Abstract
Purpose/objective(s)Radiation treatment to the regional nodes results in an improvement in survival in breast cancer according to a meta-analysis of randomized trials. However, different volumes were targeted in these studies: breast or chestwall only (WBI/CWI), inclusion of the medial supraclavicular region and axillary apex (MS + WBI/CWI) or additional inclusion of the internal mammary chain (IM + MS + WBI/CWI). The benefit of treating the medial supraclavicular region and axillary apex compared to tangential breast or chestwall irradiation only remains unclear.Materials/methodsA literature search was conducted identifying trials for adjuvant radiation volumes in nodal irradiation after breast surgery and axillary treatment. Events and effect sizes were extracted from the publications for the endpoints of overall survival (OS), breast cancer-specific survival (BCSS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional control (LRC). A network meta-analysis was performed using MetaXL V5.3 with the inverse variance heterogeneity model.ResultsWe found two randomized studies (n = 5836) comparing comprehensive nodal irradiation to sole breast treatment as well as one randomized (n = 1407) and one prospective cohort study (n = 3377) analysing the additional treatment of the internal mammary chain against sole local and supraclavicular and axillary apex radiation. Compared to WBI/CWI alone the treatment of IM + MS + WBI/CWI (HR = 0.88; CI:0.78-0.99; p = 0.036) results in improved OS unlike MS + WBI/CWI (HR = 0.99; CI:0.86-1.14; p = 0,89). These results are confirmed in BCSS: IM + MS + WBI/CWI (HR = 0.82; CI:0.72-0.92; p = 0.002) and MS + WBI/CWI (HR = 0.96; CI:0.79-1.18; p = 0.69). PFS is significantly improved with the treatment of MS + WBI/CWI (OR = 0.83; CI:0.71-0.97; p = 0.019). Both nodal treatment volumes improve LRC (MS + WBI/CWI OR = 0.74; CI:0.62-0.87; p = 0.004 and IM + MS + WBI/CWI OR = 0.60; CI:0.43-0.86; p < 0,001). Yet only the internal mammary nodes provide a benefit in DMFS (MS + WBI/CWI HR = 0.97; CI:0.81-1.16; p = 0.74 and IM + MS + WBI/CWI HR = 0.84; CI:0.75-0.94; p = 0.002).ConclusionExpanding the radiation field to the axillary apex and supraclavicular nodes after axillary node dissection reduced loco-regional recurrences without improvement in overall and cancer-specific survival. A prolongation in survival due to regional nodal irradiation is achieved when the internal mammary chain is included. This derives from a reduction in distant metastasis.
Highlights
Radiation therapy is a key component in the multidisciplinary approach of breast cancer treatment after breast conserving surgery and achieves equal oncologic results to mastectomy alone [1]
Compared to Whole breast irradiation (WBI)/Chest wall irradiation (CWI) alone the treatment of IM + MS + WBI/CWI (HR = 0.88; Confident interval (CI):0.78-0.99; p = 0.036) results in improved overall survival (OS) unlike MS + WBI/CWI (HR = 0.99; CI:0.86-1.14; p = 0,89). These results are confirmed in breast cancer-specific survival (BCSS): IM + MS + WBI/CWI (HR = 0.82; CI: 0.72-0.92; p = 0.002) and MS + WBI/CWI (HR = 0.96; CI:0.79-1.18; p = 0.69)
Progression free survival (PFS) is significantly improved with the treatment of MS + WBI/CWI (OR = 0.83; CI:0.71-0.97; p = 0.019)
Summary
Radiation therapy is a key component in the multidisciplinary approach of breast cancer treatment after breast conserving surgery and achieves equal oncologic results to mastectomy alone [1]. Surgical and radiation treatment to the lymphatic drainage of breast tumors have been implemented as standard of care. A second lymphatic drainage system is located parasternal along the internal mammary vessels coalescing with the axillary chain at the intersection with the subclavian vein. Extended radical mastectomies including a dissection of the internal mammary nodes (IMN) have been abandoned due to high complication rates and dubious oncological benefits [2, 3]. Radiotherapy (RT) was used to cover this lymphatic drainage site and resulted in equivocal results with reports of a potential benefits [4, 5] as well as no advantage [2, 6] or even harmful effects [7]. The vast majority of the 22 studies included radiation of the internal mammary chain [8]
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