Normative guidelines for radiation therapy of early stage breast cancer
Clinical Research Evidence and Types of Evidence
Evidence for breast-conserving treatment of early-stage breast cancer
– Breast-conserving treatment (breast-conserving surgery followed by radiotherapy) and radical surgery (or modified radical surgery) for early-stage breast cancer are equally effective, and there is no difference in survival and distant metastasis rates; breast-conserving treatment should be pursued in appropriate patients (Class I evidence). Shi Xuejun, Department of Medical Oncology, Yongchuan Hospital, Chongqing Medical University
– For most early breast cancers, axillary lymph node dissection at levels I and II is the standard of care (Class II evidence).
– Radiation therapy after complete local tumor resection significantly reduces the rate of local recurrence and decreases the likelihood of further mastectomy. Postoperative radiotherapy should not be omitted, even in select patients (Class I evidence).
– Radiation therapy after breast-conserving surgery for intraductal breast cancer significantly reduces local recurrence (Class I evidence).
Evidence for postoperative adjuvant therapy
– Postoperative radiation therapy in high-risk patients after radical breast cancer surgery significantly reduces local recurrence and improves long-term survival (Class I evidence).
– Ovariectomy reduces recurrence and mortality in women younger than 50 years of age with breast cancer (Class I evidence).
– Combination chemotherapy reduces recurrence and mortality in patients less than 70 years of age (Class I evidence).
– Combination chemotherapy at 4-6 months is more effective than chemotherapy at less than 4 months, and 4-6 months of chemotherapy is as effective as 8 months of chemotherapy, but the latter has increased toxicities (Class I evidence).
– Adriamycin-containing combination chemotherapy regimens were superior to CMF regimens, improving overall and disease-free survival, but with an increased risk of alopecia, cardiotoxicity, and febrile neutropenia (Class I evidence).
– High-dose chemotherapy was limited to clinical studies and was not a conventional treatment (Class II evidence).
– Triamcinolone significantly improves overall and disease-free survival in estrogen receptor-positive patients, regardless of age, primary tumor size, axillary lymph node status, and menopausal status (Class I evidence).
– Triamcinolone reduces the incidence of contralateral breast cancer (Class I evidence).
– The potential toxicities of triamcinolone include endometrial cancer, pulmonary embolism, deep vein thrombosis, and vaginal dryness, which are negligible compared to the therapeutic benefit of triamcinolone (Class II evidence).
– Chemotherapy combined with triamcinolone improves disease-free survival compared with triamcinolone alone or chemotherapy alone (Class I evidence).
– There was no evidence that close follow-up improved survival or improved quality of survival (Class II evidence).
Participants: Prof. Yu Zihao, Prof. Li Yexiong, Prof. Liu Xinfan, Prof. Qian Tunan, Prof. Gu Dazhong, Associate Prof. Han Jiazhu, Associate Prof. Lei Yingheng.
Radiation therapy after breast-conserving surgery for early-stage breast cancer
I. Indications for surgery
– Single lesion or focal microscopic calcified lesion
– Lesion ≤ 3cm
– The breast is large enough, and the appearance of the breast does not change significantly after tumor resection
– The lesion is located outside the areola area
– No clinically enlarged lymph nodes in the axilla or small, mobile lymph nodes
– No history of collagenous vascular disease or chest wall/mammary irradiation
– Patient voluntary
II. Treatment
( I ) Surgery
A. Treatment of the primary site
Extensive excision of the tumor (including 1 – 2 cm of surrounding normal breast tissue). Frozen section of the cut edge should be examined during surgery, and if there is any residual tumor, it should be enlarged again. A metal marker is made around the primary tumor for postoperative radiotherapy localization.
B. Treatment of axillary lymph nodes
– Dissect at Ⅰ and Ⅱ level
– For patients with clinical No, anterior lymph node examination can be performed
( II ) Radiotherapy
1. radiotherapy should be started within 6 weeks after the healing of surgical incision, and postoperative radiotherapy can be considered as conventional radiotherapy or intensity-modulated conformal radiotherapy.
2. Site selection
– If the axilla is not dissected or positive for anterior lymph nodes but not axillary lymph node dissection, the breast/chest wall, ipsilateral axilla, ipsilateral supraclavicular and axillary apex should be irradiated.
– For axillary dissection, if the axillary lymph nodes are negative or if there are 1-3 axillary lymph node metastases and the axilla is completely cleared, irradiation of the lymphatic drainage area is not necessary and only the breast/chest wall is irradiated; if there are 3 or 4 axillary lymph node metastases, irradiation of the breast/chest wall, ipsilateral supraclavicular and axillary apex is required.
3. Field design
(1) Breast/chest wall field: internal and external fields were used to irradiate the whole breast.
The upper border of the field: the lower border of the head of the clavicle, i.e. the lower border of the first rib. The upper border is the supraclavicular/apical axillary field or the lower border of the combined supraclavicular and axillary field.
Inferior border: 2 cm below the skin fold of the breast.
Inner border: mid-body line
Outer border: mid-axillary line or posterior axillary line
Dose: 6 MV-X, whole breast DT 50 Gy/5 weeks/25 sessions without fillers or tissue compensators, followed by primary foci.
Primary focal dose.
No primary foci were dosed for intraductal breast cancer.
Under the simulator, 2-3 cm of electron wire with appropriate energy was placed according to the intraoperative silver clip markings or around the surgical scar.
DT 16 Gy/1.5 weeks/8 times. Or apply post-mounted tissue interposition patching, DT 7 Gy/time, twice in total.
(2) Supraclavicular/apical axillary field.
Upper border of the field: at the level of the cricothyroid membrane.
Inferior border: the upper border of the mammary/chest wall field, i.e. the level of the lower edge of the first rib.
Inner border: the medial border of the sternocleidomastoid muscle along the midline of the body to the level of the sternotomy.
External border: inner edge of the humeral head.
Dose: DT 50 Gy/5 weeks/25 times, using a mixture of electron and X-ray to reduce the dose to the lung tip. Preferably with a half-field interface with the mammary tangential field. 4.
Intensity-modulated conformal radiotherapy
Objective.
– Small dose gradient for internal mammary irradiation, uniform dose distribution and improved cosmetic results.
– To reduce the irradiation dose to normal tissues such as lung, cardiovascular and contralateral breast, and to reduce the recent and long-term toxic effects.
METHODS: Treatment plan using a positive intensity modulated field midfield (still using internal and external fields). Patients who are young and have large mammary glands may benefit greatly. Note that the whole breast and surgical scar should be marked with lead wire before CT scanning to assist CT in determining the target area for whole breast irradiation and tumor bed replenishment.
III. Observation of efficacy and complications
The observation and documentation of cosmetic results should be emphasized
1. Color photographs of both breasts and upper extremities: once before and once at the end of radiotherapy, and once every six months during follow-up.
2. Detailed descriptions of breast appearance, skin changes, and softness to the touch should be included in the course record and follow-up record.
3. Arm circumference measurement of both upper limbs: the circumference of arm circumference should be measured at the reference point 15 cm above and below the ulnar horn.
The measurement should be done once before and once after radiotherapy, and once every six months during the follow-up period.
4. Bilateral mammograms and ultrasound of breast and regional lymph nodes: once before and once after radiotherapy, and once every six months during follow-up.
4. For primary tumor >3cm, if the patient requires breast preservation, preoperative chemotherapy can be done first, and then when the tumor shrinks and is suitable for breast preservation surgery (specific plan will be determined separately).
Radiotherapy after radical mastectomy or modified radical mastectomy
I. Indications
For postoperative systemic treatment including chemotherapy or/and endocrine therapy, postoperative radiotherapy should be considered for those who have one of the following high-risk factors:
(1). The maximum diameter of the primary tumor > 5 cm
(2). Axillary lymph node metastasis ≥ 4
(3). The total number of detected axillary lymph nodes ≤ 10, and 1-3 axillary lymph node metastases.
II. Postoperative radiotherapy irradiation site and dose
1. Supraclavicular/apical axillary field
Upper border of radiation field: the level of cricothyroid membrane.
Inferior border: the upper border of the breast/chest wall field, i.e. the level of the lower edge of the first rib.
Inner border: the medial border of the sternocleidomastoid muscle along the midline of the body to the level of the sternotomy.
External border: inner edge of the humeral head.
Dose: DT 50 Gy/5 weeks/25 times, with a mixture of electron and X-ray to reduce the dose to the lung tip.
2.
Chest wall field
Upper border of the field: the lower border of the head of the clavicle, i.e. the lower border of the first rib. The upper border is the supraclavicular/apical axillary field or the inferior border of the supraclavicular and axillary
The lower border of the joint field.
Inferior border: 2 cm below the skin fold of the breast.
Inner border: mid-body line
Outer border: mid-axillary line or posterior axillary line
Dose of irradiation: DT 50 Gy/5 weeks/25 times for the whole chest wall using electron beam. 3.
3. Axillary irradiation
Axillary radiotherapy can be given to patients without axillary lymph node dissection, or incomplete axillary lymph node dissection, or axillary lymph node dissection showing significant extra-lymph node tumor invasion.
The dose of the supraclavicular axillary joint field (articulated with the chest wall field) is set under the simulator, and the dose of the supraclavicular axillary joint field is calculated as 3 cm subcutaneously, and the axillary dose is supplemented by the posterior axillary field DT 50 Gy.
(1) Supraclavicular and axillary fields
Target area of the irradiated field: the whole supraclavicular and axillary area, adjacent to the breast/chest wall field.
Dose: 6 MV-X ray, supraclavicular DT 50 Gy/5 weeks/25 times. Tumor depth in the supraclavicular region was calculated as 3 cm subcutaneously.
The axillary depth was calculated based on the actual measurement, and the missing dose was applied to the posterior axillary field to make up for the DT 50 Gy.
(2) Posterior axillary field.
Target area of the irradiated field:
Upper border: inferior clavicular border.
Lower border: lower border of the axilla.
Inner border: medial border of the thorax.
External border: inner humeral border.
Dose of radiation: 6 MV-X-ray, with a supplemental dose of DT 50 Gy/5 weeks/25 times.
The thickness of the chest wall was measured by ultrasound, and the thickness of the filling (tissue compensation) was adjusted according to the thickness of the chest wall, and the energy of the electron beam used was determined to reduce the dose to the lung tissue and cardiac vessels to avoid radiological lung injury as much as possible.
Radiation therapy after neoadjuvant chemotherapy plus radical surgery or modified radical surgery for breast cancer
The indications for radiotherapy are the same as those without neoadjuvant chemotherapy.
Radiation therapy for local recurrence of breast cancer after radical or modified radical surgery
If a recurrence of breast cancer occurs in the chest wall, supraclavicular or axillary lymph nodes after radical or modified radical mastectomy, the tumor should be removed surgically first, followed by radiotherapy if possible. If surgery is not possible, chemotherapy should be given first, then surgery should be considered, followed by radiotherapy. For patients who have not had prior radiotherapy, the treatment should include the entire chest wall, supraclavicular or axillary lymph node area. If there is no recurrence of axillary or internal mammary lymph nodes, irradiation of the axillary and internal mammary areas is not required. The dose of radiation therapy is DT 50 Gy/5 weeks/25 doses at the prophylactic site, with field reduction to DT 60-66 Gy/6-6.5 weeks/30-33 doses at the recurrence site. Patients with prior radiation therapy should be given small-field local irradiation if necessary.
Table 1. Evaluation criteria for cosmetic outcome after breast preservation surgery
Ⅰ, very good: the shape of the diseased side of the breast is the same as the opposite side.
Ⅱ, good: the diseased side of the breast is slightly different from the contralateral side, the difference is not significant.
Ⅲ, fair: significantly different from the contralateral side, but no serious deformity
Ⅳ, poor: the diseased side of the breast has serious malformation.
Table 2: Radiation Oncology Group (RTOG) Acute Radiation Injury Grading Criteria
Organ tissue
Grade 0
Level 1
Level 2
Level 3
Level 4
Skin
No change
Follicular dark erythema / hair loss / dry hair loss / decreased sweating
Tender or bright erythema, patchy wet desquamation/moderate edema
fused wet peeling outside the skin folds
Ulceration, bleeding, necrosis
Lungs
No change
Mild dry cough or dyspnea on exertion
Persistent cough requiring narcotic cough suppressants / dyspnea on slight activity
Severe cough, not responding to narcotic cough suppressants, or dyspnea at rest / clinical or imaging evidence of acute radiation pneumonia / intermittent oxygen or steroid therapy
Severe respiratory insufficiency/continuous oxygen or assisted ventilation
Cardiac
No change
Asymptomatic with objective evidence of ECG changes; or pericardial abnormalities without evidence of other heart disease
Symptomatic, with ECG changes and imaging of congestive heart failure, or pericardial disease requiring no specific treatment
Congestive heart failure, angina pectoris, pericardial disease, effective for treatment
Congestive heart failure, angina pectoris, pericardial disease, arrhythmia, not effective for non-surgical treatment
Hematology
Leukocytes (X1000)
≥ 4.0
3.0-< 4.0
2.0-< 3.0
1.0-< 2.0
< 1.0
Platelets (X1000)
> 100
75-< 100
50-< 75
25-< 50
< 25 or spontaneous bleeding
Neutrophils (X1000)
≥ 1.9
1.5- < 1.9
1.0-< 1.5
0.5-< 1.0
< 0.5 or sepsis
Hemoglobin (GM%)
> 11
11-9.5
< 9.5-7.5
< 7.5-5.0
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Exhibit 3: Radiation Oncology Group (RTOG) Grading Criteria for Advanced Radiation Injury
Organ tissue
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Skin
No change
Mild atrophy, hyperpigmentation, some hair loss
lamellar atrophy, moderate capillary, vasodilatation, total
Alopecia moderate fibrosis, but asymptomatic; mild wild contracture <10% linear reduction
marked atrophy, significant capillary dilation severe sclerosis and subcutaneous necrotic tissue and decreased; wild contracture >10% linear units
Ulceration
Subcutaneous tissue
No change
Mild sclerosis/fibrosis and reduction of subcutaneous fat
Lungs
No change
Asymptomatic or mild symptoms (dry cough); mild imaging
Moderate symptomatic fibrosis or pneumonia (severe cough) Hypothermia, radiographic changes
Severe symptomatic fibrosis or pneumonia, dense imaging changes
Severe respiratory insufficiency/continuous oxygen or assisted ventilation
Cardiac
No change
Asymptomatic or mild symptoms; transient T-wave changes; sinus tachycardia >110 (at rest)
mild angina on mild exertion mild pericarditis; normal heart size; persistent abnormal T-wave and ST changes, low QRS
Severe angina; pericardial effusion; constrictive pericarditis; moderate heart failure; enlarged heart; normal ECG
pericardial tamponade/severe heart failure/moderate constrictive pericarditis
Bone
No change
Asymptomatic, no growth arrest; decreased bone density
Moderate pain or tenderness; growth arrest; irregular osteosclerosis
Severe pain or tenderness Complete arrest of bone growth; dense osteosclerosis
necrotic spontaneous fracture