From 2007 to 2012, one hundred patients affected by breast cancer were treated with conservative surgery, axillary node dissection (AND) and loco-regional (whole breast plus infra-supraclavicular fossa) hypofractionated RT. The median age at diagnosis was 60 years (range 34–83). Histology was ductal carcinoma in 76 patients (76 %). Characteristics of patients are shown in Table
1. Tumors were classified according to molecular characteristic as shown in Table
2. Axillary lymph nodes metastasis were confirmed in all women (81 patients post conservative surgery and 9 patients at diagnosis, before neo-adjuvant chemotherapy). Patients received systemic therapy: hormonal in 82 patients (82 %), neo-adjuvant chemotherapy in 9 patients (9 %), adjuvant chemotherapy in 81 patients (81 %). All the administered chemotherapy schedules contained anthracycline derivatives and taxanes. In agreement with several randomized phase III trials which have shown to improve local control with mild side effects and acceptable cosmetic outcome [
5] in our center all the patients receive a boost dose. The selected group of patients examined in this analysis received hypofractionated RT with concomitant boost as described in detail in a previous published experience [
11], Our treatment schedule was 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa (from Monday to Friday with a day off on Wednesday) with concomitant additional weekly dose of 1,2 Gy (preferibly delivered on Monday) to the lumpectomy area (total boost dose of 6 Gy in 5 fractions once a week). As reported by our previous paper, using the Linear-Quadratic cell survival model we assumed that 46Gy in 2.3 Gy fractions is equivalent to 50Gy in 2.0 Gy fractions as shown in Table
3 [
11]. The four fractions per week schedule is commonly used in our Department in order to optimize the clinical and dosimetric activities, by also allowing an easier integration of palliative treatments [
11‐
13]. Most treatments (81 %) were delivered by linear accelerator Varian Clinac 2100CD (RX, 6–15 MV), and the remaining 19 % by Tomotherapy Hi-Art® System (Accuray®, RX 6MV) when it was necessary to improve coverage of the target or minimize dose to normal tissue in selected patients in which a steep dose gradient was required. A planning computed tomography (CT GE Lightspeed Ultra) scan was made for each patient, positioned on a wing-board with both arms raised above the head. Patients were scanned from the level of the larynx to the level of the upper abdomen, including both lungs, with a scan thickness and index of 5 mm [
11]. Four tattoos were made on the thoracic skin to allow the repositioning of the patient during treatment sessions. The whole breast clinical target volume (WB-CTV) included the glandular breast tissue of the ipsilateral breast. The WB-CTV did not extend into the pectoralis major, nor the ribs, and did not include the skin [
11]. The three-dimensional tissue volumes containing the supraclavicular (SCV) infraclavicular (IFV) and III level lymph nodes were defined on CT scans by using readily identifiable anatomic landmarks on the guide of two published papers (Table
4) [
14]. In patients treated by linear accelerator (81 %), whole breast radiation was delivered by opposed tangential beams and infra-supraclavicular fossa by two or more opposing fields (main beam energy: 6 MV and, when it is necessary to improve target coverage, 15 MV). The gantry angles, the use of multileaf collimator, wedges and additional subfields were employed to achieve optimal dose distribution and maximal organ at risk avoidance (heart, left anterior descending coronary artery, ipsilateral lung, esophagus, thyroid and spinal cord). Constraints for the organs at risk are shown in Table
5, overdosages were limited within 5 %, this means that global Dmax is mantained lower than 105 % and this is possible using sub fields with MLC closed on overdosage regions. Tomotherapy Hi-Art® treatments were delivered using a 0.403 pitch, Modulator Factor (MF) ranging between 1.5–4, field dimension 2.5 cm. It was impossible to exclude the brachial plexus from the radiation fields due to its proximity to the lymph nodes region. Treatment Planning was performed in order to give 95 % of the prescribed dose to PTV; in three-dimensional (3D) conformal Radiotherapy an Eclipse v.7.3.10 Varian Treatment Planning System was used while Helical tomotherapy planning was performed with the HI-Art® Tomotherapy inverse planning system (Madison, WI, USA). Portal films were taken at least once during the first treatment day and compared to digitally reconstructed radiographs (DRR) and simulator images to ensure accurate set up. In Tomotherapy a pre-treatment daily image guidance with megavoltage (MV) CT scan was performed. After matching with the kilovoltage planning CT, corrections for translations and rotation around longitudinal axis (roll) were done. The disease control and treatment-related toxicity were analysed in follow-up visits, performed at 6, 12 months after therapy and, subsequently, annually. Particular attention was paid to late side effects correlated to radiation of infra-supraclavicular fossa. The extent of lymphedema was analysed at the department of Oncological Rehabilitation of our Institute, by measuring upper limbs circumference at two different locations obtained 10 cm above and below the antecubital fossa in both upper extremities and comparing the values with those of the contralateral arm, as suggested by other authors [
15]. Mild, moderate and severe arm lymphedema were defined as a difference of 0.5–2 cm, 2.1–3 cm and >3 cm respectively, in the circumference at one or more measurement sites between the treated and untreated sides [
15]. Patients were followed by Oncological Rehabilitation Unit to appearance of lymphedema according to its severity.
Table 1
Patients’ characteristics
Age | | |
<50 | 24 | 24 % |
50-59 | 23 | 23 % |
>60 | 53 | 53 % |
Histology | | |
DCI | 75 | 75 % |
LCI | 15 | 15 % |
Others | 10 | 10 % |
Pathological tumor stage | | |
pTis | 2 | 2 % |
pT1 | 51 | 51 % |
pT2 | 38 | 38 % |
pT3 | 2 | 2 % |
pT4 | 2 | 2 % |
Not evaluable | 5 | 5 % |
Pathological nodal stage | | |
pN0 | 9 | 9 % |
pN1 | 25 | 25 % |
pN2 | 43 | 43 % |
pN3 | 23 | 23 % |
Grading | | |
G1 | 4 | 4 % |
G2 | 54 | 54 % |
G3 | 38 | 38 % |
Not evaluable | 4 | 4 % |
Ki67 | | |
≤14 % | 27 | 27 % |
>14 % | 71 | 71 % |
Not evaluated | 2 | 2 % |
Table 2
Molecular characteristics of patients
Luminal A | 59 | 59 % |
Luminal B | 24 | 24 % |
C-erb +++ | 7 | 7 % |
Basal like | 10 | 10 % |
Table 3
BED comparison between standard and explored RT schedule [
11]
W.B. = whole breast | W.B. | B.S | W.B. | B.S | W.B. | B.S | W.B. | B.S |
B.S. = tumor bed side |
60 Gy/30 F/6 W | 75 | 90 | 60 | 72 | 109 | 131 | 90 | 108 |
(50 Gy + 10 Gy seq.boost) |
52 Gy/20/F/5 W (46 Gy + 6 Gy cc.boost) | 72 | 87 | 57 | 66 | 108 | 135 | 88 | 108 |
UK START TRIAL A | 75 | 75 | 55 | 55 | 120 | 120 | 95 | 95 |
41.6 Gy/13 F/5 W |
UK START TRIAL A | 68 | 68 | 51 | 51 | 108 | 108 | 86 | 86 |
39 Gy/13 F/5 W |
Table 4
Regional Nodal Contours: anatomical boundaries [
14]
SCV | bounded by the deep surface of the sternocleidomastoid and the deep cervical fascia | Lat: the anterior and medial borders of the anterior scalene muscle. | | the posterior border was defined by the subclavian artery | lateral edge of the trachea excluding the thyroid gland and thyroid cartilage superiorly | |
Med: medially to the carotid artery and internal jugular vein |
IFV | the deep surface of the pectoralis major muscle | subclavian-axillary artery | the most superior aspect of the pectoralis minor muscle | level of the insertion of the clavicle into the manubrium | lateral edge of the clavicle | medial border of the pectoralis minor muscle |
Table 5
Constraints for organs at risk in adjuvant radiotherapy of early breast cancer
LADCA | V20Gy = 0 % | V19Gy = 0 % |
Heart | V20Gy = 10 % V40Gy =5 % | V19Gy = 0 % |
Ipsilateral Lung | V20Gy = 25 % (exclusive periclavicular LN) | V19Gy = 25 % (exclusive periclavicular LN) |
| V20Gy = 35 % (inclusive periclavicular LN) | V19Gy = 35 % (inclusive periclavicular LN) |
Spinal cord | Max 45 Gy | Max 42 Gy |