Clinical Advantage of Chest-wall Post-mastectomy Radiation Therapy Without Bolus

Patients and Methods

Patients. Between October 2011 and December 2016, 55 patients with breast cancer received PMRT at the Gunma University Hospital. Among these patients, three who received boost irradiation with electron beams were excluded because of the difficulty in recreating the precise dose distribution of electron beams using our radiation treatment planning system (RTPS) of the XiO version 4.5 software (ELEKTA, Stockholm, Sweden). Thus, 52 patients with breast cancer who received PMRT were retrospectively analyzed, and all patients were treated with 6 MV X-ray beams without bolus. Patient characteristics are summarized in Table I. Histologically, 46 patients had invasive ductal carcinoma, three had invasive lobular carcinoma, and four had other breast cancer types. Breast cancer subtypes were defined according to the status of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and the Ki-67 index. Twenty-four patients had luminal A (ER-positive and/or PgR-positive, HER2-negative, and Ki-67 <20%), 20 had luminal B (luminal type other than luminal A), four had HER2-enriched (ER-negative, PgR-negative, and HER2-positive), and four had triple-negative (ER-negative, PgR-negative, and HER2-negative) cancer subtypes. Twelve patients had clinical and/or pathological T4 components and 36 had four or more pathologically proven lymph node metastases. The present study complied with the standards of the Declaration of Helsinki and current ethical guidelines and all patients signed an informed consent form before the initiation of therapy.

Anticancer drug therapy. Twenty-four patients received anticancer drug therapy before surgery. Among these, 16 received 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by taxane regimen, five received FEC followed by taxane and trastuzumab regimen, and three received other regimens.

Twenty-three patients received anticancer drug therapy during the period between surgery and PMRT. Among these, 10 received FEC followed by taxane regimen, five received FEC followed by taxane and trastuzumab regimen, three received FEC followed by taxane and endocrine therapy regimen, and five received other regimens.

Fifty patients received anticancer drug therapy after PMRT. Among these, 27 received endocrine therapy alone, eight received endocrine therapy and tegaful-uracil, two received FEC followed by taxane regimen, three received endocrine therapy and trastuzumab, three received trastuzumab alone, and seven received other regimens.

Radiation therapy. All patients received total mastectomy and PMRT without bolus. Sets of 2.5-mm-thick CT images were acquired for treatment planning. The three-dimensional treatment planning was performed using the XiO RTPS.

Forty-nine patients received chest wall and supraclavicular and infraclavicular lymph node irradiations and three received only chest wall irradiation. The total dose to the chest wall and/or supraclavicular and infraclavicular lymph node regions was 50 Gy in 25 fractions with 6 MV X-ray beams. Figure 1 shows a typical radiation field with dose distribution.

Dose surface histogram analyses. There are various methods for skin area definition in RTPS. a skin surface thickness of 1.0 mm was chosen (4), and the skin structures were automatically contoured using the XiO software. A 5-mm tissue-equivalent structure on each patient's surface was used as a virtual bolus in our simulated plan. The dose distributions for the skin structures without bolus (real plan) and with virtual bolus (simulated plan) were calculated on the Plan-CT. DSH parameters of the percentage of maximum dose (D_max), the doses to 2-cm³ volumes (D_2cc), and the skin areas that received at least 5, 10, 20, 30, or 40 Gy (S₅, S₁₀, S₂₀, S₃₀, or S₄₀) in the real and simulated plans were measured and analyzed.

Evaluation during follow-up and statistical analysis. After the completions of PMRT, patients were mainly followed up at our hospital. The follow-up examinations comprised interviews, physical examinations, routine blood cell counts, and blood chemistry and diagnostic imaging tests such as mammography, ultrasonography, CT images, and magnetic resonance images. Acute and late toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0 (5). Acute toxicity was defined as the highest toxicity within 3 months from the initiation of PMRT, and late toxicity was defined as the highest toxicity after 3 months from the initiation of PMRT. Survival duration was measured from the date of initiation of PMRT to the date of death or to the most recent follow-up, and disease-free survival (DFS) was measured from the initiation of PMRT to the date of the first tumor progression disease. Locoregional recurrence was defined as tumor regrowth in the irradiated field. The probabilities of overall survival (OS), locoregional control (LC), and DFS rates were calculated using the Kaplan–Meier method, and the Wilcoxon signed rank test and Student's t-test were used for statistical analysis of differences in DSH parameters. Receiver operating characteristic (ROC) curves to determine the optimal cutoff values for D_max were measured to identify severe dermatitis cases. The cutoff value was defined according to the nearest point from the coordinates (0, 1) on the ROC graph. All statistical analyses were performed using the SPSS Statistics version 23 software (IBM Institute, Tokyo, Japan). p<0.05 was considered statistically significant.