Radiotherapy of MRI-detected involved internal mammary lymph nodes in breast cancer

Research Open Access Radiotherapy of MRI-detected involved internal mammary lymph nodes in breast cancer Sean Sachdev†1, Chelain R. Goodman†1, Erin Neuschler2, Kapila Kalakota3, Daniel Cutright1, Eric D. Donnelly1, John P. Hayes1, Adam E. Prescott1, Gianna Mirabelli1 and Jonathan B. Strauss1Email author †Contributed equally Radiation Oncology201712:199 https://doi.org/10.1186/s13014-017-0934-5 ©  The Author(s). 2017 Received: 28 August 2017Accepted: 30 November 2017Published: 19 December 2017 Abstract Background The internal mammary (IM) lymph node chain, along with the axillary nodal basin, is a first-echelon breast lymphatic draining site. A growing body of evidence supports irradiation of this region in node-positive breast cancer. This study evaluated the effectiveness of radiotherapy in treating magnetic resonance imaging (MRI)-detected abnormal IM lymph nodes in newly-diagnosed non-metastatic breast cancer. Methods A structured query was performed on an electronic institutional database to identify women with radiographic evidence of abnormal IM node(s) on breast MRI from 2005 to 2013. Manual review narrowed inclusion to patients with a primary diagnosis of non-metastatic breast cancer with abnormal IM node(s) based on pathologic size criteria and/or abnormal enhancement. Results Of the 7070 women who underwent pre-treatment MRI, 19 (0.3%) were identified on imaging to have a total of 25 abnormal pre-treatment IM lymph nodes, of which 96% were located in the first two intercostal spaces and 4% in the third space. A majority of the primary tumors were high-grade (94.7%) and hormone-receptor negative (73.7%), while 47.4% overexpressed HER-2/neu receptor. Axillary nodal disease was present in 89.5% of patients, while one patient had supraclavicular involvement. At a median follow-up of 38 months, 31.6% of patients had developed metastatic disease and 21.1% had died from their disease. Of the patients who received IM coverage, none had progressive disease within the IM lymph node chain. Conclusions Radiologic evidence of pre-treatment abnormal IM chain lymph nodes was associated with advanced stage, high grade, and negative estrogen receptor status. The majority of positive lymph nodes were located within the first two intercostal spaces, while none were below the third. Radiation of the IM chain in combination with modern systemic therapy was effective in achieving locoregional control without surgical resection in this cohort of patients. Keywords BreastBreast neoplasmsLymph nodesMagnetic resonance imagingRadiotherapy Background The internal mammary (IM) lymph node chain, along with the axillary nodal basin, is a primary breast lymphatic draining site. [1] IM nodal dissection was routinely pursued in the 1950s due to reports that as many as 33% of patients had IM nodal involvement on survey biopsies. [2] Multinational trials subsequently revealed that extended radical (Urban) mastectomy with IM nodal dissection did not improve survival compared to radical (Halstead) mastectomy [3–6], eventually leading to its disuse. Historically there has been significant controversy regarding when to electively treat the IM nodal chain with radiotherapy. This controversy stems both from uncertainty concerning the therapeutic value of treating the IM chain as well as concern over the incremental additional dose delivered to heart and lung. [7] Recent advances in the delivery of radiotherapy, such as deep inspiration-breath hold, have abrogated the concerns about cardiac dose, although the magnitude of the benefit remains unclear. Prospective randomized data have demonstrated that nodal radiotherapy improves locoregional control as well as distant metastasis-free survival and reduces breast cancer mortality. [8, 9] Furthermore, the large absolute overall survival advantage of post-mastectomy radiotherapy in node positive women suggests that the inclusion of the regional nodal beds may provide at least part of this observed benefit. [10–13] These reports, however, were based on outcomes of nodal treatment in aggregate; limited data exist regarding the incremental benefit associated with including the IM chain. The Danish Breast Cancer Cooperative Group (DBCG)-IMN study, which prospectively assigned patients with left-sided breast cancer to receive radiation to the IM chain, demonstrated a significant survival benefit of IM chain irradiation. [14] To date, however, there are no randomized clinical trials evaluating this question, and there remains a lack of consensus as to which patients may benefit from the elective radiation of this region. [15–17] In this study, radiotherapeutic treatment of the IM chain was evaluated in a related setting. Rarely, patients are found to have abnormal pre-treatment IM lymph nodes on imaging. From a large pool of patients who underwent pre-treatment MRI evaluation, patients who were found to have radiologic evidence of internal mammary node involvement were identified. Clinicopathologic data, radiotherapeutic treatment parameters, and clinical outcomes were analyzed to help clarify the effectiveness of radiotherapy and modern systemic therapy in treating involved IM nodes. Methods Patient selection and search query Patients were retrospectively identified from an electronic database with records of 7070 women who underwent pre-operative breast MRI from 2005 to 2013 at a single institution. All data collection and analyses were performed after review by and approval of the institutional review board (IRB) and in accordance with medical research principles outlined by the Declaration of Helsinki. [18] Numerous search strings, such as “internal mammary node” and “IM node,” were used to identify studies with abnormal internal mammary lymph node(s) as documented by a breast radiologist. A structured query was used to obtain a comprehensive list from which duplicates were excluded. Imaging, dosimetry, and clinical review MR studies were retrieved and manual review narrowed case inclusion to women with a primary diagnosis of non-metastatic breast cancer with abnormal IM node(s) based on size and/or abnormal contrast enhancement as seen on axial fat suppressed T1-weighted and STIR Axial images. Each MRI was individually reviewed with an experienced breast radiologist and a final determination was reached regarding radiographic diagnosis of IM chain involvement. For each patient, the number and size of the involved IM lymph node(s), intercostal space location(s), radiologic evidence of extracapsular extension (ECE), as well as quadrant(s) involved by the primary malignancy were noted. Characteristics of the primary tumor including grade, evidence of lymphovascular invasion (LVI), and hormone receptor profile were recorded. Treatment-related variables including the type of breast surgery and axillary node evaluation as well as the type and sequence of systemic therapy. All available radiation treatment (...truncated)