BACKGROUND The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P = 0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P = 0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P = 0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P = 0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.)

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Internal mammary and medial supraclavicular irradiation in breast cancer

Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines

Radiation treatment to the left breast is associated with increased cardiac morbidity and mortality. The deep inspiration breath-hold technique (DIBH) can decrease radiation dose delivered to the heart and this may facilitate the treatment of the internal mammary chain nodes. The aim of this review is to critically analyse the literature available in relation to breath-hold methods, implementation, utilisation, patient compliance, planning methods and treatment verification of the DIBH technique. Despite variation in the literature regarding the DIBH delivery method, patient coaching, visual feedback mechanisms and treatment verification, all methods of DIBH delivery reduce radiation dose to the heart. Further research is required to determine optimum protocols for patient training and treatment verification to ensure the technique is delivered successfully.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/jmrs.96

Review of deep inspiration breath-hold techniques for the treatment of breast cancer

Introduction: Adjuvant left breast radiotherapy (ALBR) for breast cancer can result in significant radiation dose to the heart. Current evidence suggests a dose–response relationship between the risk of cardiac morbidity and radiation dose to cardiac volumes. This study explores the potential benefit of utilising a deep inspiration breath hold (DIBH) technique to reduce cardiac doses.

Methods: Thirty patients with left-sided breast cancer underwent CT-simulation scans in free breathing (FB) and DIBH. Treatment plans were generated using a hybrid intensity-modulated radiation therapy technique with simultaneous integrated boost. A dosimetric comparison was made between the two techniques for the heart, left anterior descending coronary artery (LAD), left lung and contralateral breast.

Results: Compared with FB, DIBH resulted in a significant reduction in heart V30 (7.1 vs. 2.4%, P < 0.0001), mean heart dose (6.9 vs. 3.9 Gy, P < 0.001), maximum LAD planning risk volume (PRV) dose, (51.6 vs. 45.6 Gy, P = 0.0032) and the mean LAD PRV dose (31.7 vs. 21.9 Gy, P < 0.001). No significant difference was noted for lung V20, mean lung dose or mean dose to the contralateral breast. The DIBH plans demonstrated significantly larger total lung volumes (1126 vs. 2051 cc, P < 0.0001), smaller maximum heart depth (2.08 vs. 1.17 cm, P < 0.0001) and irradiated heart volume (36.9 vs. 12.1 cc, P < 0.0001).

Conclusions: DIBH resulted in a significant reduction in radiation dose to the heart and LAD compared with an FB technique for ALBR. Ongoing research is required to determine optimal cardiac dose constraints and methods of predicting which patients will derive the most benefit from a DIBH technique.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1754-9485.2012.02405.x

Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer

Cardiac Side-effects From Breast Cancer Radiotherapy.

Purpose To assess the value of maximum heart distance (MHD) in predicting the dose and biologically effective dose (BED) to the heart and the left anterior descending (LAD) coronary artery for left-tangential breast or chest wall irradiation. Methods and Materials A total of 50 consecutive breast cancer patients given adjuvant left-tangential irradiation at a large U.K. radiotherapy center during 2006 were selected. For each patient, the following were derived using three-dimensional computed tomography (CT) planning: (1) mean dose and BED to the heart, (2) mean dose and BED to the LAD coronary artery, (3) MHD, (4) position of the CT slice showing the maximum area of the irradiated heart relative to the mid-plane slice, and (5) sternal and contralateral breast thickness (measures of body fat). Results A strong linear correlation was found between the MHD and the mean heart dose. For every 1-cm increase in MHD, the mean heart dose increased by 2.9% on average (95% confidence interval 2.5–3.3). A strong linear-quadratic relationship was seen between the MHD and the mean heart BED. The mean LAD coronary artery dose and BED were also correlated with the MHD but the associations were weaker. These relationships were not affected by body fat. The mid-plane CT slice did not give a reliable assessment of cardiac irradiation. Conclusion The MHD is a reliable predictor of the mean heart dose and BED and gives an approximate estimate of the mean LAD coronary artery dose and BED. Doses predicted by the MHD could help assess the risk of radiation-induced cardiac toxicity where individual CT-based cardiac dosimetry is not possible.

E. Thomas

Papers

Estimating cardiac exposure from breast cancer radiotherapy in clinical practice.