Dosimetric comparison of three intensity‐modulated radiation therapies for left breast cancer after breast‐conserving surgery

Abstract Purpose This study aimed to evaluate dosimetric differences of intensity‐modulated radiation therapy (IMRT) in target and normal tissues after breast‐conserving surgery. Methods IMRT five‐field plan I, IMRT six‐field plan II, and field‐in‐field–direct machine parameter optimization–IMRT plan III were designed for each of the 50 patients. One‐way analysis of variance was performed to compare differences, and P < 0.05 was considered statistically significant. Results Homogeneity index of plan III is lower than those of plans I and II. No difference was identified in conformity index of targets. Plan I exhibited difference in mean dose (D mean) for the heart (P < 0.05). Plan I featured smaller irradiation dose volumes in V 5, V 20 (P < 0.05) of the left lung than II. Plan I exhibited significantly higher V 5 in the right lung than plans II and III (P < 0.05). Under plan I, irradiation dose at V 5 in the right breast is higher than that in plans II and III. Patients in plan III presented less total monitor unit and total treatment time than those in plans I and II (P < 0.05). Conclusion IMRT six‐field plans II, and field‐in‐field–direct machine parameter optimization–IMRT plans III can reduce doses and volumes to the lungs and heart better while maintaining satisfying conformity index and homogeneity index of target. Nevertheless, plan II neglects target movements caused by respiration. In the same manner, plan III can substantially reduce MU and shorten patient treatment time. Therefore, plan III, which considers target movement caused by respiration, is a more practical radiation mode.


| INTRODUCTION
Breast cancer is one of the most common malignant tumors in females. 1,2 The population of breast cancer patients in China reached an annual growth rate of approximately 3% to 4% in the past years. 3 Most patients with breast cancer can receive operative treatment in the early stage with continuous increase in medical technologies and quality. Breast is a secondary sex characteristic of women, whereas esthetics has become an important treatment requirement of patients with breast cancer owing to increasing attention on esthetic effect and living quality. 4 Therefore, comprehensive therapy of chemoradiotherapy after breast-conserving surgery of breast cancer has become the standard treatment for patients with early breast cancer. 5 This therapy has also achieved curative effects similar to those of radical mastectomy. Different patients exhibit significant differences in breast shapes and widths at different parts of the breast. The common clinical two-side tangent field radiotherapy exhibits an uneven irradiation dose in the target region and high irradiation doses to key organs, such as the heart and lungs.
Fixed-field intensity-modulated radiation therapy (IMRT) shows significant advantages in improving irradiation dose distribution in the target region and reducing irradiation dose in surrounding normal tissues. [6][7][8] However, IMRT expands low-volume irradiation region of normal tissues and increases irradiation doses to the lungs and breasts at the healthy side. [9][10][11][12] In this study, IMRT fixed five-field plan, IMRT fixed six-field plan, and field-in-field (FIF)-direct machine parameter optimization (DMPO)-IMRT plan were designed for different patients according to the target region using the Pinnacle 3 (Philips Medical System, Andover, MA, USA) treatment plan system version 9.6. Dosimetric comparison was conducted on dose distribution, conformity index (CI), and homogeneity index (HI) of the target region, and irradiation dose in the heart, lungs, and healthy breast of the three IMRT plans. The present study aimed to provide references for clinical treatment after breast-conserving surgery of early breast cancer. Informed consent forms were signed by all patients. The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Jiang-Xi Cancer Hospital.

2.B | Posture fixation and computed tomography scanning
Patients lay on the Varian Acuity digital analog machine. The left arm was raised upward at 90°and fixed by a Med-Tec 250 breast bracket. The breast with cancer was exposed completely. Corresponding reference points were marked by laser positioning. Scar wire was used to mark around the anterior median line, mid-axillary line, first anterior rib level, and 2 cm below the breast wrinkle.
SOMATOM Definition AS 20 spiral computed tomography (CT) was used to scan from the supraclavicular region to 5 cm below the breast wrinkle under free-breathing state. Normal tissues and organs surrounding the target region, such as the lung, heart, liver, and contralateral breast, were covered completely. Scan thickness totaled 5 mm. CT images were transmitted to the Pinnacle 3 treatment planning system version 9.6 through radiotherapy of special local area networks. Lung tissues were excluded from PTV. Simultaneously, OARs were defined; these organs included the lungs at two sides, heart, spinal cord, and contralateral breast ( Fig. 1(a)).

2.D | Treatment planning
A radiation therapy plan was generated to deliver ideal dose distribution, which has been determined by the radiotherapist, to the target.
Three different IMRT plans were designed for each patient using the 6 MV photon beams of a Precise linear accelerator (Elekta AB, Stockholm, Sweden).
Step-and-shoot beams were used for the three IMRT plans. Dose calculations in all three plans were performed using the collapsed-cone convolution algorithm with heterogeneous corrections on a dose grid with 3.0 9 3.0 9 3.0 mm 3 resolution.
The patients were treated with postoperative radiotherapy to a prescribed dose of 5000 cGy in 200 cGy fractions for 5 days per week. All three plans require that 95% of PTV reaches the prescribed dose of 5000 cGy. On the other hand, dose limits of OARs were determined in all three plans: spinal cord: D max < 3000 cGy; lung at the left side: V 20 < 25% and mean dose (D mean ) <1500 cGy; lung at the right side: V 5 < 15% and D max < 1000 cGy; the entire lung: V 20 < 20%; heart: V 30 < 10% and V 40 < 5%; right breast: 2) IMRT six-field plan (plan II): Rack angular distribution was approximately tangent to the lung edges. Radiation fields were distributed clockwise. The first, second, and third radiation fields were staggered by approximately 10°to 20°and were located at the upper part of PTV. By contrast, the fourth, fifth, and sixth radiation fields were staggered by approximately 10°to 20°and were located at the lower part of PTV. The other planning parameters were set similar to those in plan I.

2.E | Plan analysis and evaluation
Three IMRT plans were compared in terms of HI and CI of the tar-

2.F | Statistical method
All DVH data were inputted into and analyzed by SPSS 17.0. Quantitative data were expressed as mean AE standard deviation (x AE s).
Differences in the three IMRT plans were compared by one-way analysis of variance (ANOVA). Further pair-wise comparison was conducted to determine statistical significance. Data conforming to normal distribution were investigated by ANOVA. The remaining data were analyzed by nonparametric rank and summing test.
P < 0.05 represents statistically significant difference.
3 | RESULTS Figure 2 shows the corresponding DVHs in the three treatment plans for one representative patient.

3.B | Comparison of irradiation dose and volumes
of OARs under the three IMRT plans 1. Dose and volume in the heart Table 2 lists the irradiation doses and volumes of the three IMRT plans in the heart tissues (heart). Plan I yielded a significantly higher irradiation D mean than plans II and III according to irradiation dose in the heart. The findings showed statistical difference (P < 0.05). The three IMRT plans exhibited no significant difference in high-level irradiation volumes (V 30 and V 40 ). These results indicate no statistical difference (P > 0.05). 3. Irradiation dose and volume in the right lung Table 2 summarizes the irradiation doses and volumes in the right lung of the three IMRT plans (right lung). Irradiation doses (D mean ) in the right lung of plan I are significantly higher than those of plans II and III. Results showed statistical difference (P < 0.05). The difference between plans II and III exhibited no statistical significance (P > 0.05). V 5 in the right lung of plan I is significantly higher than those of plans II and III. Plan I contains five average fields in the hemisphere. This phenomenon increases irradiation errors to tissues at the healthy right lung to some extent. This result also explains the higher V 5 of plan I than those of plans II and III (P < 0.05). Therefore, field settings of plans II and III show absolute advantages with respect to protection of the healthy right lung. Table 2 provides the irradiation doses and volumes in the right breast of the three IMRT plans (right breast). Plan I showed higher D mean dose in the right breast than plan III, showing statistical difference (P < 0.05). Plans II and III exhibited no statistically difference (P > 0.05). Plan I exhibited higher V 5 in the right breast than plans II and III. In the arrangement of tangent fields, plans II and III protected the right breast first. This condition resulted in lower irradiation dose in the right breast compared with plan I. All three plans featured small D min in the right breast.

Irradiation dose and volume in the right breast
These findings showed no statistical difference (P > 0.05).  3.C | Comparison of total monitor unit and total treatment time of patients under the three IMRT plans Table 3 shows the total monitor unit and total treatment time of patients of the three IMRT plans. Total monitor unit and total treatment time of patients in plan III measured less than those of plans I and II (P < 0.05).

| DISCUSSIONS
To date, radiotherapy after breast-conserving surgery has been the standard treatment for early breast cancer. Adjuvant chemoradiotherapy after breast-conserving surgery cannot only reduce local recurrence risk effectively but also decrease distant metastasis rate and increase survival rate and quality of life of patients significantly. 17,18 Thus, the same curative effect with radial operation or modified radical operation is achieved. However, the approximate hemisphere of the breast determines significant differences in source-skin distance at different parts. 19,20 This factor will cause poor HI and CI in the target region after breast-conserving surgery and skin ulcer, radiation pneumonitis, and cardiac trauma. Therefore, current research focuses on means for further minimizing irradiation doses/volumes of OARs and improving dose homogeneity of targets. 7 In this study, dosimetric comparison of three IMRT plans was conducted from the target region and surrounding important organs of adjuvant chemoradiotherapy after left breast-conserving surgery.
All these plans can achieve good dose coverage to the target region.
Plan III possessed slightly lower HI than plans I and II because dose uniformity in the target region is positively correlated with the number of planning radiation fields and subfields. Plans I and II, which are full IMRT modes, have a significantly higher numbers of radiation fields and subfields than plan III.
Radiation pneumonitis and pulmonary fibrosis are important complications of radiation-induced pneumonitis for breast cancer. [21][22][23] Occurrence rate of complications is significantly correlated with irradiation volume and dose in lung tissues. V 5 and V 10 in lung tissues are important factors influencing occurrence of radiation pneumonitis. 24,25 Research has shown that occurrence rate of radiation pneumonitis reaches higher than 20% when V 10 of the lung measures higher than 50%. 26  Radiotherapy-induced heart diseases correspond to a group of clinical and pathological conditions of heart injuries caused by irradiation; these injuries include ventriculus sinister functional injury and pericardium injury. Research has shown a dose-effect relationship between occurrence of radiotherapy-induced heart diseases and irradiation dose and volume in the heart. 27 When irradiation dose in the heart is smaller than 3000 cGy, occurrence rate of radiotherapyinduced heart diseases reduces significantly, whereas that of coronary ischemia caused by IMRT is low, and this result is related to the small V 30 . 28 The three plans yielded a small V 30 without significant differences and low D mean in the heart. These results indicate that all three plans can protect the heart. Plan I presented significantly higher D mean than plans II and III as it applies an incidence field that is approximately perpendicular to the breast and runs through the heart.
Low irradiation dose in the healthy breast is an important cause of right breast cancer after radiotherapy. 29 decreasing the probability of occurrence of radiation pneumonitis and radiation heart diseases. Therefore, the combination of FIF and DMPO-IMRT is a practical method of radiotherapy after breast-conserving surgery of left breast cancer.

| CONCLUSIONS
This study aimed to evaluate the dosimetric differences in three IMRT in the target region and surrounding normal tissues after breast-conserving surgery of early breast cancer. Compared with plan I, plans II and III can reduce dangerous irradiation doses and volumes to the lung, heart, and spinal cord better while maintaining satisfying CI and HI of the target region in clinical treatment. Nevertheless, plan II neglects the effect of target region movement caused by respiration on dose distribution. Therefore, plan III, which considers target region movement caused by respiration and combines FIF and DMPO-IMRT serves as a more practical radiation mode after breast-conserving surgery of breast cancer.