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The study was approved by the Ethics Committee of King Saud University. All participants provided written informed consent to participate in this study. There were, 20 consecutive eligible women presenting with breast carcinoma enrolled in this study, and were treated with PMRT (chest wall, SC region ± axilla) after modified radical mastectomy (MRM). Inclusion criteria were 1) patients with histopathological confirmed breast carcinoma, 2) patients with T1–T4, N1–N2, and 3) patients who underwent MRM with neoadjuvant or adjuvant chemotherapy.

Exclusion criteria were 1) patients with N0 status and were not candidates for SC region PMRT, 2) patients with N3 status or in whom radiotherapy to internal mammary lymph node was given, 3) patients who did not receive neoadjuvant/adjuvant chemotherapy, 4) presence of distant metastasis, 5) history of bronchial asthma and chronic obstructive pulmonary disease, 6) history of smoking, and 7) any contraindications for spirometry (unstable angina, history of myocardial infarction, or comprised cardiac functions, aorta aneurysm, cerebral aneurysms, and syncope associated with forced exhalation).

Radiotherapy techniques

All patients underwent computed tomography (CT) simulation in supine position on breast board with head turned to contralateral side of region of interest (ROI), with both arms placed above the head. CT data were obtained with a high-speed 16-slice helical scanner at 5 mm slices through the ROI. A single isocenter was marked at the level of match line between the SC and breast below the medial end of clavicle. After the acquisition of CT data, clinical target volume (CTV) including chest wall, SC region, and level III axillary lymph node region was delineated. Organs at risk (OAR) including spinal cord, heart, and both lungs were also delineated on each CT slice. For all patients, three-dimensional conformal radiotherapy plans were created using Eclipse™ (Varian Medical Systems, Inc., Palo Alto, CA, USA) version 10.0. Opposed tangential fields were designed to encompass the contoured CTV chest wall. Superior border of the CTV chest wall field was defined by the inferior extent of the SC area, which corresponded to the single isocenter. The inferior edge was placed at 2 cm below the level of infra-mammary fold of contralateral breast. The angle of tangential fields was opted to avoid too much lung volume in tangential fields. Dynamic wedges were used to maintain homogeneity within ±10%. A single antero-posterior field was matched to the superior border of the CTV chest wall tangential fields to encompass the SC region (Figure 1). A gantry angle of 5°–15° was applied to minimize the spinal cord dose. Wedges were used to create homogeneity in each plan. A dose of 50 Gy in 25 fractions (2 Gy/fraction/day) was prescribed to the chest wall, SC, and level III axillary nodes. A dose-volume histogram (DVH) was created to check the CTV dose coverage and the dose to each OAR. Treatment planning directed at good coverage of the CTV chest wall and SC and respected the International Commission on Reporting Units algorithms.

(To view a larger version of Figure 1, click here.)

Pulmonary function tests

The study employed the ndd EasyOne Pro® Spirometry Lab system. This system was used to acquire baseline PFTs before the commencement of radiotherapy, consisting of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximum mid expiratory flow (MMEF25-75), maximal oxygen consumption (VO2max), and carbon monoxide diffusing capacity (DLCO). These measurements were repeated after 30 and 90 days after completion of radiotherapy. FVC was considered as surrogate for lung volume, while FEV1 was considered a surrogate for the narrowing of large or medium-sized bronchi. MMEF25–75 was regarded as a surrogate for the narrowing of bronchioles; VO2max was defined as the oxygen uptake attained during maximal exercise intensity that could not be increased despite further increases in exercise workload, and DLCO was used as surrogate for the diffusing capacity through the alveolar-capillary barrier. Additionally, FEV1% pred (FEV1/FVC), forced expiratory flow at 50% when 50% of the FVC has been exhaled, and peak expiratory flow rate (PEFR) to assess expiratory muscle strength and large airway patency were noted down. Theoretically, FVC, FEV1, and DLCO are reduced in RIP, and all of aforementioned parameters are reduced in RIP and lung fibrosis.

DVH data

For the purpose of study, DVH to lungs and volume percentages of the ipsilateral lung absorbing 5, 10, 20, 30, 40, and 50 Gy (V5, V10, V20, V30, V40, and V50), respectively, were estimated. The continuous variables were dichotomized at respective median values.

Statistical analysis

Statistical Package for Social Science version 24.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Mean, minimum, maximum, and standard deviation were calculated for quantitative data description. A two-tailed paired Student’s t-test was subsequently used to compare mean values among the variables between the groups. A P-value of 0.05 was considered statistically significant.