International journal of radiation oncology, biology, physics · 2026
Radiobiological and Treatment Planning Evidence Supporting Particle Therapy in Aggressive Breast Cancer.
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Fede Francesca, Tessonnier Thomas, Filosa Domenico Ivan, Formicola Emilia, Elia Valerio Cosimo, Hamad Yasmin, Baltazar Filipa, Sycheva Natalia, Capasso Domenica, Hoeltgen Line, Meixner Eva, Abdollahi Amir, Manti Lorenzo, Dokic Ivana, Mairani Andrea
Аннотация
PURPOSE: Breast cancer (BC) remains the most commonly diagnosed malignancy among women worldwide, with an overall 5-year-survival rate of ∼90%. The prognosis worsens dramatically for patients with metastatic and/or aggressive subtypes. In such cases, particle therapy emerges as a promising approach, offering superior tumor control while limiting the risk of secondary pathologies.
METHODS AND MATERIALS: The radiobiological effects of x-rays were compared with those of protons, 4He and 12C ions, delivered using therapeutically realistic spread-out Bragg peaks, on 2- and 3-dimensional models of MDA-MB-231 (triple-negative [TN]) and MCF7 (estrogen receptor-positive) BC cells, whereas 16O ions were used on MDA-MB-231 cells. To achieve relevant insights, we evaluated conventional clonogenic survival and spheroid growth dynamics, mimicking tumor architecture, on both cell lines. Cell migration and invasion, tumor supernatant-induced angiogenesis, and the expression of proangiogenic factors were systematically investigated in the TN-BC subtype to assess the potential therapeutic advantages of ion irradiation in aggressive BC models. These in vitro data served as input for a comparative treatment planning study with protons, 4He, and 12C ions in 10 TN-BC cases.
RESULTS: All ions exhibited superior efficacy compared with x-ray and effectively counteracted the x-ray-induced increase in migration and invasion. 4He ions displayed a unique balance of advantages, showing greater relative biological effectiveness and inhibition of spheroid growth than protons and a reduction in migration and invasion comparable to that of 12C ions. In the planning and normal tissue complication probability study for TN-BC (α/β = 9.4 Gy), with similar organ-at-risk objectives (α/β = 3 Gy), protons and 4He ions achieved comparable CTV coverage and organ-at-risk sparing, whereas 12C ions exhibited reduced coverage mainly due to this large α/β difference.
CONCLUSIONS: These findings suggest particle therapy as a promising strategy for aggressive BC, with protons and 4He ions demonstrating good potential. Importantly, 4He ions emerge as a distinctive intermediate option between protons and heavier ions, combining physical precision, biological efficacy, and clinical applicability.
METHODS AND MATERIALS: The radiobiological effects of x-rays were compared with those of protons, 4He and 12C ions, delivered using therapeutically realistic spread-out Bragg peaks, on 2- and 3-dimensional models of MDA-MB-231 (triple-negative [TN]) and MCF7 (estrogen receptor-positive) BC cells, whereas 16O ions were used on MDA-MB-231 cells. To achieve relevant insights, we evaluated conventional clonogenic survival and spheroid growth dynamics, mimicking tumor architecture, on both cell lines. Cell migration and invasion, tumor supernatant-induced angiogenesis, and the expression of proangiogenic factors were systematically investigated in the TN-BC subtype to assess the potential therapeutic advantages of ion irradiation in aggressive BC models. These in vitro data served as input for a comparative treatment planning study with protons, 4He, and 12C ions in 10 TN-BC cases.
RESULTS: All ions exhibited superior efficacy compared with x-ray and effectively counteracted the x-ray-induced increase in migration and invasion. 4He ions displayed a unique balance of advantages, showing greater relative biological effectiveness and inhibition of spheroid growth than protons and a reduction in migration and invasion comparable to that of 12C ions. In the planning and normal tissue complication probability study for TN-BC (α/β = 9.4 Gy), with similar organ-at-risk objectives (α/β = 3 Gy), protons and 4He ions achieved comparable CTV coverage and organ-at-risk sparing, whereas 12C ions exhibited reduced coverage mainly due to this large α/β difference.
CONCLUSIONS: These findings suggest particle therapy as a promising strategy for aggressive BC, with protons and 4He ions demonstrating good potential. Importantly, 4He ions emerge as a distinctive intermediate option between protons and heavier ions, combining physical precision, biological efficacy, and clinical applicability.