Dataset Information

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy.

ABSTRACT:

Background

It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.

Methods

We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.

Results

After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045-0.966) and 0.460 (95% CI, 0.220-0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).

Conclusions

IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

SUBMITTER: Cho WK

PROVIDER: S-EPMC8209280 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown.ObjectiveTo 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 participantsThis 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.InterventionsAll 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 measuresThe primary end point was the 7-year DFS. Secondary end points included the rates of overall survival, breast cancer-specific survival, and toxic effects.ResultsA 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 relevanceThis 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 registrationClinicalTrials.gov Identifier: NCT04803266.

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.