Breast cancer remains the most common cancer diagnosed in women, accounting for 25% of new undergone considerable change in recent years. Regional lymph node management has evolved significantly since the integration of sentinel lymphnode biopsy (SLNB) into standard practice for investigating clinically negative axillae: this has resulted in fewer unnecessary surgeries with axillary lymph-node dissection (ALND) and consequently decreased treatment-related morbidity. 2 The Z0011 trial demonstrated that SLNB alone compared to ALND did not result in decreased survival in patients with limited nodal disease. 345 The AMAROS trial compared ALND to adjuvant axillary RT following a positive SLNB and confirmed that both provided equal and excellent axillary control and RT resulted in lower treatment-associated morbidity. 6 Thus, adjuvant regional nodal irradiation (RNI) is often employed to treat patients with limited nodal involvement after SLNB. Comprehensive adjuvant RNI conventionally employed a 4-field technique, which includes the standard pair of tangential fields and opposing anterior and posterior supraclavicular fields, in order to cover axillary lymph node levels, I, II, and III, internal mammary nodes, as well as the supraclavicular lymph node region. Newer techniques include intensity modulated radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT).

Despite the decreased morbidity of RNI when compared to axillary lymph node dissection, radiation oncologists have aimed to reduce the potential of treatment-associated toxicities, and some use the high tangent technique in clinical scenarios where there is potential risk of nodal involvement. Currently, guidelines for the treatment of early-stage breast cancer report the inclusion of full RNI is often at the discretion of the treating radiation oncologist. 7 Compared to the 2-field standard tangential fields (STF), high tangent fields (HTF) have the superior border raised within 2 cm of the humeral head. 8910 The HTF technique was developed with adjustments to the posterior borders using 3D planning, resulting in what is now referred to as modified-high tangent fields (mHTF). 9101112 The aim of HTF and mHTF is to limit radiation toxicity compared to comprehensive RNI whilst simultaneously providing coverage of the inferior axillary nodal levels (levels I and II). Studies have found that while mHTF increases incidental doses to the ipsilateral lung, the risk of treatmentassociated morbidity, such as radiation pneumonitis, remains low. 12 Recent surveys still suggest significant practice variation in terms of radiation field design for breast cancer patients with a clinically node-negative axilla and 1-3 positive sentinel lymph nodes (SLNs) and no ALND. 13,14. In the era of 3D CT-based radiotherapy planning, concerns have been raised about the adequacy of axillary lymph node level I and II coverage using HTF. Some studies have found that HTF provides sufficient coverage of level I and II axillary nodal regions, while others have found it to be inadequate. 8101213 Despite the lack of consensus in the literature, the mHTF technique has been informally integrated into clinical practice at our institution. Currently, the mHTF technique is utilized when only the lower axilla is likely to be at the greatest risk of harboring microscopic disease, and when the comprehensive RNI is thought to result in overtreatment. This judgement is made at the discretion of the treating oncologist; for example, a commonly considered clinical scenario is micrometastatic nodal involvement. There may be situations where the risk of nodal involvement is present but lower than cases with definite indications such as clinically node positive disease. Given the uncertainty of mHTF axillary coverage, this study aims to quantify and evaluate the coverage of the HTF technique at our institution.

In this case-series study, women diagnosed with early invasive breast carcinoma between January 1st, 2012, and December 31st, 2016 at our institution were identified through a Data Access Request. Patients with staging pT1-2 N0(i+), pT1-2N1(mic) or pT1-2N1a and pT1-2NX who received adjuvant radiation therapy using a high tangent technique, who had no evidence of distant metastasis, and were 18 years of age at diagnosis were included. Cases were confirmed to be treated with the high tangent technique by confirming they were planned to use a 2-field technique with the superior anatomic boundary up to the level of the humeral head.

Radiation CT simulation scans of patients who met the inclusion criteria for the study were retrospectively reviewed. Level I and level II axillary nodal regions were then contoured on CT stimulation scans by a single radiation oncologist; nodal volumes were contoured as per RTOG contouring guideline using Eclipse (Varian Medical Systems) software. The radiation oncologist responsible for contouring the nodal volumes was blinded to the treating oncologist, patient identifiers, and the field borders previously used for treatment. Contoured volumes were then reviewed by a separate radiation oncologist.

Dosimetric parameters were evaluated using the original treatment fields by the mHTF technique, including the minimum, maximum, and doses to axillary levels I and II based on the retrospective nodal contours, as well as the incidental doses to the heart and ipsilateral lung. Adequate coverage of an axillary level was defined as 90% or more of the volume of the said level receiving 90% or more of the prescribed radiation dose (V90 ≥ 90%). An adequate dose was defined as receiving at least 90% (D90) and 95% (D95) of the prescribed radiation dose. Patients were stratified based on having received adequate coverage of an axillary nodal region, which we defined as V90% > 90% or V95% > 95%.

Data analysis was conducted using Excel. Descriptive statistics were performed. A MannWhitney-U test was used to compare differences in coverage of axillary level II for patients receiving adequate coverage of level; alpha was set at 0.05.

For Descriptive statistics we used frequency and percent to report qualitative variables and to report quantitative one we used mean and standard deviation or median with inter-quartile range

A total of 37 patients with low-risk breast adenocarcinoma were identified as receiving radiotherapy with the high tangent technique. Twenty-eight patients received 42.5 Gray (Gy) in 16 fractions, five patients received 40.0 Gy in 16 fractions, while two patients received 50.0 Gy in 25 fractions and two patients received 50.4 Gy in 28 fractions. Patient characteristics are summarized in Table 1, with the majority (62.2%) being pT1. Figure 1 demonstrates axillary nodal volume contouring.

For Level I, the D95 was 3451 ± 1092 cGy and the D90 was 3873 ± 720 cGy which were both higher than the D95 and the D90 for Level II were 2258 ± the mean dose of 3687 ± 578 cGy delivered to Level II axilla (Table 2).

The mean V95% for Level I was 86.93% ± 13.82% and the mean V90 was 94.63% ± 7.60% which were both considerably greater than the V95% and V90% measured for Level 2 at 55.11% ± 25.85% and 73.33% ± 21.83% respectively. Similar volumetric measures were also conducted for the two main organs at risk: the ipsilateral lung and heart. For all patients, the mean V20 to the ipsilateral lung was 16.65% ± 4.68%. Of note, twenty-one of the thirtyseven patients evaluated had left-sided breast cancer and received incidental radiation to the heart with a mean V25% of 5.16% ± 3.77%. Table 2 describes the dosimetric parameters of axillary coverage for Level II. Ten patients had adequate V90% coverage of Level II with a mean V90% of 97.06% ± 3.57% while twenty-seven patients did not, with a mean V90% of 64.54% ± 18.93%. When stratifying patients based on Level II V95%, only one patient had sufficient coverage with a mean V95% of 99.57% and the remaining thirty-six patients who had inadequate coverage of Level II V95% had a mean V95% of 53.88% ± 25.09%.

Axillary coverage was stratified by nodal level and V95% and V90% (Table 3). Of those who received adequate V90 coverage to Level I axilla, more than half also received adequate V95% coverage of the Level II axilla. Of those receiving adequate V95% coverage, the mean Level II V95% was 68.31% ± 19.90%, while the mean Level II V95% for the twenty-two patients who received inadequate coverage was 46.11% ± 25.93%. The median Level II V95% for patients receiving adequate and inadequate coverage of Level I was 73.93% and 43.13% respectively; the difference in median coverage was statistically significant (P < 0.01). Few patients (n=9) had adequate coverage of Level II axilla but conversely inadequate Level I coverage with a V90 of 71.11%, and the difference was not statistically significant (P = 0.33).

Radiotherapy volumes must carefully be considered to reduce locoregional recurrence risk of breast cancer while balancing treatment-related toxicity. Comprehensive RNI uses a 4-field radiation technique, which includes two tangent fields as well as two opposing anterior and posterior supraclavicular fields. However, comprehensive RNI carries the risk of significant toxicity such as chronic lymphedema in the range of 7-15% for most patients. 1415 For many patients with no or limited nodal disease, the highest risk of regional nodal recurrence would be around the adjacent level I and II axilla. Standard tangent radiotherapy fields partially cover the axilla, and HTF has been used to possibly improve this coverage. However, there is inconsistent literature on whether such techniques provide sufficient coverage of the region.

This study shows that in the era of field-based planning, the HTF provides adequate coverage for level I nodes, but inadequate coverage for Level II. A previous study evaluated nodal irradiation to axillary lymph node levels and similarly found Level I was adequately covered in most cases. 8 When nodal volumes are specifically contoured, it appears that coverage of both level I and II nodal regions do improve. In a more modern series where nodal volumes were specifically contoured; it was found that mHTF adequately covered axillary levels I and II. 12 This would be expected as field placement would then take into account the specific target delineation. However, there are multiple studies which report inadequate coverage specifically even when volumes are contoured. For example, one study evaluated the percentage prescribed radiation dose to the axillary region for normal tangential fields versus HTF and found that while HTF increased the doses achieved in the axillary region, the average doses were below 90% of the prescribed dose. 10 Another study found similarly that high tangent fields did not sufficiently cover Level I and II axillary levels. 13 Further, a study which utilized the same field design as the AMAROS trial to assess axillary lymph node coverage with HTF found that adequate coverage of level II was not achieved. 14 Thus, even when nodal volumes are contoured, differences in planning technique and contouring style lead to inconsistent coverage of Level II axillary nodes alone.

For level I nodes, the mean V90% was 94.6%, signifying acceptable baseline dose coverage, and this finding appears to be reproducible and consistent with existing literature that suggests mean V90% coverage of level I to range between 90 to 99% in multiple studies. 1216 This result does exceed findings by studies which reported inadequate coverage. 101317 However, these studies vary in their contouring of level I axilla and based conclusions on different metrics such as D90 and D95 coverage.

Our results do identify there is a modest drop in the mean V95% to 86.9%, and this may suggest inconsistent dose coverage and variance depending on patient anatomy. Depending on institutional policies, axillary volumes may not be regularly contoured and this difference in coverage may pose a detriment towards treatment efficacy. Varying radiotherapy techniques also appear to affect the metrics of dose coverage. For example, the use of CT planning or MLC modulation can improve V95% coverage. 13 Field-in-field techniques also improve the dose homogeneity compared to simple 3D conformal technique (3DCRT) alone. 18 At our institution, we use a tangent technique with various dynamic MLC modulation techniques, and more recently, a forward planned intensity modulated radiotherapy technique. These techniques are newer and more advanced than those used in prior studies which identified poor axillary coverage, as their treatments likely used a 3DCRT technique alone.

Regardless of treatment modifying techniques, however, our study consistently shows inadequate coverage of the level II axilla, ultimately attributed to the anatomic limitations of a field based HTF in the absence of nodal contouring.

This study reports that HTF technique can provide reasonable coverage of level I axillary nodes and helps support its use in select breast cancer cases where there may be low risk of axillary nodal involvement and may benefit from treatment of the low axilla, but not to the entire regional nodes. HTF is also associated with relatively low doses to the lungs and heart organs at risk. The results of this study also emphasize that level II axilla is not adequately covered and is therefore not appropriate treatment for the mid to distal axilla. Axillary nodal coverage may be improved by contouring the nodal volumes to aid in the placement of high tangents to ensure adequate coverage. These results complement a growing body of literature which suggests adequate coverage of lower axillary nodal volumes when using HTF fields. Further research and prospective evidence would be required to ultimately define the role and indications for HTF.