Factors Affecting Heart and Anterior Descending Coronary Artery Radiation Dose during Left Breast Irradiation (Dosimetric Retrospective study)

INTRODUCTION

Breast cancer is the most common malignant disease in women around the world accounting 25.1% of all cancer in Egypt 32% of female cancer.¹

The use of adjuvant radiation therapy (ART) as per guidelines has contributed to significant improvements in disease free survival and overall survival for patients with early stage breast cancer, and even in selected patients with ductal carcinoma in situe.^2,3

Breast surgery followed by postoperative radiotherapy is the current standard therapy for early

operable breast cancer, almost in all patients after breast-conserving surgery (BCS) and most patients after modified radical mastectomy (MRM), Typically radiotherapy is administrated after finishing the adjuvant chemotherapy in these patients to reduce the risk of distant metastasis, while concurrent administration of chemotherapy and radiotherapy have been recently suggested.⁴

WBRT is associated with acute toxicities that involve the area treated (e.g., skin, muscle, and internal organs), although these complications are relatively uncommon. WBRT can also result in long-term complications, including cardio toxicity, lung injury and second malignancies, which can occur many years after treatment. However, improvements in radiation techniques over time have likely reduced the incidence of these long-term toxicities.⁵

In a recent meta-analysis included 39 studies (1.2 million breast cancer patients), adjuvant radiotherapy found to increase the risk of coronary artery disease (relative risk [RR] 1.3, 95% CI 1.13-1.49) and cardiac death (RR 1.38, 95% CI 1.18-1.62). However, the absolute risk increase for coronary artery disease and cardiac death was relatively low (76 and 126 cases, respectively, per 100,000 person-years). For coronary artery disease, the risk increased within the first decade, and for cardiac mortality, it increased in the second decade. ⁶

Tangential left breast/chest wall fields likely irradiate ALAD artery, two clinical studies had showed a correlation between the site of coronary stenosis and irradiated coronary arteries after left breast irradiation, when compared with patients received right breast radiotherapy and patients who didn’t receive any adjuvant radiotherapy.^7,8

Many factors may affect the radiotherapy dose received by heart and coronary artery, some of them are related to the patient and other to the disease itself or radiotherapy technique, in this dosimetric study, we will investigate the factors that may affect doses received by the heart and LADCA with left breast irradiation. 

This study is conducted to assess factors affecting heart and anterior descending coronary artery dose during adjuvant left breast irradiation with 3D technique.

PATIENTS AND METHODS

This dosimetric retrospective study included 69 patients with left breast cancer received adjuvant radiotherapy to the chest wall or whole breast from Jan 2017 to Jan 2019 and finished at Jun 2019, at the Clinical Oncology Department, Al-Hussein University Hospital. All patient included in this trial meet the following inclusion criteria; histopathologically proven breast cancer, stage I-IIIB, underwent surgery and has an indication for adjuvant radiotherapy.

Charts of included patients have been retrieved from the archive to collect the following patients and disease related data; Age, sex, weigh, high, quadrant of the mass, clinical extent of the disease, type of breast surgery, histopathology details (stage, capsular invasion..), chemotherapy (if received) and radiotherapy (Dose/fractions, boost and use of bolus,..)

CT simulation of the included patients have been retrieved from the planning system (Eclipse planning system version15.6), then target volumes and organs at risk (including ADCA) had been delineated once again by single radiotherapy physician (according to RTOG breast atlas delineation guidelines),⁹ while ADCA was delineated according the guidelines published by Duane et al,¹⁰ and radiotherapy plan has been reinitiated by single physicistwith same radiotherapy technique for all patients (according to the primary treating doctor prescription).

After plan approval for target volumes coverage and organs at risk constrains the dose to the heart and anterior descending coronary artery have be recorded along with the following data; breast size, heart volume, Shortest distance between heart and anterior chest wall, Maximum heart distance included inside the tangential fields, Number of segmental fields used in each plan.

STATISTICAL METHODS

Data were coded and entered using the statistical package SPSS version 23. Data was summarized using mean, standard deviation, median, minimum and maximum for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. Survival interval conspired as time between the date of histological diagnosis and the date of the last follow-up (for censored observations) or the date of death (for uncensored observations), while progression free interval was considered as time between date of the first treatment and the date of the last follow-up (for censored observations) or; date of death or disease progression whichever happen first (for uncensored observations).One-sided log-rank of Kaplan—Meier survival estimates was used for statistical analysis of overall survival and progression free survival, while the unpaired T test and one-way ANOVA test were used in the univariate analysis of the variables. Results of P-value less than 0.05 were considered statistically significant.

ETHICAL APPROVAL

The current investigation had been approved by the ethical committee, Faculty of Medicine, Al-Azhar University, Cairo, Egypt, before the start of this study. 

RESULTS

This study included 69 patients with median age 49 years (ranges: 28 -71); most of them were postmenopausal (58%). patients subjected to CBS about 24 pts (34.8%) while who subjected to MRM were 45pts (65.2%) While patients that received Chemotherapy 65 pts (94.2%) while who not received chemotherapy were 4 pts (5.8 %). All patients received the same dose 40Gy /15f), some of them received RTH with boost (34.8 %) and another received RTH with bolus to  Chest wall to increase the skin dose with boulse (14.1%). (Table 1) (Figures 1-3)

Table 1: age statistics

Fig. 1: Menopausal state (40.58% premenopausal, 29.4% postmenopausal)

Fig. 2: Type of surgery (35%CBS, 65%MRM)

Fig. 3: Received chemotherapy (94% received chemotherapy, 6% not received chemotherapy)

TNM staging explained in (Table 2).

         Table 2: TNM stage

Capsular invasion of LNs presented in 28 of pts while 41 pts were with no capsular invasion.(Figure 4)

Fig. 4: Capsular invasion (59% with capsular invasion, 41%wihout capsular invasion)

The median BMI of the patients were 33.3 (range; 23.1 to 51), median of breast size was 1044 cm3 (range: 512–1787), the heart size median was 608 cm3 (range: 442 - 899), Para sternal tissue thickness median was 3 cm (range1.95 – 5), the median shortest distance between heart and ant. Chest wall was 0.3cm (range: 0.1-2), while maximum heart distance median was 1.9 cm (range: 0 - 3.3). (Table 3)

Table 3: Factors affecting to heart and ADCA

The maximum heart distance included in tangential filed and heart size were the only factors that affect  significantly both mean heart dose and mean ADCA dose, while capsular invasion was having significant effect on mean heart dose only, on other hand none of other studied factor(Age, BSA, WT, BMI, HT, RTH dose, Number of fractions, para sternal tissue thickness, Breast Size, Shortest distance between heart and ANT chest wall, Site, Extent, Type surgery, Boost, Bolus and stage) showed significant influence on the mean heart dose and ADCA mean dose. (Table 4)

Table 4: Factors affecting to mean of heart and ADCA

We studied the factors can affect V100 (volume that received 100% of radiation dose) and V90 of the heart (volume that received 90% of radiation dose).

The maximum heart distance included in tangential  filed was the only factor that affected significantly both heart V100 % and V90 %,while heart size was having  significant  effect on heart V100 % only, on other hand none of other studied factor (age, BSA, WT, BMI, HT, RTH dose, number of fractions, para sternal tissue thickness, breast size, shortest distance between heart and ANT chest wall, site, extent, type surgery, boost, bolus and stage) showed significant influence on the Heart V100 % and V90 %. (Table 5)

Table 5: Factors affecting to V100 and V90 of heart

We studied the factors can affect V100 (volume that received 100% of radiation dose) and V90 of ADCA (volume that received 90% of radiation dose).

The maximum heart distance included in tangential filed and heart dose mean % were the only factor that affect significantly both ADCA V100 % and ADCA V90%,while heart size was having significant effect on ADCA V90% only, on other hand none of other studied factor (age, BSA, WT, BMI, HT, RTH dose, number of fractions, para sternal tissue thickness, breast size, shortest distance between heart and ANT chest wall, site, extent, type surgery, boost, bolus and stage) showed significant influence on the ADCA V100 % and ADCA V90 %. (Table 6)

We had studied Maximum heart distance in relation with ADCA dose mean and we found the significant effect started at >3cm.

The effect of Maximum heart distance was studied showing that when it was ≤3cm, the mean dose of the ADCA was 18.5±10.9 Gy while if it was >3cm, the mean dose of the ADCA was 27.9±9.1 Gy with a p-value 0.030 which is statistically significant. (Table 7)

The effect of Maximum heart distance was studied showing that when it was ≤ 2cm, the mean dose of the ADCA was 17.4±11.1 Gy while it was  > 2cm, the mean dose of the ADCA was 25.7±10.1 Gy with a p-value 0.074 which is statistically non-significant. (Table 8)

Table 6: Factors affecting to V100 and V90 of ADCA

Table 7: Maximum heart distance at 3cm effect on coronary artery D_mean

Table 8: Maximum heart distance at 2cm effect on coronary artery D_mean