Proton Therapy and Its Results in the Treatment of Bilateral Breast Cancer
Breast cancer is the most common malignant tumor disease in women, and its incidence sharply increases after the age of 50. Although its incidence shows a continuously increasing trend, the development of mortality is more favorable. Thanks to nationwide screening and more successful therapy, mortality has long been stable, even slightly decreasing. A relatively rare variant of this oncological disease is primary synchronously detected bilateral breast cancer (PSBBC). Experts from the Proton Therapy Center in Prague are focusing on the use of proton radiotherapy in the treatment of this clinical entity.
Post-radiation Toxicity as a Serious Issue
The incidence of PSBBC is reported to range between 0.3–12%. This wide range can be explained by the not entirely precise definition, as the disease is characterized differently in the literature – as breast cancer arising and diagnosed in the contralateral breast within 1 month, 2 months, 3 months, 6 months, or 1 year. Risk factors for the occurrence of PSBBC include confirmed lobular carcinoma histology, positive family history, young age, and the presence of genetic mutations, especially BRCA.
The treatment strategy is essentially no different from that of unilateral disease, and there are currently no clear recommendations. Due to the higher risk of recurrence, patients undergo radical bilateral mastectomy. For non-metastatic tumors, adjuvant radiotherapy is a standard part of treatment. Although it is very effective, its complications (especially cardiovascular and pulmonary) significantly reduce the quality of life and survival of patients. With each gray (Gy) of so-called mean heart dose, the risk of damage increases by 7.4%. There is also an increased risk of lung parenchyma damage and the development of secondary malignancy. Given the extent of the target volume in PSBBC, performing adjuvant radiotherapy represents a significant challenge for most radiotherapy departments.
Methodology and Course of Radiation in the Evaluated Patient Cohort
For the assessment, a retrospective analysis was performed on a cohort of 19 patients with PSBBC irradiated at the Prague Proton Center from November 2017 to April 2022. The patients underwent radiotherapy in the area of the chest wall bilaterally/breasts bilaterally, with some on the lymph node area unilaterally and some on the bilaterally draining lymphatic area.
For patients after segmentectomy, a hypofractionation (HF) regime was used, while for chest wall irradiation, a normofractionation (NF) regime was used. Treatment planning was based on the so-called planning CT, which is performed in deep inspiration. Target volumes are projected and delineated onto this image. Contouring of risk organs (lungs, heart, cardiac structures, and coronary arteries) is also done. The physics department then performed so-called field fitting to the target volumes; all fields were optimized together, resulting in dose distribution. Patient setup and irradiation itself were performed in deep reproducible inspiration.
For the normofractionated regime, a dose of 50 CGE (cobalt gray equivalent) in 25 fractions was used, and for hypofractionation, a dose of 42.72 CGE in 16 fractions was applied. Dosimetric parameters for risk organs were monitored. For the lungs, this included the mean lung dose (MLD) and the lung volume receiving ≥ 5, or ≥ 20 Gy (V5 and V20). For the heart, the mean heart dose (MHD), mean dose to the left coronary artery (LAD), left ventricle (LV), and the dose in 5% of the heart volume (D5) were monitored.
Results of Proton Therapy Evaluation
11 patients underwent radical bilateral mastectomy, 7 segmentectomy, and 1 a combined operation with mastectomy on the left and segmentectomy on the right. Some patients experienced side effects in the form of acute toxicity (skin toxicity G1 in 11 patients, G2 in 7 patients, G3 in 1 patient, 2 patients suffered from G1 odynophagia).
For the final dosimetric evaluation, 14 simultaneously bilaterally irradiated patients were included. The mean lung dose reached 7.11 Gy (4.081–10.572) for the NF regime and 3.868 Gy (2.288–4.708) for the HF regime. The mean heart dose was 0.428 (0.099–1.177) for the NF regime and 0.255 (0.044–0.44) for the HF regime. Compared to doses used in other radiotherapy techniques, the values achieved by proton therapy do not reach even half.
Discussion and Conclusion
Due to the low incidence of PSBBC, no randomized clinical studies comparing proton and photon radiotherapy are currently available. New photon radiotherapy techniques with demonstrably better dose distribution and reduced dose to risk organs are gradually being developed.
Proton radiotherapy appears to be a very suitable option due to its dosimetric profile, clinical benefit, and safety. Acute toxicity is comparable with other radiotherapy methods. At the same time, it brings certain advantages, especially for patients with a longer expected life span and risk of cardiac complications.
(kali)
Source: Haas A., Andrlík A., Alhamami S. F. A., Pásztorová A. Feasibility, Dosimetric Evaluation, and Early Results of Proton Radiotherapy in the Treatment of Bilateral Breast Cancer. Oncology 2022; 16 (5): 258–262, doi: 10.36290/xon.2022.049.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
