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Postoperative Radiation Treatment of the Breast


Medical editor Bjørn Naume MD
Oncologist
Oslo University Hospital
Norway

General

Postoperative radiation therapy requires adequate removal of the primary tumors and completed axillary dissections (sentinel node or adequate axillary dissection levels I and II). A ≥ 5 mm tumor-free margin to the sides should be for the goal during surgery. Re-resection is however not necessary if the resection margins are tumor-free in("ink not on tumor"). Thus there are no specific requirements on the resection margins. If there is uncertainty whether the resection margins are free, the patient must be re-operated and have a re-resection or mastectomy. The exception is when the tumor is localized close to the thoracic wall or to the skin, where smaller margins are accepted, if resected to the fascia or to the skin. 

Postoperative radiation therapy should not be given simultaneously with adjuvant chemotherapy. Radiation therapy must begin within 3-4 weeks after chemotherapy is finished.

Endocrine treatment and trastuzumab (Herceptin®) can be given simultaneously with radiation therapy.

Indications

For infiltrating breast cancer:

  • After breast conserving surgery
  • For large primary tumor (T > 50 mm)
  • For non-radical surgery (after mastectomy)
  • For lymph node positive disease (except for involvement of only intra-mammary lymph node without any other lymph node involvement)

For DCIS:

  • All grade II/III and grade I > 10 mm with BCT
  • Non-radical surgery (after mastectomy)

Radiation therapy after breast conservative treatment

DCIS (all grades II/III, grade I > 10 mm)

Radiation treatment is performed as two tangential fields. The entire breast (not the chest wall) is defined as the target volume. The medial field border will be close to the midline. The radiation must include the lateral part of the breast. Upwards, the field will extend to the sternoclavicular joint, and downwards to 1-1.5 cm under the inframammary fold.

Invasive breast cancer pT1-2pNO

Radiation treatment is performed as two tangential fields. The entire breast (not the chest wall) is defined as the target volume. The medial field border will be close to the midline. Upwards, the field will extend to the sternoclavicular joint and downwards to 1-1.5 cm under the inframammary fold.

To minimalize the cardiac radiation hypofractionated radiation towards the left side should be performed with gatting (breath synchronized radiation). This strives to maintain the heart outside the field borders with a maximal average dose of 2 Gy. On this basis it is accepted that during chemotherapy/immunotherapy the patient have synchronous irradiation. (the organ at risk avoids for the combination of chemotherapy and radiation dose).

Invasive breast cancer pT1-2pN1-2

If there is metastasis to one or more axillary lymph nodes and the largest metastasis is > 2mm, radiation therapy should be given toward the mammary gland and regional lymph nodes.

For elderly patients, an individual assessment is made with emphasis on comorbidity, biological age/expected survival time. 

The target definition for patients in this group should, in addition to the breast, include the axillae and supraclavicular lymph nodes. In large, medial tumors, the upper parasternal lymph nodes are also included. When 10 or more axillary lymph nodes are removed, level I and II of the axilla should not be irradiated. This is independent of how many lymph nodes are tumor-involved. If the surgeon notes that there is possibility for remaining tumor in the axilla or that the lymph node involvement is very wide-spread, level I and II of the axilla should also be included in the target volume to improve regional control. The same applies if there is evidence of macroscopic extranodal extension (> 2 mm) or tumor islands in the fatty tissue, even if ≥ 10 lymph nodes are removed.

After mastectomy

Invasive breast cancer pT1-2pNO or DCIS

The target area includes the chest wall located under the breast and the scar. Radiation treatment is performed as two tangential fields with field borders laterally in the medio-axillary line, medially in the mediosternal line, downwards to 1-1.5 cm under the inframammary fold of the opposite breast and cranially towards the sternoclavicular joint.

Invasive breast cancer pT1-2pN1-2

Radiation therapy after mastectomy is equivalent to what described for breast conservative treatment (largest lymph node metastasis > 2mm) with the following exceptions:

  • A boost is not usually given after mastectomy. The target volume is the chest wall located under the breast and the incision scar, axillary and supraclavicular lymph nodes and possibly the upper parasternal lymph nodes.
  • For elderly patients, an individual assessment is made with emphasis on comorbidity, biological age/expected survival time.

Goal

  • To reduce the risk for local and/or regional relapse.
  • To increase the survival after both breast conservative treatment and mastectomy.

Definitions

Target Volume

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)

GTV (= Gross Tumor Volume)

Tumor volume

Palpable or visible/identifiable area of malignant growth. Confirmed lymph nodes may be reported as GTV-N, other metastases as GTV-M.

CTV (= Clinical Target Volume)

Clinical target volume

Tissue volume containing GTV and/or subclinical microscopic malignant disease.

ITV (= Internal Target Volume)

Target volume

Volume containing CTV and an internal margin taking into account internal movements and changes in  CTV. This is the volume that should receive an optimal dose.

PTV (= Planning Target Volume)

Planning volume

Geometric volume containing ITV and one Set-up margin taking into account variation for patient movements, variations in patient positioning, and field modeling.

Planning contour: Beams-Eye-View projection of PTV.

 IM (= Inner margin) and SM (= Setup margin)

IM and SM cannot be summed linearly. Total margin must be given specifically for different tumor localizations.

GTV

Gross tumor volume is not applicable for postoperative radiation.

CTV breast

Includes breast and the axillary process of the breast,

Limits

  • Ventrally: 5 mm under skin layer
  • Dorsally: fascia covering the pectoral muscle, possibly anterior surface of ribs in deeply located tumors.

CTV boost

With CT as reference, this volume includes the tumor bed defined as the operative cavity and the visible postoperative reaction, with additional 5-10 mm surrounding tissue, or alternatively as visible operation cavity and possibly staples with about 2 cm surrounding tissue. The scar is not part of the target.

CTV parasternal lymph nodes

Routine radiation is no longer necessary. The method should be considered for:

  • large, medially or centrally localized tumors
  • positive parasternal sentinel lymph node

Limits

  • Medially: lateral border of sternum 
  • Laterally: 2 cm laterally to the medial limit
  • Dorsally: pleura
  • Ventrally: anterior edge of ribs
  • Cranially: immediately caudally to the sternoclavicular joint
  • Caudally: cranial border of ribs IV (often equals 1 cm below carina)

CTV periclavicular lymph nodes

Limits

  • Medially: 1,5 cm from trachea
  • Caudally/laterally: border to the axilla
  • Cranially: equals 1 cm caudal to vocal cords or the lower part of C6
  • Caudally: lower part of the sternoclavicular joint
  • Anteriorly: 5 mm deep to the skin
  • Dorsally: anterior to the transverse process in upper part, the ribs more caudally.

CTV axilla

Level I lateral to pectoralis minor muscle 

Level II posterior to pectoralis minor muscle 

Level III medially to pectoralis minor muscle. Lateral to the supra/infraclavicular region.

CTV thoracic wall

  • Includes the area underlying the breast as well as the operation scar. The outer 5 mm of the skin is not included in the clinical target volume. Over the scar itself and 20 mm to the sides of the scar, the clinical target volume includes the surface of the skin when the distance from the tumor to the skin is short (use of bolus). In the depth the target volume reaches the anterior rib surface. The medial border mimics the edge of the remaining breast. If this is not possible to identify, the medial border should be 25 mm lateral to the lateral edge of the sternum.

ITV=CTV

PTV

Margins are set to 5-7mm, towards the heart 0 mm. The minimum dose in PTV should be 90% of the target dose.


Preparation

  • Review of operation protocol, histology results, receptor status, and indication for radiation therapy as well as adjuvant treatment.
  • The patient is examined and informed by the physician and nurse in an out-patient setting.
  • Routine blood tests and X-ray of thorax are taken. Other necessary examinations if necessary (for example ultrasound and cytology of actual tumors/seroma, bone scintigraphy, ultrasound of liver etc).
  • Patient lies in the supine position with arm support/holder. Breast board. Wing board.
  • Drawing of target volume is CT-based and will be the basis for the treatment planning.
  • Conventional simulation is rarely used, and only when the CT-based treatment planning are not possible to perform (most often due to reduced mobility of shoulder/arm). The target volum is defined by the superficial anatomical structures and by means of X-ray.
  • Fixation (boost)

NBCG recommends that all women having curative irradiation for breast cancer should have fT4, TSH, and anti-TPO taken prior to the irradiation.

Organs at risk

  • Heart
  • Lungs
  • Spinal cord 
  • Contralateral breast
  • Brachial plexus 

Implementation

Treatment is given as a daily fractions (Monday to Friday a total of 5 fractions per week).The treatment lasts for 3-7 weeks, depending on the fractionation and whether there is indication for a boost.

An average cardiac dose of maximally 2 Gy is striven for. If this is not achieved the target volume should be reevaluated (change of CTV to an adjusted dosage volume if this is clinically acceptable) and/or risk/benefit ratio especially considered.

  • For pT1-2 lymph node positive breast cancer is usually given 25 fractions of 2 Gy (2 Gy x 25) towards the chest wall and 23 fractions (2 Gy x 23) towards regional lymph nodes. For clinically suspicion of remaining macroscopic tumor in the axilla  2 Gy x 25 should also be given towards the regional lymph nodes. For breast conserving surgery boost irradiation, 2 Gy x 8, is given towards the tumor bed, in women below 50 years of age. It is recommended that maximally 35 % of the lung should receive a dosage of 20 Gy (V20 < 35 %).
  • After breast conservation for infiltrating cancer without lymph node metastases is either given 2.67 Gy x 15 (usually) or 2 Gy x 25 towards the breast. Additionally boost radiation 2 Gy x 8 is given towads the tumor bed in women < 50 years of age. Hypofractionated irradiation for left sided cancer is performed by gatting (respiratory synchronization of the irradiation). This aims at maintaining the heart outside the field limits with an average maximal radiation dose of 2 Gy. During radiation with 2 Gy x 25 towards the breast only, less than 15% of the lung should receive a maximal dosage of 20 Gy or more. For hypofractionated irradiation with 2.67 Gy x 15 this is equivalent to V18 Gy < 15%.
  • Subsequently to breast conservation surgery for DCIS  2 Gy x 25 is given towards the breast. Usually less than 15% of the ipsilateral lung should receive a maximal dosage of 20 Gy or more.
  • After mastectomy with tumor in the resection margin and without involvement of regional lymph nodes 2 Gy x 25 is given towards the chest wall.
  • For massively non-free resection margins or remaining macroscopic tumor after mastectomy.

Radiation treatment with locally advanced/invasive breast cancer T3-4N0-3, T1-2N2-3

  • After radical surgery, the radiation treatment plan is often equivalent to radiation treatment in pT1-2pN1-3 disease. 50 Gy is given toward the thoracic wall and 46 Gy toward regional lymph node stations (applies also to N0 disease). The axilla (level I and II) is not radiated if ≥ 10 lymph nodes are removed, as long as there is no known extranodal infiltration (> 2 mm) or tumor islands in the fat tissue.

To achieve optimal dosage in the skin after mastectomy a bolus should be individually considered. After breast conservation surgery (less frequently) indication for boost should be considered.

 


Follow-up

During irradiation

  • Regular follow-up
  • Consultation with oncologist at the end of the treatment

At end of irradiation

  • The patient should be followed-up at the remitting hospital or possibly at the general practitioner, and preferentially according to the recommendations from the Norwegian Breast Cancer Group.
  • The first consultation after ended irradiation is usually after 6 months, earlier if there is indication for adjuvant treatment with trastuzumab (Herceptin) or if required. Thereafter mammography and consultation with a physician should take place annually for 10 years.

More frequent follow-ups may be relevant for young patients (below 35 years), patients with locally advanced disease and patients where the cancer developed in relation to pregnancy.

Side effects of irradiation

Acute

  • Skin reaction in the form of redness, heat, soreness and edema. Some develops more pronounced irradiation dermatitis with desquamation and ulcerations.
  • Soreness of the pharynx after irradiation of regional cervical lymph nodes.
  • Nausea, most often slight and passing

Late

  • Permanent changes of the skin in the form of fibrosis, pigmentations and teleangiectasies.
  • Varying degree of fibrosis of the lung
  • Deterioration of/persistent lymphedema of the arm on the irradiated side.
  • Contractures and reduced mobility of the shoulder on the irradiated side.
  • Reduced strength of the skeleton, especially of the ribs/clavicle on the irradiated side
  • Slightly enhanced risk for secondary cancer (very small absolute risk)
  • Previously enhanced risk for cardiovascular disease. This is not seen with modern radiation techniques.

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