Introduction
Treatment of the regional nodes is perhaps the most controversial area in radiotherapy for breast cancer. There are three nodal regions at risk:
- The supraclavicular fossa (most routinely treated site)
- The axilla (highly variable, depending on extent of axillary dissection, numbers of nodes involved and oncologist preference)
- The internal thoracic nodes (oncologist preference)
The other factor influencing debate is whether post-mastectomy or breast conserving therapy has been performed.
For post-mastectomy radiotherapy, meta-analysis by the EBCCTG has demonstrated that 5 field radiotherapy reduces local recurrence signficantly and improves overall survival by 5-10% for patients with 1-3 involved nodes and for patients with 4 or more nodes involved
For breast conserving therapy, findings have historically been drawn from the post-mastectomy radiotherapy findings of survival improvements with nodal irradiation. More recently, the unpublished MA20 trial from Canada has demonstrated a survival advantage for 5-field radiotherapy in patients with high risk tumours (> 5 cm, no nodes) or with positive nodes of any number.
Supraclavicular Fossa
Supraclavicular fossa treatment is more routine than axillary or internal thoracic nodal treatment.
Indications
Supraclavicular treatment is utilised in patients with four or more axillary lymph nodes, or with locally advanced breast cancer/inflammatory breast cancer on presentation. It is strongly indicated in patients with one-three nodes but this remains controversial in the absence of other adverse prognostic findings.
Beam Arrangement
The most common arrangement is to use a field based plan. The medial edge is the medial border of the sternocleidomastoid; the lateral border is an imaginary line drawn superiorly from the lateral border of the coracoid process (to thereby include level III axillary nodes). The inferior border matches the superior border of the breast tangents; the superior border is the top of the cricoid cartilage (should provide good dose to all over level IV). A single beam, angled at 15 degrees towards the lateral, will spare the spinal cord and deliver adequate dose to the anterior-lying supraclavicular nodes in most circumstances.
Alternatively, the fat in the supraclavicular fossa may be contoured as a clinical target volume, and an arrangement of beams to deliver dose to this volume can be designed. This volume would typically extend from the lateral border of the jugular vessels to the coracoid process, and use similar superior/inferior borders to the field based techniques.
For patients with a deep supraclavicular fossa, an AP/PA field arrangement can be used. For patients with high lung doses, the field can be angled superiorly using couch rotation to follow the curvature of the lung apex and reduce dose to that structure.
Dose/Fractionation
The most commonly used dose is 45 Gy in 25 fractions; shorter courses have been used in the hypofractionation trials but there are concerns regarding potential toxicity to the brachial plexus. Short courses remain popular in the United Kingdom.
Opinion: Supraclavicular fossa irradiation is typically indicated when there are 4+ nodes involved for both post-mastectomy or breast conserving radiotherapy. It is controversial in patients with 1-3 nodes, although less so with the evidence from the MA20 trial (breast conservation) and the significant results from the EBCCTG meta-analysis (post-mastectomy). Given that morbidity is low, I would recommend radiotherapy for patients with 1-3 nodes based on rates of recurrence.
Axilla
Deliberate delivery of radiation to the level I, II and III axillary nodes is controversial, for several reasons:
- 'At risk' Level I nodes are typically included in tangential field radiotherapy
- The likelihood of axillary nodal recurrence following axillary dissection is very low (1-2%)
- Axillary radiotherapy in particular has been associated with significant side effects, including lymphoedema, especially when combined with axillary lymph node dissection. Lymphoedema rates are about 10% with surgery or radiotherapy alone, but 20-30% with combined treatment.
Large centres typically only target the axillary nodes when:
- There has been inadequate axillary dissection (< 10 nodes)
- When sentinel nodes are positive and no axillary dissection has taken place Controversial!!
- For some added controvesrsy, the Z0011 trial demonstrated no survival difference between patients with clinically negative but < 2 biopsy positive sentinel lymph nodes who were randomised to no further treatment versus axillary dissection.
- The Z0011 trial has been criticised for failing to accrue its full quota of patients (850/1100) and for relatively short term follow up.
- These patients received no axillary radiotherapy
- It is reasonable to treat low risk women with a 1-2 sentinel nodes involved, particularly if involvement is isolated tumour cells or micrometastases only, and the tumour if OR/PR +ve, with no additional axillary therapy aside from breast tangents. Breast tangents are likely to cover the lower axillary nodes regardless.
- When there is extensive extra-capsular extension in a surgically dissected axilla
Some oncologists include an axillary boost when there is a large number of involved nodes (for instance, if 15/20 nodes are involved).
Beam Arrangement
The axilla is only treated in combination with supraclavicular and chest wall treatments, and therefore:
- Level I nodes are covered by tangents
- Level II nodes are poorly covered by either treatment
- Level III nodes are usually include in supraclavicular treatments, although there may be insufficient dose penetration with a single field
The most common solution is to extend the anterior supraclavicular field to cover level II axillary nodes and then add a posterior axillary 'boost' field to increase the dose at the location of level II/III nodes. This boost field delivers a much lower dose and simply 'tops up' the larger contribution from the supraclavicular field - 45 Gy in 25 fractions.
Alternatively, the axillary nodes can be volumed together with supraclavicular nodes and the entire volume used to base field arrangements.
Opinion: I would only recommend radiotherapy to the axilla in the setting of clinically detected nodal disease that has not undergone a full axillary dissection, or when there are under ten nodes removed (and 4+ are positive), or when > 75% of nodes are positive, or when there is significant extracapsular extension
Internal Thoracic Nodes
There is controversy regarding the treatment of the internal thoracic nodes. These nodes lie along the course of the internal thoracic artery, which passes inferiorly from the subclavian artery along the postero-lateral border of the sternum. It receives lymphatic drainage from the medial portion of the breast.
Pathologically, there is evidence of internal thoracic nodal involvement (as reported by Handley in 1975):
- In about 15% of upper inner quadrant tumours when there is no axillary nodal involvement. This rises to 50-60% when there are positive axillary nodes
- In < 10% of central or outer quadrant tumours. This rises to 40% for central tumours and 20% for outer quadrant tumours when there are positive axillary nodes.
These figures suggest that treatment of the internal thoracic nodes would be vital to cure a large number of women with breast cancer. Although there is evidence that involvement of the internal thoracic nodes is a poor prognostic feature, the rates of failure in internal thoracic nodes are very low (<1%).
Unfortunately, most randomised radiotherapy trials include all lymph node regions when evaluating regional nodal irradiation. Examples include the MA-20 trial, which randomised patients with high risk stage II and stage IIIA disease treated with breast conservation to regional nodal therapy or whole breast radiotherapy alone. The EBCCTG meta-analysis presented in 2006 demonstrated improved survival for patients with involved lymph nodes post-mastectomy, but 24/25 trials used internal thoracic node irradiation. On analysis of recurrence rates without radiotherapy (30% of cases), nearly all occur in the chest wall, axilla or supraclavicular fossa, suggesting that these are the regions 'at risk' for local recurrence.
Are there any randomised studies which compare regional nodal irradiation with and without the internal thoracic nodes? Yes - Romestaing et al have demonstrated no difference in local failure or overall survival in a randomised cohort of nearly 1400 women. These patients had at least 1 cm sized medial tumours without or without nodal involvement, or lateral tumours with nodal involvement. Randomisation was between 4 field versus 5 field radiotherapy. The study is limited by short follow up (10 years). Interestingly there was also no increase in cardiac mortality.
Two prospective randomised studies evaluated outcomes between radical mastectomy with or without removal of the internal thoracic nodes. These studies showed no difference in survival outcomes, suggesting that even though internal thoracic nodes may be involved treatment of this region surgically has no impact.
In summary, radiotherapy to the internal thoracic nodes remains highly controversial and most clinicians treat patients according to their own understanding of the evidence.
In favour of internal thoracic irradiation:
- The large randomised studies comparing post-mastectomy radiotherapy to no radiotherapy all used 5 field radiation techniques and treating with a technique other than 5 field may not produce the same results
- Internal mammary nodes are involved in over 20% of patients with positive nodes and in over 40% of patients with medial tumours with positive axillary nodes.
- Non-randomised evidence suggests internal mammary radiotherapy may improve survival outcomes
In favour of avoidance of internal thoracic irradiation:
- Despite frequent involvement of internal thoracic nodes, randomised surgical data and numerous retrospective data suggests treatment of this region has no impact on local control or distant metastases
- Patterns of recurrence post-mastectomy are most frequently in the chest wall, the axilla and the supraclavicular fossa.
- Higher rates of cardiac death have been seen with long term follow up of patients treated with internal thoracic irradiation
- Isolated internal thoracic recurrence is exceedingly rare at < 1%
- Randomised study (Romestaing) demonstrates no impact of internal thoracic node irradiation, although follow up is only 10 years and the study may not be powered to detect small differences
Opinion: My general feeling after reading the literature is that there is no established role for internal thoracic nodal irradiation in the vast majority of patients with breast cancer. The only patients I would consider treating are those with macroscopically enlarged internal thoracic nodes, or when the tumour is located so medially that the nodes would be included in the treatment volume regardless.
Beam Arrangement
There are several methods for treating the internal thoracic nodes. The highest risk nodes are in the first three interspaces. Various techniques were compared by Arthur et al in 2000.
Direct electron technique
In this technique, the medial field edge of the tangents is moved slightly medially and then an electron beam is applied with depth sufficient to reach the internal thoracic nodes. The goal is to deliver full dose to the nodal region, and this sometimes necessitates the use of a mixed electron/photon technique. Advantages of this treatment are reduced dose to lung and heart (although heart dose increases with increasing photon contribution). Disadvantages include junctioning problems at the skin surface and particularly at depth where cold or hot spots are possible.
Mini-Wide Tangents
The breast tangents are divided into superior and inferior. The superior tangent's medial edge is brought towards the contralateral side to include the internal thoracic nodes. This also increases lung and heart doses for that section. The inferior tangent is left at midline.
Dutch Technique
Instead of a small en face field to cover the internal thoracic nodes, another potential technique is to use a large electron field to cover the entire anterior chest wall, and AP/PA or AP alone fields to cover the chest wall, axilla and supraclavicular fossa.
Other Techniques
Other methods include using a wide tangent for the entire length of the field. This is discouraged as it increases heart and lung dose considerably and is not necessary if mini-wide tangents are used. IMRT could also potentially treat the IM nodes but 7- or 9- field IMRT is not in routine use for breast cancer.
