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A Biological-Driven Approach to Explore Dose-Escalated Ultra-Hypofractionation in Breast Cancer Radiotherapy.

Marco Calvaruso1, Denis Panizza2, Riccardo Ray Colciago3

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Biomedicines
|September 27, 2025
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Summary
This summary is machine-generated.

Personalized radiation therapy for triple-negative breast cancer (TNBC) may require higher doses than currently feasible. This study modeled cell lines to inform tailored treatment plans, improving on the standard LQ model for better outcomes.

Keywords:
dosimetryradiobiologytriple-negative breast cancerultra-hypofractionation

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Area of Science:

  • Oncology
  • Radiation Oncology
  • Medical Physics

Background:

  • Triple-negative breast cancer (TNBC) presents unique challenges for adjuvant radiation therapy.
  • Current adjuvant whole-breast irradiation protocols may not be optimal for TNBC.
  • Personalized approaches are needed to improve local disease-free survival (LSR) in TNBC.

Purpose of the Study:

  • To investigate a personalized radiation therapy (RT) approach for adjuvant whole-breast irradiation in TNBC.
  • To radiobiologically characterize TNBC cell lines (BT549, MDA-MB-231) for tailored dose prescriptions.
  • To evaluate the feasibility of achieving high LSR probabilities with different fractionation schedules.

Main Methods:

  • In vitro radiobiological characterization of BT549 and MDA-MB-231 TNBC cell lines.
  • Determination of alpha (α) and beta (β) parameters and α/β ratios for each cell line.
  • Calculation of required doses per fraction to achieve a near 100% LSR probability using a five-fraction schedule.
  • Simulation of treatment plans based on cell line-specific radiobiological parameters.

Main Results:

  • MDA-MB-231 cell lines exhibited α/β ratios ranging from 3.79 Gy to 15 Gy (median 7 Gy).
  • BT-549 cell lines showed α/β ratios from 5.95 Gy to 22.93 Gy (median 16.51 Gy).
  • Required doses per fraction to achieve ~100% LSR varied significantly, with higher doses needed for BT-549 (up to 9.9 Gy).

Conclusions:

  • Achieving 100% cell death effectiveness in TNBC may necessitate radiation doses exceeding current adjuvant whole-breast irradiation feasibility.
  • A personalized RT model based on intrinsic tumor radiobiological features can improve upon the classic Linear-Quadratic (LQ) model.
  • This approach offers a pathway toward more tailored RT plans for TNBC, potentially enhancing treatment efficacy.