Identifier: NCT04803266.

SUBMITTER: Kim YB

PROVIDER: S-EPMC8546620 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Effect of Elective Internal Mammary Node Irradiation on Disease-Free Survival in Women With Node-Positive Breast Cancer: A Randomized Phase 3 Clinical Trial.

Kim Yong Bae YB Byun Hwa Kyung HK Kim Dae Yong DY Ahn Sung-Ja SJ Lee Hyung-Sik HS Park Won W Kim Su Ssan SS Kim Jin Hee JH Lee Kyu Chan KC Lee Ik Jae IJ Kim Won Taek WT Shin Hyun Soo HS Kim Kyubo K Shin Kyung Hwan KH Nam Chung Mo CM Suh Chang-Ok CO

JAMA oncology 20220101 1

<h4>Importance</h4>The benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.<h4>Objective</h4>To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer.<h4>Design, setting, and participants</h4>This multicenter, phase 3 randomized clinical trial was conducted from June 1, 2008, to February 29, 2020, at 13 hospitals in South Korea. Women w ...[more]

PMID: 34695841

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Project description: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.

Project description:BackgroundInternal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT.MethodsDBCG IMN2 was a nationwide population-based cohort study prospectively allocating node-positive breast cancer patients with right-sided tumours to IMNI and patients with left-sided tumours to no IMNI in six RT centres. Exclusion criteria were prior malignancies, bilateral breast cancer, neoadjuvant systemic therapy, recurrence before RT, or non-standard RT. Systemic treatment included taxane-based chemotherapy, aromatase inhibitors, and trastuzumab. The primary end-point was OS. Secondary endpoints were breast cancer mortality and distant metastasis. Cox regression analyses were used for adjusted hazard ratios (HR). Clinicaltrial.gov ID: NCT06549920.FindingsIn the period January 2007-May 2014, a total of 4541 patients were included. Patient characteristics were distributed evenly between right- and left-sided patients. Median follow-up was 13.7 years for OS. Survival rates at 15 years were 65.0% in patients with IMNI and 60.8% without leading to an adjusted HR of 0.85 (95% CI, 0.76-0.94; p = 0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74-0.95; p = 0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78-0.98; p = 0.026) for distant metastasis. No subgroups were identified for the omission of IMNI. The 15-year cumulative incidence of death from ischemic or valvular heart disease was 0.2% (95% CI, 0.0-0.5) in right-sided and 0.7% (95% CI, 0.4-1.2) in left-sided patients.InterpretationIMNI reduced distant metastasis and breast cancer mortality and improved OS in node-positive breast cancer patients, despite treatment with newer systemic therapies and 3D-based RT.FundingThis work was supported by the Danish Cancer Society and Department of Clinical Medicine, Aarhus University, Denmark.

Dataset Information

Effect of Elective Internal Mammary Node Irradiation on Disease-Free Survival in Women With Node-Positive Breast Cancer: A Randomized Phase 3 Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Elective Internal Mammary Node Irradiation on Disease-Free Survival in Women With Node-Positive Breast Cancer: A Randomized Phase 3 Clinical Trial.

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