1. Radiation therapy after total mastectomy for breast cancer
(1) Indications
Post-total mastectomy radiotherapy can reduce the 5-year local recurrence rate from 22.8% to 5.5% in patients with positive axillary lymph nodes. After total mastectomy, patients with one of the following prognostic factors are eligible for high-risk recurrence and have an indication for postoperative radiotherapy, which is independent of the specific surgical approach to total mastectomy
1, the maximum diameter of the primary tumor ≥ 5 cm, or tumor invasion of the breast skin or chest wall.
2. Axillary lymph node metastasis ≥ 4.
3, lymph node metastasis of 1 to 3 T1/T2,
The current data also support the value of postoperative radiotherapy. Patients who include at least one of the following factors may be at higher risk of recurrence and more meaningful for postoperative radiotherapy: age ≤ 40 years, proportion of metastases > 20% when the number of axillary lymph nodes cleared < 10, hormone receptor negative, Her-2/neu overexpression, etc.
(2) Timing with systemic therapy
Patients with indications for postoperative radiotherapy after total mastectomy generally have indications for adjuvant chemotherapy, so postoperative radiotherapy should be started within 2~4 weeks after completion of the last chemotherapy. Patients with contraindications to adjuvant chemotherapy can start postoperative radiotherapy after the incision heals and the upper limb function is restored. There is no consensus on the timing of endocrine therapy in conjunction with radiotherapy, which can be carried out concurrently or after radiotherapy. Patients treated with trastuzumab can be used concurrently with radiotherapy as long as their cardiac function is normal before starting radiotherapy, but on the one hand, these patients should not be irradiated in the internal breast area; secondly, patients on the left side should be treated with three-dimensional treatment techniques as much as possible to reduce the volume of cardiac irradiation and assess the average dose of cardiac irradiation to be at least less than 8 Gy.
(3) Irradiation target area
1.Since the chest wall and supraclavicular are the most common recurrence sites, accounting for about 80% of all recurrence sites, these two areas are the main target areas for postoperative radiotherapy; however, T3N0 patients can be considered for chest wall irradiation alone.
The significance of internal breast field irradiation is now unclear due to the relatively low proportion of internal breast lymph node recurrence. For patients with possible metastasis of internal breast lymph nodes diagnosed by imaging before chemotherapy, patients whose primary tumor is located in the medial quadrant while there is metastasis in axillary lymph nodes or other patients with a high chance of internal breast lymph node metastasis need to consider internal breast field irradiation.
(4) Irradiation technique and dose
In principle, all postoperative radiotherapy target areas are given a tumor volume of 50 Gy/5 weeks/25 times, and the dose can be locally increased to 60 Gy or more for areas with high suspicion of residual or recurrent lesions on imaging (including functional imaging).
1. Regulation irradiation technique
(1) Superior/inferior clavicular field: the upper border is the level of the cricothyroid membrane, which needs to include all the clavicles, and the lower border meets the upper border of the chest wall field, which is usually located about 1 cm below the head of the clavicle. The inner border is from the midline of the body to the level of the sternotomy along the inner edge of the sternocleidomastoid muscle. The outer border is tangential to the head of the humerus. A mixture of x-ray and electron beam irradiation may be used to reduce the dose to the lung tip. Treatment is performed with the head biased to the healthy side to reduce laryngeal irradiation, and the rack angle is angled 100 to 150 to the healthy side to protect the trachea, esophagus and spinal cord. If necessary, the internal superior field should be lead blocked along the sternocleidomastoid muscle to protect the larynx and spinal cord.
The upper border is connected to the supraclavicular field, such as the upper border of simple chest wall irradiation up to the lower edge of the clavicular head, and the lower border is 1 cm below the contralateral mammary skin fold. As with whole breast irradiation after breast-conserving surgery, each boundary also needs to be fine-tuned according to the site of the primary tumor to ensure that the original tumor site is in an area of adequate dose, and also needs to include the surgical scar. For chest wall irradiation with electron beam irradiation, the boundaries of each set-up field can be referred to the tangential field. Whether X-ray or electron ray irradiation is used, chest wall tissue equivalent filler needs to be given to increase the skin dose to adequate.
③ Axillary irradiation: Ⅰ: combined supraclavicular and axillary field, irradiation area including supra/inferior clavicle and axilla, articulating with the chest wall field. The upper and inner boundaries of the joint axillary-clavicular field are the same as the supraclavicular field, the lower boundary is in the second intercostal space, and the outer boundary includes the humeral neck, which needs to ensure that the outer lower corner of the field is open. The depth of the supra/inferior clavicular region was calculated as 3-4 cm subcutaneously using 6 MV X-ray, and after reaching a tumor volume of 50 Gy/5 weeks/25 times in the supraclavicular region, the axillary depth was calculated according to the actual measurement results, and the missing dose was supplemented to DT 50 Gy using the posterior axillary field, while the supraclavicular region was reduced to the conventional supraclavicular field range, and the additional dose was added to 50 Gy using electronic wire. II: Posterior axillary field, as a supplement to the combined axillary-lock field The upper border is flat on the inferior clavicular border, the inner border is 1.5 cm inside the rib margin, and the lower border is the same as the lower border of the combined axillary-clavicular field, and the outer border is connected to the lead block of the humeral head in the anterior field, which generally includes about 1 cm of the humeral head. The light bar was rotated so that all sectors of the field could be qualified.
(4) Internal mammary field: the conventional positioning of the internal mammary field should include the first to the third intercostal space, the upper boundary should be connected with the supraclavicular field, the inner boundary should be 0.5 to 1 cm past the midline of the body, and the width should be 5 cm. In principle, 2/3 of the dose and above should be used electronic lines to reduce the dose to the heart.
(5) Three-dimensional conformal irradiation technique
Compared with 2D treatment, 3D treatment planning based on CT positioning can significantly improve dose uniformity in the target area and reduce unnecessary irradiation of normal tissues, and improve the reasonableness of dose at the field interface. The complete coverage of the target area and the reduction of radiation damage are also recommended. The outlining of chest wall and regional lymph node targets can be done according to RTOG standards or other outlining guidelines.
(6) Radiation therapy after neoadjuvant chemotherapy and modified radical surgery for breast cancer
The indications for radiotherapy are the same as those without neoadjuvant chemotherapy, and in principle, the initial staging before neoadjuvant chemotherapy should be referred to. The radiotherapy technique and dose are the same as those for modified radical surgery without neoadjuvant chemotherapy. For patients with indications for adjuvant chemotherapy, postoperative radiotherapy should be carried out after completion of adjuvant chemotherapy; if there is no indication for adjuvant chemotherapy, postoperative radiotherapy is recommended to be started within 8 weeks after surgery under the premise of good incision healing and functional recovery of the upper limb. The timing with targeted therapy and endocrine therapy is the same as that with breast-conserving therapy or modified radical postoperative radiotherapy without neoadjuvant chemotherapy.
(7) Breast reconstruction and postoperative radiotherapy
In principle, the indications for postoperative radiotherapy in patients undergoing breast reconstruction should follow those of patients undergoing mastectomy at the same time, regardless of the surgical approach chosen. Neither autologous tissue nor prosthetic reconstruction is a contraindication to radiation therapy. However, from the perspective of optimal tumor control and aesthetic balance, if autologous tissue reconstruction is used, reconstruction can be delayed until the end of postoperative radiotherapy if available, during which time dilators can be considered to maintain the space of the flap, which improves the aesthetic effect to a certain extent compared to post-phase I reconstruction with radiotherapy. When prosthetic reconstruction is used, because the blood supply and compliance of the tissues are decreased after radiotherapy, implantation of prosthesis in stage II will bring more complications, including prosthesis displacement and contracture, etc. Therefore, stage I reconstruction is recommended for patients who are considered to have indications for postoperative radiotherapy and need to use prosthesis.
The technique of radiotherapy after breast reconstruction can refer to whole-breast radiotherapy after breast-conserving surgery. Since the late cosmetic effect of the reconstructed breast depends largely on the irradiation dose, and patients with post-reconstruction radiotherapy generally have indications for irradiation in the lymphatic drainage area, improving the dose uniformity in the target area as much as possible and avoiding hot spots at the field articulation are the keys to reduce late complications. On this premise, it is recommended to use three-dimensional treatment technology to integrate the irradiation of lymphatic drainage area into the three-dimensional treatment plan as much as possible.
2.Radiation therapy after breast-conserving surgery for breast cancer
(1) Whole breast radiotherapy
1. Indications
Whole breast radiotherapy after breast-conserving surgery can reduce the 10-year local recurrence rate of early breast cancer from 29.2 per 10,000 to 10 per 10,000, so in principle, all patients after breast-conserving surgery have indications for postoperative radiotherapy. In view of the low absolute recurrence rate and the slow regression of breast edema and pain after whole-breast radiotherapy, patients above 70 years old with stage I hormone receptor positivity can be considered for simple endocrine therapy.
2.Timing with systemic therapy
Postoperative radiotherapy is recommended within 8 weeks after surgery for patients without adjuvant chemotherapy indications. Because of the dynamic changes in the volume of the operative cavity in the early postoperative period, especially in patients containing seroma in the operative cavity, it is not recommended to start radiotherapy within 4 weeks after surgery. Patients receiving adjuvant chemotherapy should be started within 2 to 4 weeks after the last chemotherapy. There is no consensus on the timing of endocrine therapy in conjunction with radiotherapy, which can be carried out concurrently or after radiotherapy. Patients treated with trastuzumab can be used simultaneously with radiotherapy as long as their cardiac function is normal before radiotherapy, but on the one hand, these patients should not be irradiated in the internal breast area, and on the other hand, patients on the left side should be treated with three-dimensional treatment techniques as much as possible to reduce the volume of cardiac irradiation, and the average dose of cardiac irradiation should be assessed to be less than 8 Gy.
3.Irradiation target area
① Patients with negative axillary lymph node dissection or sentinel lymph node biopsy, or patients with one to three axillary lymph node metastases but complete axillary lymph node dissection (≥10 axillary lymph nodes detected) and no other high-risk factors for recurrence, the irradiation target area should only include the affected breast.
② Axillary lymph node metastasis ≥
② Patients with axillary lymph node metastases ≥ 4, or 1 to 3 axillary lymph node metastases but containing other high-risk factors for recurrence, such as age ≤ 40 years, hormone receptor negative, incomplete lymph node dissection or metastasis ratio > 20%, Her-2/neu overexpression, etc. The target area of irradiation should include the affected breast, supraclavicular and infraclavicular lymphatic drainage areas.
For patients who do not have axillary dissection or anterior lymph node macro-metastasis without axillary lymph node dissection, the probability of axillary lymph node metastasis can be determined based on a combination of prognostic factors, and the need to irradiate the axilla and supraclavicular and infraclavicular areas can be decided on the basis of whole breast irradiation.
4.Irradiation techniques
① Conventional radiotherapy technique: direct field setting under the X-ray simulator, the basic fields are the inner and outer breast fields. The inner and outer borders need to exceed the gland by 1 cm each, with the upper border generally at the lower edge of the clavicular head or articulated with the supraclavicular field, and the lower border 1 to 2 cm below the breast fold. the posterior border generally includes no more than 2.5 cm of lung tissue, and the skin of the anterior border is open, leaving a gap of 1.5 to 2 cm to prevent swelling of the breast beyond the field border during the irradiation process. Also each boundary needs to be adjusted according to the specific site of the lesion to ensure adequate dose at the tumor bed.
② Radiation and dose splitting: In principle, a linear gas pedal 6 MV X-ray is used, and individual patients with larger stature can be considered for 8 to 10 MV
X-rays to avoid the formation of high doses in the internal and external tangential field incidence, but should not use higher energy X-rays, because the skin dose decreases with higher X-ray energy. Whole breast irradiation dose (45-50) Gy, (1.8-2) Gy/time, 5 times/week. In the absence of lymphatic drainage, a “large split” regimen of 2.66 Gy x 16 doses for a total dose of 42.6 Gy, or other biologically equivalent splits, may be considered. Large fractionation is not recommended for patients with large volume of normal tissue including heart and lung irradiation or large dose distribution gradients within the target area.
(iii) Tumor bed dosing: Most post-breast-conserving patients can further improve local control with tumor bed dosing on top of whole breast irradiation. Under the simulator, including the metal clip of the surgical cavity or the outer 2-3 cm around the surgical scar, the electron wire of appropriate energy is selected. In the case of the basal depth of the tumor bed more than 4 cm, it is recommended to choose the X-ray small incision field to ensure adequate dose coverage of the tumor bed and to avoid excessive skin dose caused by the high-energy electron wire. The dose is (10-16) Gy/(1-1.5) weeks/(5-8) times.
④ Three-dimensional conformal and intensity adjustment irradiation technology: CT positioning and three-dimensional treatment plan design conformal irradiation can significantly improve the target area dose uniformity and reduce unnecessary irradiation of normal tissues, especially when the treatment involves left-sided patients need to minimize the irradiation dose to the heart, the existence of field articulation, as well as the chest anatomy of special patients conventional set field can not achieve a satisfactory normal tissue safety dose, three-dimensional treatment plan on Optimization is particularly advantageous and is currently the recommended treatment technique. The requirements for outlining the whole breast target area are as follows: the upper border is 5 mm above the upper border of palpable breast tissue, the lower border is 1 mm below the breast fold, the inner border is usually located next to the ipsilateral sternum with reference to the clinical marker point, and the outer border is 5 mm below the outer border of palpable breast tissue. the anterior border is 5 mm below the skin, including adipose tissue, and the posterior border is anterior to the rib cage. Dose optimization can be performed using the wedge filter technique, forward or reverse intensity modulation technique, where the reverse intensity modulation technique requires higher technical requirements in all aspects and needs to be carried out in a unit with mature conditions.
(2) Accelerated partial breast irradiation (APBI)
1. Indications
Preliminary studies on APBI have shown that for some patients with early-stage breast cancer, APBI after breast-conserving surgery may achieve local control rates comparable to standard whole-breast radiotherapy, with the advantage of a substantially reduced course and reduced volume – dose of normal tissue irradiation, but follow-up and prospective studies are still ongoing. Patients who may achieve similar local control rates with APBI therapy as with whole breast irradiation should be in the low-risk recurrence subgroup, as per the consensus of the American Society of Radiation Oncology (ASTRO), which states that patients who strictly meet the “low-risk” criteria must also have a low risk of recurrence. According to the consensus of the American Society of Radiation Oncology (ASTRO), patients who strictly meet the criteria for “low risk” must also have the following criteria: age ≥ 60 years, unifocal mass with T1N0, no neoadjuvant therapy, negative margins, no vascular invasion, no extensive intraductal component, hormone receptor positive invasive ductal carcinoma or other invasive carcinoma with good prognosis. Although the definition of true “low-risk” is not fully agreed by different consensus, APBI is not currently recommended as routine treatment outside of clinical trials.
2.Technology selection
Regardless of the technique, the core of APBI includes the original tumor bed and a certain area of the surrounding normal breast as the clinical target volume (CTV), rather than the traditional whole breast. The most technically feasible is 3D conformal external irradiation, which can refer to the dose split of RTOG0413: 38.5Gy/10 times, twice a day, at intervals >6 h. Other techniques include brachytherapy with insertion and hydrocolloid catheter (mammosite), intraoperative radiotherapy, etc.